Download E_Book - 22th Congress of Neurology & Clinical

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22nd Congress of Neurology & Clinical Electrophysiology of Iran
12-15 May 2015
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22nd Congress of Neurology & Clinical Electrophysiology of Iran
12-15 May 2015
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22nd Congress of Neurology & Clinical Electrophysiology of Iran
12-15 May 2015
In the Name of God
22nd Congress of Neurology &
Clinical Electrophysiology of Iran
12-15 May 2015
Tehran, Iran
Abstract E-Book
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22nd Congress of Neurology & Clinical Electrophysiology of Iran
12-15 May 2015
Table of Contents
Welcome note (Dr Pakdaman)……………………………….…………….……………………….
Welcome note (Dr Nabavi)……………………………….………………….……………………….
Page
5
6
7
ORAL PRESNETATIONS……………………………………………………….….……..……………….
POSTER PRESENTATIONS……………….……………………………………….….….……………
53
Cerebrovascular Diseases…………………………………………………………………….……….
Neurology & General Medicine…………………..………………………………………………….
Dementia……………………………………………………………………………………………………….
Spinal Cord Disorders……………………………………………..………………….…………………
Neurometabolic……………………………………..………………………………………………………
Headache……………………………………………………………………………………………………….
Multiple Sclerosis & Neuroimmunology……….….……………………………………….…..
Epilepsy………………………………………………………………………………………………………….
Basic Neuroscience & Neuropharmacology…………………………………………….…….
Neuromuscular Disorders & Neurophysiology………………………………………….…
Movement Disorders …………………………………………..………..……………………….………
Neuromodulation & Neurorehabilitation…………………………………………….……….
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185
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22nd Congress of Neurology & Clinical Electrophysiology of Iran
12-15 May 2015
Welcome Letter
Dear Colleagues and Friends,
As President of Iranian Neurological Association, it is both an honor and a pleasure to
invite you to join me in attending our 22nd Iranian Congress of Neurology, which will be
held in Tehran, Iran, on May 12-15, 2015. The Iranian Neurological Association is
pleased to have the opportunity to host this conference and to welcome participants
from different cities of Iran and around the world to this exciting and stimulating event
which will bring together colleagues from around the world to discuss topical issues in
different the field of neurology.
We will discuss the major breakthroughs and developments in the field of neurology –
from clinical practice to research and technology. In addition to a top-rate scientific
program, there will be many opportunities for hands-on learning and networking as
well as exciting social events.
Our Annual Congress is a unique occasion for members of the society and the
community to gather and work together toward our common goals i.e., improvement of
our knowledge and patients’ health. We are eager to participate and discuss exciting
new findings, technologies, and opportunities in this field I am sure will leave a lasting
impression on us all.
We look forward to opening our doors to everyone to Iran for 22nd Annual Conference
2015.
Sincerely Yours,
Professor Hossein Pakdaman
President of Iranian Neurological Association
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Dear All
After announcement for the submission of abstracts for the 22nd Iran neurology
congress on November 2014, up to its deadline on March 2015, we have received more
than 164 abstracts in several topics of neurology and neuroscience fields. As an
innovation and for the first time in Iran we decided to prepare an E-book abstract panel
in the congress website. The advantages of this E-book are: global availability, ability of
rapid updating, searching capability, including the late breaking articles and lack of
paper overuse. We aim that the E-book will be accessible on the congress website at
least for 6 month then to be archived in the website of Iranian Neurological association
for the later periods.
On behalf of the scientific committee of the 22nd congress, I acknowledge the efforts of
all of my colleagues in both aspects of the scientific and executive processes.
S.M.Nabavi, MD
Congress Chairman
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ORAL PRESNETATIONS
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Motor Neuron Disease: Introduction and Diagnosis
Farzad Fatehi
Iranian Center of Neurological Research, Shariati Hospital, Tehran University of Medical Sciences, Tehran,
Iran
Amyotrophic lateral sclerosis or a more general term, motor neuron disorder, are a group of disorders
pathologically characterized by the destruction of motor neurons centrally, peripherally or in both sites in
most of the cases. In a great majority of the patients, it behaves as a grave progressive disorder primarily
manifested as weakness of limbs with ensuing weakness of bulbar muscles and respiratory muscles. The
earliest symptoms of ALS are typically obvious weakness and/or muscle atrophy. Other presenting
symptoms comprise trouble cramping, swallowing, or stiffness of affected muscles; muscle weakness
affecting an arm or a leg; and/or slurred and nasal speech. The parts of the body affected by early
symptoms of ALS depend on which motor neurons in the body are damaged first. Usually the patients
with long standing pure upper motor symptoms (such as primary lateral sclerosis) or pure lower motor
neuron disorder (progressive muscular atrophy) demonstrate better prognosis.
Usually the eye motor muscles are intact; however, People with ALS may have difficulty in making
voluntary fast movements of the eye. In addition, sphincter problems are rare or seen in late stages.
Cognitive problems are usually late findings in these patients; however, in some forms with genetic
mutations in TDP43 or C9ORF72, cognitive disorders such as frontotemporal lobe dementia are an early
finding.
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ALS mimic syndromes
Majid Ghasemi
Isfahan University of Medical Sciences, Isfahan, Iran
The term amyotrophic lateral sclerosis (ALS) mimic syndrome has been used to describe a diverse group of
conditions, the presentation and clinical features of which may resemble those of ALS at the outset. Many
diseases, both neurologic and systemic, may mimic ALS, making the differential diagnosis rather
extensive. Incorrect diagnosis of ALS is a significant problem with more misdiagnoses occurring in
patients over 60 years. Several studies over the past decade have collected data indicating that rates of
misdiagnosis in the general medical population are high. The more common misdiagnosis is falsenegative diagnosis when the patient with ALS is told that he/she has another disease. A false-negative
rate of 43% has been reported from New Jersey and of 40% from Turin, Italy. In a recent E-mail survey of
ALS patients throughout the US, 27% indicated at least one prior misdiagnosis. False-positive diagnosis
may also be a problem in which the patient is mistakenly told that he/she has ALS. A survey in Scotland
indicated that at least 8% of those initially labeled as having motor neuron disease were later found to
have other neurologic diagnoses. In patients diagnosed with ALS the absence of disease progression, the
presence of an atypical history, the presence of unusual symptoms should trigger a search for ‘mimic
syndromes’. One may approach the differential diagnosis in terms of anatomy, symptoms, clinical
presentation. For this discussion, we discuss the differential in terms of nervous system anatomy.
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ALS Management: New research highlights
Davood Fathi
Tehran, Iran
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder of the motor system, with an
annual incidence of 2/100000 and a prevalence of 5-7/100000. ALS is the commonest form of a group of
disorders called motor neuron diseases which includes classical sporadic ALS, progressive bulbar palsy,
progressive muscular atrophy, and primary lateral sclerosis. ALS is clinically manifested by progressive
muscular weakness and atrophy, with a combination of upper and lower motor neuron signs caused by
degeneration of motor neurons in the motor cortex, brain stem, and anterior horn of the spinal cord.
Electrophysiological assessment is used in patients with suspected ALS for two reasons, first: to support
the diagnosis by finding evidence of a more widespread motor neuron dysfunction than is apparent
clinically and second: to exclude other ALS-mimicking syndromes. There have been proposed several sets
of criteria to facilitate an earlier diagnosis of ALS which combine the clinical and electrophysiological
assessments. The latest consensus criteria for diagnosis of ALS which determines the best use of
electrophysiological findings is Awaji-shima criteria which has been proposed by a group of international
experts in Awaji-shima, Japan in 2006. In Awaji-shima criteria electrophysiological and clinical signs of
lower motor neuron have the same value in the decision of lower motor neuron involvement in patients.
According to this new definition, clinically probable laboratory supported ALS, which was used in revised
El Escorial criteria has been deleted in Awaji criteria. Another difference in the Awaji-shima criteria in
comparison to the revised El Escorial criteria is that the fasciculation potentials in electrophysiological
study are equivalent to fibrillations and positive sharp waves as evidence of acute denervation. According
to the Awaji criteria, clinically definite ALS is defined by the presence of clinical or electrophysiological
evidence of both lower motor neuron and upper motor neuron involvement in bulbar region and two
spinal regions or in three spinal regions. Clinically probable ALS is defined by the presence of clinical or
electrophysiological evidence of both lower motor neuron and upper motor neuron signs in at least two
regions with some upper motor neuron signs necessarily rostral to the lower motor neuron signs.
Clinically possible ALS is defined by the presence of clinical or electrophysiological evidence of both lower
motor neuron and upper motor neuron signs in only one region; or upper motor neuron signs are found
alone in two or more regions; or lower motor neuron signs are found rostral to upper motor signs. ALSmimicking syndromes must be ruled out by neuroimaging or other laboratory tests.
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Electrophysiologic assessment and diagnosis of ALS
Mohammad Yazdchi1, Haleh Mikaeili2
Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Symptom-based management of amyotrophic lateral sclerosis
Multidisciplinary ALS clinics provide care from neurologists, physical therapists, occupational therapists,
speech therapists, respiratory therapists, dietitians, social workers, and nursing care managers. Thus,
specialized clinics can guide the management of the complex issues related to ALS, which include
respiratory symptoms, nutrition, dysarthria, dysphagia, functional decline, and psychosocial problems.
Current American and European guidelines state that specialized multidisciplinary clinic referral should
be considered for patients with ALS, with the goals of optimizing health care delivery, prolonging survival,
and enhancing quality of life.
RESPIRATORY MANAGEMENT - Important aspects of pulmonary care include counseling the patient and
family about potential treatments, the use of pulmonary tests to assess respiratory function, and the
utility of noninvasive and invasive ventilation.
DYSPHAGIA AND NUTRITION — In patients with ALS, limited data suggest that percutaneous
gastrostomy tube (PEG) placement is associated with prolonged survival, although the degree of survival
advantage is uncertain. In addition, nutritional supplementation using PEG may be helpful for stabilizing
weight loss common in ALS.
SYMPTOM MANAGEMENT — Among the prominent symptoms of ALS addressed by national guidelines
are dyspnea, muscle spasm, spasticity, sialorrhea, and pseudobulbar affect. Equally important and
potentially debilitating are other problems associated with ALS. These include dysarthria, muscle
weakness, functional decline, loss of ambulation, pain, sleep problems, and psychosocial issues such as
depression.
Dysarthria — Speech therapy is rarely helpful; however, communication disorders specialists are
important resources to help with choosing appropriate alternative communication methods. These
methods may include writing with pen and paper or alphabet boards. Electronic communication devices
have been extensively developed in recent years, and they can be adapted for use with either hand or eye
controls.
Dyspnea — Trunk elevation, chest physiotherapy, and reassurance may be helpful.
For intermittent dyspnea, inhaled opiates such as morphine 5 mg may be helpful. If intermittent dyspnea
is severe, intravenous midazolam can be given slowly up to 5 to 10 mg. For anxiety, lorazepam 0.5 to 2 mg
sublingual can be useful.
Fatigue — Fatigue is occasionally associated with riluzole treatment, but more commonly is a
manifestation of the effort required to perform daily activities. For debilitating fatigue, modafinil is
sometimes helpful. Withdrawal of riluzole may be considered in patients with debilitating fatigue.
Muscle spasms — Quinine sulfate 325 mg twice a day was considered the most effective treatment option
for muscle cramps. Other medications tried for cramps include baclofen, gabapentin, and tizanidine.
Muscle weakness and functional decline — Assistive devices such as canes, ankle foot orthoses, crutches,
and walking frames can be helpful early in the course of the disease. Most patients will eventually require
a wheelchair.Higher toilet seats and bathtub lifts help to maintain toileting and bathing independence.
Sialorrhea — Drooling is a common symptom in ALS. It is caused by the combination of facial muscle
weakness and reduced swallowing ability.
Sialorrhea can be treated with Atropine, Amitriptyline, Glycopyrrolate, Botulinum toxin injection into the
salivary glands.
Pseudobulbar affect — The combination drug dextromethorphan-quinidine, Amitriptyline, Fluvoxamine
have been shown to be effective in controlled studies.
Psychosocial aspects — As examples, a questionnaire study of 25 patients with ALS found that about 44
percent reported depression. Observational data suggest that treatment of depression can improve
quality of life in ALS, even in physically debilitated patients.
Disease modifying treatment of amyotrophic lateral sclerosis:
RILUZOLE — Riluzole is the only drug to have any impact on survival in ALS. The evidence that riluzole is
beneficial comes from clinical trials. Riluzole 50 mg twice daily is recommended for patients with ALS.
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Three separate mechanisms of riluzole are thought to reduce glutamate-induced excitotoxicity: inhibition
of glutamic acid release, noncompetitive block of NMDA receptor mediated responses, and direct action
on the voltage-dependent sodium channel.
Riluzole is well tolerated, with the most significant adverse effects being gastrointestinal and hepatic.
Neutropenia is extremely rare. The most common adverse effects of riluzole are asthenia, dizziness,
gastrointestinal disorders, and elevations in liver enzyme activities. Liver function tests are indicated
monthly for the first three months of riluzole treatment and every three months thereafter.
EXPERIMENTAL THERAPY — The following illustrates the range of findings in some of studies:

Clinical trials have found no benefit for celecoxib, ciliary neurotrophic factor, gabapentin,
lamotrigine, lithium, talampanel, topiramate, valproic acid, verapamil, or minocycline.

A phase II randomized controlled trial of 185 patients with ALS showed that the free radical
scavenger coenzyme Q10, at up to 2700 mg daily, was safe. However, the trial investigators concluded
that coenzyme Q10 treatment was futile and should not be further tested as a possible treatment for
ALS.

Two preliminary human clinical trials employing recombinant insulin-like growth factor type I
(IGF-I) for ALS reported somewhat discrepant results. A third multicenter placebo-controlled trial of
330 patients with ALS found no evidence of benefit for IGF-1 on any of the primary or secondary
outcome measures at two years.
Animal models — Several animal models have been developed to investigate the pathogenesis and
treatment of ALS. Earlier studies used pure motor neurons cultured in vitro. In vitro models of cell death
based on superoxide dismutase (SOD1) dysfunction were developed after the discovery of the Cu/Zn
SOD1 gene abnormalities in familial ALS, and several mouse and rat models expressing mutant forms of
SOD1 exist. In addition, transgenic rodent models of ALS were developed based upon mutant forms of
human TDP-43. The experimentally induced mutations G93A, G37R, and G85R in the transgenic mouse
models have phenotypes similar to human ALS. There are also naturally occurring mouse models
including the motor neuron degeneration (Mnd), progressive motor neuropathy (pmn), and wobbler.
Neurotrophic factors — Trials utilizing insulin-like growth factor-I (IGF-I) and other neurotrophic factors
for ALS have been unsuccessful.
Antioxidants — Oxidative stress has been implicated in the pathogenesis of ALS due to the production of
oxygen free radicals resulting in lipid peroxidation, cytoskeletal disruption, and damage to the
mitochondria. At least two randomized controlled trials have failed to demonstrate significant benefit of
vitamin E as add-on therapy to riluzole in ALS.
Bioenergetic agents — The energy buffering agent creatine has been studied as a way to prevent or
mitigate mitochondrial dysfunction. In transgenic mouse model data, oral administration of creatine
showed dose-dependent benefit, with 1 percent creatine extending survival by 13 days and 2 percent
creatine by 26 days. This benefit seen with 2 percent creatine surpassed the extended survival seen with
riluzole in this mouse model.
Despite the promise of creatine in animal models, human randomized controlled trials failed to
demonstrate efficacy for creatine at doses up to 10 grams/day in the treatment of ALS.
Antiapoptotic agents — A tricyclic selegiline analog, TCH346 (also called CGP3466) interacts with
glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in a mechanism that may prevent programmed cell
death. It reduces the degeneration of motor neurons in many in vitro models of apoptosis, but it did not
have significant effects on survival in transgenic mice.
Current and future trials — A number of agents are under active investigation for the treatment of ALS,
including the following: Antisense oligonucleotide therapy for SOD1-associated familial ALS, Arimoclomol
for familial ALS, Ceftriaxone, Creatine, Dexpramipexole, Memantine, NP001, Stem cell treatments,
Tamoxifen
Heart drug may help treat ALS, mouse study shows
Digoxin, a medication used in the treatment of heart failure, may be adaptable for the treatment of
amyotrophic lateral sclerosis (ALS), in a new study conducted in cell cultures and in mice, scientists
showed that when they reduced the activity of an enzyme or limited cells’ ability to make copies of the
enzyme, the disease’s destruction of nerve cells stopped. The enzyme maintains the proper balance of
sodium and potassium in cells. Bonni’s results suggest the sodium-potassium ATPase plays a key role.
When he conducted the same experiment but blocked the enzyme in ALS astrocytes using digoxin, the
normal motor nerve cells survived. Digoxin blocks the ability of sodium-potassium ATPase to eject
sodium and bring in potassium.
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Chronic Migraine: Definition & Treatment
Hassan Paknejad
Neurology department, Alborz University of Medical Sciences, Karaj, Iran
Globally, the top three causes of consultation for headache, in both primary and specialist care, are
migraine, tension-type headache and the combination of these (WHO headache atlas, 2011). Tension-type
headache is the more prevalent disorder worldwide, but consultation frequencies overall for migraine
and tension-type headache only partially reflect this difference. Migraine is associated with a higher
probability (per person affected) than tension-type headache of consultation for head ache, and more so
in specialist than in primary care. Primary-care physicians, almost universally, are consulted more often
for tension-type headache, which almost certainly reflects its greater prevalence. Specialists on the other
hand see more migraine, probably a reflection of its relative severity (greater individual burden). Chronic
migraine is defined as Headache occurring on 15 or more days per month for more than 3 months, which
has the features of migraine headache on at least 8 days per month (IHS III). It can be sometimes
interchangeably missed with Medication-over use headache (MOH). Around 50% of patients apparently
with chronic migraine revert to an episodic migraine subtype after drug withdrawal; such patients are in
a sense wrongly diagnosed as chronic migraine. Equally, many patients apparently overusing medication
do not improve after drug withdrawal, and the diagnosis of Medication-overuse headache may in a sense
be inappropriate (assuming that chronicity induced by drug overuse is always reversible). Also, we
should notice "CHRONIFICATION" in the field of headache, as a new term using recently in different pain
disorders, which has special risk factors, predisposing factors, special treatment discipline.
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Neuroimaging in Headache: Where, When and How
Seyed Ehsan Mohammadianinejad
Neurology Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Since headache is the most common presenting complaint in outpatient clinics, the routine order of
imaging is not cost effective and logical. There is also the concern of missing an important cause even in a
very small number of patients with typical primary headache disorder. Considering ‘Red Flags’ as the
basis for this decision is helpful. Chronic daily and new daily persistent headaches are among the red flags
which mandate neuroimaging until we are certain that the problem is a primary benign headache. In
adult patients with typical migraine according to IHS criteria, the routine use of neuroimaging is NOT
warranted. However the final decision to image is left to the physician on a case-by-case basis. The
presence of atypical features may raise the suspicion of a secondary cause for an apparently primary
migraine headache which is then called as secondary migraine headache. It is very important to consider
the best imaging modality according to an oriented and precise history and clinical examination. The
request of a standard brain MRI or CT may easily miss a serious cause of headache which may be
detectable by other imaging modalities. MR Angiography should be part of evaluation of any patient with
thunderclap headache, family history of aneurysm and continuously ipsilateral or progressing headache
suggesting extracranial artery dissection. Early diagnosis of cervical artery dissection is possible based on
timely ordering angiography in any patient with unexplained progressive unilateral head and or neck
pain. In pregnancy MRI is preferred but contrast should be avoided because there is concern of a serious
complication called as nephrogenic systemic fibrosis in the fetus. Use of MRI with contrast, though has
limitations, should be regarded in selected conditions where it provides diagnostic clues Incidental
findings are structural abnormalities or anatomic variants that are unexpectedly discovered during a
neuroimaging study in patients with headache but are unrelated to the complaint. They are rarely if ever
the cause of headache except when the cysts are so large to produce mass effect or obstructive
hydrocephalus or when venous anomalies or telangiectasias are associated with other vascular
malformations such as cavernous angioma with hemorrhage. So correct interpretation and discussion
with the patient is important to lessen the anxiety and to avoid unnecessary additional diagnostic
procedures.
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Myasthenia Gravis Update
Mohammad Kian Salajegheh
Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts,
USA
Neuromuscular junction (NMJ) disorders are a group of neuromuscular diseases that present with pure
motor weakness that may fluctuate from time to time, and worsen with certain triggers. Myasthenia
gravis, the most common disease within this group, is due to immune attack against the NMJ, most
commonly the acetylcholine receptors (AChR). It usually presents with ocular, bulbar and proximal more
than distal extremity muscle weakness that worsens with prolonged use. Diagnosis is made by identifying
the characteristic pattern and demonstrating abnormalities on confirmatory testing. These include
decremental response on slow repetitive nerve stimulation (RNS), the presence of blocking, or abnormal
jitter, on singe fiber EMG (SFEMG) as well as identification of serum antibodies against NMJ components.
Treatment includes the use of choline esterase inhibitors (CEI), as well as prednisone and other
immunosuppressive, with more recent and targeted studies being explored through multi-centric studies.
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Visual Rehabilitation in Neurology
Behzad Mansouri
Section of Neurology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
Stroke rehabilitation is the current standard of care in many developed countries. Though highly
commonplace now, the restoration of neural circuits through perceptual training and motor exercise is a
relatively new practice. The mechanism of stroke was first described in 19th century though stroke
rehabilitation was introduced to medicine in mid 20th century. Before the 1950’s, stroke patients were
instructed to rest and hope for spontaneous partial recovery of function. The shift to strenuous repetitive
training as a therapeutic approach was arduous and slow to take hold. It was decades before
rehabilitation became the standard of care. Partial cortical blindness and other visual deficits affect a
large portion of stroke and traumatic brain injury (TBI) patients, which severely lowers quality of life.
Today’s approach to visual deficit is comparable to that of the pre-stroke rehabilitation of motor function
era. There is no standard therapeutic intervention for visual rehabilitation. Patients are simply instructed
to wait and hope for spontaneous recovery. Over the last two decades, there has been speculation of the
plasticity of the visual system and how it pertains to the potential for recovery of function. There have
been many attempts in developing medical equipments to expand the visual field and increase the
patients’ visual confidence and quality of life. The mechanism of visual expansion is hotly debated due to
inaccuracies of eye fixation and artifact control. However, it can be argued that visual rehabilitation holds
clinical value due to consistent patient satisfaction after intervention. Visual plasticity and perceptual
learning have been investigated extensively in the last two decades. However, visual rehabilitation
development is in its infancy. More research is needed to study the effect of multi-sensory visual
rehabilitation and its use in combination with other therapeutic methods such as transcranial electrical or
magnetic brain stimulation. Restoration visual rehabilitation should be used as a complement to
compensatory training i.e. frequent saccadic eye movement, and use of prisms to expand the spared
visual field, in order to provide an all-encompassing rehabilitation of visual function. It can be expected
that in time, visual rehabilitation will become the new standard of care within a multidisciplinary setting.
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An overview of PML in MS disease modifying
Vosughi R
Health Sciences Centre, Winnipeg, Manitoba, Canada
“Treating Multiple Sclerosis is becoming more and more challenging for the neurologists. Although having
multiple therapeutic choices certainly add to complexity of treatment, serious and sometimes life
threatening side effects of disease modifying drugs (DMDs) make it harder to balance the benefit of
treatment options against their harms. In this presentation, we review available literature about
Progressive Multifocal Leukoencephalopathy (PML) related to MS therapeutics: its risk with different
DMDs, risk stratification, approach and treatment.”
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An Update on Proton MR Spectroscopy of Brain
Zamani AA
Department of Radiology, Brigham and Women's Hospital, Boston, MA 02115, USA
Thirty years after introduction of clinical MRI into the practice of radiology, MR spectroscopy has evolved from
a research tool into a clinical imaging modality. Many centers now incorporate MRS with clinical MRI in
evaluation of a wide range of neurological diseases. With widespread use of 3T MR unit MRS has received a
new boost. With availability of 7T and 9.4T magnets in a few centers, MRS promises to allow detection of many
more metabolites and hopefully, assist in clinical decision making.
ADVANTAGES OF 3T over 1.5T: There is increased signal to noise ratio. There is also more chemical shift with
3T therefore allowing better separation of metabolites. This has allowed separation of glutamine from
glutamate and identification of GABA. Measuring Glutamate/ glutamine has allowed investigators to study the
glutamate/ glutamine in superior temporal lobe of schizophrenic patients. Being able to identify GABA, a
neurotransmitter has opened the door into investigation of many disorders including psychiatric disorders.
Identification of additional metabolites: Besides the usual metabolites (NAA, choline, creatine, myoinositol,
glutamate/glutamine and lactate), MRS is able to detect other metabolites such as alanine in menigiomas,
taurine in PNET and glycine in high -grade pediatric tumors. Deelchand et al report identification of 19
metabolites with 9.4 T. Detection of 2HG in gliomas is an important finding that is helpful both in diagnosing
and also in prognostication.
Isocitrate dehydrogenase enzyme exists in the cytoplasm (IDH 1) and in the mitochondria (IDH2) and converts
isocitrate to alpha-ketoglutarate. Recent studies have shown that the genes that encode this enzyme can
undergo mutations in 68-86% of grade II and III gliomas, as well as in some secondary GBMs. This mutation
causes accumulation of 2 -hydroxyglutarate (2HG) in cells. Detection of this compound is difficult as the peak
due to 2HG overlaps the peaks for glutamate and glutamine, normally abundant metabolites. Investigators,
however, have found a way of achieving this. At our institution, an echo time of 97 msec is used to optimize
visualization of this peak. Patients with IDH1 mutation have a better 5-year survival compared with those that
do not. Therefore detection of this mutation via spectroscopy may have prognostic value. On the other hand
such a mutation is relatively common so detection of 2HG via MRS is used as a differential diagnosis point in
favor of diagnosis of gliomas as this mutation is not seen in other entities. It is hoped that in the future other
metabolites will be found that will have similar diagnostic and prognostic value in other brain tumors.
MRS IN METABOLIC DISEASES: Inborn error of metabolism lends itself to MRS investigations. Examples of this
include increased NAA in Canavan disease and absence of creatine in guanidinoacetae methyl transferase
deficiency. In ornithine transcarbamylase deficiency, an enzyme in urea cycle, hyperammonemia is seen.
Ammonia is changed into glutamine in the liver. Glutamine can be detected with MR spectroscopy. With proper
treatment this peak will decrease and therefore, the course of the disease and success of treatment can be
monitored with MRS.
MRS IN NOTHER ENTITIES: In perinatal hypoxia-ischemia quantitative measurement of lactate is an early sign
of brain injury. If the lactate remains high persistently, it is an indication of poor prognosis. With widespread
use of DWI in early detection of acute infarction, MRS does not have an important role in these entities.
Diagnosing tumefactive MS with MRS is difficult as the MRS picture is not distinguishable from that of a
neoplasm.
PROBLEMS WITH MRS: Despite its availability over thirty years, MRS is considered an “investigational tool” by
many insurance companies and government agencies. This leads to lack of reimbursement and underuse. The
problem has its root in lack of standardization and lack of a consistent methodology and interpretation. The
choice of technique is a problem for the inexperienced imager. Each one of the techniques (single voxel, vs.
chemical imaging vs. whole head volume imaging) had its own advantages and disadvantages. The American
college of Radiology has created a set of guidelines to help with this choice and to ensure diagnostic studies are
generated. The individual imagers using spectroscopy should discourage the referring physicians from
ordering spectroscopy if MRS is doomed to failure. Most importantly, MRS does not work if the lesion is too
small and if it is near the skull base, sinuses, etc.
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Transition of Epilepsy from Children to Adults: Definition, Epidemiologic and Social
Aspects and Models of Transition Clinic
Jafar Mehvari
Isfahan Neurosciences Research Center, Isfahan, Iran
Definition: Overall 50% of children with epilepsy will become adults with epilepsy, which may last for
their entire Lives. Pediatric epilepsy syndromes and their treatment involve special concerns.The issue of
transfer/transition for children with chronic disease to adult medical care is receiving increasing
attention as more children with chronic diseases survive to adulthood and require special lifelong
treatment.Although the terms “transfer” and “transition” are often used interchangeably, they have very
different connotations.Transition is a process to prepare youth for adult health care.It involves learning
about the diseaseand its manifestations, about medications and how to handle them, when and how to
seek help, and how to manage problems to minimize the effect on normal adult life.Transfer is the formal
handing over of care from pediatric to adult health care providers.
Three broad groupings of patients with epilepsy will achieve transition/transfer. The first group has
epilepsy that begins early in life and persists. Many of these patients have concomitant intellectual
disability and complex causes for their disorders, particularly genetic. These young adults with epilepsy
have little expectation for independent living and will require various degrees of supervision. The second
group of patients develop epilepsy in adolescence, with a small likelihood of remission. Focal epilepsies
and juvenile myoclonic epilepsies predominate, and intellectual function is typically normal. A third
group of patients are children with epilepsy whose seizures remit completely in childhood, and yet are
left with comorbidities. Examples are childhood absence epilepsy, “benign” rolandic epilepsy, or
nonlesional focal epilepsy. Unlike the other two groups, these patients may not require expert epilepsy
care because their epilepsy is rarely active in adulthood.
Epidemiologic aspects: In the Finnish population-based cohort of patients with childhood-onset
epilepsy followed for 37 years on average, approximately 33% of cases had seizures during adulthood
and 19% never experienced remission.
Similar observations were made in the Nova Scotia population-based cohort, represented by children and
adolescents with epilepsy followed for to 30 years.In this cohort, 25% of patients with idiopathic
Generalized epilepsies with tonic–clonic seizures did not attain seizure remission.Among patients with
CAE, 35% were not in remission at last follow-up.Fifteen percentof the total childhood absence cohort
had progressed to juvenile myoclonic epilepsy (JME).Factors predicting no remission included cognitive
difficulties at diagnosis absence status prior to or during AED treatment, development of generalized
tonic–clonic or myoclonic seizures after onset of AEDs, abnormal background on initial
electroencephalography (EEG), and family history of generalized seizures in first-degree relatives.For
those with JME followed for >20 years, all seizure types had remitted in 17%, and myoclonic seizures
persisted in only 13%.15 All children with BECTS followed for 30 years after diagnosis experienced
terminal remission.Intellectually normal children with focal epilepsies not fitting into specific syndromic
categories from the same cohort were also followed for 25–30 years.43% of the partial complex group
was not in remission versus 19% of the secondary generalization group.
The partial complex group was more likely to be intractable or to have undergone epilepsy surgery. There
have been several clinical factors identified as predictors of no remission. The most consistent are
associated neurologic deficits, intellectual disability, initial high seizure frequency with poor response to
the first AED, onset at age <1 year or older than 10–12 years, and “remote symptomatic etiology.” A
“causative” lesion on magnetic resonance imaging (MRI) also predicts failure of remission, although it is
not absolute and may still be associated with remission. Combinations of risk factors may improve
prediction. The majority of patients with idiopathic generalized epilepsies also had an adverse social
outcome, which included the following: psychiatric diagnosis (27%), no high school graduation (40%),
pregnancy outside stable relationship (38%), living alone (23%), unemployment (33%), or criminal
conviction. It was found that adverse outcomes were also significantly more common in patients with
partial complex seizures. During follow-up, >50% of patients had difficult-to-control seizures and
learning and psychiatric/social problems.For those with BECTS, however, the social outcome was similar
to the general population. Approximately 20% of childhood epilepsy is associated with intellectual
disability noted during a child’s early, development. Cognitive impairment may also reflect effects of
antiepileptic drugs.30 Individual AEDs exhibit different cognitive profiles. The death risk in epilepsy is
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inversely correlated to the age at seizure onset, associate neuro-disability or underlying brain condition,
to sudden unexplained death.
Models for transition clinics: Models of care for transition and transfer vary around the world, with no
objective way to indicate which approach is most effective. One transition/transfer model will not suit all
contexts. Specialist emphasize a few basic concepts that should facilitate transition and a successful
transfer to avoid a gap between pediatric and adult care. To develop transition program, the first step is
identification of adult neurologists and epileptologists who are willing to care for these special patients.
Joint pediatric/adult transition clinics may be the most effective system
Canada: Most transition/transfer consists only of a referral letter written by the pediatric neurologist to
an adult Epileptologist. The patient is then seen in the adult setting without further communication. The
adult Epileptologist communicates with the family physician and may, out of courtesy, send a copy of this
note to the pediatric neurologist. Further follow-up by the adult Epileptologist/ neurologist often
depends on the patient being referred back by the family physician. This traditional transfer system
hasshortcomings. Prior to transfer, the patient and family need to understand clearly when a
reassessment is warranted.
Transition in France: The model involved a single, dedicated adult neurologist who was assigned to take
over the follow-up as young people with severe epilepsy grew into adultsTransfer included a transfer
summary from the pediatric epilepsy service plus complete access to all of the pediatric medical records.
There is a sense that transfer should occur in early adolescence without waiting for complete or nearly
complete seizure control.There is an attempt to create an adult multidisciplinary team for persons with
multiple disabilities
Transition in the United Kingdom: There are four options for the continuing management of a young
person at this stage. First, to be discharged back to their general practitioner; second, to remain under the
care of the pediatrician or pediatric neurologist; third, tobe referred to an adult physician or neurologist
(neither of whom may have expertise in epilepsy care); and fourth, to be seen in a dedicated epilepsytransition service.The benefit of this final option is that this operates separately from a pediatric or adult
clinic and can provide continuity of specialist epilepsy care that is not only adolescent-specific, but is able
to address specific evolving adult is transition.
Driving and Exercise: Driving: Evaluation of diagnosis, seizure control, comorbid neurologic disorders
including attention-deficit/hyperactivity disorder (ADHD) and intellectual ability, as well as risk-taking
behaviors needs to be considered when advice regarding driving is given. Information on local driving
regulations and legal liability needs to be provided. Exercise: There is uncertainty if people with epilepsy
are more sedentary than the rest of the population. Exercise rarely exacerbates seizures, and there is
limited evidence that it may improve seizure control.Exercise often improves the comorbidities of anxiety
and depression.Transition discussions can advocate exercise while offering some guidance about safer
activities
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111
Transition issues in benign epilepsies, monogenic epilepsies and neurocutaneous
disorders
Sanaz Ahmadi Karvigh
Tehran University of Medical Sciences, Tehran, Iran
There are many monogenic disorders associated with epilepsy that begin in childhood and persist into
adult life and every day with developments in genetic assessments more and more of these disorders are
introduced. Some of these patients will have well controlled isolated seizures and others may have other
progressing comorbidities. These include psychiatric features, intellectual disability, migraine, movement
disorders, musculoskeletal features such as spasticity and extrapyramidal features, and scoliosis. Specific
genetic disorders may show different seizure patterns in adult life compared with childhood. In the
transition clinic, a full reevaluation is essential when any patient with an epileptic encephalopathy
transitions to adult care. The reason is that an etiologic diagnosis may never have been made, and the
investigations have often been performed many years ago when the current modern techniques were not
available. Understanding the genetic cause is likely to inform understanding of comorbidities, prognosis,
genetic counseling and therapeutic choices.
The group of genetic epileptic encephalopathies is expanding, with new genes being identified at a rapid
rate. These often arise secondary to a de novo mutation in the patient and can have various prognoses.
The best characterized adult phenotype is for Dravet syndrome. Seizures often continue into adult life,
but the pattern changes from frequent episodes of status epilepticus to weekly or monthly brief
convulsions in sleep.
Movement disorders are associated with specific monogenic epilepsies and, in some instances, occur at an
age that is different from when the seizures present. It is noteworthy that, obtaining a history of either
paroxysmal exercise induced dyskinesia or paroxysmal kinesigenic choreoathetosis can be challenging
and patients often modify their lifestyle to avoid attacks and do not discuss them. Therefore, it is essential
that the physician specifically addresses these issues in the transition clinic in the reevaluation phase.
On the other hand, in transition clinics more benign epileptic syndromes with normal anatomic imaging,
neurologic examination, and intellectual ability may be encountered. Although the benign epilepsy of
childhood with centrotemporal spikes (BECTS) and the majority (65%) of those with childhood absence
epilepsy (CAE) are epilepsy syndromes that enters terminal remission before the general age of a planned
transition of adolescents( 16 years), approximately 15% of patients with CAE who initially remit during
their childhood years later develop juvenile myoclonic epilepsy (JME) as teenagers and less than 2% of
patients with BECTS may have a more severe course associated with treatment difficulties prior to
terminal remission, at times with a rare evolution to an epileptic encephalopathy. All the same, due to
total remission and lack of significant future social and cognitive disabilities usually no transition plans
need to be made for BECTS patients.
In contrast, a significant minority of the nonlesional focal epilepsy in otherwise normal children (NLFN)
(~35%) and most patients with JME continue to have active epilepsy into adulthood. The risk of relapse
in NLFN is low once total remission has been achieved: <1% per year and usually occurs in those who had
needed several AEDs to control the seizures (refractory epilepsy). In addition, some cognitive disorders
are reported in several large case series in CEA and JME patients that include subtle cognitive deficits and
linguistic difficulties, which are frequently complicated by ADHD or associated with affective/anxiety
disorders. There appears to be a greater risk with longer illness duration and higher seizure frequency.
More importantly, these CAE, JME, and NLFN transition patients are at risk of a number of significant
adverse social outcomes that require ongoing advice and counseling.
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112
New conception about pathogenesis of refractory and super-refractory status epilepticus
Ghaffarpour M
Iranian Center of Neurological Research, Imam Khomeini Hospital, Tehran, Iran
Refractory status epilepticus (RES) is defined as recurrent seizure activity despite two appropriately
selected and dosed antiepileptic drugs, including a benzodiazepine. In a prospective study (Novy J et al
2010), 23% of patients admitted to the hospital with status epilepticus (ES) were considered to have RSE
and retrospective studies Suggested that 31%-43% of SE episodes become refractory. The term “SuperRefractory status epilepticus (S-RSE)” was first introduced in April 2011, and defined as continuous or
recurrent seizures 24 hours or more following initiation of anesthetic agents; including cases in which
seizure control is attained after induction of anesthesia but recurs on weaning the patient off the
anesthetic agent. Approximately 9% of SE episodes fail treatment with first-line and second- line agents.
The RSE and S-RSE are unique in that, refractory Seizures are more likely to develop as a result of acute
brain injury rather than as a consequence of chronic epilepsy. RSE may also occur in previously healthy
patients, in whom SE develops de novo without a clear precipitant, referred new- onset RSE or NORSE. It
is important to understand how seizures become refractory. As status epilepticus continues, neuronal
damage and pharmacoresistancy become apparent after 30 minutes. The latter may be explained by
intensified "receptor trafficking” in which NMDA receptors at the cell surface increases and the number of
GABA receptors decreases secondary to receptor internalization. Other mechanisms include: 1)
Mitochondrial insufficiency, 2) Inflammatory processes, resulting in decreased integrity of blood brain
barrier, 3) Higher K+ levels, 4) Changes in gene expression, particularly those that encode multidrug
transporter proteins. P-glycoprotein (Pgp) was the first of these proteins, followed by multidrug
resistance-associated proteins (MRPs) and breast cancer-resistance protein (BCRP), and 5) reverberating
seizure activity between hippocampal and parahippocampal structures. In This lecture we will review
further details about pathogenesis, treatment and outcomes of RSE and S-RSE.
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113
Starting, Stopping and switching in treatment of MS
S.M.Nabavi
Neurology Department, Shahed University, Tehran, Iran
Cell Therapy Center, Royan institute, Tehran, Iran
In this teaching course we will review the possibilities of starting of disease modifying therapies in
multiple sclerosis (MS) and clinically isolated syndrome (CIS). Also we will discuss the definitions and
options of suboptimal response to therapy or treatment failure in MS. We will explain the different lines
of therapy in MS and some considerations in the sequencing or switching of therapies. Finally we will try
to explain the different scenario in stopping of MS drugs.
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114
Isotope Scanning and Neurology Practice
Arman Hassanzadeh-Rad
Department of Nuclear Medicine, Research Center for Nuclear Medicine, Shariati Hospital, Tehran University
of Medical Sciences, Tehran, Iran
In Nuclear Medicine various procedures are used for assessment of neurological function. In SPECT/PET
imaging, after injection of gamma-emitter or positron –emitter radiotracers, multiple projections are
acquired and then processed with either Filter Back Projection or Iterative Reconstruction methods to
provide functional transaxial, sagital and coronal slices as well as 3-D reconstructed format of brain.
Planar imaging is also used for specific indications like CSF-imaging and Brain Death evaluation. One
important clinical indication of nuclear medicine in neurology is evaluation of perfusion and metabolism
in dementia, making a scintigraphic diagnosis of type and severity of dementia in equivocal cases as well
as patients with Mild Cognitive Impairment and assessment of response to treatment. Post traumatic
brain injury and its impact on brain perfusion can also be evaluated by brain perfusion imaging agents
(e.g 99m-Tc-ECD, 99m-Tc-HMPAO). One example is finding hypoperfusion in orbitofrontal cortex in
patients with post-trauma hyposmia/anosmia. Localization of epileptogenic foci in patients with
refractory epilepsy is another aim of nuclear medicine imaging techniques, obtained by either
ictal/interictal perfusion SPECT imaging, or interictal FDG-PET imaging. As a guide for thrombolytic
therapy in acute cerebrovascular events, quantitative brain perfusion scan can aid in both decisionmaking and predicting patient’s outcome. CSF imaging for diagnosis and characterization of different
types of hydrocephalus (communicating/non-communicating) and in particular, intraventricular
obstruction from hemorrhage,tumor, aqueduct stenosis or communicating hydrocephalus of Normal
Pressure Hydrocephalus can be quite informative, providing incremental information. Assessment of
ventriculoperitoneal shunt patency and CSF leakage are other applications of nuclear medicine
scintigraphy. By introduction of new imaging techniques and development of new radiotracers, clinical
indications of nuclear medicine are emerging rapidly. One good example is Parkinson’s Disease
evaluation and differentiation from other syndromes with tremor by PET-CT assessment of basal ganglia
synaptic activity with18-F-FDOPA or SPECT-CT evaluation of dopamine transporter activity with 99m-TcTRODAT imaging agents. Nowadays, a lot of radiotracers and imaging techniques, used to be research
tools, are becoming established parts of clinical applications of nuclear medicine in neurological
disorders.
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115
Surgical Management of Idiopathic Intracranial Hypertension
Behzad Mansouri
Section of Neurology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
The prevalence of Intracranial Hypertension (IIH) has increased in the past decade, following the obesity
epidemic. A direct dose-relationship has been demonstrated between increasing BMI or weight gain (>515%) and an increased risk for IIH. IIH remains a diagnosis of exclusion and IIH-related visual loss and
headache requires medical and surgical management. The medical management of IIH involves (A)
investigating and treating the possible causes such as medications (e.g. steroid withdrawal, lithium,
tetracyclines, and vitamin A analogs), Systemic conditions (e.g. obstructive sleep apnea, renal failure,
coagulopathies, and anemia), (B) weight loss and (C) medications (e.g. Acetazolamide, Topiramate or
Thiazides). If maximum medical management fails the patients require surgical intervention i.e. optic
nerve sheet fenestration (ONSF) or ventriculo-lumbo/peritoneal shunting (VPS and LPS). The former
(ONSF), is reserved for patients with predominantly visual symptoms. VPS or LPS are indicated in
patients with mainly headache (with or without visual loss) though headaches should not be the sole
indication for shunting. Stereotactic placement of programmable valve for VPS are preferred. Ultimately,
the decision for which surgical procedure is best in IIH remains surgeon and institution dependent based
upon the local surgical expertise and availability.
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116
Blood pressure management in acute stroke
Amiri F
Iran University of medical Sciences, Tehran, Iran
Introduction and Pathophysiology
Blood pressure (BP) is largely a surrogate for cerebral perfusion pressure (CPP). During acute ischemic
stroke, cerebral blood flow (CBF) is predominantly influenced by mean arterial pressure (MAP), as
intracranial pressure changes are negligible. A number of other physiologic factors also influence CBF,
including oxygen and carbon dioxide partial pressure, cerebral metabolism, temperature, and blood
viscosity. CBF is kept relatively constant across a wide range of perfusion pressures by adjustments in the
diameter of vessel resistance, in a process known as autoregulation. In healthy subjects, autoregulation is
maintained over a range of CPP (50–150 mm Hg); however, when autoregulationis lost, the relationship
between CPP and CBF becomes more linear. As a result of occlusion or severe stenosis, resistance to flow
increases, and dilation of arterioles compensates by lowering resistance to flow in the downstream
arterial bed. A complex series of events, many of which are mediated in part by nitric oxide, ensures CBF
compensation for changes in MAP. One of the many effects of ischemia on brain tissue is the loss of
autoregulation. In this setting, CBF changes directly with alteration in MAP, rendering ischemic brain
vulnerable to minimal variation of the systemic BP. Furthermore, arteriolar tone and consequent changes
in CBF are the result of change in the local physiologic milieu, manifested by changes in factors such as
extracellular potassium concentration and sustained depolarization. The loss of autoregulation during
cerebral ischemia has been extensively demonstrated both in humans1 and in nonhuman primates. PET
and autoradiography shed light on the series of events that follow cerebral ischemia. In particular, in
several species, including humans, several other compensatory mechanisms occur upon reduction of CBF,
such as increase in cerebral blood volume, increase in oxygen extraction fraction, and decrease in oxygen
consumption. A detailed description of these important phenomena is beyond the scope of this review. In
brief, as CBF decreases within the cerebral tissue affected by ischemia, there are regional variations in the
execution of these compensatory mechanisms, depending on degree of ischemia, duration of ischemia,
degree of collateral circulation, and phylogenetic susceptibility to ischemia of a particular neuronal
subpopulation. As a result of these events, the ischemic tissue is divided into a core and a penumbra. The
core is considered to be tissue already severely damaged by ischemia and most likely destined to
infarction. The penumbra is the ischemic area surrounding the core that has the potential for recovery
upon restoration of normal CBF values. On the basis of these data, adequate levels of MAP play a critical
role in the survival of the penumbral tissue. Although the evidence is ample to suggest benefit of MAP
maintenance or its elevation during ischemia, it cannot be viewed independently of CBF. BP is a surrogate
for CBF and represents a transmural pressure that is distributed throughout the vascular tree.
Transmural pressure represents a potential negative influence on transmural rupture (cerebral
hemorrhage) and net bulk flow across capillary beds, thereby worsening cerebral edema (Starling’s
equation) and secondary organ injury to heart and lung. Currently it is unclear how to appropriately
weigh the benefits and risks to measure optimal outcome. The benefits and risks are not constant but
instead are interdependent on vessel diameter, transmural pressure, and possible transmural rupture.
Recommendation
1. Prospective studies are needed to evaluate CBF via imaging and physiologic continuous
monitoringafter BP manipulation during acute ischemia.
Natural history of blood pressure in acute ischemic stroke
In patients with ischemic stroke, as many as 60% of patients have a systolic blood pressure (SBP) greater
than 160 mm Hg. This elevation can persist for hours to days. Although some portion of elevated BP
might be due to a compensatory need to increase CBF, other factors such as stress, pain, discomfort, and
intrinsic hypertension likely play a role as well. Despite the etiology, BP has a tendency to normalize over
24 to 48 hours. With regard to stroke subtype, evidence suggests that lacunar stroke may be associated
with higher initial SBP16 than non-lacunar stroke. Consequently, lacunar stroke–associated BP may
decrease over 24 hours to a greater degree than non-lacunar stroke. Most data regarding the association
of initial BP on stroke outcome indicate a U-shaped curve. Patients with lower BP have worse outcome
than those with higher BP. Still, those patients with SBP greater than 180 mm Hg seem to have worse
outcome than those with BP in the 150 to 180 range. From the International Stroke Trial Registry, there
was either a 3.8% or 17.9% increase in early mortality for every 10–mm Hg change above or below 150
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mm Hg, respectively. Others have suggested that initial high BP predicts poor outcome only in
combination with impaired consciousness. However, other data suggest that initial BP is not associated
with mortality, but elevated BP over the ensuing 48 hours is associated with higher NIH Stroke Scale
(NIHSS) score and greater mortality. Whether or not high BP is a marker of disease severity or a
modifiable mediator with a direct mechanistic relationship to outcome is unclear. We propose that the
likely explanation is a component of both. At one extreme, increased BP is a secondary response to
cerebral ischemia. As the size and degree of ischemia increase, with individual variability, the BP may
increase to support perfusion. However, this response is pathologic, and, like cardiac ventricular
remodeling in response to chronic hypertension, this compensatory effort by the body can have
pathologic consequences (heart failure or brain failure). The period and setting of brain ischemia are
often confounded by other variables that may increase BP independently: anxiety, pain, fever,
inflammation, tissue plasminogen activator (tPA)–mediated hemorrhage. Ultimately, clarity with regard
to the role of BP rise in the setting of acute ischemia can be answered only with prospective, randomized
interventions. Such trials would need to have consistent management strategies for enrolled patients. It
should be noted that it is not clear whether systolic, diastolic, or mean arterial BP is superior for
determining outcomes. Although this is unproven, higher spontaneous initial BP might maintain CBF for
penumbral tissue. This elevation in BP places patients at an increased risk of hemorrhage, edema, and
secondary organ injury. Increased systemic BP increases systemic vascular resistance, thereby increasing
myocardial strain and oxygen demand. Increased resistance and myocardial strain can also lead to
pulmonary edema, especially in the setting of any volume overload. The correlation of high BP and
increased risk of intra cerebral hemorrhage is unknown. There was no association with BP and
hemorrhage in the European Cooperative Acute Stroke Study (ECASS) I, International Stroke Trial,
National Institute of Neurological Disorders and Stroke (NINDS), or Interventional Management of Stroke
trials. However, elevated BP is associated with intracerebral hemorrhage after administration of tPA,
streptokinase, or urokinase. Existing data support an increased risk of cerebral edema when there is
simultaneous high BP. The excessive risk of patients presenting with lower BP is likely secondary to
failure to maintain sufficient CBF for penumbral survival. Failure to maintain sufficient CBF is also
coupled with higher occurrence of larger stroke, cardioembolic stroke, and heart failure.
Recommendation
1.
Prospective studies are needed to determine the association of BP and the risk of hemorrhage,
cerebral edema, and secondary organ injury, which are based on stroke severity, neurologic
deterioration, infarct volume, and other factors associated with poor outcome.
Blood pressure management in the setting of thrombolytic and revascularization therapy
In the NINDS recombinant tPA trial, there was a similar incidence of hypertension in the placebo
recipients and tPA treated patients. Hypertensive patients treated with tPA who also received
antihypertensive medications had a less favorable outcome at 3 months. In contrast, treatment with
recombinant tPA in the NINDS trial was associated with greater BP reduction than placebo. Also, in
patients treated with recombinant tPA, higher SBP was associated with persistent occlusion, as assessed
by ultrasound, but without worse clinical outcomes at 3 months. Cause and effect cannot be inferred but
supported the hypothesis that elevated BP is required to maintain penumbral flow. This evidence is
supported by spontaneous reductions in BP after recanalization and increases in infarct volume in the
setting of large BP fluctuations without recanalization. Furthermore, hemorrhagic transformation after
thrombolytic therapy, consistent with recanalization and the potential for increased brain edema, was
associated with a trend toward lower SBP. Conversely, in the setting of thrombolytic therapy, there is
significant evidence supporting an association with elevated BP and intracerebral hemorrhage.
Recommendations
1. In agreement with the 2007 American Stroke Association Guidelines, SBP should be kept under 180
mm Hg and diastolic BP (DBP) under 105 mm Hg in patients who have received thrombolytic or
interventional therapy for the immediate postprocedure period. There are no data to suggest a particular
antihypertensive medication to use when it is necessary to lower BP. However, medications that can be
rapidly titrated are preferred.
2. Prospective CBF studies are needed to assess any relationship between arterial recanalization and BP
that could account for differences in collateral circulation.
3. Prospective randomized trials for BP treatment after recanalization therapy, either drug thrombolysis
or mechanical thrombectomy, are needed and should be stratified according to absence or presence of
recanalization.
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4. Prospective studies are needed to assess the natural history of BP in the setting of interventional
therapies. These studies should examine the association of infarct volume, volume of at-risk tissue,
collateral flow, recanalization flow, and location of vessel occlusion.
Lowering BP in acute ischemic stroke
Because of the direct relationship between CPP and MAP, lowering BP can diminish CBF to ischemic brain
tissue. In a multivariate analysis, accounting for NIHSS score and stroke location, BP reduction in the first
24 hours was independently associated with poor outcome. A Cochrane database review of trials aimed at
acute or subacute reduction of BP after ischemic stroke included 5 randomized trials and 218 patients.
There was insufficient evidence to support lowering BP in patients with acute stroke. In fact, 3
randomized trials testing nimodipine or _-blockers, BEST, INWEST, and VENUS, all had worse outcomes in
the active treatment group. Only interventions in BEST and INWEST were associated with BP lowering.
More recently, a trial of candesartan administration within the first 36 hours of stroke (mean time from
stroke onset to treatment _ 30 hours) compared to 7 days of placebo found no significant difference in BP
decline and a significant improvement in mortality and recurrent stroke at 1 year. The lack of effect on BP
reduction suggests a mechanism other than BP regulation for this protective effect. In another trial,
hypertensive (SBP _140 mm Hg or DBP _90 mm Hg) ischemicstroke patients were randomized to oral
lisinopril or placebo within 24 hours of stroke onset. These investigators found significant differences in
BP reduction without any difference in clinical outcome. This trial was not powered for clinical outcome.
It remains to be proven whether certain classes of antihypertensives might have beneficial effects on
stroke outcomes regardless of BP changes.
Recommendations
1. In agreement with the 2007 American Stroke Association Guidelines, for patients not receiving
thrombolytic or interventional therapy, BP medication should be withheld for the first 24 hours unless
SBP is above 220 mm Hg or DBP is above 110 mm Hg.
2. After 24 hours, BP medications may be restarted safely in a general stroke population, although there
are limited high-level data to support this recommendation.
3. Prospective outcome studies are needed to evaluate early initiation of BP therapy in the setting of
documented presence or absence of recanalization.
4. Studies are needed to determine whether hypertensive patients with persistent penumbra at 24 hours
benefit from the withholding or institution of antihypertensive therapy.
Induced hypertension
Because of the desire to improve CBF to penumbral tissue, either through a flow-limiting lesion or
through collateral circulation, several groups have attempted to induce hypertension in patients with
acute ischemic stroke. For this purpose, _-adrenergic agonists are an attractive choice, as selective
vasoconstriction of the peripheral arterial bed can be achieved without involvement of cerebral arteries.
In another report, hypertension was prospectively induced in 13 patients within 12 hours of
presentation. None of the patients had serious adverse events, and 54% had an improvement of at least 2
points on the NIHSS, attributable to the BP increase. In a retrospective report, ischemic stroke patients
with SBP _140 mm Hg were treated with hypertensive therapy (average time of stroke onset to treatment
_ 13 hours). Early improvement, defined as a 2-point decrease in NIHSS within 8 hours of therapy, was
seen in 19% of patients. Treatment was associated with 1 cardiac arrhythmia and 1fatal intracerebral
hemorrhage. Other studies of induced hypertension in the subacute phase, i.e., initiation within 7 days of
stroke onset, in patients selected for diffusion–perfusion mismatch have had mixed results. The only trial
that was randomized demonstrated a significant improvement in NIHSS score for induced hypertension.
It is unclear whether these subacute trials of induced hypertension apply in the acute periprocedural time
frame for endovascular treatment. Although there appears to be promise for induced hypertension in the
acute phase, it is unclear how best to select patients who might benefit and whether a benefit of improved
neurologic function will outweigh the potential complications of intracerebral hemorrhage, cerebral or
pulmonary edema, and myocardial infarction. Unfortunately, a prior study, Induced Hypertension for
Acute Ischemic Stroke, was terminated, in part because of poor enrollment.
Recommendations
1. Arterial hypotension (SBP _120 mm Hg) should be evaluated and corrected, given the strong
association with higher mortality.
2. Prospective, randomized trials evaluating induced hypertension are needed. Such trials should also
evaluate patient selection on the basis of presenting BP, presence of mismatch, CBF studies, timing of
induced hypertension, and agents used. Such trials should include location of vessel involvement, degree
of collateral circulation, extent of occlusion, and tissue at risk.
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Randomized trials
Only the Controlling Hypertension and Hypotension Immediately Post Stroke (CHHIPS) trial enrolled
patients no later than 12 hours from onset into a randomized BP arm. This arm will evaluate induced
hypertension in patients presenting with SBP _140 mm Hg. Although the remaining trials are important,
they are unlikely to address the question of how to manage the vast majority of hyperacute patients,
those typically within the 8-hour time window, who are undergoing an interventional procedure for
recanalization. Although not strictly a BP trial, the Safety and Efficacy of NeuroFlo Technology in Ischemic
Stroke (SENTIS) trial is currently randomizing patients within 14 hours to partial occlusion of aortic
outflow or best management. Data from deployment of this intra-aortic device, which spans above and
below the renal arteries, suggests that the procedure can elevate CBF without change in systemic BP.
Summary
Many patients with acute stroke present with hypertension. There are few data to guide the management
of BP within the first 24 hours. Substantial circumstantial evidence suggests that elevated BP might
provide needed CBF to penumbral tissue; however, this benefit is associated with higher rates of
intracerebral hemorrhage and edema, as well as secondary organ injury to the heart, lungs, and kidneys.
Those patients who present with hypotension or relative hypotension (SBP 120–140 mm Hg) are at
greatest risk for neurologic deterioration. This group likely has a complex interaction of large strokes and
substantial cardiovascular disease. In the absence of data, we agree with the current recommendations of
the American Stroke Association for acute management of BP and therefore have highlighted these
recommendations and suggested research efforts.
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117
Progressive supranuclear palsy
Roohani M
Iran University of Medical Sciences, Tehran, Iran
The term "multiple system atrophy" (MSA) encompasses three clinical syndromes: olivopontocerebellar
atrophy, Shy-Drager syndrome, and striatonigral degeneration. Striatonigral degeneration is now termed
MSA with predominant parkinsonism (MSA-P), and olivopontocerebellar atrophy is now termed MSA
with predominant cerebellar ataxia (MSA-C). The estimated annual incidence of MSA in the population
>50 years old is approximately 3 per 100,000. The mean age of onset ranges from 54 to 60 years. There
appears to be no racial or gender predilection. The main clinical features of MSA are akinetic-rigid
parkinsonism, autonomic failure, urogenital dysfunction, cerebellar ataxia, and pyramidal signs in varying
combinations. The motor features of MSA-P are characterized by akinesia/bradykinesia, rigidity, postural
instability, and/or an irregular jerky postural and action tremor. The motor features of MSA-C involve
predominant cerebellar dysfunction that manifests as gait ataxia, limb ataxia, ataxic dysarthria, and
cerebellar disturbances of eye movements. Dysautonomia is a feature of both MSA-P and MSA-C. Nearly
all men with MSA develop early erectile dysfunction. Other common early MSA symptoms include
increased urinary frequency, urgency, incontinence, or incomplete bladder emptying. Orthostatic
hypotension usually emerges after urogenital symptoms appear. The cause of MSA is unknown. Glial
cytoplasmic inclusions are the pathologic hallmark of MSA and contain alpha-synuclein, tau, and
ubiquitin. Typical sites of pathologic involvement include the putamen, caudate nucleus, substantia nigra,
locus ceruleus, pontine nuclei, inferior olivary nucleus, Purkinje cell layer of the cerebellum, and
intermediolateral cell columns.The diagnosis of MSA is based upon the clinical features. No laboratory or
imaging studies are diagnostic. Lack of sustained response to levodopa can help to distinguish MSA from
idiopathic Parkinson disease, but transient benefit from levodopa is observed in 30 to 50 percent of
patients with MSA. It is important to distinguish MSA from idiopathic Parkinson disease and other
atypical parkinsonian syndromes (progressive supranuclear palsy and corticobasal degeneration).
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118
New classification of dystonia
Habibi SA
Mashhad University of Medical Sciences, Mashhad, Iran
Dystonia is defined as a movement disorder characterized by sustained or intermittent muscle
contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are
typically patterned and twisting, and may be tremulous. Dystonia is often initiated or worsened by
voluntary action and associated with overflow muscle activation. Dystonia is classified along 2 axes: 1clinical characteristics, including age at onset, body distribution, temporal pattern and associated features
(additional movement disorders or neurological features); and 2-etiology, which includes nervous system
pathology and inheritance. The clinical characteristics fall into several specific dystonia syndromes that
help to guide diagnosis and treatment. We provide here a new general definition of dystonia and propose
a new classification. We encourage clinicians and researchers to use these innovative definition and
classification and test them in the clinical setting on a variety of patients with dystonia.
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119
Corticobasal Ganglionic Degeneration
Safa Najmi
Tabriz University of Medical Science, Neurology Department, Tabriz, Iran
Corticobasal ganglionic degeneration (CBGD) is a rare progressive neurological disorder characterized by
a combination of parkinsonisam and cortical dysfunction. CBGD appears to be closely related to another,
less rare, sporadic extrapyramidal degenerative disorder named Progressive Supranuclear Palsy (PSP). In
CBGD, cognitive symptoms dominate, while in PSP, eye movement symptoms dominate the picture. The
Parkinsonism is generally an asymetric akinetic rigid syndrome, unresponsive to levodopa. Eye
movement abnormalities are common. Neuroradiological imaging studies in CBGD demonstrate cortical
atrophy, which may be symmetrical or asymmetrical. Other cortical signs include: Alien limb
phenomenon, Apraxia, Dysphasia, Cortical sensory loss, and Pyramidal signs. Proposed diagnostic criteria
for CBGD include at least three of the following: bradykinesia and rigidity that does not respond to
levodopa, alien limb phenomena, cortical sensory signs, focal limb dystonia, action tremor, myoclonus.
The "alien limb" symptom is highly specific but it is not necessary for the diagnosis. Onset in the sixth or
seventh decade is typical. Disease progression is quicker than in Parkinson’s disease. Pathologically,
There is neuronal loss and gliosis and swollen achromatic neurons (ballooned neurons) are found in all
cortical layers, but especially so in superior frontal and parietal gyri. There is extensive loss of myelinated
axons in the white matter. Ballooned neurons are strongly reactive for phosphorylated neurofilaments
and may include the tau protein. Neuronal loss and gliosis are also observed in the nuclei of the basal
ganglia. Lewy bodys and neurofibrillary tangles are absent. The substantia nigra shows neuronal loss
with extraneuronal melanin, gliosis and neurofibrillary inclusions, called "corticobasal bodies". CBGD is
difficult to diagnose in early stages, and experienced examiners typically diagnose it correctly less than
50%. As more cortical signs develop in later stages, the disorders below may be possible to separate. As
diagnostic sensitivity is poor, neuropathological confirmation remains the gold standard. The most
important differential diagnosis are: Parkinson’s Disease, PSP, MSA and Pick disease. The cause of CBGD is
presently unknown but because the tau protein accumulates in this disorder, it may be related to a
mutation in the tau gene. Tau is a microtubule-binding protein that is normally abundant in neurons.
According to Di Maria et al (2000) and Houlden et al (2001), CBGD shares the same tau haplotype as do
PSP patients (see above), suggesting that both CBGD and PSP share the same genetic background, and
possibly the same pathologic mechanism.
Conventional Treatment: CBGD patients do not respond to levodopa. Management is based on
appropriate use of appliances, prevention of medical complications, and appropriate use of nursing.
Patients with CBGD and family should establish early on the plan regarding invasive care -- intubation,
feeding tubes, as these issues are almost certain to come up in the course of the disease.
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120
Oral therapy in MS: experiences with fingolimod
Behnaz Seddighi
Department of Neurology, Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran
Treatments of multiple sclerosis (MS) have undergone a revolution over the past 2 decades. The new
orally administered drugs approved for MS treatment represent significant therapeutic advances. The
oral route of administration clearly promotes patient satisfaction and increases therapeutic compliance.
Three oral drugs have been approved by regulatory agencies for the treatment of MS: fingolimod,
teriflunomide, and dimethyl fumarate.
Fingolimod (Gilenya®) (marela in IRAN)
Fingolimod is approved by the FDA for RRMS and in Europe by the European Medicines Agency (EMA) for
patients with RRMS and disease activity, despite first-line treatment, or in patients with evolving severe
RRMS. It is administered orally as 0·5-mg capsules daily. Fingolimod binds to sphingosine-1-phospate
(S1P) receptors on immune cells. Consequently, these immune cells are unable to egress from lymphatic
tissue, and subsequently into the CNS. Only lymphocytes that reside within secondary lymphoid organs
are affected, which account for approximately 2% of all circulating lymphocytes. In addition to the effects
on immune cells, there is emerging evidence that fingolimod may modulate S1P receptors in the CNS and
may reduce neurodegenerative processes.
The most common side effects of fingolimod are:
headache, flu-like symptoms, diarrhoea, back pain, liver enzyme elevations and cough. More severe side
effects such as cardiac complications are common, with an incidence between 1 and 10% of patients
treated with fingolimod. A first-degree atrioventricular block was reported in about 4·7% in patients
treated with 0·5 mg fingolimod. Other risks include a minor increase in blood pressure, decrease in lung
function, macular oedema and an increased frequency of viral infections, in particular varizella zoster.
Macular oedema may lead to progressive visual loss. In two Phase III trials, 13 patients developed
macular oedema, 10 of them within the first 4 months of treatment. Patients may report blurred vision or
decreased vision or may be asymptomatic. The incidence is about 0·4% in the 0·5 mg group, with a higher
incidence with patients with a history of uveitis. After termination of therapy, macular oedema usually
resolves spontaneously; (evaluation of the fundus ; prior to initiation of therapy, within 4 months after
onset of therapy and at any time of decreased visual acuity ). Eleven of the 13 patients with macular
oedema were administered a dose that is more than twice as high as the currently approved dose.
Cutaneous neoplasias were reported more often in the fingolimod group than in the IFN or placebo
control groups. Basaliomas and melanomas (in situ) were reported. (dermatology screening examination
before the initiation). In the context of one Phase II clinical trial, one MS patient died from varicella zoster
infection and consecutive hepatic failure, and another patient died from herpes simplex virus 1
encephalitis. A third patient was diagnosed with a life-threatening HSV encephalitis. All these patients
were treated with the higher, non-approved 1·25 mg dose. FDA and EMA currently recommend 6-h heart
monitoring with continuous ECG monitoring during the first administration of fingolimod. If bradycardia
occurs within the first 6 h, cardiac monitoring should be extended for another 2 h. The occurrence of
severe bradycardia, QTC interval prolongation, AV block II Wenckeback or AV block III requires overnight
observation. In patients with atrioventricular block II, significant QT-prolongation, symptomatic known
bradycardia or history of syncope, ischaemic heart disease or history of myocardial infarctions or
cerebrovascular infarction, uncontrollable arterial hypertension or congestive heart disease, fingolimod
cannot be recommended. Because of the first-dose cardiac side effects of fingolimod, cardiac monitoring
has to be repeated in all patients who experience a treatment hiatus of 14 days or longer. Additionally, the
EMA requires for repeated monitoring when the treatment is interrupted for 1 day during the first 2
weeks of treatment, or 7 days during week 3 and 4 of treatment. Moreover, the majority of cases with
macular oedema occurred within the first 3–4 months after onset of therapy. Patients may report blurred
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vision or decreased vision or may be asymptomatic. The incidence is about 0·4% in the 0·5 mg group,
with a higher incidence with patients with a history of uveitis. After termination of therapy, macular
oedema usually resolves spontaneously; (evaluation of the fundus ; prior to initiation of therapy, within 4
months after onset of therapy and at any time of decreased visual acuity).
Vaccination: during therapy with fingolimod may be less effective. Vaccination with live attenuated virus
vaccines should be avoided during, and 2 months after, fingolimod therapy as it may carry the risk of
infections. In addition, patients without a history of chickenpox or vaccination against varicella zoster
virus (VZV) should be tested for VZ antibodies. Vaccination is recommended 1 month prior to initiation
with fingolimod therapy in order to ensure immunization. Monitoring of therapy should also include
complete cell counts at initiation of therapy, months 1, 3 and 6 and in periodic intervals thereafter.
Fingolimod has been assigned to pregnancy category C by the FDA. If a patient becomes pregnant during
treatment, application of fingolimod should be terminated. Recently there were 1 report of PML.
Teriflunomide (Aubagio®)
Teriflunomide was approved in 2012 by the FDA for treatment of relapsing forms of MS. Teriflunomide
has anti-inflammatory properties. Teriflunomide is available in two doses: 7 or 14 mg once daily in the
United States and 14 mg in Europe. Adverse effects of teriflunomide include decreased white blood count
(WBC), and infections. Specifically, cases of tuberculosis were reported.
Polyneuropathy, renal failure, skin reactions, hair thinning and an increase in blood pressure have also
been observed. Teriflunomide is contraindicated in patients with severe hepatic injury. In the case of
immunodeficiency teriflunomide should not be administered.Vaccinations with live vaccines are not
recommended. Teriflunomide has been assigned category X by the FDA.
Dimethyl fumarate (Tecifidera®)
Dimethyl fumarate was approved by the FDA for treatment of RRMS, and on 21 March 2013. The CHMP at
the European Medicines Agency (EMEA) adopted a positive opinion for marketing authorization for
Tecifidera® 120-mg and 240-mg capsules for the treatment of RRMS. Flushing was reported in up to 40%
of the treated patients. In fewer than 1% of treated patients, flushing led to hospitalization.
Gastrointestinal side effects such as vomiting, abdominal pain, diarrhoea and dyspepsia were more
common in the dimethyl fumarate group when compared to the placebo group. Recently, there were two
reports of PML. Dimethyl fumarate has been assigned pregnancy category C.
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121
Rehabilitation protocols in MS: An Iranian guideline
Mojtaba Azimian
University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
Multiple Sclerosis (MS), is one of the progressive diseases which diffusely involves the central nervous
system and manifest different signs and symptoms. In modern therapeutic approach, not only the
immunomodulatory medications are administered, the rehabilitation approaches are stressed as well.
Rehabilitations are considered initially and protocols of better diagnosis and better prevention are
considered. This latter fact enables patient to have a better quality of life and social functioning from the
initial period up to the end. The harmonized cycle of prescribing suitable medical remedy based on the
appropriate guideline, will also benefit the patients likewise. Such unified success may be attributed to a
reasonable teamwork approach rather than an individually act. Team members may include physicians,
nurses, physiatrists, physical therapists, speech and language pathologists, psychologists, social workers,
recreation therapists, patients and their relatives, who have some correlations in such team work
therapy. The team can relate their experiences to assure a better and risk-free life for the MS patients.
Some possible MS complications, may be as follows:
1. Impairments, which includes the neurological symptoms of the disease
2. Disability, which declines the patient`s functional efficacy
3. Handicap, which the patient`s social participations are deteriorated
Manifestations and alternations of any following sign and symptoms, emphasizes the team intervention
based on a proper MS guidelines: fatigue, weakness, spasticity, balance and moving deterioration, pain,
cognition, mood, relationships, bowel and bladder function, swallowing, speech, sexual function,
recreation, employment, transportation, ADL (eating, bathing, dressing and household chores).
Intervention for alleviating any of the above issues, may be stated via guideline use. Each action, must be
standardized based on patients who belong to different background with different facilities. Recently, in
Iran the appropriate and native-made guidelines have been introduced, for a better and effective ways of
MS patients` treatment.
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122
Longterm Efficiacy of Beta-Interferons in Multiple Sclerosis
Thomas Berger
Clinical Department of Neurology, Medical University of Innsbruck, Austria
Multiple sclerosis (MS) is a potentially devastating inflammatory demyelinating disease of the central
nervous system (CNS) affecting approximately 1:1000 mainly young adults. Relapsing-remitting MS
(RRMS), characterized by an individual frequency of relapses, bears the risk of incomplete remissions and
further progressive disability, then termed as secondary progressive MS (SPMS).
A disease modifying therapy (DMT) describes a drug, which modulates MS disease course either as an
immunosuppressant or immunomodulator. Between 1995-2001 the first DMTs have been approved in
different countries to reduce relapses and, to some extent, delay disease progression. These standard (or
baseline) DMTs for RRMS include interferon-beta (IFNb) preparations (IFNb-1a 30 mg qw i.m., IFNb-1a
22/44 mg tiw s.c., IFNß-1b 250 mg qod s.c) In general, IFNb has a favourable benefit-risk profile, which
has been documented by longterm studies and postmarketing surveillance for more than 20 years. AE’s of
IFNb, such as injection-site reactions (including rare skin necrosis) and flu-like symptoms, usually depend
on application routes (i.m. << s.c.) and the drug itself, and are not serious, but may negatively impact
quality of life. Thus, in the treatment decision-making process we should recall that it is the patient, who
takes the risk – either for her/his potential MS disease consequences or potential DMT side-effects/risks.
Therefore, benefit-risk evaluations and perceptions are likely to vary among patients and between
patients and their physicians.
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123
Advanced Parkinson management with focus on role of Apomorphine
Angelo Antonini
Parkinson and Movement Disorders Unit, IRCCS San Camillo Hospital, Venice – 1st Neurology Clinic,
University Hospital of Padua, Italy
Apomorphine is the oldest dopaminergic medication and was initially known for its emetic properties. It
was initially used for Parkinson’s disease over 60 years ago but later ignored for many years following
levodopa introduction. It is also the most potent dopamine agonist and its administration can provide
symptom relief comparable to levodopa. Apomorphine exerts its antiparkinsonian effect by direct
stimulation of striatal postsynaptic dopamine D1 and D2 receptors. The drug has a rapid absorption after
subcutaneous injection (Cmax 20 min), and a short half-life (almost 43 min), and this is consistent with its
rapid onset of action, with effects apparent within 5–15 minutes of subcutaneous administration. Clinical
studies and evidence-based reviews generally support a role for apomorphine infusion as an effective
option for patients with PD and severe fluctuations, poorly controlled by conventional oral drug
treatment with an improvement in OFF-time between 50% and 80% as well as dyskinesia. While the
benefit on off time is consistent across all studies, dyskinesia improvement generally occurs after a few
weeks or months of continuous dopaminergic stimulation as a result of wider therapeutic window.
Moreover it can be best achieved with apomorphine monotherapy that may require high infusion doses.
Intermittent subcutaneous apomorphine (penjet) may instead be suitable for the long-term acute
treatment of OFF episodes in patients with advanced PD. Apomorphine injections can be a particularly
helpful in the management of patients who undergo surgical procedures and cannot take medication by
mouth or to treat additional severe non-motor symptoms occurring during OFF periods.
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124
Update ALS 2015
Reinhard Dengler
Department of Neurology, Hannover Medical School, Hannover, Germany
The presentation will deal with new scientific and clinical develepments in the field of amyotrophic
lateral sclerosis (ALS). In genetics, about 60 – 70 % of the mutations in familial ALS have been identified,
the most frequent being the C9ORF72 mutation. Similarly to other neurodegenerative disorders, ALS is
characterized by intracellular inclusion bodies. It could be shown very recently that they contain
aggregates of the protein TDP43 which may propagate from neuron to neuron in a prion-like manner.
TDP43 can also be found in cases with frontotemporal lobe dementia (FTLD) and it is now accepted that
about 30 % of ALS patients develop FTLD. The gold standard of ALS diagnosis are still the revised El
Escorial Criteria which have now been supplemented by the so called Awaji electrodiagnostic Criteria
(AC). The AC regard fasciculation potentials in EMG as a sign of active denervation like positive waves and
fibrillations. The detection of upper motor neuron signs in ALS may be difficult. Modern imaging is
currently not yet able to detect upper motor neuron involvement on an individual level. Special
techniques of transcranial magnetic stimulation may, however, prove helpful. Riluzole is still the only
drug approved for treatment of ALS. Unfortunately, clinical trials with various drugs in the last two
decades have remained unsuccessful. Great hope is now associated with cell transplantation and
nonsense oligonucleotides in familial ALS. Currently, however, symptomatic treatment is important to
improve quality of live including assistance in nutrition and respiration and finally palliation.
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125
Treatment of Neurodegeneration with Brain Iron Accumulation (NBIA)
Thomas Klopstock
Friedrich-Baur-Institute, Dept. of Neurology, Ludwig-Maximilians-University, Munich, Germany
Neurodegeneration with brain iron accumulation (NBIA) is a clinically and genetically heterogeneous
group of rare hereditary neurodegenerative disorders. The most common form, accounting for
approximately 50% of NBIA cases, is pantothenate kinase-associated neurodegeneration (PKAN). While
there is no proven therapy to halt or reverse any form of NBIA, symptomatic treatment including deep
brain stimulation can markedly alleviate symptoms. Beyond that, NBIA may be feasible for a causal
therapy as the accumulation of iron in the brain may be addressed biochemically by iron chelation.
TIRCON (Treat Iron-Related Childhood-Onset Neurodegeneration), an international collaborative project
funded by the European Commission´s Seventh Framework Programme, addresses this urgent and unmet
need for a therapy for NBIA/PKAN by conducting a randomized placebo-controlled clinical trial of the
iron chelator deferiprone in PKAN (duration per patient 18 months). The four study sites in Munich
(Germany), Oakland (USA), Milan (Italy) and Newcastle (UK) have already fully recruited this pivotal trial
by randomizing 89 PKAN patients. The last patient-last visit (LPLV) is scheduled for August 2016. An
extension trial, sponsored by the manufacturing company ApoPharma, has already started for the
patients who complete the randomized trial. Regular meetings of the Data Safety Monitoring Board
identified no major safety issues with deferiprone so far.
TIRCON has already succeeded in bringing together into one cohesive group the existing outstanding but
scattered expertise in NBIA research and care at the European and international level. Medical care and
research infrastructure have already noticeably improved, and the NBIA community is eagerly awaiting
the outcome of the therapy research outlined above.
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126
Normal Pressure Hydrocephalus: New Concepts in Diagnosis and Treatment
Saeed Ghazvinian
Neurology Department, Bank Melli Hospital, Tehran, Iran
Normal Pressure Hydrocephalus (NPH) was first described by Colombian neurosurgeon Salomon Hakim
in the 1960s and is thought to account for about 2-5% of dementia cases. NPH is an important entity to
recognize due is reversibility. The classic triad suggestive of NPH includes a gait disorder, cognitive
impairment and urinary incontinence. Among these elements, the gait disorder is most critical because it
is present in nearly all cases and can be helpful in making the diagnosis. The cognitive deficits are not
always dramatic and when present typically take the form of '' subcortical'' impairment. Despite the
classic triad, NPH can be challenging to diagnose considering how common these problems are in the
elderly and therefore how frequently they co-exist by chance. Because of this, the presence of NPH is best
judge as an estimate of the degree to which the hydrocephalus contributes to an individual patient's
disability. Accordingly, published guidelines recommended cases be classified as either probable NPH,
possible NPH or unlikely NPH. Management of NPH also is a challenge as not all persons who have the
syndrome respond well to treatment. Enlarge ventricles seen on CT or MRI are insufficient in predicting
who will be respond to surgical shunting of ventricles. More sophisticated neuroimaging techniques
based on ways of measuring CSF flow and hemodynamics are also sometimes employed. Depending on
the method of patient selection and how a favorable response to shunting is defined, the rate of positive
outcomes to ventricular shunting in NPH has been found to be in the range of 61-75%. New concepts
about pathophysiology, diagnosis and treatments of NPH will be discussed in congress.
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127
Survey of Autonomic Symptoms (SAS) questionnaire compared with Sympathetic Skin
Response (SSR) results in patients with diabetic autonomic neuropathy
Fariborz Khorvash, Majid Ghasemi, Mohammad Hosein Safari
Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
BACKGROUND: Diabetic autonomic neuropathy is a serious and common complication of diabetes. There
is a need to develop a simple instrument to measure autonomic symptoms in subjects with neuropathy
and to test the validity of the instrument. Using a questionnaire survey of autonomic symptoms (SAS) for
screening of diabetic autonomic neuropathy is a new procedure. Sympathetic skin response (SSR) is a
method for the study of autonomic nervous system. SSR was more often absent in patients with
symptoms of dysautonomia.
PURPOSE: Given the importance of diabetes and its complications autonomic, in this study, data obtained
from questionnaires SAS Scale test is compared with the SSR.
METHODS: This is a cross-sectional study. In patients with a diagnosis of diabetes with at least one
symptom of autonomic dysfunction, which were referred to the clinic of Neurology and Clinical
Endocrinology, after obtaining written informed consent, a SAS questionnaire was completed and SSR
was assessed by EMG recording. The Survey of Autonomic Symptoms (SAS) consists of 11 items in
women and 12 in men. Each item is rated by an impact score ranging from 1 (least severe) to 5 (most
severe).
RESULTS: The SAS was tested in 135 subjects with neuropathy and impaired glucose tolerance or newly
diagnosed diabetes. The average scores of SAS in patients was 16.82 (±12.62), the least of which was 1
and the maximum is 50, that was not significantly related to age and gender. Of the total patients, 60
(44.4%) had positive SSR response and 75 patients (55.6%) had a negative SSR response. In the
examining with independent T-test, there was a significant association between response of SSR with a
score of SAS (P<0.001). In ROC Curve Analysis, numeric value of the SAS score equal to 9.5 with a
sensitivity of 88% and specificity of 70% as the cutpoint and SAS score of 13.5 with 80% sensitivity and
90% specificity was obtained as a cutpoint for SSR response.
CONCLUSION: The SAS is a new, valid, easily administered instrument to measure autonomic symptoms
in early diabetic neuropathy and would be of value in assessing neuropathic autonomic symptoms in
clinical trials and epidemiologic studies.
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128
Trace blood elements and severity of Parkinson's disease
Ahmad Chitsaz, Rokhsareh Memar, Mohammad Reza Aghaye-Ghazvini
Isfahan University of Medical Sciences, Isfahan, Iran
BACKGROUND: Parkinson's disease (PD) is a degenerative disorder of the nervous system and it seems
that disturbances in trace elements homeostasis mediate progression of disease.
PURPOSE: The aim of this study was to compare the levels of trace elements (Fe, CU and Zn) in various
PD stage and assess their correlation with the severity of PD.
METHODS: Serum concentrations of trace elements were measured on Hitachi 902 biochemistry analysis
in 109 PD patients. Then severity of disease was evaluated according to Hohn & Yahr (HY) in four stages
of 1-1.5, 2-2.5, 3 and 4-5, and also motor part of unified PD rating scale III (UPDRS- III) were used.
RESULTS: All trace elements levels were within normal reference valves and did not differ significantly
between different HY stage (Fe: P=0.670, CU= 0.540, Zn=0.340: P=0.34). Only patients with higher HY
stage were older (P=0.026). When the severity of PD was evaluated by UPDRS-III only there were
significant association between age and severity of disease (P=0.024).
CONCLUSION: In this study, we confirmed only age as a factor that was correlated with severity of PD for
clarifying actual role of trace elements, in PD. However, more studies should be designed.
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Evaluation of the efficacy and safety of Vicia faba Extract in the treatment of patients with
Parkinson’s disease
Karim Nikkhah, Samira Aminzadeh, Ali Ghabeli Juibary, Hasan Rakhshandeh, Valyollah Kashki,
Mohammad Mahdi Charkhandeh, Hamid Sadeghian, Hamidreza Sadeghnia, Ali Shoeibi
Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
BACKGROUND: Parkinson’s disease (PD) is a chronic degenerative disease of the central nervous system
with no definitive treatment.
PURPOSE: We aimed to study the efficacy and safety of Vicia faba extract, as an easily accessible herbal
remedy, on different clinical findings of patients with Parkinson Disease.
METHODS: Twenty male and 10 female patients with definite diagnosis of PD, aged between 51 and 81
years, were enrolled in this clinical trial. PD was diagnosed based on clinical findings and on ruling out all
other causes of Parkinsonism.
RESULTS: Both Fava extract- carbidopa combination and conventional levodopa-carbidopa were
significantly effective in alleviating the main clinical findings of patients. There was no significant
difference between Fava group and levodopa-c group regarding improvement of rigidity, rising from
chair, gait disturbance, and postural instability of patients one week after consumption of the medication.
However, conventional levodopa-carbidopa was superior to Fava extract in reducing tremor at rest and
freezing. In both levodopa and extract group, serum levels were in therapeutic range (1-3 μgr/dl).
CONCLUSION: Despite the higher Levodopa serum level in patients who had received conventional
levodopa, those who had used Vicia faba extract showed almost the same clinical improvement with
significantly lower side effects.
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Association between sleep quality and cognitive status in patients with Parkinson's
disease without dementia
Narjes Sahebzadeh1, Arezou Farag Pour2
1-Faculty of Medicine, Mashhad Branch, Islamic Azad University, Mashhad, Iran
2-Shahid Beheshti University of Medical Science, Tehran, Iran
BACKGROUND: Sleep disturbances and cognitive impairment are two common non-motor symptoms of
Parkinson's disease (PD).
PURPOSE: The study aim was to evaluate the cognitive status and sleep quality and the association
between cognitive impairment and sleep quality as well as daytime sleepiness in PD patients.
METHODS: In this analytical cross-sectional study, 120 patients with PD were selected from 22-Bahman
and 17-Shahrivar hospitals. Demographic information was filled in the form and Parkinson severity was
determined using the Hoehn and Yahr scale (HY). Pittsburgh Sleep Quality Index (PSQI) and Epworth
sleepiness scale (ESS) were used for assessment of sleep quality and excessive daytime sleepiness,
respectively. Cognitive status was assessed by using Montreal Cognitive Assessment (MoCA)
questionnaire.
RESULTS: Mean age of PD patients was 65.9±11.7 yrs and 67.5% of them were male. Mean duration of PD
was 2.7±2.6 yrs. Majority of the patients were in stage I or II of the disease. Mild cognitive impairment
(MCI) was found in 113 (94.2%), poor sleep quality in 87 (72.5%) and excessive daytime sleepiness in 27
(22.5%) PD patients. Mean PSQI and ESS scores in PD patients was 9.03±4.70 and 7.38±3.73, respectively.
There was a significant association between cognitive status and sleep quality as well as daytime
sleepiness (p<0.0001).
CONCLUSION: There is a significant association between MCI and poor sleep quality. In addition
excessive daytime sleepiness and MCI is found in 100% of patients with sleep disorder. However, sleep
quality was not predictor of MCI. Therefore, assessment of cognitive status is recommended in all PD
patients with sleep disturbances.
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Improvement of spinal contusion model by cotransplanting bone marrow stromal cells
(BMSCs) and induced BMSCs into oligodendrocytes-like cells
Gholamreza Kaka
Neuroscience Research Center, Baqiyatallah University of Medical Science, Tehran, Iran
BACKGROUND: Demyelination is a common lesion in spinal cord injury. Cell therapy is one of the
approaches for replacing the lost oligodendrocytes. In this study, bone marrow stromal cells (BMSCs)
have been transdifferentiated into oligodendrocyte--like cells (OLCs) and used in cytotherapy of contused
spinal cords in rats.
METHODS: The BMSCs were collected from the rat long bones, and cultured and characterized by
different markers, then they were preinduced with dimethyl sulfoxide followed by retinoic acid, and then
the preinduced cells were induced with combination of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) and heregulin (HRG), followed by triiodothyronine (T3). The OLCs were
transplanted in the contused spinal cords of the rats, combined with undifferentiated BMSCs. Specific
markers were used in order to characterize the cells by immunohistochemistry and RT--PCR. The BMSCs
showed typical immnuoreactivity to the markers, and the OLCs were immunostained with specific
markers.
RESULTS: There was an improvement in BBB test with reduction in the cavitation in the contused rats
treated with OLCs combined with BMSCs. The transplanted cells were detected in the contused spinal
cord.
CONCLUSION: The combination of the transdifferentiated BMSCs into OLCs with the undifferentiated
BMSCs improved the contused spinal cord.
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The first study of COX-2 gene variants and risk of migraine in Iranian patients
Elahe Mozaffari1, Abbas Doosti1, Reza Nemati2, Morteza Makhlooei3
1-Biotechnology Research Center, Islamic Azad University, Shahrekord Branch, Shahrekord, Iran
2-Department of Neurology, Faculty of Medicine, Boushehr University of Medical Sciences, Bushehr, Iran
3-Department of Agriculture Science, Faculty of Agriculture, Boushehr Branch, Islamic Azad University,
Boushehr, Iran
BACKGROUND: Migraine is a common debilitating head pain disorder with reversible acute pain attacks
and complex etiology which associated to temporal changes of head blood vessels. It is characterized by
episodes of intense unilateral pulsating head pain and often associated with nausea, vomiting and
photophobia and phonophobia. It has two main types; migraine with aura and migraine without aura are
introduced by the International criteria for Headache Society (IHS).
PURPOSE: This study was performed to investigate the association between COX-2 gene polymorphisms
and the risk of migraine susceptibility and to discover its association with parent marriage types for the
first time in Iran.
METHODS: Genomic DNA of blood tissue was extracted from 100 migraine cases and 100 migraine free
subjects. The PCR was accomplished by the appropriative primers to amplification the slightly region of
COX-2 gene. Then expected fragments were digested with endonuclease restriction enzymes and the DNA
fragments were resolved by electrophoresis in 2% agarose gel.
RESULTS: There was a significant difference in the frequency of the COX-2-765G→C and COX-2-1195A→G
genotypes between controls and migraine cases (P≤0.05). Also our results show that COX-2-765CC, COX2-765CG, COX-2-1195GG and COX-2-1195AG genotypes can increase the risk of migraine significantly and
its significant relation with familial marriage was observed.
CONCLUSION: We are hopeful to achieve more useful results about the relevancy of other regions of COX2 gene, migraine, pain signals pathway and the other illnesses by repeating these experiments on more
extensive samples.
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Elevated Troponin T after acute ischemic stroke: Association with severity and location
of infarction
Siamak Abdi, Asgar Ghorbani, Shahram Oveis Gharan, Farnaz Sinaei
Neurology Department, Shariati Hospital (TUMS), Tehran, Iran
BACKGROUND: Serum Troponin elevation, characteristic of ischemic myocardial injury, has been
observed in some acute ischemic stroke patients. Its cause and significance is still controversial.
PURPOSE: The purpose of this study is to find determinants of Troponin elevation and its relationship
with stroke severity and location.
METHODS: Between January 2013 and August 2013, 114 consecutive acute ischemic stroke patients
confirmed by diffusion weighted Magnetic Resonance Imaging were recruited in this study. Serum
Troponin T level was measured as part of routine laboratory testing on admission. Ten lead standard ECG
was performed and stoke severity was assessed based on National Institutes of Health Stroke Scale
(NIHSS).
RESULTS: Troponin T was elevated in 20 (17.6%) of 114 patients. Patients with elevated Troponin were
more likely to have higher age, higher serum creatinine and ischemic electrocardiographic (ECG) changes.
Troponin levels were higher in patients with more severe stroke measured by NIHSS (7.96 (6.49 – 9.78)
vs. 13.59 (10.28 – 18.00)). There was no association between Troponin and locations of stroke and atrial
fibrillation. There were 6 (5%) patients with elevated Troponin in the presence of normal creatinine and
ECG.
CONCLUSION: Stroke severity, not its location, was associated with higher Troponin levels. Abnormal
Troponin levels are more likely, but not exclusively, to be due to cardiac and renal causes than cerebral
ones.
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The evaluation of the relationship between plasma concentrations of Carbamazepine and
Carbamazepine 10, 11 epoxide and polymorphism of SCN1A and SCN1B genes in Iranian
epileptic patients
Soha Namazi1,2, Negar Azarpira3, Katayoon Javidnia4, Mehrdad Emami5, Rahimeh Rahjoo2, Razieh
Berahmand2, Afshin Borhani-Haghighi6,7
1-Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
2- Department of Pharmacotherapy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
3-Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
4-Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz,
Iran
5-Transgenic Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
6-Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
7-Department of Neurology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
BACKGROUND: Understanding the relevance of SCN1A and SCN1B genes polymorphism to plasma
concentration of Carbamazepine (CBZ) and its active metabolite carbamazepine 10, 11 epoxide (CBZE),
may help detect inter-individual variation in response to CBZ.
METHODS: In this cross-sectional study, genotypes of SCN1A and SCN1B genes were determined using
PCR-RFLP in 70 epileptic patients on CBZ for at least 6 months. The patients had no hepatic or renal
diseases and received no medications known to have major interaction with CBZ. Serum concentration of
CBZ and CBZE was measured using High-Performance Liquid Chromatography.
RESULTS: The AA, AG and GG alleles of SCNIA were present in 23, 37 and 10 patients respectively. There
were no statistically significant differences in the mean (±standard deviation) of plasma concentrations of
CBZ (P=0.8) and CBZE (P=0.1) among these 3 groups. Likewise, there was no statistically significant
relationship between SCNIA polymorphism and CBZ concentration/dose ratio (P=0.7). Moreover, there
were no statistical associations between demographic characteristics such as age, body surface area, body
mass index, ideal body weight and the plasma levels of CBZ and CBZE, and CBZ concentration/dose ratio.
All patients had the same genotype of SCN1B gene, so we were unable to evaluate its relationship with
corresponding variables.
CONCLUSION: No significant relationship between polymorphism of SCN1A gene and plasma level of CBZ
and CBZE was found.
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Sleep disorders as differential diagnosis for epilepsy: a case series presentation
Hadi Asadpour1, Fariborz Rezaee Talab2, Lahya Afshari Saleh3
1-The sleep laboratory of Ebn-e-Sina Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
2-The sleep lab of Ibn-e-Sina Hospital and Ghaem hospital, Mashhad University of Medical Sciences,
Mashhad, Iran
3-The sleep lab of Ibn-e-Sina hospital and Department of Occupational Medicine, Mashhad University of
Medical Sciences, Mashhad, Iran
BACKGROUND: Sleep and epilepsy are common bed fellows and sleep disorders may mimic, cause or be
triggered by epilepsy phenomena and vice versa. Normal sleep phenomena (including hypnic jerks and
nightmares), parasomnias (confusional arousals, sleep terrors, enuresis), some aspects of narcolepsy
(including sleep paralysis, automatism, cataplexia) and sleep-related breathing disorders (including
obstructive sleep apneas) may mimic epileptic seizures. On the other hand, nocturnal epileptic attacks
may cause or trigger sleep disorders such as apnea, repeated arousals and excessive daytime sleepiness.
CASE PRESENTATION: Here, four cases of sleep disorders (including obstructive sleep apnea, Non-REM
parasomnia, REM-sleep behavior disorder, and narcolepsy) who were previously misdiagnosed as
epilepsy will be brought forward and their polysomnographic features (including videos) will be
presented. C
CONCLUSION: Having an appropriate knowledge of the broad spectrum of sleep disorders is essential for
neurologists who work in the field of epilepsy.
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Antidopaminergic Effects of Ascorbic Acid in Central Nervous System: A Basic and Clinical
Study
Hassan Khani1, Davood Farzin2, Mehran Zarghami2, Seyed Hamzeh Hosseini2, Sara Ehteshami2
1-Iranian Applied Research Center for Public Health and Sustainable Development (IRCPHD), North
Khorasan University of Medical Sciences, Bojnurd, Iran
2-Mazandaran University of Medical Sciences, Sari, Iran
BACKGROUND: Ascorbic acid an antioxidant vitamin is found throughout the mammalian central
nervous system. There is evidence that it may modulate neuronal activity, release of neurotransmitters
and dopamine receptors activities. There are behavioral evidences supporting the antidopaminergic
effect of ascorbic acid. The purpose of the present study was to determine the interaction between
ascorbic acid and the stereotyped licking behavior in rat and a trial of ascorbic acid in schizophrenic
patients to evaluate its therapeutic effects.
METHODS: A) In the present study, effects of ascorbic acid and different dopamine receptor antagonists
on apomorphine-induced licking behavior were examined. For the induction of licking, the dose of 0.5
mg/kg, s.c. of apomorphine was used and the number of licking was recorded over a 75 min period. B) In
a randomized, double-blind, placebo-controlled clinical trial 40 patients with schizophrenia were
assigned to haloperidol plus ascorbic acid or haloperidol plus placebo. After a washout period, 20 patients
received 20 mg/day of haloperidol plus placebo and 20 received haloperidol plus 1500 mg/day of
ascorbic acid for 6 weeks. Data analysis was done by repeated-measure analysis of variance, NewmanKeuls and Spearman’s Coefficient Rank Correlation and Chi square method.
RESULTS: A) Ascorbic acid (200-350 mg/kg, s.c.) dose-dependently reduced the licking behavior.
Subcutaneous injection of ascorbic acid (250 mg/kg, ED61) potentates the inhibitory effect of dopamine
D1 receptor antagonist, SCH 23390 (0.5 and 1 mg/kg, i.p.) but did not alter the inhibitory effect of
dopamine D2 receptor antagonist, sulpiride (25 and 50 mg/kg, s.c.). B) Over 6 weeks, the ascorbic acid
group showed significantly greater improvement in scores on total Brief Psychiatric Rating Scale and on
positive, negative and general symptoms subscales.
CONCLUSION: These results suggest that the inhibitory effect of ascorbic acid on apomorphine-induced
licking behavior is mediated by dopamine D2 receptor mechanisms. Oral supplementation of vitamin C
with conventional antipsychotic drugs can be used in the treatment of schizophrenia.
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Tumor features may predict postoperative outcome in patients with tumor-associatedepilepsy
Jafar Mehvarihabibabadi, Houshang Moein, Reza Basiratnia, Majid Barekatain, Mohammad Zareh, Elham
Rahimian, Amirali Mehvari habibabadi, Shervin Badihian
Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran & Kashani
comprehensive Epilepsy Center, Isfahan University of Medical Sciences, Isfahan, Iran
BACKGROUND: Epilepsy is a manifestation of some brain tumors that has important clinical and social
implications and can be controlled by surgery or administration of antiepileptic drugs. It is suggested that
tumor site and pathology may affect surgery outcome.
PURPOSE: In this study we investigated seizure control after surgery in different tumor locations and
histology.
METHODS: The medical records of 35 individuals (18 female and 17 male, age: 8-45) with tumor
associated epilepsy were reviewed for tumor location, histology, seizure type, ictal and interictal
pre/postoperative EEG findings. All the patients were cases of refractory epilepsy who underwent tumor
resection surgery and were followed for 2 to 4 years in Kashani comprehensive epilepsy center, Isfahan,
Iran.
RESULTS: Thirty patients (88.2%) presented with complex partial seizures (automotor and hypermotor)
and the rest had simple partial seizures and secondary generalization. Seizure type was not significantly
related to postoperative outcome. Ganglioglioma and astrocytoma were the most frequent tumors (61.8%
and 29.4% respectively). DNET was reported in 2 cases and pleomorphic xantoastrocytoma in one case.
Surgical outcome was not different in different tumor types. In our cases temporal lobe tumors consisted
64.7% of patients and the rest of tumors were located in frontal and parietal lobe (17.6% and 11.8%
respectively). Although tumor location was not significantly predictive of surgical outcome, patients with
frontal lobe tumors showed less favorable outcome. Patients who had abnormal EEG findings in parietal
lobe became free of seizures after surgery. Also patients with abnormal EEG findings in temporal lobe
showed better results compared to frontal lobe. The differences were statistically significant.
Postoperative EEG demonstrated abnormal findings in 33.3% of patients. Patients with abnormal
postoperative EEG had poorer seizure control after surgery although it was not statistically significant.
CONCLUSION: Some authors have suggested postoperative seizure control should be investigated by the
type of tumor and its location. Few studies have shown more favorable postoperative outcome in
temporal lesions compared to extra-temporal ones, while some others have reported same results in both
groups. In this study favorable outcome was seen in both groups although patients with frontal lobe
tumor had poorer seizure control. Abnormal EEG findings in frontal lobe resulted in poorer seizure
control as well. The outcome was not affected by tumor histology. It is believed that slow-growing tumors
show poorer seizure control after surgery probably due to secondary generalization. The difference may
be explained by little variation in tumor types in our study. Larger studies with more diversity of tumor
types are recommended to achieve more precise findings.
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Modified Atkins Diet in adult patients with refractory epilepsy: a controlled randomized
clinical trial
Mohammad Zare, Ali Asghar Okhovat Souraki, Ahmad Esmaillzadeh, Jafar Mehvari, Mohammad Reza
Najafi, Mohammad Saadatnia
Isfahan University of Medical Science, Department of Neurology, Isfahan Neuroscience Research Center,
Isfahan, Iran
BACKGROUND: The usefulness of the modified Atkins Diet (mAD) in refractory epilepsy in adults has
been rarely investigated.
PURPOSE: We aimed to evaluate the efficacy of mAD in adult with refractory epilepsy.
METHODS: In a controlled randomized clinical trial, we enrolled 66 refractory adult epileptic cases from
February 2010 to December 2012. The Patients were divided into two groups randomly. Case groups (22
patients) used antiepileptic drugs and mAD and control group (32 patients) only use antiepileptic drugs.
The primary outcome was at least 50% decrease in seizure frequency after 2 months of therapy.
RESULTS: Our data showed no significant difference between groups regarding baseline characteristic.
The differences of mean seizure attacks after two months (p≤0.001) and fifty percent reduction in seizure
frequency between the two groups showed significant differences [p≤0.001, Odd ratio=2.19, 95%
confidence interval (1,39, 3.47)]. There was a positive correlation between the mean urinary Ketone level
and >50% seizure reduction in case group (p=0.04). In repeated measures analysis and based on the perprotocol principle, there was a significant difference between Modified Atkins Diet and control groups
regarding mean number of seizure attacks (F=14.6, p<0.001). Such differences were also significant in the
intention- to- treat analysis (F =6.14, p=0.01).
CONCLUSION: The mAD may be effective as a co-therapy treatment for adults with refractory epilepsy
and can decrease 3.66 times seizure frequency in comparison with control groups. Trials with more
tolerant dietary regime, with larger sample size and longer duration, should be performed in the future.
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POSTER PRESENTATION
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CEREBROVASCULAR DISEASES
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Mechanical thromboembolectoy versus IV rtPA in treatment of acute ischemic stroke
Askar Ghorbani, Siamak Abdi, Vahireza Ostovan
Tehran University of Medical Sciences, Tehran, Iran
Intravenous alteplase administered within 4.5 hours after symptom onset is the only reperfusion therapy
with proven efficacy in patients with acute ischemic stroke. However, it appears to be much less effective
at opening proximal occlusions of the major intracranial arteries, which account for more than one third
of cases of acute anterior-circulation stroke. Therefore, intraarterial treatment is regarded as a potentially
important component of the therapeutic armamentarium. Intraarterial therapy can be broadly divided
into chemical dissolution of clots with locally delivered thrombolytic agents and clot retrieval or
thrombectomy with mechanical devices. Interventional Management of Stroke (IMS) III trial and
SYNTHESIS Expansion trial showed uncertainty regarding the efficacy of the catheter- based approach,
but the design of these studies had some limitations such as, a relatively long interval before intraarterial
treatment, the absence of pretreatment vascular imaging to confirm a proximal intracranial occlusion,
and the limited use of third-generation mechanical thrombectomy devices such as retrievable stents.
Recently, Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in
the Netherlands (MR CLEAN) was conducted on 500 stroke patients and revealed that intraarterial
treatment with or without intravenous alteplase was safe and more effective method in comparison to the
intra venous alteplase alone, if done in patients with a proximal arterial occlusion in the anterior
circulation within 6 hours after symptom onset (An absolute difference of 13.5 percentage points (95%
CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the
intervention (32.6% vs. 19.1%) and no significant differences in mortality or the occurrence of
symptomatic intracerebral hemorrhage). In our study we did 35 mechanical interventions that showed
this route of therapy could be consider in acute stroke.
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A clinical trial of effectiveness of the cerebrolysin drug in A cute ischemic stroke
compression with control group hospitalized patients in Farshchian hospital in Hamadan
Iran (2011-12)
Mehrdokht Mazdeh, Sajede Nazari
Farshchian Hospital of Hamadan, Hamadan, Iran
BACKGROUND: Stroke is the third common cause of mortality and the most common neurologic disease
resulting disability in the United States. Because the disability caused by this disease and its effects on the
quality of life of the patients and economic burden, is an important health problem in the societies.
Various treatments proposed for this disease that one of them is cerebrolysin administration. This agent
stimulates cell differentiation, has direct effect of neurons' regeneration, reduce the infarct size area,
reduce the apoptosis and oedama and stabilize blood circulation to involved area. The aim of this study
was evaluating the therapeutic effect of cerebrolysin in patients with stroke.
METHODS: In a randomized controlled trialed 122 patients with confirmed ischemic acute stroke
enrolled to study. The patients divided to two groups, study and control group. The study group received
10 ml cerebrolysin in 100 ml saline as an infusion for 30 minutes daily during seven days and control
group received only saline same by same way of the study group. All the patients evaluated at the days 1,
3, 7 and 30 for the CSS, MRS and Barthel Index for treatment results. The results analyzed by t- student
test and chi-square test with the SPSS software.
RESULTS: The mean of Canadian Stroke scale score at the day 7 increased about 59% in study group and
about 42% in the control group (P>0.05). There was not significant differences between two groups in
terms of subgroup different indices of CSS (GCS, tongue and physical functions) Barthel & MRS index
(P>0.05).
CONCLUSION: This study indicates cerebrolysin has not noticeable effect in the patients with acute
Ischemic stroke.
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Development of National guideline for diagnosis, treatment and follow up of stroke
patients in Iran
Kavian Ghandehari, Mohammad Reza Gheini, Mohammad Hossein Harirchian, Mohammad Hadi
Modaghegh, Mahmood Farhoudi, Mahmood Reza Azarpazhooh, Payam Sasannezhad, Human
Baharvahdat, Armin Shirvani, Rozita Davoodi, Golnaz Sabouri, Hoda Khoshmohabat
Stroke Unit, Neurocognitive Research Center, Mashhad UMS, Iran
National and international guidelines have been made for management of stroke patients in the word.
These guidelines simplifies diagnosis, work up and management of stroke patients. Development of
clinical guidelines is based on meta-analysis of numerous clinical trials by expert team. Stroke
neurologists, neurosonologist, neuroradiologist, neurointerventionist, neurosurgen, and vascular surgeon
consisted our team of experts. This guideline was conducted under supervision of executive evidence
based medicine committee of Ministry of health and medical education of Iran in 2014. Funding budget of
this guideline was provided by Mashhad University of Medical Sciences. Scientific committee analyzed
level of evidence for each diagnostic and therapeutic intervention of ischemic and hemorrhagic stroke
patients. Hyperacute, acute and chronic management of stroke as well as primary and secondary
prevention of stroke was included in the guideline. Interventional, vascular surgical and neurosurgical
managements are considered in the guideline protocol. This guideline was adjusted based on therapeutic
condition and problems in Iran. Clinical data derived from stroke clinical studies in Iran, experience of our
team members and numerous international stroke guidelines. The text of Iranian national stroke
guideline is going to be published by Iranian Ministry of Health and Medical Education and will be
distributed online. This guideline will be used by Iranian neurologists and stroke physicians. This is the
first designed national stroke guideline in the Middle East and west of Asia.
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Iranian cut off of HASBLED score in prediction of hemorrhagic complications in stroke
patients with non-valvular atrial fibrillation receiving warfarin therapy
Kavian Ghandehari, Mostafa Dastani, Siamak Yazdani, Mohammad Taghi Shakeri
Stroke Unit, Neurocognitive Research Center, Mashhad UMS, Iran
BACKGROUND: Atrial Fibrillation is the most common underlying cardioembolic cause of stroke. Taking
an oral anticoagulation (Warfarin) is an effective therapeutic prevention of ischemic stroke in these
patients but bleeding complications is common. HASBLED Criteria is used to predict hemorrhagic side
effects.
METHODS: In this cohort study we follow 112 patients with Non-Valvular atrial fibrillation in term of
major and minor bleeding complications to assess the predictive value of HASBLED Criteria. Major
bleeding complications defined as intracranial bleeding, bleeding leading to hospitalization, drop in
hemoglobin of more than 2gr/dl or requiring blood transfusion. HASBLED score were defined as
Hypertension, Liver and Renal dysfunction tests, History of Stroke, History of Bleeding, Large Fluctuations
in Coagulation Tests, old age and an Anti-platelet and NSAID and Alcohol use 1 point is awarded to each of
the above.
RESULTS: During follow up period 10 (9.1%) of patients had major bleeding and 28(25%) patients had
minor bleeding. The risk of major bleeding were significantly related to history of minor bleeding and
HASBLED scores (p<0.001). The risk of minor bleeding with warfarin toxicity and High INR were
significantly related (p<0.001). HASBLED Score higher than 3 with sensitivity of 70% and specificity of
80%was associated with the likelihood of major bleeding and scores higher than 2 were associated with
likelihood of minor bleeding with sensitivity of 93% and specificity of 66%.
CONCLUSION: Oral anticoagulant (warfarin) therapy in patients with HASBLED scores higher than 3
should be performed cautious.
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Intracranial Angioplasty and Stenting for Cerebral Atherosclerosis
Hamzehloo A
Department of Interventional Neurology, Milad Hospital, Tehran, Iran
Intracranial cerebral atherosclerosis causes ischemic stroke in a significant number of patients.
Technological advances over the past 10 years have enabled endovascular treatment of intracranial
atherosclerotic stenosis. The number of patients treated with angioplasty or stent-assisted angioplasty
for this condition is increasing. This article was written under the following of cases which performed in
my hospital in one year.
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Carotid artery intima-media thickness and opium addiction
Saadatnia M, Ebrahimi H
Isfahan University of Medical Sciences, Isfahan, Iran
BACKGROUND: Despite some evidences about protective or triggering role of opium use in patients with
coronary artery disease, the exact role of opium is still under question and there is no study to show the
effect of opium on intima media thickness (IMT). The current study aimed to address the relation of
opium addiction on IMT.
METHODS: This cross-sectional study was performed on subjects referred to neurovascular clinic. All the
subjects underwent cerebrovascular ultrasound and Carotid artery IMT was assessed. A questionnaire
containing demographic data, opium use information [based on the 4th Edition of the Diagnostic and
Statistical Manual of Mental Disorders (DSM-IV) criteria], and vascular ultrasound findings were
completed for each subject and the results were analyzed using regression test.
RESULTS: In this study, 285subjects were included. Twenty two (7.7 %) subjects were addicted to opium
and the remaining were non-addicts. After multiple regression analysis, including age, sex, body mass
index, hypertension, diabetes, smoking, hyperlipidemia and opium addiction, carotid artery IMT
remained significantly associated with age, hypertension, diabetes, and smoking and opium addiction was
not significantly associated with IMT (P=0.00, P=0.09, P=0.06, P=0.09, P= 0.64).
CONCLUSION: Opium addiction have no role in carotid IMT, one possible explanation for this finding is
that narcotics may decrease inflammation, which is directly associated with atherogenesis and plaque
disruption.
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Can HTLV-1 infection be a potential risk factor for carotid artery atherosclerosis?
Ali Shoeibi, Parvaneh Layegh, Ali Ghabeli Juibary, Sahar Darbarpanah, Mahmoudreza Azarpazhooh
School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
BACKGROUND: Chronic inflammation and infectious diseases such as HIV infection are now considered
as risk factors for atherosclerosis. In this study, for the first time, Human T-lymphotropic virus type-1
(HTLV-1) infection is examined as a potential risk factor for atherosclerosis.
METHODS: This is a match pair cross sectional study on fifty-eight HTLV1 infected cases and 55 healthy
control subjects. The subjects did not have any major cerebrovascular risk factors. Carotid IMT (intimamedia thickness) was measured for each patient using the standard protocol of the Atherosclerosis Risk
in Communities (ARIC) Study.
RESULTS: The mean age of our subjects was 42.9±10.52 years and males made up 33% of the population.
The difference between mean IMT of infected case group and healthy control group was significant
(P<0.05). Discussion: This study indicated that HTLV-infected patients had greater carotid IMT compared
with age- and sex-matched control subjects.
CONCLUSION: Having no other known risk factor for atherosclerosis, we concluded that significant
difference of IMT in our patients might support this hypothesis that HTLV1 infection is an independent
risk factor for atherogenesis.
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Cost-Effectiveness Analysis of the Unfractionated Heparin versus Low Molecular Weight
Heparin in Hospitalized Patients with Stroke due to Atrial Fibrillation in Shiraz, South of
Iran 2013
Bahmehei A, Hatam N, Sedghi R, Feiz F, Borhani-Haghighi A
Shiraz University of Medical Sciences, Shiraz, Iran
BACKGROUND: Patients with Atrial Fibrillation (AF) make a unique group of stroke. Unfractionated
Heparin (UFH) and Low Molecular Weight Heparin (LMWH) are among medications that used by
physicians for prevent of blood coagulation. The present study was done with purpose the costeffectiveness analysis of LMWH versus UFH in hospitalized patients with stroke due to AF from Iran’s
society perspective.
METHODS: In this study decision tree model was used. Costs data were collected through interviews with
patients with stroke due to AF and their companions with using of data collection form including the
medical direct costs, non-medical direct costs and indirect costs, three months after the medications
injection. Effectiveness criterion was prevention of new stroke recurrence. Therefor results of this study
were expressed as cost per new stroke prevention. Finally a one-way and probabilistic sensitivity analysis
was conducted to examine the strength of the results.
RESULTS: Our analysis results showed that effectiveness based on prevention of new stroke by LMWH
more than UFH. Also UFH medical direct costs, non-medical direct costs and also indirect cost was more
than LMWH. Cost-effectiveness ratio estimated - 150, 201, 26$ per each effectiveness.
CONCLUSION: The results of the cost–effectiveness analysis of LMWH versus UFH showed that, LMWH is
a dominant strategy for patients with stroke due to AF from Iran’s society perspective.
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The prevalence and factors contributing to hemodynamic depression in patients
undergoing carotid angioplasty and stenting
Afshin Borhani Haghighi1,2, Safoora Kokabi2, Samaneh Yousefi3, Mehrdad Emami4, Abdolhamid Shariat1,2,
Alireza Nikseresht1,2, Nahid Ashjazadeh1,2, Sadegh Izadi1,2, Peyman Petramfar1,2, Maryam Poursadegh1,2,
Abbas Rahimi Jaberi1,2, Sajjad Emami5, Hamid Agheli6, Reza Nemati7, Ehsan Yaghoubi8, Mohammad Hosein
Abdi9, Majid Panahandeh10, Seyed Moslem Heidari- Khormizi11, Salvador Cruz-Flores12, Randal Edgell13
1-Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
2-Departments of Neurology, Shiraz University of Medical Sciences, Shiraz, Iran
3-Student research Committee, Fasa University of Medical Sciences, Shiraz, Iran
4-Transgenic Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
5-Department of Neurology, Faculty of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran
6-Shahidzadeh Hospital, Behbahan, Iran
7-Department of Neurology, Faculty of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
8-Department of Neurology, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran
9-Motaharri Hospital, Marvdasht, Iran
10-Ordibehesht Hospital, Shiraz, Iran
11-Department of Neurology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
12-Departments of Neurology, Texas Tech University, El Paso, USA
13-Departments of Neurology and Psychiatry, Saint Louis University, Saint Louis, USA
BACKGROUND: Hemodynamic depression including bradycardia and hypotension are among the most
common complications of carotid angioplasty and stenting.
METHODS: A prospective, cross-sectional study was conducted at Shiraz University of Medical Sciences
in southern Iran from 2011 to 2013. Consecutive patients undergoing carotid angioplasty and stenting
were included. Demographic data, atherosclerotic risk factors, pre-procedural blood pressure, site of
stenosis, degree of stenosis, and data regarding technical factors were recorded. Hemodynamic
depression was defined as a systolic blood pressure less than 90 mmHg and/or heart rate less than 50
beat/min.
RESULTS: Totally, 170 patients (67% male, mean age: 71+9.8, 55.9% right side, 82.9% symptomatic)
were recruited. Mean degree of stenosis was 79.4% in operated side and 40.7% in non-operated side.
Predilation, post dilation, or both were conducted in 18 (10.5%), 141 (83%), 11 (6.5%) patients
respectively. Thirteen (7.6%), 41 (24%), and 12 (7%) of patients developed post-procedural bradycardia,
hypotension or both, respectively. Two patients had a stroke after CAS and peri-procedural mortality was
0%. Hemodynamic depression after CAS had a significant association with pre-procedure blood pressure
and the use of an open cell stent design, but not with atherosclerotic risk factors, site and/or degree of
stenosis, predialtion, or postdilation. Hemodynamic depression significantly increased hospital stay too.
CONCLUSION: Pre-procedural hydration and close-cell stents may decrease the risk of post-stenting
hemodynamic depression.
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148
Correlation between Dysphagia and nutritional indicators in ischemic stroke patients at
the time of hospital admission
Fatemeh Seifar, Mohamad Khalili
1-Students research committee, Neurosciences Research Center, Tabriz University of Medical Sciences,
Tabriz, Iran
2-Neuroscience Research Center, Tabriz University of Medical Science, Tabriz, Iran
BACKGROUND: Dysphagia and poor nutritional status are common complications of stroke. However,
possible associations between them are not well understood. Furthermore, it is necessary to perform a
nutritional assessment of the patient in the early hours of admission, to determine both the nutritional
status and the presence of dysphagia. So in this study, potential associations between dysphagia and
nutritional indicators in patients with acute ischemic stroke at the time of hospital admission were
evaluated.
METHODS: In this observational cross-sectional study, patients with ischemic stroke admitted to
academic medical centers were enrolled. We studied 30 patients with stroke at the time of admission. The
frequency of dysphagia and dysphasia grading score was evaluated. Nutritional indicators were assessed
by knee height, mid arm circumference, triceps skin fold thickness, and calf circumference of all the
admitted patients. The possible correlation between dysphagia and each parameter was evaluated.
RESULTS: On clinical assessments 73.33% of patients demonstrated dysphagia. Dysphagia, was
significantly associated with lower calf circumference (P<0.05), but not with other nutritional indicators
(knee height, mid arm circumference, triceps skin fold thickness).
CONCLUSION: Dysphasia is a prevalent problem in patients with acute ischemic stroke, however, in
overall view was not associated with major nutritional failure at the time of hospital admission.
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149
Gerstmann’s syndrome in non- dominant hemisphere involvement
Masoud Ghiasian, Mojtaba Khazaee, Mehrdokht Mazdeh, ElaheRaisi Rad
Department of Neurology, Hamadan University of Medical Sciences and Health Services, Hamadan, Iran
Gerstmann’s syndrome is caused by a left (dominant) inferior parietal lesion, particularly involving the
angular gyrus or subjacent white matter of the left hemisphere. The characteristic tetrad is finger agnosia,
confusion of the right and left side of body, acalculia and dysgraphia. Our patient was an 80-year-old right
handed man with sudden onset of blurred vision. In neurological examination, he had left homonymous
hemianopia and characteristic features of Gerstmann’s syndrome. CT scan showed hypo dense area in
right occipital lobe with expansion to parietal and temporal lobe.
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150
Determining level of blood pressure in patients with acute stroke in Farshchian hospital
of Hamadan, in 2013-2014
Khazaei M, Mazdeh M, Ghiasian M
Farshchian Hospital of Hamadan, Hamadan University, Hamadan, Iran
BACKGROUND: Stroke or cerebrovascular accidents are the third leading cause of mortality and the
most important cause of morbidity in adults in the most of the world. Multiple factors such as socioeconomic conditions, life style, risk factor, genetic and environmental factors may be the causes of stoke
risk differences in different societies. This study, the level of blood pressure of acute stroke patients was
investigated.
METHODS: In cross-sectional study, all patients with diagnosis of stroke in Farshchian hospital that were
admitted from March 2012 through March 2013. Their demographic data were recorded including (age,
gender), blood pressure in the acute phase and the time of discharge, history of diabetes, hyperlipidemia
and heart disease.
RESULTS: The frequency of male and female was 54% and 46% and average of age them was 65.89 and
72.67. Ischemic stroke was higher than others (65%). In 33.67% of patients before admission hospital
received or Hydralazine or nitroglycerin. Mean systolic and diastolic blood pressure in patients on
admitted were 154.64 mm 92.97 mm Hg respectively. Among them 60.22% of the patients have
recovered, 24.78% of the patients have expired and 10.11% have remained unchanged and 4.89% has
deteriorated.
CONCLUSION: Nearly 83% of the stroke patient used regulatory drugs of blood pressure that showed the
important role of hypertension in the stroke. Blood pressure in the stage of stroke acute is increased and
in the first 48 hours after the garlic bed that the average of blood pressure in the patient with a history of
hypertension was higher than normal groups.
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151
Prevalence of atrial fibrillation rhythm in patients with stroke admitted to Farshchian
hospital in the second half of 2011
Mazdeh M, Khazaei M, Ghiasian M
Farshchian Hospital of Hamadan, Hamadan University, Hamadan, Iran
BACKGROUND: It has been reported that the prevalence of stroke is approximately 750,000 per year.
The role of atrial fibrillation (AF) rhythm as one of important risk factors for stroke has been
demonstrated. In the present study, the relationship between AF rhythm and cause of stroke was
investigated.
Methods: This cross-sectional study was performed among patients (n=460) that admitted from October
through March 2011 in the stroke center at Farshchian hospital in Hamadan, Iran. The relationship
between stroke, AF rhythm and some related risk factors were evaluated.
RESULTS: In this study 52.5% of patients were female and 70.7% had ischemic stroke. The frequency of
AF rhythm was 20.7%. Average age of patients with and without AF rhythm was 85.72 and 78.68 years
(Min=60, Max=94), respectively (P<0.05). 19.3% of men and 21.59% of women have AF rhythm.
CONCLUSION: There was no significant difference in the frequency of AF rhythm between men and
women. In this study the frequency of AF rhythm in stroke patients was 20.7%.
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152
Thrombosis of the Cerebral Veins and Sinuses: Clinical Presentation, Predisposing
Factors and Outcome in Hamadan, West of Iran
Masoud Ghiasian, Maryam Mansour
Hamadan University of Medical Sciences and Health Services, Hamadan, Iran
BACKGROUND: Cerebral venous sinuses thrombosis (CVST) is an uncommon type of stroke and is
difficult to diagnose.
Objectives: To describe the clinical presentation, predisposing factors, neuroimaging findings, and
outcomes of the disease in Sina hospital in Hamadan, west of Iran.
METHODS: This is a prospective study of patients presenting to emergency department of Sina hospital
between May of 2011 to June of 2014 who were diagnosed with CVST.
RESULTS: Eighty patients were included in this study. Median age was 39 (Mean: 39.30±11.66, Range:
15-72) years. There were 63 (78.8%) women and 17 (21.3%) men. Mean age of women and men were
38.35±10.41 and 42.82±15.33, respectively. The female to male ratio was 3.70. The most common
presenting features were headache (78.8%), focal motor deficit (41.4%), mental status changes (35.0%),
papilledema (32.5%), blurred vision (18.8%) and seizure (18.8%). The mean age of patients presenting
with headache was 38.0±10.96. The most common risk factors in our patients were oral contraceptives
(47.5%), dehydration (22.5%) and hypercoagulable state (16.3%). Twenty four patients (30%) had two
and 2 patients (2.5%) had three risk factors simultaneously. Overall mortality was 13.8% (11 patients).
After 6 months follow up 70.51% were functionally independent (mRS score 0-1). 15.38% were
dependent.
CONCLUSION: In our study the most common clinical presentation was headache. Every patient
presenting with headache to emergency departments, especially young women with recent history of oral
contraceptive consumption should be examined carefully. It seems fasting and its subsequent
dehydration in women with recent use of oral contraceptives makes them more susceptible to CVST.
Septic CVST had higher mortality than aseptic CVST.
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153
Success and complication rates of carotid stenting in 500 cases
Behnam Mansouri, Mohammd Karimi
Imam Husain Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Carotid artery stenting is a procedure in which an interventionist inserts a slender, metal-mesh tube,
called a stent, which expands inside the carotid artery. In this study we are reporting the result of our
carotid stenting success and complications during past 5 years of intervention for carotid in two large
centers of stroke and carotid stenosis investigation and angiography and carotid stenting. Average
complication is generally 4 to 8% for severe neurologic complications patients (including death, major
stroke, minor strokes) and short lasting neurologic deficits in additional 4-8% of patients. Cardiovascular
complications are rare. Local (inguinal) problems occurred in average 2-4% patients. Frequently, balloon
inflation was associated with bradycardia and additional hypotension. In our study average rate of
complication was less than international rates which will be discussed in details in presentation. Also
complications will be discussed.
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154
Successful thrombectomy after failure of intra-arterial thrombolysis with rTPA: A case
report
Mohammad Reza Sobhani, Human Baharvahdat, Payam Sasanezhad, Kavian Ghandehari, Mohammad
Mousavi Mirzaei
Mashhad University of Medical Sciences, Mashhad, Iran
CASE PRESENTATION: A 56-year-old woman, who was known case of DM, HTN, IHD, and Hlp was
admitted in CCU of Ghaem hospital for acute MI and received intravenous heparin for first two days. On
fourth day of admission, she suddenly developed left hemiplegia and left gaze paresis. An infarction was
seen at right inferior MCA territory on the urgent brain MRI taken in the first hours. Initial modified
NIHSS and ASPECT was 9 and 7, respectively. Acute MI was considered as exclusion criteria of
intravenous thrombolysis with rTPA. She was transferred to neuroangiography unit and underwent intraarterial thrombolysis with 20 mg of rTPA at 5 hour after symptoms onset. However, control angiography
after injection of rTPA showed no change in vessel lumen and patient assumed as failure of intra-arterial
thrombolysis. Interventional thrombectomy with Solitaire device was performed immediately.
Vasospasm was observed on right MCA branches and intra-arterial Nimodipine served for treatment of
vasospasm subsequently. Administration of Plavix and ASA was initiated 24 hours after interventional
therapy. The modified NIHSS changed to 4 after 24 hours and to 3 at 72 hours after intervention.
CONCLUSION: Intra-arterial thrombectomy is a novel interventional management of hyperacute stroke
and could be considered in patients whom are not candidate for intravenous thrombolysis with rTPA.
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Evaluation of predictive value of ABCD2F score for recurrence of ischemic stroke or
transient ischemic attack within the first 90 days
Mostafa Almasi Dooghae1, Nader Hojjati Firoozabadi2, Mojtaba Chardoli2
1-Department of Neurology, Iran University of Medical Science, Tehran, Iran
2-Department of Emergency Medicine, Iran University of Medical Science, Tehran, Iran
BACKGROUND: Stroke is a relatively common disease and has a high disease burden. The prediction of
recurrence rate of transient ischemic attack (TIA) or ischemic stroke (IS) is helpful in the health
management of such patients. Because of major value of atrial fibrillation (AF) in IS and TIA, we evaluated
the predictive value of ABCD2F score for recurrence of IS or TIA within the first 90 days.
METHODS: In this cross-sectional study, 138 patients of Rasool-Akram and Sina hospitals of Tehran with
diagnosis of IS or TIA, from 1391 to 1392 were included. For each patient a check list composing different
demographic and clinical variables were completed. ABCD2F score was calculated by adding 1 score for
detecting AF to ABCD2 score. Then they were followed up for recurrence of IS or TIA within the first 90
days after event. Finally the data collected, coded and analyzed by 18th edition of SPSS software.
RESULTS: 106 (76.8%) patients had IS and 32 patients (23.2%) had TIA. Thirteen patients (9.42%)
conducted another stroke or TIA within 90 days. The mean ABCD2 and ABCD2F score, in patients with
recurrent stroke were 4.61±0.50 and 4.77±0.54; and in patients without recurrent stroke were 5.06±0.12
and 5.11±0.12, respectively. These differences were not statistically significant (P=0.421 for ABCD2 score
and P=0.557 for ABCD2F score). The detection of AF rhythm was associated with greater stroke
recurrence rate but it was not statistically significant (P=0.232). Among other variables, just positive
history for ischemic heart disease, no prescribing of aspirin on discharge and platelet count were
statically relevant with recurrence of stroke.
CONCLUSION: ABCD2F score, like ABCD2 score, cannot predict the recurrence of IS or TIA within the first
90 days after event and another criterion for the prediction of stroke is needed. Therefore further studies
and taking into account variables such as a history of ischemic heart disease, drug history and coagulation
laboratory tests are recommended.
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Assessment of admission platelet level and age, in responsiveness to Aspirin in ischemic
stroke patients: one year follow up
Mostafa Almasi Dooghaee1, Sadegh Rahimi2, Farzan Falahat3, Mehdi Moqaddasi1
1-Department of Neurology, Iran University of Medical Science, Tehran, Iran
2-Mashhad University of Medical Science, Tehran, Iran
3-Iran University of Science and Technology, Tehran, Iran
BACKGROUND: Stroke is seated in the first rank of leading cause disability worldwide. Aspirin inhibit the
platelet aggregation and were used as secondary preventing in ischemic stroke. The aim of present study
is evaluating possible impact of patient platelet level, age and sex on Aspirin efficacy for preventing
recurrent stroke or TIA.
METHODS: A retrospective cohort study conducted on the patient with ischemic stroke of TIA whom
admitted in Rasul-e-Akram Hospital of Tehran, Iran, during 2013. All data including demographic
variables and clinical profile on admission and discharge time were recorded in a checklist for each
patient. After three months to one year of admission, all patients have been called by expert for follow-up
about the symptoms of renewed TIA or stroke and other problems. The exclusion criteria were previous
consumption of antiplatelet before stroke event, discharge with prescription of other anticoagulants
except alone Aspirin, and lack of follow-up data. Finally four balanced age group composing under 55, 5570, 70-80, and over 80 years were defined. For analysis, SPSS edition 16th statistical software and the C5
decision tree is used.
RESULTS: From 231 patients diagnosed as ischemic stroke, 122 patients (88%) met the criteria. On
follow up, 2.60% reported renew Stroke, 4.60% renew TIA and 6.49% admitted to hospital due to
vascular diseases. In 4 age groups, mean±SD of admission platelet level were 226.255±60.5, 228.39±79.8,
202.17±68.3 and 199.55±67.4, respectively. Base on C5 decision tree, Aspirin had no significant effect on
patients over 80 years with platelet below 155/mm3 (p<0.001 according to Cochran–Mantel–Haenszel
test). This result was not banded to patient’s gender.
CONCLUSION: On follow up of the patients with ischemic stroke or TIA, we found that Aspirin had no
significant effect on patients over 80 years with platelet below 155/mm 3. For substitution of Aspirin with
another medication in these patients, more studies are required.
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157
Cerebral Venous Trombosis or Idiopathic Intracranial Hypertension, Spectrum of
Findings and Diagnostic Pitfalls
Sheida Shaafi, Masoud Nikanfar, Dariush Savadi, Maziar Hashemilar, Safa Najmi, Saeed Charsoei
Tabriz University of Medical Science, Tabriz, Iran
Dural sinus hypertension from cerebral venous outflow impairment is a cause of pseudo tumor cerebri.
On the other hand cerebral venous thrombosis is a relatively uncommon but serious neurologic disorder
that is potentially reversible with prompt diagnosis and appropriate medical care. Because the possible
causal factors and clinical manifestations of this disorder are many and varied, imaging plays a primary
role in the diagnosis. Magnetic resonance (MR) imaging, un-enhanced computed tomography (CT),
unenhanced time-of-flight MR venography, and contrast material-enhanced MR venography and CT
venography are particularly useful techniques for detecting cerebral venous and brain parenchymal
changes that may be related to thrombosis. To achieve an accurate diagnosis, it is important to have a
detailed knowledge of the normal venous anatomy and variants, the spectrum of findings (venous sinus
thrombi and recanalization, parenchymal diffusion or perfusion changes or hemorrhage), other
potentially relevant conditions (deep venous occlusion, isolated cortical venous thrombosis, idiopathic
intracranial hypertension), and potential pitfalls in image interpretation. Our aim of this study is to clarify
most challengeable issues in this fact while clinical and imaging evidences are sufficient for diagnosis, but
the management is very different. More than 100 causes of venous thrombosis have been described in the
literature. Causal factors may be classified as local (related to intrinsic or mechanical conditions of the
cerebral veins and dural sinuses) or systemic (related to clinical conditions that promote thrombosis). In
25% of cases, no cause is identified. The clinical manifestations of cerebral venous thrombosis vary,
depending on the extent, location, and acuity of the venous thrombotic process as well as the adequacy of
venous collateral circulation. Generalized neurologic symptoms (e.g., headache, experienced by 75%–
95% of patients) and focal neurologic deficits, including seizure may result. Focal neurologic symptoms
are more often seen in patients with parenchymal changes observed at imaging than in those without
such changes. Because thrombosis and endogenous thrombolysis and recanalization may occur
concurrently, the clinical manifestations may fluctuate in as many as 70% of patients, adding to clinical
uncertainty. Intracranial hypertension occurs in 20%–40% of patients with cerebral venous thrombosis
and should be excluded in patients with the specific complex of symptoms. MRI combined with MRV
examination is the preferred method of diagnosing CVST. A review of the MRI literature published in
recent 10 years enables a general description of the anatomic distribution of thrombosed cerebral venous
structures identified primarily at MRI.
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Validation of HAS_BLED score in prediction of hemorrhagic complications in patients
with brain ischemia and atrial fibrillation receiving warfarin therapy
Siamak Yazdani, Kavian Ghandehari
Sajjadieh Hospital, Torbat Jam, Iran
BACKGROUND: Cardioembolic strokes are responsible for 20 percent of ischemic stroke cases. It
happens due to atrial fibrillation (AF) in most patients. Although oral anticoagulant administration is a
reliable method which could prevent ischemic stroke, hemorrhagic events are the most common
complication of anticoagulants. The aim of this study was the use of HESBLED scoring system in
predicting hemorrhagic events.
METHODS: after ethical approval, a cohort study was designed with 112 patients with AF who used
warfarin. Patients were followed up for one year period. Hemorrhagic events were classified as major and
minor hemorrhage. Data was analyzed by SPSS version 16 with parametric and nonparametric tests.
RESULTS: Ten patients (9%) had major hemorrhage and 28 patients (25%) had minor hemorrhage.
Major hemorrhage was associated with minor hemorrhage and HESBLED score (P<0.0001). Minor
hemorrhage related to high INR and warfarin toxicity (P<0.0001). Sensitivity and specificity of HESBLED
more than 3 for predicting hemorrhagic events was 70% and 86%, respectively and associated with
probable major hemorrhage, HESBLED more than 2 was associated with future minor hemorrhage.
CONCLUSION: Our study demonstrated that patients who have HESBLED score higher than 3 and have
indications for anticoagulant therapy and have history of minor hemorrhage and warfarin toxicity history
should be observed closely.
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159
Cerebral Venous-Sinus Thrombosis: Risk Factors, Clinical Report, and Outcome a
Prospective Study in North Eastern Iran
Siamak Yazdani Neurologist, Mohammad Taghi Farzadfar, Ali Ghabeli Juibari
Sajjadieh Hospital, Torbat Jam, Iran
PURPOSE: We undertook this prospective study to determine the demographic, clinical patterns,
etiologies and prognostic factors of cerebral venous-Sinus thrombosis (CVST) in North Eastern Iran.
METHODS: All adult patients admitted with an angiographically documented diagnosis of cerebral
venous thrombosis from 2011 through 2012 in Ghaem hospital, Mashhad University of medical sciences
in north eastern Iran, were entered the study.
RESULTS: Sixty patients (8 men, 52 women) aged 18 to 83 years were identified. Fifty one cases (85%)
had a clinical picture of pseudo tumor cerebri. Causes included antiphospholipid antibodies in 3.3%,
protein C, S and anti thrombin III deficiency in 5%,1.7% and 3.3%, polycythemia in 1.7%, infections in
1.7%, postpartum in 9.6% of women, and oral contraceptives in 65.38%. We found a 10% mortality rate
on discharge and 11.9 % within 30 days 42.7% rate of death or dependency at month 6 and 12.
CONCLUSION: The findings of the study indicate that the use of OCPs was a main factor associated with
CVST. This study demonstrates that screening for inherited hypercoagulable state should be an essential
part in the diagnostic work up of CVT patients. Among patients with early intracerebral hemorrhage or
stupor on admission were at higher risk for death or dependency at month 6 and 12.
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160
Anterior Communicating Artery Aneurysm, 6 years follow up of A-com aneurysm coiling
in Milad Hospital
Karimi M, Hamzehloo A, Zandi P, Jalali A, Manteghi RF, Arami MA, Mansouri B
Milad Hospital, Tehran, Iran
BACKGROUND: Aneurysmal Subarachnoid Hemorrhage (SAH) is a devastating and often fatal form of
stroke. The aneurysm is targeted for obliteration to prevent re-bleeding and to manage the possible
complications from the event. New methods of endovascular coiling have emerged as a less invasive
alternative to conventional surgical clipping to treat aneurysms.
METHODS: This study was done prospectively in the Milad hospitals to evaluate the outcome of different
methods of endovascular coiling and we followed up them for 6 years.
RESULTS: Complications including hydrocephalus, hemiparesis and failed procedures occurred in
(3.7%).
CONCLUSION: We concluded that coiling is better for treating cases of ruptured A-com aneurysms being
less invasive and achieving a favorable outcome compared to surgery.
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161
Oral contraceptive-related cerebral venous thrombosis as an initial manifestation of
antiphospholipid syndrome in the absence of systemic lupus erythematosus
Payam Saadat1, Reza Mohseni Ahangar2
Department of Neurology, Babol University of Medical Sciences, Babol, Iran
Department of Internal Medicine, Babol University of Medical Sciences, Babol, Iran
BACKGROUND: Cerebral venous sinus thrombosis is a rare and potentially life-threatening neurologic
manifestation of antiphospholipid syndrome. Oral contraceptive pills may increase the risk of vascular
events, even in people without family history of venous thrombosis.
CASE PRESENTATION: A 31-year-old woman presented with four weeks of constant headache. She had a
history of taking OCP for one year. The results of brain magnetic resonance imaging and venography
confirmed a diagnosis of cerebral venous sinus thrombosis. The serum anticardiolipin and
antiphospholipid antibodies were elevated and a definitive diagnosis of antiphospholipid syndrome was
made.
CONCLUSION: The present report demonstrates the importance of screening for antiphospholipid
antibodies in patients presenting with cerebral venous sinus thrombosis, despite history of taking OCP.
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162
The effect of levodopa on motor function outcome in patients with ischemic stroke: A
double-blind, placebo-controlled, randomized clinical trial
Zandifar S¹, Shamsaei GR¹, Hassanzade AR¹, Nakhostin- Mortazavi A¹, Safapour N²
1-Department of Neurology, Ahvaz Jundishapur University of Medical, Ahvaz, Iran
Science
2-Department of Internal Medicine, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran
BACKGROUND: Levodopa increases neuronal plasticity and anatomical and functional changes in the
central nervous system and enhances functional recovery.
PURPOSE: To evaluate the effect of levodopa on motor function recovery of patients after a stroke.
METHODS: This was a double blinded, randomized, placebo-controlled trial to compare the effects of
levodopa-C dose of 100 mg daily versus placebo for 3 weeks. 114 patients with ischemic stroke in the
middle cerebral artery stroke after the first day, levodopa and placebo were randomly assigned to two
groups. They received the stroke routine medications during the study.
RESULTS: Finally, 113 patients (57 patients in the levodopa group and 56 patients in the placebo group)
completed the study. A significant difference was seen in terms of improvement of motor function in
criteria of RMI (p=0.006) and BI (p=0.009) after 21 days in levodopa-C (79.1%) compared to the placebo
group (49%). A review was carried in the subgroups, which indicate that patients with cortical stroke in
the levodopa group had a significant improvement compared with the placebo group (p=0.005).
Approximately 79% of patients (n=35) in levodopa-C group, mostly in the cortical stroke, obtained more
than 25% their basic motor function on the basis of criteria BI and RMI while the rate in the placebo
group was 44% (eight persons) (p=0.008).
CONCLUSION: The promising results of the efficiency of levodopa-C were observed in the subgroup of
patients with cortical stroke. Larger clinical studies involving larger numbers of patients with cortical
ischemic stroke is needed to better assess the impact.
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163
The association of seasonal and weather changes with the incidence of stroke in Zanjan
Valiasr Hospital
Golipoor F, Eshghi A
Zanjan University of Medical Sciences, Zanjan, Iran
BACKGROUND: Stroke is the second cause of death and the third reason for urological disability
worldwide. Recent studies suggest seasonal and climate changes as being involved in the incidence of
stroke. However, the overall outcome of such studies is not conclusive and no similar study so far has
been conducted in Iran. In the present study we aimed at investigating the seasonal and weather
variations in the incidence of stroke in Valiasr Hospital in Zanjan city, Iran.
METHODS: Patients admitted to the Valiasr Hospital with a firm diagnosis of a recent stroke during 20102013 were included in the study. ICD-10 coding system for classification of disease was used to extract
the relevant information form the electronic archive of the hospital. Chi-square test was used to examine
the independence in the seasonal outbreak of stroke. Negative bi nominal regression modeling was
performed to test the relationship between the incidence of stroke and air temperature.
RESULTS: Totally, 6636 patients were included in the study. A significant monthly/seasonal difference
was observed in a 3-year period (p-value<0.05), whereas the differences were not statistically significant
when each year was considered, separately. The highest 3-year incidence of stroke was found to be in
spring (April) while the incidence was the lowest in the fall (December). No significant relationship was
found between the air temperature and outbreak of stroke.
CONCLUSION: We were able to show a significant difference in the incidence of stroke by seasons. The
weather changes, however, could not justify our observations. This calls for further research to
investigate the non-climate predictors of seasonal variations in the incidence of stroke.
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164
A Comparative Study of Low-Molecular-Weight Heparin with Unfractionated Heparin in
Treatment of Cerebral Venous Sinus Thrombosis Randomized controlled trial
Daryoush Afshari, Nasrin Moradian, Freshteh Nasiri, Arash Bostani, Nazanin Razazian
Kermanshah University of Medical Science, Kermanshah, Iran
BACKGROUND: There is small randomized controlled trial for comparison of efficacy and safety of LowMolecular-Weight Heparin (LMWH) and Unfractionated Heparin (UFH) in treatment of cerebral venous
sinus thrombosis.
PURPOSE: In current study, we have compared two kinds of heparin and their effect on mortality,
severity of disability and neurologic deficits in treatment of cerebral venous sinus thrombosis (CVST).
METHODS: Our study was performed as a randomized double-blind clinical trial in 2013-2014. Fifty two
cases of cerebral venous sinus thrombosis, confirmed by brain MRI and MR venography, were included in
this study and randomly divided into two groups with similar demographic, clinical, and radiological
characteristics. Twenty six cases received LMWH and the other 26 cases received UFH for 7 days after
which 8 cases were excluded from the latter group due to loss to follow-up or transferring to other
centers. Mortality rate, neurologic deficit, and severity of disability of each group are assessed by National
Institute of Stroke Scale (NIHSS) and Modified Rankin Scale (MRS).
RESULTS: One patient died in each group, while, after one month, we observed no significant difference
in the rate of neurological deficits based on NIHSS (p value=0.76) and severity of disability (MRS) (p
value=0.95) between two groups.
CONCLUSION: This study showed that efficacy of LMWH and UFH was similar and there is no difference
in mortality rate between two types of treatments.
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New Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation
Behnam Safarpour Lima1, Khosro Jamebozorgi2
1-Department of Neurology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran,
Iran
2-Department of Neurology, Zabol University of Medical Sciences, Zabol, Iran
Vitamin K antagonists such as warfarin have historically been used to reduce the risk of stroke in patients
with atrial fibrillation as the only oral anticoagulants for decades. Atrial Fibrillation is responsible for
15% of strokes in people of all ages and 30% in people over 80. Traditionally, warfarin has been the
anticoagulant of choice in these patients and has been shown to significantly reduce the risk of stroke.
Warfarin, however, is difficult to manage as it requires frequent laboratory monitoring and has multiple
interactions with common foods and drugs. Furthermore, many people receiving warfarin therapy still
have inadequate anticoagulation. Therefore, there is a significant need for new oral anticoagulants that
are safe, effective, and convenient to use. Direct thrombin inhibitors and factor Xa inhibitors are new
anticoagulants recently approved for prevention of stroke in patients with AF. As medical providers, it is
important to be familiar with the pharmacology of these new oral anticoagulants, indications for their
use, and reversal therapy in the setting of major hemorrhage. The aim of this article was to provide a
systematic review of recently published clinical data on the direct thrombin inhibitors and factor Xa
inhibitors in the management of AF.
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166
Glycated hemoglobin in acute strokes
Alireza Vakilian1, Amir Moghadam Ahmadi2, Moslem Heidari3, Marjan Saeedinezhad4
1-Geriatric Care Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
2-Clinical Research Development Center, Ali- Ebn Abitaleb Hospital, Rafsanjan University of Medical
Sciences, Rafsanjan, Iran
BACKGROUND: Stroke is considered as the most common and most fatal neurologic condition. Some
studies have indicated the prognostic value of glycated hemoglobin (HbA1c) serum level in patients with
stroke. The current study aims measuring the HbA1c serum level in patients with ischemic stroke and
intracranial hemorrhage (ICH) and determining its relationship with the extent and severity of these
lesions.
METHODS: 120 stroke patients were studied with aspect of their HbA1c serum levels during the first 72
hours after their admission. They were classified into two groups, ischemic and hemorrhagic, base on
imaging data. The extent of lesions was measured separately in both groups. Severity of lesions also was
determined with Modified Rankin Scale (MRS). Data were analyzed using the SPSS 18 and Anova and T
test.
RESULTS: In our study, 49 male (40.8%) and 71 female (59.2%) patients were studied. The average age
was 72.03 years. Fifty eight patients were diabetic. Level of HbA1c was significantly higher in ischemic
stroke patients than hemorrhagic ones (P<0.005). Although the level of HbA1c was higher in major
ischemic stroke group than minor ones, we did not find any correlation between severity and HbA1c. The
level of HbA1c with extent and severity of hemorrhagic lesion had inverse non-significant relationship.
The only finding identified between level of HbA1c and other stroke causing-factors was higher level of it,
in hypertensive ICH patients (p=0.04).
CONCLUSION: These findings revealed that increased level of HbA1c in patients with ischemic stroke can
point to great role of diabetes in this type of stroke. We also found a relative inverse correlation between
this hemoglobin and the extent of hemorrhagic lesions.
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Investigation of family history among patients with stroke in Tohid Hospital of Sanandaj
between 2013 and 2014
Payam Khomand, Amir Ghaba sia, Ghobad Moradi, Behrooz Ahsan
Kurdistan University Medical Sciences, Kurdistan, Iran
BACKGROUND: The high prevalence of stroke and increased rates of its morbidity and mortality,
necessitate the importance of known related risk factors. Most of the risk factors are known and some
have been controlled such as hypertension, diabetes. However, some of them are still unknown or their
importance has not been completely assessed. Family history is considered as an independent factor in
some references, but there is some controversy surrounding investigations about its effects.
METHODS: This is descriptive cross-sectional study study. Cases are selected subsequently during 12
months from the patients who were admitted in the Tohid Hospital of Sanandaj. Family history of stroke
(in first-degree relatives) and other existing risk factors were compared in 100 patients with stroke and
100 controls in other wards. Type of stroke was recorded according to criteria of world health
organization.
RESULTS: Analysis of collected data was performed by STATA-11 software and performing X2-test and Ttest showed a significant association (Odds ratio, 1.29 (1.64- 1.02); P value=0.033), between stroke and
positive family history. Stroke occurs in patients older than 55 years more than 3 times compared to
patients less than 55 years. Also, in patients those have positive family history of stroke, it occurs more
than 29% of patients compared with who have not family history of stroke. The most effect of family
history was showed at first on sibling and then in mother, children and also father. For others risk factors
such as hypertension and diabetes associated with stroke in patients, there was no significant association
(Odds ratio, 0.96 (1.10- 0.85); P value=0.92).
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168
Prognostic value of early CT- Scan findings in middle cerebral artery infarction
Iranmanesh F, Gadari F, Esmeli F
Neurology Research Center, Kerman Medical University, Kerman, Iran
BACKGROUND: Some patients with massive ischemic infarction are at risk for massive brain edema and
death. Recent studies show that, early CT-Scan findings may have prognostic value for detection of
malignant course. In this study, we evaluated prognostic value of early CT scan findings in middle
cerebral artery infarction.
METHODS: In this cross-sectional study, frequencies of early CT- Scan findings within 6 h after stroke
onset in 150 patients suffering middle cerebral artery infarction were collected. The diagnosis of middle
cerebral artery infarction was confirmed by brain MRI. The patients fallowed for one month. The data
were analyzed with software SPSS16.
RESULTS: Twenty three (15.3%) patients had early CT-Scan findings. In patients who were died, 13 had
early CT scan finding and 9 patients were without any changes. This difference was statistically significant
(P≤0.05).
CONCLUSION: The present study showed that early CT scan findings have predictive value in patients
with ischemic stroke.
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169
Association between ankle-brachial index and cerebral vessels stenosis in acute ischemic
stroke patients
Hosseinali Ebrahimi, Farad Iranmanesh
Neurology Research Center, Kerman, Iran
BACKGROUND: Previous studies show that ankle-brachial index (ABI) significantly correlated with
mortality and functional outcome in patients with ischemic stroke. Some studies point to association
between specific vessels involvement and ABI. The aim of this study was to investigate, association
between ABI with intra and extra cerebral vessels stenosis in acute ischemic stroke patients.
METHODS: In this cross-sectional study, 284 patients with acute non-embolic ischemic stroke were
evaluated. The diagnosis was confirmed by physical examination, embolic evaluation and neuroimaging.
ABI measured within 24 hours after stroke. Doppler ultrasound was done in the first 5 days of stroke
onset. To analyze the data, t-test were used.
RESULTS: In this study 52.4% was male. Abnormal ABI was found in 20.4%. Patients with abnormal ABI
were more likely to have intracranial arteries stenosis. Multiple logistic regression analysis showed that
hyperlipidemia was independent factors associated with abnormal ABI.
CONCLUSION: Our data showed that the prevalence of abnormal ABI in patients with large vessels
atherosclerotic infarction is high. Abnormal ABI is associated with intracranial artery stenosis.
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170
Comparison of stroke risk factors in first-ever ischemic stroke patients and patients with
recurrence
Shafa MA, Iranmanesh F, Shafa MSH
Neuroscience Research Center, Kerman University of Medical Sciences, Iran
BACKGROUND: Stroke is the most frequent, as well as the most fatal neurologic disease. Although in
almost all societies, ischemic stroke risk factors have been identified in various countries, risk factors for
recurrence are different.
PURPOSE: The aim of our study was comparison stroke risk factors in first- ever ischemic stroke patients
and patients with recurrence.
METHODS: This study was a cross-sectional study on 250 patients with ischemic stroke. The diagnosis
was confirmed by brain MRI. Patients according to medical history and evaluation by a neurologist and
neuroimaging divided in 2 groups. The first group of patients had new stroke and other group of patients
had recurrent stroke.
RESULTS: Forty three (17.2%) patients had stroke recurrence. Recurrence was more frequent in men. In
patients with first- ever ischemic stroke hypertension, diabetes and ischemic heart disease were the more
frequent risk factors but in patients with recurrence hypertension, hyperlipidemia and diabetes were
frequent. There was significant correlation between recurrence and age, hyperlipidemia and ischemic
heart disease.
CONCLUSION: Ischemic stroke recurrence in more frequent in men. Patients with old age, hyperlipidemia
and ischemic heart disease are more susceptible to stroke recurrence.
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Prognostic value of uric acid in patients with ischemic stroke
Hamzei Moghaddam A, Iranmanesh F, Hamzei Moghaddam R, Eslami H
Neurology Research Center, Kerman University of Medical Sciences, Iran
BACKGROUND: Ischemic stroke is one of the most common neurological diseases. Impact of high level of
uric acid on ischemic stroke is still controversial. We conducted this study to investigate the correlation
between hyperuricemia and stroke recurrence in patients with ischemic infarction.
METHODS: This was a cross sectional study on patients with acute ischemic stroke. The diagnosis was
confirmed by MRI. Serum level of uric acid in the first 24 hours of admission was measured with
photometry method. The patients fallowed for three months in term of recurrence. The data were
analyzed with software SPSS16.
RESULTS: Hyperuricemia was seen in 24% of patients. Mean serum level of uric acid in patients with
recurrence was 6.6±1.3 mg/dl and in patients without recurrence was 5.2±1.5 mg/dl. There was a
significant relationship between hyperuricemia and stroke recurrence (P≤0.05).
CONCLUSION: Hyperuricemia is risk factor for recurrence in patients with acute ischemic stroke.
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172
Relation of personal stress and tension with cerebrovascular accidents
Kavian Ghandehari, Mohammad Reza Davari, Mohammad Reza Sobhani, Mohammad Mousavi Mirzaei,
Elnaz Kiadarbansari, Sara Asaadi, Mehdi Amjadi
Neurocognitive Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
BACKGROUND: Stress is among novel risk factors of stroke. Researches about influence of stress in
epidemiology and pathophysiology of stroke are scare.
METHODS: Consecutive stroke patients admitted in Ghaem hospital, Mashhad, Iran during September to
December 2014 were assessed by a standard stress questionnaire scale and compared with age and
gender matched controls. A modified version of Holmes and Rahe stress scale served for assessment of
stress. Case and control groups were categorized as high and low stress people as more than or less than
75 score respectively. Etiology of ischemic stroke was determined based on Asian Stroke Criteria by a
stroke neurologist with a standard battery of diagnostic investigations.
RESULTS: 361 stroke patients (191 Females, 170 Males) and 190 controls (100 Females, 90 Male) were
evaluated. Stroke patients included 305 brain infarction and 56 intracerebral hemorrhage (ICH). High
stress score was significantly more frequent in whole of 361 stroke patients and ICH group compared to
controls; p=0.010, OR=1.817 and p=0.000, OR=5.333, respectively. Distribution of high stress score was
not significantly different in patients with brain infarction compared to controls; p=0.178, OR=1.388.
Distribution of high stress score was not significantly different in uncertain, cardioembolic and mixed
etiologic subtypes of brain infarction compared to controls; p=0.375, p=0.207 and p=0.688, respectively.
While, high stress score was significantly more frequent in atherothrombotic subtype of brain infarction
than controls, p=0.037. Influence of gender on distribution of high stress score within our 361 stroke
patients was not significant (p=0.281). High stress score was significantly more frequent in ICH than
patients with brain infarction (p<0.0001).
CONCLUSION: Stress is an important risk factor of ICH and atherothrombotic brain infarction.
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173
Stroke Prevention in Very Old Patients: What is the Strategy of Choice?
Hossein Pakdaman1, Ehsan Sharifipour2
1-Department of Neurology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2- Neuroscience Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran
Oldest old patients (≥80 years) make up a third of ischemic stroke (IS) patients and they have higher
morbidity and mortality rate among these patients. They are not only at higher risk of experiencing
stroke, but also have multiple comorbidities that make treatment for secondary stroke prevention
challenging. Very few clinical trials specifically related to secondary stroke prevention treatment efficacy
have focused on these patients. Therefore, evidence-based recommendations for treatment specific to this
population are not available. Some of the special considerations for stroke prevention treatments in older
patients include careful titration of blood-pressure-lowering drugs to avoid hypotension, the risk of
haemorrhagic stroke with HMG-CoA reductase inhibitors (statins) and weighing the risk of recurrent
ischaemia versus bleeding in patients taking antiplatelet or anticoagulant therapy. The risk of periprocedural complications appears to be high with both carotid angioplasty and stenting and carotid
endarterectomy in older patients with carotid stenosis. Other common issues in older patients include
adverse drug events, recognizing the risk of dementia, depression and osteoporosis and deciding when to
discontinue secondary stroke prevention. In this review, we provide the practitioner with the evidence
related to specific approaches to secondary stroke prevention in older patients, and identify the
knowledge gaps that currently limit our ability to appropriately treat this vulnerable population.
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Evaluation of Cardiac Sources of Emboli by Transesophageal Echocardiography in the
Ischemic Stroke Patients in Shiraz
Sadegh Izadi1, Mohammad Amin Toodeji2, Abdolhamid Shariat1, Mohamad Hosin Nikoo3
1-Clinical Neurology Research Center, Neuroscience Research Center, Medical School, Shiraz University of
Medical Sciences, Shiraz, Iran
2-Student Research Committee, Shiraz University of Medical Sciences, Shiraz Iran
3-Department of Cardiology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
BACKGROUND: Embolus is one of the causes of ischemic stroke that can be due to cardiac sources such
as valvular heart diseases and atrial fibrillation and atheroma of the aorta. Transesophageal
echocardiography (TEE) is superior for identifying potential cardiac source of emboli. Due to insufficient
data about TEE findings in ischemic stroke in Iran, the present study was done to evaluate cardiac source
of emboli by TEE. The main aim of this study was to describe the cardiogenic sources of emboli by TEE in
the ischemic stroke patients.
METHODS: This is a hospital-based cross-sectional study conducted during a 13-month period from
January 2012 to February 2013in Shiraz Nemazee teaching hospital. Patients that referred to this center
and were admitted with stroke diagnosis were included but hemorrhagic stroke cases were excluded. 229
patients with ischemic stroke diagnosis were included and underwent TEE.
RESULTS: Causes of cardiac emboli were detected in 65 cases (40.7%) and categorized to high-risk
(29.7%) and potential risk (11%). High risk cardiac sources including atrial fibrillation (8.7%), mitral
valve disease (MS or MI) 11 cases (4.75%), aortic valve disease (AS or AI) 8 (3.5%), prosthetic valve 3
(1.35%), dilated cardiomyopathy 45 (19.65%) and congestive heart failure with ejection fraction <30% in
8 cases (3.5%). Potential cardiac sources of emboli comprising 7 cases (3.05%) septal aneurysm, 4
(1.75%) left ventricular hypokinesia, 13 (5.7%) mitral annular calcification and 9 cases (3.95%) complex
atheroma in the ascending aorta or proximal arch.
CONCLUSION: Our study showed that high risk cardiac source of emboli can be detected by TEE in a
considerable percentage of ischemic stroke patients. The most common high risk cardiac sources were
dilated cardiomyopathy and valvular heart diseases.
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175
Comparing cerebral venous sinus thrombosis in the Ramadan and non Ramadan months
in Shiraz between 2003-2013
Sadegh Izadi
Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
BACKGROUND: Cerebral venous sinus thrombosis (CSVT) was described in 1825 for the first time. It was
seen in all ages. The true prevalence rate is not clear. It was suggested that the prevalence rate increase
during fasting and in the month of Ramadan.
Methods: In a cross sectional retrospective study the data of all the patients with diagnosis of CSVT that
were admitted in the shiraz Namazi hospital in the Ramadan and non Ramadan months since 2003-2013
gathered from their charts. The selected data including age, sex, oral contraceptive pill consumption,
pregnancy, complication of CSVT and MRI findings obtained and statistical analysis was recorded.
RESULTS: Among 49 patients 27 patients (55%) in the Ramadan and 22 (45%) in the non Ramadan
months were diagnosed as CSVT. 85.7% of them were female and the mean age was 37±13.9 years. The
most frequent risk factor was OCP consumption. Total mortality rate was 8.2%.
CONCLUSION: Although the frequency and complications of CSVT was more common in the Ramadan
months but it was not statistically significant.
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176
Oral contraceptive-related cerebral venous thrombosis as an initial manifestation of
antiphospholipid syndrome in the absence of systemic lupus erythematosus
Payam Saadat1, Reza Mohseni Ahangar2
1-Department of Neurology, Babol University of Medical Science, Babol, Iran
2- Department of Internal Medicine, Babol University of Medical Science, Babol, Iran
Cerebral venous sinus thrombosis is a rare and potentially life-threatening neurologic manifestation of
antiphospholipid syndrome. Oral contraceptive pills may increase the risk of vascular events, even in
people without family history of venous thrombosis. A 31-year-old woman presented with four weeks of
constant headache. She had a history of taking OCP for one year. The results of brain magnetic resonance
imaging and venography confirmed a diagnosis of cerebral venous sinus thrombosis. The serum
anticardiolipin and antiphospholipid antibodies were elevated and a definitive diagnosis of
antiphospholipid syndrome was made. The present report demonstrates the importance of screening for
antiphospholipid antibodies in patients presenting with cerebral venous sinus thrombosis, despite
history of taking OCP.
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177
Evaluation of effect of Intravenous Magnesium Sulfate in Clinical Improvement of
Patients with Acute Stroke in MCA Territory in Alavi Hospital
Fattahzadeh A. Ghasem, Atalu Abolfazl, Ghasemi M, Tarassoli N
Ardabil University of Medical Science, Ardabil, Iran
BACKGROUND: This study evaluated the effect of intravenous magnesium sulfate in clinical
improvement of the patients with acute stroke. In various studies, there is a lot of information about the
use of magnesium sulfate in different conditions of brain ischemia. While neuroprotective effects of
magnesium sulphate as a neuroprotective agent has been demonstrated in focal and global brain ischemia
in animal models. However, the effect of this agent is still unclear.
METHODS: Eighty patients (47 percent of patients were female and 53 percent were male) with acute
ischemic stroke signs and symptoms, lasting less than 12 hours of ischemia, were included in the study.
Patients were divided into two groups; 40 patients received 4 g of MgSO4 over 15 minutes and then 16 g
over the next 24 hours, and the other 40 patients received placebo.
RESULTS: The results showed that magnesium sulphate administrated group had better clinical
improvement rate than control group. The number of patients with Grade III decreased in magnesium
received group and patients with Grade II, I increased. After 2 weeks, patients with Grade III decreased to
12.5% and the patients with Grade II and I increased to 50% and 37.5%, respectively (based on NIHSS
score).
CONCLUSION: According to this study, magnesium sulfate can be used as a neuroprotective agent in
patients with acute ischemic stroke.
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178
Efficacy of Citalopram on Ischemic Stroke Functional Outcome: A Randomized Clinical
Trial
Daryoush Savadi Oskouie1, Ehsan Sharifipour1, Masoud Nikanfar1, Mazyar Hashemilar1, Homayoun
Sadeghi Bazargani2, Samad EJ Golzari3, Saeed Ghazanfari Amlashi1, Zahra Abbaszade4, Elyar
Sadeghihokmabadi1, Reza Rikhtegar1
1-Department of Neurology, Neuroscience Research Center (NSRC), Tabriz University of Medical Sciences,
Razi Hospital, Tabriz, Iran
2-Department of Statistic and Epidemiology, Road Traffic Injury Research Center (RTIRC), Department of
Statistic and Epidemiology, Tabriz University of Medical Sciences, Tabriz, Iran
3-Department of Anesthesiology, Department of Anesthesiology and Intensive Care, Tabriz University of
Medical Sciences, Tabriz, Iran
4-Department of Psychiatry, Tabriz University of Medical Sciences, Razi Hospital, Tabriz, Iran
BACKGROUND: Stroke is one of the main causes of death and disability in the adult population and
recovery from it is considered by many researchers.
PURPOSE: The aim of the present study was to evaluate the efficacy of citalopram on 3-mounth
functional outcome of non-depressed acute ischemic stroke (AIS) patients.
METHODS: In a randomized, placebo controlled clinical trial, 144 patients with AIS were studied for 3
months. In one group, the patients received oral citalopram 20 mg (once daily) and in the other group,
they received placebo. All patients received standard care including physiotherapy. Patients with
depression were excluded from the study. Primary outcome was set to a 50% reduction in the 3-month
National Institutes of Health stroke scale (NIHSS) compared to the baseline scores.
RESULTS: Of 144 eligible patients, 123 with mean age of 66.39 (62 in citalopram group and 61 in placebo
group) were considered for the final analysis. The primary outcome of the study was obtained in 61
patients (98.3%) of citalopram group and 34 patients (68%) of placebo group (p<0.000) with the risk
ratio and number needed to treat of 10.6 (CI: 1.6-71.8) and 1.8 (CI: 1.4-2.4), respectively. No major
adverse events were found in either group.
CONCLUSION: Citalopram is a safe and tolerable medication in patients with AIS and could improve
functional outcome in these patients.
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Relation of Stroke Risk Factors with Specific Stroke Subtypes and Territories
Farhad Assarzadegan, Hanif Tabesh, Arya Shoghli, Mahmood Ghafoori Yazdi, Hadi Tabesh, Parnaz
Daneshpajooh, Mehdi Yaseri
School of Medicine, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
BACKGROUND: Although the risk factors of ischemic strokes are well defined, there is slight information
about their relations with the etiologies of ischemic strokes. This study investigates the distribution of
ischemic stroke risk factors and their connections to diverse etiologies of cerebrovascular attack (CVA)
and specific ischemic regions of brain.
METHODS: In this cross sectional study, we analyzed the data of patients with definite diagnosis of CVA,
excluding hemorrhagic strokes, registered in Imam Hossein Medical Center in Tehran, Iran. The data were
collected from entire archived medical records from March 2010 till September 2012, retrospectively.
RESULTS: Out of 1696 cases a total of 1011 subjects, 487 (48.2%) males and 524 (51.8%) females with
mean age of 68.91±13.54 were included in the study. Patients suffering from atrial fibrillation (AF),
valvular heart disease (VHD), and dilated cardiomyopathy were more prone to develop cardioembolic
stroke (OR (95%CI): 19.33(11.98-31.17) 31.91(21.69-41.96), 22.73(6.73-76.75) respectively). Those with
diabetes mellitus (DM), carotid artery stenosis and dyslipidemia (DLP) had a higher prevalence of
macroangiopathic stroke (ORs (95%CIs): 1.83(1.37-2.43), 5.75(3.89-8.48), 1.35 (1.02-1.79) respectively).
Ischemic heart disease (IHD), AF, and VHD were associated with stroke in the brain territory supplied by
middle cerebral artery (MCA) (ORs (95%CIs): 1.39(1.08-1.79), 1.96(1.33-2.89), 1.38(1.03-1.85)
respectively) while DM and carotid artery stenosis were correspondent with posterior cerebral artery
(PCA) stroke (ORs (95%CIs): 1.46(1.06-2.01), 1.47(1.04-2.08) respectively). Peripheral artery disease
(PAD) and smoking were related with watershed stroke (ORs (95%CIs): 13.27(1.30-134.61), 4.13(1.4511.73) respectively). Furthermore, we observed that opium addiction was associated with stroke resulted
from carotid arteries stenosis (OR (95%CI): 4.15(1.75-9.83).
CONCLUSION: The diagnosis of the weight of each risk factor of ischemic strokes on different etiologies
and territories of ischemia can assist care providers for a more efficient prevention of strokes. The results
of this study can also be a basis for further investigations to corroborate the pathophysiology of such
relations.
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NEUROLOGY
& GENERAL MEDICINE
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A Case Report of Neuroleptic Malignant Syndrome Following Carbamazepine Withdrawal
Reza Boostani, Ali Ghabeli Juibary
Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
CASE PRESENTATION: A 34-year-old male with a history of bipolar mood disorder and seizures was
admitted to the hospital with changes in mental status, ataxia, nausea, development of tremors, and a
temperature of 39 °C. Initial differential diagnoses included seizure, aspiration, stroke, and infection. Once
these were excluded, NMS was considered. The patient exhibited other characteristics of NMS during
hospitalization, including lead pipe rigidity, tachycardia, and high CPK level (up to 2392 IU/L). Drug
therapy on presentation included olanzapine 5 mg 1 times per day, bromocriptine BD, amantadine 100
mg BD. Carbamazepine 100 mg every 12 hours added to treatment 9 days after admission. He reportedly
had discontinued carbamazepine a month before admission. The patient received traditional treatment
for NMS, which included bromocriptine, intravenous fluids, and supportive care. The NMS resolved in 3
days after initiation of carbamazepine.
CONCLUSION: Clinicians should be aware that NMS with EPS can occur with carbamazepine withdrawal.
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181
-2518 A/G polymorphism of the Monocyte chemoattractant protein-1 (MCP-1) gene in
Tunisian Alzheimer patients in relation to β-amyloid (1-42)
Limem Khalifa, Hafsa Jawhar, Charfeddine Bassem, Dridi Hedi, Smach Mohamed Ali
Faculty of Medicine of Sousse, Sousse, Tunisia
BACKGROUND: Inflammation of the central nervous system (neuroinflammation) is now recognized to
be a feature of all neurological disorders. It is characterized by the production of various molecules that
initiate the recruitment of immune cells to the lesion sites, including in the brain. Monocyte
chemoattractant proteins (MCPs) might play an important role in Alzheimer's disease (AD) pathology
through participating to the maturation of senile plaques or APP endocytosis.
METHODS: In this study, we evaluated whether the MCP-1 (2518) polymorphism might be responsible
for susceptibility to AD, utilizing a clinically well-defined group of 173 sporadic AD patients and 150
control subjects.
RESULTS: The distribution of genotype and allele frequencies of the MCP-1 (-2518G/A) polymorphism
did not differ significantly between AD and control groups (p>0.05). Stratifying by ApoE genotype, gender
or age at onset, no differences in both allele frequencies were observed.
CONCLUSION: Our results suggest that the A-2518G polymorphism in MCP-1 gene may not play a major
role in the development of AD in the Tunisian population, but its presence correlates with lower levels of
CSF Aβ42, which can contribute to increase the inflammatory process occurring in AD.
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Neurological involvement in Degos syndrome: A comprehensive review of literature
Samaneh Yousefi1, Afshin Borhani Haghighi2,3, Anahid Safari4, Aixa Garcia-Toledo5, Lee Shapiro6
1-Student Research committee, Fasa University of Medical Sciences, Fasa, Iran
2-Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3-Deparment of Neurology, Shiraz University of Medical Sciences, Shiraz, Iran
4-Deparment of Pharmacology, Kazeroon Azad University, Kazeroon, Iran
5-Steffens Scleroderma Center, Albany, New York, USA, Albany Medical College, Albany, New York, USA
6-The Center for Rheumatology, Albany, New York, USA
BACKGROUND: Malignant atrophic papulosis (Degos disease) is an obliterative vasculopathy of unknown
origin, characterized by erythematous papular skin lesions but the central nervous system (Neuro-Degos
syndrome) and gastrointestinal tract can also be involved in its progressive course.
Review Summary: The frequency of neurologic manifestations is about 20%. The main pathological
feature of neurologic involvement is vascular occlusion resulting in ischemic changes. Central nervous
system presentations include 1) the parenchymal form presenting with brain, spinal cord manifestations
and meningo-encephalitis and meningo-myelitis and 2) the neuro-vascular form presenting with large
cerebral infarcts, intracranial hemorrhage, subarachnoid hemorrhage, subdural hematoma and venous
sinus thrombosis. Predilection to subdural hematoma or hygroma is characteristic for Neuro-Degos
syndrome in comparison to other vasculopathy and vasculitis. The peripheral nervous system
manifestations are less common and include polyradiculopathy neuropathy, and myopathy. CSF analysis
usually shows mild to moderate pleocytosis, increased protein content, and normal glucose. Brain MRI
may reveal cortical, subcortical and deep white matter ischemic lesions with possible nodular,
leptomeningeal, dural, or ependymal enhancement. Spinal cord MRI may reveal patchy lesions from the
periphery to the center or cord atrophy in progressive course. Neuro-degos has a grave prognosis, the
interval from onset of papulosis to death averages two years in patients with neurological involvement.
There is no confirmed treatment for malignant atrophic papulosis but there are promising reports with
Eculizumab and Treprostinil.
CONCLUSION: Neuro-Degos syndrome must be considered in the differential diagnosis of any disease
with atrophic skin lesions and neurologic manifestations.
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183
The assessment of asymmetry in prefrontal regions in individuals with aggression
Parichehr Ahmadi, Vida Mamagani
1-Department of Medical Sciences, Islamic Azad University, Tabriz branch, Tabriz, Iran
2-General Office of Legal Medicine, Tabriz, Iran
BACKGROUND: Several studies have been conducted to determine the criteria for diagnosis and
evaluation of aggression. Despite it still has a way to get through it, based on the evaluation of brain
function, aggressive behavior is not specified.
PURPOSE: The aim of this study was to determine the degree of asymmetry in prefrontal regions of the
brain in individuals with aggression.
METHODS: The sample consists of 30 individuals that go to the clinic for the first time to treat the
aggression and a total of 30 healthy and normal control subjects matched for age and sex with aggression
patients. For diagnosis of patients, Psychiatric Diagnosis and Aggression Questionnaire of Buss and Perry
(1992) was used. Brain activity was measured by quantitative EEG.
RESULTS: The participants in both groups were compared using analysis of variance showed that the two
groups do not differ in terms of two waves theta and delta. In individuals with aggression, increase in
alpha activity in the left, and increase in beta activity in right lobe was observed.
CONCLUSION: The results showed the importance of the prefrontal cortex in the study, assessment,
diagnosis and treatment of aggressive patients.
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184
Medical, non-vestibular causes of dizziness or vertigo
Shahir Mazaheri
Neurology Department, Farshchian Hospital, Hamadan, Iran
Dizziness and vertigo have a broad differential diagnosis. Thus, atypical signs and symptoms for an
underlying vestibular disorder combined with abnormal neurotological examination mandate a more
extensive evaluation. Approximately 50% of patients presenting with dizziness or vertigo to the
emergency department have an underlying non-vestibular medical disorder, whereas only about 33% are
diagnosed with a neurotological (vestibular) disease. The percentage of dangerous disorders in dizzy
patients presenting to the emergency room increases with age (from <10% at age ≤25 to >25% at age ≥
75 years). Frequent non-vestibular causes include vasovagal syncope and dangerous conditions such as
cardiac arrhythmia, electrolyte or fluid disturbances, cardiovascular disorders, anemia secondary to
gastrointestinal bleeding, and hypoglycaemia. Categories provided by most studies segregating the
underlying cause of dizziness or vertigo in patients presenting to the ED were oto-vestibular (13–34%),
other neurological disorders (5–11%), cardiovascular disorders including cardiac arrhythmia (4–21%),
psychiatric diagnoses (2-14%) and non-cardiovascular general medical diagnoses (8–28%). The five most
frequent non-vestibular causes according to Newman-Toker and colleagues (2008) were vasovagal
syncope (6.6%), electrolyte and fluid disorders (5.6%), cardiac arrhythmia (3.2%), anemia (1.6%), and
hypoglycaemia (1.4%). Whereas some of these disorders are recurrent and benign, others are potentially
life threatening if not recognized rapidly. Whereas (pre)syncope in general is considered a benign
disorder, the mortality rate in cardiogenic syncope reaches 30% in the first year, underlining the need to
better identify non-vestibular causes of dizziness or vertigo and initiate appropriate treatment. Reduction
or cessation of drugs inducing the patient’s complaints, administration of electrolyte supplements, and
antiarrhythmic treatment (e.g. by medication or by placing a pacemaker/implantable conversion device)
may be required—if an underlying cause can be identified at all. Treatment options for vasovagal syncope
are usually non-pharmacological and emphasize avoidance of triggers and mechanical or behavioral
strategies to decrease underlying orthostasis. Venous pooling can be counteracted by anti-orthostatic
maneuvers such as squatting or standing with the legs crossed.
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185
Approach to a Patient with Narcolepsy
Shahir Mazaheri, Akram Hosseinzadeh
Neurology Department, Farshchian Hospital, Hamadan, Iran
Narcolepsy is one of the most common hypersomnias of the central nervous system origin. Its primary
symptom is that of excessive daytime sleepiness (EDS). It is estimated to occur in 0.002–0.18% of the
general population. The US prevalence is estimated as between 0.03% and 0.07%, with the condition
estimated to occur in 1 in 2000 of Americans. The male-to-female prevalence is equal. The symptoms
usually appear in the teens and 20s but in many cases there is a 10-year period between onset and
diagnosis. Approximately 50% of adults with the disorder retrospectively report symptoms beginning in
their teenage years. The clinical tetrad of narcolepsy corresponding to the criteria of the International
Classification of Sleep Disorders includes EDS, cataplexy (70%), hypnogogic hallucinations (30%), and
sleep paralysis (25%) and only 10–15% of patients experience the full tetrad. Excessive sleepiness is
often the first reported symptom, followed by cataplexy. EDS alone or in combination with hypnogogic
hallucinations and/or sleep paralysis is the presenting symptom in approximately 90% of patients. The
pathophysiology is unclear. There is some evidence that genetic predisposition, abnormal
neurotransmitter functioning, and abnormal immunemodulation may all play a role in the development
of narcolepsy. History is important in evaluating other possible causes of EDS. Diagnostic testing with a
polysomnogram and next-day Multiple Sleep Latency Test helps to eliminate other causes of EDS such as
sleep apnea, periodic limb movements of sleep, and idiopathic hypersomnia. Narcolepsy can be
differentiated from idiopathic hypersomnia by many key features Effective pharmacotherapy can require
multiple medications. Stimulant medications are used to treat excessive sleepiness and REM-suppressant
medications are used to treat cataplexy. Sodium oxybatecan treat both EDS and cataplexy. Modafinil and
armodafinil are chosen as first-line stimulant medications due to their limited side-effect profile.
Commonly used older stimulant medications include methylphenidate and dextroamphetamine. Newer
REM-suppressant medications that are effective in cataplexy include the antidepressant venlafaxine.
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186
Electrophysiological findings landmarks in patients with auditory neuropathy
Mehrnaz Hosseini
Department of Audiology, Iran University of Medical Sciences, Tehran, Iran
BACKGROUND: Auditory neuropathy spectrum disorder, and the subtype auditory neuropathy (AN),
usually characterized by normal outer hair cell function but disordered neural conduction in the auditory
pathway, which is considered to be a functional disorder rather than an anatomical abnormality.
PURPOSE: The aim of this study is to describe the electrophysiological tests results characteristics of
patients with AN.
METHODS: Related studies were searched using the words of "auditory neuropathy" and other related
keywords, in the databases of PubMed, Scopus, Proquest, and Google scholar. Just most related articles
were selected to write this review article.
RESULTS And CONCLUSION: Abnormal responses in auditory brainstem response and stapedial reflex
(including absence of response, elevated threshold, or perturbed waveform), large cochlear microphonic
in electrocochleography, and presence of otoacoustic emissions, are the most recognizable findings in
electophysiologic tests. Variations in the results of electrophysiologic tests can be attributed to the
various site of lesions related to different pathologies triggered AN. It seems that appearance of electrical
auditory brainstem response after cochlear implantation, as a management for patients with AN, can be
considered as a good prognosis to improve speech perception after surgery in these patients.
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187
Supratentorial cortical ependymoma: An unusual presentation of a rare tumor case
report
Chitsaz A, Mohaghegh M
Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran
Ependymomas are glial tumors derived from ependymal cells lining the ventricles and the central canal of
the spinal cord. Two-thirds of ependymomas arise in the infratentorial or intraventricular, whereas onethird are located in supratentorial space but supratentorial cortical ependymomas are very rate. We
report a case of a cortical ependymoma in 17-year-old boy. The patient presented with transient
recurrent right weakness and diplopia. This tumor was located in the left parieto-occipital region and he
had gross total excision, microscopy and immunohistochemistry showed grade III differentiation
ependymoma.
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188
Psychological symptoms in patients with chronic dizziness
Ahmad Chitsaz, Fariborz Khorvash
Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran
BACKGROUND: Dizziness is one of the most commonly occurring chief complaints in neurology.
PURPOSE: The aim of this study was to differentiate patients with dizziness according to originate and
some to form vertigo and evaluate the relationship of dizziness/vertigo symptoms with psychological
symptoms in patients with chronic vertigo and dizziness.
METHODS: This multicenter, cross-sectional study was conducted on 18- to 65 year-old patients referred
into two neurology outpatient clinics in the city of Isfahan, Iran, during 2012-2013. Patients completed
the symptom check list (SCL-90-R) and vertigo symptom scale-short form (VSS-SF).
RESULTS: During the study period, 179 patients (mean age 30.9±0.1 years, 81.7 women) were included
in 74.3% of the patients (n=133) dizziness was organic and in 25.7% (n=46) of nonorganic origin,
compared with the organic group. The patients with nonorganic dizziness had much more scores on SCL90-R.
CONCLUSION: The results indicate that psychological symptoms are associated with dizziness symptoms
in patients with psychiatric disorders and it should be included in the differential diagnosis in patients
with chronic dizziness. Hence, in cases of dizziness disorders, early interdisciplinary cooperation is both
helpful and essential during diagnosis work up to include signs of somatic and psychosomatic origin and
prevent chronification and reduce the severe handicap and high medical costs.
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189
Metronidazole-induced toxicity in a patient with liver abscess
Masoume Nazeri1, Amin Abollhasani Foroughi2, Hora Heidari1
1-Department of Neurology, Shiraz University of Medical Sciences, Shiraz, Iran
2-Department of Radiology, Shiraz University of Medical Sciences, Shiraz, Iran
BACKGROUND: Metronidazole-induced CNS toxicity causes some neurologic symptoms including ataxia,
encephalopathy and peripheral neuropathy. It is associated with characteristic MRI change in the dentate
nuclei.
CASE PRESENTATION: A 31-year-old female known case of ALL was admitted in our hospital due to
abdominal pain. After completion of work ups liver abscess was diagnosed. Starting metronidazole
therapy, the patient developed diplopia and vertigo. MRI brain showed T2-weighted hyperintensities
within dentate nucleus of cerebellum. Our patient's clinical presentation and MRI findings were most
consistent with metronidazole toxicity, so we discontinued metronidazole and cerebellar symptoms were
resolved.
CONCLUSION: Metronidazole-induced neurologic toxicity is a rare complication. MR imaging is helpful in
clinically suspected patients. Discontinuation of drug results in resolution of symptoms.
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190
Is Obesity Correlated with Cognitive Impairment?
Farzad Ashrafi1, Behdad Behnam1, Mehran Arab Ahmadi1, Hossein Pakdaman2, Afsaneh Zarghi1, Lida
Shashaani3, HamidReza Rokhsatyazdi4, Hossein Delavar Kasmaei4
1-Functional Neurosurgery Research Center, Shohada Tajrish Hospital, Shahid Beheshti University of
Medical Sciences, Tehran, Iran
2-Department of Neurology, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences,
Tehran, Iran
3-Department of Internal Medicine, Shohada Tajrish Hospital, Shahid Beheshti University of Medical
Sciences, Tehran, Iran
4-Department of Neurology, Shohada Tajrish Hospital, Shahid Beheshti University of Medical Sciences,
Tehran, Iran
BACKGROUND: Because of well-established role of obesity in brain lesions, progressing cognitive deficits
in obese patients has been recently suggested. In current study and for the first time, we aimed to assess
cognition status in Iranian obese people and to compare it with non-obese individuals.
METHODS: One hundred and eighteen consecutive patients with the different cardiovascular and
metabolic primary complaints were assigned to obese group and non-obese group. Cognitive status was
assessed at initial visiting using the Montreal Cognitive Assessment (MOCA) questionnaire.
RESULTS: Mean total cognitive score in obese patients was lower than non-obese ones. In total, 25% of
obese patients and 60% of non-obese patients had normal cognitive function. No significant difference
was also found in different sub domains of cognitive ability between obese and non-obese groups. None
of the cognitive domains had significant association with BMI as the considered indicator for defining
obesity. Based on multivariate linear regression modeling, obesity could not predict cognitive deficit.
CONCLUSION: Our survey could not demonstrate an association between obesity and cognitive
impairment in a sample of Iranian patients.
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DEMENTIA
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191
Serum level of Copper, Zinc and Magnesium in Alzheimer's disease
Seyed Ali Masoud
Kashan University of Medical Sciences, Kashan, Iran
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder of unknown
etiology characterized by irreversible cognitive and physical deterioration. That result in lack of
independent function in patients. According to varies studies and their contradictory results on effects of
trace elements like copper, zinc and magnesium on AD, this study was done.
METHODS: This cross-sectional study was done on 50 patients with AD who referred to Kashan
neurology clinic and didn't consume any Cu, Zn and Mg supplements. They didn't have any disease having
significant effects on these elements. Five cc of vein blood was obtained and serum levels of these
elements were checked with spectrometry.
RESULTS: Among 50 patients, 30 persons (60%) were male and 20 persons (40%) were female. serum
Cu level of all patients was within normal range, Serum Zn level in the 3 patients (6%) was under normal
range. Forty four patients (88%) were within normal range and 3 patients (6%) were upper normal
range. Serum Mg level in 6 patients (12%) was under normal range, 40 patients (80%) was within normal
range and 4 patients (8%) was upper normal rang. There wasn’t any relation between serum Cu level and
age and gender (p=0.302 & p=0.432, respectively). There wasn’t any relation between serum Zn level and
age and gender (P=0.416 & P=0.678, respectively). There wasn’t any relation between serum Mg level and
age and gender (P=0.141 & p=0.153, respectively).
CONCLUSION: Regarding to these results, trace elements had no significant changes in patients with AD,
and that may related to effects of diet behaviors, weather, geographic region and genetic factors on
incidence and prophylaxis of AD.
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192
Arthrophytum Scoparium Pomel Extract
acetylcholinesterase activity in mice brain
improves cognitive
performance
and
affects
Med Ali Smach, Jawhar Hafsa, Bassem Charfeddine, Hedi Dridi, Khalifa Limem
Department of Biochemistry, Faculty of Medicine Sousse, Sousse, Tunisia
BACKGROUND: Arthrophytum scoparium Pomel has been widely used in traditional Tunisian medicine
to treat eye and enhance memory.
PURPOSE: This study investigates the neuroprotective effect of Arthrophytum scoparium aqueous extract
(ASAE) in mice through behavioral and biochemical parameters.
METHODS: In this latter investigation, mice injected intraperitoneally with 250 µL of saline (control
group), galactose (10%), or aqueous A. Scoparium extract (300mg/kg body weight) for a period of 7 days.
Cognitive function was assessed by Y-maze active test after a double training and an initial acquisition
trial.
RESULTS: The ASAE had high total phenolic contents (32 mg gallic acid equivalents/g dried extract) and
flavonoids (1.81 mg catechin equivalents/g dried extract). It exhibited a significantly (p<0.05) hydroxyl
radical-scavenging activity (IC50 = 13.9 μg/ml). IC50 value of AChE inhibition of extract was 2.913
mg/ml. The LD50 value was greater than 3000 mg/kg for the aqueous extract of A. scoparium. The mice
treated with 300 mg/kg exhibited a significant decrease in avoidance and discrimination errors during a
retention trial compared to control group (p<0.05). AChE activity significantly decreased in treated mice.
CONCLUSION: The ASAE potentiated memory retention in adult male mice and confirming their use in
traditional medicine.
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193
The role of astrocytes in Alzheimer’s disease
Athena Sharifi Razavi
Department of Neurology, Mazandaran University of Medical Science, Sari, Iran
Alzheimer's disease (AD) is a neurodegenerative disease characterized by the aggregation of amyloid βpeptide (Aβ) into β-sheet-rich fibrils. Plaques containing Aβ fibrils have been viewed as the conventional
hallmark of AD. However, the actual role of astrocytes in AD remains elusive, as they seem to adopt
different functions dependent on disease progression and the extent of accompanying parenchymal
inflammation. Increased production of Aβ and altered processing of tau in AD are associated with
synaptic dysfunction, neuronal death and cognitive and behavioral deficits. Neuroinflammation is also a
prominent feature of AD brain and considerable evidence indicates that inflammatory events play a
significant role in modulating the progression of AD. The role of microglia in AD inflammation has long
been acknowledged. Substantial evidence now demonstrates that astrocyte-mediated inflammatory
responses also influence pathology development, synapse health and neurodegeneration in AD.
Astrocytes may contribute to the clearance of Aβ and restrict the spread of inflammation in the brain.
Conversely, they may contribute to neurodegeneration in AD by releasing neurotoxins and neglecting
crucial metabolic roles. Several anti-inflammatory therapies targeting astrocytes show significant benefit
in models of disease, particularly with respect to tau-associated neurodegeneration. However, the
effectiveness of these approaches is complex, since modulating inflammatory pathways often has
opposing effects on the development of tau and amyloid pathology. An increased understanding of
interactions between astrocytes and neurons under different conditions is required for the development
of safe and effective astrocyte-based therapies for AD and related neurodegenerative diseases.
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194
The naming disorder in dementia
Elham Seihei1, Alireza Mollaei2
1-Musculoskeletal Rehabilitation Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz,
Iran
2-Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
BACKGROUND: Dementia is a group of symptoms related to memory loss and overall cognitive
impairment. Most types of dementias continue to worsen and are usually irreversible. The effects of
dementia etiology and severity on the confrontation naming ability of individuals with Alzheimer's,
Huntington's, and Parkinson's diseases and multi-infarct dementia are investigated. Naming impairment
is a common feature of the language disorder of dementia, yet agreement has not been reached on its
mechanisms.
PURPOSE: The aim of this review is the naming disorder in dementia.
METHODS: Science Direct, Pubmed (2000 through 2015) were searched for English-language studies
using a list of keywords. The books about dementia and speech therapy were studied too.
RESULTS: Naming dysfunction occurred even in mild dementia, in patients whose overall language
function remained normal, and worsened in proportion to the degree both of language deficit and of
overall cognitive dysfunction. Perceptual difficulty and word frequency, but not word length, were
important determinants of naming performance in demented patients. Although naming impairment is
reported as a consequence of dementing illness, confrontation naming is not found to be significantly
impaired in mildly involved patients. Further, although moderate Huntington's and Parkinson's patients
made more naming errors than normals, only moderate Alzheimer's disease patients are found to be
significantly different.
CONCLUSION: Regardless of etiology, most misnamings are found to be semantically related or
semantically and visually related to the stimulus. Results challenge the theory that misnamings of
dementia patients result primarily from misperception.
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195
Studying the Relation of Metapsychoplasticity and behavioral inhibition/activation
systems of brain in university students with Emotional/Cognitive Dysfunction
Abbas Alimadadi
University of Science and Culture, Tehran, Iran
BACKGROUND: The term called Plasticity is the specific endowment of nervous system to develop and
also to react or adjust to the internal/external environment changes. While, Neuroplasticity refers to
changes of neurons or glial cells while the brain develop. Neuroplasticity mechanisms are triggered by
various natural/artificial stimuli, which may arise in the internal/external environment and they may
differ quantitatively/qualitatively. Plasticity effects can lead to the Positive/Negative development which
occurs by learning with regard to the cell changes. Based some study, in longtime frequency of experience
emotional problem and cognitive dysfunction has a special plasticity of it down which is negative.
Metaplasticity is a level higher than plasticity and also includes the prior synaptic process. The concept of
Metapsychoplasticity is consisted of three basic construction sets (Temperament, Attachment style,
Defense mechanisms) which of occurs older than the other psychological phenomena such as personality.
The formation type of these construction leads to health or pathology in mental or biological and
cognitive level. It seems that these structures (Metapsychoplasticity) are probably related to brain
functions of behavioral inhibition/activation systems, so lead to cognitive problems. Studying the relation
of these factors can be a guide in clinical section especially in the prevention programs.
PURPOSE: The aim of this study was investigating the level of Metapsychoplasticity and behavioral
inhibition/activation systems of brain in University students with Emotional/Cognitive Dysfunction.
METHODS: 287 university students participated in research. High and low 20 percentages were selected
based GHQ-28 scale. Also short form Adult Temperament Questionnaire (ATQ), Adult Attachment scale
(AA), defense mechanisms questionnaire (ESQ/40) and The Cognitive Failures Questionnaire were used
as instrumental research.
RESULTS: Data analysis showed that the metapsychplasticty elements and behavioral
inhibition/activation systems are significant different between two groups. Students in group with
Emotional/Cognitive Dysfunction had insecure attachment, abnormal temperament, immature defense
mechanisms and disturbance in behavioral inhibition/activation systems.
CONCLUSION: The concept of metapsycholplasticity refers to the basic formation psychological function
which has a main role in health and pathology. It seems that person with Emotional/Cognitive
Dysfunction is under the influence of these basic factors and also the result of brain inhibition/activation
systems functions. These issues may refer to the strong correlation between the metapsychoplasticity and
neuroplasticity phenomena. The recent finding would have very important positive effects in therapeutic
and preventive plans.
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196
Bosweilia Serrata in preventing dementia in patients with mild cognitive impairment: a
randomized clinical trial in Iran
Behnaz Sedighi, Kave Shafie, Abbas Pardakhti, Soheila Rezakhani
Kerman University of Medical Sciences Kerman, Iran
BACKGROUND: Mild cognitive impairment (MCI) is the first stage of dementia. Due to the progression of
irreversible dementia, the best time to do any preventative measure is the MCI stage. Currently, no
effective treatment has been confirmed at this stage. Bosweilia Serrata, from the earliest times, among of
Iranian and Muslims had been used for enhancing memory and learning skills. The present study aimed
to investigate the effect of Bosweilia Serrata on the improvement of MCI.
METHODS: In a randomized double-blind clinical trial, in Kerman in southeastern Iran 80 patients were
enrolled in the intervention group and the placebo group. At baseline, after evaluation by The Montreal
Cognitive Assessment (MoCA) test received intervention and follow-up after 3 months and then were
evaluated by MoCA test. The t-test to compare groups and mixed model was used.
RESULTS: The mean was significantly different between the two groups. The results showed that the
memory component had the greatest impact on the average final score (All p-values were ≤0.0001).
CONCLUSION: The results showed that the use of Bosweilia Serrata can be effective in preventing
dementia in patients with mild cognitive impairment.
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197
Comparison of Post-ischemic Administration of Ginkgo Biloba and Treadmill Running on
Ischemia-induced Memory Deficit and Hippocampal Oxidative Stress in Adult Rats
Ladan Vaghef, Hassan Bafandeh Gharamaleki
Tabriz University, Tabriz, Iran
BACKGROUND: General cerebral ischemic leads to neuronal damage and impaired brain function,
particularly cognitive functions. The purpose of the present investigation was to compare possible
neuroprotective effects of Ginkgo biloba extract and treadmill running exercise on learning and memory
in rats were subjected to transient global cerebral ischemia.
METHODS: Adult male rats were subjected to transient cerebral ischemia induced by bilateral common
carotid occlusion. Then, rats were submitted to treadmill running or were given Ginkgo biloba extract
treatment for 2 weeks after cerebral ischemia. Morris water maze (MWM) and shuttle-box test were used
to assess effects of treadmill exercise and Ginkgo biloba extract on learning and memory. Then, oxidative
stress markers including Superoxide Dismutase, Glutathione Peroxidase, Catalase, and Malondialdehyde
were measured in the hippocampus tissue.
RESULTS: The results of the shuttle box and MWM tasks showed a decrease in learning and memory in
rats subjected to cerebral ischemia. Furthermore, hippocampal oxidative stress was higher in ischemic
rats than in controls. The effect of exercise on learning and memory was more pronounced than Ginkgo
biloba extract. Indeed, exercised Ischemic rats showed significantly better performances in the both
MWM and shuttle box tasks. In ischemic rats treated with Ginkgo, significantly improved performance
was seen only in the MWM task. Although these rats displayed better learning and memory in shuttle box
task compared to untreated rats, but the differences did not reach statistically significant. Decreased
hippocampal oxidative stress was also observed in both exercise - and Ginkgo -treated ischemic rats
compared with untreated ischemic rats.
CONCLUSION: Taken together, these findings suggest that although both exercise and Ginkgo biloba
extract ameliorated cerebral ischemia-induced memory deficit and hippocampal oxidative stress,
exercise, however, was more effective than Ginkgo.
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SPINAL CORD DISORDERS
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Diagnosis of deformity in neuro-skeletal disorders (Kyphosis & Lordosis) by imagingbased quantitative biomechanical analysis method
Mohammadreza Saraei, SeyedEsmaeil Hashemiaghdam, Zohreh Norouzi
Tabriz University of Medical Science, Tabriz, Iran
BACKGROUND: Imaging-based quantitative biomechanical analysis method (IQBA) is non-invasive,
computational and more accurate than existing methods for initial diagnosis of neuro-skeletal disorders.
PURPOSE: Diagnosis of abnormality and deformity by using IQBA method in neuro-skeletal disorders of
the upper limb including CL, LL and TK.
METHODS: This cross-sectional study is done by imaging peripheral areas of the TK, CL, LL and
computing those. First, the coordinates of the virtual markers placed on body dysmorphic relative to the
vertical axis LLi, MLi, RLi (the vertical axis is aligned and has equal length with 2.5 cm distance of each
other, the horizontal axis is tangent to the metatarsus.) measured in both normal and abnormal. Second,
the graph of each of them is drew, compared, and quantitative evaluated. At last, the algorithm of detects
the type and amount of deformity was presented.
RESULTS: The average deviation of normal deformation in cm from the LLi / MLi / RLi in the areas of C,
T, L, S, is computed respectively follow as head-on. CL: {(0.1295), (-0.0146), (0.023), (0.027) / (-0.1353),
(0.0273), (-0.0150), (-0.0030) / (-0.1231), (0.0277), (-0.0040), (-0.0044)}, TK: {(0.0020), (-0.0404),
(0.0205), (0.0241) / (0.0132), (0.0558), (-0.0108), (-0.0098) / (0.0110) (0.0572) (-0.0111), (-0.0121)}
and LL: {(0.0821), (0.0221), (0.1589), (0.0406) / (-0.0490), (0.0066), (-0.1382), (0.00004) / (-0.0389),
(0.0046), (-0.1375), (0.0169)}.
CONCLUSION: According to the results obtained in each of the above anomalies, in the target regions,
there are significant differences to the zero line of the vertical axis either increase or decrease that
indicates the deformity in those regions.
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Diagnostic Approach to Myelopathies
Masoud Ghiasian
Department of Neurology, Hamadan University of Medical Sciences & Health Services, Hamadan, Iran
Myelopathy is a broad term that refers to spinal cord involvement of multiple etiologies. Spinal cord
diseases often have devastating consequences, ranging from quadriplegia and paraplegia to severe
sensory deficits due to its confinement in a very small area. Many of these diseases are potentially
reversible if they are recognized on time, hence the importance of recognizing the significance of
magnetic resonance imaging when approaching a multifactorial disease considered as one of the most
critical neurological emergencies, where prognosis depends on an early and accurate diagnosis.
Traumatic injuries, vascular diseases, infections and inflammatory or autoimmune processes may affect
the spinal cord due to its confinement in a very small space. The history, an adequate neurological
examination and the study of the cerebrospinal fluid guide the diagnosis of spinal cord injuries. However,
imaging is of great importance in order home to determine diagnosis and classify the etiology
appropriately.
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Stem cell therapy in spinal cord injury: focused on human umbilical cord blood stem cells
Ruhollah Hosseini, Gholamreza kaka, Kayvan Yaghoobi, Seyed Homayoon Sadraie, Korosh Mansouri,
Alireza Mohammadi
Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Isfahan, Iran
Spinal cord injury (SCI) is a major cause of disability. Furthermore at present there is no universally
accepted treatment. The functional decrease taking after SCI is contributed to both direct mechanical
injury and secondary pathophysiological mechanisms that are induced by the initial trauma. There have
been many efforts to recover neuronal function from spinal cord injuries, but there are a few
confinements in the treatment of spinal cord injuries. The neural stem cell has been noted for its
pluripotency to differentiate into various neural cell types. A marked increase in the utilization of
umbilical cord blood (UCB) transplantation has been observed in recent years. In this review, we present
the recent findings on the therapeutic potential of hUCB as a safe, plausible and powerful cellular source
for transplantation in SCI. These multifaceted protective and restorative effects from hUCB grafts may be
interdependent and they act in harmony to promote therapeutic benefits for SCI.
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NEUROMETABOLIC
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201
Rett's syndrome, clinical review and genetic update: Report of Five Cases from Northern
Iran
Mohammadreza Salehi Omran, Ali Ghabeli Juibary
Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
& Neurology Department, Ghaem hospital, Mashhad, Iran
Rett’s syndrome (RS), a pervasive neurodevelopmental disorder, is being increasingly recognized all over
the world, but there is paucity of reports from Iran. Due to its manifestations at any stage of development,
it is important to arrive at a correct diagnosis. Five cases are presented, highlighting the need to recognize
this relatively uncommon disorder and to differentiate it from various other neurodegenerative
disorders.
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Rubinstein-Taybi Syndrome (broad thumb-hallux syndrome): A Case Report
Mohammadreza Salehi Omran, Hadi Sorkhi, Yaser Asghari Vostakolaee, Ali Ghabeli Juibary
Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
& Neurology Department, Ghaem hospital, Mashhad, Iran
Rubinstein-Taybi syndrome is a rare genodermatosis with characteristic feature including downward
sloping palpebral fissures, broad thumbs and halluces, and mental retardation. Systemic features may
involve the cardiac, audiology, ophthalmologic, endocrine, neurologic, and respiratory systems. The
syndrome is sporadic in nature and has been linked to microdeletion at 16p13.3 encoding CREB-binding
protein gene (CREBBP). We report a 15-year-old girl that was a known case of chronic renal failure with
downward slanting palpebral fissures toward the ears, hypertelorism, short stature, beaked nose,
micrognathia, strabismus, dental anomalies, large toes, broad thumbs, and mental retardation.
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Overview of Charcot-Marie-Tooth type 1A
Parisa Aob1, Mohammad Reza Ranjouri2, Mahmoud Shekari Khaniani1,2
1-Medical Genetic Department, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
2-Medical Genetic Department, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Charcot-Marie-Tooth (CMT) is one of the sensory and motor neuropathies with a frequency of 1 in 2500.
The syndrome represents a genetically and clinically heterogeneous group of inherited disorders that
classified into demyelinating and axonal. This disorder has related to mutations in more than 40 genes
affecting glial or neuronal functions. In addition, there are many forms of CMT disease, including CMT1,
CMT2, CMT3, CMT4, and CMTX. In addition, the disease is characterized by slowly progressive weakness
in the feet and hands, high arches, hammertoes, scoliosis and slow nerve conduction velocity. Symptoms
generally begin in childhood or adolescence, but some individuals develop symptoms in mid-adulthood.
The severity of symptoms varies greatly among individuals and even among family members with the
disorder. The inheritance pattern in this disorder can be autosomal dominant, autosomal recessive and Xlinked. CMT1, caused by abnormalities in the myelin sheath, has five subtypes: CMT1A, CMT1B, CMT1C,
CMT1D, and CMT1X. CMT type 1A is the most common form of CMT, affecting 50% of all CMT cases and
70% of patients with CMT1. CMT1A is associated with a genetic locus on chromosome 17p11.2 that
Resulting from duplication of PMP22 gene. This gene encodes an integral membrane protein that is a
major component of myelin in the peripheral nervous System. It should be noted that there is no cure for
this neuropathy. However, treatments can help relieve symptoms, aid mobility and increase quality of life
for people with the condition. Several techniques can be used for the molecular diagnosis of CMT1A such
as RFLP-PCR, FISH, Multiplex PCR and MLPA. The MLPA method is a new technique for measurement of
gene copy number. Many studies demonstrate that MLPA was able to detect duplication in all the patients
with CMT1A. This review explains differential diagnosis of CMT1 from other neuromuscular diseases.
Furthermore, it discusses advantage and disadvantage of the various techniques for the genetic diagnosis
of CMT1.
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Can mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS)
syndrome begin in adulthood, without significant previous history?
Mostafa Almasi Dooghaee1, Mohammad Reza Motamed1, Masoud Mehrpour1, Yalda Nilipour2
1-Department of Neurology, Iran University of Medical Science, Tehran, Iran
2-Pediatric Pathology Research Center, Mofid Children Hospital, Shahid Beheshti Medical University, Tehran,
Iran
BACKGROUND: Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a
mitochondrial metabolic disease with multisystem involvement which can cause stroke-like episodes and
status epilepticus.
CASE PRESENTATION: A-48-year-old female with history of early fatigability, migraine-type headaches
and bilateral sensory-neural hearing loss presented with two episodes of serial seizures. On admission
she was affected by Wernicke aphasia and then right hemiparesis. Investigations showed elevated arterial
lactate and ragged red fibers on muscle biopsy.
CONCLUSION: Several cases of adult-onset MELAS syndrome were reported. This syndrome should be
considered in patients with stroke-like events in adults without cerebrovascular risk factors and difficultto-treat seizures.
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HEADACHE
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Frequency of migraine headache precedence in patients with ischemic stroke referred to
Farshchian hospital during 2012-2014
Mehrdokht Mazdeh, Sahar Rasooli
Farshchian Hospital of Hamadan, Hamadan University of Medical Sciences, Hamadan, Iran
BACKGROUND: An association between migraine and ischemic stroke has been observed for many years
but the exact mechanisms by which migraine can lead to stroke are currently still under investigation.
METHODS: In a descriptive cross-sectional study we evaluated all patients with ischemic stroke who had
been hospitalized in Farshchian hospital from October 2012 to October 2014. Life time history of
Migraine headache was diagnosed according to the International Classification of Headache Disorders
(ICHD-II). All the data were put into questionnaire and compared with X2 and one way ANOVA test and by
using SPSS 16 software.
RESULTS: Frequency of migraine headache in 323 patients with ischemic stroke hospitalized was 11.2%
(n=36). Migraine headache in female group (8.1%) and participants who were >60 years old (7.1%) was
more common than male group and the other age groups. Compared with participants without headache,
migraine and non-migraine headache have no significant correlation with ischemic stroke. Also there was
no significant correlation between migraine headache and location of lesion in ischemic stroke patients.
CONCLUSION: in our study no significant correlation between ischemic stroke, location of WML and
migraine headache was noted. Migraine headache in female group (8.1%) who were >60 years old (7.1%)
was more common than male group. More research is necessary in large population-based samples to
more fully understand the effects of migraine headaches, both with and without aura therewith within a
long period is recommended.
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A comparison between the efficacy of pharmacological treatment and pharmacological
treatment plus biofeedback in prevention and treatment of migraine headache attacks
Ghoreishy Abdoreza, Ghoreishi Abolfazl, Tehrani M.R.H
Department of Neurology, Zanjan University of Medical Sciences, Zanjan, Iran
BACKGROUND: Migraine is an occasional headache which is manifested by neurological and digestive
signs and changes in autonomic nervous system. WHO introduces migraine as the first among 20
debilitative disorders. Treatment of migraine headaches can be achieved via two modes of treatment:
pharmacological and non pharmacological.
PURPOSE: The purpose of this study which was carried out at Zanjan Vali-e Asr Hospital in 2012-2013,
was to compare the effects of Biofeedback vs Pharmacological treatments to put forward the best one for
migraine headaches.
METHODS: 86 subjects referred to the neurology and psychological clinic of Vali-e Asr Hospital
diagnosed with migraine by a neurologist and psychologist a according to HIS criteria were randomly
entered into this study. Then, they were plugged into 2 separate groups; one group was labeled as
pharmacological group and the other as Biofeedback and pharmacological group.
RESULTS: Many of the individuals in both groups were between 31-45 years old (60.5% and 41.9%).
Females were the dominant gender (90.7% in the case group and 81.4% in the control group) and the
difference in groups was not statistically significant. The history of headache was more than 1 year in
most participants (67.4% in the case group and 51.2% in the control group). The pulsatile headache was
the most frequent. In both groups, most participants never had met a doctor to take painkillers until the
time of our study (60.5% in the case group and 69.8% in the control group). These differences were not
statistically significant. During the treatment until week 8, the reduction rate in the frequency of attacks,
severity of attacks, MIDAS score and the need to use drugs was significantly higher in biofeedback group,
but in week 10 (P value=0.026,0.311,0.371,0.192) and week 12 (P value=0.035,0.488,0.118 and 0.0001),
the reduction was not significant. Concerning the reduction in the frequency of attacks, the difference was
significant. Meanwhile, the average of frequency of attacks in the case group was 2.68 and in the control
group was 1.65.
CONCLUSION: Biofeedback and pharmacological treatment provides more rapid response than only
pharmacological treatment while simultaneously it is more effective in the treatment of frequency of
attacks. However, its effect on the reduction of headache severity and other consequent disabilities
reaches to equal levels in both groups after a while.
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CADASIL: Report of a family and review
Mazyar Hahemilar, Masoud Nikanfar, Dariyush Savadi Oskoui, Sheida Shaafi
Neurology Department, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
A 33-year-old man presents to our outpatient clinic with a complaint of a chronic paroxysmal headache of
moderate to severe severity since 3 years ago. His family history is negative for any type of chronic
headaches. He has typical visual auras before his headaches. The neurological examination is
unremarkable. A brain MRI is requested to rule out the secondary headache disorders shows T2 and
FLAIR hyper-intensities diffuse in cerebral white matter and circumscribed subcortical lesions
predominantly within the centrum semiovale, thalamus, and basal ganglia, suggestive of small infarcts.
His father who died at the age of 59 following repeated strokes had multiple bouts of unresolved
vomiting. His mental status had declined significantly when he died. The patient’s brother recently
presented with a mild right hemiparesis and his brain MRI showed changes similar to his brother.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
is an inherited, autosomal dominant condition with high penetrance and varying expression. It is an
important cause of protracted disability in young adults, with recurrent strokes, psychiatric dysfunction,
and dementia. Although some families were identified in the 1950s, the syndrome was characterized and
named only in 1993. The prevalence remains unknown, but numbers are increasing in parallel with wider
medical recognition. In this report we discuss a family of three cease of CADASIL and review this disease
in brief.
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Pharmacological treatment for migraine headache based on evidence based medicine
Abbas Ghorbani
Neurology Department, Isfahan University of Medical Sciences, Isfahan, Iran
PURPOSE: We tried to find what pharmacologic therapies are oven effective for migraine prevention.
METHODS: We reviewed published studies from June 1999 to May 2014 to classify available medications
for migraine prevention.
RESULTS: The search strategy used the MeSH term “headache” and a published search strategy for
identifying randomized controlled trials (RCTs) published between June 1999 and May 2007.
Classification of migraine preventive therapies as the following items: Level A: Medication with establish
efficacy (>2 Class trials) Level, B: Medications are probably effective (1 Class I class II studies Level, C:
Medications are possibly effective (1 Class II study), Level U: Inadequate conflicting data support or refute
medication use. Recommendation: Level A) The following medications are established as effective and
should be offered for migraine prevention: Antiepileptic drugs (AEDs): divalproex sodium, sodium
valproate, topiramate. Beta-Blockers: metoprolol, propranolol, timolol Triptans: frovatriptan for shortterm MAMs prevention. Level B) The following medications are probably effective and should be
considered for migraine prevention: Antidepressants: amitriptyline, venlafaxine. Beta-Blockers: atenolol,
nadolol Triptans: naratriptan, zolmitriptan for short term MAMs prevention. Level C) The following
medications are possibly effective and may be considered for migraine prevention: ACE inhibitors:
lisinopril Angiotensin receptor. Beta-blockers: candesartan. Alpha-Agonists: clonidine, guanfacine. AEDs:
carbamazepine. Beta-Blockers: nebivolol, pindolol. Level U) Evidence is conflicting or inadequate to
support refute the use of the following medications for migraine prevention: AEDs: gabapentin.
Antidepressants: Selective serotonin reuptake inhibitor/selective serotonin-norepinephrine reuptake
inhibitors: fluoxetine, fluvoxamine. Tricyclics: protriptyline. Antithrombotics: acenocoumarol, coumadin,
picotamide. Beta-Blockers: bisoprolol. Calcium-channel blockers: nicardipine, nifedipine, nimodipine,
verapamil Acetazolamide Cyclandelate. Level A negative. The following medication is established as
ineffective and should not be offered for migraine prevention: • Lamotrigine Level B negative. The
following medication is probably ineffective and should not be considered for migraine prevention: •
Clomipramine.
RECOMMENDATIONS FOR FUTURE RESEARCH: Although many preventive therapies reviewed herein
are rated as Level C or U on the basis of the quality of evidence available, for some treatments extensive
clinical experience supports a possible role in migraine prevention. Many of the older approaches to
treating episodic migraine lack the financial justification or high-quality clinical study because they are
not currently patentable drugs or otherwise do not promise a financial return for the cost of a major
study. Until such treatments can be accurately studied practitioners are cautioned not to discount these
agents because Class I prospective clinical studies are lacking. A case-by-case evaluation of these agents
as treatment options is prudent. Future direction should include validating these initial clinical
observations in scientifically sound RCTs.
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The efficacy of Topiramate administration in benign paroxysmal torticollis of infancy:
report of four cases with successful treatment
Omid Yaghini, Negin Badihian, Shervin Badihian
Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
BACKGROUND: Benign paroxysmal torticollis (BPT) is a rare paroxysmal dyskinesia and one of the
childhood periodic syndromes presenting with recurrent stereotypic episodes of torticollis usually
accompanied with some of the non-headache features of migraine such as vomiting, ataxia. Although the
nature of the disease may seem to be benign, its recurrent episodes may mimic the attacks of epilepsy and
expose the infant to unnecessary hospitalization and side effects of inappropriate medications. There is
no approved medication for the disease yet though very limited studies has suggested Cyproheptadine
which is not confirmed to be effective for these patients and has limitation to be used in children under 2
years.
CASE PRESENTATION: We report four patients that showed successful response to the treatment with
Topiramate and their episodes stopped to occur. Considering the underlying relation of BPT with
migraine, satisfying response of our cases to Topiramate and the safety of this medication in neonates and
children, Topiramate seems to be an effective and safe medication in reduction and elimination of BPT
episodes. Also one of our cases (patient 4) confirms this finding by showing an explicit dependence in the
regularity and duration of her attacks with Topiramate.
CONCLUSION: Topiramate seems to be an effective medication in prophylaxis of BPT episodes. Further
studies and clinical trials need to be done.
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Migraine in Iran: A systematic review of literature from 2000 to 2014
Hassan Khani, Fariba Ezazi, Mahsa Kowsari, Mahnaz Najarian, Amaneh Ghorbani
Iranian Applied Research Center for Public Health and Sustainable Development (IRCPHD), North Khorasan
University of Medical Sciences, Bojnurd, Iran
BACKGROUND: Migraine is a chronic neurological disorder and attacks are usually unilateral and mostly
pulsating. This disease occurs in about 10% of the general population and affects their quality of life and
performance.
PURPOSE: The purpose of this study was to investigate the epidemiology, clinical and pharmacological
interventions for the treatment of patients with migraine.
METHODS: A literature review of articles published in the Persian Language by Iranian researchers from
1 January 2000 up to 30 December 2014 was conducted using the Scientific Information Database
(through SID). The headings Migraine, chronic headache, used to execute the search.
RESULTS: The results suggest that most patients with migraine signs include nausea, vomiting,
photophobia, noise aversion, unilateral and bilateral headaches, the most important factors in the
occurrence of migraines, insomnia, fatigue, stress, food greasy, fragrance, climate change, anemia,
condiments is. On the other hand, the prevailing epidemiological indicators can be more migraine
prevalence in the age range 15-45 years, women and educated people mention. In the study conducted by
sodium valproate and Anala Preiļi reduce further attacks of migraine have been sought. The
questionnaire used to identify patients with migraine has been studied in the literature include:
demographic and headache questionnaire IHS, MIDAS and has several questionnaires. Descriptive studies
and case studies based on questionnaires and were classified.
CONCLUSION: It seems self-care training, stress management training to identify patients aged 15-5
years, new pharmacological interventions can help in reducing the risk of migraines.
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Study of acetazolamide effect on severity, frequency and duration of cough headache
Abolghasem Rahimdel, Mehdi Heidari, Samaneh Rahimdel
Department of Neurology Shahid Sadoughi University, Yazd, Iran
BACKGROUND: Cough headaches are an a type of headache triggered by coughing, sneezing, laughing,
crying or any act which causes pressure on pain-sensitive structures in the head following the Valsalva
maneuver. Any medication or practice that reduces the production of cerebrospinal fluid or accelerates
its rate of absorption is effective in the treatment of such headaches. The aim of this study was to
compare the effect of acetazolamide comparing to placebo in treatment cough headache.
METHODS: This is a before-after clinical trial with simple sampling. This study performed with 20
patients who had cough headache with our studies criteria. At first patients had been treated by placebo
during 3 months then they have not used any drugs during 1 month. Patients had been treated
acetazolamide during 3 month as placebo duration. They were visited every month and evaluated by
questionnaire of study. This questionnaire consists of different questions of cough headache aspects such
as severity, frequency, duration, associated symptoms, and adverse laboratory changes. Patients’
questionnaire were been gradually completed.
RESULTS: In this study, no statistically significant differences in side effects were found between
acetazolamide and placebo in patients.
CONCLUSION: Acetazolamide is more effective than placebo in treatment of intensity, frequency and
duration of cough headache.
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Comparative study of serum magnesium levels in migraine patients and normal subjects
Fariborz Khorvash, Fatemeh Esteki, Ahmad Chitsaz, Majid Ghasemi
Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
BACKGROUND: Migraine has been known as one of the common diseases in all communities and
especially in our society. So far, several studies have been conducted regarding the etiology and
epidemiology of this disease that some of them suggest the association between migraine and serum
magnesium levels. But these studies had contradictory results. Until now, we didn’t see any study in this
regard, in Iran. So, this study aimed to compare the serum magnesium levels in migraine patients and
normal subjects without migraine.
METHODS: This investigation was a case control study conducted at the Alzahra medical center in 2013.
Participants were included 55 patients with the migraine who referred to the Neurology Centre and 55
normal subjects without migraine referred to other departments of Alzahra. Two groups were matched
for age and sex. To determine serum levels of magnesium, 5 ml of venous blood was taken from the
patients and was sent to the laboratory. Also, the demographic information of all participants such as age,
sex, history of migraine, headache intensity, headache duration and frequency were asked with a
questionnaire and collected. Data were analyzed by SPSS 22 software.
RESULTS: The mean of serum magnesium levels in patient and control groups were 43.0±73.1 mg/dl and
3.0±12.2 mg/dl, respectively. The serum magnesium levels were significantly lower in the migraine
patients compare to the control group (p<0.001). Also, in 28 patients with migraine and 5 subjects in the
control group the serum magnesium levels were seen lower than normal (49.1% versus 9.1%). And the
frequency of magnesium deficiency in patients was significantly higher than control group (p<0.001).
CONCLUSION: Migraine patients faced with the shortage levels of magnesium and due to the safety, the
low cost of this mineral and its beneficial effect on the other physiologic reactions, its usage is
recommended in these patients. Also, according to our findings approximately 10% of the general
population has magnesium deficiency. In this regard, it is necessary to carry out more investigations to
remove Magnesium deficiency in the general population, especially vulnerable groups such as pregnant
females and children.
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Comparison of the somatoform dissociation, fatigue severity and pain behavior in
patients with migraine headache and healthy individuals, and its relationship with
coping strategies
Abolfazl Atalu, Ghasem Fattahzade, Vida Aghazae
Ardebil University of Medical Science, Ardebil, Iran
BACKGROUND: Migraine is a common disorder with mild to severe recurrent headaches with an
unexplained pathology and has several physiological, psychological and social side effects. About 20
percent of people experience the disease in their lifetime. It is believed that genetic and environmental
factors play a role in migraine.
PURPOSE: The purpose of this study was comparison of somatoform dissociation, fatigue severity and
pain behavior in patients with migraine headache and healthy individuals, and its relationship with
coping strategies.
METHODS: This study was a comparative study. The study population included all patients with migraine
who referred to Alavi Hospital in Ardabil in 2014. The number of participants was 120, which was
selected by simple random sampling, as well as 120 healthy subjects were selected. Data collection and
analysis was according to the somatoform dissociation questionnaire (SDQ-20), fatigue intensity scale,
pain behavior scale and coping strategies was used. For data analysis, the mean, standard deviation and
T-Test and Pearson correlation test was used.
RESULTS: This study showed that the comparison of the somatoform dissociation in migraineur and
healthy subjects was significant (P value <0.0001). Also in pain behavior scale, help searching subscale
and pain compliant was significant, and avoidance subscales (p value <0.151) was not significant between
the two groups. Comparison of fatigue intensity in patients with migraine and control group was
meaningful (P value <0.05). The results showed a statistically significant and positive correlation between
all three scale of somatoform dissociation, fatigue severity, pain behavior and coping strategies (P value
<0.05).
CONCLUSION: This study showed that the average comparison of the somatoform dissociation, fatigue
intensity, pain behavior and coping strategies in patients with migraine and control groups was
significant. Also significant statistical and positive correlation between all three scales of somatoform
dissociation, fatigue severity, pain behavior and coping strategies in patients with migraine and healthy
individuals was observed. These symptoms seem to play an important role in this disease. The evaluation
and attention to these essential factors in the treatment of migraine headache is warranted.
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Evaluation the effect of aerobic training on selected physiological factors in patients with
migraine
Ahmad chitsaz, Vazgen Minacians, Freshteh Karimi
Isfahan University of Medical Sciences, Isfahan, Iran
BACKGROUND: Migraine is complex disorder of the nervous system related to carotid blood vessel
vasodilation of intracranial blood vessels around the brain and stimulated the sensory nerves, trigeminal
pain pathways. This study investigates the effect of aerobic training on selected physiological factors in
migraine headache.
METHODS: This was a semi experimental trial. Subjects included 22 women with migraine, the age range
of 22 to 53 years who non randomly were selected and divided into experimental and control groups. The
experimental group consists of 13 patients with migraine and participates in an aerobic exercise 3 times a
week, 60 minute, for 12 weeks.
RESULTS: After 12 weeks aerobic exercise there was a significant reduction in headache severity,
calcitonin gene related peptide and fat percent and increase in maximal oxygen uptake, flexion and
extension of neck, lateral flexion, range of motion, flexion and extension of shoulder in experimental
group.
CONCLUSION: The findings show that aerobic exercise can be an effective treatment for migraine
headache.
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MULTIPLE SLCEROSIS
& NEUROIMMUNOLOGY
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Updates on treatment optimization in multiple sclerosis
Mohammad Hossein Harirchian
Tehran University of Medical Sciences, Tehran, Iran
Thanks to the vast investigations in recent years, the treatment of multiple sclerosis has become possible
with disease-modifying therapies (DMTs) which have had a significant impact on those living with this
disease. Unfortunately, these drugs are not curative and many patients with multiple sclerosis continue to
have relapse or progression in spite of treatment. Besides, several adverse reactions have been reported
with these agents, usually more serious and frequent in more efficient agents. In this regards the DMTs
have been categorized in escalating categories and it is now important to pay attention on monitoring the
results of the chosen therapy and deciding whether or not a patient has compliance for regular use of
drug and is responding well to treatment. Several recommendations have been considered on how
neurologists can assess the status of patients on DMTs and decide when it may be necessary to modify
treatment in order to optimize outcomes. In this paper recent updates on treatment optimization in
multiple sclerosis have been discussed.
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Frequency of first clinical manifestations in Multiple sclerosis patients in clinics of
neurology in Hamadan, IRAN during 2013-2014
Mehrdokht Mazdeh, Amin Elahi Far
Farshchian Hospital of Hamadan, Hamadan, Iran
BACKGROUND: Multiple sclerosis (MS) is one of the most common neurologic diseases which has a
growing prevalence. This disease is common among the young population and causes them sever
neurological disability. Early diagnosis and treatment can reduce the number of attacks and their severity
in patients and plays an important role in enhancement of patients’ health level and their quality of life.
As the primary clinical manifestations of MS are variable and nonspecific, and also different studies
statistically have declared different comments about them, so in this study the prevalence of each
possible primary clinical manifestation in MS patients of Hamadan is reviewed on the basis of age, sex and
the type of clinical manifestation.
METHODS: In this study 500 MS cases that were referred to neurologic clinics and MS institute of
Hamadan and had the entrance criteria were studied and a questionnaire including demographic
information and most common primary clinical manifestations was completed for each of them. After
that, the collected data was analyzed by SPSS 16 software.
RESULTS: In this study 394 patients (78.8%) were female and 106 of them (21.2%) were male. Study
population had a range of 20-40 years old in their age. Mean age in onset of MS was 29.4±8.7 (range of 1162 year). The most common primary clinical manifestations of MS were visual symptoms in 31.6%,
sensory symptoms in 19.8%, balance symptoms in 16.7%, and motor symptoms in 13.8% of the patients,
respectively. No significant difference was seen prevalence of primary clinical manifestations between
males and females.
CONCLUSION: In this study, visual symptoms (optic neuritis and diplopia) were the most common
primary clinical manifestations in all age ranges of the study population of MS patients followed by
sensory symptoms as the second common primary clinical manifestations. As a conclusion, these results
show the necessity of medical team alertness including general physicians, neurologists and
ophthalmologists about early diagnosis of MS. It is recommended to perform studies with more extended
population involved in order to have a more reliable comparison between the prevalence of MS clinical
manifestations on the basis of their age, sex and location.
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Copper, Lead, Zinc and Cadmium Status in Serum of Multiple Sclerosis Patients in the
comparison with healthy peoples by polarography in Iran
Ghoreishy Abdoreza1, Mehran Mohseni2, Raziyeh Amraei2
1-Department of Neurology, Zanjan University of Medical Sciences, Zanjan, Iran
2-Food & Drug Department, Faculty of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran
Multiple sclerosis (MS) is the most common disease caused by an inflammatory demyelinating process in
the central nervous system, characterized by disseminated demyelination of nerve fibers of the brain and
spinal cord. MS is a leading cause of disability in young adults with considerable disability and
socioeconomic consequences. Globally, the average estimated prevalence of MS is 30 per 100000. In Iran,
prevalence of MS is 20 per 100000 in a year. The cause of MS is still unknown. It is believe that, the
disease is triggered by as-yet-unidentified environmental factor(s) in a person who is genetically
predisposed to respond. It seems that, environmental exposure to heavy metals maybe associated with
higher incidence of MS. In this work, we found a possible relationship between serum zinc, cadmium, lead
and copper levels and development of MS. The serum levels of zinc (Zn), cadmium (Cd), lead (Pb) and
copper (Cu) were measured in 50 Iranian patients with MS and 50 healthy person as as control group.
They were matched on age, sex, race, smoking and drinking status. After sample preparation serum
concentrations of zinc, cadmium, lead and copper were determined by polarography. Significantly higher
serum Cu, Zn and Cd levels were found in the MS patients compared with the controls (p<0.05). There
was no significant difference between the serum Pb levels of patients and controls (p>0.05). Serum levels
of Zinc, cadmium and copper were significantly higher in patients with MS compared to controls (p<0.05).
No significant association was found between serum lead levels of multiple sclerosis patients compared
to controls (p>0.05).
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Anti-N-methyl-d-aspartate-receptor encephalitis: case report and literature review
Fariborz Rezaee Talab, Ali Ghabeli Juibary
Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Anti-N-methyl-d-aspartate-receptor (NMDA-R) encephalitis is a newly described autoimmune disorder,
often paraneoplastic in nature, presenting with complex neuropsychiatric symptoms and identification of
the symptom complex is the key to diagnosis. Diagnosed serologically, this disorder is frequently
responsive to immunosuppressant therapy. We herein report the case of a 56-year-old man with NMDA-R
encephalitis presenting with bilateral ophthalmoplegia and spastic tetraparesis. His symptoms initiated
two months before admission. Neurological examination showed mild consciousness disturbance and
bilateral ophthalmoplegia, spastic tetraparesis with limbs hyperreflexia on admission. Cerebrospinal fluid
samples showed mild pleocytosis and high protein content. CSF examination for herpes simplex virus and
mycobacterium tuberculosis by polymerase chain reaction method was negative. Brain MRI disclosed
small subcortical hypersignal lesion in the FLAIR and T2 weighted images. Anti-NMDA-R antibody was
detected in the serum. The patient received IVIG and admitted to intensive care unit but unfortunately
died two weeks after admission.
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Melatonin can improve inefficient oxidative stress defense enzymes in peripheral blood
mononuclear cells from patients with relapsing-remitting multiple sclerosis
Solaleh Emamgholipour1, Mohammad Ansari1, Arash Hossein-nezhad2, Mohammad Ali Sahraian3,
Fatemeh Askarisadr4
1-Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
2-Miller School of Medicine, University of Miami, United States of America
3-MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
4-Shahid Beheshti University of Medical Sciences, Tehran, Iran
BACKGROUND: Oxidative stress has a crucial role in pathogenesis of multiple sclerosis (MS). Melatonin
possesses a central role in modulation of oxidative stress pathways. The purpose of present study was to
evaluate and compare the effect of melatonin on expression and activity of sirtuin1 (SIRT1), Manganese
superoxide dismutase (MnSOD) and catalase in peripheral blood mononuclear cells (PBMCs) from
patients with relapsing-remitting multiple sclerosis (RRMS) and healthy subjects.
METHODS: This study was performed on twelve RRMS patients and fourteen healthy subjects (women
with 20-40 years old). PBMCs were isolated and treated with melatonin (one millimolar) for 12 hours.
Gene expression and activity of SIRT1, MnSOD and catalase were evaluated in PBMCs of controls and
patients.
RESULTS: Before melatonin treatment, the expression and activity of catalase was higher in patients,
which was along with a decreased activity and expression of MnSOD and Sirt1 activity. We found that
melatonin significantly increases activity and mRNA expression of SIRT1, MnSOD and catalase in patients.
Pearson correlation analysis showed a significant correlation between SIRT1 activity with catalase and
MnSOD activity in healthy subjects before melatonin treatment, while SIRT1 activity had no correlation
with activity of MnSOD and catalase in patients. After melatonin treatment, a significant correlation was
observed between SIRT1 activity and catalase activity in PBMCs of both patients and healthy subjects.
Also, in controls but not patients we found a significant correlation between SIRT1 activity and MnSOD
activity in melatonin-treated PBMCs.
CONCLUSION: Our findings demonstrate that melatonin can improve impaired oxidative stress defense in
MS patients through upregulation of SIRT1, Mn-SOD and catalase. In addition, melatonin could partly
improve interrupted regulatory mechanism related to SIRT1- mediated modulation of antioxidant
defense in MS patients via restoring interrupted correlation between SIRT1 activity and catalase activity
in PBMCs of MS patients.
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miR-214 suppressing Th17 differentiation via inhibiting JAK-STAT signaling pathway in
patients with relapsing remitting–multiple sclerosis patients
Ahmadian-Elmi M1, Ghaedi K2,3, Bidmeski Pour A1, Nasr Esfahani MH3
1-Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran
2-Division of Cellular and Molecular Biology, Department of Biology, Faculty of Sciences, University of
Isfahan, Isfahan, Iran
3-Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology,
ACECR, Isfahan, Iran
BACKGROUND: Multiple sclerosis (MS) is one of the most prevalence autoimmune diseases in women
than men with the myelin damage in the central nervous system. Studies revealed that TH 17 cells play a
critical role in the pathogenesis, inflammation and autoimmunity of several autoimmune diseases such as
MS. MicroRNAs are small conserved endogenous non-coding RNAs that can affect cellular function by
regulating gene expression in post transcriptional manner. Recently, researchers interest to focus them as
therapeutic targets.
METHODS: We use in silico analysis to find how miR-214 can affect differentiation pathway of naïve T
cells into TH 17 cells. So we investigated interaction of miR-214 and their validated and predicted targets
in miRWalk database that especially expressed in lymph node and thymus. Ultimately to find signaling
pathway enrichment analysis of miR-214 targetomes given list was imputed in the database annotation,
visualization and integrated discovery (DAVID) online database, version 6.7. DAVID database outputs the
results from Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to recognize the mainly
statistically related signaling pathways and molecular networks via miR-214 targetomes.
RESULTS: Functional annotation tool of DAVID database specified several KEGG signaling pathway
according of targetomes list of miR-214 which is statistically significant that pertain to imputed genes and
including Prostate cancer, Neurotrophin signaling pathway, Endometrial cancer, Pancreatic cancer,
Colorectal cancer and interestingly JAK-STAT signaling pathway for miR-214.
CONCLUSION: According of our bioinformatics studies miR-214 can inhibit JAK-STAT signaling pathway
by targeting STAT2, STAT3 and IL6R. So that can lead to suppress differentiation of TH17 cells by
inhibiting expression of IL17A as a master transcription factor of TH 17 cells. However, we need to
confirm our finding by in vitro and in vivo experiment.
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miR-214 function in patients with multiple sclerosis based on in-silico methods
Ahmadian-Elmi M1, Ghaedi K2,3, Bidmeski Pour A1, Nasr Esfahani MH3
1-Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran
2-Division of Cellular and Molecular Biology, Department of Biology, Faculty of Sciences, University of
Isfahan, Isfahan, Iran
3-Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology,
ACECR, Isfahan, Iran
BACKGROUND: Multiple sclerosis (MS) is a neurodegeneration and defective immune regulation diseases
with the myelin damage in the central nervous system. Studies revealed that TH 17 cells play a key role in
the pathogenesis, inflammation and autoimmunity of several autoimmune diseases including MS. IL-17 is
a hallmark production in T helper 17 (TH 17) cells that recognized as pro-inflammatory cytokine.
MicroRNAs are small endogenous non-coding RNAs that can affect cellular function by regulating post
transcriptional gene expression. Recently, researchers interest to select them as therapeutic targets.
METHODS: We use in silico analysis to find what microRNAs that they can affect differentiation of TH 17
cells from naïve T cells. So we candidate 64 genes that deregulated of them cause different autoimmune
diseases. So our bioinformatics analysis indicated that 8 microRNAs such as miR-214 have strong
interaction with some genes that play crucial roles in TH 17 cells development and differentiation. These
data investigated from 10 databases.
RESULTS: Our bioinformatics data demonstrated that miR-214 show deregulation in MS patients. Several
genes such as STAT6, TSC1, mTOR act as positive regulators that inhibit naïve T cells differentiation into
TH17 cells. So miR-214 has interaction with them and reduces their expression, therefore suppress TH17
differentiation.
CONCLUSION: According of our bioinformatics studies miR-214 can be used as therapeutic targets to
decrease progression symptoms of MS. However, we need to confirm our finding by in vitro and in vivo
experiment.
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Herbal Medicine and immunosuppressive drugs in multiple sclerosis
Jamile Sadat Havaeji1, Mansore Vahhabzade2, Zeinab Vesali Jamshid1, Azam Moslehi3, Masoumeh Dolati1
1-Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
2-Qom Azad University of Medical Sciences, Qom, Iran
3-School of Medicine, Qom University of Medical Sciences, Qom, Iran
Multiple Sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system
in young adults. It is Pathologically Known as infiltrating macrophages and autoreactive T cells,
particularly in the white matter damage myelin. MS is dominated by inflammation, oxidative damage and
cytokines injuries and Based on this understanding; the initial therapeutic strategies were directed at
immune modulation and inflammation control. Although several immunomodulatory drugs are now
available, mostly present significant side effects over the long-term use. And it seems that Current
therapies are not sufficient. On the other hands there are researches on the herbal treatment of MS, but
these drugs is overwhelming clinical evidence of the efficacy of herbal drugs. A number of herbal products
are in use for their immunosuppressive effects. This capacity of herbs maybe had useful applications in
immune-mediated disorders including autoimmune diseases and organ transplant rejection. Plants such
as Salvia miltiorrhiza and Tripterygium wilfordii has been shown to reduce inflammatory cytokines and
mediators, indicating their value in the treatment of acute graft rejections and autoimmunity. Herbal
drugs decrease the level of inflammatory cytokines and subsequently cause reduction of
neuroinflammation and improve remyelination in the spinal cord. Herbal Medicine has targeted antiinflammatory mechanisms to inhibit or slow down the disease progression. However studies indicate that
Herbal Medicine has no serious side effect. But, further studies are needed to elucidate the involved
possible mechanisms.
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MS or not MS
Nastaran Majdinasab
Department of Neurology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous
system in young and middle-age adults, but also affects older people. As a consequence there is an
important role for MRI in the diagnosis of MS, since MRI can show multiple lesions (dissemination in
space), some of which can be clinically occult, and MRI can show new lesions on follow up scans
(dissemination in time). MS has a typical distribution of WMLs. This can be very helpful in differentiating
them from vascular lesions. Typical for MS is involvement of corpus callosum, U-fibers, temporal lobes,
brainstem, cerebellum and spinal cord. This pattern of involvement is uncommon in other diseases. In
small vessel disease there may be involvement of the brainstem, but it is usually symmetrical and central,
while in MS it is peripheral. One of the most common questions in daily radiology practice when we see
an image is 'Do we have to think of Multiple Sclerosis? or are these white matter lesions the result of small
vessel disease, as in a hypertensive patient? or should we think of more uncommon diseases? However
the list of possible diagnoses of WMLs is long. This topic discuss about differential diagnosis MS based of
MRI finding.
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The Effect of Fluoxetine on Fatigue, Sleep quality, Depression and Clinical Status in
Patients with Multiple Sclerosis
FardinFaraji1, Shayan Amjadi2, Bahman Sadeghi3, Afsoon Talaie4
1-Department of Neurology, Medicine Faculty, Arak University of Medical Sciences, Arak, Iran
2- Students Research Committee, Arak University of Medical Sciences, Arak, Iran
3-Department of Social Medicine, Medicine Faculty, Arak University of Medical Sciences, Arak, Iran
Iran4-Health Department, Islamic Azad University, Arak Branch, Iran
BACKGROUND: Expression of the inflammatory cytokines which have been associated with fatigue is
increased during MS.
PURPOSE: The aim of the present study was to determine the anti-inflammatory effects of fluoxetine on
fatigue in patients with relapsing remitting MS and also to survey the changes in sleep quality and
depression.
METHODS: In a triple-blind, placebo-controlled exploratory study, 75 patients with relapsing remitting
MS were randomized to oral fluoxetine 20 mg or placebo daily for 24 weeks. Fatigue, sleep quality and
depression evaluation performed at baseline and end of study period by assessing FSS (Fatigue Severity
Scale), PSQI (Pittsburgh Sleep Quality Index) and BDI (Beck Depression Inventory). Clinical activity of MS
was also studied by assessing EDSS (Expanded Disability Status Scale).
RESULTS: Thirty seven patients in intervention group and 36 patients in placebo group completed the
study. The number of patient with fatigue showed a significant decrease in the fluoxetine group in
comparison with placebo group (p=0.001). Patients who received Fluoxetine showed a significant
(p<0.05) improvement in sleep quality, and fluoxetine significantly improved depression severity in
comparison with placebo (P<0.001). However treatment with placebo produced a significant (p<0.05)
increase in the EDSS but there was no significant different in intervention group (p>0.05). A significant
correlation was observed between changes in EDSS and FSS (P<0.023), BECK (P=0.014) and PSQI
(P=0.014).
CONCLUSION: This proof-of-concept study shows that fluoxetine tends to increase stability in clinical
course in patients with MS. It was determined that fluoxetine reduced patients’ fatigue level and
improved their sleep quality and their mood. Further studies with this compound are warranted.
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Sleep quality and Depression in patients with Multiple Sclerosis in Arak in 2012
Fardin Faraji1, Shayan Amjadi2, Afsoon Talaie3
1- Department of Neurology, Medicine Faculty, Arak University of Medical Sciences, Arak, Iran
2- Students Research Committee, Arak University of Medical Sciences, Arak, Iran
3- Health Department, Islamic Azad University, Arak Branch, Iran
BACKGROUND: Multiple Sclerosis (MS) is a common demyelinating disease of CNS. Depression and Sleep
disorders are common in MS patients and effect on patients’ quality of life.
PURPOSE: The aim of the present study was to determine prevalence of poor sleep quality and
depression in patients with MS in Arak in 2012.
METHODS: In a cross-sectional study sleep quality and depression severity evaluated in patient with MS
during 3 months of study period by assessing Pittsburgh Sleep Quality Index (PSQI) and BECK Depression
inventory (BDI) questionnaire.
RESULTS: 99 patients (79 female and20 male) with MS were evaluated. Mean (SD) of age was
33.07(8.03). Mean (SD) of BECK score was 13.17 (8.96) only 38% of patients were not depressed. Mean
(SD) of PSQI score was 5.77 (3.68) and poor sleep quality was observed in 52% of patients.
CONCLUSION: This proof-of-concept study showed that 62% of patients with MS suffer from depression
and low sleep quality was observed in 52% of patients.
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Peripheral blood monocytes in multiple sclerosis patients and healthy controls
Mehrdad Farokhi1, Masoud Etemadifar1, Maryam Sadat Jafary Alavi2, Sayyed Hamid Zarkesh-Esfahani3,
Mohaddeseh Behjati4, Ali Rezaei5, Ali Amani Beni1
1-Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran &
Multiple Sclerosis and Neuroimmunology Research Center, Isfahan, Iran
2-Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran
3-Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran
4-Heart Failure Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical
Sciences, Isfahan, Iran
5-Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode
Island, USA & Department of Neuroscience, Brown University, Providence, Rhode Island, USA
BACKGROUND: Aberrant immune responses are evident in the pathogenesis of multiple sclerosis (MS)
and it has been proposed that the spectrum of cytokines influence disease outcomes. Leptin and
lipopolysaccharide (LPS) of gram-negative bacteria are both potent cellular stimulators for production of
pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α). The aim of this study was to
compare the TNF-α production by peripheral blood monocytes from MS patients with healthy controls.
METHODS: Peripheral blood samples were stimulated with LPS or leptin. After blocking the Golgi
apparatus, intracellular cytokine production was assessed using a monoclonal antibody against human
TNF-α by the flow cytometry technique. Moreover, expression of TLR4 on the surface of monocytes was
evaluated using flow cytometry. Plasma level measurement of cytokines was performed using enzymelinked immunosorbent assay.
RESULTS: Intracellular levels of TNF-α were 16.80±8.21 and 16.52±8.23in MS patients and healthy
controls which showed no statistically significant difference between them (P=0.850). Leptin-stimulated
and LPS stimulated TNF-α production showed no significant difference between MS patients and the
control group (P=0.263 and P=0.191, respectively). However, after treatment with leptin, a weak
significant difference was shown between cases and control group (P=0.049).There were significant
differences between cases and controls regarding serum levels of IL-6 and Toll-like receptor-4 (TLR-4)
before and after stimulation with leptin and LPS, separately (P<0.05).
CONCLUSION: Taken together, we cannot definitely conclude that TNF-α does not play an important role
in pathogenesis of MS. However, other characteristics of monocyte activation such as IL-6 or TLRs can
elucidate implication of peripheral blood monocytes in MS pathogenesis.
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Serum level measurement of soluble IL-6 receptor and soluble glycoprotein-130 in
relapsing remitting multiple sclerosis and neuromyelitis optica patients
Mehrdad Farrokhi1,2, Ali Rezaei3,4, Ali Amani Beni1,2, Masoud Etemadifar1
1-Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran &
Multiple Sclerosis and Neuroimmunology Research Center, Isfahan, Iran
2-Medical student, Faculty of Medicine, Isfahan University of Medical Sciences, Esfahan, Iran
3-Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode
Island, USA
4-Departments of Neuroscience, Brown University, Providence, Rhode Island, USA
BACKGROUND: Multiple sclerosis (MS) is a T-cell mediated autoimmune demyelinating disease of central
nervous system that normally conduces to alternate neurological impairmentsfollowed by disability
progression. Increased production of pro-inflammatory cytokines can be found during MS pathogenesis.
It is well known that IL-6 is also a pro-inflammatory cytokine. This cytokine plays its role through an
oligomeric membrane-bound receptor containing two subunits: IL-6R which especially binds to IL-6 and
glycoprotein 130 which regulates the response of cell to IL-6 cytokine and also transduces signals that are
producedthrough this receptor.
PURPOSE: In this study we aimed to investigate levels of soluble IL-6 receptor (sIL-6R) and soluble
glycoprotein 130 (sgp130) in serum of patients with relapsing remitting multiple sclerosis (RRMS) and
neurmyelitis optica (NMO) and also healthy controls.
METHODS: The study groups consisted of 61 RRMS patients and 31 patients with NMO. We also chose 59
healthy controls that were matched well in terms of age and sex. Serum level measurement of sIL-6R and
sgp130 was performed using ELISA.
RESULTS: The mean concentrations of sIL-6R and sgp130 of patients were significantly higher than
healthy controls. Furthermore, serum levels of them in NMO patients were significantly higher than RRMS
patients. In addition, serum concentrations of these two markers were significantly correlated with EDSS.
CONCLUSION: We have found that IL-6 is involved in MS pathogenesis; especially in patients with NMO.
Furthermore, this study suggested that soluble forms of IL-6 receptor can be served as markers of MS
activity.
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Increased serum level of IL-37 in patients with multiple sclerosis and neuromyelitis
optica
Mehrdad Farrokhi1,2, Ali Rezaei3, Ali Amani Beni1,2, Masoud Etemadifar1,Ebrahim Kouchaki4, Abolfazl
Zahedi5
1-Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran &
Multiple Sclerosis and Neuroimmunology Research Center, Isfahan, Iran
2-School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3-Department of Neuroscience, Brown University, Providence, Rhode Island, USA
4-Department of Neurology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
5-School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
BACKGROUND: Multiple sclerosis (MS) is a common autoimmune disease of central nervous system in
which neurodegenerative and inflammatory mechanisms cause alternate neurological impairments. Many
inflammatory and anti-inflammatory cytokines were suggested as contributor in MS pathogenesis and the
balance between these opposing cytokines can regulate MS severity. IL-37, an anti-inflammatory
cytokine, is the most recently identified member of IL-1 family act as a natural inhibitor of innate
immunity. However, the role of IL-37 in MS has not investigated so far.
PURPOSE: In this study we aimed to measure serum level of IL-37 in patients with relapsing remitting
multiple sclerosis (RRMS) and neuromyelitis optica (NMO).
METHODS: In a case-control study, plasma was collected from healthy controls (n=49) and also patients
with RRMS (n=22) and NMO (n=31). Serum level measurement of IL-37 was performed using enzymelinked immunoassay method.
RESULTS: The serum levels of IL-37 were 247.46±74.02 and 312.00±86.72, and 114.63±20.58in RRMS
and NMO patients and healthy controls, respectively, showing statistically significant difference between
them (P=0.00). Furthermore, we found a positive correlation between serum levels of progranulin and
EDSS of patients (r=+0.31 and P=0.00).
CONCLUSION: In summary, the serum level of IL-37 was found to be significantly increased in MS
patients compared to healthy controls. Furthermore, serum level of IL-37 was correlated with disease
severity. This suggests that IL-37 may be part of a feed-back loop to control underlying inflammation in
MS pathogenesis. However, further studies will be required to indicate exact role of IL-37 in MS
pathomechanisms.
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Serum level measurement of progranulin in relapsing remitting multiple sclerosis and
neuromyelitits optica patients
Ali Amani Beni1,2, Mehrdad Farrokhi1,2, Ali Rezaei3, Masoud Etemadifar1, Ebrahim Kouchaki4, Abolfazl
Zahedi5
1-Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran &
Multiple Sclerosis and Neuroimmunology Research Center, Isfahan, Iran.
2- School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3-Department of Neuroscience, Brown University, Providence, Rhode Island, USA
4-Department of Neurology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
5-Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran
BACKGROUND: Multiple sclerosis (MS) is a complex autoimmune disease of central nervous system with
unknown etiology and variable clinical evolution. Although the role of serum progranulin levels in the
pathogenesis of MS remains unclear, it is well known that progranulin is involved in several physiological
and pathophysiological process of CNS including modulation of neurite outgrowth, neuronal
differentiation, and neuronal survival.
PURPOSE: In this study we aimed to measure serum levels of progranulin in patients with neuromyelitis
optica (NMO) and relapsing remitting multiple sclerosis (RRMS) in comparison with healthy control
subjects.
METHODS: In a case-control study, plasma was collected from healthy controls (n=49) and also patients
with RRMS (n=122) and NMO (n=31). Serum level measurement of progranulin was performed using a
sandwich ELISA method.
RESULTS: The serum levels of progranulin were 62.34±16.13, 51.44±13.88, and 41.26±10.04 in NMO and
MS patients and healthy controls, respectively, showing statistically significant difference between them
(P=0.00). Furthermore, we found a positive correlation between serum levels of progranulin and EDSS of
patients (r=0.42 and P<0.001).
CONCLUSION: The present study demonstrated that progranulin is up-regulated in MS patients and our
findings strengthen the evidence for progranulin being involved in pathogenesis of MS. However, further
studies will be required to establish progranulin as an important marker for MS.
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Epidemiological investigation of Neuromyelitis Optica in Khuzestan Province, South West
Iran
Davood Kashipazha, Seyed Ehsan Mohammadiany Nejad, Mostafa Azizi, Majid Jafari
Department of Neurology, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
BACKGROUND: Neuromyelitisoptica (NMO) is an uncommon neuro-inflammatory syndrome that has
shown to be distinct from multiple sclerosis and associated with the autoantibody marker NMO –IgG.
There are still only a few studies regarding the epidemiology of NMO in Iran. In the present study we tried
to describe the epidemiology of NMO in Khuzestan as one of the densely populated regions in Iran.
METHODS: A cross-sectional study was performed during the period 2013-2014. Multiple regional
sources of data were used including hospital records, details from neurologists and MS society database.
The diagnosis of NMO was based on clinical presentation, abnormal findings on neuro-imaging and
serological tests.
RESULTS: Fifty-one (51) Caucasian patients (36 patients with NMO and 15 with NMO-spectrum disorder)
were identifiedwith a female/male ratio of 7.5:1. The crude prevalence of NMO was 1.1/100,000
population. The mean age at onset was 29.2±6.1 years and the mean duration of symptoms was 5±0.4
years. A majority of patients (60.8%) were classified as having mild disability (EDSS= 0-3.5). Among of 35
patients whose titer of NMO-IgGwas measured, 19 (54.2%) were seropositive.
CONCLUSION: Our study suggests that NMO prevalence rate in South West Iran (Khuzestan Province) is
much lower than that reported for MS prevalence rate (16.2/100000) and our patients had a lower age at
onset presentation and milder course of the disease than western countries.
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A metastatic ductal cell carcinoma following use of mitoxantrone
Masoud Ghiasian, Mojtaba Khazaee, Mehrdad Afsharee, Sahar Moradi
Department of Neurology, Hamadan University of Medical Sciences & Health Services, Hamadan, Iran
A 38-year-old woman who was known case of multiple sclerosis from 6 year ago was candidate for
mitoxantrone administration because progression of the lesions in brain and cervical MRI and clinical
worsening. In the course of treatment she was stable with no progression of symptoms and sign. Until one
month before the seventh and the last pulse, she came with intractable pain in the sternum region. In
further evaluation metastatic skeletal lesions due to breast cancer was diagnosed.
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Psychological Approach to the Diagnosis and Treatment of Sexual Dysfunction in Patients
with Multiple Sclerosis
Mahmoud Hedayatnejad
University of Tehran, Tehran, Iran
Multiple Sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system. The
most common age of onset is 20 to 45 and the ratio of infected women to men is 2 to 1. MS patients have
numerous problems because it is a refractory disease and has gradual progression of the disability and
severity of the symptoms. Some common symptoms of MS are Muscle Weakness, Muscle Spasms & Pain,
Tremble, Difficulties with Balance, Emotional Symptomatology (Depression), Bladder and Bowel
Difficulties, Visual & Hearing Problems, Dysarthria and Sexual Difficulties. Sexual dysfunction is very
common in MS patients and is variable from 5% to 7% depending on the type of disease. Despite the high
prevalence of these problems, due to culture and customs of society, it is less posed by the patient as a
problem. However, because of timidity and modesty, teaching these concepts are often ignored. This
dysfunction in women is appeared as Loss of Sexual Desire, Loss of Pleasure and Dyspareunia and in men
as Erectile Dysfunction, Decreased libido and Fatigue. Such disruptions can be resultant from symptoms
of disease with psychological nature including emotional symptomatology, stress and anxiety, feelings of
inadequacy, drug side effects or can be directly related to damage of nerve receptors paths which have
important role in the vital interplay of body such as sexual activity. Sexual activity is a complex
phenomenon and is influenced by biological, psychological and social factors. One factor that has a
significant role in sexual ties is that how a person sees themselves as male or female and what are their
mental images from themselves? Feeling of being interesting and attractive will seriously change due to
physical disability caused by MS. These patients feel that due to having MS, they cannot have a happy
marital relationship. Treatment of these disorders in MS patients includes special treatment and
problems associated with that treatment such as Emotional Symptomatology, Fatigue, Pain, Bladder and
Bowel Difficulties, so on. This review, descriptive study and the results have indicated that psychologists,
psychiatry and support measures and establishment of specific sexual counseling centers for MS patients
are an important part of the rehabilitation program. For healthcare team, MS is considered as a crisis
intervention and expert advice and interdisciplinary of neurologists, urologists, psychiatrists and clinical
psychologist, MS specialist for medical programs management, career advice, and social worker is a
serious necessity which enhances the biological, psychological and social life quality of these patients. At
the end, it is noteworthy that human and its needs should be regarded by the holistic approach and his
behavior should be perpended as a creature with various dimensions (Bio, Psycho-Social) and providing a
successful treatment comprehensive program especially in patients with MS will be possible particularly
with regard to the three factors mentioned above.
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Basal Level of Hypothalamus-Pituitary-Adrenal Axis Hormones in Remission Period of
Multiple Sclerosis Patients
Arash Mosarrezaii‚ Neda Valizadeh‚ Nazila Azimi‚ Vahid Ghazizadeh
Urumia Medicine University, Urumia, Iran
BACKGROUND: MS (multiple sclerosis) is an autoimmune and degenerative disease of central nervous
system. Several studies indicate to the role of HPA axis and stressful life events in the susceptibility to the
disease. In this study‚ we investigated the activity of HPA axis and level of its hormones in these patients.
METHODS: In this study 50 patients with clinically definite MS and in remission period‚ 10 patients
during acute relapse and 20 healthy subjects were studied. No patients were receiving steroid or other
immunomodulatory therapy during 3 months. Plasma cortisol and adrenocorticotropic hormone (ACTH)
were measured using ELISA and radioimmunoassay respectively.
RESULTS: In this study‚ 80 subjects were studied whose mean age was about: remission period
(36.9±1.6) ‚ attack (30.4±3.5) and control (37.15±2.6). 54 subjects were female and 21 were male. Level
of cortisol was respectively 25.24±1.42 ‚ 16.28±1.75 and 15.5±3.7 ng and level of ACTH was 10.16±1.31 ‚
3.41±1.47 and 7.83±1.82.
CONCLUSION: Cortisol levels in patients with remission period are higher than healthy control and attack
groups and there is no difference between healthy control and attack groups. ACTH levels are also higher
than two other groups. But Adrenocorticotropic hormone levels during the attack are less than healthy
control group. The information available suggests the HPA axis activity can affect the incidence and
prevention of attacks in multiple sclerosis.
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What factors are associated with olfactory dysfunction in patients with multiple
sclerosis?
Mostafa Almasi Doghaee, Mohammad Roohani, Mohammad Ali Sahraeean, Hamid Reza Ezzati
Department of Neurology, Faculty of Medicine, Iran University of Medical Sciences, Iran
BACKGROUND: Impaired sense of smell has remarkable value in quality of life and has a great prevalence
in some neurodegenerative diseases. In this study we assessed the olfactory dysfunction in patients with
multiple sclerosis (MS) by means of sniff magnitude test (SMT).
METHODS: A cross-sectional study was conducted on 48 patients with MS. After taking clinical history
and performing physical examination, a questionnaire including demographic and clinical variables
completed for each patient. The SMT was used for evaluation of olfaction.
RESULTS: the olfactory dysfunction was found in 14.6% of patients, including 8.3% hyposmia and 6.3%
anosmia. The older age, higher duration of MS and count of the admission in hospital, lower mini mental
status examination score and type of secondary progressive MS had significant relationship with olfactory
dysfunction.
CONCLUSION: Olfactory dysfunction in patients with MS is associated to more severe disease and lower
cognitive function. Thus olfactory function may use as a marker of severity of neurologic disability in
these patients and routine screening of olfaction in workup of MS patients is recommended.
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Effect of vitamin D on nitrite level in endothelial cell treated by sera from multiple
sclerosis patients
Leila Dehghani1,2, Vahid Shaygannejad1, Amirmohammad Abedini2
1-Isfahan Neurosciences Research Center, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan,
Iran
2-Department of Medical Sciences, School of Medicine, Najafabad Branch, Islamic Azad University, Isfahan,
Iran
BACKGROUND: Multiple Sclerosis (MS) is a progressive neurodemyelinative disease in which neural
sheath and endothelial cell (EC) can be affected. In brain, functional changes in ECs contribute to
reductions in resting blood flow. Furthermore, vitamin D3 has beneficial effects on endothelial
dysfunction. This study presents direct experimental evidence associating free radicals and endothelial
apoptosis as a basis of MS pathogenesis and response to vitamin D3 therapy.
METHODS: Human umbilical vein ECs (HUVECs) were treated with sera from MS patients and sera from
healthy volunteers (each group, n=30). 1. cells were only treated by sera from MS for 24 h, 2. cells were
treated by 1,25(OH)2D3 for 24 h and then sera from MS was added to these cells for another 24 h. 3. cells
were exposed in the sera of MS for 24 h and then 1,25(OH)2D3 was added to these cells for another 24 h.
In the fourth group, cells were treated by sera from healthy individuals for 24 h free radical level was
determined by nitric oxide (NO) assay kit. Nitrite (NO2−) levels were determined in the culture
supernatants.
RESULTS: vitamin D3 prevented the production of Nitrite by the serum of patients. The mean±SD of NO2−
concentration showed significantly greater levels of dissolved NO2/NO3 metabolite in the culture media
of untreated HUVECs by vitamin D3 as compared with control, while the rate of NO significantly
decreased when vitamin D3 was presented in culture both in the pretreatment and in the post treatment
group.
CONCLUSION: It could be concluded that EC treated with sera from MS patients activates apoptosis in
HUVECs; this effect was reversed by vitamin D3 treatment. This can be proposed as a therapeutic
approach for MS. In this study, we discovered that NO2 − concentration and were significantly higher in
the HUVEC media treated by MS serum as compared with the control, and elevation levels of dissolved
NO2/NO3 metabolite was significantly reduced by co incubation of vitamin D3 in the pretreatment and
post treatment groups of serum.
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Quality of Life in Iranian patients with Multiple Sclerosis: A systematic review of
literature from 2000 to 2014
Hassan Khani, Yalda Rabbani, Amaneh Ghorbani, Ata Ghorbani
Iranian Applied Research Center for Public Health and Sustainable Development (IRCPHD), North Khorasan
University of Medical Sciences, Bojnurd, Iran
BACKGROUND: Multiple sclerosis (MS) is a unique central nervous system inflammatory disease with a
broad spectrum of clinical presentations, which are time- and disease progression-related. It usually
affects young adults, with a female predominance of 3:1. Quality of life in patients with MS is an important
outcome. There are many published studies about MS in Iran, but quality of life of MS patients is
uncertain.
PURPOSE: This paper reviews such studies to shed more light on the topics.
METHODS: A literature review of articles published in the Persian Language by Iranian researchers from
1 January 2000 up to 30 December 2014 was conducted using the Scientific Information Database
(through SID). The headings multiple sclerosis, quality of life, stress, anxiety, depression, health mental
used to execute the search.
RESULTS: Instruments were used to measure quality of life in multiple sclerosis patients. a) General
Quality of Life Questionnaires: SF-36, SF-8, WHOQoL; b) Special Quality of Life Questionnaires for
multiple sclerosis patients: MS-QoL-38, MS-QoL-58, MSIS-29; c) Psychology Determinants
Questionnaires: Billings and Moos Questionnaire, Jaloos Questionnaire, Kohen Questionnaire, Coudron
Questionnaire, Beck Depression Questionnaire, Beck Anxiety Questionnaire, Depression Anxiety Stress
Scale (DASS-21, DASS-42), Mental Health Questionnaire (GHQ), Endler & Parker Questionnaire, d)
Chronic Patients Careers: Ferel and Grant Questionnaire and several researcher made Questionnaire.
Findings categorized on the basis of Questionnaires and type of studies. In 16 descriptive studies shown
quality of life in MS patients was significantly low from general population. In 34 interventional studies
shown after interventions were significantly quality of life promotions in MS patients.
CONCLUSION: At seems that quality of life among Iranian MS patients is Inappropriate. We suggest
neurologists should be In addition to drug therapy, Use of health education and promotion programs
included self-care, yoga and exercise, stress management, emotional release, social supports, family
supports for quality of life promotion.
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Socio-demographic, risk factors and clinical characteristics of multiple sclerosis in
Isfahan
Omid Mirmosayyeb1,2, Mahdi Barzegar1,2, Zahra Heidari3, Vahid Shaygannejad1,2
1-Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2-Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
3-Department of Epidemiology and Statistics, School of Health, Isfahan University of Medical Sciences,
Isfahan, Iran
BACKGROUND: Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) and in
many countries it is the most important cause of non-traumatic neurologic disability in young adults.
Inflammation, demyelination and axonal damage are pathological trademarks contributing to the
distinctive multifocal CNS lesions seen in MS. MS seems improbable to result from a single causal event;
instead, the disease appears to develop in genetically predisposed populations as a consequence of
environmental contacts. Whilst its particular etiology remains mysterious, a number of risk factors have
been described; including female sex, low sunlight exposure, low vitamin D levels, Epstein Barr virus
infection, and smoking.
PURPOSE: Our aim was to investigate demographic and clinical factors in MS in Isfahan.
METHODS: In this cross-sectional study which was conducted from 2013-2014 data of 1473 MS patients
referred to MS clinic of Kashani Hospital collected. All the cases were assessed by a neurologist and
included in the study whenever they met the McDonald diagnostic criteria.
Results were presented as mean±error of mean (SEM) for quantitative variables and were summarized by
number (percent) for qualitative variables. Independent t-test and Analysis of variance (ANOVA) was
used for comparing the Expanded Disability Status Scale (EDSS) score among studied groups. Bonferroni
post hoc test was used for pairwise comparisons. P <0.05 was considered as statistically significant level.
RESULTS: The database is composed of 1473 patients with definite MS with the mean age of
35.06±0.25.Relapsing-Remitting (RR) course was the most type (84.0%) of MS among patients. The
female to male ratio is 3.75 with78.9% of females MS patients and 21.1% males. Patients were divided in
three groups according to their disability as measured by the EDSS. Most patients (86.1%) had an EDSS of
3.5 or less. Significant relations were seen between EDSS and gender, marital status, employment status,
education level, MS type and smoking. There weren’t significant associations between EDSS and positive
family history or psychological stresses.
CONCLUSION: MS risk factors and characteristics reported contrarily in population based studies. This
study demonstrates that majority of MS patients are 20-40 years-old females who develop Relapsing
Remitting Multiple Sclerosis (RRMS), though males who had Secondary progressive Multiple Sclerosis
(SPMS) developed more disabling course. A past history of smoking, seizures and respiratory disorders
made patient’s experience more debilitating MS. More investigates particularly accompanied with
patient’s follow up need.
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Multiple Sclerosis and Androgenic Hormones in Pregnancy
Omid Mirmosayyeb1,2, Mahdi Barzegar1,2, Leila Dehghani1, Vahid Shaygannejad1,2, Nahid Eskandari3
1-Isfahan Neurosciences Research Center, Isfahan University of Isfahan, Isfahan, Iran
2-Department of Neurology, Alzahra Hospital, IUMS, Isfahan, Iran
3-Department of Immunology, Medical University of Isfahan, Isfahan, Iran
BACKGROUND: Multiple sclerosis (MS) is an inflammatory, demyelinating neurological disease that
causes severe disability. MS is known to have a hormonal component. Women are more susceptible than
men, even though the prognosis is less good for males. Pregnant women suffering from MS do better
during pregnancy. So, the aim of this study was to evaluate the role of androgens on MS.
METHODS: The studies (up to July 2014) with the association between MS and androgenic hormones
included in the analysis.
RESULTS: Most studies showed that MS has no negative effects on pregnancy and fetus. It confirms that
MS does not necessitate the termination of pregnancy. It showed that a 70% decrease in attack frequency
during the third trimester as compared to 1 year before pregnancy. In contrast, the attack increased in the
postpartum stage. Due to increase of estrogen level during pregnancy, CD4 and CD25 of immune cells rise,
so dominancy of Th2 to Th1 prevents the autoimmune response in MS. Others showed progesterone
increase demyelination and protect myelin sheaths. Some studies showed a helpful effect of estriol
treatment on MRI in MS.
CONCLUSION: Elevation of androgenic could have a positive effect on Th1/Th2 ratio. More clinical and
population-based studies need to clarify impact of Pregnancy situation on MS. So, this could be as a key to
use as a treatment for MS diseases.
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Investigation of PPAR gamma gene expression in peripheral blood mononuclear cell of
multiple sclerosis compared to healthy control subjects
Emamgholipour S, Askarisadr F, Shojaie M, Ansari M
Loghman Hospital, Tehran, Iran
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activated
transcriptional factor involved in the regulation of glucose and lipid metabolism, has gained interest as a
potential therapeutic target in multiple sclerosis (MS) due to its potent immunoregulatory properties and
the therapeutic efficacy of its ligands in experimental autoimmune encephalitis (EAE). Elevated
expression of PPARγ has been observed in the spinal cord of EAE mice and in an in vitro model of antigeninduced demyelination. Global gene expression analysis using cDNA microarrays has proven to be a
sensitive method to gain insight into molecular pathways mediating multiple sclerosis (MS) activity.
Peripheral blood mononuclear cells (PBMC) gene expression can be used as a fingerprint of end- organ
cerebral neurological disease. PBMC gene expression patterns in MS patients contain information about a
remote-target disease process that may by useful for diagnosis and tailoring of therapeutic strategies. MS
patients exhibited decreased PPAR-γ levels in PBMC compared with controls, but CSF levels of PPARγ
were pronouncedly elevated in MS patients. Aiming to identify a possible alteration, the present study
assessed the levels of PPARγ in the PBMC of new MS patients same as CSF report.
METHODS: Blood samples were taken and PBMC were isolated by Ficoll Hipaque separation. Then RNA
and c DNA prepared and with real time PCR, PPAR measured.
RESULTS: We report a pronounced elevation in the PBMC levels of PPARγ in new MS patients (n=10)
compared to non-inflammatory controls (n=13) with p<0.05.
CONCLUSION: Corroborating with prior experimental findings, these results may contribute to our
understanding about the role of PPARγ in different stages of MS.
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A descriptive study of Multiple Sclerosis in Isfahan
Mahdi Barzegar1,2, Omid Mirmosayyeb1,2,Zahra Heidari3, Vahid Shaygannejad1,2
1-Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2-Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
3-Department of Epidemiology and Statistics, School of Health, Isfahan University of Medical Sciences,
Isfahan, Iran
BACKGROUND: Multiple sclerosis (MS) is a demyelinating autoimmune disease of the CNS, and is the
leading cause of disability in middle-aged people. The epidemiology of MS has been extensively studied
and some of them have shown the fluctuating demographic pattern of MS. In other hand, prevalence of MS
in Isfahan is so high. Therefore, we performed this study in order to evaluate these changes with a large
number of patients.
METHODS: This cross-sectional study was conducted during two years (2013-2014) in MS clinic of
Kashani Hospital in Isfahan. Demographic and clinical records of 1473 definite MS patients were
reviewed. Results were presented as mean±error of mean (SEM) for quantitative variables and were
summarized by number (percent) for qualitative variables. Independent t-test and Analysis of variance
(ANOVA) was used for comparing the EDSS score among studied groups.
RESULTS: The mean age of patients was 35.06±0.25. 70.7% of them were married and the mean of EDSS
was 2.07±.03. 70.1% of patients were educated but 38.0% of them were employed. Among married
women, 64.8% had childbirth that 55.1% of them were caesarian. Prevalence of past viral infections in
patients was 35.7% (73.3% of them were chicken pox). 79.1% of patients had psychological stress and
the most prevalent stress was family issues (36.7%). 7.4% of patients were smoking. least patients diet
was fish.
CONCLUSION: Previous demographic pattern in another studies proved in our investigation. As same as
the other diseases, prevention is better than cure. Therefore, more descriptive studies need to determine
them.
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Evaluation of serum auto antibodies in multiple sclerosis patients, a case control study in
Shiraz (2013 to 2014)
Sadegh Izadi1, Saeede Khoshniat2
1-Clinical neurology Research Center, Shiraz University of Medical Sciences, Shiraz Iran
2-Medical student, Shiraz University of Medical Sciences, Shiraz Iran
BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease in which the insulating covers of
nerve cells in the brain and spinal cord are damaged. The cause of MS is unknown, however, it is believed
to occur as a result of some combination of environmental factors such as infectious agents and genetics.
Additionally MS is believed to be an immune-mediated disorder that develops from an interaction of the
individual's genetics and as yet unidentified environmental causes. The prevalence of autoantibodies in
multiple sclerosis (MS) patients and their clinical associations differ between various studies, some
studies shows increase of some auto antibodies level such as: APLA (anti-phospholipid), ANA (antinuclear
antibodies), ANCA (anti-neutrophilic antibodies), anti-β2GPI (anti-beta-2-glycoprotein I), anti-ds-DNA
(anti-double strand DNA) and ACLA (anti-cardiolipin antibodies).
METHODS: This cross case-control study investigated APLA, ANA, ACLA, p-ANCA, c-ANCA, anti-β2GPI and
anti-dsDNA in 54 patients with MS and clinically isolated syndrome (CIS). The results were compared
with 25 healthy individuals as control group.
RESULTS: Among 54 patients with relapsing- remitting MS (RRMS) or CIS, abnormal tests were found in
15 patients (27.9%); 6 (11.1%) had positive antinuclear antibodies, 3 (5.6%) had positive ACLA, 47
(11.2%). None of the patients had any clinical manifestations other than MS symptoms. In patients group
ds-DNA was positive in 5.6% of cases that had no significant difference with control group (0%) (P=0.7),
but APLA and B2GP were negative in all patients and control group. The females had more positive auto
antibodies in comparison to males, but they were not significant.
CONCLUSION: The results of this study showed that significant number of patients with multiple
sclerosis have positive serum auto antibodies tests without clinical expression of any other autoimmune
disease.
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Effect of Fingolimod treatment on the number of LAG-3 expressing T regulatory cells in
Multiple Sclerosis patients
Nahid Sedaghat1,2,Sayyed Hamid Zarkesh-Esfahani3, Fereshteh Alsahebfosoul1,2, Masoud Etemadifar2,4,
Vajihe Ostadi1, Fariborz Kianpoor1, Mojtaba Akbari4
1-Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2-Isfahan Multiple Sclerosis (MS) and Neuroimmunology Researches Center, Isfahan, Iran
2-Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran
3-Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran &
Isfahan Multiple Sclerosis (MS) and Neuroimmunology Researches Center, Isfahan, Iran
4-Shiraz University of Medical Sciences, Shiraz, Iran
BACKGROUND: Multiple sclerosis (MS) is a chronic, inflammatory and autoimmune disease of the central
nervous system. The disease is considered as a T cell mediated with an abnormal immune response. It is
the result of breakdown in the mechanisms that control self-reactive lymphocyte and immune tolerance.
Regulatory T lymphocytes play a crucial role in the control of autoimmune disorders. It is generally
believed that CD4+Foxp3+ regulatory T cells (Treg) are functionally impaired in MS patients and
restoring their function will be beneficial for MS patients.
PURPOSE: The aim of this study was to evaluate the effect of Fingolimod on the number of CD4+Foxp3+ T
regulatory cells expressing LAG-3 (an inhibitory marker).
METHODS: Total number of T regulatory cells CD4+Foxp3+ expressing LAG-3 were measured in
peripheral blood samples of 20 MS patients before and after Fingolimod treatment using three color flow
cytometry (BD FACSCalibuar). Flow cytometry data were analyzed using CellQuest PRO software and
SPSS program.
RESULTS: There was an increase (p<0.005) in the total number of CD4+Foxp3+LAG3+ Treg after 1 month
of fingolimod therapy when compared with baseline.
CONCLUSION: In conclusion, fingolimod therapy enhances Treg numbers expressing LAG-3 which may
contribute to the improvement of the disease. These findings could be a new aspect in therapeutic target
for MS.
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High Dose vitamin D on Interleukin-10 in Multiple Sclerosis
Fereshteh Ashtari, Nafiseh toghianifar, Sayyed hamid Zarkesh-Esfahani, Marjan Mansourian
Isfahan University of Medical Sciences, Isfahan, Iran
BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system.
Vitamin D has been related to prevention of MS development and modulating its course. This study
compared the effects of high dose vitamin D on interleukin-10 levels on MS patients in a double blind
randomized clinical trial.
METHODS: 94 patients with relapsing remitting multiple sclerosis (RRMS) were randomized to
treatment vs placebo groups. Both groups received conventional MS treatments. The intervention group
received 50,000 IU vitamin D every five days for 3 months. Demographic characteristics, EDSS score,
disease duration, number of attacks and medications were recorded. Serum levels of Vitamin D and
interleukin 10 (IL-10) were measured and compared at baseline and after 3 months.
RESULTS: Serum levels of IL-10 were 41.66±85.16pg/ml and 21.08±35.62 in the intervention and
placebo group at baseline, respectively (p=0.161). After 3 months, IL-10 levels were 71.07±16.65 and
32.23±38.49 in the intervention and placebo group, respectively (p=0.158). In linear regression model,
interleukin levels showed significant difference in intervention and placebo groups (p=0.022, β=0.032).
CONCLUSION: IL-10 levels are reduced significantly in RRMS patients after taking high dose vitamin D for
3 months. High dose vitamin D might be useful in reducing inflammatory state in RRMS patients.
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Frequency of common etiologies of late onset seizure in elderly patients with seizure
diagnosis in department of neurology of Sina hospital in Hamadan over a 10-year period
Mehrdokht Mazdeh, Abbas Khosravi
Farshchian Hospital of Hamadan, Hamadan University of Medical Sciences, Hamadan, Iran
BACKGROUND: After cerebrovascular disorders and dementias, epileptic seizures constitute the third
most frequent neurologic problem encountered in the elderly. Epilepsy can affect any one at any age. The
incidences of seizures and epilepsy in the population show a peak after 65 years of age. Due to the lack of
reported clinical aspects of seizure and epilepsy in the older patients in our region in Iran, this study was
conducted to describe etiology, the clinical manifestation, seizure types and subtypes.
METHODS: A retrospective study was performed on all elderly patients with final seizure diagnosis,
referred to the Sina hospital in the city of Hamadan, Iran over a 10-year period. All medical records and
previous medical histories were reviewed. A total of 270 patients aged 65 years or above with new onset
seizure were included.
RESULTS: In this study, a total of 270 patients with late-onset seizure were studied. Cerebrovascular
accident was found to be the most common cause of late-onset seizure in elderly (41.9%). In 108 patients
(40%) etiology was unknown, 18 patients (6.6%) had brain tumors, 10 patients (3.7%) had history of
head trauma, 10 patients (3.7%) had degenerative disorders and 15 patients (5.4%) had rare causes like
withdrawal, brain infection, HTN crisis and drug. Most seizure type was generalized seizure (76.7%). The
most frequent clinical symptom of seizure was generalized tonic–clonic seizures.
CONCLUSION: the most common cause of late-onset seizure in elderly was cerebrovascular accident,
most seizure type was generalized seizure and the most frequent clinical symptom of seizure was
generalized tonic–clonic seizures. Since seizures were associated with a central nervous system disease
and the elderly are the most rapidly growing segment of the population in our country careful
investigation is necessary. Referring older patients to a specialist or a specialist epilepsy center allows
speedy assessment, appropriate investigation and treatment, and less likely to miss the diagnosis. We also
recommend better control of risk factors for cerebrovascular diseases in our country.
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Antiepileptic Drug Induced Hypersensitivity and the HLA Complex
Hossein Ali Ebrahimi, Ali Nasiri
Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran
Epilepsy is considered to be among the most prevalent neurological disorders and one of most important
health issues. The first choice of treatment is antiepileptic drugs (AEPs). One of the problems in AEPs
treatment is adverse effects. Two type adverse effects are seen, at first cutaneous eruption in first months
after initiation of drug, and the second is late adverse effects. In individuals taking AEDs, the overall
maculopapular eruption incidence rate is 2.8%; incidence rates of rash caused by PHT, LG, and CBZ are
higher at 5.9%, 4.7%, and 3.7%, respectively. In-depth genetics studies on AEDs-induced adverse
reactions suggest that incidence rates of AEDs-induced Stevens-Johnson Syndrome/Toxic Epidermal
Necrolysis (SJS/TEN), vary among ethnic groups and that the associations with relevant loci are different.
Although the incidence rates of SJS and TEN are low, mortality rates nevertheless reach 10– 50%. Thus,
avoiding SJS/TEN is one of the major challenges during AEDs treatment. Recent studies have indicated
that Sever Cutaneous Reactions (SCRs) such as SJS and TEN induced by AEDs are associated with the
HLA-B*1502 allele. This HLA type in Europe is rare, but in southeastern of Asia is common. In individuals
of Northern European ancestry, CBZ-SJS/TEN incidence is not associated with HLA-B*1502, but it is
associated with HLA-A*3101. In Japan, HLA-B*5901 and HLA-B*5801 loci are risk factors for CBZSJS/TEN. In Iran there is not study for this issue. We decided to done HLA typing in SJS/TEN patients due
to lamotrigine. We will discuss the clinical utility of HLA typing as predictive or diagnostic testing for
drug-induced hypersensitivity and results of study.
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Infantile Masturbation and Paroxysmal Disorders: Report of Three Rare Cases from
Northern Iran and Literature Review
Mohammadreza Salehi Omran, Mohammad Ghofrani, Ali Ghabeli Juibary
Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
BACKGROUND: A recurrent paroxysmal presentation in children leads to different diagnoses that among
them neurologic and cardiac etiologies are in above the list. Infantile masturbation is not a well known
entity and can not be differentiated easily from other disorders. Aim of this study is elucidating and
differentiating this condition from epileptic seizures.
CASE PRESENTATION: We report 3 cases of 10 to 30 month old girls of infantile masturbation that their
symptoms initiated at 2, 3 and 8-month-old. These present with contraction and extension of lower
extremities, scissoring of legs, perspiration, changing face color. In 2 cases body rocking and legs rubbing
initiated then after.
DISCUSSION: Masturbation is one of the paroxysmal non epileptic conditions of early infancy and is in
differential diagnosis of epileptic seizures. With detailed history taking and close observation we can
prevent useless studies and treatments.
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Sturge-Weber syndrome: Case Series and Literature Review
Mohammadreza Salehi Omran, Ali Ghabeli Juibary
Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
PURPOSE: Sturge-Weber syndrome (SWS) is a rare congenital sporadic disease with neuro-ocular,
cutaneous and vascular findings. Clinically, the full-blown condition consists of a facial port-wine stain
(PWS) involving the V1 facial trigeminal skin area, alone or in combination with V2 and V3 PWS, seizures
and ocular abnormalities (glaucoma and choroidal angioma). Radiologically, a leptomeningeal (pial)
capillary and venous malformation, mostly located in the parieto-occipital area, cerebral atrophy and
calcifications are demonstrated.
METHODS: A retrospective review of the records of patients diagnosed of SWS (facial nevus flammeus at
least over the first branch of the trigeminal nerve and ipsilateral leptomeningeal angioma) was
performed. Eight patients with Sturge-Weber studied.
RESULTS: The nevus flammeus was unilateral in 7 patients and bilateral in 1 patient and in one patient
on the same side of the leg. All of these patients had cerebral lesions. Seizures, most of which were focal,
were present in 6 patients (75%) usually contralateral to the nevus flammeus. Seizure presentation
coincided with febrile episodes in none of these patients. Total seizure control was obtained in all
patients.
CONCLUSION: Early evaluation of newborns with nevus flammeus affecting the first branch of the
trigeminal nerve must be done, including an MR with contrast and an ophthalmological exam.
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Effects of Teucrium polium Extract on the Seizure Induced by Picrotoxin in Mice
Elahe Fereidouni1, Samira Fatahi2, Mojgan Safaee2
1-Department of Physiology, Kermanshah University of Medical Sciences, Kermanshah, Iran
2-Department of Nursery, Kermanshah University of Medical Sciences, Kermanshah, Iran
BACKGROUND: Neurological effects of Teucrium polium have been recognized for many years. In this
study, the anticonvulsant activity of methanolic extract of the plant was investigated in mice. Picrotoxin
with doses of 6 and 12.5 mg/kg were used for induction of seizures. The effects of different doses of
methanolic extract of the plant on the variation of beginning time of seizures, the incidence of tonic and
clonic seizures and mortality rate were determined.
METHODS: The beginning time of tonic seizures induced by picrotoxin (6 & 12.5 mg/kg IP) were delayed
significantly in group which received extract (50 mg/kg IP) 20 min before picrotoxin administration.
RESULTS: Latency of beginning time of tonic seizures in mice which receive picrotoxin 6 mg/kg were
increased significantly from 10.58 min to 15 min (P<0.05) and in case of 12 mg/kg of picrotoxin from
5.87 to 10.82 min (P<0.01). The incidence of clonic seizures and mortality rate were decrease in this
group of animals (P<0.05, P<0.01).
CONCLUSION: The results indicated that Teucrium polium extract may be effective on generalized tonic,
clonic and tonic- clonic seizures and the dose of 50 mg/kg was enough to produce effective concentration
for anticonvulsive activity of the extract in mice.
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The role of High-Frequency Oscillations in epileptic surgery
Nasim Tabrizi
Department of Neurology, Mazandaran University of Medical Sciences, Sari, Iran
Detection of high frequency oscillation (HFO) is a new clinical diagnostic method in epilepsy and epilepsy
surgery. HFOs seem not only a spatial marker of the focus of epileptogenicity, but also a temporal marker
for epileptic intensity. They also could be useful to evaluate treatment effect. Obviously, identification of
epileptogenic zone is the main goal of presurgical evaluation in epileptic patients. Recent studies have
shown that identification of HFOs appears capable of improving presurgical diagnosis and surgical
outcome by introducing a new area called HFO zone. Removal of HFO zone seems to predict good
outcome, even better than removal of the ictal onset zone. Specificity of HFOs has been proved in both
temporal and extratemporal epilepsy. Several studies with microelectrodes conclude that fast ripples are
most specific for the epileptogenic zone, but in clinical studies with macroelectrodes it is useful to include
both ripples and fast ripples in the evaluation of the potential epileptogenic region. Although HFOs have
been seen on scalp electroencephalography (EEG), the best way to record them is intracranial EEG which
limits their usage. But due to promising results, it may be the time to include HFO information in the
clinical workup of epilepsy surgery patients to improve surgical outcome and to reduce the need for
traditional long-term recordings.
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New conceptions about drug-resistant epilepsy
Majid Ghaffarpour
Iranian Center of Neurological Research, Imam Khomeini Hospital, Tehran, Iran
Epilepsy is a common neurological disorder, affecting approximately 1 to 2 of population. A communitybased study estimated that up to 22.5% of epilepsies are drug resistant, which have increased premature
death, injuries, psychological dysfunction and a reduced quality of life. According to global consensus of
international league against epilepsy (ILAE), drug resistant epilepsy is defined as a failure of adequate
trials of two (or more) tolerated, appropriately chosen and dosed antiepileptic drug regimens (whether
administered as monotherapies or in combination) to achieve freedom from seizures. This definition was
based on the observation that if complete seizure control is not achieved with two appropriate drugs, the
likelihood of success with subsequent regimens is much reduced. Although drug resistance may remit
over time, at a rate of 4% per year among adults and higher rate in children, seizure relapse is common. It
is important to rule out pseudoresistancy and to understand how seizures become drug resistance. The
mechanisms of drug resistance are variable and multifactorial. Major hypotheses include over-expression
of drug transporter proteins (failure of drug to reach targets) such as p-glycoprotein and multidrug
resistance proteins (MRP1-7), alteration in drug targets, drug missing the real target and inherent disease
severity. Pharmacoresistancy become also apparent in patients with status epilepticus when seizure
continues for more than 30 minutes, which is explained by intensified over expression of NMDA receptors
and internalization of the GABAA and AMPA-receptors. In This lecture we will review further details
about pathogenesis of drug resistance and reasons of pseudoresistancy, treatment and outcomes of RSE
and S-RSE.
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Neonatal Capsaicin effects on PTZ-induced convulsions in 20-day-old Rats
Elnaz Khorasanian, Ali Moghimi, Masoud Fereidoni
Research Center For Neuroscience & Behavior, Department of Biology, Faculty of Science, Ferdowsi
University of Mashhad, Iran
BACKGROUND: During postnatal development, sensory experiences play critical roles in the organization
and plastic changes of cortical connections. Degeneration of peripheral sensory neuron terminals lead to
functional alterations of substrates at cortical levels. Epilepsy is a neurological disorder characterized by
spontaneous, recurrent seizures. There is a little knowledge about neonatal event impact on epilepsy
etiology. Capsaicin, the hot chemical in chilies, can destroy polymodal nociceptive primary afferent
neurons and has epileptic effect when injected i.c.v.
PURPOSE: Here, we assesse C-fiber elimination effect which induced by neonatal capsaicin
intraperitoneally injection (50mg/kg, i.p) on latency and duration of Seizures induced by
pentylenetetrazole (PTZ) in 20th after birth.
METHODS: Two –day-old pups were divided into experimental (N=7) and sham groups (N=7) and (i.p)
treated with Capsaicin or Capsaicin vehicle (tween 80, ethanol and salin, 10:10:80), respectively. C-fiber
destructions were confirmed by Ammonium hydrochloride (wipe test) on the day 14th. Seizures were
induced with PTZ (50mg/kg. i.p). On the day 20 after birth and the latency of unset and duration of
generalized epileptiform convulsion was recorded.
RESULTS: Capsaicin -treated group shows significant difference in unset latency of behavioral
convulsions (P<0.05) and duration of seizures induced by PTZ (P<0.05) in comparison with sham group.
CONCLUSION: It may be that C-fibers are involving in the inhibitory system development in neonate rat
during the critical period of brain development, so C-fibers destruction can lead to elimination or
diminishing the brain inhibitory system specially GABAergic one, so it potentiate the effect of PTZ induce
seizure.
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Effect of hydroalcoholic extract of cannabis sativa l. flower tops chronic administration
on severity and duration of pentylenetetrazole induced convulsions in neonate rat
Samane Afroozi, Ali Moghimi, Masoud Fereidoni
Research Center For Neuroscience & Behavior, Department of Biology, Faculty of Science, Ferdowsi
University of Mashhad, Iran
BACKGROUND: Epilepsy is a serious neurological disorder, which is outcome of disturbing the natural
balance between excitation and inhibition in the central nervous system and caused by intermitted and
abnormal electrical discharges in the brain neurons. Considering the prevalence of epilepsy and the
failure of available treatments for many epileptic patients, finding more effective drugs in the treatment
of epilepsy seems necessary. Cannabis Sativa L. is an ancient and medicinal plant that has been used for
treatment of insomnia, inappetence, and nausea in traditional medicine. Phytocannabinoids in Cannabis
Sativa L. have different pharmacological targets on the nervous system.
PURPOSE: The aim of this study was to investigate the effect of hydroalcoholic extract of Cannabis Sativa
L. flowertops on duration time of epileptic seizure stages induced by pentylenetetrazol in neonate rats.
METHODS: Neonate wistar rats (4 days old) were divided into four groups, including a group receiving
interaperitoneal (i.p) solvent and three experimental groups (receiving the hydroalcoholic extract in 3
doses 1,10,50 mg/kg/i.p) started from 4th day of birth to 9th day of birth. In 14 day after birthday,
pentylenetetrazol (50 mg/kg/i.p) was injected and convulsive behaviors were recorded by a camera
during 60 minutes and different phases of seizures and duration of convulsions were scored.
RESULTS: The extract injection in dose of 50 mg/kg/i.p showed significant reduction of duration time in
tonic-clonic seizures compared with the group receiving solvent (p<0.05).
CONCLUSION: Our study indicated that the hydroalcoholic extract of Cannabis Sativa L. has an
appropriate anticonvulsant effect, maybe by activation GABAergic system as other researches claimed it
is hypnotic effects, our results may due to the same mechanisms, which needs more study to clarify.
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Tamoxifen mimics the effects of endogenous ovarian hormones on repeated seizures
induced by pentylenetetrazole in rats
Somaieh Mansouri, Maryam Ataei, Mahmood Hosseini, Alireza Ebrahimzade Bideskan
Mashhad University of Medical Science, Mashhad, Iran
PURPOSE: In the present study, the effects of tamoxifen on pentylenetetrazole (PTZ)-induced repeated
seizures and hippocampal neuronal damage in ovariectomized rats were investigated.
METHODS: Thirty seven virgin female Wistar rats were divided to: (1) control, (2) sham-PTZ, (3) shamPTZ-tamoxifen (sham-PTZ-T), (4) Ovariectomized -PTZ (OVX-PTZ) and (5) OVX-PTZ-tamoxifen (OVXPTZ-T) groups. The animals of groups 3 and 5 were injected by tamoxifen (10 mg/kg) on 7 consecutive
days. After 7 days of tamoxifen injection, they also were then injected by tamoxifen 30 min prior each PTZ
injection. PTZ (40 mg/kg) was injected on 6 consecutive days and the animal behaviors were observed
for 60 min. The histological methods were then used to determine dark neurons in hippocampus.
RESULTS: A significant decrease in the seizure score was seen in OVX-PTZ group compared to Sham-PTZ.
The animals of OVX-PTZ-T group had a significant higher seizure score compared to OVX-PTZ group. The
dark neurons in DG of OVX group were lower than sham group (p<0.01). The numbers of dark neurons in
CA1 area of OVX-PTZ-T group was higher than OVX-PTZ group (p<0.05) compared to control, the
numbers of dark neurons in CA3 area showed a significant increase in Sham-PTZ and OVX-PTZ group
(p<0.05 and p<0.01 respectively). Dark neurons in OVX-PTZ-T group were higher than OVX-PTZ group
(p<0.05).
CONCLUSION: It is concluded that pretreatment of the ovariectomized rats by tamoxifen increased PTZinduced seizure score and dark neurons. It might be suggested that tamoxifen has agonistic effects for
estrogen receptors to change the seizure severity.
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Epilepsy surgery as a treatment option for patients with Lennox-Gastaut syndrome
Mahmoud Abedini, Nasim Tabrizi, Ashraf Zarvani, Narges Karimi
Department of Neurology, Mazandaran University of Medical Sciences, Sari, Iran
Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy of childhood onset characterized by
mixed seizure types, cognitive dysfunction, and electroencephalogram (EEG) pattern of slow spike-waves.
Seizure types typically include tonic, atonic, and atypical absence, but may include other types, such as
tonic–clonic, myoclonic, or partial seizures. Because patients with LGS experience a range of different
seizure types, the condition is extremely difficult to treat and seizures in LGS are usually not fully
controlled. LGS is often the result of bihemispheric pathology, but seizures may be caused by focal
abnormalities of the brain, such as tumors, cortical tubers, and cerebral malformations. Up to 25% of
patients with LGS have persistent focal abnormalities or asymmetry of slow spike-wave discharges on
EEG. Patients with LGS who are refractory to antiepileptic medications may be considered candidates for
surgical intervention. Several presurgical investigations are required including video-EEG monitoring,
magnetic resonance imaging (MRI) and age appropriate neuropsychological or developmental
assessment. Also some supportive tests may be utilized in the surgical evaluation of patients including
those that aid in localizing the region for resection such as PET, SPECT and MEG and those that are useful
to delineate eloquent cortex to minimize neurologic deficits related to surgery (e.g., Wada, functional MRI
and electrocorticography). The major strategies for surgical treatment in these children are cortical
resection and corpus callosotomy (CC). Resection may be a curative surgery, whereas CC is considered a
palliative surgery, usually considered when resective surgery is not suitable. Recent studies have shown
that resective surgery in patients with LGS with dominance of EEG discharges in one hemisphere can be
successful in terms of seizure reduction in majority of patients. Results of studies on CC in patients with
LGS have also shown that this surgery can reduce seizure frequency in a significant way. But due to
complications of surgery, few trials of radiosurgical techniques have been reported with similar efficacy
but with fewer postsurgical side effects. Vagus nerve stimulation (VNS) is also considered a palliative
surgery option for patients lacking a resectable seizure focus. CC and VNS often result in similar rates of
seizures reduction; however, CC may be more effective for atonic seizures and VNS is associated with
milder complications. With major advances in imaging technology and surgical techniques and improving
safety, continuing studies are warranted for surgery in the treatment of LGS.
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The effect of Vitamin E on the seizure frequency, EEG findings and biochemical
parameters of epileptic patients treating with Carbamazepin, Sodium valproate and
Levetiracetam
Zare M, Gholami F, Mahvary J, Agha Ghazwyni MR, Najafi MR, Alavi AM
Isfahan University of Medical Science, Department of Neurology, Isfahan Neuroscience Research Center,
Isfahan, Iran
BACKGROUND: Epilepsy is one of the common neurological disorders characterized by seizures caused
by electrical brain disorders with great destructive impact on people's social and economic life. Vitamin E
is a natural antioxidant without any significant complication which is easily used.
PURPOSE: This study aimed to evaluate the effect of this vitamin on increasing the effects of antiepileptic
drugs.
METHODS: This double-blind, placebo-controlled clinical trial have done on 66 patients with epilepsy
treated with antiepileptic drugs referred to Kashani hospital and private clinics in Isfahan. Non-random
simple sampling 33 patients were allocated to intervention and control groups. The intervention group
was given daily supplements of 400 IU vitamin E and the control group gave similar pills of vitamin E as
placebo. Patients were examined monthly about the seizure frequency and EEG and blood biochemical
markers at the end of sixth months. Data were analyzed by SPSS software using Chi square test and T-test.
RESULTS: The mean of total antioxidant in cases before treatment was 6.2±2 and significantly increased
to 7.7±2.1 after treatment (P-value=0.001), but in controls was increased of 7.3±1.9 to 7.4±2.1 (Pvalue=0.91). The mean of catalase in cases was 14.3±5.1 and significantly increased to 17.5±5.4 after
treatment (P-value<0.0001), in controls was 17.5±5.2 and increased to 17.4±6 (P-value=0.44). The mean
of glutathione in cases after treatment was significantly increased compare to before treatment (13.6±6.1
to 18.5±8.2, P-value<0.0001), in controls (16.4±5.7 to 16.3±5.4 respectively, P-value=0.88).
Malondialdehyde decreased but was not statistically significant in case (P-values = 0.1), but in control
don’t decreased (p-value=0.53). The mean number of seizure in cases after treatment was significantly
decreased compare to before (2.25±0.62 to 1.34±0.83, P-value<0.0001), but in controls was similar
(2.36±1.1 to 2.57±1.2, P-value<0.0001). Changes in the positive EEG findings in cases observed more than
control group (50% versus 12.1% respectively, P-value=0.001).
CONCLUSION: Our results showed that vitamin E in addition to antiepileptic drugs improved antioxidant
parameters and seizure frequency and positive EEG finding in compare to placebo, but no significant
effect on reduced oxidative stress (respect to Malondialdehyde enzyme).
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Association of Family History of Epilepsy with Earlier Age onset of juvenile myoclonic
epilepsy
Mohammad Reza Najafi1,2, Mohammad Amin Najafi2,3, Ali Safaei2,3
1-Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran
2- Isfahan Neurosciences Research Centre (INRC), Isfahan University of Medical Sciences, Isfahan, Iran
3-Isfahan University of Medical Sciences, Faculty of Medicine, Isfahan, Iran
BACKGROUND: Juvenile myoclonic epilepsy (JME) is assumed to be the most frequent subtype of
idiopathic generalized epilepsies (IGE).
PURPOSE: The aim of this study was to determine the prevalence of JME and comparison of patients'
demographics as well as timeline of the disease between positive family history epileptic patients (PFHE)
and negative family history epileptic patients (NFHE) among sample of Iranian epileptic patients.
METHODS: 1915 definite epileptic patients (873 females and 1042 males) were evaluated in this study.
JME was diagnosed by its specific clinical and EEG criteria. Patients were divided into two groups: PFHE
and NFHE patients and the data were compared between these two groups.
RESULTS: JME was responsible for 10% (194 patients) of all types of epilepsies. 53% of our JME patients
were female and 47% were male. 40% of JME patients had family history of epilepsy. No significant
differences between PFHE and NFHE groups in terms of gender (p-value>0.05). Age of epilepsy onset was
significantly earlier in PFHE patients (15 vs. 22, P-value<0.001). Occurrence of JME before 18 years old
among PFHE patients was significantly higher (OR=2.356, P-value=0.007).
CONCLUSION: Our study demonstrated that a family history of epilepsy is associated with an earlier age
of onset in patients with juvenile myoclonic epilepsy.
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Role of Family history in diagnosis of epilepsy in Iranian patients with epilepsy
Mohammad Reza Najafi1,4, Mohammad Amin Najafi2,4, Ali Shahsavari2,4, Ramin Shayan Moghadam2,
Farzaneh Najafi3, Rokhsareh Meamar4, Ali safaei2,4, Ali Kamal2, Amirsalar Nurbakhsh2, shayan mostafaei5
1-Professor of Neurology, Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran
2-Medical student, Isfahan University of Medical Sciences, Faculty of Medicine, Isfahan, Iran
3-Postdoctoral researcher, Cold Spring Harbor Laboratory, Cold Spring Harbor, USA
4-Isfahan Neurosciences Research Centre (INRC), affiliated to Isfahan University of Medical Sciences, Isfahan,
Iran
5-Divisions of Biostatistics, Department of Epidemiology and Biostatistics, School of public Health, Isfahan
University of Medical Sciences, Isfahan, Iran
BACKGROUND: Role of family history on epilepsy classifications, etiology and patients’ demographics
still remains unclear.
PURPOSE: The aim of this study was to investigate the effect of family history of epilepsy on
classification, etiology and timeline of disease.
METHODS: 1915 definite patients with epilepsy (873 females and 1042 males) enrolled in this
retrospective study. Positive family history and negative family history patients were identified and
compared in terms of gender, age, age of epilepsy onset, classification (generalized, partial and unknown)
and etiology (Idiopathic, symptomatic and cryptogenic) of epilepsy.
RESULTS: 33.4% of patients (n=1915) had a history of epilepsy in their family. 21.6% had a first-degree
relative with epilepsy, and 11.8% had a second-degree epileptic relative. The mean age of epilepsy onset
was 21. Positive family history patients showed an earlier age of onset (16 vs. 24; independent-T test,
p<0.001). Idiopathic, symptomatic and cryptogenic epilepsy were significantly different between the two
groups (chi-square test, p<0.001). Generalized and unknown types of epilepsy were also significantly
different between positive and negative family history patients (chi-square test, p<0.05).
CONCLUSION: Family history has a significant impact on the classification, etiology and timeline of
epilepsy. These findings may be affected by the high incidence of consanguineous marriage seen in our
population.
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Evaluation of brain MRI findings in Iranian patients with seizure and normal neurologic
examination
Omid Hesami1, Mostafa Asadollahi1, Mahyar Noorbakhsh2
1-Departmentof neurology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran,
Iran
2-Neurologist, Tehran, Iran
BACKGROUND: This study was set up to determine the rate of abnormal brain MRI findings in Iranian
patients with seizure who have a normal neurologic examination.
METHODS: This is a cross-sectional, retrospective study. Data of 148 patients with definite seizure
diagnosis and available brain MRI report who were admitted to Imam Hossein hospital during 1387-1390
were recruited and entered in study. All the patients had been imaged using MRI sequences of T1, T2,
FLAIR and epilepsy protocol on 1.5 tesla system. Frequency of abnormal MRI was determined in relation
to patients’ age, gender, type of seizure and EEG findings.
RESULTS: 68 patients were female (46 %) and 80 ones were male (54%). Mean age of patients was
43.6±22.7 years. 56 patients had pathologic finding in brain MRI (38.2%) and 92 ones had normal MRI
(61.8%). Mean age of the patients with MRI abnormality was compared to those without. The values were
49.7±21.2 and 39.9±22.8 respectively and the difference was significant (P=0.035). 20 females (29.8%)
and 36 males (45.5%) had abnormal MRI and the difference between two genders was not significant
(P=0.105). The frequency of abnormal brain MRI was not significantly different among various seizure
types (P= 0.336). In total, EEG was normal in 36 patients (24.5%) and abnormal in 112 ones (75.5%). In
patients with abnormal EEG, 45 ones (40.3%) and in those with normal EEG, 11 ones (32%) had
abnormal MRI and the difference was not significant (P=0.460).
CONCLUSION: Older patients were more likely to have abnormal MRI than younger ones and therefore
the older should be imaged more urgently. However, Patients’ gender and seizure type were not
determinant factors in prediction of MRI abnormality. Also a normal EEG could not implicate that brain
MRI is also normal and one should not forbear brain imaging on basis of a normal EEG.
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Descriptive review of surgery outcome in 35 cases with refractory epilepsy
Jafar Mehvarihabibabadi, Houshang Moein, Reza Basiratnia, Majid Barekatain, Mohammad Zareh, Elham
Rahimian, Amirali Mehvari habibabadi, Shervin Badihian
Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
& Kashani Comprehensive Epilepsy Center, Isfahan University of Medical Sciences, Isfahan, Iran
BACKGROUND: Both medical and surgical treatments have been suggested for patients with tumor
associated epilepsy. However, in recent studies, surgical treatment has been considered because of the
reducing rate of seizure recurrence after surgery. The aim of this study was to investigate surgery
outcome in patients with refractory epilepsy.
METHODS: The medical records of 35 individuals (18 female and 17 male, age: 8-45) with tumor
associated epilepsy were reviewed. All the patients were cases of refractory epilepsy that underwent
tumor resection surgery and were followed for 2 to 4 years in Kashani comprehensive epilepsy center,
Isfahan, Iran.
RESULTS: Most patients presented with 30 seizures or more per month (57.6) which consisted of one or
two types of seizure at time of admission (57.1% and 37.1% respectively). They were on one to three
anticonvulsant drugs in most cases (75.8%). Carbamazepine, Sodium Valproate, and Phenobarbital were
mostly used. After required evaluations, almost all the patients underwent lesionectomy by the same
neurosurgeon which resulted in paresis and language deficit in 8.6% and 2.9% of cases respectively.
Ganglioglioma was reported in 62.9% of cases, Astrocytoma in 27.6%, and DNET in the rest. After two to
four years follow-up, 65.6% of patients were seizure free. In terms of Engels class, 79% of cases were
classified as class I, 8.8% class II, 2.9% class III, and 5.9% class IV. Anticonvulsant drugs were
discontinued in 18.8% of patients successfully without any recurrent seizure and 53.9% of patients
experienced less frequent seizures postoperatively with lower dosage of antiepileptic drugs or fewer
numbers of them. The rest remained on the same amount of medication for their seizure control and
5.9% experienced no change or even more seizures.
CONCLUSION: A variety of medical and surgical treatments has been suggested for patients with tumor
associated epilepsy. Despite studies have addressed the issue, the best choice of therapy has remained
controversial yet. Our study showed a favorable outcome of surgery in patients with tumor associated
epilepsy which is compatible with several previous studies. Given the considerable postoperative
outcome in our patients, and long-term effects of seizures and drug use on individuals and their quality of
life, earlier surgical treatment may lead to better results. It seems the optimal management of these
patients requires a multidisciplinary approach including either drug treatment or surgical treatment or a
combination of those.
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Current management and surgical outcomes of intractable epilepsy in Rasmussen's
encephalitis: investigation of two cases with literature review
Jafar Mehvari habibabadi, Seyed Mohammad Ghodsi, Fatemeh Fadaie, Seyed Sohrab Hashemi Fesharaki,
Mohammadmehran Poorsina, Marzieh Gharakhani, Masoumeh Najafi Ziarani, Elham Rahimian, Amirali
Mehvari Habibabadi
Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
& Kashani Comprehensive Epilepsy Center, Isfahan University of Medical Sciences, Isfahan, Iran
BACKGROUND: Rasmussen’s encephalitis (RE) is a rare but severe immune-mediated brain disorder
leading to unilateral hemispheric atrophy, associated progressive neurological dysfunction with
intellectual decline, and intractable seizures. The only established therapy that will cure the seizures and
allow the patient to resume a satisfactory life is hemispherectomy. There is accumulating evidence that
disconnective techniques are associated with a lower incidence of complications as compared to
anatomical hemispherectomies. This study described two patients who were a known case of Rasmussen
encephalitis and did functional hemispherectomy.
CASE PRESENTATION: The first case was an 18 year old male presented with epilepsia continua and
right hemiparesis. The disease has being started since he was 10 year old. Habitual seizure consisted of
right side clonic jerks which at times led to secondary GTCS. Data coming from Video EEG Monitoring
pointed to left fronto-parietal as a source of seizure. MRI showed left side atrophy and scar particularly
on the frontotemporal region. Overall data suggested Rusmussen encephalitis. Case two was a 26 year old
female presented with a history of intractable seizures since she was 23 year old. During these years she
gradually developed left hemiplegia and speech problem. During 24-hour admission in EMU, she had
frequent attacks of staring which are started from left paracentral with theta activity. MRI showed right
temporal and frontal atrophy with a mild generalized atrophy. Clinical presentation, EEG and MRI suggest
Rasmussen encephalitis. Result: For both cases, functional hemispherectomy was done and the seizures
became under controlled in both cases. Case one was well up to 2 weeks after surgery but at that time, he
developed meningitis and become aphasic. Since then he had no seizure but aphasia and right hemiplegia.
CONCLUSION: Epilepsy surgery has played a major role in the management of RE. Hemispherectomy and
its modern variants are highly effective in achieving seizure freedom and offer the only ‘cure’ for
preventing disease. Surgical option should weigh the severity of deficits to be expected after
hemispherectomy in relation to the severity of epilepsy and the consequences of its treatment. In such
patients with affection of the non-dominant hemisphere and with handicapping epilepsy,
hemispherectomy should be considered relatively early on. Our experience has suggested that patients
with RE and refractory epilepsy in particular may benefit from hemispherectomy.
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Therapeutic approaches to super-refractory status epilepticus
Khosro Jamebozorgi1, Behnam Safarpour Lima2
1-Department of Neurology, Zabol University of Medical Sciences, Zabol, Iran
2-Department of Neurology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran,
Iran
Super-refractory status epilepticus is defined as status epilepticus that continues or recurs 24 h or more
after the onset of anaesthetic therapy, including those cases where status epilepticus recurs on the
reduction or withdrawal of anaesthesia. It is an uncommon but important clinical problem with high
mortality and morbidity rates. This article reviews the treatment approaches. There are no controlled or
randomizes studies, and so therapy has to be based on clinical reports and opinion. The published world
literature on the following treatments was critically evaluated: anaesthetic agents, anti-epileptic drugs,
magnesium infusion, pyridoxine, steroids and immunotherapy, ketogenic diet, hypothermia, emergency
resective neurosurgery and multiple subpial transection, transcranial magnetic stimulation, vagal nerve
stimulation, deep brain stimulation, electroconvulsive therapy, drainage of the cerebrospinal fluid and
other older drug therapies.
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BASIC NEUROSCIENCE &
NEUROPHARMACOLOGY
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The New Event Related to the Pharmacotherapy of Myasthenia Gravis: A Review
Zahra Tolou_Ghamari
Isfahan Neurosciences Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran
BACKGROUND: The autoimmune or hereditary neuromuscular disorder, myasthenia gravis could lead to
muscle faintness and tiredness. Pharmacotherapy using acetylcholinesterase to improve muscle function
and immunosuppressive drugs to reduce the autoimmune process seem to be beneficial for patients.
PURPOSE: To provide a review article related to different pharmacotherapy strategy of myasthenia
gravis.
METHODS: Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), Library,
Information Science and Technology Abstracts (LISTA, EBSCO publishing) and Web of Science with key
words relevant to the topic of this review were searched.
RESULTS: Suggestive management for myasthenia gravis with acetylcholine esterase inhibition is usually
joined with immunosuppression. According to recent publication the disease should be categorized as
antibody specificity such as 1) acethylcholine, 2) muscle-specific receptor tyrosine kinase 3), low-density
lipoprotein receptor, and 4) seronegative. Also thymitis, thymoma or its atrophy and type of disease
course ocular or generalized seem to be important. Related to previous published articles, azathioprine,
cyclosporin, cyclophosphamide, methotrexate, mycophenolate mofetil and tacrolimus seem to be drugs of
choice. Study performed in 10 patients confirmed that in 3 with ocular and 7 with generalized disease
intranasal neostigmine could lead to improvement of symptoms of disease. In another study performed in
19 patients confirmed that in 84.2% concurrent prescription of intravenous immunoglobulins and
antibiotic therapy might provide higher clinical efficiency. A 12 months study related to pharmacotherapy
using tacrolimus with a dose of 2-6 mg daily showed muscle strength in 69 patients.
CONCLUSION: At the present time the therapeutic and pharmacotherapy strategies are still indicative.
They mark immunological indicators more gamely than precise myasthenic gravis symptoms. In severe
exacerbations, intravenous immunoglobulin, plasmapheresis and immunoadsorption are equally
effective.
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Hazardous effect of acrylamide on development of cerebellum and protective role of
vitamin C
Hengameh Dortaj, Morteza Anvari, Maryam Yadegari, Mohammad Hosseini
Shahid Sadoughi University of Medical Sciences, Yazd, Iran
BACKGROUND: Acrylamide (ACR) according to the method of cooking foods is increasingly used and its
adverse effects on multiple organ systems have been described sporadically in the literature. The purpose
of this study was to evaluate the effects of ACR on development and changes in cortical layer of the
cerebellum and cerebellar Purkinje cells in neonates of rat by using histological, morphometric and
stereological technique.
METHODS: In this study 20 adult female Wistar rats weighing 180 gr and aged two months were used.
Animals were randomly divided into four groups. Female pregnant rats were orally administered 10
mg/kg ACR and/or 200 mg/kg vitamin C (vit C). To study the neonatal period, 6 infants at day 21
randomly selected and placed under deep anesthesia and transcardial perfusion. The cerebellum was
taken out and fixed and cerebellum changes were evaluated by crysel violet and Hematoxylin-Eosine
staining method. The cerebellar cortex layers volume and the number of Purkinje cells were investigated
by Cavalieri's principle and physical dissector method. Data were analyzed by SPSS software and by
ANOVA and LSD Test.
RESULTS: Histological and stereological examinations revealed that the cerebellar volume was decreased
in ACR and ACR+vit C group vs control (P˂0.001). While in vit C group the cerebellar volume was
increased (P˂0.05). ACR in newborn decreases brain weight, thickness of cerebellum and the number of
purkinje cells with P˂0.001. The extent of this reduction in the weight of the cerebellum was significant
with P˂0.05.
CONCLUSION: ACR exhibits a harmful effect on the development of the cerebellar cortical layers, which
may be prevented by administration of vit C as an antioxidant.
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Effect of acrylamide and vitamin C and Glycyrrhiza Glabra on hippocampal
Aghdas M, Dashti M, Dortaj H, Anvari M, Yadegari M
Shahid Sadoughi University of Medical Sciences, Yazd, Iran
BACKGROUND: Acrylamide is a chemical compound which can produce in carbohydrate rich food during
high- temperatures cooking process. The neurotoxicity of acrylamide was reported in the previous
studies. The aim of the present study was to evaluate the effects of co-administration of Glycyrrhiza
Glabra and Vitamin C on acrylamide-induced motor deficits and learning and memory in rats.
METHODS: In this experimental study, 40 male Wistar rats of 28 days of age were divided into five
groups of 8 rats including Control, Acrylamide, Acrylamide + Vitamin C, Acrylamide + Glycyrrhiza Glabra
and Acrylamide +Vitamin C + Glycyrrhiza Glabra. All treatments were administered (oral) daily for two
months. Thereafter, locomotor activity indices, learning and memory, antioxidant activity of blood and
brain apoptotic rate were measured.
RESULTS: The results showed that motor deficit were significantly improved in vitamin C + Glycyrrhiza
Glabra group comparing to Acrylamide group, but treatment with vitamin C or Glycyrrhiza Glabra had no
significant effect. In addition, animals that treated with the combination of vitamin C and Glycyrrhiza
Glabra significantly decreased escape latency in comparison with Acrylamide group. Glycyrrhiza Glabra
alone could increased time spent in target quadrant. Total antioxidant activity of serum was increased in
all treated group comparing to control. Hippocampal apoptotic rate did not reveal significant changes
among treated groups with control.
CONCLUSION: This study showed that the co-administration of vitamin C and Glycyrrhiza Glabra can
retards the locomotors dysfunction and improve learning and memory in acrylamide-treated rats. Also,
the co-treatment elevates total antioxidant activity of serum in rats without change in Hippocampal
apoptotic rate.
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Effect of Boswellia serrata gum resin on anxiety behavior in young male rats following
prenatal stress exposure
Mohammad Hosseini-sharifabad, Razieh Kamali Ardakani
Shahid Sadoughi University of Medical Sciences, Yazd, Iran
BACKGROUND: Evidence indicates that stressful circumstances during gestational period could induce
long-term effects on anxiety behaviors. Although there is numerous anti-anxiety drugs, finding suitable
herbal drugs attracted the attention of psychopharmacologists. Boswellia serrata gum resin
(Frankincense or olibanum) is an herbal extract that their anti-nociceptive and neuroprotective effects
reported. Therefore, this study aimed to determine the effect of Frankincense on anxiety and
corticosterone levels in prenatal stressed rat offspring.
METHODS: In this experimental study, one-old male Wistar rats whose mothers were exposed to
restraint stress in plastic tube from gestational day 15 to 21 divided into control and experimental
(frankincense) groups. Experimental group received orally the aqueous extract of the Boswellia serrata
(100 mg/kg/day for 1 month) and equivalent volume of saline administered to controls. The anxiety
behaviors were assessed applying Elevated plus Maze and Territory Discrimination Test. Data were
analyzed with SPSS software using student t-test.
RESULTS: The basal level of corticosterone didn’t differ between two groups but the amount of
corticosterone 2 h after stress exposure in experimental animals was statistically lower than controls.
Data also showed that experimental rats (36.3±6.88%) compared to controls (11.9±3.61%) spend more
time in open arm of Elevated plus Maze (P<0.0001). In territory discrimination test, frankincense-treated
rats had less latency to enter in unknown compartment and spend more time in this compartment
compared to control group.
CONCLUSION: Results of this study indicated that administration of frankincense (100 mg/kg/day for 1
month) could decrease the prolongation of corticosterone secretion response and also anxiety behaviors
in prenatally stressed rats.
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The effect of peripheral kisspeptin 10 administration on serum gonadotropin and
histology of ovary in experimental hypothyroid rats
Raheleh Assaei1, Afshin Hasanvand2
1-Department of Physiology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
2-Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran
BACKGROUND: Kisspeptins, a hypothalamic neuropeptide transmitter, are targets for metabolic
hormones, such as thyroid hormones, which regulate reproductive function. Considering hypothyroidism,
a huge metabolic disturbance, associated to hypogonadotropism, we hypothesized that defective
gonadotropin secretion in hypothyroidism might affect through kisspeptins.
PURPOSE: To test this hypothesis, we evaluated histology of ovary and FSH and LH responses to
kisspeptin, in experimental hypothyroidism in female rat.
METHODS: In this study adult female wistar rats were used. The animals were divided into 8 groups: I.
control + normal saline, II. Control + kisspeptin group: rats used tap water and kisspeptin injected
(50x10-8nmol, i.p) daily for 9 days. III. Hypothyroid +kisspeptin: Hypothyroid rats were injected
kisspeptin (50x10-8nmol, i.p) daily for 9 days. IV. hypothyroid+ normal saline: Hypothyroid rats, were
injected normal saline daily for 9 days, V: hypothyroid + kisspeptin + ovariectomized: in hypothyroid
ovariectomized rats kisspeptin were injected (50x10-8nmol, i.p) daily for 9 days, VI: hypothyroid +
normal saline+ ovariectomized: in hypothyroid ovariectomized rats normal saline were injected (50x108nmol, i.p) daily for 9 days, VII: Control + normal saline+ ovariectomized, In this group, normal saline was
injected to euthyroid ovariectomized rats daily for 9, VIII: Control + kisspeptin + ovarectomized: In this
group, kisspeptin was injected to euthyroid ovariectomized rats daily for 9 days. Hypothyroidism was
induced by administration of methimazole at a concentration of 0.1 % in the drinking water for 14 days.
The blood samples were collected in first day, fourth day and ninth day, 1 hour after injections. Serums
LH, FSH and histopathology of ovary were determined.
RESULTS: Serum LH concentration decrement in hypothyroid animals returned to normal level 1 hour
after injection of kisspeptin and remain at normal level after 4 and 9 days injection. Serum LH increment
in hypothyroid ovariectomized animals increased after kisspeptin injection compared to hypothyroid
ovariectomized rats. The number of antral type follicles decreased in hypothyroid animals that restore to
the number of antral type follicles in control group, after 9 days kisspeptin injection.
CONCLUSION: Altogether, these data support that kisspeptin administration ameliorates the
hypogonadotropic and ovarian histology phenotype of hypothyroidism.
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The effect of peripheral kisspeptin 10 administration on serum estradiol and
progestrone and estrous cycle in experimental hypothyroid female rats
Afshin Hasanvand1, Raheleh Assaei2
1- Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran
2-Department of Physiology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
BACKGROUND: Kisspeptins, a hypothalamic neuropeptide transmitter are targets for metabolic
hormones, such as, thyroid hormones, which regulate reproductive function. Considering
hypothyroidism, a huge metabolic disturbance, associated to hypogonadotropism. Defective
gonadotropin secretion in hypothyroidism might affect through some drugs.
PURPOSE: In this study, we evaluated the effect of peripheral kisspetin 10 administration on serum
estradiol and progesterone and esterous cycle in experimental hypothyroid female rats.
METHODS: The female wistar rats were divided into 4 groups: I. control+normal saline, II.
control+kisspeptin group: rats used tap water and kisspeptin injected (50×10-8 nmol, i.p) daily for 9
days. III. hypothyroid+kisspeptin: Hypothyroid rats were injected kisspeptin (50×10-8 nmol, i.p) daily for
9 days. IV. hypothyroid+ normal saline: Hypothyroid rats, were injected normal saline daily for 9 days, in
this group, normal saline were injected to euthyroid ovarectomized rats daily for 9 days. Hypothyroidism
was induced by administration of methimazole at a concentration of 0.1 % in the drinking water for 14
days. The blood samples were collected in first day, fourth day and ninth day, 1 hour after injections.
Serum estradiol and progesterone and estrous cycle were determined in experimental hypothyroid
female rats.
RESULTS: Estradiol and progesterone concentration decreased in hypothyroid animals and returned to
normal level after injection of kisspeptin 10 after 4 and 9 days injection. Irregular estrous cycle resulted
in hypothyroid rats returned to normal pattern after 5 days kisspeptin10 injection.
CONCLUSION: Altogether, these data support that kisspeptin10 injection ameliorates the ovarian steroid
and cyclicity of estrous cycle of hypothyroid rats.
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Study of transcected sciatic nerve repair by chitosan/Polyethylene oxide scaffolds and
human mesenchymal stem cells from Wharton's jelly in Wistar rats
Moattari M1, Kouchesfahani H1, Kaka GH R2, Sadraie H2
1-Department of Biology, School of Medicine, Kharazmi University, Tehran, Iran
2-Research Scientific Center, Baghatallah Medical University, Tehran, Iran
PURPOSE: The aim of this study was to determine the effects of chitosan/Polyethylene oxide scaffolds
and human mesenchymal stem cells from Wharton's jelly on regeneration of the sciatic nerve injury in
Wistar rats.
METHODS: In this research 42 male adult rats weighting 200-250g were divided into six groups
including-Normal group: healthy rats without any injuries. In Control group: sciatic nerve was cut in the
middle region of thigh and epineuria were sutured. In Sham group: culture medium was injected on the
sciatic nerve damaged. In Cs/PEO group: scaffold with a thin Cs/PEO were used around the sciatic nerve
damaged. In cell group: 500000WJ-MSCs injected in the site of nerve damaged. In Cs/PEO with cell group:
scaffold with a thin Cs/PEO and 500000WJ-MSCs were used around the sciatic nerve. After 8 weeks, the
rate of recovery was studied by SFI (Sciatic Functional Index) and electroctrophysiological assessments.
RESULTS: At the end of the eight week, SFI index showed improvement in Cs/PEO and WJ-MSCs group
(P˂0.05). Mean SFI index showed relative improvement in treated groups compared to the control and
sham groups. The results of latency and amplitude of electrophysiology showed that Cs/PEO and WJMSCs group was significantly better than control, sham, Cs and WJ-MSCs groups (P˂0.05).
CONCLUSION: The results suggested that Cs/PEO had potential capability of regeneration of sciatic nerve
injury.
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Histomorphometric evaluation of chitosan/poly ethylen oxide scaffold and human
mesenchymal stem cells from Wharton's jelly on the repair of transcected sciatic nerve in
wistar rat
Moattari M1, Kouchesfahani H1, Kaka GH R2, Sadraie H2
1-Department of Biology, School of Medicine, Kharazmi University, Tehran, Iran
2-Research Scientific Center, Baghatallah Medical University, Tehran, Iran
PURPOSE: The aim of this study was to test the effects of chitosan-polyetylene (Cs/ PEO) scaffold and
WJMSCs on sciatic nerve regeneration in rat.
METHODS: In this study, forty-two male Wistar rats weighting 200-250 g were used. Animals were
randomly divided into 6 experimental groups including normal, control, sham, Cs/PEO group, cell
transplantation group and Cs/PEO and cell transplantation group. Normal group includes intact animals
without sciatic nerve damage. In other groups sciatic nerve were cut in middle region of thigh and
epineuria were sutured. Control group in which the nerve cut and was sutured. In sham group, culture
medium was injected on the sciatic nerve damaged. In Cs/PEO group, scaffold with a thin Cs/PEO were
used around the sciatic nerve damaged. In cell group, 500000 WJMSCs was injected on the sciatic nerve
damaged. In Cs/PEO and cell group, scaffold with a thin Cs/PEO and 500000WJMSCs were used around
the sciatic nerve damaged. The improvement rate was evaluated by histology.
RESULTS: Mean number of nerve fibers in the Cs/PEO and WJMSCs groups significantly increased when
compared to control and sham groups (P<0.05). Mean size of largest nerve fibers showed no significant
decrease in all groups compared to control and sham groups (P<0.05).
CONCLUSION: It seems that Cs/PEO and WJMSCs transplantation appears to be effective in the repair of
damaged nerve.
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A review on effectiveness of the combination of memantine plus vitamin D on cognition
in patients with Alzheimer disease
Mahdieh Rahimoghli, Ehsan Pourmemar, Maryam Dadashzade
Tabriz University of Medical Science, Tabriz, Iran
BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia. In addition to a decrease in
brain cholinergic activity some of preclinical and experimental researches suggest that vitamin D
enhances the efficacy of memantine in terms of neuronal protection and prevention of cognitive decline in
AD. Thus this article reviews the last literatures and investigations of vitamin D and memantine therapy
for AD and improvement of outcomes and outgoing efforts to translate the preclinical findings into
clinical investigations.
METHODS: For this purpose, we have searched the relevant articles (2010-2014) in scientific databases
and eliminate repetitious and invalid articles.
RESULTS: According to studied papers, AD is also marked by glutamatergic excitotoxicity that results in
neuronal death. Memantine's modulation of NMDA receptors has been reported to prevent the neuronal
necrosis induced by glutamatergic calcium neurotoxicity, but not the neuronal apoptosis resulting from
oxidative stress. This observation calls for new drug regimen strategies based on memantine combined
with molecules having antioxidant effects, in order to create a multi-target therapy to increase neuronal
protection and prevent AD progression. On the other side, vitamin D is a secosteroid hormone that is
suggested to have neuroprotective effects that include regulation of neuronal calcium homeostasis, as
well as antioxidant, neurotrophic and anti-inflammatory properties.
CONCLUSION: Accordingly it seems that the combination of memantine plus vitamin D may represent a
new multi-target therapeutic class for the treatment of AD.
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A review on CAD106 immunotherapy in Alzheimer’s disease
Mahdieh Rahimoghli, Ehsan Pourmemar
Student Neurosciences Research Committee (SNRC), Tabriz University of Medical Sciences, Tabriz, Iran
BACKGROUND: Alzheimer disease (AD) is the most common cause of dementia and may contribute to
60-70% of cases. The cause and progression factors of AD are not well understood but have been thought
that protein misfolding, beta amyloid (Aβ) plaques and tau proteins accumulation in brain are cardinal
factors in this way. Some of preclinical and experimental researches suggest that Aβ immunization results
in brain Aβ remove. CAD106 is a novel immunotherapy designed to stimulate the generation of antibodies
against a small Aβ peptide fragment and Treatment with CAD106 induced an antibody response against
Aβ and Qβ in most patients. Thus, this review focused on last literatures and investigations related
CAD106 immunotherapy antibody response against Aβ in the brain.
METHODS: For this purpose, we have searched the relevant articles (2000-2014) in scientific databases
and eliminate repetitious and invalid articles.
RESULTS: According to studied papers, CAD106 is immunotherapy designed to stimulate the generation
of antibodies against a small Aβ peptide fragment (Aβ1–6) acting as a B-cell epitope and avoiding an Aβspecific c T-cell response. Immunization with CAD106 reproducibly prevented brain amyloid plaque
accumulation in two transgenic mouse models of Alzheimer’s disease, with reductions of up to 80% in the
plaque area compared with controls.
CONCLUSION: It seems that, in the future, the CAD106 immunotherapy, antibody response against Aβ
may provide a possible treatment option and help to AD progressing prevent.
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A review on beta amyloid-based immunotherapy in Alzheimer’s disease
Ehsan Pourmemar, Mahdieh Rahimoghl, Saeed Sadigh-Eteghad Neurosciences Research Center (NSRC),
Tabriz University of Medical Sciences, Tabriz, Iran and Student Neurosciences Research Committee (SNRC),
Tabriz University of Medical Sciences, Tabriz, Iran
BACKGROUND: Alzheimer disease (AD) is the most common cause of dementia and may contribute to
60-70% of cases. The cause and progression factors of AD are not well understood but have been thought
that protein misfolding, beta amyloid (Aβ) plaques and tau proteins accumulation in brain are cardinal
factors in this way. Some of preclinical and experimental researches suggest that Aβ immunization results
in brain Aβ remove. Thus, this review focused on last literatures and investigations related to passive or
active immunotherapies targeting Aβ in the brain.
METHODS: For this purpose, we have searched the relevant articles (2000-2014) in scientific databases
and eliminate repetitious and invalid articles.
RESULTS: According to studied papers, immunotherapy in AD aimed at Aβ covers 2 types of active and
passive vaccination. In active vaccination against Aβ, patients receive injections of the antigen itself and in
passive vaccination patients receive injections of monoclonal antibodies against Aβ. Three of the peptide
vaccines for active immunizations, CAD106, ACC001 and Affitope are in phase II clinical trials. Three of
the monoclonal antibodies namely, solanezumab, gantenerumab and crenezumab are in phase II and III
clinical studies.
CONCLUSION: It seems that, in the future, the Aβ-based immunotherapies may provide a possible
treatment option and help to AD progressing prevent.
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A review on role of Deferoxamine in preventing and treatments of stroke patients
Safa Savadi Oskuee, Mona Zamanpour, Saeed Sadigh-Eteghad
Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran
BACKGROUND: Stroke is the third leading cause of death in developed countries and it is the most
common disabling neurological disorder in the world. Some of preclinical and experimental researches
suggest that Deferoxamin (DFO) has preventing and treating effects on stroke. Thus, this article reviews
the last literatures and investigations of DFO therapy for stroke and improves outcome, and ongoing
efforts to translate the preclinical findings into clinical investigations.
METHODS: For this purpose, we have searched the relevant articles (2001-2012) in scientific databases
and eliminate repetitious and invalid articles.
RESULTS: According to the studied papers, during a stroke, iron is released in brain cells as part of the
free radical damage and DFO is a high affinity iron chelator. Also it may treating iron overload and may
improve the patient’s condition via related mechanisms.
CONCLUSION: It seems that DFO can be an important complementary therapy in stroke patients and
improve the life quality of them.
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Prescription of Lipitor or Atrova after Stroke
Zahra Tolou_Ghamari
Isfahan Neurosciences Research Centre, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan,
Iran
BACKGROUND: By independent method related to the levels of cholesterol, it seems that pretreatment
with atorvastatin could improve ischemic brain damage after tentative stroke. Also in patients with
previous stroke or transient ischemic attack pharmacotherapy with atorvastatin may improve renal
function.
PURPOSE: The aim of this study was to investigate the frequency of pre- or post- prescribed atorvastatin
after stroke.
METHODS: A cross-sectional study located at the Neurology ward of the Isfahan Alzahra Hospital was
carried out on 50 patients with stroke. Demographical, clinical and pharmacological information were
recorded in d-Base.
RESULTS: Of the total population studied 60% were males. With a minimum of 31 and a maximum of 93,
the mean age of patients was 73 years old. The frequency of prescribed atorvastatin in patients with
stroke was 80%. Within this population 65% of males received atorvastatin (13 females versus 24 males).
There was not a significant difference between the mean and the maximum age of males and females
(p>0.05). The minimum age of male patient with a value of 31 years old was significantly lower than the
female with a value of 52 years old (p<0.05).
CONCLUSION: However neurological disorders are widespread globally but cerebrovascular diseases,
reported for 55% of those disorders. Stroke could be mentioned as one the most important reason of
enduring disability, cognitive and motor disorders and dementia. It could influence the task and
composition of blood-brain hedge, the loss of cerebral blood flow regulation, oxidative stress,
inflammation and the loss of neural associations. Finally, to protect patients from cerebral
ischemia/reperfusion injury and to reduce inflammation and thrombogenesis effects, pre- or posttreatment with atorvastatin might promote anti-inflammatory and antioxidant effects in such patients.
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Evidence-Based Preliminary Study of Antibiotics Pharmacotherapy in 50 Hospitalized
Patients with Stroke
Zahra Tolou_Ghamari, Mohamad-Reza Najafi, Fariborz Khorvash
Isfahan Neurosciences Research Centre, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan,
Iran
BACKGROUND: According to previous publication stroke associated pneumonia could be accounted
between 7-22% for early mortality after ischemic stroke. Rickettsial infections, Gram-negative bacilli
included Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumonia and many other Infections
might occur in 30% of stroke patients and could be connected with negative outcomes.
PURPOSE: The aim of this preliminary study was to investigate the frequency and type of prescribed
antibiotics in stroke.
METHODS: A cross-sectional study located at the Neurology ward of the Isfahan Alzahra Hospital was
carried out on 50 patients after stroke. Demographical, clinical and pharmacological information were
recorded in d-Base.
RESULTS: For 16 out of 50 patients antibiotic (32%) were prescribed. The minimum age of those who
received antibiotics was 31 years old and the maximum age was 92 years. The mean age of all studied
population was 76.5 years old. The highest rate for prescribed antibiotics was belonged to Ceftriaxone in
8 occasions. The lowest value for tendency toward prescription belonged to Cephalexin in 1 event. There
were propensity for administration of Cefepime (n=2), Ceftazidime (n=2), Meropenem (n=2) and
Clindamycin (n=3).
CONCLUSION: The leading cause of death worldwide (30%) needs much more attention regarding to
overall supervision and pharmacotherapy management in Iranian population. In addition to
administration of sensible antipyretic, routine O2 supplementation and attention to early mobilization
also should be considered vigilantly. Prescription of the most common beta-lactams such as Ceftazidime
and Cefepime in patients with severe kidney disease after stroke should be always with cautious due to
the potential neurotoxicity. Finally, to found whether protective antibiotic therapy in acute stroke could
increase clinical outcome by inhibiting infection, further study in this direction recommended.
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Neurologic Disorders: a Brief and Quick Review into the Domain of Pharmacotherapy
Zahra Tolou_Ghamari
Isfahan Neurosciences Research Centre, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan,
Iran
There is a great need for discovery of new drugs in clinical neurology such as seizure, multiple sclerosis,
Parkinson, amyotrophic lateral sclerosis and many other neurological disorders. According to recent
publication, by Shimohata T et al., in 2015, rotigotine and apomorphine are the new drugs that could be
prescribed for patients with Parkinson. Kim W and colleagues in 2015 explained three oral drugs that
have been approved by regulatory agencies for MS treatment: fingolimod, teriflunomide, and dimethyl
fumarate. Regarding to the field of seizure Lee SK et al., in 2015 compared new versus old antiepileptic
drugs (AEDs). Efficacy and pharmacokinetic behaviors has been the main concern of focus in this
comparison. It seems that the efficacy of old generation is stronger than the new ones. The response to
both generation of AED varies inter and intra individually. Epstein C et al., in 2015 published that anterior
thalamic stimulation is associated with a 69% reduction in seizure frequency and a 34% serious devicerelated adverse event rate at 5 years. Werhahn KJ et al., in 2015 concluded that in the initial monotherapy
of focal epilepsy in the elderly, 1-year retention to levetiracetam was higher compared to controlledreleased carbamazepine due to better tolerability. Retention of lamotrigine was intermediate and close to
levetiracetam, but did not differ significantly from either comparator. A recent prospective study
performed by Helfert S, et al., confirmed the concept of personalized pharmacological treatment of
neuropathic pain.
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NEUROMUSCULAR DISORDERS
& NEUROPHYSIOLOGY
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Ultrasound in Neuromuscular Disorders
Hamid Ebadi1, CanadaVera Bril2
1-Department of Neurology, University of Calgary, Toronto, Canada
2- Department of Neurology, University of Toronto, Canada
Ultrasound (US) has been widely used for the investigation of the neuromuscular disorders since last
decade. Although it has been 30 years it was originally used for assessment of muscular dystrophies in
children, new generation of higher frequency ultrasound machines have provided the opportunity of
excellent visualization of small sized nerves such as sural and superficial peroneal. It has been shown that
peripheral nerve ultrasound provides additional information to enhance clinical and EMG diagnosis in
40% of patients with focal neuropathies and in another 40% of them it confirms EMG findings. There are
growing studies regarding the important role of US in inflammatory polyneuropathies such as CIDP and
MMN. Muscle US has also been used for assessment of muscular dystrophies, detection of fasciculation (in
some studies as sensitive as EMG), and as a guide for needle examination of diaphragm. This article will
be reviewing clinical application of US in diseases of peripheral nerves and muscles. The main focus
would be on the focal neuropathies which US is extremely useful but we will also discuss the recent
trends and studies focused on polyneuropathies and myopathies. There are also videos and pictures of
different interesting cases have been studied for the past two years in the US laboratory of the
neuromuscular clinic of the University of Toronto.
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Chronic inflammatory demyelinating polyradiculoneuropathy: what are the treatment
options?
Narges Karimi, Mahmood Abedini, Ashraf Zarvani
Department of Neurology, Mazandaran University of Medical Sciences, Sari, Iran
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) has been used to identify patients
with a chronically progressive or relapsing symmetric sensorimotor disorder with cytoalbuminologic
dissociation and interstitial and perivascular endoneurial infiltration by lymphocytes and macrophages. It
can be considered the chronic equivalent of acute inflammatory demyelinating polyradiculoneuropathy.
CIDP is an autoimmune disorder, as demonstrated by a great deal of evidence, such as the finding of
inflammation at the site of the lesion, response to immunomodulatory treatment and possibly the
presence of autoantibodies against myelin antigens. Long-term prognosis of CIDP has been correlated to
age at onset, response to treatment, and time from onset to the beginning of treatment: young patients
with acute onset are more likely to respond to treatment than elderly ones and proximal impairment has
been linked to a better prognosis than distal weakness. The main negative prognostic factors of CIDP are
progressive course and axonal degeneration Peripheral nerve injury results from a synergistic interaction
of cell-mediated and humoral immune responses directed against peripheral nerve antigens that have not
been completely characterized. Since inflammation is the core of the disease, it is not surprising that
immunomodulatory treatments have a positive effect. Nevertheless, it is not yet possible to predict
disease progression on the basis of biological markers, because it is likely that under the general
definition of “CIDP” a broad spectrum of different forms is included. Currently available treatments for
CIDP are corticosteroids, immune globulin, plasma exchange, and chronic immunosuppressive agents.
Treatment choice will depend on several variables such as initial disease severity, age, general health
status, and potential contraindications. If a patient has only mild symptoms, a nerve biopsy could help to
confirm the diagnosis and establish the need for intervention if axonal degeneration has already occurred.
Mild symptomatic patients should be followed up regularly with repeated neurophysiological
examinations since relapses are unpredictable and oblige to start the treatment. Treatment with
corticosteroids or IVIG should be offered to patients with moderate or severe disability. First-line
treatment choice depends on several factors, such as disease severity, the presence of a pure motor form
of CIDP, contraindications and side effects of long-term therapy, costs, and local availability of PE or IVIG.
An alternative approach, the subcutaneous administration of immunoglobulins (SCIG) via a small
portable pump, has been initiated for these disorders. This regimen is well established for children.
Application of SCIG with a small portable pump at home can significantly improve quality of life by
reducing the frequency of hospitalizations and also reduced side effects and significant cost has
demonstrated. Fingolimod is intended to be used as second line therapy for the treatment of patients with
chronic inflammatory demyelinating polyneuropathy (CIDP). If licensed, fingolimod would offer an
additional treatment option for patients with CIDP who currently have few (well-tolerated) effective
therapies available. The tumor necrosis factorα antagonist etanercept is beneficial in rheumatoid
arthritis. Three of 10 patients with treatment-resistant CIDP were considered to gain significant benefit
from it. Rituximab is a chimeric (mouse/human) monoclonal antibody against CD20+ B lymphocytes. In
CIDP, it was reported to have been beneficial in 12 of 17 patients in published case reports and small
series. Autologous peripheral blood stem cell transplantation is an extreme form of immunosuppression
in which the patient is treated with high dose cyclophosphamide and then granulocyte stimulating factor
to allow harvesting of bone marrow stem cells from the blood. The patient is then treated with very high
dose cyclophosphamide, anti-T cell antibodies and, in some regimes, whole body irradiation to ablate
their immune system.
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Comparison of diagnostic value of cross sectional area of median nerve in with highresolution ultrasound and electro-diagnostic study results in patients with carpal-tunnel
syndrome
Mohamadali Nahayati, Reza Boostani, Saedi
Torbate Heydarieh University of Medical Sciences, Mashhad, Iran
BACKGROUND: Carpal tunnel syndrome (CTS) is the most common form of peripheral nerve entrapment.
Our aim was to assess the optimal discriminatory ultrasonography (USG) criteria in patients with CTS and
to evaluate quantitative USG as a tool for diagnosis and treatment of patients in comparison with
electrophysiological study (EDS).
METHODS: Two hundred and five patients with CTS (30 male, 175 female) were assessed by clinicians in
during 2009-2010 and underwent USG of the wrists. We considered each wrist separately in clinical
diagnosis, thus in total 410 hands were analyzed in this work. EDS testing was done for all patients.
RESULTS: In this study sensitivity of USG was 89% and specificity was 84% in right hand, and 90% and
89% for left hand, respectively. The false negative and false positive results of USG were 11%and 15%,
respectively. There was a high degree of correlation between the conduction abnormalities of the median
nerve as detected by EDS and the measurement of the cross-sectional area of the nerve by US (P<0.05).
Various levels of disease severity could also be detected by USG.
CONCLUSION: High-frequency USG examination of the median nerve and measurement of its crosssectional area should be strongly considered as a new alternative diagnostic modality for diagnosis and
treatment of CTS, with evaluation of disease severity.
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Carpal Compression test, Phalen’s test and Tinel’s test: which ones are better for Carpal
Tunnel Syndrome?
Mostafa Almasi Doghaee1, Reza Boostani2, Morteza Saeedi2, Amir Moghadam Ahmadi3
1-Rasool Akram Hospital, Department of Neurology, Faculty of Medicine, Iran University of Medical Sciences,
Tehran, Iran
2-Department of Neurology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3-Department of Neurology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
BACKGROUND: Carpal Tunnel Syndrome (CTS) is one of the causes of hand dysfunction and because of
its high prevalence, early diagnosis is very important. The aim of this study was to compare the sensitivity
and specificity of the clinical tests of this syndrome.
METHODS: Electrodiagnostic tests were performed on 89 consecutive patients suspected to CTS from
2011 to 2012, after assessing their medical history and undertaking physical examinations including
Carpal Compression test (CCT), Tinel’s and Phalen’s tests. Then data analyzed with SPSS software and the
sensitivity and specificity of clinical tests and the agreement between them were calculated.
RESULTS: CTS was diagnosed in 80.9% of patients. There was no statistically difference in age, gender,
employment and type of occupation between CTS and non-CTS patients. The highest sensitivities and
specificities levels were obtained for the CCT (80.6% and 52.9%), Tinel/s (65.3% and 47.1%) and
Phalen’s (59.7% and 35.3%) tests, respectively. There was a negative agreement between the Tinel’s and
CCT tests in non-CTS patients (k= -0.524, P= 0.030) and a positive agreement between the Phalen’s and
Tinel’s tests in CTS patients (k= 0.409, P<0.001).
CONCLUSION: According to the findings of this study we suggest that clinicians should use the carpal
compression test and Tinel’s test routinely for screening of patients suspected of suffering from CTS.
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Serum level of Vitamin D in Patients with Acute Ischemic Stroke
Farhad Assarzadegan
Department of Neurology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran,
Iran
BACKGROUND: Vitamin D deficiency is common among the elderly and may contribute to
cerebrovascular diseases.
PURPOSE: We tested the hypothesis that low plasma concentrations of 25-hydroxyvitamin D are
associated with increased risk of symptomatic ischemic stroke in patients with diagnosis of acute
ischemic stroke.
METHODS: In a case-control survey, 70 patients with diagnosis of acute ischemic stroke (AIS) admitted to
Imam Hossein Hospital considered as case group and 72 patients with limbs trauma considered as
control group. Matching between 2 groups was done based on age, sex, BMI, blood pressure and diabetes
history. The serum level of vitamin D, calcium, P, ESR, CRP was measured in all participants.
RESULTS: The serum level of calcium, P, ESR, CRP was not significantly different in both case and control
groups. However, the serum level of 25(OH) D was significantly lower in patients with ischemic stroke
(19.04±14.5 ng/ml) in comparison with control group (28.89±14.62 ng/ml; p <0.001).
CONCLUSION: The serum level of vitamin D in patients with ischemic stroke was significantly lower than
control group. These findings suggest that 25(OH) D may be an independent prognostic factor for
ischemic stroke. However, evaluation level of 25(OH) D and severity symptoms and complication of
stroke need to the more investigation.
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MOVEMENT DISORDERS
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Basal ganglia calcification due to Cockayne syndrome: case report
Chitsaz A, Ansari B
Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran
BACKGROUND: Cockayne syndrome is a rare, autosomal disorder characterized clinically by short
stature, atypical retinopathy, enophthalmos, dental caries, skeletal and neurological abnormalities. We
present case of 25-year-old male with Cockayne syndrome with neurological dysfunction and basal
ganglia calcification.
CASE PRESENTATION: The cachectic 25-year-old male presented with dysmorphic and neurological
abnormalities, the child’s parents were both healthy. They have only one child. There was no parental
consanguinity. The mother described her pregnancy was normal. She didn’t report any illness and
hospitalizations during the pregnancy. Vaginal delivery was normal. The parents first became concerned
about the child at approximately age 3 months because his head didn’t grow and his visual was decreased.
His development continued to be delayed. The ophthalmologic evaluation revealed retinopathy and
intermittent exotropia and cataract formation. His scalp was dry; his hair was dry, sparse and brittle.
Dental caries was started from childhood and all of teeth decayed until 7 year’s old. No other significant
abnormalities of the soft or hard structures of orofacial region were apparent. His skin was loose and his
scrotum was small. Serial photographs show that Cockayne fancies. He walked unsupported at 15 years
old. Irregular gait at 15 years was followed by spasticity and required wheelchair lengthening at 20 years.
Hyperactive tendon stretch reflexes were obtained. There was frequent fall in these years. Intention
tremor and titubation of the head were documented at 17 year’s old. Optic atrophy was detected at age 10
years, retinitis pigmentosa and lens opacities at age 13 years, Vision became limited at age 15 years and
he was blind at age 20 years. In neurological examination, he was alert; spasticity in all of limbs with
hyper reflexes was detected. Computed tomography revealed marked ventricular dilatation, cerebral and
cerebellar atrophy and calcification of basal ganglia. Magnetic resonance imaging was showed white
matter demyelination, brain atrophy and basal ganglia calcification. Tests for lipid profile, liver enzyme,
renal function, thyroid function, pyruvate, lactate and vascular tests were normal. Parathyroid hormones
were small elevation. (PTH=85 normal range was 14-74) Because of dysmorphic features, dental caries,
ophthalmological abnormalities and basal ganglia calcification, we assigned him to the Cockayne
syndrome.
CONCLUSION: Cockayne syndrome is a rare autosomal recessive disease but dental caries are common in
this syndrome. So in patient with basal ganglia calcification with typical dysmorphic feature, visual,
cutaneous and neurological findings with prominent dental caries, we should considered Cockayne
syndrome and further study to evaluation of genetic test should be performed.
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Evaluating function of parathyroid gland axis in Parkinson's disease
Ahmad Chitsaz, Rokhsareh Meamarit
Esfahan University of Medical Sciences, Isfahan, Iran
BACKGROUND: Parathyroid hormone (PTH) levels can make changes in serum biomarkers and effect
progression symptoms of many diseases like Parkinson's disease (PD). According to previous studies it
seems that parathyroid gland function is effective in severity of symptoms of PD. This study aimed to
explore the role of PTH in PD, progression regarding the lack of researches in this field in the Middle East.
METHODS: This case control study was carried out in Alzahra hospital, Isfahan, Iran. 125 patients with
PD diagnosed by experienced neurologists and 112 healthy controls matched for age and gender with
patient group. They were asked to participate during September to November 2011. At base line, the
severity of PD was evaluated with motor part of the unified PD rating scale III (UPDRs III), the level of
PTH, calcium, phosphorus, and 25- hydroxyl vitamin D were measured.
RESULTS: The mean±SD of PTH level was significantly lower in patients group (45.2±18.8 IU/I),
compared to controls (70.8±28.5 IU/I; P=0.0001); There are not any significant correlation between
hormone level, elements and severity of PD. We observed that men had motor risk of PD than women
(odds ratio=2.53, [CI: 1.27-5.03)], P=0080).
CONCLUSION: This study could not confirm the relationship between the level of parathyroid gland
function, the level of serum PTH and severity of motor symptoms in PD. It could be explained by the lack
of a sufficient number of Hypo and hypercalcemia, phosphatemia and hypoparathyroidism in our
samples.
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NEUROMODULATION
& NEUROREHABILATION
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Augmentative and Alternative Communication (AAC) for adults with aphasia
Elham Seihei1, Alireza Mollaei2
1-Musculoskeletal Rehabilitation Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz,
Iran
2-Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
BACKGROUND: Aphasia is the result of damage to the brain's language centers affecting production,
comprehension, or both, and can cause severe, chronic language impairment Individuals with aphasia
often communicate using a combination of speech, gestures, and aided communication; the proportion of
each may change as the person recovers, and depends on the context and the individual's skills.
PURPOSE: The aim of this review is Augmentative and Alternative Communication (AAC) for adults with
aphasia.
METHODS: ScienceDirect, Pubmed (2000 through 2015) were searched for English-language studies
using a list of keywords. The books about AAC, neurology and speech-language pathology were studied
too.
RESULTS: Depending on their language and cognitive skills, those with aphasia may use AAC
interventions such as communication and memory books, drawing, photography, written words, speech
generating devices and keyboards. Visual scene displays have been used on communication devices with
adults who have chronic, severe aphasia; these feature photos of people, places or events that are
meaningful to the individual and facilitative of communicative interaction. Approaches such as
"Supported Conversation for Adults with Aphasia" train the communication partners to use resources
such as writing key words, providing written choices, drawing, and using items such as photographs and
maps to help the individual with aphasia produce and comprehend conversation. Published data support
the use of aided and unaided AAC with adults with severe aphasia in controlled treatment contexts.
Reported gains in communication typically have not generalized to everyday settings.
CONCLUSION: AAC has much to offer for supporting aphasic communication, not only for people with a
very severe aphasia, who do not benefit from disorder‐oriented therapy, but also for people with a
moderate or mild aphasia. Research into AAC and aphasia, focusing on functional use, is needed in order
to build and refine communication aids that are easy to use and can be tailored individually.
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How do ankle muscles activities in post stroke patients alter while locomotors intensity
changes?
Roghayeh Mohammadi, Mohammad Reza Hadian, Saeed Talebian Moghadam, Chetan P. Phadke, Mir
Saeed Yekaninezhad
Tehran University of Medical Sciensces, Tehran, Iran
BACKGROUND: Plantar flexor muscles produce propulsive force in the second half of stance phase,
obviously muscle weakness lead to progressive decline in force production and adequate propulsion at
push off phase of gait following stroke.
PURPOSE: This study examined whether walking on an inclined surface increased muscle activity in
stroke patients and whether it resulted in increased muscle activity during walking speed increasing.
METHODS: To test these hypotheses, 19 post-stroke patients (14 males and 5 females) walked on a
standard treadmill at three grades and three different speeds. We quantified the puss off phase
electromyographic activities of the ankle muscles, Medial Gastrocnemius (MG), and Tibialis anterior (TA).
RESULTS: MG muscle activity at the affected side in the push off phase increased when walking speed
went up in any slope (p<0.05). Also its activity was significantly greater at 3 and 6 degree incline
compared with no incline in the non paretic side of people with stroke (P<0.05) but not in the paretic side
(P>0.05). No change was seen in TA muscle activity in the paretic side of people with stroke (P>0.05) but
reduction in its activity was seen on non paretic side with increasing walking speed (P<0.05). On average,
compared to level walking, MG muscle activity increased to walk up higher grade on non affected side of
patients. In contrast, changes in muscle activations on paretic side were seen with faster walking speed.
CONCLUSION: We conclude that both sides of the patients apply distinct muscle recruitment strategies
generally across walking speeds and progressively with steeper grade.
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Subcortical Encoding of Speech Cues in Children with Attention Deficit Hyperactivity
Disorder
Zahra Jafari1, Saeed Malayeri Audiologist2, Reza Rostami3
1-Department of Basic Sciences in Rehabilitation, School of Rehabilitation Sciences, Iran University of
Medical Sciences (IUMS), Tehran, Iran
2-Newsha Hearing Institute, Tehran, Iran
3-Department of Psychology, Tehran University, Tehran, Iran
BACKGROUND: There is little information about processing of nonspeech and speech stimuli at the
subcortical level in individuals with attention deficit hyperactivity disorder (ADHD). The auditory
brainstem response (ABR) provides information about the function of the auditory brainstem pathways.
PURPOSE: We aim to investigate the subcortical function in neural encoding of click and speech stimuli in
children with ADHD.
METHODS: The subjects include 50 children with ADHD and 34 typically developing (TD) children
between the ages of 8 and 12 years. Click ABR (cABR) and speech ABR (sABR) with 40 ms synthetic /da/
syllable stimulus were recorded.
RESULTS: Latencies of cABR in waves of III and V and duration of V-Vn (P=0.027), and latencies of sABR
in waves A, D, E, F and O and duration of V-A (P=0.034) were significantly longer in children with ADHD
than in TD children. There were no apparent differences in components the sustained frequency
following response (FFR).
CONCLUSION: We conclude that children with ADHD have deficits in temporal neural encoding of both
nonspeech and speech stimuli. Significance: There is a common dysfunction in the processing of click and
speech stimuli at the brainstem level in children with suspected ADHD.