Download Neurology Residents Gary Gallagher

Neurology Residents
Gary Gallagher - The Yield of Procedures and Imaging in the initial evaluation of peripheral neuropathy
Introduction: Peripheral neuropathy encompasses a heterogeneous group of disorders, including distal
symmetric polyneuropathy, mononeuropathy, multiple mononeuropathies, demyelinating neuropathies,
amongst many others. Peripheral neuropathy is a prevalent condition affecting approximately 2% of the
general population and as many as 8% of those over the age of 55. Several recent studies have been
published regarding the laboratory work-up in the initial evaluation of peripheral neuropathy, with the highest
level of evidence supporting fasting blood glucose, vitamin B12 and SPEP (only level C). A significant
proportion of patients also undergo evaluation with EMG and MRI. Given the current health care climate, which
places a premium on cost-effective medicine, further studies are needed to determine which tests should be
performed in these patients.
Methods: We will perform a retrospective chart review of patients presenting to the University of Michigan
Neuromuscular Clinic, a tertiary referral center, from 1/1/2007 through 12/31/2008. Patients with symptoms
(parasthesias, numbness, pain, weakness) and exam findings (sensory findings, weakness, hyporeflexia) of
peripheral neuropathy will be included. Those patients with evidence of compression neuropathy, traumatic
neuropathy, and radiculopathy will be excluded. Patients will be evaluated for evidence of a neuropathy
subtype other than distal symmetric poly neuropathy. The suspected pre-test etiology will be determined by
review of the electronic medical record. We will then determine if a procedure (EMG) or imaging modality (MRI)
resulted in a change in the suspected etiology or a change in management. We will also include data from a
previous evaluation by a PCP or previous neurologist was performed.
Results/Conclusions:
We will categorize the number of tests order by referring neurologist and by neuromuscular specialists.
We will examine the yield of lab tests, EMG and MRI studies.
Data collection and analysis are currently in progress.
Hypothesis: A change in management or the pre-test etiology will be low as a consequence of an EMG or MRI
study.
Rahul Karamchandani - Choice Of Anticonvulsant Prophylaxis And Risk Of Delayed Seizures, Delayed
Cerebral Ischemia, And Poor Outcome After Aneurysmal Subarachnoid Hemorrhage
Introduction
Some retrospective studies have suggested an association between Phenytoin burden
and poor neurological outcomes after aneurysmal Subarachnoid Hemorrhage (aSAH).1
Other studies report an increased rate of seizures with short-term use of Levetiracetam
versus use of Phenytoin for longer duration,2 as well as the possible occurrence of
Delayed Cerebral Ischemia (DCI) in association with late seizures after aSAH.3 Our
objective was to evaluate the risk of in-hospital seizures, DCI, and poor outcomes in
patients treated with Levetiracetam versus Phenytoin in patients with aSAH.
Methods
The medical records of patients with aSAH admitted between January 2005 and April
2009 were reviewed. Anticonvulsants were administered for at least 48 hours after
admission in all patients. EEG monitoring was not routinely performed. Delayed
Cerebral Ischemia was defined as the composite of symptomatic vasospasm and/or
delayed infarction on imaging.4 Poor outcome was defined as modified Rankin scale
(mRS)>2 at first follow-up.
Results
Only 3 of 148 (2%) patients had a seizure following initiation of anticonvulsant
prophylaxis. Overall, 52 (35%) developed DCI and 61 (41%) had mRS>2 at follow up.
Following multivariate logistic regression analysis, only age, DCI, and non-use of
Phenytoin (OR 3.42, 95%CI 1.14-10.29, p=0.03) were found to be statistically significant
associations with mRS>2. In contrast, use of Phenytoin versus Levetiracetam in the first
72 hours was not associated with poor functional outcome.
Conclusions
In-hospital seizures are rare when anticonvulsant prophylaxis with any agent is used
after aSAH. The choice of anticonvulsant was not found to influence the risk of DCI,
although the use of Phenytoin beyond the first 72 hours was associated with better
functional outcomes at follow-up. Prospective, randomized clinical trials are required to
inform the choice of anticonvulsant prophylaxis after aSAH.
REFERENCES
1. Naidech AM, Kreiter KT, Janjua N, Ostapkovich N, Parra A, Commichau C, Connolly ES, Mayer SA,
Fitzsimmons BF. Phenytoin exposure is associated with functional and cognitive disability after
subarachnoid hemorrhage. Stroke. 2005 Mar;36(3):583-7. Epub 2005 Jan 20.
2. Murphy-Human T, Welch E, Zipfel G, Diringer MN, Dhar R. Comparison of short-duration levetiracetam
with extended-course phenytoin for seizure prophylaxis after subarachnoid hemorrhage. World
Neurosurg. 2011 Feb;75(2):269-74.
3. Sampson TR, Dhar R, Zipfel GJ. Cerebral infarction following a seizure in a patient with subarachnoid
hemorrhage complicated by delayed cerebral ischemia. Surg Neurol Int. 2011 Jan 31;2:14.
4. Frontera JA, Fernandez A, Schmidt JM, Claassen J, Wartenberg KE, Badjatia N, Connolly ES, Mayer
SA. Defining vasospasm after subarachnoid hemorrhage: what is the most clinically relevant definition?
Stroke. 2009 Jun;40(6):1963-8. Epub 2009 Apr 9.
Benjamin Bly - The Prevalence of Impaired Olfaction in Parkinson Disease is Higher than Previously
Estimated.
Background/Objectives
There is a strong relationship between impaired olfaction and Parkinson Disease (PD). Estimates of
prevalence range from about 50% to 75% [1], and even 90% [2]. Factors affecting these estimates include the
type of olfactory test, sample size, normative comparison data, gender and age distribution [1]. An additional
factor is the uncertainty of clinical classification in patients with symptoms suggestive of a diagnosis of PD.
Subjects without evidence of dopaminergic denervation (SWEDDs) may contribute significantly to low
estimates of the prevalence of dysosmia in PD.
Dopaminergic imaging has become a de facto gold standard for diagnosis of PD when concordant with clinical
signs. Brain imaging to confirm PD is costly and guidelines for imaging have not been adopted widely. If an
inexpensive screening test can be identified for PD, it may have a large impact on health care costs.
Our objective is to estimate the prevalence of olfactory dysfunction in patients with clinical signs of PD
confirmed by imaging evidence of nigrostriatal denervation. If high, impaired olfaction may be a useful
screening test for diagnosis of PD and will allow more appropriate selection of suitable candidates for
presynaptic dopaminergic radioligand imaging in clinical practice.
Ross Coleman - Appropriateness of Deep Brain Stimulation Referrals to a Tertiary Medical Center
Background: Deep brain stimulation (DBS) is an effective surgical therapy for Parkinson's disease (PD),
essential tremor (ET) and dystonia, and patient selection is critical to its success. Very few studies have
analyzed the appropriateness of referrals made to a DBS center.
Objective: To retrospectively evaluate the quality of DBS referrals to the University of Michigan Surgical
Therapies Improving Movement (STIM) program in order to determine general knowledge in the medical
community regarding DBS candidacy.
Methods: Medical records of all patients referred to the University of Michigan STIM program for DBS from
9/1/2007 to 12/31/2011 were reviewed. Referral reason, referring physician type, number of
appropriate/inappropriate patients for DBS and reason for not offering DBS were recorded.
Results: A total of 243 candidates were referred to the STIM program during the time period reviewed, 158 for
PD, 68 for ET/Multiple Sclerosis tremor, 16 for dystonia, and 1 for chorea. Of the 158 patients with PD, 50 were
ultimately approved for DBS, while 66 were deemed inappropriate candidates. The majority of PD patients
approved for DBS were referred by movement disorder specialists (68%), followed by general neurologists
(26%). Of the 66 inappropriate PD candidates for DBS, 50% were referred by general neurologists and 26%
by movement disorders specialists.
Conclusions: In our DBS center, general neurologists referred only a quarter of the PD patients who were
offered DBS surgery, but referred 50% of the inappropriate DBS candidates with PD. This suggests a lack of
knowledge among the general neurology community regarding appropriate DBS referrals for PD.
Michael Soileau - Caregiver Burden in Parkinson’s Disease Patients Undergoing Deep Brain
Stimulation
Objective: To investigate the factors associated with caregiver burden in Parkinson's disease (PD) patients
undergoing deep brain stimulation (DBS).
Background: While caregiver burden has been studied in PD, little is known about caregiver burden in PD
patients who are being considered for DBS. Factors associated with caregiver burden are important to define
in these patients as both motor and cognitive problems may contribute, but only motor symptoms would be
expected to improve with DBS.
Methods: We retrospectively reviewed data from a registry of PD patients who have undergone
multidisciplinary DBS evaluation at our institution since January 2008. Fifteen PD patients (11 men/4 women)
had caregivers who filled out the Caregiver Burden Inventory (CBI), a 24 item questionnaire measuring the
amount of perceived burden across 5 separate domains. Clinical evaluations for PD patients included the
Unified PD Rating Scale (MDS-UPDRS), Parkinson Fatigue Scale (PFS), Marin Apathy Scale (MAS), Geriatric
Depression Score (GDS), State-Trait Anxiety Inventory (STAI), Mini-Mental State Exam (MMSE), and a
comprehensive neuropsychological battery.
Results: The 15 patients included in this analysis had a mean age 63.2± 8.4 years, mean disease duration of
11 years ± 4.6 years, mean levodopa equivalent dose of 1340.8 ± 580.7, and mean MDS-UPDRS motor offmedication score of 41.5 ± 10.5. There was a positive correlation between the CBI and the motor aspects of
experiences of daily living portion of the MDS-UPDRS (R=0.67, p=0.007) and the total Frontal Systems
Behavior Scale (FrSBe) score (R=0.73, p=0.002). CBI did not correlate with the motor portion of the MDSUPDRS, PFS, MAS, GDS, STAI, or the MMSE.
Conclusion: In PD patients undergoing DBS, increased caregiver burden is associated with greater behavioral
changes associated with frontal lobe dysfunction and more difficulty performing motor aspects of daily living,
but not the severity of motor symptoms. This may be important when counseling patients and caregivers on
post-surgical expectations as DBS may improve motor aspects of daily living, but not dysexecutive type
behavioral changes.
Shiao-Pei Weathers - Risky driving is related to cholinergic but not nigrostriatal dopaminergic
denervation in Parkinson's disease
Background: Parkinson’s disease (PD) can affect driving skills and behaviors, though the underlying reason is
not well understood and may be due to a variety of factors including motor and cognitive dysfunction. The
association between risky driving (a history of traffic citations or accidents) in PD and dopaminergic and
cholinergic denervation on PET imaging has not been explored.
Objective: To investigate differences in self-reported driving behaviors as well as dopaminergic and cholinergic
uptake on PET imaging between patients with and without a history of risky driving.
Methods: A driving survey was mailed to 21 subjects with PD who had undergone(+)-[11C]
dihydrotetrabenazine (DTBZ) vesicular monoamine transporter 2 and [11C]methyl-4-piperidinyl propionate
(PMP) acetylcholinesterase (AChE) PET imaging in a prior research study. This driving survey asked
questions regarding a subject’s personaldriving history, and included the Driving Behavior Questionnaire
(DBQ), a self-report survey that assesses 3 main types of aberrant drivingbehaviors (errors, lapses, and
violations).
Results: Twenty subjects (8F/12M) returned driving surveys, 1 in Hoehn-Yahr (HY) stage 1, 3 in HY stage 2,
11 in HY stage 2.5, and 5 in HY stage 3. Six subjects had a history of risky driving (been pulled over, had a
traffic citation, or been in an accident since PD onset) while 14 had no such history (safe drivers). There was
no significant difference in age, disease duration, levodopa equivalent dose, HY stage, total score/subscoresof
the DBQ, or DTBZ binding between risky and safe drivers. However, there was significantly less cholinergic
uptake on PMP PET imaging in the cortex (0.021 +/- 0.003 vs. 0.024 +/- 0.003, p=0.048), thalamus (0.048 +/0.006 vs. 0.057 +/- 0.005, p=0.003) and limbic areas (0.044 +/- 0.006 vs. 0.052 +/- 0.008, p=0.049) in the risky
drivers compared to the safe drivers.
Conclusions: Risky driving is related to cholinergic but not nigrostriatal dopaminergic denervation in
Parkinson's disease. There was no difference in self-reported driving behaviors in those with a history of risky
driving compared to those without, suggesting that PD patients may lack awareness of the severity and types
of driving errors they commit. paminergic denervation in Parkinson's disease
Jessica Stulc - Traumatic Brain Injury as an Independent Risk Factor for Stroke
Background: A recent population based study demonstrated an increased risk of stroke in patients who
sustained a traumatic brain injury (TBI) as long as 5 years after the event (1). Little is understood about the
pathophysiology that would link trauma to an increased long term stroke risk. We sought to determine whether
this finding was reproducible and to explore several hypotheses regarding the relationship of stroke and TBI: 1.
Is the relationship mediated by TBI severity? 2. Is the relationship specific to TBI or to trauma in general? 3.
What is the temporal relationship between TBI and stroke?
Methods: We plan to use a data from the California State Inpatient and Emergency Department databases
from 2005-2009 to perform a retrospective cohort study. Our patient population will include a cohort of patients
who present to the ED with mild trauma including TBI and a series of patients with closed fractures. The
exposure of interest, TBI, will be characterized using ICD-9 codes. This strategy will enable the broader mild
trauma population to serve as a control group. To isolate the relationship between TBI and stroke from other
risk factors, we will risk adjust for other known stroke risk factors including: age, sex, hypertension,
hyperlipidemia and diabetes mellitus as defined by ICD-9 codes. We will also adjust for the severity of trauma
using the IMAP-90 risk adjustment scheme. Cox proportional hazard regression analysis will be used to
determine the association between TBI and recurrent stroke risk independent of other stroke risk factors.
Secondary analyses will include: narrowing the definition of TBI (only TBI discharged from the ED, only
concussion ICD-9 codes), excluding patients with short term stroke, excluding patients admitted for their initial
trauma evaluation.
Results: Pending
Conclusions: pending
Lindsey Foy - “Predictors of Epilepsy in Acute Life Threatening Events in Infants”
An acute life threatening event, (ALTE), is defined by the National Institute of Health Consensus as “an
episode that is frightening to the observer and is characterized by some combination of apnea (central or
occasionally obstructive), color change (usually cyanotic or pallid, but occasionally erythematous or plethoric),
marked change in muscle tone (usually marked by limpness), choking, or gagging.” ALTE itself is usually not
a primary diagnosis, but simply a presenting symptom of an underlying disease. The most common diagnosis
in a patient presenting with an ALTE is gastroesophageal reflux disease (GERD) or idiopathic. However, the
differential diagnosis is broad and includes seizures. A Brazilian study reported the prevalence of epilepsy as
a cause of ALTE in children presenting to the emergency department of a tertiary hospital, where two of thirty
(6%) of infants presenting were given a diagnosis of epilepsy. However, diagnosing seizures in an ALTE is
often difficult to make as interictal EEGs are often normal, and ictal EEGs are not frequently available, as the
event can be a single isolated occurence. There is no reported evidence of the predictive value of presenting
symptoms or other key features of the clinical history or exam (clinical description of the event, family history of
epilepsy, developmental delay, dysmorphic features, birth history) which may clue the practitioner into a
diagnosis of seizure. We therefore hypothesize in infants presenting with an apparent life threatening event,
there are common signs and symptoms to their clinical presentation, history and/or physical examination, that
when present, increase the likelihood of seizure as the diagnosis and etiology of the ALTE.
This is an observational study of patients presenting to the emergency department or admitted to the hospital
with symptoms concerning for an ALTE. The study design is a retrospective chart review of children
presenting to the emergency department between January 2005-December 2008 with an apparent life
threatening event and include a 2yr follow up to determine who was eventually given a diagnosis of epilepsy.
Patient cohort will be selected from infants 0-12months of age, seen in the University of Michigan Emergency
Department and admitted to C.S. Mott Childrens Hospital.
Data will be analyzed with the use of a regression model to identify which factors would be predictors of
seizures/epilepsy in the study subjects.
Dane Breker: “Development of Increased Vertical Fusional Amplitudes in Patients with Thyroid Eye
Disease”
Introduction: Increased vertical fusional amplitudes are considered the sine qua non of congenital fourth nerve
palsies, and not thought to be present in cases of acquired diplopia. We present 10 cases of patients with
thyroid eye disease (TED) who developed increased vertical fusional amplitudes over the course of their
disease, in several cases leading to resolution of their diplopia. In reviewing both standard texts and a
Pubmed search we found no other similar reported cases.
Methods: Review of charts from neuro-ophthalmology practice at a tertiary referral center. The diagnosis of
TED was made on clinical criteria (proptosis, lid retraction, lid lag) and neuroimaging.
Results: Of the 10 cases reviewed, all were female with ages ranging from 43-81 years. All presented with
persistent or intermittent diplopia and one also complained of vision loss. Duration of disease was variable
from 6 months to 10 years. One was described only as “years” duration. Vertical fusional amplitudes ranged
from 5-25 diopters. Three of the cases developed a head posture which helped them fuse. Prisms were
recommended during the course of disease in four cases but were only utilized in three cases.
Conclusion: From these cases it can be seen that large vertical fusional amplitudes can develop over time in
patients with TED. One thought is that these patients had a head posture in which they could fuse, allowing
them to develop increased fusion and increase their range of single binocular vision. As the most common
longstanding acquired diplopia, versus ischemic cranial nerve palsies which resolve quickly, this gives insight
into the plasticity of the vergence system and suggests that perhaps prism therapy and longer followup would
reduce the number of patients who need surgical correction or reduce the amount of surgery needed.
Dustin Nowacek: Amyotrophic Lateral Sclerosis In-hospital Mortality
Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that results from
dysfunction of upper motor neurons (UMN) and lower motor neurons (LMN) that typically results in death within
years of diagnosis. The most common causes of mortality are secondary to respiratory arrest or malnutrition.
The average time from symptom onset to death is approximately 45 months in limb onset ALS and 36 months
in bulbar onset ALS. As a disease process, ALS is quite novel in that it progresses with minimal cognitive
decline, thus providing patients with a unique degree of control over end-of-life decisions. In this project, we
aim to evaluate the incidence of ALS in-hospital mortality compared to the total incidence of ALS mortality.
Methods: Data was drawn from two sources to estimate the proportion of ALS patients that die in the hospital.
First, to determine the total number of ALS deaths in 2009 we used the Centers for Disease Control and
Prevention (CDC) Multiple Cause Mortality files which categorize all death certificates in the United States.
Death certificates with any diagnosis of ALS (ICD-10 G122) were categorized as ALS deaths. Next, we used
the Nationwide Inpatient Sample (NIS) to estimate the number of in-hospital ALS deaths in 2009. NIS is a
nationally representative database of all hospital discharges in the United States. By dividing the number of inhospital deaths by the total number of ALS deaths we estimated the proportion of in-hospital ALS deaths.
Results: In 2009, there were a total of 7,004 ALS deaths in the United States and a total of 14,188 (95% CI
13,718-14,658) ALS hospitalizations. An estimated 1,500 (1,329-1,671) ALS patients died in the hospital
representing 21.4% (95% 19.0%-23.9%) of all ALS deaths.
Discussion/Conclusions: ALS is usually a fatal disease, and many patients die in the hospital. This may give
us an opportunity to improve the quality of end-of-life care.
Future Aims:
Evaluate for any potential association between the distance ALS patients live from an ALS center and inhospital mortality.
Assess the association between ALS patients who want all life sustaining measures (PEG tube/mechanical
ventilation) and in-hospital mortality.
Design studies and protocols to evaluate if telemedicine may result in decreased ALS in-hospital mortality for
those who do not have easy access to an ALS center.
Clinical Neurophysiology Fellows
Fawad Khan - Effects of Dexmedetomidine on Transcranial Electric Motor Evoked Potential Monitoring
in Pediatric Spinal Correction Surgery
Introduction: Dexmedetomidine (Dex) is a potent and specific alpha-2 adrenergic receptor agonist with
sympatholytic, sedative, amnestic, and analgesic properties approved by the Food and Drug Administration
(FDA) as a sedative and as an adjuvant to anesthesia. Studies have suggested that Dex has negligible effects
on TceMEPs up to target plasma concentrations of 0.4 ng/ml. However, unpublished reports have claimed that
Dex may affect TceMEP amplitudes.
Method: 200 orthopedic spinal procedures with TceMEP, somatosensory evoked potential (SSEP), and
electromyography (EMG) monitoring were reviewed.
Results: 68 (41.2%) monitored surgeries observed a decreases in bilateral intrinsic hand and foot abductor
TceMEPs of greater than 70% when compared to reliable obtained baselines. 37 (22.4%) monitored surgeries
observed a complete loss or absence of compound muscle action potentials (CMAPs), rendering TceMEP
monitoring unreliable for the surgery .
Discussion: Understanding the effects of available anesthetics on TceMEP is required to avoid erroneous
conclusions that changes in amplitude represent neurologic injury during surgical manipulations rather than
anesthetic effects. Our study provides evidence of substantial attenuation of TceMEP CMAP amplitudes with
use of Dex. Further analysis of Dex levels and dosing are warranted to study appropriate anesthetic regimens
for the pediatric population undergoing procedures requiring reliable TceMEP monitoring.
Victoria Wong
1. The Care and Feeding of a Montage Set
The University of Michigan Department of Neurology and Department of Pediatric Neurology provide
comprehensive clinical services to patients with epilepsy. Diagnostic testing including electroencephalography
(EEG), in-patient long term monitoring (LTM), electrocorticography, and Wada testing are all performed at the
University of Michigan. In interpreting these studies, epileptologists use a set of montages that allow them to
display the data in numerous ways. Although there are a number of generally accepted standard montages
used by the epilepsy community to interpret these studies, montages can be customized to the user. Such
edits to preexisting montages result in redundancy, with an unwieldy number of 59 montages cluttering the
montage menu. With this A3 Report, our goal is to create an organized list of montages with a standardized
naming system that provides enough variety to appease all local epileptologists while keeping the list to a
manageable number.
2. The portrayal of seizures and epilepsy on YouTube (to be presented with Matt Stevenson)
With the rapid growth of social media and increased ease of sharing personal video recordings since the
advent of YouTube, thousands of Internet videos currently reference seizures and epilepsy. Prior studies have
noted that in nearly all forms of media including fictional literature, music, movies, television, magazines, and
newspapers, seizures are often dramatized or presented in association with negative stereotypes. This has
continued with social media on the Internet, with a large proportion of derogatory seizure “tweets” on Twitter
and persistent negative attitudes about seizures within the comments on the most popular YouTube videos
referencing epilepsy and seizures. However, YouTube distinguishes itself from other types of media in that it
allows for persons with epilepsy to give personal accounts that may be more sympathetic. Our present study
suggests that content related to seizures and epilepsy on YouTube may be more positive than in other forms of
media.
Sleep Medicine Fellows
Anthony Barber - The Effect of Positive Airway Pressure (PAP) on Sleep State Perception in
Obstructive Sleep Apnea (OSA) Patients
Introduction: Sleep State Misperception (SSM) is typically seen in insomniacs; however, limited research has
shown this phenomenon to occur in sleep apnea patients as well. The goal of this study is to investigate the
effects of PAP therapy on SSM in OSA patients.
Methods: A data base review of 302 OSA patients (≥18yo) diagnosed and titrated between January 2010 and
April 2011 was done. Of these patients, 64% were males, with a mean age of 50.2 years (+/-13.2) and had a
mean BMI of 35.1 (+/- 9.1).
Computing the ratio of the patient’s subjective and objective TST, we defined
SSM as a deviation of >12.5%. Deviation of 12.5% was used as a cut off based on the assumption that
misperception >1 out of 8 hours of sleep is clinically significant (>1 STD). Utilizing a 12.5% cutoff, patients
were identified as showing SSM on baseline and titration studies. The demographic/PSG variables of these
patients were compared to identify patients that remained under-perceivers during PAP titration.
Results:
Of the 302 patients, 24.8% (N=75) showed under-perception on PSG. 57.8% (N=43) of the under-
perceivers showed no misperception or over-perception of their TST during their titration. Only 15.4% of
patients with no misperception on PSG showed under-perception on their titration. Upon comparison (T-test)
of the demographic, Epworth Sleepiness Scale and PSG variables between patients with and without
persistent under-perception; age (p<0.001), TST (P=0.039), arousals/hour of sleep (p=0.016), sleep latency
(P=0.001), AHI (P=0.008), and RDI (P=0.009) achieved statistical significance. A regression model to predict
those who remain under-perceivers was applied, only age was found to correlate (older age being protective)
(OR=0.956, CI=0.935-0.976).
Conclusion: Majority of OSA patients with under-perception on their diagnostic PSG transform to having no
misperception or over-perception of TST during titration. Despite PAP titration, younger OSA patients are
likely to remain under-perceivers.
2. Title: Sleep State Misperception in Obstructive Sleep Apnea .
Introduction: Clinical observations and small studies suggest that sleep state misperception (SSM) occurs in
patients with obstructive sleep apnea (OSA). However, the frequency of SSM is unknown. The primary goal of
this study was to investigate the frequency of SSM in OSA and specifically the proportion of those who underperceive sleep time.
Methods: A retrospective review was performed on patients attending a sleep laboratory between January 1,
2010 through April 15, 2011 . OSA was considered present if the apnea/hypopnea index (AHI)>5. The ratio of
subjective:objective total sleep time (TST), sleep-onset latency (SOL), and sleep efficiency (SE) was calculated
and SSM was defined as any value ±12.5% of the mean value for each parameter. The threshold of 12.5%
was based upon an assumption that >1 hour of discrepancy per 8 hours of sleep is clinically significant. Three
subgroups were defined for each sleep parameter: under-perception, no misperception and over-perception.
Results: The population included 302 subjects (64% male). Mean age was 50.2±13.2years and mean BMI
was 35.1±9.1kg/m2.
SSM was noted in 89.8%, 52.9% and 49.5% as measured by SOL, TST and SE
respectively. For TST, 142 (47%) patients showed no misperception, 75 (24.8%) had under-perception and 85
(28.2%) exhibited over-perception. For SE, frequencies were similar. Considering SOL, over-perception was
found in 68%, and under-perception was found in 22%. Subjects with under-perception of TST, compared to
those without, were significantly younger (44.4±12.5 vs 52.2±12.9 years, p<0.001), had higher sleep efficiency
(81.6±78.6, p=0.021), fewer arousals/hr (15.1±9.5 vs. 18.8 ±13.5, p=0.012) and had a shorter latency to sleep
(19.3±16.6 vs 24.4±24.1, p=0.047). In a regression model, age was the only independent variable associated
with under-perceiver (OR=0.956, CI=0.935-0.976).
Conclusion: SSM is common in OSA. Younger subjects are more likely to under-perceive TST.
Kaanchan Gangal - Anorexia as a feature in Kleine-Levin syndrome
Kleine-Levin syndrome (KLS) is a rare disorder characterized by recurrent episodic hypersomnia with
associated behavioral abnormalities1. It predominantly affects males, causing symptoms for 2 days to 4
weeks, and classically includes features of hyperphagia, hypersexuality, autonomic symptoms, cognitive
impairment, altered perception, and psychological changes1,2.
The patient is an otherwise healthy 22-year-old man with attention deficit hyperactivity disorder (ADHD) who
presented with cyclical episodes of hypersomnolence at age 15. During his episodes, he spends 7-20 days
sleeping 20-23 hours a day. He is preoccupied with sex. He fears darkness and must be comforted by his
parents. He has a difficult time maintaining oral intake and needs to be coaxed into eating; normally, he has a
healthy appetite. He was on methylphenidate for ADHD but reports that taking it during the episodes triggered
anxiety, while other symptoms remained unchanged.
The patient had an extensive work-up. Evaluation with an MRI of the brain with specific attention to the
hypothalamus was normal. Prolonged monitoring with electroencephalography during an episode did not show
epileptiform discharges. When the patient was at his baseline, he had a polysomnogram that showed an
apnea-hypopnea index (AHI) of 0.10 events/hour and multiple sleep latency testing (MSLT) that demonstrated
three sleep-onset REM (SOREM) periods with a sleep onset latency (SOL) of 10.4 minutes. During one of his
hypersomnia episodes, he had another polysomnogram that revealed an AHI of 5.8 events/hour and MSLT
performed that demonstrated five SOREMs and a SOL of 2.2 minutes.
KLS is classically linked with hyperphagia, but a case series showed that 34% of KLS patients had associated
anorexia2. Atypical features within a global pattern of recurrent hypersomnia should not deter clinicians from a
diagnosis of KLS3. Furthermore, polysomnography, while not diagnostic, can provide useful information to
assess for other sleep disturbances and highlight ictal and interictal differences.
Hillary Lowenstein - Vagus Nerve Stimulation and Sleep: an indication for polysomnogram?
Introduction:
Epilepsy and obstructive sleep apnea (OSA) frequently coexist and use of vagus nerve stimulation (VNS) as
adjunctive treatment for partial epilepsy is typically well tolerated. Recent evidence suggests that VNS affects
nocturnal respirations and has been shown to worsen pre-existing OSA. Our case outlines how it can also
complicate treatment of OSA.
Case:
Patient R is a 22-yo man with mild static encephalopathy and medically intractable partial epilepsy who
experiences excessive daytime sleepiness, witnessed apneas, and snoring. He was diagnosed with OSA in
2001, apnea-hypopnea index (AHI) 6.1, and underwent adenotonsillectomy with uvuloplasty.
Repeat
polysomnogram (PSG) with esophageal manometry in 2003 demonstrated persistent sleep-disordered
breathing (SDB)--AHI 1.3 and excessively negative esophageal pressures.
Continuous positive airway
pressure (CPAP) of 5 cm of water was initiated based on titration study results. Subsequently, he underwent
VNS implantation in 2008 for intractable epilepsy.
PSG in 2010 (post VNS implantation) demonstrated OSA (AHI 22.3), with obstructive apneas occurring almost
exclusively during VNS activation, set at 30s on-3 min off-20 Hz. Subsequent titration study performed with the
VNS firing rate reduced to 30s on-5 min off-20 Hz did not find an effective pressure between 4-12 cm of water
to treat the SDB; however, most of the scored respiratory events were now hypopneas (in contrast to
obstructive apneas noted on the previous study), still in a 1:1 association with VNS firing.
Conclusion:
VNS activation worsens sleep disordered breathing and makes CPAP titration a challenge. Apneas and
hypopneas are found to occur more frequently during VNS activation than during non-activation. This may
also lead to difficulty in treating the sleep disordered breathing. Therefore, baseline PSG prior to and following
VNS implantation should be considered. Further investigation is needed regarding CPAP titration in patients
with VNS.
Madhukar Kumar - Paradoxical insomnia: a precursor to mania?
Paradoxical insomnia may predate the development of manic mood disturbance and serve as an early warning
sign of future mania or bipolar affective disorder, as outlined by this case.
Patient L, a 57 year old married male presented to the sleep clinic with a chief concern regarding a reduction in
his total sleep time (TST) to 4hours/night over the last one year. He also described a highly variable sleep
onset latency and wake after sleep onset time with previous normal sleep duration. He reported several
periods of up to 72 hours without any sleep. His wife stated she had observed him in bed, quietly sleeping,
during these periods of self-described environmental awareness. There were no complaints of daytime
somnolence and daytime impairment was limited to mild changes in his short term memory. Two weeks before
his evaluation, he described a period of suicidal ideation followed by several days of expansive mood and
hyperactivity, resulting in psychiatric hospitalization and a diagnosis of mania.
Physical examination: BMI 22.9; Friedman palate position II; Neck circumference 15 inches. Polysomnography:
No sleep disordered breathing. TST - 279min, Stage N1 - 8%, Stage N2 - 50%, Stage N3 - 0%, Stage R 21%.The patient reported no subjective sleep. A diagnosis of paradoxical insomnia was given to the patient.
Subjective lack of sleep is a common complaint and insomnia is a useful clinical indicator of the onset of new
(or relapse of existing) mood disorders, particularly depression. Paradoxical insomnia is an uncommon
condition characterized by a subjective complaint of severe insomnia without evidence of objective sleep
disturbance and without daytime impairment commensurate with the degree of the reported sleep deficit. The
significance of this condition remains poorly understood. Paradoxical insomnia may serve as a marker for the
future development of mania, as observed in this patient.
2. Final Disposition of patients seen in the Alternatives to CPAP Clinic: A 13 year Experience
Introduction:
Although treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) is the
gold standard, compliance remains problematic. An estimated 46-83% of patients use CPAP for less than an
average of 4 hours/night. The goal of a multispecialty alternatives clinic is to offer CPAP intolerant patients
other treatments for OSA.
Methodology:
1739 patients with a documented history of OSA and CPAP intolerance, who were interested in alternative
treatments, were seen in the Alternatives to CPAP Clinic between December 1997 and December 2011. All
patients underwent a same day evaluation by a Sleep Medicine Physician, Otolaryngologist, Oral Maxillofacial
Surgeon and Prosthodontist. Evaluation of each patient included a comprehensive medical and sleep history,
review of polysomnography and PAP treatment parameters, head and neck examination (with flexible
nasopharyngoscopy - Muller’s maneuver), cone beam computed tomography or cephalometric analysis, and
dental evaluation.
Results:
Alternative treatments were recommended by group consensus, and patient preference was incorporated in
the final treatment plan. Alternative treatments were chosen by 27% of patients. Of this group, 24% underwent
surgery and 3% (n= 54) received an oral appliance. 70% of patients (n=291) who elected to undergo surgery
underwent oropharyngeal and/or hypopharyngeal procedures and 30% (n=125) underwent maxillomandibular
advancement. Over 50% of patients seen decided to make additional supervised attempts at positive airway
pressure therapy and the remainder decided to abandon additional attempts at treatment.
Conclusion:
A multidisciplinary alternatives to CPAP clinic can facilitate the treatment of CPAP intolerant patients and
improve communication between sleep physicians, otolaryngologists, oral surgeons, and prosthodontists.
Although labor intense and time consuming, such a clinic provides an effective means to treat a subset of
CPAP intolerant patients and plays a key role in the management of this challenging patient population.
Shilpa Patel - A Rare Case of Large Antralchoanal Polyp presenting as Obstructive Sleep Apnea in an
Adult
Introduction:
In rare cases, obstructive sleep apnea (OSA) can be caused by upper airway masses.We present an unusual
case of a large antralchoanal polyp presenting as obstructive sleep apnea in an adult.
Antralchoanal polyps are benign, polypoid lesions arising from the mucosa of maxillary antrum. They most
often present in childhood with uni- or bilateral nasal obstruction or rhinorrhea. Three case reports of children
with antralchoanal polyps presenting as OSA have been described, but adults presenting with OSA have not
been reported to date.
Case Report:
A 26 year old male presented to our sleep clinic with a 10 year history of loud snoring, severe nasal obstruction
and daytime sleepiness. His wife reported witnessed apneas. He was of normal body weight. A baseline
polysomnogram revealed OSA with an apnea hypopnea index (AHI) of 8.0, worse in REM sleep. The patient
was unable to tolerate CPAP, largely because of nasal obstruction. He was referred to otolaryngology for
surgical correction of his OSA and/or nasal obstruction.
Flexible nasopharyngoscopy showed a large mass emanating from his left maxillary ostia and almost entirely
obstructing his naso-pharynx. A subsequent CT scan demonstrated a polypoid mass originating in the left
maxillary antrum and occupying virtually the entire nasopharyngeal lumen compatible with an antrochoanal
polyp. The lesion was removed endoscopically.
Post-operatively, the patient’s snoring and nasal obstruction was significantly decreased and his wife no longer
noticed apneic episodes.
He endorsed marked improvement in his daytime sleepiness. A post-operative
polysomnogram was recommended, but declined due to the resolution of his symptoms.
Conclusion:
This represents the first reported case of an adult with antralchoanalpolyp presenting as OSA. The patient had
resolution of his symptoms after removal of the mass. Even when dealing with common disease entities such
as OSA the hoof beats we hear may occasionally be from zebras.
Gabriel Tudose - Polysomnographic Findings in Children with Bullying Behaviors
Study Objectives: Survey data suggest that elementary schoolchildren with aggressive behaviors such as
bullying are more likely than their peers to have parentally-reported symptoms of sleep-disordered breathing
(SDB) and daytime sleepiness. This pilot study was conducted to explore whether objective evidence of SDB
and daytime sleepiness may also be more frequent in children with bullying behaviors.
Methods: As part of a larger survey study in elementary schoolchildren, a subset of children with and without
frequent bullying behavior, as identified from the Conners’ Parent Rating Scale, were invited to undergo
laboratory-based polysomnography and a Multiple Sleep Latency Test (MSLT) on the following day.
Esophageal pressure (Pes) was monitored during the polysomnograms. Studies were scored by a registered
polysomnographic technologist who was masked to subject group.
Results: A total of 23 children (11 with bullying behaviors) were enrolled. Mean age was 9.4±1.3 years, BMI
was 19.2±3.8kg/m2, and n=6 subjects were male. Compared to controls, children with bullying behaviors did
not demonstrate differences in standard polysomnographic variables such as the arousal index (9.0±1.7 vs.
8.0±1.0; p=0.12), apnea-hypopnea index (0.8±0.8 vs. 0.9±0.2; p=0.84), respiratory disturbance index (1.1±0.9
vs. 1.0±0.2; p=0.84), or oxygen saturation nadir (92.9±2.0% vs. 93.6±2.0%; p=0.46). However, in non-rapid
eye movement sleep, there were trends for children with bullying behaviors to have more negative mean Pes
values (-9.6±2.8 cmH2O vs. -7.5±1.9 cmH2O; p=0.09) and Pes nadirs (-21.1±6.6 cmH2O vs. -14.9±5.0
cmH2O; p=0.05). Children with bullying behaviors spent a greater proportion of sleep time with Pes <-10
cmH2O (38.6% vs. 8.1%; p=0.03). There was no difference in mean nap latency as measured by MSLT
(19.8±8.2 minutes vs. 19.6±5.7 minutes; p=0.97).
Conclusions: Esophageal pressures and increased work of breathing may distinguish more effectively
schoolchildren with bullying behavior than do other measures of SDB.
Warangkhana Wongba - OSA Patients Managed By Sleep Medicine Specialist Demonstrate Superior
Compliance with Positive Airway Pressure Therapy.
Background: Obstructive sleep apnea (OSA) is the most common sleep related breathing disorder and is
associated with significant comorbidity. Prior studies have proved benefits in the treatment of obstructive sleep
apnea 3, 4 with Positive Airway Pressure (PAP). PAP is the gold standard treatment for OSA though
adherence with this therapy can be challenging.
Our hypothesis is that extensive patient education, an integral part of the clinic encounter with a sleep
medicine physician is associated with better PAP compliance and adherence.
Methods: We conducted a single center, retrospective chart review of the patient who had an attended
overnight polysomnogram performed at the Sleep Disorders center, University of Michigan with available
objective PAP compliance download from January 1st, 2010 and December 31st, 2010.
Results: Total of 224 patients were included, 52 patients who received care by sleep medicine specialist
and172 patients who received care by a primary care physician. Patients under treatment with sleep medicine
specialist had significantly higher percent of number of days of PAP use (80.29 ± 2.7 vs. 62.3 ± 1.22 , p-value
<.0001) , higher compliance [PAP ≥ 4 hours] ( 67.45± 24.6 vs.47.4± 15.4, p-value < .0001) and average time
(minutes) of PAP used per session (329.8 ± 15.0, 233.4 ± 4.13, p-value < .0001). There were no different in
the patient’s AHI, NREM-AHI, REM-AHI, percent of time spent for O2 saturation below 88% during baseline
polysomnogram, the maximum pressure setting between these 2 groups. Higher BMI was associated with
higher AHI, REM-AHI and older patients had less total day of PAP used.
Conclusion: Patients receiving care for OSA by a sleep medicine physician have higher rates of compliance
with PAP therapy. Severity of sleep apnea in patients followed by sleep specialist did not differ significantly
from the ones managed by a primary care physician.
Neurosurgery Residents
Shawn Hervey-Jumper, MD
Embryonal tumors are malignant neoplasms, which predominantly affect children. According to the 2007 World
Health Organization (WHO) classification of central nervous system tumors, there are three types of embryonal
tumors including medulloblastoma, atypical teratoid/rhabdoid tumor (AT/RT), and primitive neuroectodermal
tumor (PNET) (Louis et al., 2007, WHO Classification of Tumors of the CNS ed. Louis et al IARC 2007). PNET
tumors are further subdivided into neuroblastoma, ganglioneuroblastoma, medulloepithelioma,
ependymoblastoma, and PNET not otherwise specified (NOS). Included within the PNET NOS category, the
WHO describes an embryonal tumor with abundant neuropil and true rosettes (ETANTR) that has been
considered a variant rather than a specific category.
The first description of ETANTR was made in 2000 by Eberhart et al (Eberhart et al., 2000). This initial report
of nine pediatric patients described tumors with hybrid features of both neuroblastoma and ependymoblastoma
along with unique histological, immunohistochemical, and ultrastructural characteristics. The composite
features of ETANTR initially observed by Eberhart et al. included fine and abundant fibrillary neuropil,
undifferentiated neuroepithelial cells arranged in clusters, and several types of rosettes (Eberhart et al., 2000).
Recently a specific amplification of 19q13.42 region containing a cluster of miRNA coding genes was found in
embryonal tumors with multilayered rosettes, which can be helpful in narrowing the diagnosis of these primitive
tumors (Korshunov 2010, Li 2009, Pfister 2009).
ETANTR is associated with a high potential for malignancy and a poor prognosis (La Spina et al., 2006). The
TSC theory suggests that the tumorigenic potential of central nervous system tumors is limited to a
subpopulation of cells with stem-like properties (CD133, CD15 (Son 2009, Rich et al). It has been further
suggested that these subpopulations confer chemotherapy and radiation resistance by their slow growth and
ability to remain dormant, evading conventional therapeutic strategies (Raya 2001). ETANTR remains poorly
characterized clinically as well as pathologically. The characterization of tumor stem like cells in ETANTR will
improve our understanding in this disease, leading to a better understanding of tumor biology and treatment
design. In this study, we investigate the presence of stem-like-cell tumor markers CD133, CD15, and nestin
from initial diagnosis, tumor recurrence, and within different regions of a single ETANTR tumor.
We observed an increase in the protein level and transcript number of the cancer stem cell marker CD133
suggesting that this population of cells had some degree of chemotherapy resistance in ETANTR. It may be
necessary to develop multifaceted and targeted therapeutic strategies including those that target tumor stem
like cells to treat these highly aggressive embryonal tumors.
Khoi Than, MD - Intradiscal Injection of Simvastatin Results in Radiologic, Histologic, and Genetic
Evidence of Disc Regeneration in a Rat Model of Degenerative Disc Disease.
Introduction:
A large percentage of back pain can be attributed to degeneration of the intervertebral disc (IVD). Bone
morphogenetic protein-2 (BMP-2) is known to play an important role in the chondrogenesis of the IVD.
Simvastatin is known to up-regulate the expression of BMP-2. Thus, we hypothesized that intradiscal injection
of simvastatin in a rat model of degenerative disc disease (DDD) would result in retardation of DDD.
Methods:
Disc injury was induced in 272 rats via 21-gauge needle puncture. After six weeks, injured discs were treated
with simvastatin in saline or a hydrogel carrier. Rats were sacrificed at predetermined time points. Outcomes
measures assessed were radiologic, histologic, and genetic. Radiologically, the MRI index (the number of
pixels multiplied by the corresponding image densities) was determined. Histologically, disc spaces were read
by three blinded scorers based on a previously used grading scale. Genetically, nuclei pulposus were
harvested and polymerase chain reaction was run to determine relative levels of aggrecan and collagen type II
gene expression.
Results:
Radiologically, discs treated with 5 mg/ml simvastatin in hydrogel or saline demonstrated MRI indices that were
normal through 8 weeks post-treatment, although this was more sustained when delivered in hydrogel.
Histologically, discs treated with 5 mg/ml simvastatin in hydrogel demonstrated improved grades in comparison
with discs treated at higher doses. Genetically, discs treated with 5 mg/ml of simvastatin in hydrogel
demonstrated higher gene expression of aggrecan and collagen type II than control.
Conclusions:
Degenerate discs treated with 5 mg/ml simvastatin in a hydrogel carrier demonstrated radiographic and
histologic features resembling normal, non-injured IVDs. In addition, gene expression of aggrecan and
collagen type II (important constituents of the IVD extracellular matrix) was up-regulated in treated discs.
Injection of simvastatin into degenerate IVDs may result in retardation of disc degeneration and represents a
promising investigational therapy for the conservative treatment of DDD.
2. A Novel Model of Disc Degeneration in Yorkshire Swine via a Lateral Trans-Psoas Approach and
Stab Injury.
Introduction:
Prior studies have determined that the large animal, non-primate spine most biomechanically similar to
humans’ is that of the pig. Previous porcine models of degenerative disc disease (DDD) have involved
miniature or juvenile pigs. We sought to develop a reproducible and efficiently-performed model in a larger
porcine species, namely the Yorkshire pig.
Methods:
Ten Yorkshire pigs were anesthetized and placed in the right lateral position. Akin to a lateral trans-psoas
approach and using sterile technique, fluoroscopy and a guide-wire were used to localize the mid-portion of the
lumbar vertebral column. Incisions were planned and performed over the L1-L2, L3-L4, and L5-L6 disc spaces
(pigs have six lumbar vertebrae). A series of METRx dilators (Medtronic, Minneapolis, MN) were used to gain
access to the aforementioned disc spaces. Stab injury was induced to each disc (approximately midway, as
verified by antero-posterior and lateral fluoroscopy) as follows: a 12/64” trocar at L1-L2, an 11-blade scalpel at
L3-L4, and a 9/64” trocar at L5-L6. Pigs underwent magnetic resonance imaging (MRI) and sacrifice at 4, 6,
and 8 weeks post-injury.
Results:
The surgical procedure was facile, taking approximately 30 minutes per animal. One animal (the first that
underwent surgery) developed left hind leg monoplegia and was sacrificed; another (the last animal) died en
route from the surgical facility to the animal housing facility due to causes unrelated to surgery. The remaining
8 animals recovered without evidence of neurologic deficit. Considering the three injury mechanisms, the 9/64”
trocar was the most consistent for the early time points, although by 8 weeks all mechanisms showed evidence
for disc degeneration on MRI. Histologic data is pending.
Conclusions:
In this large animal model of DDD, disc injury was induced efficiently, effectively, and repeatably. This large
animal model may prove useful to researchers interested in studying the pathophysiology and treatment of
DDD.
Wajd Al-Holou, MD - Prevalence and Natural History of Arachnoid Cysts in Adults
Object. Arachnoid cysts are a frequent finding on intracranial imaging. The prevalence and natural history of
these cysts in adults are not well-defined.
Methods. We retrospectively reviewed the electronic medical records of a consecutive series of adults
who underwent brain MRI over a 12-year interval to identify those with arachnoid cysts. The MRIs were
reviewed to confirm the diagnosis. For those patients with arachnoid cysts, we evaluated presenting
symptoms, cyst size, and cyst location. Patients with clinical and imaging follow-up greater than 6 months
were included in a natural history analysis.
Results. A total of 48,417 patients underwent brain MRI over the study period. Arachnoid cysts were
identified in 661 patients (1.4%). Men had a higher prevalence than women (p < 0.0001). Multiple arachnoid
cysts occurred in 30 patients. Arachnoid cyst location was most often middle fossa (34%), retrocerebellar
(33%), or convexity (14%). Middle fossa cysts were predominantly left-sided (70%; p < 0.001). Thirty-five
patients were considered symptomatic and 24 underwent surgical treatment. Suprasellar cysts were more
likely to be considered symptomatic (p < 0.00001). Middle fossa cysts were less likely to be considered
symptomatic (p = 0.007). The criteria for natural history analysis were met in 203 patients with a total of 213
cysts. After a mean follow-up of 3.8 ± 2.8 years, 5 cysts increased in size (2.6%) and 2 cysts decreased in size
(1%). Only 1 patient (0.05%) developed new or worsening symptoms over the follow-up period.
Conclusions. Arachnoid cysts are a common incidental finding on intracranial imaging in all age groups.
Although arachnoid cysts are symptomatic in a small number of patients, they are associated with a benign
natural history for those presenting without symptoms.
William Stetler, MD - Prasugrel is Effective and Safe for Neuro-Interventional Procedures
BACKGROUND: Clopidogrel bisulfate and aspirin are routinely administered as dual antiplatelet agents for
many neuro-interventional procedures, especially for intravascular stent placement. Many patients are nonresponsive to clopidogrel, either secondary to drug interactions or from variations of cytochrome P450
enzymes. Prasugrel (brand name Effient, Eli Lilly and Company) is a new antiplatelet agent that has been
utilized extensively in patients undergoing cardiovascular procedures, but its safety and efficacy during neurointerventional procedures have not been evaluated.
OBJECTIVE: To examine whether prasugrel is a safe and effective alternative to clopidogrel for neurointerventional procedures, especially in those patients who are either non-responders or allergic to clopidogrel.
METHODS: We retrospectively reviewed medical records of all patients undergoing neuro-interventional
procedures at our institution who received prasugrel between January 2009 and July 2011 at our institution. A
systematic chart review was performed and the following data points were recorded: demographics, aneurysm
location, endovascular techniques, peri- and post-procedural complications, hemorrhagic complications,
clinical outcome, and angiographic outcome.
RESULTS: Sixteen patients undergoing neuro-interventional procedures received prasugrel over a 2-year
interval. All patients who had follow-up studies of P2Y12 inhibition had immediate therapeutic response to
prasugrel. There were no complications related to ischemic or intracranial hemorrhage.
CONCLUSION: Prasugrel is a viable alternative to clopidogrel for patients undergoing neuro-interventional
procedures who are non-responders to clopidogrel. Further study is needed to evaluate the safety, efficacy,
and cost-effectiveness of prasugrel compared to clopidogrel for patients undergoing neuro-interventional
procedures.
Thomas Wilson, MD - Comparison of the accuracy of ventricular catheter placement using free-hand
placement, ultrasound guidance, and stereotactic neuronavigation
Objective: To compare the accuracy of 3 methods of ventricular catheter placement during CSF shunt
operations, including free-hand technique using surface anatomy, ultrasound guidance, and stereotactic
neuronavigation.
Methods: This retrospective cohort study included all patients from a single institution who underwent a
ventricular CSF shunting procedure where a new ventricular catheter was placed between January 2005 and
March 2010. Data abstracted for each patient included age, sex, diagnosis, method of ventricular catheter
placement, site and side of ventricular catheter placement, Evans ratio, and bifrontal ventricular span.
Postoperative radiographic studies were reviewed for accuracy of ventricular catheter placement. Medical
records were also reviewed for evidence of shunt failure requiring revision through December 2011. Statistical
analysis was then performed comparing the 3 methods of ventricular catheter placement and to determine risk
factors for inaccurate placement.
Results: There were 249 patients included in the study; 170 ventricular catheters were free-hand
passed, 51 were placed using stereotactic neuronavigation, and 28 were placed under intraoperative ultrasonic
guidance. There was a statistically significant difference in accuracy between free-hand catheters and
stereotactic-guided catheters (P < 0.001), as well as between free-hand catheters and ultrasound-guided
catheters (P < 0.001). The only risk factor for inaccurate placement identified in this study was use of the freehand technique. The use of stereotactic neuronavigation and ultrasonic guidance reduced proximal shunt
failure rates (P < 0.05) in comparison to free-hand technique.
Conclusion: Stereotactic- and ultrasound-guided ventricular catheter placements are significantly more
accurate than free-hand placement and the use of these intraoperative guidance techniques reduced proximal
shunt failure.
T-32 Training Grant
Kathy Wilson - Importance of Bedtime Routines in Low-Income Preschool Children
Background: Sleep problems are common in preschool-age children; children growing up in poverty may be at
higher risk. A regular bedtime routine and consistent bedtime is recommended to improve sleep. We sought
to better define benefits of a bedtime routine and consistent bedtime among low-income preschool children.
Methods: Parents of Head Start preschoolers completed sleep questionnaires as part of a larger study.
Validated sleep surveys included: 1) General Sleep Information Questionnaire (GSI) to evaluate sleep
schedules and sleep duration, 2) Children’s Sleep-Wake Scale (CSWS) to evaluate sleep behaviors, and 3)
Children’s Sleep Hygiene Scale (CSHS) to evaluate sleeping environment and bedtime routines.
Results: Among 381 preschool children (mean age 4.1 ±0.5, range 2.8-5.0 years), 49.9% were boys, 61.7%
were Caucasian, and 16.3% of parents did not have a high school degree. Overall, 84.5% of children were
reported to have a bedtime routine and 89.2% a consistent bedtime; average routine lasted 41.4 minutes (±
26.8 min). T-tests revealed that children with regular routines and consistent bedtimes went to bed earlier
compared to children who did not (all p’s reported < 0.05); children with a regular routine also obtained an
additional 2.3 hours of sleep per week(p=0.03). Bedtime routines were associated with fewer problems going
to bed (p=0.02). Consistent bedtimes were associated with easier return to wakefulness in the morning
(p=0.003). Both bedtime routines and consistent bedtimes were associated with fewer sleep problems
(p<0.001).
Conclusion: Regular bedtime routines and consistent bedtimes are associated with increased sleep duration
and fewer sleep problems among Head Start preschool children. Although this correlational study cannot
prove causality, establishing adequate routines and bedtimes may be important for low-income children, who
may be especially vulnerable to consequences of sleep deficiency and sleep problems.
Kaia Skaggs -Neurogenesis and regeneration in response to QA-induced lesioning in adult zebrafish
telencephalon
Zebrafish is an attractive system for the study of neurogenesis following injury because, unlike other
vertebrates such as mouse and human, they are able to regenerate damaged neurons. We have developed a
brain injury model to study the process of brain repair by adult-born neurons in zebrafish telencephalon. In this
system, intracerebral injection of the excitotoxin quinolinic acid (QA) is used to lesion a portion of the right
telencephalon. We assay for proliferation, migration, and fate of neural progenitor progeny in the lesioned
hemisphere compared to the intact hemisphere, and to vehicle-injured or intact brains. Results indicate that
proliferation markedly increases through 3-4 days post-injury and then gradually declines to baseline levels.
Proliferative cells are found in increased numbers in both the medial (subpallial) and lateral (pallial) neurogenic
zones that surround the telencephalic hemispheres and at the site of injury. By 4- and 7-days post-injury,
BrdU-labeled cells appear throughout the lesioned hemisphere and are localized in increasing numbers at the
site of injury. Although both QA- and vehicle-induced injuries stimulate proliferation and migration of neuronal
progenitors, the excitotoxic injury induces a more robust regenerative response. We have also used
immunofluorescence and various transgenic zebrafish lines to label adult-generated neurons that arise from
adult progenitor cells following injury. Following QA lesioning, many newly generated cells appear in the pallial
and subpallial neurogenic zones and in increasing numbers over time at the site of injury. Immunofluorescence
double labeling indicates that many of these cells are neural progenitors and newly generated neurons that
incorporate BrdU, co-express neural progenitor markers such as PSA-NCAM, the early neuronal marker HuC,
-tubulin. These results indicate that QA-induced excitotoxic lesioning
potently stimulates proliferation of adult neural progenitors, leading to the generation of new neurons that
migrate to the site of injury, express neuronal markers, and contribute to regeneration and repair of brain injury
in the adult zebrafish telencephalon.
Katiuska Molina-Luna - Cerebellar physiology in the hesitant (Atcay) dystonic mouse model
Dystonia is a movement disorder that causes the muscles to contract involuntarily and produces abnormal
postures and twisting of the trunk and limbs. Some forms of dystonia in humans have been suggested to be of
cerebellar origin, but the precise role of the cerebellum in dystonia is unclear. We used a mouse mutant
defective in a homolog of the human Cayman ataxia gene, ATCAY, to investigate the role of the cerebellum in
dystonia. The hesitant (Atcay) mouse displays a markedly dystonic gait with prominent, non-progressive limb
stiffness that begins at around postnatal day 12 (P12), is clearly apparent by P15 and peaks at around P21.
Brain structure in this mouse is normal, suggesting that functional changes in the brain account for the motor
phenotype. Moreover, reduction of cerebellar output by lesioning the deep cerebellar nucleus improved the
stiffness. To address the physiology of cerebellar neurons in dystonic hesitant mice, we used the patch-clamp
technique to record from Purkinje cells and neurons of the Deep Cerebellar Nuclei (DCN) in acute cerebellar
slices. Unlike Purkinje neurons from wild-type controls that displayed tonic repetitive firing, adolescent/weaning
age Purkinje cells (P19-23) of hesitant mice showed a lack of normal spontaneous repetitive firing and an
inability to sustain high rates of repetitive firing in response to injected current. At around P24-27 and into
adulthood (6 – 8 weeks), hesitant Purkinje cells have established a tonic and repetitive firing comparable to the
pattern of firing observed in wild type Purkinje cells. Slice recordings of DCN neurons showed that juvenile
cells (P12 – 15) displayed a burst-firing pattern similar to that seen in vivo in the genetically dystonic rat. In
contrast to the dystonic rat, however, this burst-firing pattern became regular at weaning age (P16-P17). These
results suggest that there is a delay in the maturation of physiology of Purkinje neurons of hesitant mice. Our
results suggest that while the abnormal cerebellar physiology is involved in manifestation of motor symptoms in
hesitant mice, the locus of dystonia is likely not restricted to the cerebellum alone.
Vikas Kotagal: Diabetes is associated with Postural Instability and Gait difficulty in Parkinson Disease
independent of nigrostriatal dopaminergic denervation: a case-control study
Objective: To investigate the association between Parkinson disease motor subtype, striatal dopaminergic
denervation, and the presence of diabetes.
Background:Sources of vascular injury and inflammation, including a history of diabetes, represent possible
risk factors for neurodegenerative diseases and are of increasing interest with regard to neuroprotective
strategies in neurodegenerative disorders. Parkinson disease (PD) occurs more commonly in patients with a
history of diabetes though the mechanisms underlying the putative increased risk are not known. PD exhibits
significant motor subtype heterogeneity, which is not accounted for by the severity of nigrostriatal dopaminergic
denervation.
Methods:We performed a case-control study (n=33) involving 11 subjects (age 67.1 yrs±6.7; duration of
disease 7.1yrs ±4.6; UPDRS motor score 41.1±16.5) with PD and diabetes compared to 22 age and
duration-of-disease-matched subjects with PD but without diabetes. All subjects underwent (+)-[C-11]DTBZ
(VMAT2) monoaminergic PET imaging to assess striatal DTBZ distribution volume ratio (DVR) and modifiedUPDRS clinical examination to determine rigidity, bradykinesia, tremor, and postural instability and gait
difficulty (PIGD) sub-scores.
Results:After controlling for nigrostriatal dopaminergic denervation, PD subjects with diabetes displayed
greater PIGD sub-scores (t = 3.46, p = 0.015) but not greater bradykinesia, rigidity, or tremor sub-scores in
comparison to PD subjects without diabetes. There were no significant differences in striatal DTBZ binding
between the two groups.
Conclusions:Diabetes may be associated with a specific motor subtype of PD.
Graduate Research Assistant-UM Sleep Disorders Center
Jocelynn T. Owusu - The Relationship between Snoring and Pregnancy Outcomes in Pregnant Women
at Korle Bu Teaching Hospital (KBTH), Accra, Ghana
Background: Ghana has an overwhelming maternal mortality ratio of 450 per 100,000 live births, with 12%
attributable to hypertensive disorders of pregnancy, particularly pre-eclampsia. Research suggests that
pregnant women who snore (a marker of sleep-disordered breathing) are at increased risk for hypertensive
disorder of pregnancy, along with perinatal morbidity. However, this has not been previously studied in
developing countries like Ghana. Therefore, we hypothesized that snoring may contribute to the high
prevalence of pre-eclampsia in Ghana.
Methods: As a part of a larger study, Ghanaian women were recruited from maternity wards at KBTH within 48hours of delivery and interviewed about their maternal sleep quality. Snoring was defined as a positive
response to: “Did you snore loudly in the past week?”. Demographic data and pregnancy outcomes were
obtained from medical records.
Results: Among the 234 women approached, 232 (99%) agreed to participate. Twelve participants were
excluded due to missing data in medical records, thus the final sample size was 220. Mean age was 28.9±5.7
years, and mean parity was 1.35±1.38. Overall, 26 women (12%) had pre-eclampsia, and 53 women (24%)
reported snoring. Women who snored, compared to those who did not, were significantly more likely to have
pre-eclampsia (23% vs. 8%, p=0.005). We found no difference in gestational age at delivery (38.6±2.5 vs.
38.5±3.0 weeks; p n.s.) or birth weight (3083.27±629.56 vs. 3041.70±676.01 grams; p n.s.) of infants born to
women with and without snoring. In a logistic regression, the presence of snoring was independently
associated with preeclampsia with adjusted odds ratios 3.52 (95%CI 1.48-8.36, p=0.004).
Conclusions: Findings are consistent with similar studies in Western countries, suggesting that snoring during
pregnancy may confer a risk to maternal morbidity in Ghana. Screening for snoring during pregnancy may
improve maternal health outcomes in developing countries like Ghana where maternal morbidity rates are high.