Download Treatment

SYMPTOMATIC TREATMENT
IN
NEUROLOGY
Abdel-Latif Moussa Osman, MD
Founder of Departments of
Neurology, Al-Azhar University
Faculty of Medicine
Winner of the Encouraging
State Prize in Medical Sciences
& Medal of Excellency of the First Class
CAIRO
2010
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To the Memory of
My Father & Mother
To Laila .. My Pearl
The God Gift
in the Difficult Days
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ACKNOWLEDGMENTS
Thanks are particularly devoted to Dr. Tarek Awny, Professor of
Neurology, Al-Azhar University Faculty of Medicine, for his
kind, meticulous, and perfectionist revision of this text.
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CONTENTS
STROKE
 Ischemic Stroke
 Hemorrhagic Stroke.
 Intracerebral Hemorhage (ICH)
 Subarachnoid Hemorhage (SAH)
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MOVEMENT DISORDERS
Treatment of Spasticity
Treatment of Cerebellar Dysfunction
Treatment of Drug-induced Extrapyramidal
Syndrome
Treatment of Parkinson's Disease (PD).
Treating Problems Associated with Advancing PD.
Treatment of Sydenham's (Rheumatic) Chorea.
Treatment of Huntington's Disease.
Treatment of Willson's Disease.
Treatment of Hemiballismus
Treatment of Dystonia Musculorum Deformans
Treatment of Spasmodic Torticollis
Paroxysmal Choreo- athetesis & Dystonia.
Treatment of Tics
Treatment of Tremor
Treatment of Myoclonus
Treatment of Restles Leg Syndrome.
Treatment of Cerebellar Ataxia.
PAROXYSMAL DISORDERS
Epilepsy.
Treatment of Narcolepsy.
Migraine
Cluster Headache
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Tension- Type Headache
Headache Presenting in the Emergency Department
Treatment of Status Migrainosus.
Trigeminal Neuralgia.
ALZHEIMER'S DISEASE
 Disease- Modifying Drugs
 Disease- Specific Treatments
 Adjunctive Therapy
 Non-cognitive Drug Treatment:
 Depression
 Anxiety.
 Agitation
 Delusions
 Insomnia.
 Cognitive Enhancers
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DEMYELINATING DISORDERS OF THE CNS
Multiple Sclerosis (MS)
Treatment of Optic Neuritis
Treatment of Acute Transverse Myelitis.
Treatment of Acute Disseminated
Encephalomyelopathy (ADEM).
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CNS INFECTIONS
Pyogenic Meningitis.
Tuberculous Meningitis.
Brain Abscess.
Subdural Empyema.
Spinal Epidural Abscess.
Neurosyphilis.
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Brucellosis.
Lyme Disease
Leptospirosis.
Fungal infetions of the CNS
Viral Meningitis.
Viral Encephalitis.
Rabies.
Poliomyelitis.
Herpes Zoster.
Slow Viruses & Progressive Multifocal
Leucoencephalopathy (PML).
Toxoplasmosis.
Amebic Meningoencephalitis.
Neurocysticercosis.
Acquired Immunodeficiency Syndrome (AIDS)
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CNS NEOPLASMS
CNS Tumors in Adults
Pseudotumor Cerebri.
CNS Tumors in Children.
Spinal Cord Tumors.
Neurologic Complications of Radiotherapy.
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CRANIOSPINAL TRAUMA
 Head Injury
 Spinal Cord Injury
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DISC SYNDROMES, SPONDYLOSIS & LBP
 Disc Syndromes.
 Spondylosis.
 Spondylolysis & Spondylolisthesis.
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 Other Diseases of the Spine.
 Low Back Pain (LBP)
NEUROMUSCULAR DISORDERS
Myasthenia Gravis (MG)
Lambert-Eaton Myopathic Syndrome (LEMS)
Congenital Myasthenic Syndromes
Botulism.
Tetanus.
Episodic Muscle Weakness:
Familial Hypokalemic Periodic Paralysis.
Familial Hyperkalemic Periodic Paralysis.
Muscular Dystrophies.
 Duchenne Muscular Dystrophy.
 Myotonic Dystrophy
Polymyositis.
Polyneuropathies:
 Guillain-Barre Syndrome (GBS)
 Chronic Inflammatory Demyelinating
Polyradiculoneuropathy (CIDP)
 Other Chronic Neuropathies.
Bell's Palsy.
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AMYOTROPHIC LATERAL SCLEROSIS (ALS)
NEUROLOGICAL COMPLICATIONS OF
SYSTEMIC DISEASE
 Diabetes Mullitus (DM)
 Renal Failure
 Hepatic Disease.
AUTONOMIC DYSFUNCTION
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SLEEP DISORDERS
CHANNELOPATHIES
NEUROIMMUNOLOGY
Behcet's Disease.
Antiphospholipid Antibody Syndrome.
Systemic CNS Vasculitides
Neuropsychiatric Systemic Lupus Erythematosus
(SLE)
MITOCHONDRIAL DISORDERS
LEUKODYSTROPHIES
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PREFACE
Neurological disorders may be either acute or chronic. Acute
disorders necessitate intensive care treatment. Examples of such
disorders include acute strokes, Guillain Barre Syndrome
(GBS), acute multiple sclerosis (MS) episodes, myasthemic
crisis, status epilepticus, serial seizures or prolonged seizures,
acute migraine attacks or status migrainosus, hypokalemic
periodic paralysis, acute meningitis, encephalitis, or meningoencephalitis, acute intracranial hypertension, critical illness
polyneuropathy, respiratory failure in amyotrophic lateral
sclerosis (ALS), acute pain syndromes, … etc. Chronic
neurological disorders on the other hand, need symptomatic
treatment. Examples of such disorders include heredofamilial &
neurodegenerative disorders. However, specific treatment is
becoming available for many neurological diseases, in the form
of drug treatment, surgery, & interventional procedures.
Symptomatic treatment improves the patient's quality of life
through relieving pain, aborting seizures,… etc. However, it is
not a substitute for specific therapy. The later should be sought
for in every neurological disorder.
This book will focus on symptomatic treatment only.
Therapeutic protocols on the other hand, will be fully discussed
later in another text.
I hope this book meets your needs in the appropriate
management of common neurological disorders.
Abdel-Latif M. Osman, MD
Cairo 2010
E-mail: [email protected]
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LIST OF ABBREVIATIONS
bided
5-HTP
ABC
ABG
AChR-Ab
ACT
ACTH
AD
AD
ADEM
ADH
AED
AF
AIDS
ALD
ALS
AMN
A-P
ASA
AVM
bided
BDNF
Bi PAP
Bl.
BP
BUN
C.S
C.V.death
C/I
Ca
CACH
cap
= twice daily
= 5-hydroxy tryptophan
= airway, breathing, & circulation
= arterial blood gases
= acetylchoine receptor antibodies
= antichymotrypsin
= adrenocorticotrophic hormone
= Alzheimer's disease
= Alexander's disease
= acute disseminated encephalomyelopathy
= antiduiretic hormone
= antiepilaptic drugs
= atrial fibrillation
= acquired immunodeficiency syndrome
= adrenoleukodystrophy
= amyotrophic lateral scelrosis
= adrenomyeloneuropathy
= antroposterior
= aspirin
= arteriovenous malformation
= twice daily
= brain-drived neurotrophic factor
= Bi-level positive airway pressure
= blood
= blood pressure
= blood urea nitogen
= cesarian section
= cardiovascular death
= contraindication
= calcium
= childhood ataxia with CNS hypomyelination
= capsule
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CAP
CBC
CBF
CE
CHF
CIDP
CJD
CMV
CNS
CP
CPAP
CPK
CPMS
CPP
CR
CSF
CT
CT-1
CTS
CVL
CVP
d
D/C
D/W
DA
DBS
DCA
DDAVP
DHA
DHE
dl
DM
DMD
= Cellulose acetate polymer
= complete blood count
= cerebral blood flow
= carotid endarterctomy
= congestive heart failure
= cronic inflammatory demyelinating
polyradiculoneuropathy
= Creutzfeldt- Jakob diseae
= cytomegalovirus
= central nervous system
= cerebral palsy
= continuous positive airway pressure
= creatine phosphokinase
= chronic progressive MS
= cerebral perfusion pressure
= controlled release
= cerebro spinal fluid
= computerized tomography
= cardiotrophin-1
= Carpal tunnel syndrome
= central venous line
= central venous pressure
= day
= discontinue
= dextrose water
= dopamin agonist
= deep brain stimulation
=
= vasopressin (minirin)
= docosahexaenoic acid
= Dihydroergotamine
= decileter
= diabetes mellitus
= Duchene muscular dystrophy
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DVT
é
ECG
ECT
EEG
EMG
Exam
FSH
FVC
g
GBS
GDNF
GH
GI
GLD
GOC
GPi
GPI
gr.
h
H.V
HCL
Hct
HD
HIV
HS
HTN
HZ
IC
ICS
ICT
ICU
ICU
IFN
= deep venous thrombosis
= with
= electrocardiogram
= electroconvulsiva therapy
= electroencephalography
= electromyography
= Examination
= Follicle stimulating hormone
= forcid vital capacity
= gram
= guillain- barré syndrome
= glial- derived neurotrophic factor
= growth hormone
= gastrointestinal
= globoid cell leukodystrophy
= Guglielmi electrodetachable coils
= globus pallidus pars interna
= general paralysis of insane
= granules
= hour
= hyperventilation
= hydrochloride
= Hematocrit
= huntington's disease
= human immunodeficiency virus
= Herpes simplex
= hypertension
= Herpes zoster
= intracranial
= intracranial hemorrhage
= intracranial tension
= intensive care unit
= Intansive care unit
= interferon
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IGF-1
IgG
IM
INH
inj
INR
IPPB
IPPV
IQ
IT
IV
IVIg
L.F.T
LBP
LCFA
LCHAD
LEMS
LL
LMN
LP
MAOI
max
MCA
MCFA
mcg
mg
MG
MI
min
MLD
mm
mm Hg
MND
MRI
= inulin- like growth factor-1
= immunoglobulin-G
= intramuscular
= isonioizid
= injection
= international normalized ratio
= intermittent positive pressure breathing
= Intermittent positive pressure ventilation
= intelligence quationt
= itnrathecal
= intravenous
= intravenous immunoglobulin
= liver function test
= low back pain
= long-chain fatty acid
= long-chain 3-hydroxyacyl coenzyme A deficiency
= Lambert-eaton myathenic syndrome
= Lower limb
= lower motor neurone
= Lumbur puncture
= monoamine oxidase inhibitors
= maximum
= meddle cerebral artery
= medium-chain fatty acid
= microgram
= mille gram
= myasthenia gravis
= myocardial infarction
= minute
= metachromatic leukodystrophy
= millimeter
= mullimeter mercury
= motor neurone disease
= magnetic resonance imaging
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MS
mtDNA
Na
NAB
NARP
NBS
nDNA
NE
NGT
NGT
NIPPV
NMDA
NPP
NSAID
NT-3
NT-4
od
P.P
PCO2
PD
PEEP
PEG
PLEX
PLM
PMD
PME
PML
PMLE
PN-1
PO
PO2
PPMS
prm
pt
= multibol scelorsis
= mitocondrial DNA
= sodium
= Neutralizing antibodies
= neuropathy, ataxia & retinitis pigmentosa
= neuro-Behcet's syndrome
= nuclure DNA
= norepinephrine
= nasogastric tube
= Nasogastrictube
= non-invasive positive pressure ventilation
= N-methyl D-aspertate
= normal perfision pressure
= nonsteroidal antienflammatory drugs
= Neurotrophin-3
= Neurotrophin-4
= once daily
= periodic pralysis
= CO2 pressure
= Parkinson's disease
= Positive end-expiratory pressure
= percutaneous endoscopic gastrostomy
= plama exchange
= periodic limb movements
= Pelizaeus merzbacher disease
= petit mal epilepsy
= progressive multifocal leucoencephalopathy
= progressive multifocal leukoencephalopahty
= protease-nexin-1
= Orally
= Oxygen pressure
= primary progressive MS
= as required
= patient
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PT
PTT
qid
QL
R.F.T
REM
RF
RIG
RIND
RLS
RRMS
rTPA
SA
SAH
SAP
SC
SIADH
SL
SLE
sp
SPG2
SPMS
SR
SSPE
SSPI
STN
sup
supp.
tab
TCA
TCD
TDD
TENS
TIA
= prothrombin time
= partial thromboplastin time
= for times daily
= quality of life
= renal function test
= rapid eye movement
= renal failure
= radiologically inserted gastrotomy
= reversibol ischemic neurologic deficit
= restless legs syndrome
= relapsing remitting MS
= recombinant tissue plasminogen activator
= subarachnoid
= subarachnoid hemorrhage
= stress activated protein kinase
= subcutaneous
= syndrome of inappropriate ADH
= sublaingual
= systemic lupu erythematosus
= spinal
= spastic paraplegia 2
= secondary progressive MS
= slow release
= subacute sclerosing panencephalitis
= selective sertonin re-uptake inhibitors
= subthalamic nucleus
= suspension
= suppositories
= tablet
= Tricyclic antiedepressant
= transcranial duppler
= telecommunication device for the deaf
= transcutaneous electrical nerve stimulation
= transient ischemic attack
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tid
U
UT
VA
VC
VC
VD
VER
VIM
Vit
VP
VW
wk
wt.
y
= three times daily
= unit
= urinary tract
= ventriculoatrial
= vital capacity
= vasoconstriction
= vasodilatalion
= visual-evoked response
= ventral intermedius (nucleus of thalamus)
= vitamin
= ventriculoperitoneal
= Vanishing white matter disease
= week
= weight
= years
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STROKE
I. Ischemic stroke.
II. Hemorrhagic stroke:
 Intracerebral Hemorrhage (ICH).
 Subacrachnoid Hemorrhage (SAH).
ISCHEMIC STROKE
Strategies for reducing the burden of stroke:
I. Primary Prevention:
 Lifestyle Changes
 Smoking cessation.
 Abstaining alcohol intake.
 Improving diet.
 Increasing exercise.
 Risk Factor Modification
 Control HTN, DM, Hyperlipidemia, ...... etc.
II. Acute Treatment
 To reduce morbidity & mortality.
III. Rehabilitation
 To reduce disability & dependence
IV. Secondary Prevention
 To reduce stroke recurrence.
Stroke Prevention:
I. Primary Prevention of Stroke
A. Control Risk Factors
 Control HTN.
 Control DM.
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 Control hyperlipidemia e.g. low-fat diet.
 Cessation of cigarette smoking.
 Abstaining alcohol.
 Reducing body weight in obesity
 Regular physical exercise.
 Relaxation therapy.
 Avoiding oral contraceptives in high-risk women.
 Treating heart disease e.g. AF, MI.
 Treating TIAs:Antiplatelets/Anticoagulant therapy; carotid
endartcrectomy.
B. Aspirin (100-325 mg/d) →18% risk reduction of nonfatal
MI, nonfatal stroke, & C.V. death.
II. Secondary Prevention of Stroke
A. Control Risk Factors
B. Antiplatelet Therapy
 Aspirin (ASA).
 Aspirin (ASA) + Dipyridamole (Persantin).
 Clopidogrel (Plavix).
C. Anticoagulant Therapy: for high-risk pts e.g. AF
 Low-dose heparin, 5000 U, s.c. bid.
 Warfarin (Marevan).
D. Pts with Recurrent TIAs, Stroke, MI
 Add dipyridamole to aspirin.
 ↑ dose of aspirin.
E. Pts with Carotid Stenosis ≥70
 Carotid Endarterectomy (CE).
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Antihypertensive Treatment in Acute Ischemic Stroke:
Systolic BP <220mmHg
Diastolic BP < 120 mmHg
Diastolic BP > 120 mmHg
Systolic BP slightly
increased over repeated
measures
Systolic BP > 220 mmHg &
/or
Diastolic BP > 110-120
mmHg
 Do not treat
 Do not treat
a) Nitroglycerin 5 mg iv or 10
mg po
b) Sodium nitroprusside
(Niprlde)
a) Nifedipine (Adalat) 10 mg sl
b) Clonidine (Catapres)
0.075mg sc
c) Urapidil 12.5 mg i.v.
Acute Ischemic Stroke Therapy
Two major approaches:
1. Thrombolytic therapy (Recanalization)
2. Neuroprotective therapy
Thrombolytic Therapy for Acute Ischemic Stroke
 Thrombolytic Therapy →Recanalization
 Therapeutic Time Window:
 3 hrs: Approved.
 6 hrs: Doubtful.
 "Too soon is unnecessary, too late is useless".
Inclusion Criteria:
 Acute ischemic stroke with clearly definable time of onset.
 Pt presenting within 3-6 hrs from onset of symptoms.
 A base-line brain CT scan excluding ICH.
 Patient's age between 25-75 yrs.
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Exclusion Criteria:
 Pts with history of stroke or serious head trauma within the
preceding 3 months.
 Pts who had undergone major surgery within 14 days.
 Pts who had a history of ICH.
 Pts who had a systolic BP > 185 mmHg.
 Pts who had a diastolic BP > 110 mmHg.
 Pts who had rapidly improving or minor symptoms.
 Pts who had symptoms suggestive of SAH.
 Pts who had G.I. hemorrhage or U.T. hemorrhage within the
previous 21 days.
 Pts who had arterial puncture at a non-compressible site within
the previous 7 days
 Pts who had a seizure at the onset of stroke.
 Pts who were taking anticoagulants within 48 hrs preceding
the onset of stroke & had elevated PTT.
 Pts with PT > 15 seconds.
 Pts with platelet counts < 100.000/cubic mm.
 Pts with glucose concentrations < 50 mg/dl, or > 400 mg/dl.
Tissue Plasminogen Activator (rt-PA) (Actilyse)
 Dose: 0.9 mg per kg body wt (max. 90 mg)
 10% of this dose is given as a bolus
 Followed by i.v. infusion of the remaining 90% over a period
of 60 min.
 No anticoagulants or antiplatelet agents be given for 24 hrs
after treatment.
 BP should be maintained within pre-specified values.
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BP Management after tPA for Ischemic Stroke
1. If diastolic BP is > 140 mm Hg, start an infusion of sodium
nitroprusside (Nipride) (0.5-10 mcg/kg/min).
2. If systolic BP is > 230 mm Hg &/or diastolic BP is 121-140
mmHg, start labetalol (Trandate) 10 mg I.V. over 1-2
minutes. The dose may be repeated &/or doubled every 10
minutes up to 150 mg total. Continue BP measuring q 15
minutes. If labetalol cannot be used or is ineffective,
nitroprusside (Nipride) or nifedipine (Adalaf) may be used.
3. If systolic BP is > 180-230 mm Hg &/or diastolic BP is >
110-120 mm Hg on two readings 5-10 minutes apart, give
labetalol (Trandate) 10 mg I.V. over 1-2 minutes. The dose
may be repeated or doubled every 10-20 minutes, up to 150
mg total. If labetalol is contraindicated (e.g. CHF), use
nifedipine (Adalat), 10 mg PO or SL
Neuroprotective Therapy
 Neuroprotection aims at preventing or limiting the brain tissue
damage that occurs in areas of reduced CBF (e.g. the
penumbra region surrounding an infarct)
 Hypothermia has a CNS neuroprotective effect:
 Transient mild to moderate hypothermia (30 - 35°C)
→↓infarct size during temporary but not permanent focal
ischemia .
 CNS hypothermia can be achieved by:
 Blankets containing ice
 IV iced saline
 IV drugs e.g. barbiturate coma
Examples of Currently Available Neuroprotectants:
 Phenytoin (Epanutin)
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 Nimodipine (Nimotop)
 Naloxone (Narcan)
 Piracetam (Nootropil)
 Lubeluzole (Prosy nap)
Prophylactic Measures in Acute Stroke
 Immobilisation causes several problems in stroke pts, e.g.
DVT, pressure ulcers, & infection.
 All stroke pts are at risk of DVT & should receive
prophylactic treatment.
 DVT may cause pulmonary embolism, which may be fatal.
 Pneumatic stockings & / or s.c. heparin should be used.
 Heparin dose is adjusted to prolong the PTT to 1.2-1.5 times
control values
 Another option is the use of coumadin to prolong the PT to
1.2-1.5 control values.
 Frequent turning (every 2 hrs) & early identification &
treatment of pressure ulcers is essential
 C.V.L., urinary catheters, & endotracheal tubes are prone to
cause infection & should be discontinued as soon as possible.
 Frequent turning, suctioning, & chest percussion prevent
atelectasis & mobilize pulmonary secretions.
 Swallowing disorders ↑ the risk of aspiration pneumonia.
 NGT feeding is used in pts who are unable to tolerate oral
nutrition.
 Percutaneous gastrostomy & tracheostomy may be needed for
pts with severe swallowing or aspiration difficulties.
 Stress ulcer prophylaxis is needed in stroke pts. (Zantac i.v.
daily)
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Therapeutic Protocol of Ischemic Stroke
1. Care of the comatose (or bedridden) patient
2. Control risk factors
3. Anticoagulants in:
 Stenotic lesions (+ surgery)
 TIAs, RIND, Stroke - in - evolution
 Completed stroke with a minor deficit
 Embolic lesions e.g. in AF, MI
 If embolic source is unknown use:
Warfarin (Marevan) for several months, then Antiplatelets
(e.g. Aspirin)
Avoid anticoagulants in infective endocarditis & in
massive infarcts
Heparin
 IV bolus: 5000 - 10000 units
 IV infusion: 1000 - 1500 units / hr
Check PTT initially & daily
Adjust the dose to keep PTT at 1.5 - 2 times that of
control
Antidote: Protamine i.v.
Marevan (Warfarin)
 5 mg tid on first day
 5 mg bid on 2nd day
 5 mg o.d. on 3 rd day & afterwards
Check PT initially & daily for 1 wk, then every 2-3 wks
Adjust the dose to keep PT at 1.5-2 times that of control
Antidote: Vitamin K i.v. 50 mg + fresh frozen plasma
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4. Antiplatelet Agents:
 Aspirin (ASA) 150 -325 mg daily & / or
 Persantin (Dipyridamole) 75 nig tid
 Or: Plavix (Clopidogrel) 75 mg o.d.
5. Surgery:
 Carotid endarterectomy (Stenosis ≥70%)
 Posterior fossa decompression in massive cerebellar
infarction & brainstem compression
 Symptomatic extracranial vertebral artery disease,
subclavian steal, & aortic arch disease
 Temporal artery to MCA anastomosis is not superior to
medical treatment
6. Anti-edema Agents
7. Anticonvulsants for seizures
8. Vasodilators must be avoided in acute stroke as they reduce
perfusion to ischemic areas (Intracerebral steal).
9. Thrombolytic Therapy (rt - PA)
 Therapeutic time window : 3 - 6 hrs
 Inclusion & Exclusion Criteria shoud be adopted.
 Dose: 0.9 mg/kg wt., Max. 90 mg i.v.
10% as an i.v bolus,
90% as infusion over 60 min.
10. Neuroprotectants :
 Epanutin (Phenytoin)
 Nootropil (Piracetam)
 Narcan (Naloxone)
 Nimotop (Nimodipine)
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11. Other Medications:
 Trental (Pentoxifylline), 400 mg bid - tid
 Duxil (Almitrin+Raubasine), bid
 Dilution therapy : Low-molecular weight dextran
12. Physical Therapy & Rehabilitation
 Occupational Therapy
 Speech Therapy
HEMORRHAGIC STROKE
INTRACEREBRAL HEMORRHAGE
Treatment:
 Care of the comatose (or bedridden) pt.: as usual
 Blood pressure control
 Anti-edema agents: Steroids, Mannitol or Glycerol
 Surgery: Evacuation of hematomas in accessible locations
 Anti-convulsants for seizures
 Correction of clotting abnormalities.
 Platelets for thrombocytopenia.
 Fresh-frozen plasma & vit. K for coumarin overdose.
 Protamine for heparin overdose.
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Surgical or Nonsurgical Treatment of Intracerebral
Hemorrhage (modified from Minematsu &. Yamaguchi)
ICH location
Putamen
Clinical/CT features
Alert, small ICH(<30cc)
Comatose, large ICH
(> 60 cc)
Drowsy, intermediate
ICH (30-60 cc)
Caudate
Treatment
Non-surgical
Non-surgical
Consider evacuation
Alert or drowsy, with
intraventricular
hemorrhage &
hydrocephalus
Thalamus
Drowsy or lethargic, with
blood in 3rd ventricle &
hydrocephalus
Lobar white matter Drowsy or lethargic, with
intermediate ICH (20-60cc),
Progressive decline in level
of consciousness
Pons, midbrain,
medulla
Consider
ventriculostomy
Cerebellum
Evacuation
recommended,
preceded by
ventriculostomy if
patient is actively
deteriorating
Non-comatose, with ICH >3
cm in diameter, & /or
hydrocephalus, &/or
effacement of
quadrigeminal cistern
Consider evacuation
Consider evacuation
Non-surgical
SUBARACHNOID HEMORRHAGE (SAH)
Therapeutic Protocol:
 Surgery is the treatment of choice for suitable pts whose
aneurysms are surgically accessible
 A VMs may or may not be amenable to surgery
-28-
A. Pre-operative measures:
1. General precautions:
 Control HTN by antihypertensive drugs
 Sedation with Phenobarbital or Diazepam
 Prophylactic anticonvulsants to prevent seizures
 Stool softeners to prevent straining
 Darkened quite room
 Volume expansion in hypovolemia (from hemorrhage)
2. Antifibrinolytic agents:
 Epsilon-aminocaproic acid (Amicar), '30 mg/day, mixed in
1 liter of 5 % dextrose & 0.45% normal saline & given IV
over 24hrs. or 4g PO q3hrs. Continued until the time of
surgery or for 6 wks
3. Antiedema agents: Dexamethasone, Mannitol, or Glycerol
for ↑ ICT
Management of vasospasm:
 Vasospasm →drowsiness or focal neurologic signs starting 2-3
days after SAH & maximum at 7 days, due to release of
vasoactive compounds e.g. serotonin, catecholamines,
peptides & endothelin
 Vasospasm is diagnosed by TCD
 IV isoproterenol & nitroglycerin are useful
 Volume expansion by 5% albumin IV (C/I in low cardiac
output & CHF). Monitored CVP (adjusted to 8-12 mm Hg).
Hypervolemia may be combated with phlebotomy &
hemodilution to achieve a hematocrit of 30-35%
 Dilatation of vasospastic segments of cerebral arteries using
balloon angioplasty
 Nimodipine (Nimotop), 30-60 mg PO q 4 hrs (avoid
hypotension) may prevent vasospasm following SAH.
-29-
B. Surgery:
 Contraindications:
 Coma
 Severe neurologic deficits
 Timing:
 Early aneurysm surgery in the first 24-48 hrs is now
preferred (before vasospasm)
+ Irrigation of the S.A. space to remove blood
± Instillating tissue plasminogen activator to dissolve
adherent clot after clipping the aneurysm
Procedures:
 Clipping the neck of the aneurysm is the most common
procedure
 Wrapping the aneurysm with muscle
 Coating the aneurysm with plastic material
 Occluding the internal carotid artery in the neck
 Endovascular occlusion of the aneurysm with Guglielmi
electro-detachable coils (GOC)
 Endovascular application of cellulose acetate polymer (CAP)
 Block resection or ligation of the major arteries is done for
AVMs
 Balloon occlusion of giant aneurysms of I.C. carotid artery.
 Radiotherapy of AVMs using a proton beam, or using the
gamma rays from a cobalt source
 Shunt for hydrocephalus complicating SAH .
 Embolization of aneurysm in pts in whom surgery is
contraindicated, using horse hair or fine coils.
-30-
Guidelines
vasospasm
for
management
of
symptomatic
cerebral
o Discontinue any antihypertensive or diuretic agent
o Insert pulmonary catheter
o Start volume replacement with albumin 5 %, 250 ml, or hypertonic saline & add
dobutamine, 5-15 mg/kg/min, to attain cardiac index ≥ 41/min/m2 & pulmonary
artery wedge pressure of 12-14 mmHg
o If no clinical improvement within l-2h, Transcranial Doppler ultrasonography
(TCD)
o TCD velocity > 120 m/s, consider phenylephrine, 10 mg/min, & increase mean
arterial pressure to 20 mmHg above baseline. Consider discontinuation of
nimodipine for 24 hours
o No success, perform cerebral angiography
o Focal cerebral vasospasm, consider angioplasty
o Diffuse cerebral vasospasm, consider intra-arterial papaverine
Comparison of microsurgery, endovascular embolization &
radiosurgery in treatment of cerebral AVM
Microsurgery
Endovascular
embolization
Invasivcness
High
Low
Accessibility
Sometimes difficult in Relatively easy
deep seated AVMs
Effect on adjacent brain Larger
Smaller
Functional evaluation of Difficult
Possible
the adjacent hrain
(Superselective
Amytal testing)
Complete cure
Usually possible
Rare (10-20%)
Radiosurgery
Low
Easy
Smaller
Difficult
Rare
85 - 90 % in small
AVMs
None
Hemorrhagic
complications
Ischemic complications Rare
Radiation dose
0
2-5%
None
2-10%
1000-2000 rad
Adverse effect of
radiation
Length of
hospitalization
None
Rare
Rare
2000 - 3000 rad
(marginal dose)
2-10%
1-2 weeks
3-7 days
2-3 days
Normal perfusion
pressure (NPP)
Sometimes occurs
(especially in large,
high flow AVMs)
Rare
-31-
MOVEMENT DISORDERS
Treatment of Spasticity, Rigidity, Flexor Spasms:
R/ Dantrolene sodium (Dantrium) 25 mg cap
(25 mg qid, slowly ↑ to 100mg qid over 1 month)
OR: Baclofen (Lioresal) 10 mg & 25 mg tabs.
(10 mg qid, slowly ↑ to 30-100mg qid).
OR: Diazepam (Valium) 2mg & 5 mg tabs.
(6mg qid, slowly ↑ to 60 mg qid)
OR: Tizanidine (Sirdalud) 2 mg & 4 mg tabs.
( Up to 36 mg daily in divided doses)
OR: Clonidine (Catapres) (0.15 mg tab. tid)
OR: Phenytoin (Epanutin) 100mg cap.
(100 mg tid).
OR: Vigabatrin (Sabril) 500 mg tabs
(500 mg tid).
Other Therapies of Spasticity:
 Intrathecal Alcohol or Phenol → incontinence.
 Botulinum toxin (Botox) in C.P., MS, Stroke,…
 Peripheral nerve blockade with local anesthetic, if successful,
permanent block with alcohol or 5% phenol injection.
 Selective posterior rhizatomy in C.P.
 Transcutaneous electrical nerve stimulation (TENS).
 Cerebellar, dorsal column electrical stimulation
 Physiotherapy.
 Orthopedic procedures.
Treatment of Cerebellar Dysfunction:
R/ Physostigmine
(8 mg daily).
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OR: 5-Hydroxytryptophan
(10 mg / kg/ day, for dysarthria & dysequilibrsium).
 Physiotherapy.
 Ventrolateral thalamotomy (for tremor).
Treatment of Drug-induced Extrapyramidal Syndromes:
(1) Acute idiosyncratic dyskinesia & dystonia:
R/ Benztropine (Cogentin), (1 mg i.m. or i.v.)
OR: Biperidin (Akineton), (1 mg i.m. or i.v.)
OR: Diphenhydramine (Benadryl), (50mg i.v.)
(6mg qid, slowly ↑ to 60 mg qid.)
(2) Parkinsonism:
R/ Benztropine (Cogentin), (0.5-4 mg bid.)
OR: Biperidin (Akineton), (1 -2 mg tid..)
OR: Trihexyphenidyl HCL (Artane), (1-5mg tid.)
(3) Akathisia (Motor Restlessness)
R/ Diazepam (Valium),( 2-5 mg tid.)
OR: Clonidine (Catapres) (0.15 mg tab tid.)
OR: Amantadine HCL (Adamine), (100 mg bid.)
* Anticholinergics are partially effective.
(4) Tardive (Late) Dyskinesias:
(e.g. chorea, athetosis, dystonia, akathisia & orobuccal dyskinesia)
R/ Tetrabenazine (Nitoman) 25mg tabs,
(1/2 tab. ↑ slowly to 200mg daily)
OR: Reserpine (Serpasil) 0.25mg tab.
(1 tab daily, ↑ slowly to 2-4 mg/day)
OR: Baclofen (Lioresal), (10-25mg tid.)
Valproic acid (Depakine), (200-500mg tid.)
Amantadine (Adamine), (100 mg bid.)
Clonidine (Catapres) (0.15mg tab. tid)
Carbidopa/ Levodopa (Sinemet).
-33-
Treatment of Parkinson's Disease (PD):
Neuroprotectants:
 Vitamin E (1000 I.U. once daily)
 Riluzole (Rilutek), (50mg bid)
 Co-enzyme Q-10 tid.
 L- Carnitine. tid
 Ginkgo biloba o.d.
 COX-2 inhibitors e.g. celecoxib (Celebrex) (200 mg Cap bid).
 Selegiline (Jumex), (5mg bid).
Anticholinergics:
R/ Benztropine (Cogentin) 2mg tab. (0.5-2mg bid)
OR: Biperidin (Akinetin) 2mg tab. (1-2mg bid- tid).
OR: Trihexyphenidyl (Artane) 2 & 5mg tab. (0.5-1mg bid, ↑up
to 2mg tid).
OR: Orphenadrine (Disipal).
OR: Procyclidine (Kemadrin).
Dopamine receptor agonists:
R/ Bromocriptine (Parlodel) 2.5 & 5mg tab.
(1.25 mg/d, ↑ up to 5-10 mg tid).
OR: Pramipexole (Sifrol) 0.125, 0.25, 0.05, 1 & 1.5 mg tab.
(0.125 mg tid, ↑ up to 0.05-1.5 mg tid).
OR: Pergolide (Permax) 0.05, 0.25 & 1 mg tab. (0.05mg/d, ↑up
to 1 mg tid).
OR: Ropinirole (Requip) 0.25, 0.5, 1, 2 & 5 mg tab.
(0.25mg tid, ↑ up to 8 mg tid).
OR: Cabergoline (Dostinex, Cabaser),
(0.25mg qid, ↑ up to 0.5-5 mg/d.)
OR: Lisuride (Dopergin), (0.2 mg qid, ↑up to 1-2mg/d.)
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Amantadine HCL:
R/ Adamine (100 mg cap, bid)
OR: Amantine (100 mg cap, bid).
OR: Symmetrel (100 mg cap, bid).
Catechol- o- methyltransferase inhibitors:
R/ Entacapone (Comtan) 200 mg tab.
(200 mg with each dose of levodopa)
Dopamine Precursors:
R/ Levodopa/ Carbidopa (Sinemet, Sinemet CR).
Levodopa + Carbidopa+ Entacapone:
R/ Stalevo (50 mg tid)
OR: Stalevo (100 mg tid)
OR: Stalevo (150 mg tid).
Surgery:
 Fetal nigral transplantation.
 Ventrolateral thalamatomy.
 Pallidotomy.
 Deep Brain Stimulation (DBS). e.g:
 Subthalamic Nucleus (STN) stimulation.
 Thalamic (VIM nucleus) stimulation.
 GPi stimulation.
Procedure
Tremor
Thalamotomy
Pallidotomy
DBS- thalamus
DBS- GPi
DBS- STN
Fetal nigral
transplantation
+++
++
+++
++
+++
Rigidity/
Bradykinesia
+/++
+/+++
+++
++
++
-35-
Dykinesia
Advers events
+/+++
+/+++
+++
Great risk
Great risk
Moderate risk
Moderate risk
Moderate risk
++/-
Minimal risk
Treating Problems Associated with Advancing PD:
Motor complications:
A. Motor Fluctuations:
 No response: ↑doses of Sinemet.
 Suboptimal peak response:
Begin combination therapy:
 Parlodel or Sifrol + Sinemet.
 Comtan + Sinemet (Stalevo).
 Jumex + sinemet.
 Surgery.
 Wearing- off phenomenon:
 Parlodel or Sifrol + Sinemet.
 ↑ frequency &/or dose of Sinemet.
 Comtan + Sinemet.
 Add: Sinemet CR.
 Add: Jumex.
 S.C. Apomorphine.
 Surgery.
 Unpredictable "on" & "off" in PD:
 Parlodel or Sifrol + Sinemet.
 Add: Comtan or use Stalevo.
 S.C. Apomorphine.
 Postpone dietary protein to evening meal.
 Surgery.
 Freezing in PD:
 Present during time of peak levodopa response. ↑
dopaminergic therapy
o Review suboptimal peak response.
 Present during "of" phase only:
o Review "wearing-off" phenomenon.
 Not confined to "off" state
o Change dose of dopaminergic agents
-36-
o Assistive devices.
 Anxiety-induced:
o Review Neuropsychiatric problems.
o Behavioral impairment.
B. Dyskinesias (Choreiform Dyskinesias & Dytonia)
 Choreiform Dyskinesias:
 Peak dose dyskinesia:
o Use: Sinemet CR
o D/C Jumex .
o ↓ dose of Levodopa.
o Add: Parlodel or Sifrol.
o Add: Adamine 100 mg bid.
o Consider surgery
 Diphasic dyskinesia:
 Convert from sinemet CR to sinemet
 ↑ dose of sinemet
 Use comtan
 Restrict sinemet to early & midday doses.
 Consider surgery.
 Review Neuropsychiatric problems
(Behavioral impairment)
 Dystonia in PD:
 Early- morning foot dystonia:
o Nocturnal Sinemet CR.
o Nocturnal Sifrol or Parlodel.
o Add: Comtan.
o Early morning Sinemet.
 "Peak-dose" effect:
o ↓dose of Sinemet.
o Add or ↑ dose of Sifrol or Parlodel.
o Consider surgery.
 "End- of dose" effect:
-37-
o Review "wearing- off".
Constipation in PD:
 ↑ fluids, fibre & bulk in diet.
 Exercise.
 D/C cogentin, akineton, …….. etc.
 Stool softners e.g.
R/ Lactulose (Duphalac).
R/ Cisapride (Prepulsid).
R/ Enemas (Enemax)
R/ S.C. Apomorphine.
Nocturia in PD:
 ↓ evening fluid intake.
 Oxybutinin (Uripan, Ditropan).
 Propanthetine (Pro- Banthine).
 Consider Urologic evaluation.
Erectile Dysfunction in PD:
 Review medications.
 Urologic evaluation.
 Viagra, Cialis, …… etc.
Orthostatic Hypotension in PD:
 D/C Antihypertensives.
 Behavior modification.
 ↑ salt & fluid intake.
 Elevate head of bed.
 Fludrocortisome (Astonin- H) bid.
 Midodrine (Gutron).
 Erythropoietin (Eprex).
-38-
Impaired Thermoregulation (Hyperhidrosis) in P.D:
 ↓ motor fluctuations.
 Propranolol (Inderal).
 Medical evaluation.
Drug- resistant PD or Dystonia:
 Consider pallidotomy.
 Consider DBS/ STN stimulation.
 Consider fetal nigral transplantation.
Cognitive impairment in PD:
 Treat medical problems.
 Discontinue:
 Sedatives & Anxiolytics.
 Anticholinergics e.g. Cogentin.
 Tricyclic Antidepressants e.g. Tryptizol.
 Amantadine e.g. Adamine.
 Selegiline (Jumex)
 DA e.g. Parlodel
 ↓ Sinemet
Hallucinations/ Delirium in PD:
 Same as in cognitive impairment.
 Begin low-dose Clozapine (Leponex).
Behavioral Impairment in PD:
(Depression, Agitation, Anxiety,/ Panic)
Treatment of Depression in PD:
 Apathetic:
 SSRIs e.g. Cipralex 10 mg tabs.o.d
 TCAs e.g. Trittico 50 mg & 100 mg tabs. o.d.
 ECT.
-39-
 Agitated:
 TCAs e.g. Trittico 50 or 100 mg tabs. o.d.
 ECT.
Treatment of Anxiety & Panic Attachs in PD:
 If related to "off" state:
 Adjust antiparkinsonian drugs.
 Try Benzodiazepines, Clonazepam (Rivotril) or Busparone
(Buspar).
 Try TCAs.
 If not related to "off" state:
 Counseling.
 Clonazepam or Busparone.
 TCAs for 3 months, then cautious discontinuation.
Delirium in PD:
 If drug-incuced:
 ↓ or discontinue Anticholinergic; Amantadine; Selegiline;
DA; Sinemet (in this order).
 If not drug-induced:
 Assess if related to electrolyte imbalance, dehydration, or
infection.
 If yes: treat abnormality.
 If no: mild delirium.
Mild delirium: Trazodone (Trittico) 50 or 100 mg tab. o.d.
Moderate to severe: Clozapine (Leponex) 25 mg tab o.d.
Insomnia in PD:
R/ Diphenhydramine (Amydramine)
(25-75mg at bedtime)
OR: Chloral hydrate (Chloral Syrup)
(250-850mg at bedtime).
-40-
OR: TCAs e.g. Tryptizol 10mg & 25mg tab.
(10-100 mg at bedtime)
OR: Trazodone (Trittico) 50 mg & 100 mg tab.
(50-200mg at bedtime)
OR: Temazepam (Normison)
(15-30 mg at bedtime)
OR: Diazepam (Valium) 2mg & 5mg tab.
(1-5 mg at bedtime)
OR: Clonazepam (Rivotril) 0.5mg & 2 mg tab.
(0.5-1 mg at bedtime)
OR: Zolpidem (Stilnox) 10mg tab.
(5-10 mg at bedtime)
Daytime Somnolance in PD:
 Treat depression.
 ↓ sedatives.
 Polysomnogram to assess for primary sleep disorder.
 Correct night time insomnia.
 Add: Selegiline (Jumex), Caffeine, Methylphenidate (Ritalin)
10mg tab.
Nightmares in PD:
 ↓ or D/C noctumal dose of anti-PD drugs.
 ↓ or D/C hypnotics & TCAs.
 Treat depression.
Restless Legs Syndrome in PD:
 ↑ Sinemet nocturnal dose.
 Bromocriptine (Parlodel) or Pramipexole (Sifrol), 1 tab. tid.
 Clonazepam (Rivotril), 0.5mg tid.
 Propoxyphene (Darvon).
-41-
 Carbamazepine (Tegrctol), 200 mg tid.
 Clonidine (Catapres), 0.1mg tid.
Treatment of Sydenham's (Rheumatic) Chorea:
 Bed rest.
 Penicillin i.m.
 Ospen 500-1000 mg daily or Erythrocin 250mg bid until age
20 yrs.
 Haloperidol (Safinace) 1.5mg o.d.- tid.
 Reserpine (Serpasil) 0.25 mg qid.
 Chlorpromazine (Largactil, Neurazine) 25mg tid.
 Steroids if associated with carditis.
Treatment of Huntington's Disease:
A. Drug Treatment of Movement Disorders in Huntington's
Disease:
Chorea:
 Typical Neuroleptics:
R/ Haloperidol (Safinace) 1.5 mg & 5 mg tab.
(0.5-1 mg/d. ↑ up to 10-15 mg daily).
OR: Thioridazine (Melleril) 25mg & 100mg tab.
(10-25mg/d. ↑ up to 200 mg daily)
OR: Pimozide (Orap) 4 mg & 8 mg tab.
(1-2 mg /d. ↑ up to 10 mg daily)
OR: Fluphenazine (Modecate)
(0.5-1 mg/d. ↑ up to 10 mg daily)
 Atypical Neuroleptics:
R/ Risperidone (Risperdal) 2mg & 4 mg tab.
(0.5-1 mg/d. ↑ up to 6 mg daily)
OR: Clozapine (Leponex) 25 mg & 100 mg tab.
(25-50 mg/d. ↑ up to 150mg daily)
-42-
OR: Olanzapine (Zyprexa) 5 mg & 10 mg tab.
(5 mg/d. ↑ up to 20 mg daily)
OR: Quetiapine (Seroquel) 25mg , 50 mg & 100mg.
(25 – 50 mg/d. ↑ up to 750 mg daily)
 Dopamine Depletion or Receptor Blockade:
 Haloperidol (Safinace, Serenace, Haldol).
 Chlorpromazine (Largactil, Neurazine)
(50mg tid).
 Tetrabenazine (Nitoman).
 Reserpine (Serpasil) 0.25mg tab.
(0.5 mg qid in Sydenham's chorea).
 Propranolol (Inderal) 10mg & 40mg tab.
(For action tremor).
 Dantrolene Sodium (Dantrium) 25 mg cap.
(for chorea & hemiatrophy).
Dystonia:
R/ Trihexyphenidyl (Artane) 2mg & 5mg tab.
(1-2 mg bid. ↑ up to 4-5 mg tid).
OR: Baclofen (Lioresal) 10mg & 25 mg tab.
(5 mg/d. ↑ up to 60-80mg/d on tid or qid schedule)
OR: Clonazepam (Rivotril) 0.5 mg & 2 mg tab.
(0-25 mg/d. ↑ up to 6mg/d).
&/OR: Botulinum toxin (Botox A):
- Blepharospasm: 30-50 U.
- Torticollis: 200 U or more.
Myoclonus: (Brief Shock- like Jerks):
R/ Valproate (Depakine) 200mg & 500 mg tab.
(200 mg tid, ↑ gradually to achieve a serum level of 50-100
ug/ ml).
-43-
&/OR: Clonazepam (Rivotril) 0.5 mg & 2 mg tab.
(0.25 mg bid. ↑ up to 6mg/d).
Tics: (Repetitive stereotyped motor or vocal behaviors).
R/ Haloperidol (Safinace) 1.5 mg & 5 mg tab.
(0.5-1 mg/d. ↑ up to 10-15 mg/d).
OR: Pimozide (Orap Forte) 4mg & 8 mg tab.
(1-2 mg/d. ↑ up to 10 mg/d).
Rigidity & Spasticity:
R/ Tizanidine (Sirdalud) 2 mg& 4 mg tab.
(2 mg at bedtime. ↑ every wk up to 12-24 mg/d).
OR: Diazepam (Valium) 2 mg& 5 mg tab.
(2 mg tid. ↑ up to 10 mg tid-qid).
OR: Baclofen (Lioresal) 10mg& 25 mg tab.
(5 mg bid. ↑ up to 60-80 mg/d on tid or qid schedule).
Hypokinesi a Parkinsonism:
R/ Levodopa / Carbidopa (Sinemet) 250/25 mg tab
(100 mg/25 mg tid).
Seizures:
R/ AEDs
B. Drug Treatment of Psychiatric Symptoms in Huntington's
Disease (HD):
Mood Disorders:
 Selective Serotonin Reuptake Inhibitors (SSRIs):
R/ Fluoxetine (Prozac) (20mg – 60mg /d.)
OR: Sertraline (Lustral) (50mg- 250 mg / d)
OR: Paroxetine (Seroxat)( 20 mg – 40 mg / d)
OR: Citalopram (Cipram) (20mg- 60 mg/d)
-44-
OR: Escitalopram (Cipralex) (10mg- 20mg/d)
OR: Fluvoxamine(Faverin) 50mg&100mg (up to250-300mg/d)
 Other Antidepressants:
R/ Bupropion (Wellbutrin) (75-100 mg/ morning. ↑ up to 100
mg bid-tid.)
OR: Venlafaxine (Efexor) 37.5 mg, XR 75mg cap. & XR 150
mg cap
(37.5 mg/d. ↑ up to 75 mg XR bid- tid.).
OR: Nefazodone (Serzone) (100 mg tid)
OR: Mertazapine (Remeron) 30 mg tab.
(15-45 mg at bedtime.)
OR: Methylphenidate (Ritalin) 10 mg tab.
(5 mg morning. ↑ up to 10 mg/morning &/ noon).
Anxiety Disorders:
R/ Buspirone (Buspar) (5 mg / morning ↑ up to 10-60 mg/d.)
OR: Hydroxyzine (Atarax) (25mg o.d.- qid.)
OR: Alprazolam (Xanax) (0.5mg o.d- qid)
OR: Bromazepate (Lexotanil/ Calmepam) (1.5& 3 mg tab. o.d.
– tid.)
OR: Clorazepate (Tranxene) 5 mg tab. (5mg o.d.- tid)
Aggression, Irritability, & Dyscontrol:
R/ Propranolol (Inderal) 40 mg tab. (40 mg qid)
R/ Lithium (Priadel, Prianil) 300mg tab. (300-1200 mg/d).
Apathy:
R/ Methylphenidate (Ritalin) 10mg tab.
(5mg/ morning. ↑ up to 5 mg/morning& noon, then ↑by
5mg/ 3-4 days until response is achieved).
-45-
Psychosis:
R/ Risperidone (Risperdal) 2mg & 4 mg tab.
OR: Olanzapine (Zyprexa) 5 mg & 10 mg tab.
OR: Quetiapine (Serequel) 25 mg & 100 mg tab.
OR: Haloperidol (Safinace) 1.5 mg & 5 mg tab.
Insomnia:
R/ Mertazapine (Remeron) 30 mg tab.
(15-45 mg at bedtime).
OR: Trazodone (Trittico) 50 mg & 100 mg tab.
(100-600 mg at bedtime).
Sexual Disorders: (e.g. hypersexuality)
R/ Medroxyprogesterone acetate
R/ Leuprolid (Gonadotropin- RH agonist).
R/ SSRIs, (e.g.: Prozac, Faverin)
Other Therapies in Huntington's Disease:
 ECT in depression.
 Physical therapy.
 Speech therapy.
 Psychotherapy.
 Genetic Counseling.
 Riluzole (Rilutek)
(50mg bid. It ↓chorea & HD)
 Co-enzyme Q-10.
 Striatal transplantation.
Treatment of Wilson's Disease:
 Low copper diet: Avoid shellfish, liver, nuts, mushroom &
chocolates
-46-
R/ D-penicillamine (Artamin, Cuprimine)
(250 mg qid 30 min before or 2 hrs after meals).
OR: Trientine (Syprine)
(250mg qid 30 min before or 2 hrs after meals.)
R/ Zinc acetate (Gelzin)
50 mg tid for adults.
25mg bid for children < 6 yrs.
25 mg tid for children 6-16yrs.
Therapy for Neurologic Symptoms:
 Tremor.
 Parkinsonism.
 Dystonia.
 Chorea.
Therapy for Complications of Liver Failure:
Hepatic encephalopathy:
 Low-protein diet.
 Lactulose (Duphalac) (15-30 cc o.d- tid).
 Neomycin 250mg. tab (250- 500 mg qid)
Ascites & L.L. edema:
 Salt restriction.
 Aldactone 25mg & 100 mg. tab (25-100mg o.d.- bid).
 Electrolyte management.
Therapy for Psychiatric Symptoms:
 Anticopper therapy.
 Antipsychotics.
Surgery:
 For varices.
-47-
 Tendom lengthening.
 Hepatic transplantation.
Treatment of Hemiballismus:
R/ Reserpine (Serpasil) 0.25mg qid.
OR: Tetrabenazine(Nitoman) 2 & 5 mg tab. tid.
R/ Phenothiazines e.g. Stellazine 5mg tid.
OR: Haloperidal (Safinace) 1.5& 5 mg tid.
 Ventrolateral thalamotomy for chronic cases.
Treatment of Dystonia Musculolrum Deformans:
R/ Levodopa/ Carbidopa (Sinemet).
(250mg qid 30 min before or 2 hrs after meals.)
 Ventrolateral thalamotomy.
 Orthoses.
Treatment of Spasmodic Torticollis:
R/ Botulinum toxin (Botox A) injections.
 Sectioning the spinal accessory fibres & intradural section of
C1- C3 anterior nerve roots.
 Positional feedback therapy.
Paroxysmal Choreo-athetosis & Dystonia:
 Kinesogenic form of choreo athetosis:
R/ Carbamazepine (Tegreto) 200 mg tabs & 400 mg CR tab.
(200-400mg tid).
OR: Phenytoin (Epanutin) 50 mg & 100 mg cap.
(50-100 mg tid).
 Paroxysmal nonkinesogenic dystonia:
R/ Clonazepam (Rivotril) 0.5mg & 2 mg tab.
-48-
Treatment of Tics:
(e.g. Gilles de la Tourette's syndrome)
R/ Haloperidol (Safinace) 1.5mg & 5 mg tab.
(1.5-5mg tid)
OR: Pimozide (Orap) (12mg/d. ↑up to 16mg /d)
OR: Clonidine (Catapres), (0.1mg/d. ↑up to 2 mg/d).
OR: Tetrabenazine (Nitoman)
&/OR: Ca channel blockers:
R/ Nifedipine (Adalat, Epilat) 10 mg& 20mg.
OR: Flunarizine (Sibelium) 5mg&10 mg.
OR: Verapamil (Isoptin)
&/OR: Botulinum toxin (Botox A).
ADHD responds to:
R/ Desipramine (Norpramine)
R/ Clozapine (Leponex, Clozapex) 25mg & 100 mg tab.
OCD responds to:
R/ Fluoxetine (Prozac) 20mg cap.
(20-40 mg/d).
R/ Clomipramine (Anafranil) 25mg tab. & 75 mg SR tab.
(25mg tid, up to 75mg bid)
Treatment of Tremor:
 Action Tremor:
(Physiologic, Familial, Senile & Essential)
R/ Diazepam (Valium, Valpam, Valinil) 2mg , 5mg & 10 mg
tab. (2-5mg tid)
R/ Propranolol (Inderal), (40-240mg/d)
OR: Metoprolol (Lopressor), (50-100 mg bid)
OR: Nadolol (Corgard), (40-80mg / d)
-49-
R/ Primidone (Mysoline), (250-500mg/d)
R/ Glutethimide, (250-1000 mg/d)
± Botulinum toxin A (Botox A) in essential, rubral & cerebellar
intention tremor of limbs, but no head tremors.
 Orthostatic Tremor:
R/ Clonazepam (Rivotril, Apetril, Amotryl) 0.5 mg& 2mg tab.
(0.5-1mg/d)
 Asterixis:
(in metabolic disorders e.g. renal, hepatic, pulmonary, in
Wilson's disease, drug-induced e.g. AEDs, metoclopramide
(Plasil) Treat the cause.
Treatment of Myoclonus:
R/ Clonazepam (Rivotril) 0.5mg & 2 mg.
(1.5mg/d. ↑ over 4 wks up to 6-12mg/d).
R/ Valproic acid (Depakine) 200mg & 500mg
(up to 1600mg/d in posthypoxic type)
R/ Piracetam (Nootropil)
(18-24 gm/d)
R/ 5-Hydroxy tryptophan (5-HTP)
(150-1600mg PO daily in 2-4 doses ± Carbidopa).
R/ Tetrabenazine (Nitoman)
(in spinal myoclonus).
Treatment of Restless Legs Syndrome:
R/ Clonazepam (Rivotril) (0.5mg tid)
R/ Carbamazepine (Tegretol), (200mg tid).
R/ Levodopa/ carbidopa (Sinemet), (100/10 mg tid.)
R/ Bromocriptine (Parlodel), (2.5 mg tid)
R/ Clonidine (Catapres), (0.1 mg tid)
-50-
Treatment of Cerebellar Ataxia:
R/ Amantadine (Mantadix, Symmetrel, Adamine, Amantine)
100mg cap. (100mg/d. ↑ up to 100mg bid-tid).
R/ Buspirone (Buspar) 5 mg & 15mg tab.
(5mg o.d. or bid. ↑ up to 10-30mg/d).
R/ Acetazolamide (Diamox, Cidamex) 250 mg tab.
(250-500mg/d. ↑ up to 1000 – 4000 mg/d) It improves
episodic ataxia & vertigo
R/ Clonazepam (Rivotril, Apetril, Amotryl) 0.5 mg & 2 mg tab.
(0.5-6mg/d. Can reduce cerebellar tremor. May worsen
ataxia).
R/ Baclofen (Lioresal) 10mg & 25mg tab.
(10-25mg tid. It improves spasticity & nystagmus, but may
worsen ataxia).
R/ Physostigmine (Prostigmine).
(Oral or s.c. may be useful)
R/ Isoniazid (INH) 50, 100 & 200 mg tab.
(100-200 mg tid. Useful in kinetic tremor. May cause acute
cerebellar syndrome)
R/ Propranolol (Inderal) 10 mg & 40 mg tab.
(10-40 mg tid. Useful for postural tremor)
R/ Primidone (Mysoline) 250mg tab.
(Useful for postural tremor, but may worsen ataxia).
R/ Carbamazepine (Tegretol) 200 mg & 400 mg tab.
(200mg bid- tid improves cerebellar tremor)
R/ Gabapentin (Neurontin) 300 mg & 400 mg cap. (400 mg tid).
R/ Fluoxetine (Prozac) 20 mg cap.
(20mg/ morning. It improves pseudobulbar affect & motor
dysfunction)
R/ Botulinum toxin type A (Botox A)
(15-25 U per muscle. Controls head nodding & tremor)
-51-
 Thalamatomy or Thalamic Stimulation control tremor
unresponsive to drugs.
 Physical & Speech therapy are helpful.
 Complementary Medicine e.g. acupuncture & chiropractic
may relief pain.
 Antioxidants e.g. Vit. E, Coenzyme Q-10, Riluzole (Rilutek).
-52-
PAROXYSMAL DISORDERS
EPILEPSY
Antiepileptic Drugs (AEDs):
 Conventional AEDs:
 Phenobarbital (Luminal, Sominal) 60 mg tab.
 Phenytoin (Epanutin) 50 mg & 100 mg cap, Susp.
 Carbamazepine (Tegretol). 200 mg, CR 200 mg, CR
400mg, Syrup
 Primidone (Mysoline).250 mg tab., syrup
 Ethosuximide (Zarontin) for PME. 250mg cap. syrup
 Methsuximide (Celontin) for PME.
 Valproic acid (Depakine) Broad spectrum. 200 mg, Chromo
500 mg, Syrup, Drops
 Clonazepam (Rivotril) for PME & Myoclonus. 0.5 mg & 2
mg tab., drops
 Diazepam (Valium i.v.) for status epilepticus. 10mg amp. &
5 mg rectal tubes
 ACTH for infantile spasms, 40-60 U/d i.m.
 New AEDs:
 Clobazam (Frisium). 10 mg tab.
 Oxcarbazepine (Trileptal). 150 mg, 300 mg & 600 mg tab.,
surup 60 mg/ml
 Tiagabine (Gabitril).
 Topiramate (Topamax). 25mg , 50mg & 100 mg tab.
 Vigabatrin (Sabril). 500 mg tab.
 Zonisamide (Excegran).
 Gabapentin (Neurontin).300mg & 400mg cap
 Lamotrigine (Lamictal).25mg , 50 mg & 100mg tab.
 Felbamate (Felbatol).
 Levitiracetam (Keppra, Tiratam). 250 mg & 500mg & 1000
mg tab., syrup
-53-
Choice of AEDs According to Seizure Types:
Partial Seizures (without secondary generalization):
● Clobazam (Frisium)
● Tiagabine (Gabitril)
● Felbamate (Felbatol)
● Topiramate (Topamax)
● Gabapentin (Neurontin)
● Vigabatrin (Sabril)
● Lamotrigine (Lamictal)
● Zonisamide (Excegran)
● Oxcarbazepine (Trileptal)
Primary Generalized Tonic- Clonic Seizures:
● Clobazam (Frisium)
● Phenytoin (Epanutin)
● Lamotrigine (Lamictal)
● Phenobarbital (Luminal)
● Topiramate (Topamax)
●Carbamazepine(Tegretol)
● Zonisamide (Excegran)
●Valproic acid (Depakine)
Atonic Seizures:
● Clobazam (Frisium)
● Felbamate (Felbatol)
● Lamotrigine (Lamictal)
● Vigabatrin (Sabril)
● Zonisamide (Excegran)
Myoclonic Seizures:
● Clobazam (Frisium)
● Lamotrigine (Lamictal)
● Zonisamide (Excegran)
● Levitiracetam (Keppra, Tiratam)
Absence Seizures:
● Clobazam (Frisium)
● Zonisamide (Excegran)
● Loreclezole
● Primidone (Mysoline)
●Valproic acid (Depakine)
● Ethosuximide (Zarontin)
●Methsuximide (Celontin)
●Valproic acid (Depakine)
-54-
Treatment of Status Epilepticus:
Minutes
0-5
6–9
Action
 Confirm diagnosis by observing seizure activity or one
additional seizure.Oxygen by nasal cannula or mask;
control head position & airway; evaluate for intubation
if ventilatory assistance needed
 Obtain & record vital signs, continue to observe; treat
any abnormalities; establish ECG recording
 Obtain IV access, keep open with 0.9% saline; use
glucometer or draw venous blood for glucose, serum
chemistries, hematology, toxicology & AED
levelsEvaluate oxygenation with oximetry or arterial
blood gas determination
 If hypoglycemic, or if blood sugar measurement is not
available, give glucose: adults 100 mg thiamine IV followed
by 50 ml 50% glucose by IV push; children 2 ml/kg of 25%
glucose
10 –20


20+

In adults, administer IV either 0.1 mg/kg lorazepam
(Ativan) at 2 mg/min up to 4 mg total dose, or 0.2
mg/kg of diazepam (Valium) at 5 mg/min up to 20 mg
maximumDiazepam can be repeated if seizures
continue after 5 minutes
Diazepam must be followed by loading with phenytoin
(Epanutin)
Load with 20 mg/kg phenytoin no faster than 50
mg/min in adults & 1 mg/kg/min in children; monitor
ECG and blood pressure during infusion; IV fluids
must be 0.9% salineFosphenytoin may be given at 150
phenytoin equivalents/min as a safe substitute for
phenytoin
-55-
>60





If status continues after 20 mg/kg phenytoin, give
additional phenytoin or fosphenytoin at 5 mg/kg until a
maximum of 30 mg/kg
If status persists, give 20 mg/kg of phenobarbital IV
at 60 mg/min
Expect apnea, particularly if the patient has received
benzodiazepines
Assist ventilation; intubation will be required
If status persists, use anesthesia with Pentobarbital
(Nembutal), midazolam (Dormicum), or proprofol
(Diprivan), intubation, ventilation & vasopressors will
be required
Protocol for Refractory Status Epilepticus:
 The patient must be managed in an ICU, intubated & placed
on a mechanical ventilator. Control of airway & ventilation
will prevent aspiration pneumonia. The patient must be
monitored with an intensive care protocol that includes
recording BP, temperature, pulse & respiratory function.
Arterial access will allow assessment of blood gases.
Cardiovascular monitoring is facilitated by placement of a
Swan-Ganz line. Strict input & output require bladder
catheterization with a Foley catheter.
 Venous access is required, either a triple- lumen port or largebore peripheral IV for fluid bolus or dopamine administration.
 Midazolam (Dormicum): load with 0.2 mg/kg as a slow bolus
& maintain at 0.75-10 µg/kg/min.
 Propofol (Diprivan): initiate with 1-2 mg/kg & maintain at 210 mg/kg/hr.
 Pentobarbital (Nembutal): continuous EEG monitoring is
required during induction of the pentobarbital coma. Loading
dose is 10-15 mg/kg IV at an infusion rate of 50 mg/min until
a burst suppression pattern or electrocerebral inactivity is
-56-






observed on the EEG. Strive for 1 to 2 seconds of bursts & 5
to 10 seconds of suppression on the EEG. Pentobarbital
plasma level should be measured immediately after
administration of the initial or loading dose.
The maintenance dose of pentobarbital is 0.5-1.0 mg/kg/hr.
If hypotension develops, the rate of administration of the
loading dose can be decreased to 25 mg/min. this change in
the maintenance dose can be achieved by decreasing the dose
to 0.5 mg/kg/hr. hypotension is managed with fluid bolus or
dopamine to maintain a serum level of 10-20 mg/ml initially.
Maintain general anesthesia for an initial 12 hours, then
assess a minimum of every 24 hours if seizures continue.
All other AEDs should be continued while the patient is
initially controlled with pentobarbital coma.
Record an EEG daily
Continue to follow a schedule of anesthetic tapering &
assessment.
Treatment of Febrile Convulsions:
 Control fever by sponging & antipyretics.
 Control convulsions by I.V. diazepam 0.3 mg / kg.
 Intermittent rectal diazepam therapy at the onset of fever or at
the onset of a seizure.
 Chronic treatment with Phenobarbital (4-5 mg/kg) in a single
nocturnal dose for 2 years.
OR:
 Chronic treatment with Sod. Valproate (20-30 mg/kg/d) for 1
year.
N.B.: Phenytoin & Carbamazepine are apparently ineffective in
febrile convulsions.
-57-
Treatment of Intractable Epilepsy:
 New AEDs.
 Vagal Nerve stimulation.
 Epilepsy surgery:
 Resections- lesionectomy.
 Hemispherectomy-multilobar resections.
 Multiple subpial transactions.
 Commissurotomy-corpus callosotomy
(for 1 ry & 2ry generalization & atonic seizures)
Treatment of Narcolepsy:
 Sleep attacks, hypnagogic hallucinations & sleep paralysis:
R/ Methylphenidate (Ritalin) 10 mg tab.
(20-200 mg/d in 2-3 doses)
OR: Methamphetamine HCL (Fetamin)
(20-200 mg/d. in 2-3 doses)
OR: Dextroamphetamine Sulfate (Dexedrine),
(20-200mg / d in 2-3 doses)
OR: Phenelzine sulfate (Nardil)
(15-75. mg/d. in 3-4doses)
OR: Tranylcypromine (Parnate)
(10-30mg/d in 2 doses)
OR: Isocarboxazid (Marplan)
(10-30 mg/d in a single dose)
 Cataplexy (Attacks of loss of postural tone):
R: Imipramine (Tofranil) 25mg tab.
(50-100 mg/d in 1-3 doses)
 Sleep Attacks & Cataplexy:
R: Imipramine (Tofranil), (25mg tid.)
R: Methylphenidate (Ritalin), (5-10mg tid)
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MIGRAINE
Migraine Treatment:
1- Nonpharmacologic treatments.
2- Treatment of the acute attack.
3- Long-term prophylactic therapy.
Nonpharmacologic Approaches:
 Avoidance of trigger factors e.g. alcohol & tyramine
containing foods.
 Regular exercise & mealtimes, adequate sleep.
 Relaxation
techniques,
biofeedback,
hyponosis
&
psychotherapy.
 Dark quiet room.
 Ice packs on head.
 Blocking the greater & lesser occipital nerves in the
suboccipital crease:
Treatment of Prodrome:
R/ Domperidone (Motilium) 10 mg tab.
(30 mg dose).
OR: Metoclopramide (Primperan)
Treatment of Aura:
 Inhaling 10% CO2 with 90% O2 → v.d. → Aborting migraine
aura.
 Low-dose amyl nitrite inhalation & sublingual nefedipine
(Adalat) 10 mg.
 Sodium valproate (Depakine) for persistent visual aura.
 I.V. prochlorperazine(Compazine) 10-25mg or corticosteroids.
Treatment of Migraine Attacks;
R/ Aspirin 325 tab. (650mg/ 4 hrs).
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OR: Paracetamol (Panadol) 500 mg tab. (2 tabs prn)
OR: Diclofenac potassium (Catafast) 50 mg Graunles.
(1 sachet prn)
OR: Ketoprofen (Orudis) (75mg tid).
OR: Ibuprofen (Brufen) 200, 400, 600 & 800 mg tab.
(400-800 mg tid).
OR: Naproxen (Naprosyn)
(250 mg tid)
OR: Mefenamic (Ponstan) 250 mg & 500 mg tab
(250mg bid - tid)
OR: Diclofenac (Voltaren) 25 mg, 50 mg , 75mg , 100mg tab,
75mg amp. & 100mg supp.
(25 mg tid, 50 mg bid, 75-100mg o.d).
OR: Indomethacin (Indocid) 250mg cap & 500 mg supp.
R/ Ergotamine (Cafergot, Migrainil, ….) tab., supp.
(2tabs or 1 supp. prn)
OR: Dihydroergotamine (DHE) inj., intranasal
(1ml i.m. or i.v. , or intranasal prn).
OR: Sumatriptan (Imigran)
(50&100 mg tab. or 6mg s.c., or intranasal prn).
OR: Zolmitriptan (Zomig) 2.5 mg tab.
OR: Risatriptan (Maxalt) 5 mg & 10 mg tab.
OR: Naratriptan (Naramig) 2.5 mg tab.
(1 tab prn).
Migraine Prophylactic Treatment:
R/ Propranolol (Inderal) (80-320 mg/d.)
OR: Atenolol (Tenormin) (50-100 mg/d.)
R/ Flunarizine (Sibelium) (5-10 mg/d.)
OR: Verapamil (Isoptin) (30-60 mg daily)
R/ Pizotifen (Mosegor) tab (1 tab tid)
-60-
OR: Methysergide (Deseril) (4-8 mg/d).
OR: Cyproheptadine (Periectin) (4-16 mg/d)
R/ Amitriptyline (Tryptizol) (10-50mg/d).
OR: Nortriptyline (Motival) (25-75mg/d)
R/ Clonidine (Catapres) 0.1, 0.2 & 0,3 mg tab.
(0.1 mg tid)
CLUSTER HEADACHE
Abortive Treatment:
R/ Oxygen 100% inhalation
(by face mask, at 7 L/min. for 15 min. prn)
R/ Dihydroergotamine (DHE) intranasal solution
(1m/hr. up to 3 ml/ day)
R/ Lidocaine (Xylocaine) 4% solution
(15-16 drops to affected nostril prn up to 4 times/d).
R/ Phenylephrine (Neo-Synephrine) 0.5% nasal solution.
(3-5 min before intilling lidocaine).
R/ Cocaine HCL 10% nasal solution
(2 drops into affected nostril or both nostrils qid prn).
R/ Ergotamine tartrate + Cafeine (Cafergot or Migrainil) tabs or
supp.
(2 tabs at onset, repeat every 30 min up to 6 tabs/ d., or 1
supp at onset, repeat in 1 hr if needed, up to 2/d).
Prophylactic Treatment:
R/ Methysergide maleate (Deseril)
(2mg tid)
R/ Prednisone (Hostacortin)
(40mg/d in divided doses)
OR/ Methylprednisolone (Urbason)
(16mg/ other day).
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R/ Ergotamine tartrate+Phenobarbital+ Bellafoline (Bellergal-S)
(1 tab bid)
R/ Lithium Carbonate (Priadel, Prianil)
(300 mg tid)
R/ Verapamil (Isoptin).
(240 mg/d)
TENSION- TYPE HEADACHE
Treatment:
 Coping with stress.
 Relaxation exercises.
 Neck or back massage.
 Biofeedback
 Antidepressant for depressed pts:
R: Amitriptyline (Tryptizol).
OR: Desipramine (Norpramin).
OR: Doxepin (Sinequan).
OR: Impiramine (Toframil).
OR: Nortriptyline (Aventyl).
OR: Protriptyline (Triptil)
OR: Trazodone (Trittico).
OR: Fluoxetine (Prozac).
OR: Bupropion (Wellbutrin)
OR: Maprotiline (Ludiomil).
OR: Sertraline (Lustral).
OR: Paroxetine (Seroxat).
Headache Presenting in the Emergency Department e.g.:
1. Subarachnoid hemorrhage (SAH).
2. Meningitis .
3. Temporal arteritis.
-62-
4.
5.
6.
7.
Hypertension (HTN).
Migraine.
Cluster headache.
Tension- type. headache.
Treatment:
 Treatment of the cause.
 Symptomatic Treatment:
R/ Dihydroergotamine mesylate (D.H.E. 45).
(1mg i.m or slowly i.v. up to 2 mg/d, 6 mg/wk).
+ Metoclopramide (Primperan) 10 mg i.m.
OR: Sumatriptan (Imigran)
(6 mg s.c., repeated after 1hr, max 12mg/d).
R/ Ketorolac (Toradol)
(60 mg i.m, up to 120 mg/d)
R/ Chlorpromazine (Largactil, Neurazine)
(50-100 mg i.m. / 4 hrs for 2 injections/d or 100mg rectal
prn).
R/ Naproxen sodium (Naprosyn) tab.
(25mg / 4 hrs up to 750 mg/d).
OR: Ketoprofen (Orudis)
(50 mg/4hrs up to 200 mg/d).
OR: Ibuprofen (Brufen)
(800 mg/4 hrs up to 3200 mg/d).
Treatment of Sstatus Migrainosus:
R/ Dihydroergotamine (D.H.E. 45) (1mg slowly i.v.).
R/ Chlorpromazine (Largactil, Neurazine)
(1 mg / kg slowly i.v/ 12 hrs)
OR: Dexamethasone acetate (Decadron)
(16mg i.m. or 1.5mg p.o. bid).
-63-
TRIGEMINAL NEURALGIA
Drug Treatment:
R/ Carbamazepine (Tegretol)
(200-600 mg/d)
OR: Oxcarbazepine (Trileptal)
(150-600 mg bid)
R/ Phenytoin (Epanutin) 50 & 100 mg cap.
(200-400mg/d)
R/ Gabapentin (Neurontin) 300 & 400 mg cap.
(400mg tid)
R/ Amitriptyline (Tryptizol) 25 mg tab.
(25-75mg/d)
R/ Baclofen (Lioresal) 10 & 25 mg tab.
(30-80 mg/d)
Surgical Treatment:
 Glycerol injection (85% effective).
 Radiofrequency rhizotomy (90% effective)
 Microvascular decompression (90% effective).
-64-
ALZHEIMER'S DISEASE (AD)
A- Disease-Modifying Drugs:
 Neurotropic drugs (For apoptosis).
 Antioxidant Vitamins & drugs (for oxidative stress):
R/ Vitamin E 1000 1x1
R/ Omega-3 1x1.
R/ Antox tab. 1x1.
R/ Selenium 1x1
 Glucocorticoids (for inflammation: complement, acute phase
response)
R/ Solupred 20 mg tab. o.d.
 Hydroxychloroquine, Colchicine (for inflammation, microglia)
R/ Colmediten tab. bid-tid.
 NSAIDs, Glucocorticoids (for inflammation: Cyclooxygenase)
R/ Brufen tab. (400-600 mg bid)
R/ Solupred 20mg tab. (o.d.)
 Colchicine, Antiaggregants, Cholinergic drugs (for amyloid
deposition).
R/ Colchicine (Colmediten) tab. bid-tid.
R/ Aspirin (Jusprin) tab. o.d.
R/ Donepezil, Rivastigmine, … etc. (see later).
 Glutamate antagonists (for excitotoxicity).
R/ Memantine (Ebixa) 10 mg tab. bid.
 Calcium- channel blockers (for calcium influx).
R/ Flunarizine (Sibelium) (5mg/d).
 Chelators (for heavy metal toxicity).
R/ D-penicillane (Artamin) (250 mg cap qid).
B. Disease- Specific Treatments:
 Cholinesterase Inhibitors:
R/ Donepezil (Aricept) 5 & 10 mg tab.
-65-
(5-10 mg o.d.)
OR/ Rivastigmine (Exelon) 1.5 , 3 & 6 mg tab.
(1.5-6 mg bid)
OR/ Galantamine (Reminyl)
(16-24 mg bid)
 Glutamate Antagonists:
R/ Memantine (Ebixa) 10 mg tab.
(10 mg bid)
C. Adjunctive Therapy:
 Non-cognitive drug treatment:
R/ Venlafaxine (Efexor XR) 75mg & 150 mgcap.
(75-300 mg/d)
OR/ Escitaloram (Cipralex) 10 mg tab.
(10-20 mg/d)
OR/ Sertraline (Lustral) 50 mg tab.
(50-200 mg/d)
OR/ Fluoxetine (Prozac) 20 mg cap.
(20-40 mg/d)
OR/ Paroxetine (Seroxat) 10 mg
(10-40mg/d)
Anxiety:
R/ Lorazepam (Ativan) (0.5-1mg tid)
OR/ Alprazolam (Xanax) (0.25-1.25mg tid)
OR/ Buspirone (Buspar) (5-10 mg tid)
Agitation:
R/ Trazodone (Trittico) (50-100 mg/d).
OR/ Haloperidol (Haldol, Safinace) (0.5-3 mg/d).
OR/ Risperidol (Risperdal) (0.5-3mg / d).
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OR/ Thioridazine (Melleril) (30-60 mg/d).
Delusions:
R/ Risperidol (Risperdal) (0.5-3mg/d).
OR: Olanzepine (Zyprexa)
(2.5-15mg/d)
OR: Clozapine (Leponex)
(6.25-50 mg/d)
OR: Quetiapine (Serequel)
(25-100 mg/d)
Insomnia:
R: Trazodone (Trittico) (50-100mg/d)
OR: Zolpidem (Stilnox) (5-10 mg/d)
 Congitive- Enhancers:
R: Ginkgobiloba (Tebonina) (40mg tid)
OR: Piracetam (Nootropil) (800 mg tid)
OR: Pyritinol (Encephabol) (200 mg tid)
OR: Meclofenoxate (Lucidril) (500 mg bid)
R: Co-Dergocrine (Hydergine) (1.5 mg bid)
OR: Piribedil (Trivastal) (50 mg bid)
OR: Nicergoline (Sermion) (5-10 mg tid)
OR: Cinnarizine (Stugeron) (25mg tid).
R: Naftidrofuryl (Praxilene) (200 mg bid)
OR: Pentoxifyline (Trental) (400 mg bid)
OR: Vincamine (Oxybral) (30 mg bid)
R: Flunarizine (Sibelium) (5mg/d)
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DEMYELINATING DISORDERS OF THE CNS
MULTIPLE SCLEROSIS (MS)
Therapeutic- Protocol of MS:
1. Symptomatic Treatment.
2. Immunotherapy.
3. Aerobic Exercise Program, 3 times/wk.
4. Neurorehabilitation.
A. Symptomatic Treatment in MS:
Spasticity:
R/ Baclofen (Lioresal) (10 & 25 mg tab)
(30-100 mg/d, Intathecal up to 200mg /d)
OR: Tizanidine (Sirdalud) 2 & 4 mg tab. (6-24mg/d)
OR: Dantrolene (Dantrium) 25mg cap (100-400 mg/d)
OR: Diazepam (Valium) 2,5&10 mg tab. (2-30mg/d)
&/OR: Botulinum toxin (Botox-A) (For local infiltration)
Fatigue:
R/ Amantadine (Adamine) (100 mg cap, bid)
OR: Pemoline (Cylert), (37.5 mg/d)
OR: Aminopyridine (Fampridine) (10 mg bid-tid)
R/ Fluoxetine (Prozac) (20-40 mg/d)
MS- related acute pain:
R/ Carbamazepine (Tegretol) (100-200 mg bid-tid)
R/ Baclofen (Lioresal) (10-25 mg tid)
MS-related chronic pain:
R/ Amitryptiline (Tryptizol) (25-50 mg tid)
R/ Carbamazepine (Tegretol) (100-200 mg bid-tid)
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R/ Baclofen (Lioresal) (10-25 mg tid)
+ Physiotherapy ± Surgical procedures.
Musculoskeletal Pain:
R/ Ibuprofen (Brufen), (600-800 mg bid.)
Pain due to Paroxysmal Symptoms:
R/ Carbamazepine (Tegretol)
(100-200 mg tid)
R/ Gabapentin (Neurontin) cap
(400 mg tid)
Pain due to Spasticity: (see spasticity)
Bladder Dysfunetion:
R/ Oxybutynin (Uripan) 5 mg tid.
R/ Desmopressin (Minirin)
 Clean intermittent self- catheterization (CISC)
Tremors:
 Medical treatment:
R/ Carbamazepine (Tegretol)
R/ Clonazepam (Rivotril)
R/ Primidone (Mysoline)
R/ Propranolol (Inderal)
R/ Clozapine (Leponex)
 Surgical:
Stereotactic surgery
 Physical:
Weight application.
Sexual Dysfunction:
R/ Papaverine (Vasorin) (intracorporeal inj)
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OR: Prostaglandin E (Caverject) (Intracorporeal inj)
OR: Sildenafil (Viagra) (50-100 mg PO prn).
+ Lubricants
 Penile prosthesis is rarely done nowadays.
Vertigo:
R/ Ondansetron (Zofran).
OR: Dramamine tab (tid).
OR: Betasere 8mg & 16mg (tid)
Temperature & Exercise Sensitivity & Weakness:
R: 4-aminopyridine (Fampridine)
Seizures & Other Paroxysmal Disorders (AEDs):
Depression: SSRIs or TCAs
Forced Pathological Crying & Emotional Instability: SSRIs.
B. Immunotherapy of MS:
1. Glucocorticoids & ACTH: for MS relapses:
R/ IV Methylprednisolone (Solu- Medrol)
(500-1000 mg/d. for 3-5-10 days)
R/ Oral Prednisone (Hostacortin) 5 mg tab.
(1 mg/ kg/ d).
R/ ACTH (Synacthen- Depot) Amp.
(1 inj im. every 3-7 days)
2. Conventional Immunosuppressive Treatments:
R/ Azothioprine (Imuran) 50 mg
(for RRMS, 50 mg PO tid)
OR/ Cyclophosphamide (Cytoxan, Endoxan), for CPMS
(IV 400-500 mg / d for 2 wks)
OR/ Cyclosporin (Sandimmun)
(5 mg/ kg/d. in 2 divided doses)
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3- Immunomodulators:
 Interferon (IFN-β):
R/ Interferon B-1b (Betaferon)
(low:6m/u & High: 8 m/u, s.c./other day)
OR: Interferon β-1a (Avonex)
(6 M/U i.m. every week)
OR: Interferon β-1a (Rebif)
(Low: 6MIU s.c. 3 times wk, High: 12MIU s.c. 3 times/ wk)
 Copolymer-1 (Copaxone), 20 mg s.c./ d.
4. Acyclovir (Zovirax), PO 800 mg tid.
5- Other Drugs:
 IV Immunoglobulin (IV Ig)
 Methotrexate (Rheumatrex)
(Po 2.5 mg 3 times weekly, in SPMS & PPMS)
 Cladribine (Leustatin)
(0.07 mg/ kg s.c. 5days each month for 10months in CPMS).
 Mitoxantrone (Novantrone)
(12mg / m2 or 5mg/m2 i.v. every 3 months)
 Sulfasalazine (Salazopyrin).
(PO 2 gm daily, in RRMS & SPMS)
Immunotherapy of MS (Summary):
R/ Solu-Medrol (For relapses)
(500-1000mg i.v. infusion over 2hrs daily for 5 days)
R/ Solupred 20mg tab.
OR/ Hostacortin 5 mg tab.
(1mg/kg body wt/ morning, to be gradually ↓ to 10-20 mg
daily maintenance dose)
± Synacthen- Depot Amp.
(1 injection every 3-7 days)
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 First- line treatment with IFN- beta:
R/ Betaferon (8 MIU s.c. / other day)
OR: Rebif (12 MIU s.c. 3 times/ wk)
OR: Avomex (6 MIU i.m./ wk)
 Second-line treatment with Copaxone, IV IgG
or
Immunosuppressants:
R/ Copaxone (20 mg s.c./ d)
R/ Intragram (IV IgG) (0.2 gm/ kg i.v./ month)
OR/ Gammagard (IV IgG) (0.2 gm/ kg i.v./ month)
R/ Imuran 50 mg tab. (2-3 mg/kg/d in 1-3 doses)
Management of Side Effects due to treatment with IFN- beta,
Copaxone, IV IgG or Immunosupressants:
 Injection- site reactions (with IFN-beta & Copaxone):
 Proper injection techniques.
 Rotation injection sites.
 Cold application & Topical steroids.
 Warming of the drug to room temp. prior to inj.
 Flu-like symptoms (with INF- beta):
 Start at low dose (25-50%) for 2-4 wks.
 Panadol, Aspirin, Brufen prn.
 Analgesics 4hrs prior to inj, at the time of inj. 4 hrs after
inj & before bedtime.
 Depression (é. INF- beta): Antidepressants.
 Neutralizing antibodies (NAB) with INF beta:
 Change to a second- line treatment.
 Thromboembolic complications (with IV IgG):
 Stop treatment
 Eczema: Steroids.
 Headache: Aspirin.
 High fever (with Immunosuppressants): Aspirn.
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OPTIC NEURITIS
Treatment of Optic Neuritis:
R/ Methylprednisolone (Solu- Medrol)
(250mg / 6 hrs or 100 mg/d. for 3-5 days), followed by:
R/ Prednisone (Hostacorten 5 mg tab), or Solupred 20 mg tab.
(1mg/ kg body wt daily for 11 days)
ACUTE TRANSVERSE MYELITIS
Treatment of Acute Transverse Myelitis:
(May be idiopathic, postvaccinal, or postinfectious, or due to
MS)
R/ Methylprednisolone (Solu- Medrol)
(500-1000 mg i.v. daily for 5 days), followed by:
R/ Hostacorten 5 mg tab.
(1 mg/kg body wt daily)
ACUTE DISSEMINATED ENCEPHALOMYELITIS
Treatment of Acute Disseminated Encephalomyelitis(DEM):
(May be postvaccinal or postinfectious)
R/ Methylprednisolone (Solu- Medrol)
(500mg/d q12 hrs for 3 days), followed by:
R/ Prednisone (Hostacorten) 5 mg tab.
(60-80 mg/d for 7 days, then taper by 20mg each wk)
R/ Mannitol 20% i.v. 250 ml over 20 min, for cerebral edema.
R/ AEDS for Seizures.
+ Supportive measures.
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CNS INFECTIONS
PYOGENIC MENINGITIS
General Medical Care:
1. Treatment of Systemic Complications:
 Septic shock: volume replacement + pressors
 Shock with infarction of adrenals : Steroids.
 Avoid overhydration.
 Control fever: Aspegic i.v. or Paracetamol, & baths in
tepid water
 Isolation
2. Treatment of Predisposing Factors: Paraneningeal septic
foci: Antibiotics ± Drainage.
 Foci of systemic sepsis: Prolonged antibiotics.
A. Initial Therapy of Bacterial Meningitis:
 Neonates:
R/ Ampicillin.
+ R/ Gentamicin (Garamycin)
OR
R/ Ampicillin.
+ R/ Ceftriazone (Rocephin)
OR
R/ Vancomycin (Vancocin)
+ R/ Gentamicin (Garamycin)
 Infants & Children:
R/ Ampicillin.
+ R/ Chloramphenical.
OR: Ceftriaxone (Rocephin)
OR
R/ Erythromycin (Erythrocin)
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+ R/ Choramphenicol.
 Adults:
R/ Ampicillin.
+R: Ceftriaxone (Rocephin)
OR
R/ Erythromycin (Erythrocin)
+ R/ Choramphenicol.
 Neurosurgical Infection:
R/ Vancomycin (Vancocin).
+R: Ceftazidime (Fortum)
OR
R/ Vancomycin (Vancocin)
+ R/ Gentamicin (Garamycin)
 Basilar skull facture or CSF leak:
R/ Vancomycin (Vancocin).
+R: Ceftazidime (Fortum)
OR
R/ Erythromycin (Erythrocin)
+ R/ Choramphenicol.
 Immunosuppression or Malignancy:
R/ Ampicillin.
+R: Ceftazidine (Fortum)
OR
R/ Erythromycin (Erythrocin)
OR: Vancomycin (Vancocin)
+ R/ Gentamicin (Garamycin)
B. Antibiotic Therapy for Bacterial Meningitis of Known
Etiology:
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Organism
Drug of choice
Gram-positive organisms
Streptococcus pneumoniae Ceftriaxone plus
(pneumococcus)
vancomycin
Streptococcus, groups A & Penicillin G
B
Optional
Alternative (for pts.
intrathecal
allergic to penicillin)
drug
Ceftriaxone plus
rifampin
Erythromycin
Erythromycin
Streptococcus, group D
(enterococcus)
Staphylococcus
Penicillin
&gentamicin
Oxacillin or nafcillin
Vancomycin &
gentamicin
Vancomyicn
Listeria monocytogenes
Ampicillin
Penicillin G
Trimethoprimsulfamethoxazole
Chloramphenicol
Third-generation
cephalosporin
Chloramphenicol
Chloramphenicol
Gram-negative organisms Penicillin G
Meningoccvcus
Haemophilus influenzae
Ampicillin or thirdgeneration
cephalosporin
Enteric gram-negative
Third- generation
rods
cephalosporin or
(Escherichia coli, proteus ticarcillin plus
species, Klebsiella
gentamicin
species)
Pseudomonas aeruginosa Ticarcillin (or
ceftazidime) plus
gentamicin
Gentamicin
Bacitracin
Gentamicin IV & IT Gentamicin
Gentamicin IV & IT Gentamicin
C. Intrathecal Antibiotics:
 Intralumbar, intracisternal, or intraventricular, garamycin in
gram-negative meningitis & in enterococcal meningitis.
 Intathecal Bacitracin 5000-10000 units in staphylococcal
meningitis.
Corticosteroid Therapy of Bacterial Meningitis:
1. Infants & Children:
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R/ Dexamethasone (Decadron)
(0.15 mg/kg wt q6 hrs for the first 4 days)
2. Adults:
R/ Prednisone (Hostacortin) 40-80 mg/d.
3. For cerebral oedema.
4. If suspecting adrenal necrosis.
Prophylactic Treatment of Contacts:
1. Chemoprophylaxis:
R/ Rifampin (Remactone)
 Adults: 600 mg PO q 12 hrs for 4 doses.
 Infants & Children: 10 mg/kg q 12 hrs for 4 doses.
 Close contacts:
R/ Procaine Penicillin G
(600.000 units i.m. q 6 hrs for 6 doses), then
R/ Penicillin V.
(500 mg PO q 8 hrs for 8 days)
2. Vaccination confers protection after 5 days.
3. Children < 6 yrs of age who are contacts of pts with H.
influenzae meningitis
R/ Rifampin (Rimactane)
(20 mg/kg PO daily for 4 days)
Treatment of Shunt Infection:
 Removal of the Shunt.
 Systemic antibiotics.
 Vancomycin (Vancocin) instillation via the drainage cannula.
Treatment of Complications of Meningitis:
1. ↑ ICP:
 Avoid repeated L.Ps.
 Avoid overhydration.
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 1500 ml of normal saline / d in adults.
 500 – 750 ml half normal saline in 5% D/W.
R/ Dexamethasone (Decadron)
(10 mg i.v. initially, then 4-6 mg i.v. q 6 hrs for few days, then
gradual tapering of dose to zero over 5-10 days).
R/ Mannitol 20%
Adults: 1-1.5 gm/kg initially, then 0.25-0.5gm/kg q 4 hrs for 3
doses.
Children: 0.25-1 gm/kg i.v, over 10-30 min.
R/ Furosemide (Lasix) 0.5 mg/kg.
2. Seizures: AEDs
3. Hydrocephalus:
 Early: Treatment by constant ventricular drainage of infected
CSF.
 Ventriculoperitoneal or Ventriculo- atrial shunt is placed
after CSF become sterile.
4. Subdural Effusion:
 Repeated percutaneous aspiration of the fluid ± Excision of
membrane.
5. Subdural Empyema:
 Surgical drainage + appropriate antibiotic after culture &
sensitivity test.
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TUBERCULOUS MENINGITIS
(CNS T.B. includes: T.B. meningitis, Tuberculoma, T.B.
encephalitis & T.B. CNS vasculitis with brain infarcts).
Treatment:
1. Antituberculous Therapy:
a) First- line drugs:
 Isoniazid (INH) (Inhibex), 5mg/kg / day PO in adults, &
10-20 mg/kg/day in children +Pyridoxine, 50mg/day for
all pts > 6yrs old, to prevent pyridoxine-deficiency
syndromes (neuropathy, encephalopathy, seizures, &
anemia)
 Rifampin (Rimactane, Rifadin), 600mg/day PO in adults
& 10-20mg/kg/day PO in children, not to exceed
600mg/day
 Pyrazinamide (Tebrazid, Pyrazid) 500mg tabs, 15-30
mg/kg/ day PO in both children & adults, divided into 3
or 4 doses. Max. 2gm/day.
 Ethambutol (Myambutol, Etibi, 100, 200, 400mg tabs),
15-25 mg/kg/day PO in both adults & children. Max. 2.5
gm/day
b) Second-line drugs:
 Streptomycin, 15mg/kg/day (max. 1gm/day) in adults
&20-40mg/kg/day in children IM, for not more than 12
wks (8th n. & renal toxicity)
 Ethionamide 0.5-lgm daily PO divided into 2-4 doses
(GI, liver, & CNS toxicity)
 Ciprofloxacin (Ciprobay, Ciprodar, Ciproflox), 750mg
PO bid.
c) Antituberculous Regimen:
 For the first 2 mns, 4 drugs:
 Isoniazid, 300mg/day, &
 Rifampin, 600mg/day, &
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 Pyrazinamide, 15-30mg/kg/day,&
 Streptomycin, 15mg/kg/day I M, or Ethambutol, 15 20mg/kg/day
 Thereafter, 2 drugs are used;
 Isoniazid &
 Rifampin
 The minimum duration of therapy is 6 months to 1 yr.
 Noncompliant pts may be kept on a twice weekly
schedule:
 Isoniazid, 15 mg/kg (max. 900mg), twice/wk, &/ or
 Rifampin, 600mg, twice/ wk, &/ or
 Pyrazinamide, 50-70mg/kg, twice/wk, &/or
 Ethambutol, 50mg/kg, twice/wk.
2. Steroids:( ↓ICP, inflammatory exudate & arteritis):
R/ Dexamethasone (Decadron)
(10 mg i.v. initially, then 4-6 mg i.v. q 6 hrs) + Mannitol in acute ↑
ICP.
R/ Prednisone (Hostacortin) 5 mg tab.
(60-80 mg/d. for 2-3 wks, then slowly tapered over 1 month).
3. Tuberculomas:
 Antituberculous Chemotherapy.
 Surgical excision if > 2 cm, ↑ ICP, seizures.
BRAIN ABSCESS
Treatment:
1. Surgical drainage by needle aspiration, stereotactic aspiration,
or total excision.
2. Medical therapy:
 Pre-operative antibiotics.
 Postoperative antibiotics i.v. for at least 4 wks.
 Mannitol 20%, 1-1.5 gm/kg i.v. over 20-30 min.
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 Dexamethasone (Decadron), 4-6mg i.v. q4-6 hrs for 1-2wks.
 Phenytoin (Epanutin).
Recommend Empiric Antibiotic Therapy
(According to the source of infection)
1. Sinusitis & Congenital heart disease:
R/ Penicillin G, 16-24 million units/day IV divided into 6
doses,
OR: Ampicillin, 12 gm/day IV divided into 6 doses; &
R/ Metronidazole (Flagyl), 30mg/kg/day divided into 4
doses
2. Otitis media, Mastoiditis, & Lung Abscess:
R/ Penicillin or Ampicillin, as in (1), &
R/ Ceftriaxone (Rocephin), 4-6 gm/day IV divided into 2
doses, &
R/ Metronidazole (Flagyl) i.v. drip/8hrs
3. Posttraumatic & Postsurgical brain abscess:
R/ Oxcicillin (Prostaphlin), 10-12 gm/day IV divided into 6
doses, &
R/ Ceftriaxone (Rocephin).
4. Unknown source: Same as in (2)
If Pseudomonas infection:
R/ Carbenicillin (Pyopen), 5gm IV q 6hrs
R/ Ceftaudime (Fortuni), 2gm IV q 8hrs
SUBDURAL EMPYEMA
1. Immediate surgical drainage.
2. Pre- operative antibiotics.
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3. Postoperative antibiotics according to culture & sensitivity
test
4. Dehydration therapy (Mannitol & Decadron).
SPINAL EPIDURAL ABCESS
Treatment of Spinal Epidural Abscess:
1. Surgery:
 Drainage of acute abscesses + culture & sensitivity test
 Surgical removal of chronic abscesses + culture &
sensitivity test
2. Antibiotics:
 Preoperative dose of antibiotics:
 Oxacillin (Prostaphilin), 2gm IV
 Or Vancomycin (Vancocin), 1gm IV
 + Gentamicin (Garamycin), 1mg/kg IV or IM
 Postoperative antibiotic therapy guided by culture &
sensitivity test, for 3-4 wks & for 6 - 8 wks in presence of
vertebral osteomyelitis.
3. Steroids to minimize spinal cord edema:
 Dexamethasone (Decadron), l0mg IV preoperatively, then
4-6 mg IV, IM, or PO q 6hrs postoperatively for 7-10 days,
followed by a 10- to 14-day steroid taper.
NEUROSYPHILIS
A. Treatment of Asymptomatic Neurosyphilis:
R/ Aqueous Penicillin G
(4 million units i.v. q4hrs for 14 days).
OR: Procaine Penicillin G
(2.4 million units/d. i.m. for 14 days).
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+ R/ Probenecid (Benemid)
(500 mg PO qid for 14 days)
OR
R/ Benzathine Penicillin G
(2.4 million units i.m. weekly for 3 doses).
For penicillin- allergic pts:
R/ Tetracycline (Hostacycline)
(500 mg PO qid for 30 days)
OR/ Erythromycin (Erythrocin)
(500 mg PO qid for 30 days).
B. Treatment of Symptomic Neurosyphilis:
[Meningovascular Neurosyphilis & Parenchymatous
Neurosyphilis (Tabes dorsalis, G.P.I. & Optic atrophy)]
1. Antibiotic Therapy:
R/ Aqueous Penicillin G
(12-24 million units i.v./d. in 6 doses, for 14 days).
OR: Procaine Penicillin G
(2.4 million units i.m. daily + Probenecid (Benemid) 500
mg PO qid for 14 days).
* Either program should be followed by:
R/ Benzathine Penicillin G
(2.4 million units i.m. weekly).
* In pts allergic to penicillin:
R/ Tetracycline (Hostacycline)
(500 mg PO qid for 30 days)
OR: Erythromycin (Erythrocin)
(500 mg PO qid for 30 days).
OR: Chloramphenical (Chloromycetin)
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(1 gm i.v. q6hrs for 6 wks)
OR: Ceftriaxone (Rocephin)
(2 gm i.v. or i.m. daily for 14 days)
2. Steroids (for syphilitic uveitis & labyrinthitis)
R/ Prednisone (Hostacortin) 5 mg tab.
(80 mg PO every other day).
3. Treatment of Complications:
 Communicating hydrocephalus:
(Treated by: Ventricular shunting)
 Lighting pains in tabes dorsalis:
Treated by:
R/ Carbamazepine (Tegretol), 200 mg tid.
OR: Oxcarbazepine (Trileptal), 300 mg tid.
OR: Gabapentin (Neurontin), 300 mg tid.
4. Treatment of Congenital Neurosyphilis:
R/ Aqueous Penicillin G,
(250.000 units/ kg/ d i.v. for at least 10 days).
5. Jarisch- Herxheimer reaction:
(Fever, Chills, Myalgia, Headache, Tachycardia,
Tachypnea, Leucocytosis, ↓BP. Resolves in 24 hrs)
 Prevented by: a dose of steroids with the initiation of
therapy.
 Treated by: Hydration & Antipyretics.
BRUCELLOSIS
 Early → a flulike illness ± acute lymphocytic meningitis.
 Late → chronic meningoencephalitis.
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Radiculopathies, myelitis, or encephalomyelitis may
dominate.
Treatment:
R/ Rifampin (Rimactane)
(600 mg PO daily for 6 wks to 1 yr).
R/ Ceftriaxame (Rociphen).
(2gm i.v/d. 75-100mg/kg in chidern, for 6wks).
R/ Trimethoprim + Sulfamethoxazole (Septrin, Bactrim)
(160 mg PO qid for 6 wks to 1 yr).
OR/ Doxycycline (Vibramycin),
(100 mg PO bid for 6 wks to 1 yr)
LYME DISEASE
 A tick- borne spirochetal disease (Brucella burgdorferi).
 Three stages:
 Stage 1: A flulike illness ± erythema chronicum migrans.
 Stage 2: A fluctuating meningoencephalitis→ headache,
stiff neck, facial diplegia, polyradiculopathy.
 Stage 3: Arthritis & Seizures, encephalopathy, ataxia &
MS- like syndrome.
Treatment:
 Early disease (Stage 1):
R/ Doxycycline (Vibramycin), (100 mg PO bid)
R/ Tetracycline (Hostacycline),
(500 mg PO qid. for 21- 30 days)
R/ Erythromycin (Erythrocin),
(250 mg PO qid, for children: 30 mg/kg/ d. in 4 doses).
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 Stage 2 & 3:
R/ Aqueous Penicillin G
(20-24 million units/d i.v. in 6 doses for 2-3 wks)
OR: Ceftriazone (Rocephin),
(2gm i.v./d 75-100 mg/kg/d in children, for 14 days)
OR: Cefotaxime (Claforan).
(2 gm i.v. q8hrs for 14 days)
OR: Chloramphenicol (Chloromycetin),
(250 mg i.v. q6hrs for 14 days).
LEPTOSPIROSIS
 Leptospira interrogans from contact with urine of infected
animals.
 Common in farmworkers, veterinarians & pet owners
 Self- limited flulike illness → conjunctival injection &
myalgia
 Severe illness → aseptic meningitis, myelitis, encephalitis &
cranial nerve palsies.
Treatment:
R/ Penicillin G, (1 million units i.v.q 6 hrs for 7- lodays)
OR: Doxacycline (Vibramycin).
OR: Erythromysin (Erythrocin).
OR: Chloramphenicol (Chloromycetin).
FUNGAL INFECTIONS OF THE CNS
 Therapy should be continued for at least 6 wks, or for 1
month after the last +ve CSF culture.
R/ Amphotericin (Fungizone 50 mg i.v.)
(0.5- 1.5 mg/kg/ day i.v. infusion in 5% dextrose)
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(It is effective against all fungi)
R/ Fluorocytosine (5-FC) (150 mg/ kg/ d.P0)
(Active in Cryptococus, Candida, Aspergillus, Torulopsis &
Chlorblastomycosis)
R/ Ketocanazole (Nizoral 200mg tabs & 20 mg/ml oral susp.),
(400-800 mg/d)
(Active in coccidioidomycosis, histoplasmosis&
candidainfection)
R/ Fluconazole (Diflucan 200mg cap. & i.v. infusion 2 mg/ml
in saline), 400 mg/d. po
(Active in cryptococcal meningitis & in coccidioidal
meningitis)
 Antifungal Therapy (Summary):
Organism
Primary Therapy
Cryptococcus
Candida
Amphotericin, 0.5 mg/kg/d IV
5-Fluorocytosine (5-FC), 150
mg/kg/d PO
Amphotericin B, 1.5 mg/kg/d IV
Amphotericin B, 0.5 mg IT , 2
doses/wk
Amphotericin B, 1.5 mg/kg/d IV
Aspergillus
Amphotericin B, 1.5 mg/kg/d IV
Phycomycetes
Amphotericin B, 1.5 mg/kg/d IV
Histoplasma
Amphotericin B, 1.5 mg/kg/d IV
Blastomyces
Amphotericin B, 1.5 mg/kg/d IV
Coccidioides
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Optimal adjunctive
therapy
Subarachnoid
amphotericin B
Intraventricular
amphotericin B
5-FC, 150 mg/kg/d PO
Subarachnoid
amphotericin B
5-FC 150 mg/kg/d PO
Subarachnoid
amphotericin B
Subarachnoid
amphotericin B
Subarachnoid
amphotericin B
Subarachnoid
amphotericin B
 Steroids in fungal meningitis:
1. ↑ CSF pressure (Exclude hydrocephalus by CT or MRI).
2. Hydrocortisone is injected with intrathecal fungizone.
 Hydrocephalus in fungal meningitis:
1. Ventriculoatrial (VA) or ventriculoperitoneal (VP) shunt
is placed after the CSF is sterile.
2. constant ventricular drainage if the CSF is still infected.
 Intraparenchmal fungal infection of the CNS:
→Abscess or gramuloma + fungal meningitis.
1. Accessible lesions: Surgical excision with pre-operative
antifungal therapy 48 hrs prior to surgery.
2. Multiple or inaccessible lesions: Maximum dosages of
Amphotericin B (Fungizone) ±5-FC.
 Actinomycetes: → Barin abscess ± Sp. Cord abscess & meningitis
R/ Pencilin G, 24 million units/d in adults 200.000 units/kg/d
in children in 12 divided doses for 8 wks to 5 months.
OR/ Erythromycin, 4 gm/d i.v. in adults, 50 mg/kg/d i.v. in
children in 4 divided doses.
 Nocardia Species:
R/ Trimethoprim- sulfamethoxazole (Bactrim,Septrim), 1520 mg/ kg/d i.v. in 4 doses.
R/ Cycloserine (D-cycloserine tabs, 250mg)
(15 mg/ kg/ d- PO in 4 divided doses).
VIRAL MENINGITIS
Treatment:
 Supportive measures: Analgesics, antipyretics, anti-emetics,
AEDs.
 Hydrocephalus calls for V-A or V-P shunting.
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VIRAL ENCEPHALITIS
Examples: Herpes Simplex Encephalitis (H. S)
Cytomegalovirus Encephalitis (CMV).
Treatment:
 Edema: Mannitol 20% i.v. infusion over 20 minutes+
Dexamethasone (Decadron): Centraindicated in H.S.
encephalitis.
 Seizures: AEDs.
 Specific Antiviral Therapy:
1. H.S. Encephalitis:
R/ Acyclovir (Zovirax)
(10-12.5 mg/kg i.v q8 hrs for 10-14 days. Each dose is
infused over 60 min).
2. CMV Encephalitis; ventriculitis, myelitis, polyradiculopathy; &
retinitis in immuno-compromized
R/ Ganciclovir (Cymevene I.V.)
(5mg/kg i.v. q12hrs, infused over 1 hr)
R/ Fsdvstmry
(60mg/kg i.v. 98hrs, for 14 days, infused over 1 hr).
RABIES
Clinically: Brainstem encephalitis
Treatment:
 Intensive respiratory support & nursing care.
 Rabies vaccine & antiserum.
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POLIOMYELITIS
Clinically: Acute febrile illness + LMN paralysis.
Prophylaxis: Immunization against poliomyelitis.
Treatment: Supportive measures.
HERPES ZOSTER
 Caused by reactivation of latent varicella zoster virus
(Chickenpox) in dorsal root & cranial nerve. ganglia.
 Clinically:
1. Involve thoracic dermatomes in 50% of cases→ pain,
paresthesia & vesicular eruption.
2. LMN facial palsy + vesicles in external auditory canal or
tympanic membrane (Ramsay Hunt syndrome).
 Treatment:
R/ Carbamazepine (Tegretol) (200 mg tid)
OR/ Oxcarbazepine (Trileptal) (300 mg tid)
R/ Gabapentin (Neurantin) (300-400 mg tid)
OR/ Pregabalin (Lyrica) (75mg o.d. - tid)
R/ Imipramine (Tofranil) 25mg (50mg at bedtime)
OR/ Amitriptyline (Tryptizol) 25 mg ( 50 mg at bedtime)
R/ Capsaicin cream (Topically) 250 mg injection.
R/ Acyclovir (Zovirax), (5mg/kg i.v. q8hrs for 7 days)
SLOW VIRUSES & PROGRESSIVE MULTIFOCAL
LEUKOENCEPHALOPATHY (PMLE)
A. Creutzfeldt- Jokob disease (CJD)
 Clinically: Ataxia, myoclonus, coma & death.
 EEG: Periodic sharp wave complexes.
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 CSF: Normal.
 No specific treatment.
B. Subacute Sclerosing Panencephalitis (SSPE):
 Clinically: Occurs in childhood →
 Personality change & intellectual deteriorastion.
 Myoclonic seizures, ataxia & visual impairment.
 Death in months or years.
 EEG: Periodic sharp wave complexes.
 CSF: Elevated gamma globulin with ↑ titers of anti-measles
antibodies.
 Treatment:
R/ Isoprinosine (Inosiplex)
(100 mg/ kg/ d. PO for 3-6 months).
R/ Interferon α (Roferon A).
(100.000 IU/m2 surface area,↑to 106IU/m2 on 5th day x 30).
C. Progressive Multifocal Leukoencephalopathy (PML):
 Caused by the papovavirus JC → demyelination → focal
neurologic signs.
 Affects AIDS pts & transplant recipients & pts with
lymphoma.
 No specific treatment, however:
R/ Cytosine arabinoside (ara-C)
R/ Interferon α (Roferon A), Cydofavir, & Topotecan, each
→ clinical & Yadiological improvement.
TOXOPLASMOSIS
 Caused by Toxoplasma gondii.
 Clinically: 2 types:
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(1)Congenital toxoplasmosis: Chorioretinitis, retardation, I.C.
calcifications,±microcephaly, hepatosplenomegaly, jaundice
& rash.
(2)Acquired
toxoplasmosis:
Encephalitis,
meningitis,
intracerebral mass ± spinal cord abscess & myositis.
 Treatment:
R/ Sulfadiazine, (100mg/kg/d. Max. 8 gm/d).
R/ Pyrimethamine.
(1mg/kg/d. Max. 100mg/d with 100-200mg loading dose), ±
R/ Folinic acid (Leucovorin) (10mg/d)
In sulfa-allergic pts:
R/ Pyrimethamine alone, or
R/ Clindamicin (Dalacin C), (1200-2400 mg/d in 4 divided doses)
AMEBIC MENINGOENCEPHALITIS
 Naegleria (in warm freshwater) → acute meningoencephalitis
with purulent CSF & hemorrhagic brain lesions.
 Wet fresh CSF → Mobile large organisms.
R/ Metromidazole (Flagyl).
OR/ Septrin or Bactrim.
OR/ Amphotericin (Fungizone) may be tried.
ACQUIRED IMMUNODEFICIENCY SYNDROME
(AIDS)
Treatment:
1. Anti-HIV chemotherapy:
R/ Azidothymidine (Zidovudine)
(200 mg 6 times/d. PO, or 1.5 mg/kg q4-8hrs i.v.)
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R/ Didanosine.
Pts > 75 kg: 300 mg bid.
Pts 50-75kg: 200 mg bid.
Pts 35-49 kg: 125 mg bid.
R/ Zalcitabine (0.75 mg tid.)
2. Opportunistic Infections of the CNS in AIDS pts:
 Toxoplasma gondii.
 Cryptococcal meningitis.
 C.albicans & C. immitis.
 Cutaneous varicella zoster eruptions:
R/ Acyclovir (Zovirax) for 10 day.
 Progressive multifocal leukoencephalopathy.
R/ Cytosine arabinoside intrathecal or i.v.
R/ Interferon alpha.
3. Focal Brain Lesions in AIDS pts (or HIV +ve):
 Anti-Toxoplasma therapy.
 Brain biopsy.
4. Neoplasms in pts with HIV infection:
 Primary CNS lymphoma or lymphomatous meningitis.
NEUROCYSTICERCOSIS
(CEREBRAL CYSTICERCOSIS)
 CNS infection with larvae of the pork tapeworm taenia solium.
 Clinically: may be asymptomatic, or cause epilepsy,
hydrocephalus, stroke, chronic basilar meningitis, dementia,
encephalitis & acute chemical meningitis.
 Intracranial cysts→ progressive focal neurologic deficit.
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 Treated by:
R/ Praziquantel (Bilricide)
(50mg/kg/d. PO in 3 divided doses for 14 days).
R/ Albendozole (Vermizole).
(15mg/kg/d. in 3 divided doses for 21 days).
 Acute inflammatory reaction to the dying organisms →
headache, seizures, ↑ICT, or focal neurologic deficits &
respond to:
 Analgesics.
 Anticonvulsants.
 Dexamethasone (Decadron), (8mg i.v. or PO q8hrs).
 Surgical excision of cysts.
 Ventricular shunting for hydrocephalus.
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CNS NEOPLASMS
Classification
Common CNS tumors &. their sites of predilection
o Metastatic tumors
Supratentorial Cerebral
Hemispheres o Meningiomas
tumors
o Gliomas
Extradural
o Astrocytoma
o Pituitary adenomas
o Oligodendroglioma
o Pineal tumors
o Craniopharyngiomas
oAcoustics chwannomas
o Metastases
o Meningiomas
o Hemangioblastomas
o Cerebellar astrocytomas
o Medullblastomas
o Ependymomas
o Brainstem gliomas
o Metastases
Intradural
o Extramedultary
Midline
tumors
Infratentorial In adults
Tumors
In children
Spinal cord
tumors
oMalignant glioma:
*Anaplastic
astrocytoma
*gliohlastoma
multifonne
o Meningiomas,
Schwannomas,
Neurofibromas
o Intramedullary
o Ependymomas
o Astrocytomas
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Genetic Syndromes:
1. Neurofibromatosis with spinal neuromas, acoustic neuromas,
meningiomas & gliomas
2. Tuberous sclerosis with astrocytomas
3. Von Hippel-Lindau disease with hemangioblastomas
Symptoms:
1. ↑ ICP→ headache, vomiting, blurring of vision (papilledema)
2. Focal neurologic deficit (e.g. hemiparesis, aphasia, ataxia,
visual loss)
 Tumors in silent regions of the brain→ personality &
behavior changes
3. Seizures, focal & /or generalized
4. Hemorrhage into a brain tumor → stroke -like syndrome
 Examples: Glioblastoma multiforme, & metastases from
chorocarcinoma, melanoma, & anaplastic lung cancer
Diagnosis:
1. CT scan with IV contrast
2. MRI (brain or spine)
3. Cerebral angiography is rarely needed
4. L.P. is potentially dangerous in ↑ ICP
Differential Diagnosis:
Enhancing cerebral infarcts, brain abscesses, large MS
plaques, & 1C granulomas.
Treatment:
I. Tumor-related brain edema:
1. Steroids: Dexamethasone (Decadron)
2. Osmotic diuretics for lowering ICP acutely:
R/ Mannitol 20%.
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II.. Surgical therapy of 1C tumors:
1. Histologic confirmation
2. Restoration of impaired neurologic function:
 Surgical resection can be palliative →internal decompression
3. Possibility of cure:
 Complete removal of extra-axial tumors → cure
 Examples: Schwannomas, meningiomas, pituitary adenomas
4. Surgical risks:
 Deliberate resection or inadvertent compression,
retraction,
or devascularization of the brain →
irreversible deficits
 Surgical removal can be hazardous & complete resection
impossible in tumors of hypothalamus. III ventricle
region, brainstem, clivus & foramen magnum, & tumors
in the vicinity of carotid artery or sagittal sinus
 Resection of large tumors ↑ the risk of an adverse
outcome
 The risk of anesthesia & neurosurgery ↑ in the presence
of heart disease, pulmonary disease, or disseminated
cancer
5. Operative techniques:
 Craniotomy.
 Stereotactic biopsy
 Extensive tumor resection.
 Gammaknife techniques.
 Radiofrequency techniques.
6. Operative complications:
 Hemorrhage
 Brain edema
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 Infection
 Seizures:
i. All pts with a history of seizures prior to surgery
should continue on anticonvulsant therapy
ii. Prophylactic anticonvulsant therapy is not routinely
given.
iii. Falx & parasagittal meningiomas carry the highest risk of
postoperative seizures. Prophylactic anticonvulsant
therapy should be given preoperatively & continued at
least 4 months thereafter
 Communicating hydrocephalus
 Neuroendocrine disturbances:
I. The syndrome of inappropriate ADH (SIADH)
secretion
ii. Panhypopituitarism, diabetes insipidus, or both may
follow surgery in the region of hypothalamic-pituitary
axis.
CNS TUMORS IN ADULTS
Malignant Glioma:
1- Craniotomy & extensive radiation.
2- Radiation therapy:
 4000 c Gy whole brain radiation.
+2000 c Gy coned-down radiation to the tumor bed.
 Brachytherapy using stereotactically placed interstitial
radionuclide implants in recurrent tumor after traditional
radiotherapy.
3- Chemotherapy: in younger pts with minimal deficits:
 Carmustine (BCNU) i.v. (200mg/m2 body surface area
every 8 wks).
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 Other agents: Procarbazine, oral lomustine (CCNU) &
streptozocin.
 Immunotherapy:
 Active immunization with irradiated autologous tumor
cells.
 Adoptive immunotherapy (intratumoral or i.v. injection of
immune cells).
 Humoral immunomodulators (e.g. interferons) .
 Monoclonal antibody therapy.
Recurrent Glioma:
 A second look surgical procedure.
 High dose steroids.
Supratentorial Astrocytomas & Oligodendrogliomas :
1. Craniotomy & tumor resection.
2. postoperative radiation therapy (5500cGry to the tumor
bed).
Primary CNS Lymphoma:
1. High- dose steroids:
R/ Octreotide (Sandostatin) ↓ G.H
R/ radiation therapy to tumor bed, whole brain &/or spinal
irradiation.
2. pre- & post- irradiation chemotherapy + Intrathecal
methotrexate in meningeal disease.
Meningioma:
Complete surgical removal → cure.
radiotherapy for subtotally resected meningiomas & for
recurrent meningiomas.
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Surgical resection for incidental meningiomas with mass effect.
Acoustic Schwannomas:
1. Surgery: complete surgical excision.
2. Stereotactic radiotherapy (the gamma knife) in elderly pts &
in pts with increased risk of surgery.
Pituitary Adenomas:
1. Surgery:
 Transphenoidal Surgery using the Operating microscope.
 Modern microsurgical technology
 Corticosteroids to prevent adrenal insufficiency during
surgery.
2. Postoperative irradiation: (5000-6000 cGy over 5-6 wks)
3. Stereotactic radiosurgery in recurrent adenomas after
microsurgery.
4. Medical treatment:
R/ Bromocriptine (Parlodel)
(2.5-5 mg tid)
R/ Octreotide (Sandostatin) (a somatostat in analogiue)
(↓ the size of G H- secreting ademoma)
Cerebral Metastases:
A. Intraparenchymal metastases:
 High- dose steroids:
R/ Dexamethasone (Decadron), 25 mg q6 hrs.
 Surgery for accessible solitary metastases
+ Whole brain radiotherapy (2500-4000 c Gy over 2-4 wks)
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 Radiotherapy for pts with multiple metastases or inaccessible
solitary metastasis
( 2500-5000 cGy to the whole brain over 2-4 wks).
 Stereotactic Radiotherapy using the linear accelerator or
gamma knife.
B. Meningeal Carcinomatosis & Meningeal Lymphomas:
Treatment:
 Craniospinal irradiation
(4000 cGy to the brain & 3000 cGy to the spine)
 Intrathecal Chemotherapy with methotrexate 12mg, Cystosine
arbinoside 50mg, or thiopta 10mg + whole – brain irradiation.
R/ Methotrexate inj.
(12mg bi-weekly or 1mg/12 hrs)
OR/ Intraventricular administration through an indwelling
Ommaya reservoir.
PSEUDOTUMOR CEREBRI
Treatment:
1. Diet & Lifestyle:
 Reduce weight.
 Salt & water restriction.
 Rice diet.
 Tyramine-free diet.
2. Drug Treatment:
R/ Acetazolamide (Diamox, Cidamex)
(250-500 mg/d. ↑ up to 1000-4000 mg/d in 2-3 divided
doses)
R/ Furosemide (Lasix)
(20-80 mg/d in adults, 2 mg/kg up to 120 mg/d or 200 mg/
other day in children)
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R/ Prednisone (Hostacortin)
(2mg/ kg/ d. for 2 wks with tapering over 2 wks)
R/ Methylprednisolone (Solu-Medrol)
(IV 250 mg qid for 5 days with an oral taper beginning at 80
mg/d over 4-8 wks)
3- Lumbar Puncture (L.P.) & Drainage:
 L.P. in the 4 th or 5th L. interspace, in a lateral decubitus
position.
 Measure the CSF pressure.
 Remove CSF for cell, protein, glucose & culture studies.
 Remove CSF to ↓ closing pr. to < 200 mm Hg.
4- Surgery:
 Lumbar peritoneal shunting.
 Optic nerve sheath decompression.
 Bariatric surgery to ↓ weight.
 Horizontal gastroplasty, or
 Vertical-banded gastroplasty.
5. Emerging Therapies:
R/ Octreotide (Sandostatin) ↓ G.H .
+Hyperbaric oxygen.
CNS TUMORS IN CHILDREN
Cerebellar Astrocytoma:
 Surgical excision.
 Surgery or radiotherapy for recurrence.
 Radiotherapy if re-growth occurs.
Medulloblastoma:
 Resection of tumor mass±
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 Ventricular shunt .
 Radiotherapy of the entire neuraxis.
(5000-6000 c Gy to the tumor & 3600 c Gy to the brain &
spinal cord, with ↓ doses for children< 3 yrs).
Ependymoma:
 Extensive surgical resection +
 Ventricular shunt.
 Postoperative radiotherapy.
(4500-6000 c Gy over 4-6 wks).
 Craniospinal irradiation for tumor seedling.
 Pre-or postoperative chemotherapy.
Brainstem Glioma:
 It is inaccessible to surgery.
 Radiotherapy to the brain stem
(4000-6000 cGy over 4-6 wks)
 High dose dexamethasone (Decadron).
Craniopharyngioma:
 Microsurgical removal (recurrence in 20-30%).
 Postoperative radiotherapy.
 Postoperative hormonal therapy.
Tumors of the Pineal Region:
 Ventricular shunting (for obstructive hydrocephalus).
 Radiotherapy (for pts with ↑ α-fetoprotein).
 Surgical exploration with complete resection.
 Craniospinal irradiation for spinal seedling.
 Chemotherapy in recurrences after surgery & radiotherapy.
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SPINAL CORD TUMORS
Schwannoma (Extramedullary- intradural):
 Complete surgical removal.
 Dumbbell tumors → recurrence need a second operation.
Spinal Meningiomas (Extramedullary-intradural):
 Complete surgical excision.
 Recurrence is likely in meningiomas anterior to the cord.
Spinal Astrocytomas & Ependymomas (Intramalullary):
 Decompression laminectomy, partial resection & opening the
dura matter + opening the syringomyelic cavity (60% of cases)
to allow drainage.
 Postoperative radiotherapy to the sp.cord (3500-4500 cGy).
Metastatic Spinal Tumors:
(Epidural spinal compression)
 High dose dexamethasone.
R/ Decadron, 25 mg q6 hrs for several days.
 Posterior decompression laminetomy+ radiotherapy (3000
cGy over 3 wks.
 Anterior decompression & stabilization of the spine.
 Radiotherapy alone.
 Direct (anterior) resection &/or stabilization of the spine.
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NEUROLOGIC COMPLICATIONS
OF RADIOTHERAPY
1. Delayed cerebral radiation necrosis:
 High-dose steroids +
 Surgical exploration & removal of the necrotic mass.
2. Symptomatic communicating hydrocephalus:
 High-dose steroids.
 Ventricular shunting.
3. Radiation- induced myelopathy:
 High-dose steroids.
4. Radiation- induced brachial plexopathy:
 Surgical exploration of the brachial plexus.
 Neurolysis ± Omental grafting.
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CRANIOSPINAL TRAUMA
HEAD INJURY
Initial Medical Management for Trauma Pts:
Airway, breathing, & circulation (ABCs) are first priorities:
A. Airway:
 Adequate airway is the first priority
 endotracheal intubation
 nasotracheal intubation
 tracheostomy or cricothyroidotomy: not needed in
responsive pts.
 Hypoxia suppress cerebral function
 Hypercarbia ↑ICP, while hypocarbia rapidly ↓ ICP
B. Breathing:
 Use 100% O2 initially in intubated pts, H.V. (12-14
breaths/min. at 750- 1000ml)
 Check ABGs.
C. Circulation:
 Loss of cerebrovascular autoregulation is frequent
 Hypotension is corrected by blood volume. replacement
 IV line is placed in a nontraumatized extremity, or
subclavian or jugular vein
 Blood sample for: CBC, PT, PTT, platelets, BUN, blood
sugar, toxic screen, blood grouping & cross matching
 Avoid hypervolemia (overcorrection of hypovolemia)
 Packed RBCs may be given to keep the Hct > 30% for
neuronal oxygenation
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D. Shock:
1. Hemorrhagic shock is rare with head injury & may
indicate internal hemorrhage
2. Spinal shock (an acute sympathectomy) → hypotension &
bradycardia
3. Responds to: intravascular volume expansion ± alphaadrenergic agents or atropine
Emergency Treatment of Head-Injured Patient:
A. Severe head injuries need the co-operation of neurosurgeon,
neurologist, & other specialists.
B. The ABCs must be instituted & monitored -+- frequent
checking of vital signs
C. Deteriorating neurologic function despite adequate O2 & BP
suggests ↑ ICP from a hematoma or cerebral edema, & is
treated by:
D. H. V. to achieve PCO2 of 28 - 30 mm Hg
E. Elevation of the head to ↓ venous pressure
F. Mannitol, 1 gm/kg IV bolus
G. Furosemide (Lasix), 0.5 mg/kg IV
H. Avoid jugular kinking or compression
I. Phenytoin (Epanutin), 15mg/kg at 25-50 mg/min. IV, to
prevent seizures
J. DIC may occur in 50% of cases of severe brain injuries, as the
brain has very high levels of tissue thromboplastin. Freshfrozen plasma IV + management guided by the results of
clotting studies.
K. Dexamethasone (Decadron), l0mg IV initially, then 4mg
q6hrs in selected pts.
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Neurosurgical Treatment:
A. Epidural Hematoma:
Treatment:
1. In herniating pts, intubation, H.V., & mannitol dehydration
+ surgery
2. CT scan, if possible, to exclude other lesions
B. Subdural Hematoma:
Treatment:
 Acute subdural hematoma:
 Surgery + ICP monitoring & treatment of edema
 Chronic subdural hematoma:
 In reliable pts, with small hematomas, follow up by
serial neurologic exam. & CT scans until resolving
spontaneously
 In pts with severe or progressive deficits or those who
cannot be followed reliably, surgery is recommended.
Burr holes & drainage of a hypodense CT collection.
Repeat drainage via burr holes is ineffective,
craniotomy & evacuation of the solid clot is needed
 Children with open fontanelles: An 18-to 22-gauge
short-beveled subdural needle with a stylet is
introduced at the lateral corner of the anterior fontanelle
at least 3 cm from the midline for repeated "subdural
taps". If failed, "temporary shunt" or " craniotomy"
may be indicated.
C. Intracerebral Hematoma:
Treatment:
 Observation & supportive measures for small hemorrhages
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 Large 1C hematomas in eloquent areas of the brain may be
treated with H.V. mannitol, & dexamethasone (Decadron),
with ICP monitoring
 Large accessible hematomas need surgery, particularly
"temporal lobe hematomas" for fear of uncal herniation
(→coma & death)
D. Intraventricular Hemorrhage:
Treatment:
 Minor hemorrhages without hydrocephalus resolve
spontaneously
 Larger hemorrhages need an "external ventriculostomy"
for CSF drainage & ICP monitoring. It is removed after
several days, when the blood clears, & in most pts a
permanent shunt is not necessary.
E. Skull Fractures:
Treatment:
 Hospitalization
 Analgesics e.g.. paracetamol, aspirin, or NSAIDs &
monitoring, for uncomplicated pts
 More complicated pts need more prolonged admission &
observation
 Most CSF leaks will stop spontaneously with head
elevation
 Profuse or persistent leaks require continuous lumbar
drainage or surgical repair to prevent meningitis.
F. Scalp Lacerations:
 In the absence of an underlying fractures may be debrided,
irrigated, & sutured. In fractures, exclude a penetrating
injury
 Treatment for tetanus
 Antibiotics
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Medical Treatment of Head Trauma:
 Exclude a surgically treatable mass lesion
 Pts with concussion & normal neurologic exam. may be
discharged if no loss of consciousness, or kept under
observation for the next 24 hrs (a “head trauma sheet” is
filled)
 Pts with neurologic deficits are admitted to an ICU, &
managed as follows:
A. Airway:
 “Endotracheal or nasotracheal intubation” with frequent
suctioning of secretions
 If intubation is required for a week or more due to coma
or copious secretions or other pulmonary problems
”tracheostomy” is advisable.
B. Breathing:
 Episodes of ↑ ICP are treated by H.V. using Ambubag
 Persistent ↑ ICP is treated by H.V. through a ventilator
 PCO2 should be kept between 28 – 30 mm Hg
 PO2 should be kept > 90 mm Hg
 Positive end – expiratory pressure (PEEP) may be needed
to normalize PO2
C. Circulation:
 An arterial line is needed for pts with persistent coma
 BP monitoring & ABGs determinations
 C.V.P. catheter placement, if systolic BP is < 95 mmHg,
to guide volume replacement.
 Dopamine IV drip may be needed for BP support
 HTN can cause ↑ ICP or hemorrhage into contused brain
 Avoid systolic BP > 170 mm Hg
 HTN is controlled by Labetalol (Trandate), 5 – 10 mg IV
 Nitroprusside (Nipride) IV infusion, or nitroglycerin infusion
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can elevate ICP, & only used if ICP is not a problem
 Saline is used for gentle rehydration (if intravascular
volume expansion is required)
 Blood or albumen is used for acute hydration
D. ICP:
 ICP monitoring devices are needed in unresponsive pts
with head trauma
 Responsive pts can be followed by neurologic
examination
 An intraventricular catheter, epidural, & subdural
monitors are available for ICP monitoring. The
fiberoptic subdural device is the simplest & most widely
used
 Transient ↑ ICP → neurologic deterioration
 Persistent ↑ICP about 18 mm Hg → ↓ cerebral perfusion
pressure (CPP) (CPP = mean arterial BP- mean ICP) →
a worse neurologic outcome
Treatment include the following sequential measures:
 Elevate the head of the bed → promotes venous drainage
→ ↓ ICP
 Ventricular drainage
 H.V. with an Ambubag in transient ↑ ICP, or H.V. with a
ventilator in chronic ↑ ICP (keep PCO2 between 28 – 30
mmHg)
 Mannitol, 100 – 200 ml of 20% sol., ↓ ICP & improves
perfusion in 20 min, for 2 – 6 hrs, 100 ml q4hrs may be
needed to keep ICP < 15 – 20 mm Hg. Check serum
osmolality & electrolytes. Avoid hyperosmolality (> 310
mOsm)
 Furosemide (Lasix), 0.5 mg/kg, or 20 –40 mg for an
adult, IV.
-111-

E.
F.
G.
H.
Barbiturates, 50 – 100 mg of pentobarbital IV bolus &
repeated qhr as needed to maintain ICP < 15 – 20 mm
Hg.
 Hypotension & suppressed neurologic exam. (Coma
& EEG suppression) call for D/C barbiturates.
 Barbiturates → ↓ ICP, block free – radical
production, thus ↓ brain damage, & ↓ cerebral
metabolic O2 consumption
 Weaning require 1 – 2 days for reversal of drug
effect
 A repeat CT scan should be done to exclude a newly
developed hemorrhage or hydrocephalus
 The use of steroids in head-injured pts is controversial
Urinary drainage:
 A Foley’s catheter in acute cases or with osmotic diuretic
use, then
 A condom catheter or intermittent catheterization
NGT to evacuate stomach contents, administer antacids,
medicines, & feeding
Nursing care:
 Hand & foot restraints to prevent self-injury or pulling
out tubes
 Frequent turning (q 2 –3 hrs) to prevent bed –sores
 Sterile endotracheal suctioning of secretions
 Physiotherapy to prevent flexion contractures
Fluids & Electrolytes:
1. Maintenance IV infusion of 0.45% NaCl in 5% D/W +
KCL, 20-40 mEq/liter (check serum electrolytes,
osmolality & BUN).
 Keep osmolality.290 mOsm, & Na > 140 mEq for
the 1st wk after a severe head injury.
-112-

I.
J.
K.
L.
M.
For intravascular volume expansion, use colloid
crystalloid
 If hematocrit is < 30%, use packed RBCs.
2. Diabetes insipidus → high volume, hyponatremic
urinary output, with serum hypernatremia &
hypertonicity. Exclude diuresis
Treatment: Adequate fluid replacement + pitressin or
desmopressin (DDAVP)
3. Inappropriate ADH secretion: due to hypothalamic
injury → hyponatremia with concentrated urine → ↑
cerebral edema, ↓ neurologic function, or precipitate
seizures.
Treatment:
 Restrict free water
 Furosemide (Lasix)
 Hypertonic saline in severe cases
Nutrition:
 IV nutrition in acute cases (2500 kcal/day)
 NGT feeding if GI function is adequate
Seizure prophylaxis with phenytoin (Epanutin), 5mg/kg/day
GI ulceration is common.
Ranitidine (Zantac), 150mg q12hrs,or
Cimetidine (Tagamet), 300mg qid, &
Antacids
Sucralfate ,Igm PO qid
Bowel regimen in comatose pts:
Stool softeners, rectal disimpaction & enemas.
Pneumatic compression boots (Airboots)
To protect against DVT; & the associated risk of pulmonary
thromboembolism.
-113-
Delayed Complications of Head Injury:
A. Posttraumatic epilepsy:
 Immediate (at the time or within few min of injury) e.g.
in IC hematoma
 Early (occurring within the first wk): reflect an initial
brain damage
 Late (occurring after the first wk)
 Incidence: 50% in penetrating injuries, & 5% in blunt
injuries
 EEG → alpha suppression & focal theta or delta slowing
 Seizures may be focal or generalized
 Remission ( with a 2-yr seizure-free period) occurs in
50-75 % of cases.
Treatment:
 If brief coma, with no brain injury, hematoma, or
neurologic deficit, no treatment is given
 Pts with cerebral contusion, prolonged coma, &
hematoma are given prophylactic phenytoin (Epanutin)
for 1-wk (loading dose 15 mg/kg, or1000mg in adults,
over the 1st 24 hrs, then a maintenance dosage of 5 mg/
kg, or 300 - 400 mg, daily in adults IV or via NGT) +
periodic. serum levels.
 Prophylactic anticonvulsants are given only for a 1-wk
period
 If immediate seizure occurs or the pt is at high risk, a 1 to
3-month course of AEDs may be continued
 Pts with posttraumatic epilepsy need AEDs regimen to
attain a 2-yr seizure-free, then gradually discontinued
over 2-3 mns.
-114-
B. Postconcussion encephalopathy
C. Infection:
Meningeal & encephalitic, especially after compound &
basilar fractures.
D. Leakage of CSF is frequent after basilar skull fracture.
 It often stops spontaneously
 If not, continuous lumbar drainage may ↓ CSF pressure
→ sealing of tear
 Surgical repair of the dural tear if this fails
SPINAL CORD INJURY
Treatment of Spinal Cord Injured Patient:
 An airway, ventilation & treatment of associated injuries
 Methylprednisolone (Solu-Medrol) 30 mg/kg IV bolus dose
over 15 min., followed by 5.4 mg/kg/hr maintenance dose to
begin 45 min. after the bolus & to continue for 23 hrs. The
infusion must begin within 8 hrs of injury. If Solu-Medrol
infusion begun between 3 & hrs after injury, it should last 47
hrs. It probably acts by inhibiting lipid peroxidation &
secondary increase in arachidonic acid
 Ranitidine (Zantac) + Antacids are given to prevent peptic
ulcer
Acute Surgery:
Indications:
 Open reduction of dislocation, with or without fracture in
cervical region, if traction & manipulation have failed
 Cervical fractures with partial cord lesions, to remove
compressing bony fragments
 Cervical injuries with partial cord lesions, to remove
extruded disk material
 Depressed fragments of the neural arch
-115-


Compound injuries with foreign bodies or bone fragments in
the sp. canal
Partial cord lesions, with gradual worsening of the
neurologic exam. raise the suspicion of a hematoma. Repeat
MRI prior to surgery.
Treatment of the Vertebral Injury:
 Achieve cardiopulmonary stability
 Traction using cranial tongs or halo-traction apparatus.
Initial needed wt=5 lb/level (e.g. for fracture at C5, one
should use 25 lb). Wt should be added under fluoroscopic
guidance, or a lateral cervical spine x-ray should be checked
with each wt change.
 Traction is not helpful for thoracic or lumbar fractures
Cervical injuries:
1) Atlantooccipital dislocation: is usually fatal due to vertebral
artery injury or direct medullary compromise. Survivors may
need tracheostomy & occipitocervical fusion is needed.
2) Jefferson fracture is a bilateral fracture through the posterior
arch of C1. The mouth-open view x-ray is diagnostic.
Fractures will heal with halo-vest fixation. An occipital-C1 –
C2 fusion may be needed.
3) Atlantoaxial injuries: 4 groups:
a. Ligamentous injuries
 Open-mouth views may show intact odontoid
 Lateral views show abnormal separation of the
odontoid from C1 anteriorly (normal predental space
is < 3 mm in adults & 5 mm in children)
 Early C1- C2 fusion is required
b. Odontoid tip fracture (type 1) need halo-vest
stabilization
-116-
c. Fractures through the odontoid base (type 2): C1 – C2
fusion is needed
d. Fractures involving C2 body (type 3) need halo-vest
immobilization
4) Hangman’s fracture: A bilateral pedicle disruption of the
arch of C2 with C2 – C3 dislocation. It occurs in
hyperextension
injury.
Mostly
heal
following
immobilization. Rarely an anterior C2 – C3 fusion is needed
5) Locked (or jumped) facets: May be unilateral or bilateral
 Unilateral injuries: → partial (<50%) compromise of the
sp. canal
- Root injury ± cord injury may occur
- A – P x-ray shows rotation in the normal vertebral
alignment of the spinous processes
- Lateral x-ray shows vertebral subluxation
- Oblique films confirms the facet dislocation
- Traction will relocate the unilateral locked facet at
higher cervical levels
- Lower cervical segments may need surgical
intervention
 Bilateral injuries: → spinal injury & more easily realigned by traction
- All facet disruptions remain unstable due to
ligamentous injury
- They easily dislocate necessitating fusion
6) Flexion teardrop fracture:
- A wedge-shaped fracture of the anterior vertebral body
→
- Disruption of the inter- spinous & other posterior
ligaments → instability
- Significant neurologic deficit from anterior inpingement
of the sp. cord
-117-
7) Dislocations through the “disc space” need surgical fusion
8) Fracture dislocation of the “ vertebral body” fuse after
immobilization
Thoracic injuries:
 They are relatively stable because of the buttressing effect of
the rib cage
 Traction is not helpful
 Surgery is needed for severe misalignment & if further
future angulation is expected
 Less severe misalignment need bed rest & immobilization
with a form-fitted plastic jacket
Thoracolumbar injuries:
 Burst of the vertebral body with bone displacement into sp.
canal → conus or cauda equina lesion
 Surgical decompression, realignment & fusion → neurologic
improvement in partial lesions
General Nursing Care:
 Bladder care: (to obtain a pt- controlled reflex bladder that
is free of infection)
 Intermittent, sterile, “no touch” catheterization 2 –3
times daily
 Acidifying the urine with ascorbic acid (Vit. C), 1gm qid
 Bowel care: (To obtain a pt –controlled reflex evacuation)
 Rectal tube or enemas for the initial bowel distention
 When peristalsis returns, use Metamucil, or stool
softeners
 As the bowel becomes more active, use suppositories
instead of enemas
 Exam. frequently for fecal impaction
-118-




Skin care: (To prevent pressure-sores)
 Blankets & bed sheets are drawn tight & smooth, & are
kept dry
 Pt is nursed on a mattress or foam pad placed on a hard,
flat surface
 Pt should be turned q 2hrs, day & night, manually, or by
a rotating bed
Care of Nutrition:
 A high-calorie, high-protein diet
 If unable to eat, parenteral supplements, or NGT feeding
 Check fluid & electrolytes closely
Pain control:
 Aspirin, propoxyphene (e.g. Darvon), codeine
 Benzodiazepines (e.g. Valium) to control anxiety
 Phenytoin (Epanutin), Carbamazepine (Tegretol),
Amitriptyline (Tryptizol) for dysthesiae
Psychiatric care
Complications of Spinal Cord Injuries:
 Urinary calculi
 Decubitus ulcers (Bedsores)
 Muscle spasms:
 Precipitated by: urethritis, cystitis, bedsores, rectal
vesical distention
 Treated by:
- Diazepam
(Valium), baclofen (Lioresal),
dantrolene sodium (Dantrium)
- Intrathecal baclofen pumps
- Intrathecal injection of phenol
- Rhizotomy is rarely done
 Contractures: are prevented by the early use of range
-119-
or
&
of


motion exercises & slplinting
DVT: is common & may → pulmonary embolism
(tachycardia, dyspnea, chest pain, or hypotension).
Prophylactic elastic stockings & pneumatic compression
devices + s.c. heparin 5000 U q 12 hrs help preventing DVT
Atelectasis & pneumonia: are prevented by postural
drainage, assistive coughing, use of humified air &
suctioning
Rehabilitation of Spinal Cord-Injured Pts:
 Physiotherapy: Massage, passive exercises, strengthening
exercises
 Vocational therapy:
 Preparing pts for future gainful employment.
 Multiple devices are available to permit a wide range of
activities
 Sports e.g. Wheelchair basketball, road racing,
swimming,…..etc.
 Psychiatric therapy.
-120-
DISC SYNDROMES SPONDYLOSIS & LBP
DISC SYNDROMES
Lumbar Disk Herniation
Treatment:
a. Conservative Treatment:
1. Pts ē mild symptoms:
 Avoid bending or straining + instructions of proper
posture
 Bed-rest
 Local heat application
 Analgesics
 Strengthening exercises
 A lumbar corset
2. Pts ē severe pain:
 Strict bed-rest on a firm bed ē supporting boards
underneath the mattress, for few days to few wks.
 Analgesics, Muscle relaxants, NSAIDs ± Pelvic
traction
b. Surgery:
1. If conservative therapy fails
2. Midline disk compression of cauda equina
3. Nerve root compression associated ē motor deficit
c. Chemonucleolysis (Injection of the disk ē “chymopapain”)
Cervical Disk Herniation
Treatment:
a. Conservative Therapy
 Cervical traction + same measures outlined for lumbar
disc
b. Surgery:
-121-



Early surgery in cervical cord compression
Nerve root compression ē neurologic deficit
Failure of conservative therapy
Thoracic Disk Herniation
Treatment:
 Conservative therapy may benefit those ē root compression
alone
 Surgery is indicated for pts ē cord compression. Technically
difficult.
SPONDYLOSIS
Treatment:
 Conservative therapy: as in disk syndromes
 Surgery is indicated in cord compression, paresis, or
intractable pain.
 Enlarging the intervertebral foramina: in root
compression
 Laminectomy ± Diskectomy: in cord compression
SPONDYLOLYSIS & SPONDYLOLISTHESIS
Treatment:
 Conservative therapy: Restriction of activity + flexion
exercises + corset
 Surgery (Spinal fusion ): if conservative therapy failed
NEUROLOGIC COMPLICATIONS OF
DISEASES INVOLVING THE SPINE
Ankylosing Spondylitis
 Early → L.B.P.
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


Rarely → Sciatica
Uncommonly → Cauda equina lesion (late)
Ankylosing spondylitis progresses → muscle wasting, pain,
& sensory loss in the legs +loss of sphincter control
Treatment: is symptomatic
Rheumatoid Arthritis
 → Subluxation of one vertebra onto another
 Most commonly: Atlantoaxial subluxation → Pain ± Spinal
cord compression
 C3 – 4 subluxation is also common → Painless cord
compression
Treatment:
 Immobilization of the affected joint:
 Temporarily ē a “hard four – posterior collar”
 Spinal fusion at the involved space
Paget’s Disease
(Osteitis Deformans)
Clinically:
 It causes back pain ± cord compression
 Cord compression by:
 Narrowing of the sp.canal by hypertrophic bone
 Interference ē the arterial supply of the cord,
 Extramedullary hematopoiesis
 Vertebral collapse ē dislocation of vertebral bodies
Treatment:
 Is palliative è back brace & analgesics
-123-
Metastatic Disease of the Spine
(e.g. in lung, breast, & prostate cancer)
Clinically:
 Back pain by involvement of vertebrae or spinal roots
 Sp.cord compression by vertebral collapse or extramedullary
deposits
Diagnostic Tests:
 Plain x-ray spine
 Isotope bone scan
Treatment:
 Treatment of the 1ry tumor &/or radiation therapy to the
involved vertebrae → relief of pain
 Prompt myelography & surgical decompression in spinal
compression
 Some pts benefit from steroids & radiation therapy
Metabolic Bone diseases
(e.g. Osteoporosis, Osteomalacia, Hyperparathyroidism)
Clinically:
 Frequently → back pain
 Rarely → neurologic deficits by spinal cord or root
compression
Treatment:
 Is that of the underlying condition e.g.
 D/C steroids
 Give vitamin D & Ca
 Back brace& analgesics
 Treat malabsorption or renal failure
 Remove parathyroid adenomas
-124-
Spinal Epidural Abscess
 Direct spread from vertebral osteomyelitis or local skin
infection
 Hematogenous spread from a distant infection
 Clinically: → severe back pain + local tenderness + spinal
cord compression
 Myelography prior to surgical removal of the abscess & 4 –
6 wks of IV antibiotic therapy
Psychiatric Causes of Back Pain
 Depression nay present with back pain which responds to
tricyclic antidepressants
 Back pain may occur in the context of various psychiatric
diseases
 Back pain in impotent pts.
LOW BACK PAIN (LBP)
Treatment:
Diet & Lifestyle:
 Abstinence from tobacco may help to prevent LBP.
 Occupational LBP occurs in settings of heavy work, lifting,
prolonged sitting or standing, bending & twisting, vibration,
monotonous work, job dissatisfaction, & poor relationships
with co-workers.
 Bed rest.
Drug Treatment:
 NSAIDs.
 Acetaminophen.
 Muscle relaxants are useful in acute LBP.
 Tramadol is useful in chronic LBP.
 Opioid analgesics are reserved for acute severe LBP.
-125-
 Nortriptyline is useful in chronic LBP.
 Oral corticosteroids are not recommended for LBP.
Interventional Procedures:
 Comfort control measures include injection of
corticosteroids, local anesthetics, & other substances
including opioid analgesics.
 Epidural injections of a corticosteroid, a local anesthetic, or
both has no role in acute LBP without radiculopathy,
however they are useful for short-term relief of radicular
pain.
 Epidural steroid injections may be of short-term benefit for
chronic LBP.
Surgery:
 Lumbar disc surgery should only be considered if:
1. Pt has severe disabling sciatica & LBP;
2. Pain or associated neurologic deficits persist without
improvement for > 4 wks or progress; &
3. There is a physiologic evidence of dysfunction of a
specific nerve root & a neuroimmaging evidence of disc
herniation. Lumbar disc surgery:
1. Standard discectomy
2. Microdiscectomy.
3. Chemonucleolysis (dissolving nucleus pulposus by
enzyme injection) using chymopapain.
 Lumbar fusion for the treatment of chronic LBP:
 Instrumented (placement of metallic hardware) & non
instrumented fusions
Assisstive Devices:
 Shoe insoles (inserts into both shoes) may be helpful for pts
with acute LBP.
 Shoe lifts.
 Lumbar corsets & support belts.
-126-
Physical Therapy & Exercise:
 Pts may be taught self-application of heat or cold to the back
at home.
 Low stress aerobic exercise.
 Exercise therapy (such as specific back, abdominal, flexion,
extension, static, dynamic, strengthening, stretching, or
general aerobic exercises) is effective for treatment of
chronic LBP.
Other Therapies:
 Acupuncture ??.
 Behavior therapy.
 Spinal manipulation is helpful for pts with acute LBP
without radiculopathy.
 Pt education about LBP symptoms.
 Back schools (structured program of LBP education)
 Spinal traction is not recommended in acute LBP.
 Transcutaneous electrical nerve stimulation (TENS) is not
recommended in acute LBP.
Emerging Therapies:
 Percutaneous vertebroplasty in compression fractures of
spine resistant to conservative therapy.
 Intradermal electrothermal annuloplasty may be helpful for
chronic LBP due to disc degeneration.
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NEUROMUSCULAR DISORDERS
MYASTHENIA GRAVIS (MG)
Therapeutic Protocol of MG:
 Cholineterase inhibitors
 Thymectomy
 Immunosuppression
Cholinesterase Inhibitors:
 Start low, go slow
 Keep the patient slightly under-medicated
 Begin Pyridostigmine (Mestinon) at 60 mg tid, ↑ the dose
progressively to achieve the best response, or until the
patient becomes cholinergic (develop diarrhea)
Thymectomy:
 Thymectomy is recommended in all patients with
generalized MG whose symptoms began before age 50
 Thymectomy is recommended in children with MG if they
have functionally disabling weakness despite adequate
treatment with cholinesterase inhibitors
Immunosuppressive Therapy (Immunotherapy):
 Immunotherapy in MG is usually a lifetime commitment
 Prednisone (Hostaacortin) Initially 60 mg/d; Maintenance
10mg/d.
 Azathioprine (Imuran)150mg/d. (50mg tid) [Monitor
L.F.Ts.& CBC]
 Cyclosporine (Sandimmun)150 mg bid [Monitor R.F.Ts.]
 Prednisone +Azathioprine/Cyclosporine
 IV immunoglobulin (IVIG) → Rapid, temporary improvement of MG
-128-



Plasma Exchange(PLEX) → Rapid, temporary improvement
of MG
N.B.: 50% of pts with ocular myasthenia & 20%of those
with generalized MG are seronegative (i.e. have no AChRAb)
N.B.: The serum AChR-Ab level is not useful in monitoring
the effect of treatment
Crisis
(Acute weakening in a myasthenic pt.)
 Myasthenic crisis → ↑ weakness & requires ↑ dose of drugs
 Cholinergic crisis due to excessive anticholinesterase
therapy. Atropine masks the warning side effects, & ↑
weakness will be the only sign of toxicity
Treatment of crisis:
 Intensive care, endotracheal intubation, determine the type
of crisis
 Edrophonium (Tensilon) test can be used in nonapneic pts.
 If improvement occurs, ↑ the anticholinesterase dosage &
observe.
Treatment of MG in pregnancy:
 MG may become worse, improve, or remain unchanged
during pregnancy
 Therapeutic abortion is not indicated. Spontaneous abortion
is common in the first trimester.
 Labour is shorter in myasthenics. IM anticholinesterases are
used during labour
 Local or regional anesthetics are preferred to general
anesthesia, & caution is required with sedatives
 C.S is done only for obstetric indications
-129-

Contraception: Voluntary sterilization or contraception
should be suggested in severe MG.
LAMBERT- EATON
MYASTHENIC SYNDROME (LEMS)
Therapeutic Protocol of LEMS :
 Effective cancer therapy
 Pyridostigmine (Mestinon), 30-60 mg q4 to 6hrs, &
Guanidine HCl, 5-10
mg / kg / day orally, divided
throughout the waking hrs [Monitor CBC, LFTs, RFTs.]
 Plasma Exchange (PLEX) or IV Immunoglobulin (IVIG)
(for rapid transitory improvement)
 Immunosuppressants (for more sustained improvement)
 Prednisone (Hostacortin)
 Azathioprine (Imuran)/ or Cyclosporine (Sandimmun)
CONGENITAL MYASTHENIC SYNDROMES
Establishing the diagnosis is based on the presence of:
(Myasthenic symptoms & signs in a child:)
 Neonatal myasthenia (if the mother has MG)
 Autoimmune acquired MG (is seronegative in 50%, i.e. have
normal AChR-Ab)
 EMG → myasthenic reaction
 AChR-Ab are elevated in 50% of cases
D.D. of Congenital Myasthenic Syndromes:
 Neonatal myasthenia:

The mother has MG

Improves spontaneously with supportive care
-130-
Therapeutic Protocol of Congenital Myasthenic Syndromes:
 Cholinesterase inhibitors.
 3,4- Diaminopyridine (DAP).
 Ephedrine.
Neonatal myasthenia
 It occurs in 20% of babies born to myasthenic mothers
 It is transitory & is usually gone in 24-36 hrs.
 Symptoms usually begin within 3 days of birth
 Signs include: mask-like face, poor sucking, difficulty
swallowing, regurgitation, & resp. distress
Treatment:
 Symptomatic, to prevent aspiration, provide nutrition, &
maintain respiration
R/ Neostigmine (Prostigmine), 1-2 mg PO
(Parenteral dose is 1/30 the oral dose) q4hrs,
OR/ Pyidostigmine (Mestinon), 4-10 mg PO, may be needed
for a short time
BOTULISM
Treatment:
 Trivalent (A,B,E) antitoxin, 10,000 units IV in one dose.
 It is horse serum, so skin-testing & precautions for
anaphylaxis are needed
 Allergic reactions occur in 15-20 % of pts & treated by
antihistaminics
&
corticosteroids.
Emergency
endotracheal intubation in severe reactions
 Emetics, cathartics, & enemas to eliminate any toxin in the
GIT
-131-


Guanidine HCI, an acetylcholine agonist, 35-40 mg/kg /day,
PO q4hrs.
Resp.care : Resp. failure is frequent.
 Elective intubation if vital capacity falls to 1000 cc
Nasogastric . or endotrached intubation in severe dysphagia
to prevent aspiration.
TETANUS
Treatment :
1. Antitoxin:
 Human hyperimmune globulin is the antitoxin of choice,
3000 -10,000 units IM or IV in a single dose.
 Horse serum antitoxin (after skin testing for sensitivity),
50,000 units IM followed by 50,000 units in a slow IV
infusion ± small amount injected locally
2. Surgical excision of the area of the wound & drainage +
Procaine Penicillin, 1.2 million untis IM or IV q6hrs for 10
days or Tetracycline, 500 mg PO or IV q6hrs for 10 days
3. General measures:
a. Care of skin, bladder, bowel, fluids, nutrition, &
respiration
b. Painful spasms are controlled by:
A dark, quite room
Sedation: Diazepam (Valium), 2-10 mg IV q4 –
12hrs, or Meprobamte, Barbiturates, or chlorpromazine.
Avoid using diazepam with barbiturates as they cause
resp. & cardiac arrest
c. Neuromuscular blockers e.g. Pancuronium (Pavulon) +
intubation, Intrathecal baclofen (Lioresal) infusion can
control spasms.
d. Symptomatic treatment of autonomic dysfunction (HTN,
-132-
hypotension, hyperpyrexia, & cardiac arrhythmia)
4. Prophylaxis:
 Immunization against tetanus beginning at 2 months of
age, using tetanus toxoid, 0.5 ml in 3 inj. 4 wks apart +
Booster inj. every 10 yrs
 Thorough washing & debridement of acute injuries:
 In fresh, clean wounds:
The toxoid course should be completed if not so
A booster dose of toxoid is given if pt has not had
one in the past 10 yrs
 In dirty or infected wounds:
Toxoid booster is given if none has been received
for 5 yrs + Human antitoxin (250 units IM) to pts
who have not received earlier immunization.
N.B.: Contracting tetanus does not confer immunity & The
series of toxoid injections is required in these pts.
EPISODIC MUSCLE WEAKNESS
A. Familial Hypokalemic Periodic Paralysis
Treatment of Acute Attack:
 Potassium either Po (10-15gm of Kcl infuid), or IV Kcl (4060mEq in 500ml infused over several hrs.
B. Familial Hyperkalemic Periodic Paralysis
Prophylaxis:
 High-K, low –Na diet .
 Spironlactone (Aldactone) 100mg PO daily or bid.
 Thiamine Hcl (Vit-B1) 50-100mg /d.
 Treatment of hyperthyroidism.
 Acetazolamide (Diamox), 250-500 mg PO q 4-6 hrs, to
cause mild metabolic acidosis.
-133-
Treatment of Acute Attack:
 IV infusion of 10% Ca gluconate, 10 – 20 ml
Prophylaxis:
 Acetazolamide (Diamox),250 mg PO qid
 Hydrochlorothiazide (Esidrex), 50 – 100 mg PO daily
MUSCULAR DYSTROPHIES
DUCHENE MUSCULAR DYSTROPHY (DMD)
Treatment:
Diet &Lifestyle:
 Weight control
 Prophylaxis for pneumonia:
- Annual flu vaccine
- Pneumovax every 5yrs.
- No smoking (both active & passive)
 Family management:
- Emotional support of pt & family
- Teaching caregivers appropriate lifting & transfer.
- Provide assistive equipments
Drug Treatment:
 Growth hormone inhibitors (Sandostatin 0.1 s.c. amp).
 Dantrolene (Dantrium), 25mg tid.
 Prednisone (0.75 mg/kg/ d).
 Prednisone, long-term
 Prednisone, alternate day
 Prednisone or Azathioprine (Imuran 50mg tid).
 Deflazacort, alternate day
 Deflazacort (0.75 mg/ kg/ d.)
 Coenzyme Q-10
 Creatine monohydrate
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Surgery:
 Scoliosis repair
Assistive Devices:
 Pulmonary rehabilitation devices:
Assistive cough therapy, human therapy, mechanical
therapy, chest percussion therapy & intermittent positive
pressure breathing.
+ Bronchodilators
 Other devices:
- Wheelchair (manual & electric)
- Noninvasive positive pressure ventilation (IPPV).
Physical Therapy & Exercise:
 Strengthening exercises
 Stretching or range of motion exercises
 Analgesics, massage & stretching improves muscle pain
 Modified physical education (avoid exhaustion)
 Swimming
Emerging Therapies:
Gene therapy for DMD:
 The use of a mini-gene (or a portion of the dystrophin gene)
& the adeno-associated virus vector
Retrovirus- mediated transduction:
 Replicating satellite cells were transduced & expressed
dystrophin
Creatine, glutamine & gentamycin:
 Creatine or N-methyl- guanidinoacetic acid is manufactured
in the liver & kidneys from the amino acids glycine, arginine
& methionine
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

Glutamine is a "conditionally essential" amino acid in DMD
pts.
Aminoglycoside antibiotics (e.g. gentamycin) can be an
alternative splicing.
Treatment of Muscular Dystrophies:
Mild cases
 Need no therapy. Follow up every 6-12 months.
Severe cases:
 Faithful compliance prolongs the pt’s independence
 Pts can remain in normal schools until they cannot climb
stairs
 Pts with Duchenne type often have low IQ & need special
schools
 The family & the pt should be encouraged to maintain as
normal a life as possible for as long as possible
 Prednisone (0.5 mg/kg/day) can improve strength in
Duchenne dystrophy. But avoid wt gain. Give zoster
immune globulin if exposed to chickenpox during steroid
therapy.
 Physical Therapy:
 Intensive physiotherapy to maintain independent
ambulation, good alignment, proper positioning in bed &
in a chair, prevent contracture
 Respiratory care:
 Dysphagia & dyspnea occur in severe generalized
dystrophy & in pharyngeal dystrophy .
 Pulmonary function tests often are abnormal:
 Encourage pts to develop diaphragmatic breathing
 Breathing exercises
 IPPR & postural drainage in late stages
 A rising CO2 is a bad prognostic sign in dystrophy
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

Gait maintenance:
 Prevent & treat obesity to improve walking & ventilation
 Pts should walk 3 hrs in divided periods
 Independent ambulation can be maintained by crutches,
braces, & surgical procedures. The wheelchair is avoided
until ambulation is impossible
 Avoid bed rest.
Preventive Therapy (Genetic Counseling):
(Advising the family about recurrence rates in future
generations)
a. Sex-linked recessive disorders (Duchenne dystrophy):
1. A known carrier: Has one chance in 2 of producing a
dystrophic male or a carrier female.However 1/3 of
pts have -ve family history
2. Carrier detection:
 Serum CPK is elevated in ½ of obligate carriers
 Single-fiber EMG
 Muscle biopsy
3. Prevention: in families who carry the abnormal gene:
 Voluntary sterilization or contraception, or
 In-utero determination of sex & of the disorder
may allow abortion of all affected males
4. Spontaneous mutation occurs in 1/3 of
Duchenne dystrophy pts
b. Autosomal dominant disorders
(FSH dystrophy, Myotonic dystrophy, & Late distal
dystrophy):
 The pt has one chance in 2 of having an affected
offspring
 No carriers
 Prevention: is by contraception
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c. Autosomal recessive disorders
(Limb-girdle dystrophy):
 Both parents must be carriers to have an affected
offspring. 1 in 4 will have the disease, 2 will be
carriers, & 1 will be normal.
 Prevention:
Contraception & avoidance of consanguineous
marriage
MYOTONIC DYSTROPHY
Treatment:
 Phenytoin (Epanutin), 5mg/kg/day PO is the first choice
 Procainamide (Pronestyl), 50mg/kg/day PO in 3 or 4 doses
 Quinine, 5-10 mg/kg/day PO, divided into 6 doses
 Corticosteroids in severe cases:
 Prednisone, 0.75 mg/kg/day, in a single morning dose, or
double this dose is given on alternate days
 Respiratory care:
 Intercostal myotonia interfere ē regular breathing
 Oropharyngeal dysfunction ē aspiration pneumonia is
common
 Physiotherapy
POLYMYOSITIS
Treatment:
1. Corticosteroids: accelerate remission & ↓ morbidity
 Usually used in combination ē either methotrexate or
azathioprine.
 Prednisone, 60-100 mg PO every morning, gradually reduced
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ē improvement to 40 mg & maintained for several mns.
 The rate of dosage reduction is 5-10 mg every 3-7 days
 In 6-12 mns most pts can be kept on 15-20mg every
morning, or 30-40mg every other day.
 Response to therapy & relapse can be monitored by
muscle enzyme determination
 Attempting to D/C steroids should be made after 2 yrs of
therapy
 Steroid myopathy may occur (more in females), & calls
for dose reduction
2. Immunotherapy:
May be of benefit in chronic progressive cases.
 Immunosuppressive drugs may be effective if used alone
or combined with smaller dosage of prednisone.
 Methotrexate IV over 20-60 min, starting at 0.4
mg/kg/treatment, & ↑ to max. of 0.8mg/kg/treatment in
2-3 wks. Given weekly until improvement occurs, reduce
to biweekly, then triweekly, then monthly doses are
given for 10-24 mns.
 Stomatitis & GI symptoms call for ↓ of dosage
 Leukopenia & hepatic toxicity require discontinuation
 Azathioprine (Imuran), 1.5-2 mg/kg PO, either alone or
with prednisone. Dosage is gradually. ↑until the WBC
count ↓ & that dosage is continued until remission of
polymyositis.
 Bone marrow suppression, anorexia, nausea, vomiting,
& jaundice are the major side effects
3. Other therapeutic measures:
 Bed rest in acute cases
 Physical therapy on improving.
 Braces & other physical measures for chronic weakness
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ACUTE PERIPHERAL NEURITIS
Landry – Guillain – Barré Syndrome
(Acute Idiopathic Demyelinating Polyradiculoneuritis-AIDP)
Ttreatment:
 Plasma exchange used within 7 days shorten recovery in 2/3
(3 –5 exchanges, every other day)
 I.V. Immunoglobulin, 0.4 g/kg in 1000ml saline over 6-8 hrs.
 Corticosteroids: are of little benefit in acute cases
 Resp. care: Intubation if vital capacity drops to 25-30 % of
normal
 Feeding: by i.v. fluids, NGT, or gastrostomy in bulbar palsy
 S.C. heparin, 5000 U/12 hrs to prevent DVT & pulm.
embolism
 Bowels: Suppositories & enemas to prevent fecal impaction
 Physiotherapy: Positioning, passive exercises, active
exercises, a footboard
 Edema:
 Intermittent elevation of extremities
 Intermittent compression of extremities for 60-90 min +
Massage + Elevation
 A pressure stocking
 Pain:
 Analgesics (Aspirin 600mg q3-4 hrs)
 Local heat + exercises
 A brace or cock-up splint + physiotherapy
 Restorative surgical procedures may improve function
 Autonomic disorders:
 Phenoxybenzamine, 20-60mg in divided doses
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CHRONIC INFLAMATORY DEMYELINATING
POLYRADICULONEUROPATHY (CIDP)
Treatment:
 Prednisone, 100mg daily for 2-4 wks, then every other day
for 3-6 mns, then taper to maintenance dosages of 5-20mg
every other day for life
 Plasma exchange (2 exchanges/wk for 3 wks) if no
improvement in the 1st wk or2
 Azathioprine (Imuran), 50mg tid (Monitor LF Ts & CBC)
 I.V. IG treatment is effective in pts ē refractory disease.
(0.4g/kg in 1000ml of saline i.v. over 6-8 hrs)
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AMYOTROPHIC LATERAL SCLEROSIS (ALS)
Treatment Plan for ALS problems:
 Speech & Communication.
 Swallowing & Salivation.
 Sleep & Fatigue.
 Respiration.
 Activities of daily living (ADL).
 Ambulation.
To enhance speech & communication
 "Low tech" (e.g., paper/pencil, erasable pad)
 Communication board
 Typed communications
 Crespeaker (converts single words to speech)
 "Higher tech" instruments (e.g., Light Writer); anticipates
word endings.
 Personal computers:
 Access to the internet
 Environmental controls
 Single letter or phrase through scanning &
microswitches
 Voice preservation
 TDD (telecommunication device for the deaf); essential for
anarthric patients
To enhance swallowing
 Assessment by speech pathologist
 Body weights at every visit
 Nutritional supplements for protein & caloric maintenance
 Thickeners for thin liquids
 Feeding tubes
Nutrition in MND:
 Assessment & monitoring of dietary intake in relation to the
energy, fluid, vitamin & mineral needs of the patient.
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



Advice on maintaining a healthy diet
Monitoring of weight & anthropometric measures
Assessment of the need for & timing of percutaneous
endoscopic gastrostomy / gastrojejunostomy (PEG) or
radiologically inserted gastrostomy (RIG)
Advice on PEG or RIG feeding &care of feeding
tubesE
Excessive Salivation
Medication
Amitriptyline (Tryptizol)
Glyopyrrolate
Imipramine (Tofranil)
Methantheline
Methylphenidate (Ritalin)
Propantheline (Probanthene)
Trihexphenidyl (artane)
Dosing schedule*
10 mg hs or am and hs
1-2 mg q4h
50-200 mg hs
50-100 mg q4h
10-20 mg q6h
15-30 mg q4h
2-10 mg q4th
*Usual adult dosage used as needed (prn)
Symptoms & Signs of Respiratory Insufficiency in MND
Symptoms
Orthopnoea
Dyspnoea on exertion or
talking
Disturbed night time sleep
Excessive daytime sleepiness
Fatigue
Anorexia
Depression
Poor concentration &/or
memory
Morning headache
Signs
Increased respiratory rate
Use of accessory muscles
Paradoxical
movement
abdomen
Decreased chest movement
Sweating
Hyperdynamic circulation
Weight loss
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of
Respiratory Management of Patients with ALS
Discuss respiratory complications & management options early
in disease course
Encourage patient / family involvement in major treatment
decisions (including periodic review of "code status")
Meticulous pulmonary toilet
Pneumococcal / influenza vaccines
Aggressive treatment of respiratory infections
Maintenance of adequate nutritional status
Regular monitoring of vital signs / measurement of FVC at
every clinic visit
Instruction concerning techniques to avoid aspiration
Resistive inspiratory training
Home use of noninvasive ventilatory assistive devices (e.g.,
IPPB, CPAP, BiPAP, chest cuirass)
Tracheostomy & mechanical ventilation
Pharmacologic management: Low-dose theophylline to increase
respiratory muscle strength after resistive breathing;
diuretics for fluid overload; nebulizer breathing treatments
(e.g. Albuterol) to loosen secretionsCurrent criteria for
considering assisted ventilation:
Patients should have
1. Symptoms relating to respiratory muscle weakness
2. Symptoms suggesting nocturnal hypoventilation
3. Evidence of respiratory muscle weakness
4. Evidence of nocturnal hypoventilation (abnormal
polysomnography)
Measures for Assisting in Activities of Daily Living


Home visit at selected times
Bathing
 Grab bars
 Chair / bench
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 Handheld shower
 Toileting
 Raised toilet seat
 Grab bars
 Dressing
 Assistive devices for buttons / zippers
 Casual, loose-fitting clothing with elastic waistbands
 Feeding
 Large - handled utensils
 Alternative food preparation (e.g., purees)
 Grasping
 Large handles
 “Reachers”
 Home management
 Assistances with shopping, household chores
Various Other Problems & Complications of ALS
 Head control
Neck brace
 Rotator cuff tendinitis / impingement
Range -of- motion exercises
NSAIDs (nonsteroidal antiinflammatory drugs)
Proper lifting by caregivers
 Painful cramps
Quinine
Diazepam (Valium)
Phenytoin (Epanutin)
 Other pains
Treat symptomatically
 Spasticity
Baclofen (Lioresal) (orally or via implantable pump)
 Pseudobulbar affect
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Tricyclic antidepressants (TCAs)
SSRIs (selctive serotonin reuptake inhibitors)
Therapeutic Agents in ALS
Drug class
Antiglutamate
Agents
Status
Riluzole
Approved
(Rilutek)
Phase III (approved as
Gabapentin
an AED)
(Neurontin)
Antioxidant
Vitamin E
Preclinical
Neurotrophic
CT-I
Preclinical
factors
IGF-I
Phase III
GDNF
Phse I
NT-3
Preclinical
NT-4
Preclinical
Axokine
Preclinical
Protease inhibitor ACT
Preclinical
PN-I
Preclinical
ACT = µ1-antichymotrypsin; BDNF = brain-derived
neurotrophic factor; CT-I = cardiotrophin-I; IGF-I = insulin-like
growth factor-I; GDNF = glial-derived neurotrophic factor; NT3 = neurotrophic factor-3; NT-4 = neurotrophic factor-4; PN-I =
protease nexin-IDrug Treatment:
Riluzole (Rilutek)
Is it a useful drug in MND?

Riluzole is a benzothiazole derivative with complex effects
on glutamate neurotransmission including inhibition of
presynaptic glutamate release
Mechanisms of action of riluzole
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Effect
Blockade of presynatic glutamate
release
NMDA receptor antagonism
Inhibition of glutamate evoked Ca
2+ entry
Prevention of neuronal
depolarization
? Inhibition of apoptosis
Mechanism
 Uncertain: ? effects on Na+
channels; activation of G-protein
linked signal transduction
 Direct, non-competitive receptor
blockade
 Activation of G-protein mediated
signal transduction
 Inactivation of neuronal Na+
Channels
 Inhibition of stress-activated
protein kinase (SAPkinase)
Symptomatic Treatment of ALS
Symptoms
Weakness/ ambulation
Exercise
Activities of daily living
Cramping
Treatment
Physical therapy, orthopedic & assistive
devices, canes, walkers, specialized
wheelchairs
Exercise in grade 4 or 5 muscles only
Safety devices for bath & toilet, dressing &
feeding
Assistive devices
Quinine, diazepam, phenytoin
Baclofen(Lioresal)
Spasticity
Pain
Dysphagia/ swallowing/
weight loss
Salivation
Loss of speaking
Depression/insomnia
Analgesics, opiates,
Transcutaneous electical nerve stimulation
(TENS)
Blenderized food, supplements, feeding tube,
percutaneous gastrostomy (PEG)
Suction machines; amitriptyline or atropine
Paper & pencil, specialized voice ability
synthesizers, Etran communications board,
TDD (telecommunication device for the deaf),
microcomputer-based instruments
Antidepressants (offer universally), anxiolytics,
electrically powered adjustable bed
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Sleep disturbance
Respiratory/pulmonary
weakness
Infections
Clonazepam or Sinemet CR; ventilatory
assistance (BiPAP or nasal CPAP)
Antisecretory agents, cough medication,
tracheostomy; BiPAP, CPAP, chest cuirass
volume ventilators
Antibiotics; prophylactic vaccines
(pneumococcal, influenza)
Hospice
Some common symptoms in ALS & their treatment
Symptoms
Cramps
Cause
? Changes in motor
neurone Na+ channel
function
Spasticity
Corticospinal tract
damage
Sialorrhoea
Bulbar weakness
Emotional
Lability
Pseudobulbar
syndrome
Treatment
Quinine sulphate 200mg bid
Carbamazepine (Tegretol)
Phenytoin (Epanutin)
Magnesium
Verapamil
Baclofen 10-80mg daily Tizanidine
6-24mg daily Dantrolene 25-100mg daily
Intrathecal baclofen Memantine 10-60mg
daily
Atropine eye drops sub-lingual
Atropine 0.25-0.75 mg tds (tabs/liquid)
Benztropine (tabs/liquid)
Benzhexol (tabs)
Hyoscine (tabs/transdermal patches)
Amitriptyline (Tryptizol) (tabs/liquid)
Glycopyrrolate (liquid: sc/im/via PEG)
Salivary gland irradiation
Transtympanic neurectomy (?)
Botox injection to salivary glands (?)
Amitriptyline (Tryptizol)
SSRIs (e.g., citalopram, fluvoxamine)
Agents Approved or Under Investigation for the Treatment of
ALS
 Glutamate antagonists
 Riluzole (approved for the treatment of ALS)
 Gabapentin (commercially available for treatment of
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


seizure disorders)
Neurotrophic factors
 Insulin-like growth factor-1 (IGF-1)
 Glial-derived neurotrophic factor (GDNF)
 Cardiotrophin-I (CT-1)
 Neurotrophin-3, neurotrophin-4 (NT-3, NT-4)
Protease inhibitors
 1Antichymotrypsin (ACT)
 Protease-nexin-1 (PN-1)
Antioxidants
 Vitamin E
ConclusionsPeople affected by MD (ALS) are best served by a
multi-professional team approach that is 'user-centred'. New
models of user-involvement are being developed.
2. Riluzole is associated with improved survival at 12 & 18
months, but the survival gain (estimated at 2-3 months at 18
months) beyond 18 months is unknown. Riluzole is safe &
well-tolerated.
3. Recent trials of neurotrophic factors (e.g., subcutaneous &
intrathecal BDNF) & related agents have been essentially
negative.
4. PEG is associated with prolonged survival & improved
nutrition but is hazardous in patients with VC <50%
predicted. RIG may offer advantages over PEG in patients
with low VC (<50%).
5. New evidence suggests that both survival & QL is improved
by non-invasive positive pressure ventilation (NIPPV) but as
yet there are no agreed criteria for initiating NIPPV.
Currently 10-20% of patients in Europe have NIPPV but this
varies widely in different centers.
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6. Palliative care encompasses the entire course of MND, not
only the final phase. Symptom control is important at all
stages.
7. Advance directives are seldom but increasingly used in
Europe. Ethical concerns about end of life decisions (e.g.,
ceasing ventilatory support: physician assisted suicide) are
under debate.
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NEUROLOGICAL COMPLICATIONS OF
SYSTEMIC DISEASES
Diabetes Mellitus (DM)
Treatment of Diabetic Neuropathy
I. Therapies to correct the underlying pathogenetic mechanism.
II. Symptomatic treatment.
I. Therapies to correct the underlying pathogenetic
mechanism:
 Control of blood glucose level:
 Normalization of blood glucose levels prevents
microvascular complications including neuropathy.
 Aldose reductase inhibition :
 Drugs that inhibit aldose reductase can reduce
accumulation of alcohol sugars in the nerves.
 Supplementary dietary intake of myoinositol may be
useful.
II. Symptomatic Treatment
1. Physical Approaches:
- Foot care.
- Proper footwear.
- Treat local infection aggressively.
- Cessation of wt. bearing to allow healing of plantar
ulcers.
- Alternating hot & cold soaks for painful foot.
- Avoidance of repeated trauma in compression
neuropathy.
- Avoidance of crossing of legs & leaning on elbows.
- Nocturnal splinting for pts. with CTS.
- Avoidance of intra-operative pressure or traction
trauma to nerves.
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- Physiotherapy for pts. with focal neuropathies.
2. Pharmacological Approaches:
- Carbamazepine, (Tegretol): for the lancinating or
lightning pains.
Dose: 100 mg. tid., to 200 mg. tid.
Action: It ↑ membrane stability.
- Gabapentin (Neurontin), 400-800 mg tid for
neuropathic pain
- Antidepressants e.g. Amitriptyline (Tryptizol) or
Doxepin( Sinequan): for burning steady pain.
- Mexilitine (Mexitil) improves peripheral nerve blood
flow.
- Simple analgesics.
Non-Ketotic Hyperosmolar Coma
 Treatment:Lactic acidosis is treated by IV sodium
bicarbonate & treatment of its cause.
 Non-ketotic hyperosmolar coma is treated by little
insulin + fluid replacement.Uremic Encephalopathy
Treatment of Uremic Encephalopathy
 Dialysis or renal transplantation is mandatory in irreversible
progressive RF
 Anticonvulsants in low doses to control convulsions.
 Hyponatremia makes seizure control difficult & must be
corrected.
 We must be cautious in prescribing certain drugs for uremic
pts., e.g.:
 Aminoglycosides (vestibular damage).
 Furosemide (cochlear damage).
 Nitrofurantoin, INH, & Hydralazine (peripheral
neuropathy).
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Dialysis Encephalopathy (Dialysis Dementia)
Treatment:Diazepam (valium) or Clonazepam (Rivotril)
controls seizures.
 Desferoxamine improves other symptoms.
 Removing Aluminium from dialysate water prevents the
epidemic form.Uremic Neuropathy
Treatment of Uremic Polyneuropathies:
 Long-term hemodialysis → stabilization of the symptoms.
 Rapid hemodialysis may worsen the polyneuropathy.
 Peritoneal dialysis is more successful in improving
polyneuropathy.
 Successful renal transplantation → complete recovery over
6-12 months, through eliminating the causative toxins e.g.
methylguanidine & myoinositol.
 Carbamazepine (Tegretol), 400-600mg/d PO in 3 doses.
 Gabapentin (Neurontin), 400-800mg tid
 Clonazepam (Rivotril), 0.5mg PO tid, ↑ by 0.5/2-3 days up
to 20mg/d.
Seizures in RF
Treatment of Seizures:
 Correction of the underlying metabolic problem.
 Dialysis for uremic encephalopathy-induced seizures.
 AEDs:
 Phenytoin (Epanutin) in usual dosages.
 Phenobarbital (Sominal, Sominalette) in lower dosages.
 Diazepam (Valium), up to 10 mg IV, or
Lorazepam (Ativan), 2-4 mg IV.
 Valproic acid (Depakine) in usual dosages.
 Carbamazepine (Tegretol) in usual dosages.
 Ethosuximide (Zarontin) in usual dosages.
 Seizures during hemodialysis, due to the disequilibrium
syndrome are controlled by:
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1. The rate & duration of dialysis & ↑ its frequency.
2. Phenytoin (Epanutin), 100 mg tid for hemodialysis pts.
Muscle Cramps
 Occur during or immediately following dialysis → pain.
 Treated by:
 Quinidine sulfate, 320 mg PO at the beginning of each
dialysis.
Hepatic Encephalopathy
Portal-Systemic EncephalopathybHepatic Stupor & Coma
Treatment of Hepatic Encephalopathy
General Principles:
 Restriction of dietary protein.
 Oral Neomycin or Kanamycin to reduce bowel flora.
 Enemas.
 Lactulose orally → acidification of colonic contents.
 Liver transplantation for intractable liver failure.
 Other therapies:
 Bromocriptine (Parlodel) -a dopamine agonist-enhance
dopaminergic transmission.
 Keto-analogues of essential amino acids -a nitrogen-free
source of essential amino acids.
Elimination of predisposing factors:
 Avoid sedatives, tranquilizers, & analgesics
 Correct fluid & electrolyte balance
 Correct hypokalemia & alkalosis. Avoid potassiumwasting diuretics
 Maintain intravascular volume to prevent prerenal
azotemia
 Treat hyponatremia promptly but cautiously (to avoid
central pontine myelinolysis)
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
A careful search for occult infection; e .g. peritonitis, &
treatment of any infection
 Acute inflammation (e .g pancreatitis), trauma, & surgery
Supportive measures:
 Foley’s catheter, skin care, fluid balance.
 Tracheal intubation in deeply comatose.
Dietary protein restriction:
 Protein – free diet until improvement of neurologic function;
 Feeding; oral, NGT, or parenteral.
 Enough calories (at least 500 kcal/day) to inhibit
proteolysis (1500 ml of 10% D/W → 600 kcal).
 A mixture of 10 %or 20% D/W & lipids via NGT to give
1500 – 2000 kcal/day .
 Cathartics on admittance
Mg citrate, 200 ml, or Sorbitol, 50 gm in 200 ml water via
NGT or PO
 GI bleeding may precipitate hepatic coma:
 Vigorous treatment of GI bleeding
 Aspirate bl.in stomach through a NGT
 Enemata followed by cathartics
Repeated doses of Sorbitol, 50 gm in 200ml water to ↑ one
loose motion q4 hrs.
 Adequate vit. supplementation, ê daily doses of folate, 1mg,
vit.k, 10mg, & multivitamins.
 As the pt improves, a diet of 20 gm protein/day is provided,
& ↑ daily protein intake by 10 gm every 2 – 3 days (up to 50
gm/day)
Decrease gut ammonia absorption:
 Neomycin, 1gm qid PO, or by retention enema.
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It may → Hearing loss, renal impairment, colitis,
candidiasis of bowel, & malabsorption.
 Lactulose, 30-50ml (0.65gm/ml) tid PO, by NGT, or by
retention enema → acidify the stool & ↓ ammonia
absorption.
 Flumazenil (Anexate), an inverse agonist of the
benzodiazepine receptor, 1-3 mg by IV infusion, may reverse
some of the neurologic effects.
L–Dopa have no long-term benefit in pts ê hepatic
encephalopathy.
Monitoring Therapy:
 Hepatic Encephalopathy Stages:
 Stage 1 (Precoma): Mild confusion & mental slowness.
No asterixis or EEG slowing
 Stage 2 (Impending coma): Disorientation, drowsiness,
asterixis ± mild EEG slowing
 Stage 3 (Pt is asleep most of the time, confused +
asterixis + EEG slowing
 Stage 4 (Coma): Pt responds only to pain + hypotonia +
marked EEG slowing
In mild stages of encephalopathy, a handwriting chart
& tests of constructional ability (e.g. drawing a clock
or constructing a star ê match sticks)
 Blood ammonia levels correlates ê clinical status. Arterial
levels correlate better than venous levels.
 EEG slowing correlates ê the pt’s clinical status in deeper
stages of hepatic encephalopathy. Abnormalities in VERs
have a similar correlation
 CSF glutamine concentrations correlates with the presence
& degree of hepatic
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encephalopathy.
Chronic Management:
 Low– protein diet (usually 50 gm/day) + Vit.
supplementation.
 Pt should have at least one bowel motion each day.
 Neomycin, 500 mg PO bid – qid for a few wks or even
months.
 Lactulose (Duphalac), 10 – 30 ml tid, is equally effective &
safer.
 Surgical exclusion of the colon from the bowel → high
mortality & morbidity.
Acquired Chronic Hepatocerebral Degeneration (Achd)
 Clinically: → dementia, dysarthria, cerebellar ataxia,
tremor, spastic paraparesis, & choreoathetosis. Often
superimposed on recurrent bouts of hepatic encephalopathy.
 Treatment:
 No specific treatment
 It is preventable through appropriate management of
liver disease & prevention of bouts of hepatic
encephalopathy
 Choreoathetosis respond to neuroleptics.
 Behavioral abnormalities respond to protein restriction.
 Bromocriptine (Parlodel) - a dopamine receptor agonist
improves mental status. It is given PO, 2.5 mg/day in 3
or 4 divided doses, ↑ by 2.5 mg every 3 days up to 15
mg/day, improves mental status.
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Acute Liver Failure
Clinically → CNS dysfunction, coma & death, if not treated
Treatment:
 Bl. ammonia by protein restriction
+ neomycin or lactulose
 Mannitol 20% for ↑ ICP
 IV dextrose to correct hypoglycemia
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AUTONOMIC DYSFUNCTION
General Management:
Orthostatic hypotension
 Patient education to avoid factors that precipitate a fall in
BP.
 Patients should be made aware of the hypotensive effects of
certain drugs, large meals, environmental temperature
increases, & physical activities.
 A high-fiber diet to lessen straining resulting from
constipation & the use of physical maneuvers that help to
increase postural tolerance e.g. crossing the legs, lowering
the head in a stooped position, bending forward, & placing a
foot on a chair or squatting, are helpful
 Sleeping with the head of the bed elevated 15 to 30 cm
(reverse Trendelenburg position) to avoid supine hypertension & decrease nocturnal natriuresis & volume depletion. This maneuver alone may reduce postural
hypotension in the morning.
 To reduce postprandial hypotension, patients should eat
smaller, low-carbohydrate meals more frequently & drink
strong coffee.
 Custom fitted elasticized garments may reduce venous
pooling in the legs.
 Volume expansion by adequate hydration (2 to 2.5 liters of
fluid/day) & increasing sodium intake (150 to 250 mEq, or
10 to 20 gr).
 Fludrocortisone (Astonin-H) expands blood volume by its
mineralocorticoid action.
 The initial dose is 0.1 mg po qd; this is increased slowly in
0.1 mg increments at 1 to 2 week intervals.
 Side effects include volume expansion, CHF, supine
hypertension, & hypokalemia.
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Vasoconstricting sympathomimetic agents:
 Indirect sympathomimetic drugs, such as ephedrine &
methylphenidate (Ritalin), release NE both centrally &
peripherally & therefore may produce tachycardia, anxiety,
& tremor.
 Direct alpha agonists, such as phenylpropanolamine or
phenylephrine, may be helpful but have erratic
gastrointestinal absorption, a short duration of action, an
increased risk of supersensitive hypertensive responses, &
tachyphylaxis.
 Midodrine, a pro drug metabolized in the liver to
desglymidrodrine, is a potent alpha-1 adrenergic agonist that
acts on both the arteries & the veins.
 All sympathomimetic agents may produce supine
hypertension & should not be used at night.
 Dihydroxyphenylserine is a synthetic amino acid that is
decarboxylated by L-amino acid decarboxylase to NE, thus
bypassing the step of catecholamine synthesis.
 It is therefore the agent of choice for the treatment of
hypotension
in
patients
with
inherited
dopamine-beta-hydroxylase deficiency.
 Recombinant erythropoietin alpha (25 to 75 U/kg sc 2-3
times/wk) corrects the mild anemia frequently seen in
patients with severe autonomic failure & may increase BP &
orthostatic tolerance.
 Ergotamine
tartrate,
dihydroergotamine,
MAOIs,
yohimbine, & NSAIDs may be of benefit in orthostatic
hypotension.
 Severe supine hypertension at night may be prevented by
sleeping in the reverse Trendelenburg position, avoiding VC
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drugs in late afternoon, & eating a small carbohydrate-rich
snack before bedtime.
A short-acting vasodilator agent (e.g., nifedipine 10 mg po)
may also be used at night.
Neurogenic Bladder:
Detrusor Hyperreflexia without Outlet Obstruction:
 It is treated by an anticholinergic drug such as oxybutynin
(Ditropan, Uripan), propantheline (Probanthine), or
dyclomine.
 Timed voiding & moderate fluid restriction are helpful in
reducing frequency, urgency, & urge incontinence.
 DDAVP (Minirin) may also be useful in patients with significant incontinence & nocturia.
 In patients with severe spasticity, both intrathecal baclofen
(Lioresal) infusion & dorsal rhizotomy may be effective.
 Augmentation cystoplasty has its place in the treatment of
patients with MS & refractory detrusor hyperreflexia.
Detrusor Hyperreflexia with Outlet Obstruction.
 Alpha-1 antagonists such as phenoxybenzamine or prazosin
may decrease bladder-outlet sphincter tone.
 Dantrolene (Dantrium), baclofen, or benzodiazepines may
reduce the tone of the striated external sphincter.
 The most useful method is the combined use of
anticholinergics & intermittent self-catheterization.
 Surgical external sphincterotomy or diversion procedures
are treatments of last resort.
Detrusor Areflexia or Poor Bladder Contractility:
 Bethanechol hydrochloride is a muscarinic agonist that has a
relatively selective action on the urinary bladder & may be
effective in treating patients with chronic detrusor atony or
hypotonia.
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


Other options include the use of adrenergic antagonists,
prostaglandins, & narcotic antagonists.
The simplest & most effective form of management in
patients with hypotonic bladder & detrusor areflexia is
intermittent self-catheterization.
Some patients may require an indwe1ling catheter or
suprapubic diversion.
In patients with conus or cauda equina lesions,
alpha-adrenergic
agonists
(e.g.,
ephedrine
or
phenylpropanolamine) may be used to increase bladder outlet
resistance.
Sexual Dysfunction:
 Treatment of organic impotence includes treatment of
secondary psychological problems & eliminating
aggravating factors such as poor sleep, chronic pain,
malnutrition, alcohol use, & some medications.
 Yohimbine can be used orally to increase penile arterial VD
& enhance relaxation of the cavernous trabeculae.
 Direct injection of papaverine (Vasorin), phentolamine, or
prostaglandin E1 into the corpora cavernosa may be
effective but poses the risks of priapism & scarring of the
tunica albuginea.
A vacuum device may also be used to enhance corporal
filling.
Gastrointestinal dysmotility:
 The principles of management of any gastrointestinal
motility disorder include restoration of hydration & nutrition by the oral, enteral, or parenteral route, suppression of
bacterial overgrowth, use of prokinetic agents or stimulating
laxatives, & resection of localized disease.
-162-
Bowel Hypomotility:
 The first line of treatment of bowel hypomotility is to
increase dietary fiber as well as water intake & exercise.
 Psyllium or methylcellulose with a concomitant increase in
fluid intake may be used to further increase stool bulk.
 In diabetic patients, high fiber may pose a risk of distention,
cramping, & potential bezoar formation in the presence of
gastroparesis.
 Stool softeners (e.g., docusate sodium) or lubricants (e.g.,
mineral oil) together with all osmotic agents (e.g., milk of
magnesia or lactulose) may be used.
 Glycerine suppositories or sodium phosphate enemas
promote fluid retention in the rectum & thus stimulate
evacuation.
 Contact cathartics such as diphenylmethane derivatives
(e.g., phenolphthalein, bisacodyl) or antraquinones (e.g.,
senna & cascara) should be used sparingly because these
agents may damage the myenteric plexus, producing a
"cathartic bowel."
 Prokinetic agents e.g.metoclopramide (Plasil, Primperan),
which has antiemetic effects due to blockade of central
dopaminergic D2 receptors & indirect prokinetic effects
through cholinergic mechanisms; cisapride (Prepulsid),
which increases the release of acetylcholine from neurons of
the myenteric plexus; erythromycin, which mimics the
prokinetic actions of motilin, a gastrointestinal polypeptide;
& misoprostol, a synthetic prostaglandin E1 analog.
 Patients who do not respond to medical therapy may require
colonic surgery.
Bowel Hypermotility:
 Diarrhea may result from bacterial overgrowth in patients
with intestinal hypomotility.
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











Tetracycline or metronidazole is generally used in patients
with unexplained chronic diarrhea, particularly if
steatorrhea is present.
Prokinetic agents may paradoxically improve diarrhea in
this situation.
If these measures fail, synthetic opioid agonists such as
loperamide or diphenoxylate can be used.
Opioid agonists decrease peristalsis & increase rectal
sphincter tone.
Clonidine (Catapres), an alpha 2 agonist, has been used to
treat diarrhea associated with diabetic dysautonomia.
Idiopathic fecal incontinence may be associated with
delayed conduction in the pudendal nerves & denervation
changes in the sphincter muscles.
High-fiber bulking agents may be beneficial because
semi-formed stools are easier to control than liquid feces.
Fecal disimpaction is indicated in some patients.
Daily tap water enemas aid in clearing the residue from the
rectum between evacuations & may improve continence.
Biofeedback may be successful in some cases.
Patients who undergo surgical sphincter repair may gain
some continence for solid stool, although the presence of
pudendal neuropathy is associated with a poor outcome.
Other surgical treatments include: colostomy, artificial anal
sphincters, & creation of a new sphincter with muscle graft.
-164-
SLEEP DISORDERS
Narcolepsy
Treatment:
Drug
(Class/Name)
Psychostimulant
Methylphenedate
Hydrochloride
(Ritalin)
Daily
Dose
(Mg)
Plasma
EliminAtion
HalfLife (H)
50 – 60
1–2
Methylphenedate
extended release
Dextroamphetamine
Sulfate (Dexedrine)
Dextroamphetamine
extended release
Pemoline (Cylert)
20 – 40
7 – 14
Anorexiant
(Maxindol)
1–4
Selegiline hydrochloride
(Jumex)
10 - 30
50 – 60
10 –40
Comments
Clinical effect lasts for 3 –6 h
Usually associated with fewer side
effects than dextroamphetamin.
Should be taken 30 – 45 min
before meals for proper
absorption.
Clinical effect lasts for about 8h.
Clinical effect lasts for 3 – 6 h.
9 – 14
Irritability & BP changes may limit
use.
Clinical effect lasts for 10 –12h
36
Structurally unrelated to
amphetamine, once or twice
daily dosing.
Liver function needs to be
monitored.
Structurally unrelated to
amphetamine but with similar
pharmacologic effects.
Once or twice daily dosing with an
8 –15 h duration of action.
Should be taken 1 h before meals
Two studies currently in press
from different clinics showing
the efficacy of the drug in
narcolepsy. Has some effects on
sleep architecture similar to those
of methylphenidate.
37.5 – 112
Periodic Limb Movement (PLM) Disorder
Treatment:
 Clonazepam (Rivotril)
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 Selegiline HCI (Jumex)
 Levodopa (Sinemet)
 Codeine-containing & long-acting analgesics
 Elimination of Caffeine
 Relaxation techniques
Restless Legs Symdrome (RLS)
Ekbom's Syndrome:
Treatment:
 ↓Caffeine
 Benzodiazepines
 High dose selegiline (Jumex)
Stimulant-Dependant Sleep Disorder
Drugs that cause insomma:
CNS stimulants (sustained use)
 Sympathomimetics
 Ephedrine
 Pseudoephedrine
 Albuterol
 Theophyllines
 Amphetamines
 Cocaine
 Caffeine
 Chocolate, coffee, tea,
cola
 Nicotine (Tobacco)
Antidepressants (also cause
drowsiness)
 Amitriptyline (Tryptizol)
-166-






Clomipramine
(Anafranil)
Imipramine (Tofranil)
Trimipramine
Tranylcypromine
(Parnate)
Fluoxetine (Prozac)
Trazodone (Trittico)
Cancer chemotherapeutic
agents
 Aminoglutethimide
 Flutamide (Eulexin)
Anticonvulsants
 Clonazepam (Rivotril)
Opiates (withdrawal)
 Phenytoin (Epanutin)
Major tranquilizers
 Ethosuximide (Zarontin)
Cardiovascular drugs
 Chlorpromazine
(sustained use)
(Largactil, Neurazine)
 Atenolol (Tenormin)
 Haloperidol (Halodol,
 Propranolol (Inderal)
Safinace)
 Captopril (Capoten)
 Trifluoperazine
 Lisinopril (Sinopril)
(Stelazine)
 Verapamil (Isoptin)
Thyroxine (Eltroxin)
Alcohol (sustained use and
Others
withdrawal)
 Selegiline (Jumex)
Anti-inflammatory
 Levodopa (Sinemet)
 Diclofenac (Voltaren)
 Aspirin
 Ibuprofen (Brufen)
 Naproxen (Naprosyn)
Corticosteroids
Circadian Rhythm Disorders
(Delayed sleep phase syndrome)
Treatment:
R/ Lithiun (Priadel)
R/ Sodium Valproate (Depakine)
R/ Carbamazepine (Tegretol)
Parasomnias
(e.g. Sommambulism, Enuresis, Night terross, Sleep Seizures)
Treatment:
 Avoidance of alcohol, sleep deprivation, & Psychosocial
stress.
 Low-dose benzodiazepines e.g.
R/Clonazepam (Rivotril)
 Psychotherapy
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REM Sleep Behavior Disorder (Oneirism)
(Acting out of dreams & REM motor parasomnia)
Treated by:
R/ Clonazepam (Rivotril) 0.5-1mg at bedtime
R/ Desipramine (Norpramin)
R/ L- Tryptophan (Trofax, Tryphan)
R/ Carbidopa/ Levodopa (Sinemet)
R/ Clonidine (Catapres)
Nocturnal Paroxysmal Dystonia
Treated by:
R/ Carbamazepine (Tegretol) in los doses
Nocturnal Panic Disorders
Treated by:
R/ TCAs (e.g Tryptizol or Tofranil)
R/ Clonazepam (Rivotril)
R/ Alprazolam (Xanax)
Nighttime Problems in Parkinson's Disease
Treatment:
R/ Levodopa 100mg + Carbidopa 25mg (Sinemet)
(at bedtime + A2nd dose at 2,or 3am)
R/ Sinemet CR 250mg (may improve nighttime akinesia)
R/ Clonazepam (Rivotril)
R/ Tofranil or Tryptizol
R/ Clozapine (Leponex)
(improves nighttime vocalization & visual hallucinations)
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CHANNELOPATHIES
Channeloathies affecting the chloride&sodium channels
without periodic paralysis.
 Myotonia Congenita of Thomsen
Treatment:
- Exercise
- Antimytomnia therapy e.g.:
R/ Mexiletine
- Achilles tendon stretching
- Heel cord-lengthening surgery
 Recessive Generalized Myotonia
Treatment:
- Exercise, avoid prolonged rest
R/ Mexiletine
 Acetazolamide Responsive Sodium Channel Myotonia
Treatment:
R/Acetazolamide
R/ Mexiletine
 Myotonia Fluctuans:
Treatment:
R/ Mexiletine
- Avoid high-potassium diet
Channelopathies of the sodium & calcium channels with
periodic paralysis
 Paramyotonia Congenita
R/ Mexiletine
- Mild exercise
- Keep patient warm
-163-





Paramyotonia Congenita with Hyperkalenic Periodic
Paralysis
- Mild exercise
- Thiazides
- Mexiletine
- Tocainide
Hyperkalemic Periodic Paralysis with Myotonia
- Thiazides
- Acetazolamide
- Dichlorphenamide
- Sodium restriction
Hyperkalemic Periodic Paralysis without Myotonia
- Thiazides
- Acetazolomide
- Dichlorphenamide
- Sodium restriction
Anderson's Syndrome with Potassium Sensitive Paralysis
- Mild exercise
- Glucose
- High sodium intake
- Acetazolamide
- Dichlorphenamide
Hyperkalemic Periodic Paralysis
- Acetazolamide
- Dichlorphenamide
- Potassium
- Spironolactone
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
Thyrotoxic Periodic Paralysis
- Acetazolamide
- Propranolol
- Restoration of euthyroidstate
- Oral potassium
- Spironolactone
Treatment of Channelopathies:
Diet& Lifestyle:
 Avoidance of prolonged inactivity
 Keeping muscle "warmed up"
 Warm-up contractions of muscles
 Diets generous in complex carbohydrates in patients with
soolum channelopathies
 Intermittent carbohydrate snacks↓serum potassium (release
insulin →↑K+ uptake by cells)
 Low-intensity exercise ↓ hyperkalemic & hypokalemic
periodic paralysis attacks.
 Avoid high carbohydrate diets in pts with calcium
channelopathies causing hypokalemic periodic paralysis
 Low-sodium intake prevents attacks of hypokalemic
weakness.
 Avoid exposve to cold in pts with paramyotonia congenital
(a sodium channelopathy)
Drug Treatment:
R/ Mexiletine (Mexitil)
(150-200 mg bid-tid with food or antacid).
(in chloride channel & sodium channel myotnia & in
paramyotonia congenita )
OR/ Tocainide (Tonocard) (200-400 mg bid-tid).
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R/ Acetazolamide (Diamox, Cidamex) (250mg bid-tid)
(in hypokalemic periodic paralysis)
OR/ Dichlorphenamide (Oratrol) (50 mg bid)
R/ Hydrochlorothiazide (Hydrex) (12.5- 50 mg/d)
(in hyperkalemic periodic paralysis)
R/ Triamterene (Thiametrene) (50-100 mg/d)
(in hypokalemic paralysis that is made worse by
acetazolamide)
OR/ Spironolactone (Aldactone) (50-100mg/d)
R/ Propranolol (Inderal) (20-40mg bid)
(in thyrotoxicosis & prevents recurrence of attacks in
hypokalemic & thyrotoxic periodic paralysis)
R/ Potassium chloride
Oral potassium as preventive therapy in hypokalemic p.p. (2040 mEq of Slow K at-bedtime)
- Acute attack: 25 mEq of kCI orally at 30 min. intervals
- Severe attacks may need i.v. KCI. (with ECG monitoring
& serum K+ level
(given in 5% Mannitol at 0.05-0.1 mEq/ kg body wt
I.V.bolus)
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NEUROIMMUNOLOGY
BEHCET'S DISEASE
Treatment:
Drug Treatment:
Glucocorticoids
R/ Methylprednisolone (Solu-Medrol)
(IV 1000mg/d for 5-7 days)
Followed by:
R/ Prednisone (Hostacortin) 5 mg tab.
(Oral 1mg/ kg/d to be tapered over 1-3 months, then
maintained on 8- 16mg/d or every other day for at least
another 3 months)
For refractory mucocutaneous lesions:
R/ Prednisone (Hostacortin) 5mg (5- 20mg/d orally)
Colchicine (Colmediten)
R/ Colchicine (Colmediten) tab.
(0.5-1.5mg/d orally)
Azathioprine (Imuran)
R/ Azathioprine (Imuran) 50mg tab
(2.5mg/kg/d in divided doses, with food up to 150-200 mg/d
in adults, to be reached over 4 wks, CBC& L.F. Ts initially &
monitored/ wk for 1 month; every 2 wks for the next 2
months & monthly thereafter).
R/ Cyclosporin (Sandimmun)
(5 mg/kg/d orally)
R/ Chlorambucil (Leukeran)
(0.1-0.2 mg/kg/ d for several months, then tapered to 2 mg/d
or every other day, to be discontinued 6 months after
remission. Regular CBC & LFTs monitoring is needed.
-167-
WBC count of 3000/ML is an indicator of therapeutic
level).
Interferon alfa (Roferon A)
(6 million LU. S.c. 3 times a wk initially maintained on 3
million IU s.c. 3 times a wk)
Thalidomide
(100-300mg/kg/d, orally divided in 2 doses)
Cyclophosphamide
(Endoxan, Cytgoxan) (Orally 2-3 mg/kg/d, or IV 700- 1000 mg/
m2 body surface area monthly + IV glucocrticoids+ antiemetic
IV hydration + continuous bladder irrigation or infusion of
mesna to prevent hemorrhagic cystits. Adjust Endoxin dose to
maintain WBC count of 2500-4000 cells/ML)
Interventional Coil insertion for aneurysms.
Physical/ Speech Therapy & Exercise:
 For pts with CNS- Neuro- Behcet syndrome & neurologic
deficits (with UMN & cerebellar signs)
 Assistive appliances (canes, walkers, ankle-foot orthotics,
knee braces, or other rehabilitation devices)
 Stretching exercise & Baclofen (Lioresal) relieve spasticity
Other Therapies:
 IV IG in CNS-NBS
 Tacrolimus (a macrolide) inhibits T-cell activation & the
synthesis of several cytokines. It is used to treat ocular
inflammation in Behcet's disease.
 Other immunosuppressants e.g. methotrexate, imnunomodulators e.g. levamisole (Ketrax) & pentoxifylline (Trental)
Aspirin & dipyridamole (persantin) have been used
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ANTIPHOSPHOLIPID ANTIBODY SYNDROME
Treatment:
Diet & Lifestyle:
 Control HTN & DM
 Stop cigarette smoking
 Treat heart alisease appropriately
 Discontinue alcohol use
 Treat hyperlipidemia
 Encourage physical activity
Drug Treatment:
R/ Warfaren (Marevan) tab
(5mg/d initially, to be adjusted according to the INR level, to
be kept between 2&3)
R/ Clopidogrel (Plavix) 75mg tab. (75 mg/d)
R/ Dipyridamole & Aspirin (Persantin Plus)
(200mg Dipyridamole + 25 mg Aspirin bid)
R/ Prednisone (Hostacortin) 5mg tab.
(60 to 100mg/d. orally)
R/ IVIg (IV Globulin)
(IV 0.4mg/kg body wt/d for 2-5 days)
Other Treatments:
 Plasmapheresis (2-3 liters are removed 3 times /wk)
SYSTEMIC CNS VASCULITIDES
Therapeutic Regimens:
 Wegener's granulatosis:
- Cyclophosphamide/ prednisone
- Trimethoprim- sulfamethoazole
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 Polyarteritis nodosa:
- Cyclophosphamide- Prednisone
 Churg- Srauss syndrome:
- Cyclophos phamide- Prednisone
 Temporal arteritis:
- Prednisone
 Isolated angiitis of the CNS:
- Cyclophosphamide- Prednisone
 Takaysu's arteritis:
- Antiplatelets
- Prednisone- Cyclophosphamide
 Behcets disease:
- Azathioprine (Imuran)
 Seconday Vasculitides:
- Viral: (Interferon alpha)
- Other infections (Appropriate antibiotics)
 Kawasaki's disease: (IVIg)
 Toxic vasculitides: (Remove the cause)
Drug Treatment
 Antiplatelets: Aspirin, (325mg/d)
 NSAIDs: Ibuprofen (Brufen), (400mg/ 4.6 hrs)
 Selective cox2 in hibitors:
R/ Rofecoxib (Vioxx), 25-50 mg/d.
OR: Celecoxib (Celebrex), 200mg bid
 Glucocorticoids:
R/ Prednisone (Hostacortin), 30mg/d
R/Methylprednisolone (Solu- Medrol)
(4mg is equivalent to 5 mg prednisone)
R/ Dexamethasone (Decadron) IV
 Cyclophosphamide (Endoxan)
(Orally 1.5-2 mg/kg/d. or IV 300-800 mg/ 3-4 wks)
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 Cyclophosphamide / prednisone (Endoxan/ Hostacortin)
R/ Cyclophosphamide (Endoxan)
(IV500mg/ 3 wks for 1yr., or oral 100-150mg/d for 1yr.)
R/ Prednisone (Hostacortin) 5mg tab.
(Oral 40-60mg/d for 6 months & maintained at 10-15mg/d
for at least 6 months before slowly tapering)
 Methotrexate:
R/ Methotrexate (15-30mg orally weekly)
 Chlorambucil (Leukeran)
(0.1-0.2 mg/kg/d for 3-6 weeks).
(High- dose therapy is 30 mg/m2 every 2wks)
 Mycophenolate mofetil (Cellcept)
 Thalidomide
(100-300mg orally at bedtime)
 Interferon alpha (Roferon A)
(3 million IU s.c. 3times weekly in chronic hepatitis C)
Agents that interfere with tumor necrosis factor-α
 Entarencept
(25mg s.c twice a wk, in rheumatoid arthritis)
 Infliximab
(10mg/kg IV, in Crohn's disease)
 Gene therapy
Interventional Procedures:
 Plasmapheresis
(6 exchanges, 2-3 liters each over the first 2 wks, then 1
exchange monthly). Start Azathioprine (Imuran) to maintain
the therapeutic effect)
 IVIg (for Kawasaki's disease)
(A single IV dose of 2gm/kg body wt)
 Surgery (for Takayasu's disease):
Bypass+Angioplasty + stenting of stenotic subclavian artery
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NEUROPSYCHIATRIC SYSTEMIC LUPUS
ERYTHEM ATOSUS
Therapeutic Regimens:
Manifestation
Symptomatic
Immune modulation
High-dose
AEDs
 Seizures
glucocorticoid
Treatment of extraNo specific
neural disease
 Delirium
treatment
activeity
Antipsychotics
 Psyvhosis
High-dose
Anticoagnlants or glucocorticoids +
 Cerebral
Antiplatelets
cytotoxic
vasculopathy
immunosuppressives
Effective treatment of
Anticoagulants
extraneural disease
 Stroke
Antiplatelets
activity
No specific
 Transverse
treatment
myelopathy
Treatment:
Diet & Lifestyle:
 Maintain low-sodium, low-fat, & low-carbohydrate diet
 Avoid alcohol intake
 Encourage pts to reduce stress & to avoid fatigue
Drug Treatment:
Glucocorticoids
R/ Prednisone (Hostacortin) 5mg tab (orally, 1mg/kg body wt/d.)
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R/ Methylprednisolone (Solu-Medrol)
(IV 1 gm in 100 ml of normal saline over 1-2hrs daily or
every other day for 3-6 doses)
Hydroxychloroquine sulfate (Plaquentil, Hydroquine)
R/ Plaquentil
(Initially: 200mg o.d- bid. Maintainance: 200-400 mg/d)
Nonsteroidal anti-inflammatory drygs (NSAID):
R/ Ibuprofen (Brufen) 400 mg tab- (400mg tid-qid)
COX-2 Inhibitors:
R/ Rofecoxib (Vioxx) 75mg tab.(1 tab daily)
OR: Celecoxib (Celebrex) 200mg cap (1 cap bid)
R/ Cyclophosphamide (Cytoxan, Endoxan) 25& 50 mg. tab.
(Orally: 1-5 mg/kg 2 times/ wk Pulsed IV therapy: 750- 3000
mg/ m2 Doses > 1000 mg are divided over 3-5 days)
Azathioprine (Imuran)
R/ Azathioprine (Imuran) 50 mg tab.
(1 mg/kg/d in 1 or 2 divided doses)
Methotrexate (Methotrexate)
R/ Methotrexate 2.5mg tab
(10-25mg/wk orally, or 0.5mg -0.8mg/kg IV once a wk to
once a month)
Intravenous Immunoglobulin (IVIg)
R/ IV Globulin [2gm/ kg IV over 5 days (0.4mg/kg/d) initially,
followed by 2 or more maintenance infusions of 0.4- 1gm/kg
at 4-8 wk intervals]
Inteventional Procedures:
 Plasmapheresis
(Removal of 4-6 liters of plasma over several hours for 4-6
exchanges over 7-14 days)
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Other Treatments:
Treatment of psychological problems:
 Individual supportive psychotherapy
 Group therapy
 Family therapy
 An exercise regimen
 Relaxation exercises
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MITOCHONDRIAL DISORDERS
Mitochondrial defects involving energy metabolism
Defects of pyruvate metabolism
o Pyruvate dehydrogenase deficiency
o Pyruvate carboxylase deficiency
Defects of Kreb's cycle:
o Fumarate deficiency
o α-ketoglutarate dehydrogenase deficiency
Defects of respiratory chain:
o Individual respiratory chain deficiencies
o Multiple respiratory chain deficiencies
o Defects of mitochondrial DNA (mtDNA)
o Defects of intergenomic signaling
Defects of fatty oxidation:
o Carnitine cycle disorders
o Intra-mitochondrial fatty oxidation disorders
o Long-chain fatty acids
o Medium-chain fatty acids
o Short-chain fatty acids
Treatment:
Diet & Lifestyle
Pyruvate dehydrogenase deficiensy
 Ketogemic diet:
At least 80% of energy is derived from fat
Pyruvate carboxylase deficiency
 Avoid fasting
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 Continuous glucose supplementation or high carbohydrate
diet
Respiratory chain & kreb's cycle disorders
 Avoid a hypercaloric diet & use a low- carbohydrate diet
Fatty acid oxidation disorders
 Avoid fasting, prolonged aerobic exercise, infections, &cold
exposure
 A high- carbohydrate, low-fat diet: 70- 75% carbohydrates
&10-15% fat- with frequent feeding throughout the day
 Monitor essential fatty acids
 Restrict medium & long- chain fatty acids (LCFA) in
multiple –coenzyme A dehydrogenase deficiency & in
medium & short chain fatty acid oxidation disorders.
 Long-chain fatty acids (LCFA) are restricted in LCFA
oxidation disorders, whereas MCFA are given.
 Medium-chain triglyceride oil (a source of MCFA) can be
given in LCFA oxidation disorders at a dose of 0.5mg/kg/d.
& ↑up to 1-1.5 gm/kg/d. in infants < 1 yr old, ↑ dose up to 23gm/kg/d.
 Oral docosahexaenoic acid (DHA) triglyceride (25mg/d in pts
< 20 kg& 30 mg/d in pts > 20 kg) prevent pigmentary
retinopathy in DHA deficiency. It improves long-chain 3hydroxyacyl coenzyme A (LCHAD) deficiency & severe
neuropathy.
 Uncooked cornstarch 1-2.5 gm/kg/d at bedtime is useful in
some children.
Drug Treatment:
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
Cofactors and vitamins including thiamine, riboflavin,
biotin, and alpha-lipoic acid.
 Enzyme activators such as dichloroacetate.
 Electron transporters including CoQ 10 and analogues, and
vitamin C.
 Free radical scavengers such as CoQ 10 and analogues,
vitamin C, and vitamin E.
 L-carnitine.
 Others including steroids, creatine monohydrate, growth
hormone, and folic acid.
Thiamine:
 100 to 500 mg per day up to 2000 mg per day, and from 10
to 40 mg/kg per day up to 200 mg/kg per day.
Riboflavin:
 10 to 400 mg per day. In infants and young children, doses
range from 10 to 150 mg per day and in older children and
adults dosages are up to 300 to 400 mg per day.
Biotin
Alpha-lipoic acid:
 10 to 50 mg/kg per day.
Dichloroacetate:
 25 to 50 mg/kg per day orally is given in most cases. Higher
doses of more than 100 mg/kg per day are generally given
via intravenous administration.
Coenzyme Q10 and its analogues:
 60 to 300 mg per day or 2 to 5 mg/kg per day.
Artificial electron acceptors:
 Vitamin C dose is 2 to 4 g per day. Vitamin K3 dose is 20 to
500 mg per day.
Free radical scavengers:
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
Vitamin C dose is 2 g per day. Vitamin E doses 200 to 400
IU per day or 50 to 100 mg/kg per day.
L-carnitine:
 50 to 200 mg/kg per day.
Oxaloacetate precursors:
 There is no standard dosage for these compounds, and
titration following biochemical and clinical response is
recommended.
Steroids:
 Dosages are variable, i.e., 0.75 mg/kg per day, 2 to 16 mg
every other day or 30 mg per day. Fatal metabolic acidosis
has been reported as a complication of steroid treatment in
mitochondrial disorders.
Creatine monohydrate:
 Dosages for adults are 10 to 20 g per day and for children
are 0.1 to 0.2 g/kg per day.
Growth hormone:
 The dosage used in this report was 0.07 U/kg per day
administered subcutaneously.
Supportive Therapy:
 Early detection and symptomatic treatment of medical
problems in patients with mitochondrial disorders can
improve quality of life and prevent further complications.
They include the following:
 Treatment of seizures with conventional antiepileptic drugs.
 Caution should be taken with valproic acid, because it has
been associated with severe hepatic dysfunction in patients
with underlying mitochondrial disorders.
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
Concomitant treatment with L-carnitine is recommended,
because valproic acid inhibits plasma membrane L-carnitine
uptake.
 Conventional medical management for endocrinologic
complications
such
as
pancreatic
dysfunction,
hypoparathyroidism, or adrenal insufficiency.
 Blood transfusions and haematopoietic growth factor in
Pearson syndrome.
 Correction of electrolyte imbalance in cases with renal
tubular acidosis and Fanconi syndrome.
 Correction of folic acid deficiency associated with Kearns
Sayre syndrome.
 Pacemaker to prevent fatal cardiac arrhythmias.
Physical/Speech Therapy and Exercise:
 In patients with mitochondrial myopathy, biochemical and
functional measures improved with training.
 In mitochondrial myopathies, aerobic training may have
significant beneficial effects.
 DCA may have additive effects to aerobic training in a
patient with complex IV deficiency who had a substantial
improvement of aerobic capacity and oxidative metabolism.
Aerobic exercises:
 For mitochondrial myopathies.
Other Treatments:
 Gene therapy:Gene therapy for both nDNA and mtDNA
disorders is still a remote possibility for treatment of
mitochondrial diseases.
 Different strategies that have been proposed include the
following:
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
 For cytosolic synthesis of mitochondrially-encoded
proteins: this approach consists of expressing a normal
copy of a defective mtDNA gene in the nucleus, with
synthesis of the polypeptide in the cytosol followed by
import into the mitochondria. This approach would be
applicable for missense mtDNA mutations involving
protein-encoding genes, such as Leber’s hereditary optic
atrophy and NARP.
 For complementation by mitochondrial gene expression:
this approach consists of introducing normal copies of
the mutated allele directly into the mitochondria;
however, the delivery system for this approach remains
problematic.
 For sequence-specific inhibition of mutant mtDNA
replication: this approach consists of selectively
inhibiting the replication of mutant mitochondrial
genome to give the wild type genome a distinct
replicative advantage. This approach would be
applicable for heteroplasmic mtDNA mutations.
Another therapeutic approach with indirect genetic
manipulation is induction of muscle regeneration: this
approach consists of inducing muscle damage to stimulate
replication of satellite cells that have low levels of mutation,
thus shifting the relative proportion of mutant and wild-type
mtDNA. This strategy would be indicated in heteroplasmic
mtDNA mutations limited to skeletal muscle. This approach
has been tried in an attempt to restore levator function in
patients with progressive external ophthalmoplegia and
Kearns Sayre syndrome who have ptosis. These patients
received bupivacaine injections in the levator, but failed to
show any improvement.
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LEUKODYSTROPHIES
Neurometabolic Genetic Disorders
With Brain White Matter Involvement
GM1 Gangliosidosis:
 No specific treatment
Salla Disease
 No specific treatment
Glutaric Aciduria Type I
Treatment:
 Diet low in protein, lysine & tryptophan & high in riboflavin
& carnitine prevents acute deterioration.
 Vinyl-GABA (vigabatrin) has been used to treat the
dystonia.
Hyper Phenyl Alanenia
Treatment:
 Diet
 Dopamine
Maple Syrup Urine Disease
Treatment
Acute deterioration:
 exchange transfusion,
 peritoneal or hemodialysis,
 high energy carbohydrate and lipid intake,
 insulin,
 Formula that lacks branched-chain amino acids prevents
acute metabolic deterioration.
 Thiamine supplement
Hyperhomocyteinemias
Treatment:
 Oral vitamin B low in methionine & cystine for partial
deficiency of cystathionine synthesis.
 Folic acid for all.
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
Hydroxycobalamin, methionine & betain for defects of
intracellular cobalamin metabolism.
Mitochondrial Disorders
 No effective treatment.
Pyruvate Carboxylase Deficiency:
Treatment:
 No effective treatment is available.
 One patient partially responded to biotin.
Cockayne Syndrome:
Treatment:
 Supportive therapy includes physical therapy for the
contractures and protective cream for the skin.
Cerebrotendinous Xanthomatosis:
Treatment:
 Chenodeoxycholic acid may reverse dementia and motor
dysfunction, improve peripheral nerve motor conduction and
evoked potentials.
 Other cholesterol-lowering agents may be useful.
 Early treatment can prevent complications.
Sjogren-Larsson Synrome:
Treatment:
 Acitretin therapy for skin symptoms.
 No effective therapy for neurologic disease.
Niemann-Pick Disease Type C:
Treatment:
 No specific treatment available.
 Supportive treatment for dystonia, seizures & cataplexy.
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PRIMITIVE LEUKODYSTROPHIES
A. Primitive Leukodystrophies with Biochemical Markers:
Adrenoleukodystrophy (ALD) &
Adrenomyeloneuropathy (AMN):
Treatment:
 Bone marrou transplantation in patients with early onset
cerebral forms.
Metachromatic Leukodystrophy (MLD):
Treatment:
 Bone marrou transplantation in juvenile or adult forms.
Globoid Cell Leukodystrophy (GLD or Krabbe)
Treatment:
 Bone marrou transplantation in late onset forms
Canavan Disease
 No specific treatment.
B. Primitive Leukodytrophies with Genetic Markers:
Pelizaeus Merzbacher Disease (PMD).
Spastic Paraplegia 2 (SPG2)
Treatment:
 No Specific treatment
18q No available treatment
Alexander Disease (AD)
 No available treatment
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C. Primitive Leukodystrophies with Unknown Etiology
Childhood Ataxia with CNS Hypomyelination (CACH) Or
Vanishing White Matter Disease (VW)
 No Specific treatment
Aicardi Gouttieres Syndrome
 No available treatment.
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