LMCC PreparationLMCC PreparationBack to BasicsBack to Basics

NeurologyNeurology

Dr. C.R. SkinnerDr. C.R. Skinner

17 April 200817 April 2008

Major Topics

• Neurology Made Simple Review• Headache• Trauma• Infections• Cerebrovascular Disease• Demyelination• Seizures• Degenerative Diseases• Sleep Disorders

Neurology Made SimpleNeurology Made SimpleQuestionsQuestions

• Is the Problem Neurological?Is the Problem Neurological?

• If So , Where Is It in the Nervous If So , Where Is It in the Nervous System ?System ?

• What Is the Most Likely Cause ?What Is the Most Likely Cause ?

• Is This Problem Serious Enough toIs This Problem Serious Enough to Require Urgent Referral ? Require Urgent Referral ?

• How to Stabilize the Patient DuringHow to Stabilize the Patient During Transport Transport

NEUROLOGY MADE NEUROLOGY MADE SIMPLESIMPLE

IS THE PROBLEM NEUROLOGICAL?IS THE PROBLEM NEUROLOGICAL?

Are there hard organic features ?Are there hard organic features ?

Is the behaviour bizarre ?Is the behaviour bizarre ?

Is there a history of seizures, drugIs there a history of seizures, drugaddiction or of psychiatric illness ?addiction or of psychiatric illness ?

Do the signs and symptoms make sense ?Do the signs and symptoms make sense ?

NEUROLOGY MADE NEUROLOGY MADE SIMPLESIMPLE

INTRODUCTIONINTRODUCTION

NEUROLOGICAL PROBLEMNEUROLOGICAL PROBLEM

WHERE IS THE LESIONWHERE IS THE LESION

WHAT IS THE CAUSEWHAT IS THE CAUSE

INVESTIGATIONINVESTIGATION

TREATMENTTREATMENT

PROGNOSISPROGNOSIS

MuscleNeuromuscular Junction

Peripheral nerve

Spinal Cord

Brain Stem

Deep White Matter/Basal Ganglia/Thalamus Cortex Cerebellum

Mental Status

Cranial Nerves

Motor

Reflexes

Sensory

Coordination

Gait

Localization Matrix

NEUROLOGY MADE NEUROLOGY MADE SIMPLESIMPLE

INTRODUCTIONINTRODUCTION

NEUROLOGICAL PROBLEMNEUROLOGICAL PROBLEM

WHERE IS THE LESIONWHERE IS THE LESION

WHAT IS THE CAUSEWHAT IS THE CAUSE

INVESTIGATIONINVESTIGATION

TREATMENTTREATMENT

PROGNOSISPROGNOSIS

Drugs Inflammatory Metabolic Vascular Electrical Trauma Neoplastic Degenerative Genetic

Acute

Subacute

Chronic

Etiology Matrix

NEUROLOGYNEUROLOGY MADE SIMPLEINVESTIGATIONS

History

Physical

According to presumed localizationand etiology

Metabolic systemic CSF

Structural

Neurophysiological

Time Sequence

• When was the person last neurologically normal?• What was the speed of onset of the symptoms?• What was the state of the patient’s health in the

last few days, weeks, months?• What medications is the patient taking and has

there been any recent changes?• Are there any significant other medical or surgical

problems?

HeadacheHeadache

Loss Of ConsciousnessLoss Of Consciousness

WeaknessWeakness

Difficulty With Vision , Hearing , Difficulty With Vision , Hearing , TasteTaste

NumbnessNumbness

WeaknessWeakness

DizzinessDizziness

Lightheadedness , Vertigo, Off Lightheadedness , Vertigo, Off balancebalance

FatigueFatigue

Loss Of BalanceLoss Of Balance

Loss Of CoordinationLoss Of Coordination

Difficulty Swallowing, ChewingDifficulty Swallowing, Chewing

Urinary And Stool IncontinenceUrinary And Stool Incontinence

Sexual DysfunctionSexual Dysfunction

Sleep DifficultiesSleep Difficulties

ESSENTIAL HISTORICALHISTORICAL FEATURESHISTORY OF PRESENT ILLNESS

Drugs Inflammatory Metabolic Vascular Electrical Trauma Neoplastic Degenerative Genetic

Acute

Subacute

Chronic

Etiology Matrix

NEUROLOGY MADE SIMPLESIMPLELOCALIZATION ANALYSIS

MuscleMuscle

Neuromuscular junctionNeuromuscular junction

Peripheral nervePeripheral nerve

Spinal cordSpinal cord

Brain stemBrain stem

Thalamus or basal gangliaThalamus or basal ganglia

CortexCortex

CerebellumCerebellum

MuscleNeuromuscular Junction

Peripheral nerve

Spinal Cord

Brain Stem

Deep White Matter/Basal Ganglia/Thalamus Cortex Cerebellum

Mental Status

Cranial Nerves

Motor

Reflexes

Sensory

Coordination

Gait

Localization Matrix

Muscle

Neuromuscular Junction

Peripheral Nerves

Lateral Medullary SyndromeLateral Medullary Syndrome• IpsilateralIpsilateral

– Pain numbness, impaired Pain numbness, impaired sensation over half of facesensation over half of face

– Ataxia of limbs with Ataxia of limbs with falling towards side of falling towards side of lesionlesion

– Vertigo, nausea, vomitingVertigo, nausea, vomiting– Horner’s syndromeHorner’s syndrome

• ContralateralContralateral– Impaired pain and Impaired pain and

temperature sensation temperature sensation over half of the body and over half of the body and some of the facesome of the face

Lateral Pontine SyndromeLateral Pontine Syndrome• IpsilateralIpsilateral

– Horizontal, vertical Horizontal, vertical nystagmus vertigo, nausea, nystagmus vertigo, nausea, vomiting, oscillopsiavomiting, oscillopsia

– Facial paralysisFacial paralysis

– Paralysis of conjugate gaze Paralysis of conjugate gaze to side of lesionto side of lesion

– Deafness, tinnitusDeafness, tinnitus

– AtaxiaAtaxia

– Impaired sensation over faceImpaired sensation over face

• ContralateralContralateral

– Impaired pain and thermal Impaired pain and thermal sense over half of bodysense over half of body

Ventral Midbrain SyndromeVentral Midbrain SyndromeWeber’s SyndromeWeber’s Syndrome

• IpsilateralIpsilateral

• Diplopia, dilated Diplopia, dilated pupilpupil

• AtaxiaAtaxia

• ContralateralContralateral

• Hemiplegia, Hemiplegia, mainly upper mainly upper limb and facelimb and face

CORRELATIVE FACTORSCORRELATIVE FACTORSCAPSULE, THALAMUS AND BASAL GANGLIACAPSULE, THALAMUS AND BASAL GANGLIA

• Hemi-sensory or motor signsHemi-sensory or motor signs

• Sensory signs of primary modalitiesSensory signs of primary modalities

• Sensory involvement of the trunkSensory involvement of the trunk

• Lack of cortical signsLack of cortical signs

• Uniform motor signs in arm ,Uniform motor signs in arm ,leg and faceleg and face

• Hypertension risk factorHypertension risk factor

CORRELATIVE FACTORSCORRELATIVE FACTORSCORTICALCORTICAL

• Aphasia and right sided weaknessAphasia and right sided weaknessfluent, non - fluent, paraphasiafluent, non - fluent, paraphasia

• Weakness - arm and face more than legWeakness - arm and face more than leg

• Visual field defectsVisual field defects

• Cortical sensory disturbanceCortical sensory disturbanceinattentioninattentionleft-rightleft-rightacalculiaacalculiaagnosiaagnosiaapraxiaapraxia

CerebellumBasal Ganglia

•Modulating structuresModulating structures

•Rule out other systems firstRule out other systems first

•Ipsilateral Rule for pure Ipsilateral Rule for pure cerebellar lesionscerebellar lesions

FINAL CHECKLISTTHINGS NOT TO MISS

MUSCLEPOLYMYOSITIS, POLYMYALGIA RHEUMATICA

NEUROMUSCULARMYASTHENIA

PERIPHERAL NERVEGUILLAIN - BARRE SYNDROME

SPINAL CORDACUTE SPINAL CORD COMPRESSION

FINAL CHECKLISTCHECKLISTTHINGS NOT TO MISS

BRAIN STEMBRAIN STEM

STROKE, MULTIPLE SCLEROSISSTROKE, MULTIPLE SCLEROSIS

MENINGITISMENINGITISLISERIA, TBLISERIA, TB

GUILLAIN - BARRE - FISHER VARIANTGUILLAIN - BARRE - FISHER VARIANT

TUMORSTUMORS

FINAL CHECKLIST

THINGS NOT TO MISS

CORTEX

STROKE

HERPES ENCEPHALTIS

SEIZURES

TUMORS

SUBARACHNOID HEMORRHAGE

Circulation du LCRCirculation of CSF

This 20 year old man presents with This 20 year old man presents with a three day history of abnormal a three day history of abnormal behaviour consisting of hallucinations, behaviour consisting of hallucinations, delusions of grandeur and memory delusions of grandeur and memory loss for recent events.loss for recent events.

He had been " up north " fishing just He had been " up north " fishing just prior to the onset of these symptoms.prior to the onset of these symptoms.

Case Case

•Physical ExamPhysical Exam

•Fever 38.0 CFever 38.0 C

•InattentiveInattentive

•Poor short term memoryPoor short term memory

•Left upper quadrantopsiaLeft upper quadrantopsia

•Hyperflexia Left upper and Hyperflexia Left upper and lower limblower limb

Case Case

Case 1Case 1

• Where is the lesion?Where is the lesion?– why?why?

• What is the cause?What is the cause?

• What are the immediate treatment What are the immediate treatment priorities?priorities?

Herpes Simplex Encephalitis

• Any time of year, any age, any sex

• Selective infection of temporal lobes

• New onset seizures or behaviour disturbance

• Treat if you suspect - Acyclovir 30 mgm/kg-day

Herpes SimplexHerpes SimplexTreatmentTreatment

• Acyclovir IVAcyclovir IV

• Management of ICP (max at 8 – 10 Days)Management of ICP (max at 8 – 10 Days)– Head upHead up– HyperventilationHyperventilation– MannitolMannitol– Hypertonic SalineHypertonic Saline

• Seizure treatmentSeizure treatment

CASE 2

This 24 year old soldier was doing his This 24 year old soldier was doing his early morning run with his regimental early morning run with his regimental company. He developed an acute severe company. He developed an acute severe headache which caused him to stop and fall headache which caused him to stop and fall to the ground. to the ground.

On examination, he was alert, oriented, On examination, he was alert, oriented, moving all four limbs with a normal moving all four limbs with a normal neurological examination.neurological examination.

Where is the lesion ?Where is the lesion ?

CT Scan

without contrast

Subarachoid Hemorrhage

CT ScanSubarachnoid

Blood

Subarachnoid HemorrhageSubarachnoid Hemorrhage

• Worse headache of lifeWorse headache of life• Sudden onset, often with activitySudden onset, often with activity• Signs of meningeal irritationSigns of meningeal irritation

– Kernig, BrudzinskiKernig, Brudzinski

• Focal signsFocal signs• Signs of comaSigns of coma• Positive CT scanPositive CT scan• Positive LPPositive LP

Subarachnoid Hemorrhage

• Blood in subarachnoid space

• Require urgent referral for angiogram

• Use acetaminophen not ASA for headache

Subarachnoid HemorrhageInvestigations

• CT Scan - 90 - 95% sensitive• LP - nearly 100% sensitive

– rbc in CSF– xanthochromic in CSF after 12 – 18 hours

• Angiogram• Treatment

– surgical clipping– coiling

Subarachnoid HemorrhageTreatment

• Clipping

• Coiling

Giant Aneurysm

GDC Coil

Headache in the Emergency Headache in the Emergency RoomRoom

1. Distinguish ominous from benign 1. Distinguish ominous from benign headacheheadache

2. Treat effectively the benign headaches2. Treat effectively the benign headaches

Assessment ApproachAssessment ApproachAirwayAirway

BreathingBreathing

CirculationCirculation

DrugsDrugs

EvaluationEvaluation

Assess, secure Assess, secure Not a problem unless obtundedNot a problem unless obtunded

Assess, assistAssess, assist

Not a problem unless obtundedNot a problem unless obtunded

O2 not necessaryO2 not necessary

IV line with crystalloid to restore volumeIV line with crystalloid to restore volume

No drugs until diagnosed, unless required to No drugs until diagnosed, unless required to stablize circulationstablize circulation

In particular, no analgesics until diagnosedIn particular, no analgesics until diagnosed

Rapid neurological assessmentRapid neurological assessment

Investigations as necessaryInvestigations as necessary

The Spectrum of Ominous The Spectrum of Ominous HeadachesHeadaches

• Subarachnoid hemorrhageSubarachnoid hemorrhage

• meningitismeningitis

• increased intracranial pressureincreased intracranial pressure

Danger SignalsDanger Signals

• the worse headache everthe worse headache ever

• onset with exertiononset with exertion

• decreased level of consciousnessdecreased level of consciousness

• meningeal irritationmeningeal irritation

• abnormal physical signs (including abnormal physical signs (including feverfever))

• worseningworsening

All Clear SignalsAll Clear Signals

• previous identical headachesprevious identical headaches

• patient bright and alertpatient bright and alert

• neck suppleneck supple– Kernig, Brudzinski’s signsKernig, Brudzinski’s signs

• normal examinationnormal examination

• improving without analgesicsimproving without analgesics

CT ScanCT Scan

• detects most conditions causing increased detects most conditions causing increased ICPICP

• misses 10 - 15 % of subarachnoid misses 10 - 15 % of subarachnoid hemorrhagehemorrhage

• misses nearly all cases of meningitismisses nearly all cases of meningitis

Modified HIS Diagnostic Modified HIS Diagnostic Criteria for MigraineCriteria for Migraine

• multiple previous attacksmultiple previous attacks

• duration of attacks a few hours to a few daysduration of attacks a few hours to a few days

• headaches have at least two of:headaches have at least two of:

• hemicranialhemicranial

• severesevere

• pulsatingpulsating

• worse with activityworse with activity

• headaches accompanied by at least one of:headaches accompanied by at least one of:

• nausea and or vomitingnausea and or vomiting

• aversion to light or noiseaversion to light or noise

• no evidence of ominous disease in history or examinationno evidence of ominous disease in history or examination

Classification of Primary Classification of Primary HeadachesHeadaches

• MigraineMigraine– with aura, without aurawith aura, without aura

– Ophthalmoplegic, retinalOphthalmoplegic, retinal

• Tension HeadacheTension Headache

• Cluster HeadacheCluster Headache

• Miscellaneous without structural Miscellaneous without structural lesionlesion

Treating Migraine in the ERTreating Migraine in the ER

1. Restore intravascular volume1. Restore intravascular volume

2. Identify contraindications2. Identify contraindications

3. Choose appropriate medication3. Choose appropriate medication

Narcotic - AntinauseantNarcotic - Antinauseant

• Meperidine 75 - 100 mg plusMeperidine 75 - 100 mg plus

• Prochlorperazine 5-10 mgProchlorperazine 5-10 mg

• IV slow pushIV slow push

DHE - AntinauseantDHE - Antinauseant

• Metoclopramide 10 mg IV, followed in 10 Metoclopramide 10 mg IV, followed in 10 minutes byminutes by

• DHE 0.5 - 1.0 mg IV by slow pushDHE 0.5 - 1.0 mg IV by slow push

ChlorpromazineChlorpromazine• Ensure patient is normovolemicEnsure patient is normovolemic

– 250 - 500 cc crystalloid250 - 500 cc crystalloid

• Prepare CPZ for injectionPrepare CPZ for injection– 25 mg (1ml) CPZ diluted to 5 ml by adding 4 ml of 25 mg (1ml) CPZ diluted to 5 ml by adding 4 ml of

crystalloidcrystalloid

– each ml contains 5 mg CPZeach ml contains 5 mg CPZ

• Inject into IV tubing 5 mg CPZ every 10 - 15 Inject into IV tubing 5 mg CPZ every 10 - 15 minutes, stopping when minutes, stopping when – improvement clearly occurring, orimprovement clearly occurring, or

– 25 mg given25 mg given

– Watch for hypotension and sedationWatch for hypotension and sedation

Nasal SpraysNasal Sprays

• DHEDHE

• SumatriptanSumatriptan

SumatriptanSumatriptan

1 mg SC if:1 mg SC if:• no ergot or DHE in past 24 hoursno ergot or DHE in past 24 hours• no contraindicationno contraindication

Patient Instructions:Patient Instructions:GuidelinesGuidelines

• Do not drive a car or operate machineryDo not drive a car or operate machinery

• Do not drink alcohol or take Do not drink alcohol or take tranquillizers, antihistamines, or other tranquillizers, antihistamines, or other drugs that affect the CNSdrugs that affect the CNS

• Store in child-resistant containersStore in child-resistant containers

• Neurological followup if frequent or Neurological followup if frequent or incapacitatingincapacitating

Cluster HeadacheCluster Headache

• 1/10 as common as migraine1/10 as common as migraine

• Not genetically determinedNot genetically determined

• M:F 6:1M:F 6:1

• Later OnsetLater Onset

• RhythmicityRhythmicity

• Severe unilateral orbital, supraorbital Severe unilateral orbital, supraorbital and/or temporal painand/or temporal pain

Cluster HeadacheCluster Headache

• IpspilateralIpspilateral– conjunctival injectionconjunctival injection– nasal congestionnasal congestion– forehead and facial swellingforehead and facial swelling– miosismiosis– ptosisptosis– eyelid edemaeyelid edema

• Every 2 - 8 times per dayEvery 2 - 8 times per day

Cluster HeadacheCluster Headache

• TriggerTrigger– alcoholalcohol

• PathophysiologyPathophysiology– Role of proximal internal carotid arteryRole of proximal internal carotid artery– Role of histamineRole of histamine

• TreatmentTreatment

• Acute attackAcute attack– ergotamineergotamine

Cluster HeadacheCluster Headache

• ProphylaxisProphylaxis– SansertSansert

– SteroidsSteroids

– LithiumLithium

– Calcium channel blockersCalcium channel blockers

– CombinationsCombinations

Inflammatory HeadachesInflammatory Headaches

• Most people who think they have sinus Most people who think they have sinus headaches usually have migraine or headaches usually have migraine or muscle contraction headachemuscle contraction headache

• Diagnosis requires acute sinusitisDiagnosis requires acute sinusitis

• Nasal congestion, post nasal drip, fever, Nasal congestion, post nasal drip, fever, pain over the involved sinusespain over the involved sinuses

• Tender on percussionTender on percussion

• Sinus xray confirmsSinus xray confirms

• TreatmentTreatment– Antibiotics or drainage Antibiotics or drainage

Temporal ArteritisTemporal Arteritis

• Progressively obliterative granulomatous Progressively obliterative granulomatous arteritisarteritis

• Temporal or occipitalTemporal or occipital

• Can involve cerebral and ophthalmic Can involve cerebral and ophthalmic arteriesarteries

• 50% will go blind and have a stroke50% will go blind and have a stroke

• Greater than > yearsGreater than > years

Temporal ArteritisTemporal Arteritis

• Usually temporal headacheUsually temporal headache• Malaise, anorexia, night sweats, myalgia, Malaise, anorexia, night sweats, myalgia,

+/- fever, jaw claudication+/- fever, jaw claudication• ESR > 50ESR > 50• DiagnosisDiagnosis

– Superficial temporal artery biopsySuperficial temporal artery biopsy

• TreatmentTreatment– Prednisone 60 -100 mgm dailyPrednisone 60 -100 mgm daily

Meningeal IrritiationMeningeal Irritiation

• Meningitis and subarachnoid Meningitis and subarachnoid hemorrhagehemorrhage

• Occurs due to inflammation and Occurs due to inflammation and intracranial pain sensitiveintracranial pain sensitive

• structures.structures.• Subarachnoid hemorrhage - sudden Subarachnoid hemorrhage - sudden

onset meningitisonset meningitis• Meningitis - more gradual.Meningitis - more gradual.

Meningeal IrritiationMeningeal Irritiation

• Occipital and nuchal pain.Occipital and nuchal pain.• Interscapular and low back pain.Interscapular and low back pain.• Aggravated by movementsAggravated by movements• Photophobia, vomitingPhotophobia, vomiting• FeverFever• DiagnosisDiagnosis• History and physicalHistory and physical• CT LPCT LP

Headache and Headache and Brain tumorBrain tumor

• Traction on intracranial pain sensitive Traction on intracranial pain sensitive structures.structures.

• Progressively worsening headache.Progressively worsening headache.

• Morning headaches.Morning headaches.

• Worsen in head down position.Worsen in head down position.

• Worsen with cough and strainingWorsen with cough and straining

• May be localized (constant).May be localized (constant).

• Focal neurologic signs.Focal neurologic signs.

Benign Headaches Hierarchy of Treatment

• Acute Treatment– Low tech first– Prevention– Acetaminophen alternate with NSAID– Adequate doses and timing according to body

weight– Avoid codeine

Hierarchy of Treatment

Acetaminophen/NSAIDSAcetaminophen/NSAIDS

Muscle Relaxants/Topiramate/ValproateMuscle Relaxants/Topiramate/Valproate

Narcotics/Steroids/OxygenNarcotics/Steroids/Oxygen

Triptans/ChlorpromazineTriptans/Chlorpromazine

Hierarchy of Prevention

Risk Factors – Headache DiaryRisk Factors – Headache Diary

Alcohol/Foods/Sleep deprivation/Meals/Stress management/Repetitive Stress Alcohol/Foods/Sleep deprivation/Meals/Stress management/Repetitive Stress injuryinjury

Amitriptyline/Beta blockers/pizotyline/SingulairAmitriptyline/Beta blockers/pizotyline/Singulair

Lithium/DBSLithium/DBS

Valproate/ChlorpromazineValproate/Chlorpromazine

Case Case

• 22 year old man develops double vision 22 year old man develops double vision especially when looking up or to either sideespecially when looking up or to either side• He has noted some increased fatiguability of his He has noted some increased fatiguability of his musclesmuscles• EOM shown in videoEOM shown in video• Exam otherwise normalExam otherwise normal

Case Case

• He is then given 10 mgm of IV Tensilon He is then given 10 mgm of IV Tensilon (Edrophonium)(Edrophonium)

• His extra ocular movements are then His extra ocular movements are then reexaminedreexamined

Case Case

• Where is the lesion?Where is the lesion?

• What other tests might be used?What other tests might be used?

• What is the commonest treatment?What is the commonest treatment?

• What are the long term risks of the disease?What are the long term risks of the disease?

Myasthenia GravisDefinition

* Autoimmune disease with destruction Of neuromuscular junctions

* Symptoms

- Progressive fatigibility over time

Myasthenia GravisSymptoms

* Progressive fatigibility over time

* Double vision

* Drooping of eyelid(s)

* Difficulty swallowing

* Change in voice

* Difficulty breathing

Myasthenia GravisSigns

* Weakness of eyes movements

* Weakness of facial muscles

* Weakness of swallowing, cough

Or gag

* Weakness of limbs

* No sensory loss

Myasthenia Gravis

Myasthenia GravisInvestigations

• Tensilon Test

• EMG

• Anti-acetylcholine receptor antibodies

Myasthenia GravisTreatment

• Mestinon (pyridostigmine)

• Steroids

• IV IgG

• Plasma exchange

• Thymectomy

CASE

This 65 year old man present with acute This 65 year old man present with acute aphasia and right sided weakness.aphasia and right sided weakness.

On examination, he has a right facial droop, On examination, he has a right facial droop, weakness of the right arm greater than the leg weakness of the right arm greater than the leg and global aphasia.and global aphasia.

Where is the lesion ?Where is the lesion ?

What is the etiology ?What is the etiology ?

CT Scans

Left ACA and MCA Territory Infarction

CT Scans

Left Carotid StenosisLeft Carotid Stenosis

AngiogramAngiogram PathologyPathology

StrokeStroke

• 50,000 new cases per year50,000 new cases per year

• #3 cause of death#3 cause of death

Risk FactorsRisk Factors

• age - doubles every decade after 55 yearsage - doubles every decade after 55 years• sex - males 25% greater than femalessex - males 25% greater than females• blood pressure - 5 timesblood pressure - 5 times• CholesterolCholesterol• Sleep apnea – 3 –4 timesSleep apnea – 3 –4 times• smoking - 4 timessmoking - 4 times• alcohol abuse - 3 timesalcohol abuse - 3 times• diabetes - 3 timesdiabetes - 3 times• homocysteinhomocystein

DefinitionDefinition

• Transient ischemic attackTransient ischemic attack– Focal cerebral ischemic event resolving Focal cerebral ischemic event resolving

within 24 hourswithin 24 hours

• Completed StrokeCompleted Stroke– No resolution of symptomsNo resolution of symptoms

Causes of StrokeCauses of Stroke

• 85% infarct -85% infarct -– 60% cerebral atherosclerosis60% cerebral atherosclerosis– 20% lacunar20% lacunar– 15 cardiogenic emboli15 cardiogenic emboli

• 15% hemorrhage – 15% hemorrhage – – intracerebralintracerebral– subarachnoid hemorrhagesubarachnoid hemorrhage

Cerebral Circulation 2 Vertebral Arteries Basilar• 2 Carotid Arteries• Circle of Willis

CT Angiogram

Vascular DistributionVascular Distribution

LacuneLacune

• Fibrinoid degeneration of penetrating Fibrinoid degeneration of penetrating arteriesarteries

• Most commonly due to hypertensionMost commonly due to hypertension

• Involves deep white matter pens and Involves deep white matter pens and basal gangliabasal ganglia

Cardiogenic EmholiCardiogenic Emholi

• NVAF -45%.NVAF -45%.

• IHD - acute MI -15%IHD - acute MI -15%

• - ventricular aneurysm -10%- ventricular aneurysm -10%

• RHD -10%RHD -10%

• Prosthetic valve -10%Prosthetic valve -10%

• Other -10%.Other -10%.

Stroke SyndromesStroke SyndromesCarotid CirculationCarotid Circulation

Internal Cerebral ArteryInternal Cerebral Artery

• HemiplegiaHemiplegia

• Hemisensory lossHemisensory loss

• Aphasia (L)Aphasia (L)

• Neglect (R)Neglect (R)

Anterior Cerebral arteryAnterior Cerebral artery

• Contralateral lower limb paresis and Contralateral lower limb paresis and hyperreflexiahyperreflexia

• upper limb relatively sparedupper limb relatively spared

PCA Infarct

Vertebrobasilar CirculationVertebrobasilar Circulation

• Multiple stroke syndromes depending on Multiple stroke syndromes depending on vessels in sitevessels in site

• DysarthriaDysarthria

• AtaxiaAtaxia

• Bilateral weaknessBilateral weakness

• Bilateral sensory complaintsBilateral sensory complaints

• Bilateral visual complaintsBilateral visual complaints

Pontine InfarctPontine InfarctLocked-In SyndromeLocked-In Syndrome

Lacunar InfarctLacunar Infarct

• Multiple stroke syndromes but in general Multiple stroke syndromes but in general produces pure motor or pure sensory produces pure motor or pure sensory strokestroke

Isolated Symptoms Rarely due Isolated Symptoms Rarely due to Stroke or TIAto Stroke or TIA

• Vertigo. dizzinessVertigo. dizziness

• DiplopiaDiplopia

• Loss of consciousnessLoss of consciousness

• ConfusionConfusion

Differential DiagnosisDifferential Diagnosis

• Transient Ischemic attackTransient Ischemic attack

• Focal seizureFocal seizure

• HypoglycemiaHypoglycemia

• Carpal tunnel syndromeCarpal tunnel syndrome

• MigraineMigraine

• HysteriaHysteria

Ddx Vertebrobasilar TIADdx Vertebrobasilar TIA

• SyncopeSyncope

• LabyrinthitisLabyrinthitis

• Myasthenia gravisMyasthenia gravis

• Meniere's diseaseMeniere's disease

InvestigationInvestigation

• CT, CTA, CT perfusion CT, CTA, CT perfusion

• MRI/MR angiogram MRI/MR angiogram

• CBC. differential and plateletsCBC. differential and platelets

• INR, PTTINR, PTT

• Cholesterol, triglycerideCholesterol, triglyceride

• DopplerDoppler

• EchocardiogramEchocardiogram

Vertebrobasilar CirculationVertebrobasilar Circulation

• As above but no DopplerAs above but no Doppler

• TreatmentTreatment

• Prevention:Prevention:

• Controlled risk factorsControlled risk factors

Carotid CirculationCarotid Circulation

• If no severe carotid stenosis or cardiac embolusIf no severe carotid stenosis or cardiac embolus• antiplatelet agents. specifically aspirin, Plavix antiplatelet agents. specifically aspirin, Plavix

or Ticlid.or Ticlid.• Cardiac embolus is treated with CoumadinCardiac embolus is treated with Coumadin• Carotid stenosis severe than 70% is treated Carotid stenosis severe than 70% is treated

with carotid endarterectomy or angioplasty with carotid endarterectomy or angioplasty and stentingand stenting

• Risk factor managementRisk factor management

Acute ThrombolysisAcute Thrombolysis

PrePre

PostPost

Treatment of Acute Stroke

• NINDS protocol– < 3 hours since onset– < 1/3 of MCA territory– No recent bleeding or surgery– IV r-tpa and/or intraarterial tpa angioplasty,

stent

Brain AttackDistribution of Hemorrhages

Case History

• 22 yr old male assaulted in a bar at 2400 hrs

• Had been drinking

• Loss of consciousness ??

• Vomited twice

• Brought to ED by car at 0100

• “Alert and oriented” x3 @ RN

Case cont’d

• Seen by EP at 0230:– ambulatory; not distressed– GCS 15– amnesia x 5 min before injury– object recall 3/3– forehead contusion but no signs of open or

basilar #

Case cont’d

What would you do?

a) observe overnight

b) do CT scan immediately

c) do CT scan in a.m.

d) discharge home with head injury sheet

Case cont’d

• Discharged home with friends

• Returned 36 hrs later c/o headache and dizziness

• Ambulatory; not distressed

• GCS 15

• Neurologically intact

• CT ordered

Skull fracture

epiduralWhat would be the symptoms and signs? What would be the treatment?

ACUTE EPIDURAL HEMATOMA • Note the biconvex

hyperdense area (arrows). The blood collection is between the skull and dura.

• It crosses dural attachments, but not sutures. The etiology is secondary to a lacerated meningeal artery or dural sinus.

• The Subdural windows may help to discern extra-axial collections such as blood in this case.

ACUTE SUBDURAL HEMATOMA WITH SUBFALCINE HERNIATION

• The arrow heads point to the presence of subfalcine herniation (midline shift). This is secondary to the mass effect caused by the moderate sized acute subdural hematoma (arrow) overlying the right fronto-temporal convexity.

Acu

te o

n c

hro

nic

SD

H What would be the symptoms and signs? What would be the treatment?

RIGHT FRONTAL PETECHIAL HEMORRHAGIC CONTUSION

• Contusions may be hemorrhagic or nonhemorrhagic. They are part of the spectrum of cranio-cerebral trauma. Although there is no obvious mass effect, and there may not be neurologic deficits solely due to the presence of this particular lesion, there are usually areas of associated brain injury known as diffuse axonal injury (DAI) which may account for more severe neurologic deficits.

• An MRI will demonstrate more subtle anomalies which cannot be demonstrated on CT scan examination.

Subdural hematomaSubdural hematoma

• Drowsiness. headacheDrowsiness. headache

• Evolves over days to weeksEvolves over days to weeks

• History of head trauma not always History of head trauma not always presentpresent

Subdural HematomaSubdural Hematoma

Case

• 24 year old woman presents with decreased vision in right eye

• No history of recent febrile illness

• Exam shows decreased colour vision in right eye and bilateral hyperreflexia

• Where is the lesion?

Multiple SclerosisMultiple SclerosisMRIMRI

Demyelinating DiseaseDemyelinating DiseaseClassificationClassification

• Multiple sclerosis.Multiple sclerosis.

• Diffuse cerebral sclerosis.Diffuse cerebral sclerosis.

• Post viral or post vaccinial disseminated Post viral or post vaccinial disseminated encephalomyelitis.encephalomyelitis.

• Necrotizing hemorrhagic encephalomyelitis.Necrotizing hemorrhagic encephalomyelitis.

• Metabolic toxicMetabolic toxic

• postanoxic encephalopathypostanoxic encephalopathy

• CPMCPM

Dvsmvelinating DisordersDvsmvelinating Disorders

• ALDALD

• MLDMLD

• Krabbe'sKrabbe's

• Canavan'sCanavan's

• Chediak HigashiChediak Higashi

• Neuraxonal dystrophyNeuraxonal dystrophy

• Pelazeus MerzbacherPelazeus Merzbacher

Multiple SclerosisMultiple Sclerosis

• Dissemination of lesions in time and spaceDissemination of lesions in time and space

• MacDonald CriteriaMacDonald Criteria

• EDSS or Kurtze ScaleEDSS or Kurtze Scale

• Prevalence 0.1%Prevalence 0.1%

• Female:male = 3:2Female:male = 3:2

• 20 to 40 years old (peak age 28 years)20 to 40 years old (peak age 28 years)

The Expanded Disability Status Scale (EDSS), or Kurtzke scale, gauges the extent of a person's disability by measuring the level of neurologic impairment. Following is a breakdown

of the EDSS:

• 0 – 1 No disability, minimal signs on one FS* (functional system)• 1 – 2 Minimal disability in 1 FS• 2 – 3 Moderate disability in 1 FS or mild disability in 3-4 FS, though fully

ambulatory• 3 – 4 Fully ambulatory without aid, up and about 12 hours/day, despite

relatively severe disability; able to walk without aid for 500 meters• 4 – 5 Ambulatory without aid for about 200 meters; disability impairs full

daily activities• 5 – 6 Intermittent or unilateral constant assistance required to walk 100

meters with or without resting• 6 – 7 Unable to walk beyond 5 meters even with aid, essentially restricted

to wheelchair, wheels self, transfers alone• 7 – 8 Essentially restricted to bed or chair or perambulated in wheelchair,

but may be out of bed much of day; retains self-care functions, generally effective use of arms

• 8 – 9 Helpless bed patient, can communicate and eat• 9 - 9.5 Unable to communicate effectively or eat/swallow• 10 Death due to multiple sclerosis

Practical use of MRI in the diagnosis and management of patients with

MS

Key Features for the Diagnosis of MS

• Dissemination in time and space of lesions typical of MS

• Exclusion of other better explanations for the clinical features

Lesions in Space

• Clinical evidence must be an objective sign

• MRI evidence should meet 3 out of 4 Barkhof criteria

(minimum of 2 to 9 lesions depending on use of gadolinium and location of lesions), or

2 lesions and abnormal CSF

Lesions in TimeClinical attacks should be: • >24 hours duration and separated by > 30 days• Consistent with demyelination• Not a pseudoattack • Requires an objective finding

MRI attacks can be: • A new gadolinium enhancing lesion or • A new T2 lesion • Separated by > 3 months from clinical event

Paraclinical TestsMRI

Most sensitive and specific

Visual evoked potentials Can be used as objective clinical evidence Delayed with preserved wave form

CSF required for:Equivocal MRIPPMS diagnosisUnusual clinical picture

What is a Positive MRI (Barkhof Criteria)?

3 out of 4 of the following:• 9 T2 lesions or 1 Gad-enhancing lesion• 1 infratentorial lesion• 1 juxtacortical lesion• 3 periventricular lesion

Minimum lesions required 5 (2 if Gad used)

Note: 1 spinal cord lesion = 1 brain lesion

What is MRI Evidence for Dissemination in Time?

At least 3 months after the clinical attack:1 Gad-enhancing lesion

At least 3 months after the last MRI scan:1 new T2 lesion or 1 Gad-enhancing lesion

Definite MS (DMS) Requirements:

2 Clinical attacks2 objective signs

1 objective sign

0–1 MRI required None ― but recommended

(Caution if MRI and CSF are normal)

3 of 4 Barkhof criteria

or 2 MRI lesions and abnormal CSF

1 Clinical attack2 objective signs

1 objective sign

1–3 MRIs required Gd lesion > 3 months after clinical attack

orNew T2 or Gd lesion > 3 months after 1st MRI

2–3 MRIs required Positive 1st MRI AND Gd lesion > 3 months

after clinical attack

TreatmentTreatment• Acute AttacksAcute Attacks• Steroids.Steroids.

– SolumedrolSolumedrol– Prednisone not for optic neuritisPrednisone not for optic neuritis

• ProphylaxisProphylaxis– Beta interferonBeta interferon– CopolymerCopolymer– MitoxandroneMitoxandrone– NatalizumabNatalizumab

• SymptomaticSymptomatic• SpasticitySpasticity

– BaclofenBaclofen– DantriumDantrium– BenzodiazepinesBenzodiazepines

TreatmentTreatment

• Paroxysmal DisordersParoxysmal Disorders– TegretolTegretol– DilantinDilantin

• Bladder DysfunctionBladder Dysfunction– Anticholinergic drugs eg. (Ditropan)Anticholinergic drugs eg. (Ditropan)– Antibiotic treatmentAntibiotic treatment

• DepressionDepression– Tricyclic antidepressantsTricyclic antidepressants

• FatigueFatigue– AmantidineAmantidine

Seizures

• Seizures originate from the cortex

• Case

Simple Partial Seizures.Simple Partial Seizures.

1. motor1. motor

2. somatosensory or special sensory2. somatosensory or special sensory

3. autonomic3. autonomic

4. psychic4. psychic

Complex Partial SeizuresComplex Partial Seizures

• Partial seizure with altered awarenessPartial seizure with altered awareness

• SP -CPSP -CP

• CPCP

• + automatisms.+ automatisms.

Partial SeizuresPartial Seizures - to secondary generalization - to secondary generalization

• SP-GTCSP-GTC

• CP - GTCCP - GTC

• SP -CP-GTCSP -CP-GTC

Generalized Seizures Generalized Seizures (convulsive and non convulsive)(convulsive and non convulsive)• AbsenceAbsence

– TypicalTypical

– AtypicalAtypical

• MyoclonicMyoclonic• ClonicClonic• TonicTonic• Tonic-clonicTonic-clonic• Atonic.Atonic.

HistoryHistory• How did the seizure startHow did the seizure start

– staringstaring

– eye deviationeye deviation

– jerking or one limbjerking or one limb

• Patient's description of auraPatient's description of aura• Post ictal statePost ictal state• Age of onsetAge of onset• Family historyFamily history• Past historyPast history• Alcohol or drug abuseAlcohol or drug abuse

Physical ExamPhysical Exam

• Todds paralysisTodds paralysis

• Eye deviationEye deviation

• Cranial bruitCranial bruit

• HyperventilationHyperventilation

• Skin examinationSkin examination

• IncontinenceIncontinence

InvestigationInvestigation

• Glucose. BUN, Calcium. SodiumGlucose. BUN, Calcium. Sodium

• CT, MRICT, MRI

• EEGEEG

TreatmentTreatmentPartial SeizuresPartial Seizures

• CarbamazepineCarbamazepine

• PhenytoinPhenytoin

• PrimidonePrimidone

• PhenobarbitalPhenobarbital

• Valproic AcidValproic Acid

Tonic ClonicTonic Clonic

• Valproic acidValproic acid

• CarbamazepineCarbamazepine

• PhenytoinPhenytoin

• PhenobarbitalPhenobarbital

• PrimidonePrimidone

AbsenceAbsence

• ValproateValproate

• EthosuximideEthosuximide

MvoclonicMvoclonic

• ValproateValproate

• ClonazepamClonazepam

• NitrazepamNitrazepam

Add On Meds

• Gabapentin

• Lamictal

• Vigabatrin

• Topiramate

CASE

• This 23 year gay man has had progressive This 23 year gay man has had progressive cognitive impairment in the last 3 months cognitive impairment in the last 3 months which has been complicated by PCP which has been complicated by PCP pneumonia from which he is recovering.pneumonia from which he is recovering.

• On examination, he has general mental On examination, he has general mental slowing with some tremor in the left upper slowing with some tremor in the left upper limb. limb.

• Where is the lesion ?Where is the lesion ?

CT ScanCT Scan

DementiaDementia• A loss of intellectual ability of sufficient A loss of intellectual ability of sufficient

severity to interfere with social or occupational severity to interfere with social or occupational functioning.functioning.

• Memory impairment.Memory impairment.• At least one of:At least one of:

– impaired abstract thinkingimpaired abstract thinking

– Impaired judgementImpaired judgement

– Other disturbances of higher cortical functioning -Other disturbances of higher cortical functioning -

– aphasia. apraxia, agnosia. constructional difficultyaphasia. apraxia, agnosia. constructional difficulty

– Personality changePersonality change

IrreversibleIrreversible

• Alzheimer’s Disease, Frontotemporal Dementia Alzheimer’s Disease, Frontotemporal Dementia (tauopathies)(tauopathies)

• MSA, PD, CBD, Lewy Body (synucleinopathies)MSA, PD, CBD, Lewy Body (synucleinopathies)• HIVHIV• MIDMID• PrionopathiesPrionopathies

– CJDCJD

– CJDvCJDv

– Gerstmann-Straussler-SkenkerGerstmann-Straussler-Skenker

– Fatal Familial InsomniaFatal Familial Insomnia

Reversible• Drugs

– Alcohol, alcohol, alcohol

• Metabolic– B12– T4

• Infectious– Syphilis

• SOL– Subdural– Meningioma

• NPH• Sleep Apnea• Pseudodementia

Alzheimer's DiseaseAlzheimer's Disease

• 50 to 60% of cases of dementia.50 to 60% of cases of dementia.

• Greater than 65 years old - Greater than 65 years old - – prevalence 1-6%.prevalence 1-6%.

• 4th most common cause of death4th most common cause of death

Diagnostic CriteriaDiagnostic Criteria"Probable (clinically ascertained) "Probable (clinically ascertained)

A.D.A.D.• DementiaDementia

• Onset 40 to 90 yearsOnset 40 to 90 years

• Deficits present in greater than 2 Deficits present in greater than 2 cognitive spherescognitive spheres

• Progressive deterioration.Progressive deterioration.

• No disturbance of consciousness.No disturbance of consciousness.

• No other illness to account for symptoms.No other illness to account for symptoms.

"Definite" (pathologicallv confirmed) "Definite" (pathologicallv confirmed) ADAD

• Clinical criteria.Clinical criteria.

• Histopathological evidence.Histopathological evidence.– neurofibrillary tanglesneurofibrillary tangles– neuritic plaquesneuritic plaques– granulovacular degenerationgranulovacular degeneration– Hirano bodiesHirano bodies

Alzheimer’s DiseaseAlzheimer’s DiseasePathophysiologyPathophysiology

• Acetylcholine (memory)Acetylcholine (memory)– Nucleus Basalis of MeynertNucleus Basalis of Meynert– diagonal band of Brocadiagonal band of Broca– medial septal nucleimedial septal nuclei

Multi-Infarct DementiaMulti-Infarct Dementia

• Greater than 50-100% of cerebral Greater than 50-100% of cerebral hemisphere destroyedhemisphere destroyed

• Multiple strokes involving both Multiple strokes involving both hemisphereshemispheres

• Bilateral pyramidal signsBilateral pyramidal signs

• Pseudobulbar signsPseudobulbar signs

Vitamin B12 DeficiencyVitamin B12 Deficiency

• Insidious onsetInsidious onset

• May have normal smear and normal May have normal smear and normal neurologic exam except for dementianeurologic exam except for dementia

• Look for paresthesias plus signs of dorsal Look for paresthesias plus signs of dorsal column and corticospinal tract column and corticospinal tract involvement.involvement.

Normal Pressure Normal Pressure HydrocephalusHydrocephalus

• TriadTriad– AtaxiaAtaxia– IncontinenceIncontinence– DementiaDementia

• 6-12 months• usually idiopathic• CSF Pressure Measurements• CT and RISA• Rx - VP shunt

DepressionDepression" Pseudodementia"" Pseudodementia"

• Commonly have history of previous Commonly have history of previous psychiatric disorder.psychiatric disorder.

• Brief duration.Brief duration.• Complaint of cognitive deficit but make Complaint of cognitive deficit but make

little effort to performlittle effort to perform• even with simple tasks.even with simple tasks.• Frequent "don't know" answers.Frequent "don't know" answers.• Associated features of depression.Associated features of depression.

Creutzfeldt-Jacob DiseaseCreutzfeldt-Jacob Disease

• Onset to death usually months.Onset to death usually months.

• Dementia. myoclonus. UMN. basal Dementia. myoclonus. UMN. basal ganglia.ganglia.

• Characteristic EEG - periodic discharge Characteristic EEG - periodic discharge 1/sec,1/sec,

• Caused by prionsCaused by prions

Environmental FactorsEnvironmental Factors

• Head traumaHead trauma

• Infectious agentsInfectious agents

• NeurotoxinsNeurotoxins

• AlcoholAlcohol

Down's Syndrome and ADDown's Syndrome and AD

• Neuropathologic similaritiesNeuropathologic similarities

• Role of chromosome 21Role of chromosome 21

InvestigationInvestigation

• CT, MRICT, MRI

• EEGEEG

• B12. folateB12. folate

• CBC, differential. plateletsCBC, differential. platelets

• VDRLVDRL

• Thyroid function testsThyroid function tests

• BUN. creatinine.BUN. creatinine.

InvestigationInvestigation

• AST. ALTAST. ALT

• LytesLytes

• ESRESR

• CXRCXR

• Neuropsychological testingNeuropsychological testing

• Lumbar punctureLumbar puncture

Case 6

• This 28 year old man presented with a three week history of a headache and weakness on the left side

• The day of admission he suffered a generalized seizure which was characterized by initial twitching to the left side of the face

Case 20Case 20

• Neuro exam showsNeuro exam shows• InattentiveInattentive• Left facial weaknessLeft facial weakness• Mild left upper and lower limb weakness Mild left upper and lower limb weakness

and hyperreflexiaand hyperreflexia• Normal sensationNormal sensation• Decreased RAM of left upper and lower Decreased RAM of left upper and lower

limbslimbs

Where is the lesion?Where is the lesion?

CT ScanCT Scan

Brain TumorsBrain TumorsGBMGBM

Meningioma

Brain TumorsBrain TumorsMedulloblastomaMedulloblastoma

TumorTumor

• Often in frontal lobe.Often in frontal lobe.

• Grasp, suck. snout reflexesGrasp, suck. snout reflexes

• "slowness" in carrying out tasks"slowness" in carrying out tasks

• Impaired smellImpaired smell

• Tumors obstructing 3rd or 4th ventriclesTumors obstructing 3rd or 4th ventricles

Case 19Case 19

• This 70 year old lady noted a 9 month This 70 year old lady noted a 9 month history of tremors and clumsiness in both history of tremors and clumsiness in both her hands and feether hands and feet

• Physical examPhysical exam– See videoSee video

Parkinson’s DiseaseParkinson’s Disease

• 70 to 80 years old70 to 80 years old

• rarely less than 40 years oldrarely less than 40 years old

• 1/1.0001/1.000

Cardinal FeaturesCardinal Features

• a. tremor.a. tremor.

• b. rigidityb. rigidity

• c. bradykinesiac. bradykinesia

• d. postural instabilityd. postural instability

TremorTremor

• resting tremorresting tremor

• "pill rolling""pill rolling"

• 5 to 6 Hz5 to 6 Hz

• unilateral earlyunilateral early

• increases with stressincreases with stress

• decreases with movementdecreases with movement

RigidityRigidity

• "lead pipe""lead pipe"– bilateralbilateral– 1 side greater than the other1 side greater than the other

BradykinesiaBradykinesia

• masked faciesmasked facies

• decreased blink frequencydecreased blink frequency

• decreased rapid alternating movementsdecreased rapid alternating movements

• decreased extraocular movementsdecreased extraocular movements

• hypophonia, palilalia. aprosodyhypophonia, palilalia. aprosody

• sialorrheasialorrhea

• micrographiamicrographia

BradykinesiaBradykinesia

• decreased spontaneous movementdecreased spontaneous movement• difficulty rising from chair or rolling difficulty rising from chair or rolling

over in bedover in bed• slow ADLslow ADL• characteristic stooped gait with small characteristic stooped gait with small

stepssteps• and decreased arm swingand decreased arm swing• "freezing"freezing

Postural instabilityPostural instability

• retropulsionretropulsion

• festinationfestination

• sit "en bloc"sit "en bloc"

• fallingfalling

Clinical StagesClinical StagesStage IStage I

• Mild unilateral tremor or rigidity with or Mild unilateral tremor or rigidity with or without bradykinesiawithout bradykinesia

Stage IIStage II

• Moderate bilateral tremor or rigidity and Moderate bilateral tremor or rigidity and bradykinesia.bradykinesia.

Stage IIIStage III

• Significant tremor. rigidity and or Significant tremor. rigidity and or bradykinesia plus impairedbradykinesia plus impaired

• postural reflexespostural reflexes

• gait disturbance, mild daily fluctuations gait disturbance, mild daily fluctuations +- dementia+- dementia

Stage IVStage IV

• Severely disabled but still mobile and Severely disabled but still mobile and able to functionable to function

• independently - with or without daily independently - with or without daily periods of completeperiods of complete

• immobility; +- dementiaimmobility; +- dementia

Stage VStage V

• Loss of ability to function independentlyLoss of ability to function independently

Autonomic dysfunctionAutonomic dysfunction

• constipationconstipation

• dysphagiadysphagia

• neurogenic bladderneurogenic bladder

• droolingdrooling

• orthostatic hypotensionorthostatic hypotension

• diaphoresisdiaphoresis

Primary sensory symptomsPrimary sensory symptoms

• vague parasthesiavague parasthesia

EtiologyEtiology

• Abnormal processing of synuclein Abnormal processing of synuclein proteinprotein

• ToxinsToxins

• Infectious agentsInfectious agents

• Immunological factorsImmunological factors

• Genetic factorsGenetic factors

• MPTPMPTP

PathophysiologyPathophysiology

• Progressive loss of presynaptic Progressive loss of presynaptic dopaminergic neurons in the substantia dopaminergic neurons in the substantia nigranigra

• cortical pathological changes like AD in cortical pathological changes like AD in 50%.50%.

• Changes in post synaptic striatal dopamine Changes in post synaptic striatal dopamine receptorsreceptors

TreatmentTreatmentMild DisabilityMild Disability

• AnticholinergicAnticholinergic

• AmantadineAmantadine

• SelegilineSelegiline

Moderate DisabilityModerate Disability

• L-DopaL-Dopa

• RopineroleRopinerole• PramipexolePramipexole

Severe DisabilitySevere Disability

• Increased doses of L-Dopa and Increased doses of L-Dopa and Dopamine AgonistDopamine Agonist

• COMT InhibitorCOMT Inhibitor

Long Term Complications of Long Term Complications of Treatment with L-DopaTreatment with L-Dopa

• DyskinesiaDyskinesia

• Daily fluctuations in level of functionDaily fluctuations in level of function– End of dose deteriorationEnd of dose deterioration– freezing episodesfreezing episodes– "on-off" phenomenon"on-off" phenomenon

• Dementia and drug induced confusionDementia and drug induced confusion

• Progressive drug failure.Progressive drug failure.

Case StudyCase Study

• 34 year old woman with one year history of difficulties with voice and swallowing with weakness in right hand

Case Case ExamExam

• Cranial NervesCranial Nerves• DysarthriaDysarthria• Fasciculations of tongueFasciculations of tongue

• MotorMotor– Upper and lower limb weakness and wastingUpper and lower limb weakness and wasting– Upper and motor limb hyperreflexiaUpper and motor limb hyperreflexia

• SensorySensory– NormalNormal

Case Case

• Where is the lesion?Where is the lesion?

• What is the cause?What is the cause?

• What is the prognosis?What is the prognosis?

Amyotrophic Lateral Sclerosis (ALS)

Natural History * Progressive asymmetrical muscular Wasting and weakness

* Initially weakness begins in one or Two muscles

* Adjacent muscles intact and Compensating for weakness Of involved muscles

* Hyperexcitability of involved Muscles associated with Muscle cramps and fasciculation

Amyotrophic Lateral Sclerosis (ALS)

Natural History * PROGRESSIVE COURSE LEADING TO DEATH* PROGRESSIVE COURSE LEADING TO DEATH MONTHS TO YEARS UNTIL COMPLETEMONTHS TO YEARS UNTIL COMPLETE PARALYSISPARALYSIS

* RANGE 1 TO 15 YEARS* RANGE 1 TO 15 YEARS

* 50% DIE WITHIN 4 YEARS* 50% DIE WITHIN 4 YEARS

* 20% LIVE FOR FIVE YEARS* 20% LIVE FOR FIVE YEARS

* 10% LIVE FOR TEN YEARS* 10% LIVE FOR TEN YEARS

* AGE LESS THAN 65 AVERAGE* AGE LESS THAN 65 AVERAGE DURATION OF LIFE 3 YEARSDURATION OF LIFE 3 YEARS

* AGE GREATER THAN 65, AVERAGE* AGE GREATER THAN 65, AVERAGE DURATION OF LIFE 2 YEARSDURATION OF LIFE 2 YEARS

Amyotrophic Lateral SclerosisNatural History

* Apparent stabilization of the Disease may be compensation By other muscle groups

* Age of onset more than 50 years Median age of onset 55

* Rarely develops before age 30

* Median age seems to be increasing

ALS ALS SignsSigns

• In pseudobulbar group, disorders of pursuit movements are common

• Minor losses of sensory function

• Little involvement of autonomic system

• Dementia is uncommon, unless age or

• Premiered dementia cause co-existence of ALS and dementia

ALS ALS SignsSigns

* Atrophic weak limb with hyperreflexia

* Mixture of upper and lower Motor neuron signs, Characteristic of bulbar form

* Hyperactive jaw jerk with a sucking Reflex, common in bulbar form

* Pseudobulbar emotional incontinence

* Paralysis of extraocular movement or loss of bowel and bladder Continence

Amyotrophic Lateral SclerosisSymptoms

* No pattern to site of onset

* Fatiguability early complaint

* Hyperactive DTRs with spasticity

Amyotrophic Lateral SclerosisSymptoms

* Asymmetrical fatigue,cramping, Fasciculations, weakness And atrophy of muscles

* Atrophied and normal muscles may Be found adjacent in the same limb

* When disease begns in the muscles Of the tongue,lips and throat, Limb weakness is usually not present Initially but progresses later

* Early recognition of bulbar symptoms

ALS Signs

* Minor losses of sensory function

* Little involvement of autonomic system

* Dementia is uncommon,unless age or Premorbid dementia cause co-existence Of als and dementia

ALSTreatmen

t * Supportive

* Prevention of complications

* Respiratory - Pneumonia - Tracheostomy - Ventilation

* Nutrition - Feeding tube

* Musculoskeletal - Splints - Contractures

ALSTreatmen

t

* Social

- Acceptance of diagnosis - Early decisions re: trach and Ventilator - Support of dying patient

Case Study

• 30 year old male referred for evaluation• Fell asleep while driving causing an accident• Occurred in early afternoon• Snores at night, witnessed apneas in sleep• BMI 33.9• Normal - Neuro exam• Thick neck, redundant soft palate

Obstructive Sleep ApneaClinical Features

Middle Aged MalesExcessive Daytime Sleepiness (EDS)

Snoring - Loud, Gutteral, Inspiratory

Observed Respiratory Pauses in Sleep

Irresistable Sleep Attacks

Behavioral Automatisms With Amnesia

Marked Nocturnal Movement

Enuresis

Morning Headache

Late Cyanosis

Polycythemia

Edema

Dyspnea

Nocturnal Death

Pickwickian Syndrome

The Sleep Apnea Syndromes

• Apnea defined as cessation of airflow at the nostrils and mouth lasting ten seconds or more

• Obstructive secondary to sleep induced airway obstruction

• Central apnea due to decrease activity of muscles of respiration

• Mixed apnea from a combination of both

Sleep Apnea

• Nasal-CPAP improves EDS• Effect is objectively measurable with the multiple

sleep latency test (MSLT)• Epworth Score Increased • Adult prevalence of sleep apnea/hypopnea

syndromes is about 2-4%.• Bed partner best witness• Cofactors:BMI, use of alcohol,CNS depressants • PSG confirmation

Risk Factors

Obesity

Micrognathia

Enlarged Tonsils and Adenoids

Enlarged Thyroid

Acromegaly (enlarges tongue)

Nasal Septal Defects

Neuromuscular Disease

Miscellaneous:Assoc’d With Narcolepsy-cataplexy (“-20%)

Relation to Sudden Infant Death Syndrome

Management• Causal

– weight loss– removal of T and A– mandibular advancement surgery

• Relieve obstruction– continuous nasal positive pressure in sleep– uvolo-palato-pharyngoplasty– tracheostomy

• Drugs – medroxyprogesterone - (pure Pickwickians)

Abstinence from alcohol, hypnotics, sedatives

Driving Recommendations for Patients With Obstructive Sleep Apnea

• Patients with obstructive sleep apnea (documented by a sleep study), who are compliant with CPAP or have had successful UPPP treatments should be safe to drive any type of motor vehicle.

Case Study

• 30 year old tow truck driver with history of EDS

• Episodes of uncontrolled sleepiness with paralysis

• Episodes of loss of posture with extreme emotion

• No family history

Case Study

• Neuro Exam – Normal• HLA-DQB1*0602 – pending

• Patients receives Letter from MTO suspending licence – unable to work, no private insurance

• OSS and MSLT ordered

MSLT PretreatmentMSLT Pretreatment

MSLT Post treatmentMSLT Post treatment

Narcolepsy

Cardinal symptoms– Sleep attacks and EDS– Cataplexy– Sleep paralysis– Vivid hypnagogic hallucinations

Ancilliary symptoms– “Microsleeps”– Automatic behavior– Memory problems– Visual problems– Non-restorative night sleep– Nightmares

Narcolepsy

• Genetics

• HLA Linkage - DQB1*0602 – same HLA relationship has also been observed

for essential hypersomnia (EHS).

Etiology

• Genetic and Sporadic Cases– Abnormal hypocretin receptor– HLA DR 15 (DR2), DQB1*0602

Sporadic alone (60% of cases)– Precipitating Factors

Irregular Prior Sleep/Wake Patterns Flu-like Illnesses

• Symptomatic Cases (Rare)– Demyelinating Disease– Tumoral – Post-traumatic (all in hypothalamus)

Treatment• CNS Stimulants for EDS

– methylphenidate– Amphethamines

• CNS Alerting Drugs– Modafinil

• REM Suppressants– tricyclics – clomipramine – desipramine – Imipramine– SSRIs– MAO inhibitors

• Experimental Drugs– gamma-hydroxybutyrate– zimelidine– naloxone

Driving recommendations for narcoleptic patients:

• Patients with a diagnosis of narcolepsy supported by a sleep study and with uncontrolled episodes of cataplexy during the past 12 months (with or without treatment) should not drive any type of motor vehicle.

• Patients with a diagnosis of narcolepsy supported by a sleep study and with uncontrolled daytime sleep attacks or sleep paralysis in the past 12 months (with or without treatment) should not drive any type of motor vehicle.

Occupational RiskOccurrence

• Sudden incapacitation –

• Cognitive Decline

• Psychomotor Slowing

• Secondary Complications

Occupational Risk Groups • Low

– Operators of Private Motor Vehicles– Office workers– Physicians– Retail Workers

• Intermediate– Taxis, ambulances, buses– Surgeons, EMT– Mechanics, electricians

• High– Pilots, divers, Drivers Class A, B, C, D– Chemical, nuclear industry– Operators of weapons of mass destruction

Huntington’s DiseaseHuntington’s Disease

• Prevalence 5-10/100,000Prevalence 5-10/100,000• Motor. cognitive and behavioural Motor. cognitive and behavioural

manifestationsmanifestations• Mean age of onset 36 years.Mean age of onset 36 years.• Duration 19 years.Duration 19 years.• Autosomal dominant with complete Autosomal dominant with complete

penetrancepenetrance• 10-15% -juvenile onset10-15% -juvenile onset

Huntington’s DiseaseHuntington’s Disease

• Westphal variantWestphal variant

• 90% from affected father90% from affected father

• 10-15% - greater than 55 years old10-15% - greater than 55 years old

• slower declineslower decline

NeuropathologyNeuropathology

• Caudate and putamenCaudate and putamen

• Atrophy. neuronal depletion. gliosisAtrophy. neuronal depletion. gliosis

• Decreased GABA and acetylcholineDecreased GABA and acetylcholine

Gene DefectGene Defect

• Short arm of chromosome 4Short arm of chromosome 4

ComaComa

• A. AirwayA. Airway

• B. BreathingB. Breathing

• C. CirculationC. Circulation

• Neurological ExaminationNeurological Examination

• 1. Respiration1. Respiration

• 2. Pupils, oculomotor function2. Pupils, oculomotor function

• 3. Skeletal motor3. Skeletal motor

RespirationRespiration

• Bilateral encephalopathy - Cheyne StokesBilateral encephalopathy - Cheyne Stokes

• Upper pens - hyperventilationUpper pens - hyperventilation

• Pontine tegmentum - apneustic breathingPontine tegmentum - apneustic breathing

• Lower pons - cluster breathingLower pons - cluster breathing

• Meduila - ataxic breathingMeduila - ataxic breathing

PupilsPupils

• Bilateral hemisphere diencephalonBilateral hemisphere diencephalon– Small reactiveSmall reactive

• III nerve. III nerve. – Uncal mass with herniationUncal mass with herniation

• Tectal - large fixedTectal - large fixed

• Midbrain - mid position. regular fixedMidbrain - mid position. regular fixed

• Pons -Small pinpoint.Pons -Small pinpoint.

Extra-Ocular MovementsExtra-Ocular Movements

• conjugateconjugate

• deviateddeviated

• skewskew

• bobbing; nystagmusbobbing; nystagmus

Reflex eye movementsReflex eye movements

• Doll's eyesDoll's eyes

• Calorics (COWS) Calorics (COWS)

• Dysconjugate -MLFDysconjugate -MLF

• Lost - brainstem nucleiLost - brainstem nuclei

Motor ResponsesMotor Responses• HemisphereHemisphere

– appropriate ipsilateralappropriate ipsilateral– flexion contralateralflexion contralateral

• Hypothalamus and midbrainHypothalamus and midbrain– decorticatedecorticate

• Lower midbrain - Lower midbrain - – decerebratedecerebrate

• Medulla - Medulla - – Flexion of upper limbs.Flexion of upper limbs.– rudimentary flexion of lower limbs.rudimentary flexion of lower limbs.

Differential Diagnosis of ComaDifferential Diagnosis of Coma

• Supratentorial mass lesions.Supratentorial mass lesions.

• Midbrain or pontine destructive lesions.Midbrain or pontine destructive lesions.

• Intratentorial mass lesions.Intratentorial mass lesions.

• Diffuse multifocal disorders.Diffuse multifocal disorders.

• PseudocomaPseudocoma

InvestigationsInvestigations

• Glucose, BUN. creatinine, Glucose, BUN. creatinine,

• Gas. ASTGas. AST

• LytesLytes

• Toxic screenToxic screen

• CTCT

• EEGEEG

• LPLP

SeizuresSeizures

• alcohol withdrawal seizuresalcohol withdrawal seizures

• 12 to 48 hrs following cessation of alcohol 12 to 48 hrs following cessation of alcohol intakeintake

• generalized tonic clonic seizuresgeneralized tonic clonic seizures

• 2-3 seizures2-3 seizures

• risk of delerium tremensrisk of delerium tremens

Neurology of AlcoholismNeurology of Alcoholism

• RUM fitsRUM fits

• Seizure induced by alcoholSeizure induced by alcohol

Seizure Induced by AlcoholSeizure Induced by Alcohol

• usually focalusually focal

• reflect intrinsic CNS diseasereflect intrinsic CNS disease

• often post traumatic due to multiple fallsoften post traumatic due to multiple falls

• rule out subdural hematoma and rule out subdural hematoma and meningitismeningitis

Wernickes EncephalopathyWernickes EncephalopathyDue to Thiamine DeficiencyDue to Thiamine Deficiency

• Ocular changesOcular changes– nystagmusnystagmus– 6th nerve palsy6th nerve palsy– paralysis of conjugate gazeparalysis of conjugate gaze

• AtaxiaAtaxia

• ConfusionConfusion

Korsokoff's PsychosisKorsokoff's Psychosis

• extension of confusion of Wernickesextension of confusion of Wernickes

• permanent severe memory impairment permanent severe memory impairment with confabulationwith confabulation

TreatmentTreatment

• Thiamine 100 mg IVThiamine 100 mg IV

• Repeat daily until patient is back on normal Repeat daily until patient is back on normal diet.diet.

• Intravenous glucose - always give with Intravenous glucose - always give with thiaminethiamine

• - glucose depletes thiamine stores and- glucose depletes thiamine stores and

• can give rise to Wernickes encephalopathycan give rise to Wernickes encephalopathy

PolyneuropathyPolyneuropathy

• Nutritional and toxicNutritional and toxic

• Distal weakness and paresthesiaDistal weakness and paresthesia

• TreatmentTreatment– dietdiet– abstinence from alcoholabstinence from alcohol– multivitaminsmultivitamins

Cerebellar DegenerationCerebellar Degeneration

• males more than femalesmales more than females

• trunchal ataxia and lower limb dysmetriatrunchal ataxia and lower limb dysmetria

• TreatmentTreatment– diet and vitamins.diet and vitamins.– abstinence from alcoholabstinence from alcohol

Delerium TremensDelerium Tremens

• 72 to 96 hours72 to 96 hours

• Severe tremulousnessSevere tremulousness

• Hallucinations - visual and auditoryHallucinations - visual and auditory

• autonomic hyperactivity - hypertension. autonomic hyperactivity - hypertension. fever. dilatedfever. dilated

• pupils and diaphoresispupils and diaphoresis

• Can be fatalCan be fatal

TreatmentTreatment

• ThiamineThiamine

• FolateFolate

• Lorazepam, diazepamLorazepam, diazepam

Duchenne Muscular Dystrophy (DMD)

• Commonest lethal x-linked dystrophy• 1/4,000 live male births• Delayed motor development• 1/2 unable to walk by 18 months• Waddle• Lordosis• Problem running and climbing stairs• Toe walking• Frequent fall

Duchenne Muscular Dystrophy• Gower’s manoeuvre• Proximal weakness• Calf hypertrophy• Hyporeflexia• Wheelchair by 7 to 12 years• Contracture scoliosis• Obesity or cachexia• Death by teens or early 20’s from respiratory or cardiac• complications• Lower IQ with 1/3 mentally retarded• Cardiomyopathy