Case

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

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

Case

•Physical Exam•Fever 38.0 C• Inattentive•Poor short term memory•Left upper quadrantopsia•Hyperflexia Left upper and lower limb

Case

Case 1

• Where is the lesion?– why?

• What is the cause?• What are the immediate treatment

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 SimplexTreatment

• Acyclovir IV• Management of ICP (max at 8 – 10 Days)

– Head up– Hyperventilation– Mannitol– Hypertonic Saline

• Seizure treatment

CASE 2

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

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

Where is the lesion ?

CT Scan

without contrast

Subarachoid Hemorrhage

CT ScanSubarachnoid

Blood

Subarachnoid Hemorrhage

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

– Kernig, Brudzinski

• Focal signs• Signs of coma• Positive CT scan• Positive 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 Room

1. Distinguish ominous from benign headache

2. Treat effectively the benign headaches

Assessment ApproachAirway

Breathing

Circulation

Drugs

Evaluation

Assess, secure Not a problem unless obtunded

Assess, assist

Not a problem unless obtunded

O2 not necessary

IV line with crystalloid to restore volume

No drugs until diagnosed, unless required to stablize circulation

In particular, no analgesics until diagnosed

Rapid neurological assessment

Investigations as necessary

The Spectrum of Ominous Headaches

• Subarachnoid hemorrhage• meningitis• increased intracranial pressure

Danger Signals

• the worse headache ever• onset with exertion• decreased level of consciousness• meningeal irritation• abnormal physical signs (including fever)• worsening

All Clear Signals

• previous identical headaches• patient bright and alert• neck supple

– Kernig, Brudzinski’s signs

• normal examination• improving without analgesics

CT Scan

• detects most conditions causing increased ICP

• misses 10 - 15 % of subarachnoid hemorrhage

• misses nearly all cases of meningitis

Modified HIS Diagnostic Criteria for Migraine

• multiple previous attacks• duration of attacks a few hours to a few days• headaches have at least two of:

• hemicranial• severe• pulsating• worse with activity

• headaches accompanied by at least one of:• nausea and or vomiting• aversion to light or noise

• no evidence of ominous disease in history or examination

Classification of Primary Headaches

• Migraine–with aura, without aura–Ophthalmoplegic, retinal

• Tension Headache• Cluster Headache• Miscellaneous without structural

lesion

Treating Migraine in the ER

1. Restore intravascular volume

2. Identify contraindications

3. Choose appropriate medication

Analgesic - Antinauseant

• Toradol• Metoclopramide • IV slow push

DHE - Antinauseant

• Metoclopramide 10 mg IV, followed in 10 minutes by

• DHE 0.5 - 1.0 mg IV by slow push

Chlorpromazine• Ensure patient is normovolemic

– 250 - 500 cc crystalloid

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

crystalloid– each ml contains 5 mg CPZ

• Inject into IV tubing 5 mg CPZ every 10 - 15 minutes, stopping when – improvement clearly occurring, or– 25 mg given– Watch for hypotension and sedation

Nasal Sprays

• DHE

• Sumatriptan

Sumatriptan

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

Patient Instructions:Guidelines

• Do not drive a car or operate machinery• Do not drink alcohol or take

tranquillizers, antihistamines, or other drugs that affect the CNS

• Store in child-resistant containers• Neurological followup if frequent or

incapacitating

Cluster Headache

• 1/10 as common as migraine• Not genetically determined• M:F 6:1• Later Onset• Rhythmicity• Severe unilateral orbital, supraorbital

and/or temporal pain

Cluster Headache

• Ipspilateral– conjunctival injection– nasal congestion– forehead and facial swelling– miosis– ptosis– eyelid edema

• Every 2 - 8 times per day

Cluster Headache

• Trigger– alcohol

• Pathophysiology– Role of proximal internal carotid artery– Role of histamine

• Treatment• Acute attack

– ergotamine

Cluster Headache

• Prophylaxis–Sansert–Steroids–Lithium–Calcium channel blockers–Combinations

Inflammatory Headaches

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

• Diagnosis requires acute sinusitis• Nasal congestion, post nasal drip, fever,

pain over the involved sinuses• Tender on percussion• Sinus xray confirms• Treatment

– Antibiotics or drainage

Temporal Arteritis

• Progressively obliterative granulomatous arteritis

• Temporal or occipital• Can involve cerebral and ophthalmic

arteries• 50% will go blind and have a stroke• Greater than > years

Temporal Arteritis

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

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

– Superficial temporal artery biopsy• Treatment

– Prednisone 60 -100 mgm daily

Meningeal Irritiation

• Meningitis and subarachnoid hemorrhage

• Occurs due to inflammation and intracranial pain sensitive

• structures.• Subarachnoid hemorrhage - sudden

onset meningitis• Meningitis - more gradual.

Meningeal Irritiation

• Occipital and nuchal pain.• Interscapular and low back pain.• Aggravated by movements• Photophobia, vomiting• Fever• Diagnosis• History and physical• CT LP

Headache and Brain tumor

• Traction on intracranial pain sensitive structures.

• Progressively worsening headache.• Morning headaches.• Worsen in head down position.• Worsen with cough and straining• May be localized (constant).• 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 Prevention

Risk Factors – Headache Diary

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

Amitriptyline/Beta blockers/pizotyline/Singulair

Lithium/DBS

Valproate/Chlorpromazine

Hierarchy of Treatment

Acetaminophen/NSAIDS

Muscle Relaxants/Topiramate/Valproate

Narcotics/Steroids/Oxygen

Triptans/Chlorpromazine

Case

• 22 year old man develops double vision especially when looking up or to either side• He has noted some increased fatiguability of his muscles• EOM shown in video1• Exam otherwise normal

Case

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

• His extra ocular movements are then reexamined

•Video 2

Case

• Where is the lesion?

• What other tests might be used?

• What is the commonest treatment?

• 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 aphasia and right sided weakness.

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

Where is the lesion ?

What is the etiology ?

CT Scans

Left ACA and MCA Territory Infarction

CT Scans

Left Carotid Stenosis

Angiogram Pathology

Stroke

• 50,000 new cases per year• #3 cause of death

Risk Factors

• age - doubles every decade after 55 years• sex - males 25% greater than females• blood pressure - 5 times• Cholesterol• Sleep apnea – 3 –4 times• smoking - 4 times• alcohol abuse - 3 times• diabetes - 3 times• homocystein

Definition

• Transient ischemic attack– Focal cerebral ischemic event resolving

within 24 hours

• Completed Stroke– No resolution of symptoms

Causes of Stroke

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

• 15% hemorrhage – – intracerebral– subarachnoid hemorrhage

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

CT Angiogram

Vascular Distribution

Lacune

• Fibrinoid degeneration of penetrating arteries

• Most commonly due to hypertension• Involves deep white matter pens and

basal ganglia

Cardiogenic Emholi

• NVAF -45%.• IHD - acute MI -15%• - ventricular aneurysm -10%• RHD -10%• Prosthetic valve -10%• Other -10%.

Stroke SyndromesCarotid Circulation

Internal Cerebral Artery

• Hemiplegia• Hemisensory loss• Aphasia (L)• Neglect (R)

Anterior Cerebral artery• Contralateral lower limb paresis and

hyperreflexia• upper limb relatively spared

PCA Infarct

Vertebrobasilar Circulation

• Multiple stroke syndromes depending on vessels in site

• Dysarthria• Ataxia• Bilateral weakness• Bilateral sensory complaints• Bilateral visual complaints

Pontine InfarctLocked-In Syndrome

Lacunar Infarct

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

Isolated Symptoms Rarely due to Stroke or TIA

• Vertigo. dizziness• Diplopia• Loss of consciousness• Confusion

Differential Diagnosis

• Transient Ischemic attack• Focal seizure• Hypoglycemia• Carpal tunnel syndrome• Migraine• Hysteria

Ddx Vertebrobasilar TIA

• Syncope• Labyrinthitis• Myasthenia gravis• Meniere's disease

Investigation• CT, CTA, CT perfusion • MRI/MR angiogram • CBC. differential and platelets• INR, PTT• Cholesterol, triglyceride• Doppler• Echocardiogram

Vertebrobasilar Circulation

• As above but no Doppler• Treatment• Prevention:• Controlled risk factors

Carotid Circulation

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

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

with carotid endarterectomy or angioplasty and stenting

• Risk factor management

Acute Thrombolysis

Pre

Post

Treatment of Acute Stroke

• NINDS protocol– < 4.5 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

HWhat 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 hematoma

• Drowsiness. headache• Evolves over days to weeks• History of head trauma not always

present

Subdural 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 SclerosisMRI

Demyelinating DiseaseClassification

• Multiple sclerosis.• Diffuse cerebral sclerosis.• Post viral or post vaccinial disseminated

encephalomyelitis.• Necrotizing hemorrhagic encephalomyelitis.• Metabolic toxic• postanoxic encephalopathy• CPM

Dysmyelinating Disorders

• ALD• MLD• Krabbe's• Canavan's• Chediak Higashi• Neuraxonal dystrophy• Pelazeus Merzbacher

Multiple Sclerosis

• Dissemination of lesions in time and space• MacDonald Criteria• EDSS or Kurtze Scale• Prevalence 0.1%• Female:male = 3:2• 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

Treatment• Acute Attacks• Steroids.

– Solumedrol– Prednisone

• Prophylaxis– Beta interferon– Copolymer– Mitoxandrone– Natalizumab– Fingolimod (Gilenya)– Teriflunomide (Aubagio)– Dimethyl fumarate (Tecfidera)

Symptomatic

• Spasticity– Baclofen– Dantrium– Benzodiazepines

• Pain– Gabapentin– Pregabalin– Carbamazepine

Treatment

• Paroxysmal Disorders– Tegretol– Dilantin

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

• Depression– Tricyclic antidepressants– SSRI– SNRI

• Fatigue– Amantidine

Seizures

• Seizures originate from the cortex• Case

Simple Partial Seizures.

1. motor

2. somatosensory or special sensory

3. autonomic

4. psychic

Complex Partial Seizures

• Partial seizure with altered awareness• SP -CP• CP• + automatisms.

Partial Seizures - to secondary generalization

• SP-GTC• CP - GTC• SP -CP-GTC

Generalized Seizures (convulsive and non convulsive)• Absence

– Typical– Atypical

• Myoclonic• Clonic• Tonic• Tonic-clonic• Atonic.

History• How did the seizure start

– staring– eye deviation– jerking or one limb

• Patient's description of aura• Post ictal state• Age of onset• Family history• Past history• Alcohol or drug abuse

Physical Exam

• Todds paralysis• Eye deviation• Cranial bruit• Hyperventilation• Skin examination• Incontinence

Investigation

• Glucose. BUN, Calcium. Sodium• CT, MRI• EEG

TreatmentPartial Seizures

• Carbamazepine• Phenytoin• Primidone• Phenobarbital• Valproic Acid• Lamotrigine• Levetiracetam• Lacosamide

Tonic Clonic

• Valproic acid (Divalprpoex)• Carbamazepine (Tegretol)• Phenytoin (Dilantin)• Phenobarbital• Primidone (Mysoline)• Levetiracetam (Keppra)• Lacosamide (Vimpat)

Absence

• Valproate• Ethosuximide

Myoclonic

• Valproate• Clonazepam• Nitrazepam

Add On Meds

• Gabapentin• Lamictal• Vigabatrin• Topiramate

CASE

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

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

• Where is the lesion ?

CT Scan

Dementia• A loss of intellectual ability of sufficient severity

to interfere with social or occupational functioning.

• Memory impairment.• At least one of:

– impaired abstract thinking– Impaired judgement– Other disturbances of higher cortical functioning -– aphasia. apraxia, agnosia. constructional difficulty– Personality change

Irreversible• Alzheimer’s Disease (amyloidopathies) • Frontotemporal Dementia (tauopathies)• MSA, PD, CBD, Lewy Body (synucleinopathies)• HIV• MID

– Large vessel– Small vessel

• Prionopathies– CJD– CJDv– Gerstmann-Straussler-Schenker– Fatal Familial Insomnia

Reversible• Drugs

– Alcohol, alcohol, alcohol• Metabolic

– B12– T4

• Infectious– Syphilis

• SOL– Subdural– Meningioma

• NPH• Sleep Apnea• Pseudodementia

Alzheimer's Disease

• 50 to 60% of cases of dementia.• Greater than 65 years old -

– prevalence 1-6%.

• 4th most common cause of death

Diagnostic Criteria"Probable (clinically ascertained)

A.D.• Dementia• Onset 40 to 90 years• Deficits present in greater than 2

cognitive spheres• Progressive deterioration.• No disturbance of consciousness.• No other illness to account for symptoms.

"Definite" (pathologicallv confirmed) AD

• Clinical criteria.• Histopathological evidence.

– neurofibrillary tangles– neuritic plaques– granulovacular degeneration– Hirano bodies

Alzheimer’s DiseasePathophysiology

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

Multi-Infarct Dementia

• Greater than 50-100% of cerebral hemisphere destroyed

• Multiple strokes involving both hemispheres

• Bilateral pyramidal signs• Pseudobulbar signs

Vitamin B12 Deficiency

• Insidious onset• May have normal smear and normal

neurologic exam except for dementia• Look for paresthesias plus signs of dorsal

column and corticospinal tract involvement.

Normal Pressure Hydrocephalus

• Triad– Ataxia– Incontinence– Dementia

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

Depression" Pseudodementia"

• Commonly have history of previous psychiatric disorder.

• Brief duration.• Complaint of cognitive deficit but make

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

Creutzfeldt-Jacob Disease

• Onset to death usually months.• Dementia, myoclonus, UMN, basal

ganglia.• Characteristic EEG - periodic discharge

1/sec,• Caused by prions

Environmental Factors

• Head trauma• Infectious agents• Neurotoxins• Alcohol

Down's Syndrome and AD

• Neuropathologic similarities• Role of chromosome 21

Investigation

• CT, MRI• EEG• B12. folate• CBC, differential. platelets• VDRL• Thyroid function tests• BUN. creatinine.

Investigation

• AST. ALT• Lytes• ESR• CXR• Neuropsychological testing• Lumbar 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 20

• Neuro exam shows• Inattentive• Left facial weakness• Mild left upper and lower limb weakness

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

limbs

Where is the lesion?

CT Scan

Brain TumorsGBM

Meningioma

Brain TumorsMedulloblastoma

Tumor

• Often in frontal lobe.• Grasp, suck. snout reflexes• "slowness" in carrying out tasks• Impaired smell• Tumors obstructing 3rd or 4th ventricles

Case 19

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

• Physical exam– See video

Parkinson’s Disease

• 70 to 80 years old• rarely less than 40 years old• 1/1.000• Video 1• Video 2• Video 3• Video 4

Cardinal Features

• a. tremor.• b. rigidity• c. bradykinesia• d. postural instability

Tremor

• resting tremor• "pill rolling"• 5 to 6 Hz• unilateral early• increases with stress• decreases with movement

Rigidity

• "lead pipe"– bilateral– 1 side greater than the other

Bradykinesia

• masked facies• decreased blink frequency• decreased rapid alternating movements• decreased extraocular movements• hypophonia, palilalia. aprosody• sialorrhea• micrographia

Bradykinesia

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

in bed• slow ADL• characteristic stooped gait with small

steps• and decreased arm swing• "freezing

Postural instability

• retropulsion• festination• sit "en bloc"• falling

Clinical StagesStage I

• Mild unilateral tremor or rigidity with or without bradykinesia

Stage II

• Moderate bilateral tremor or rigidity and bradykinesia.

Stage III

• Significant tremor. rigidity and or bradykinesia plus impaired

• postural reflexes• gait disturbance, mild daily fluctuations

+- dementia

Stage IV

• Severely disabled but still mobile and able to function

• independently - with or without daily periods of complete

• immobility; +- dementia

Stage V

• Loss of ability to function independently

Autonomic dysfunction

• constipation• dysphagia• neurogenic bladder• drooling• orthostatic hypotension• diaphoresis

Primary sensory symptoms

• vague parasthesia

Etiology

• Abnormal processing of synuclein protein

• Toxins• Infectious agents• Immunological factors• Genetic factors• MPTP

Pathophysiology

• Progressive loss of presynaptic dopaminergic neurons in the substantia nigra

• cortical pathological changes like AD in 50%.

• Changes in post synaptic striatal dopamine receptors

TreatmentMild Disability

• Anticholinergic• Amantadine• Selegiline

Moderate Disability

• L-Dopa/Carbidopa• Pramipexole (Mirapex)• Ropinoral (Requip)

Severe Disability

• Increased doses of L-Dopa and Dopamine Agonist

• COMT Inhibitor

Long Term Complications of Treatment with L-Dopa

• Dyskinesia• Daily fluctuations in level of function

– End of dose deterioration– freezing episodes– "on-off" phenomenon

• Dementia and drug induced confusion• Progressive drug failure.

Case Study

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

Case Exam

• Cranial Nerves• Dysarthria• Fasciculations of tongue

• Motor– Upper and lower limb weakness and wasting– Upper and motor limb hyperreflexia

• Sensory– Normal– Video

Case

• Where is the lesion?

• What is the cause?

• 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 MONTHS TO YEARS UNTIL COMPLETE PARALYSIS

* RANGE 1 TO 15 YEARS

* 50% DIE WITHIN 4 YEARS

* 20% LIVE FOR FIVE YEARS

* 10% LIVE FOR TEN YEARS

* AGE LESS THAN 65 AVERAGE DURATION OF LIFE 3 YEARS

* AGE GREATER THAN 65, AVERAGE DURATION 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 Signs

• 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 Signs

* 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

ALSTreatment

* Supportive

* Prevention of complications

* Respiratory - Pneumonia - Tracheostomy - Ventilation

* Nutrition - Feeding tube

* Musculoskeletal - Splints - Contractures

ALSTreatment

* 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 Pretreatment

MSLT 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 Disease

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

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

penetrance• 10-15% -juvenile onset

Huntington’s Disease

• Westphal variant• 90% from affected father• 10-15% - greater than 55 years old• slower decline

Neuropathology

• Caudate and putamen• Atrophy. neuronal depletion. gliosis• Decreased GABA and acetylcholine

Gene Defect

• Short arm of chromosome 4

Coma

• A. Airway• B. Breathing• C. Circulation• Neurological Examination• 1. Respiration• 2. Pupils, oculomotor function• 3. Skeletal motor

Respiration

• Bilateral encephalopathy - Cheyne Stokes• Upper pens - hyperventilation• Pontine tegmentum - apneustic breathing• Lower pons - cluster breathing• Meduila - ataxic breathing

Pupils

• Bilateral hemisphere diencephalon– Small reactive

• III nerve. – Uncal mass with herniation

• Tectal - large fixed• Midbrain - mid position. regular fixed• Pons -Small pinpoint.

Extra-Ocular Movements

• conjugate• deviated• skew• bobbing; nystagmus

Reflex eye movements

• Doll's eyes• Calorics (COWS) • Dysconjugate -MLF• Lost - brainstem nuclei

Motor Responses• Hemisphere

– appropriate ipsilateral– flexion contralateral

• Hypothalamus and midbrain– decorticate

• Lower midbrain - – decerebrate

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

Differential Diagnosis of Coma

• Supratentorial mass lesions.• Midbrain or pontine destructive lesions.• Intratentorial mass lesions.• Diffuse multifocal disorders.• Pseudocoma

Investigations

• Glucose, BUN. creatinine, • Gas. AST• Lytes• Toxic screen• CT• EEG• LP

Seizures

• alcohol withdrawal seizures• 12 to 48 hrs following cessation of alcohol

intake• generalized tonic clonic seizures• 2-3 seizures• risk of delerium tremens

Neurology of Alcoholism

• RUM fits• Seizure induced by alcohol

Seizure Induced by Alcohol

• usually focal• reflect intrinsic CNS disease• often post traumatic due to multiple falls• rule out subdural hematoma and

meningitis

Wernickes EncephalopathyDue to Thiamine Deficiency

• Ocular changes– nystagmus– 6th nerve palsy– paralysis of conjugate gaze

• Ataxia• Confusion

Korsokoff's Psychosis

• extension of confusion of Wernickes• permanent severe memory impairment

with confabulation

Treatment

• Thiamine 100 mg IV• Repeat daily until patient is back on normal

diet.• Intravenous glucose - always give with

thiamine• - glucose depletes thiamine stores and• can give rise to Wernickes encephalopathy

Polyneuropathy

• Nutritional and toxic• Distal weakness and paresthesia• Treatment

– diet– abstinence from alcohol– multivitamins

Cerebellar Degeneration

• males more than females• trunchal ataxia and lower limb dysmetria• Treatment

– diet and vitamins.– abstinence from alcohol

Delerium Tremens

• 72 to 96 hours• Severe tremulousness• Hallucinations - visual and auditory• autonomic hyperactivity - hypertension.

fever. dilated• pupils and diaphoresis• Can be fatal

Treatment

• Thiamine• Folate• Lorazepam, 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

Back Pain

• 33 year old left handed HVAC worker• Develops left hip pain in Oct 2012, treated

with NSAIDs and rest• Recurrence summer 2013 when diving into

lake• January 2014, sudden left leg pain and

numbness radiation anterolateral aspect of left leg

History

• Treated conservatively with physio and chiropractor

• Physical Exam– Weakness L plantar flexor, loss of ankle jerk

Localization

• Muscle• Neuromuscular Junction• Peripheral Nerve• Spinal Cord