.

.

knowledge

case scenario investigation, diagnosis and treatment

Seizure/epilepsy

Neuro-infectious disease

Stroke: ischemic infarct, hemorrhagic

Headache: migraine

Degenerative disease: Parkinson, Dementia

Seizure/epilepsy

alteration of conscious seizure syncope TIA

(seizure) (epilepsy)

(seizure) (epileptiform discharge)

(epilepsy)

: syncope

Seizure vs Syncope

Bhidayasiri R. et al. Neurological differential diagnosis 2005

Partial seizure ()

simple partial seizure

complex partial seizure frontal temporal

Generalize seizure ()

tonic clonic, tonic, clonic, atonic, absence, myoclonic

70 years of AED development

20 years of new AED development

Antiepileptic drug classification

Old generation

1800s Bromide Solution 1912 Phenobarbital 1938 Phenytoin 1960 Ethosuximide 1973 Carbamazepine 1978 Valproate

New generation

1993 Felbamate 1993 Gabapentin 1994 Lamotrigine 1996 Fosphenytoin 1996 Topiramate 1997 Tiagabine 1999 Vigabatrin 2000 Oxcarbazepine 2000 Levetiracetam 2005 Pregabalin

Epilepsy Management

* Brodie MJ and Kwan P. CNS Drugs 2001;18:1-12

phenytoin

Status epilepticus

definition of SE

Lowenstein DH (1999) SE > 5 minutes

Key

treat early as possible step up AED is depended on stage of

SE

add on therapy is needed monitor EEG regularly, even if no

obvious seizure

Define stage of the status epilepticus

Pre-monitory status(0-5 min) Early status(5-30 min) Established status(30-60 min) Refractory status(>60 min)

Drug used

diazepam, phenytoin(Dilantin), valproic acid(Depakine), levetirazetam(Keppra)

Phenobarbital, propofol, midazolam, thiopental

Topiramate(feed)

drug use depend on stage of status

stage of status AED treatment

Premonitory (0-5 min) Diazepam (i.v. bolus)

Early (5-30 min)Diazepam (i.v. bolus) followed by

phenytoin (iv load) or sodium valproate (i.v. loading) or levetiracetam (i.v.)

Established (30-60 min) half dose i.v. load of previous drug, if seizure dont stop, load another drug

Refractory ( > 60 min)Propofol (i.v.), or midazolam (i.v.), or

thiopental (i.v.) or phenobarbital (i.v.) or topiramate (feed)

Neuro-infectious disease

Meningitis Meningitis is a disease caused by the inflammation of

the protective membranes covering the brain and spinal cord known as the meninges.

Clinical symptoms: fever, headache, stiffness of neck, sign of IICP, photophobia, alteration of conscious

Diagnosis: Lumbar puncture shows pleocytosis

Cause: infection (viral, bacteria, parasite), inflammation (autoimmune), cancer

CT or not CT in meningitis

Aseptic meningitis Lymphocytic pleocytosis, normalm CSF sugar, normal/slightly high

protein

Causes:

Viral: enterovirus(Coxsackie, echo, polio), HZV, VZV, arbovirus, EBV, etc.

Bacteria: partially treated bacterial meningitis, parameningeal infection, mycoplasma pneumoniae, Treponema pallidum

Fungal: crypto, histoplasma,

Parasitic: Toplasma, cysticercosis,

Drug: NSAIDs, Bactrium, amoxicillin)

Cancer: carcinomatous meningitis, lymphomatous meningitis

Vasculitis: CNS vasculitis, Behcet disease, SLE

Eosinophilic meningitis CSF presents eosinophilia of at least 10% of the total CSF

leukocyte count.

Cause:

Parasitic: angiostrongyliasis, gnathostomiasis

Non-parasitic infection: Tuberculous meningitis, Cryptococcal meningitis, syphilitic meningitis

Hematologic: Hodgkins disease, non-Hodgkins lymphoma, and eosinophilic leukemia

Non-Hematologic: carcinomatous meningitis

HIV infection

Viral Encephalitis Diagnosis:

clinical: fever, alter mental status, seizure, focal neurological deficit

CSF: aseptic profile

MRI, CT brain: brain lesion (fronto temporal involvement suggest Herpes simplex encephalitis)

PCR: HSV, CMV, HZV

EEG: periodic sharp wave

Treatment: acyclovir 10 mg/kg/dose q 8 hrs

HSE

Neurological disorder in HIV

Primary HIV-induced neurologic syndromes

OIs

Brain mass in HIV

The concomitance of negative toxoplasmosis serology + a single lesion on radiographic imaging -> sufficient to warrant the performance of a stereotactic biopsy

Median time to response of Toxoplasmosis

74% 7 days -> 91% 14 days

Lymphoma vs Toxoplasmosis

Large lesion size (>4 cm)

Extensive white matter involvement

Periventricular location/subependymal spread

Contrast enhancement along ventricular surface

Extension across or involvement of corpus callosum

Large number of lesions

Involvement of basal ganglia

Hemorrhagic lesions

Responses to anti-toxo drugs, usually within 7-14 days

Favors Lymphoma Favors Toxoplasma

A HIV patient with alteration of consciousness for 3 days

Neuromuscular disorder

Neuromuscular disorder

Neuropathy: polyneuropathy, cranial neuropathy

NMJ disorder: Myasthenia gravis

Muscle disease

Differential diagnosis of neuropathies by clinical course

Nerve conduction study: reveals demyelination of nerve (or axonal degeneration in axonal type)

Treatment of GBS

ABCD support

IVIG or plasma exchange: effective

Combination treatment: no additive effect

Corticosteroid: not effective

NMJ disorder

Myasthenia gravis

Botulism

Lambert Eton Myasthenic Syndrome (LEMS)

Cause of MG caused by autoantibodies specific for the human

nicotinic acetylcholine receptor (AChR)

Ach released per impulse normally decline on repeated activity= presynaptic rundawn

Autoimmune cause: The most important known cause is thymic tumour

3060% of thymomas : associated with MG

10% of MG: have a thymoma

Diagnosis should be based on positive results from at least two of the main diagnostic tests

AChR antibody assay (+ 75% in Generalize MG)

Edrophonium (Tensilon) test or Neostigmine test

repetitive nerve stimulation

single-fibre electromyography

Associated disorder Disorder of thymus

Thymoma Hyperplasia

Other autoimmune disorder Hashimoto thyroiditis Graves disease RA SLE

Disorder or circumstance that may exacerbate MG Hyperthyroidism Occult infection Medical Rx of other condition

(aminoglycoside, quinidine, antiarrhythmic drug)

Disorder that may interfere therapy TB,DM,PU,GI bleed ,Asthma, osteoporosis

Treatment base therapy

Symptomatic therapy Short acting

cholinesterase inhibitor Pyridostigmine bromide

(mestinon) Long acting

cholinesterase inhibitor Neostigmine(prostigmin

) Mestinon timespan

Immunosuppressive therapy Long term

immunosupression Medical

Corticosteroid Immunosupressive drug

Surgical thymectomy

Short term immunosupression Plasma exchange IVIG

Myasthenic crisis MG with

Respiratory failure

Bulbar involvement

Treatment

Respiratory support

Plasma exchange or IVIG

No role of steroid / no role of anti-AChE in MG crisis

Stroke

Stroke SubtypesIschemic Stroke (83%)Hemorrhagic Stroke (17%)

Atherothrombotic Cerebrovascular Disease (20%)

Embolism (20%)Lacunar (25%) Small vessel disease

Cryptogenic and Other Known Cause (30%)

Intracerebral Hemorrhage (59%)

Subarachnoid Hemorrhage (41%)

Albers GW, et al. Chest. 1998;114:683S-698S. Rosamond WD, et al. Stroke. 1999;30:736-743.

3.1%

3.6%

18.2%

0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0%

seizures

toxic/metabolic

PN palsy

tumour

SDH

confusional state

migraine

psychogenic

dementia

syncope/presyncope

MS

vertigo

TGA

SAH

miscellaneous

% of all stroke mimics (n=670)

Condition that mimic stroke

What Is the Cause of Ischemic Stroke? Atherothrombosis Embolus:

Material: Red (fibrin rich) or White (platelet rich) Source: Cardiac? Aortic? Carotid Artery?

Small artery disease Hypoperfusion: Hemodynamic Others: arterial dissection, arteritis, etc.

Lacunar Syndromes

Strategies for Preventing Stroke and Reducing Stroke Disability

First stroke

blood pressure glucose smoking lipids

mass popl. strategy

hypertension TIA Atrial fibrillation other vascular disease

high risk strategy

stroke mortality

acute treatment

Secondary prevention

recurrent stroke

Stroke related disability

Rehabilitation

Stroke: Well-Documented and Modifiable Risk Factors

Hypertension

Diabetes

Dyslipidemia Atrial fibrillation

Other cardiac conditions

Cigarette smoke

Asymptomatic carotid stenosis Sickle cell disease Postmenopausal hormone

therapy Diet and nutrition Physical Inactivity Obesity and body fat

distribution

Since 1995 rt-PA era

IV rtPA (recombinant tissue plasminogen activator ) 31 51 % 3 20 30%

Death rate at 3 months and 1 years is equal both group

Intracranial hemorrhage 6.4%

Thrombolysis

3-4.5

Need check list

1. age > 80 years2. NIHSS > 253. Previous stroke with

diabetes4. Receiving anti-coagulant

Additional exclusion criteria for rtPA within 3-4.5 hours

Stroke Treatment

3-4.5 H O

U R

S

Call emergency

services

A+E stroke team

Activated

Brain scan

Thrombolysis Drugs

Full recovery

Stroke onset Secondary prevention

Activate fast track when clinical stroke occur within 2-3.5 hours

CT brain, non-contrast

sensitivity 100%

Minor or subtle signs : loss of lentiform nucleus, loss of insular ribbon, loss of gray-white differentiation and sulcal effacement

Major complication of cerebral infarction

Subfalcine (A) Uncal (B) Central (C) Extradural (D) Tonsillar (E)

Herniation syndrome

Treatment IICP 20-30

(Jugular vein)

osmotherapy: Mannitol* 0.25-0.5 g/kg 20 4-6

10% Glycerol 250 ml 30-60 4

50% Glycerol 50 ml 4 / Furosemide 1 mg/Kg

Treatment IICP

hypotonic solution

Hyperventilation Pco2 30-35 mmHg

steroid

Hemicraniectomy in malignant middle cerebral artery infarction

Malignant MCA infarction : MCA (> 50% of MCA territory) brain herniation

Signs Contralateral weakness Eye deviate to ipsilateral lesion Global aphasia in dominant hemisphere Hemispatial neglect in nondominant hemisphere Signs of IICP, brain herniation

Dementia

Amnestic and dementia syndrome

Amnestic syndrome Profound loss of the episodic memory Dementia Acquired and persistent compromise in multiple cognitive, domains that are severe enough to interfere with every day functioning Delirium or acute confusional state(ACS) Prominent deficits or fluctuations in attention processing

Dementia diagnosis: DSM IV criteria The development of multiple cognitive deficit that include memory impairment and at least

one of the following

Aphasia, Apraxia, Agnosia, Disturbance of executive function

The cognition deficit must meet the following criteria

Be sufficiently severe to cause impairment in occupational or social functioning

Represent a decline from a previous from a previous higher level of functioning

Diagnosis should not be diagnosed if the cognitive deficit occur exclusively during the course of delirium. However, a dementia and a delirium both may be diagnosed if the dementia is present at times when the delirium is not present

Dementia may be related etiologically to a general medical condition, to the persisting effects of substance abuse(including toxin exposure), or to a combine of these factor

Dementia approach

Dementia

Reversibel dementia

- Drug - Syphilis - Hypothyroid - Vitamin deficiency - Organ failure

Irreversible dementia

StableProgressive

- Vascular - Post traumatic - Post encephalitis - etc

NeurodegenerativeNon-neurodegenerative

- CJD - ADC - Vascular

Alzheimers disease

Non-Alzheimers disease

- Parkinsons disease dementia - DLB - Parkinson plus syndrome - Genetic (Wilson, Huntington)

Alzheimers disease Clinical manifestation

Progressive, degenerative CNS disorder

Characterized by memory impairment plus one or more additional cognitive disturbances

Gradual decline in three key symptom domains

Activities of daily living (ADL), Behavior and personality and Cognition

Most common cause of dementia in people aged 65 and over

Clinical manifestation

Cognitive dysfunction

memory loss language

disturbance

visuospatial disturbance

Neuropsychiatric symptoms

affect or mood disturbance

psychosis (delusion/hallucination)

personality change behavioural

(agitation/wondering)

Diagnostic studies

MRI/CT brain

generalized brain atrophy

medial temporal lobes reveals a disproportionate atrophy of the hippocampi

http://www.elements4health.com/mri-scans-accurately-diagnose-alzheimers-disease.html

Headache

Patient presents with complaint of a headache

Critical first step:Hx taking, physical exam

Red flag signs or alarming signs

Meets criteria for primary headache disorder?

Migraineheadache

Tension-type headache

Cluster headache and other TACs

Red flag signs

Investigation

Secondary headache disorder

Other (rare) headache disorder

(+)(-)

(+)

Alarming signs and symptoms

Alarming s/s suggest the possibility of secondary headache

The studies Headache sample (specific or non-

specific)

Pool analyzed data => guideline

, (Migraine with aura) ! (Common migraine)

Migraine without aura

Treatment

Life style modification Acute treatment Prophylactic treatment

(trigger factors)"

!

!

!

(trigger factors)"

!

!!

Pharmacotherapy of acute migraine attack

Non-specific Acetaminophen, NSAIDs caffeine opioids neuroleptic

Specific Dihydroergotamine Ergotamine Triptan

DHE injection form

Ergotamine tartrate+ Caffeine

Evers, S et al. European Journal of Neurology 2009, 16: 968981

Analgesics with evidence of efficacyEFNS migraine treatment guideline 2009

Evers, S et al. European Journal of Neurology 2009, 16: 968981

Triptans

Preventive Medication

Aim

Reduce attack frequency, severity, and duration

Improve responsiveness to acute headache therapies

Improve function and reduce disability Reduce overall cost associated with migraine

treatment

Indication for preventive treatment in migraine

Recurring migraine that significantly interferes with quality of life

Frequency of migraine attacks > 1/weeks Frequency of acute medication use>2/week Failure of, contraindication to, or trouble AE from acute

medication

Uncommon migraine: hemiplegic migraine, basilar migraine, prolonged, disabling or frequent aura, or migrainous cerebral infarction

Pract Neurol 2007; 7: 383393

ConceptRight drug

Right person

Right dose

Preventive medication that was proven the efficacy

Consider patient profiles, and co-morbidities

Titrate into the appropriated dose

Right duration

On the preventive therapy long enough

Recommended medication for

migraine prevention EFNS guideline

2009

Evers, S et al. European Journal of Neurology 2009, 16: 968981

Drugs Relative indicationsRelative

contraindication Adverse effect

Amytriptiline (TCA)

Propranolol (B-blocker)

Flunarizine (CCB)

Valproic acid (AED)

Topiramate (AED)

Other pain disorders, depression, anxiety,

insomnia

Hypertension, angina

Hypertension, vertigo

Epilepsy, mania, anxiety

Epilepsy, mania, anxiety

Mania, urinary retention, heart blocks,

glaucoma

Asthma, depression, CHF, Raynauds disease

Obesity, depression, PD

Liver disease, bleeding disorder

Renal calculosis, liver disease

Drowsiness, dry mouth, increase appetite,

weight gain

Fatique, lethargy, nausea, depression, dizziness

Drowsiness, weight gain, depression, PD

Nausea dyspepsia, sedation, increase

appetite, weight gain

Paresthesia, weight loss, alter taste, language

disturbance

Indications, contraindications, and adverse effects of conventional migraine preventive drugs

F. Galletti et al. Progress in Neurobiology 89 (2009) 176192

Continue preventive medication for 4-6 months

Thunderclap Headache (TCH)

The sudden severe headache

DDx thunderclap headache

Cerebral venous sinus thrombosis (CVST)

Cervical artery dissection Acute hypertensive crisis Ischemic stroke Pituitary apoplexy

Dodick DW. JNNP 2002;72;6-11

Schwedt TS et al. Lancet Neurol 2006;5: 621-31

Reversible cerebral vasoconstriction syndrome

Retroclival hematoma Third ventricular colloid cyst Intracranial infection

Primary thunderclap headache Primary cough, sexual,

exertional headache

Subarachnoid hemorrhage (SAH)

Sentinel headache

Subarachnoid hemorrhage (SAH)

SAH is the most common cause of TCH 11-25% of TCH may have SAH associated symptoms... loss of consciousness (1/3), seizure

(6-9%), delirium (16%), stroke, visual disturbance, N/V, dizziness, neck stiffness and photophobia

70% of patients presented with headache alone

Linn FH et al. Lancet 1994. 344: 590-93

Diagnostic tool

CT brain: within 12 hours: near 100% sensitivity within 1 weeks: about 20% sensitivity

Lumbar puncture: look for Xanthochromia Conventional angiography: to identify

aneurysm

Edlow JA. et al. N Eng J Med 2000;342:29-36

Diagnostic approach in TCH

CT

Positive Negative

Subarachnoid hemorrhage Stroke CVST Pituitary apoplexy Retrochival hematoma PRES

Lumbar puncture

Positive Negative

Subarachnoid hemorrhage MRI

Positive Negative

Stroke SIH Pituitary apoplexy Retrochival hematoma PRES

MR angiography or magnetic resonance venography

Positive Negative

Aneurysm CVST Dissection RCVS

Primary TCH

Schwedt TS et al. Thunderclap headache. Lancet Neurol 2006;5: 621-31

Thank you for your attention and hope you all get great

score on your exam!