EPILEPSY - 10 Marks

Definition

Classification (ILAE 2017)

By Seizure Onset:

Focal Seizures:

• Focal aware (formerly simple partial) - consciousness intact
• Focal impaired awareness (formerly complex partial) - consciousness impaired
• Focal to bilateral - spreads to both hemispheres (formerly secondary generalized)

Generalized Seizures:

• Motor: Tonic-clonic (grand mal), tonic, clonic, myoclonic, atonic
• Non-motor (absence): Petit mal - brief staring spells with 3 Hz spike-wave on EEG

Etiology

• Structural: Tumors, stroke, cortical dysplasia, hippocampal sclerosis
• Genetic: Channelopathies (SCN1A mutation in Dravet syndrome)
• Infectious: Neurocysticercosis, meningitis, encephalitis
• Metabolic: Hypoglycemia, hyponatremia, uremia
• Immune: Autoimmune encephalitis (anti-NMDAR)
• Unknown/Idiopathic: Juvenile myoclonic epilepsy (JME)

Pathophysiology

• Seizures arise from imbalance between excitatory (glutamate) and inhibitory (GABA) neurotransmission
• Abnormal sustained depolarization of neurons = Paroxysmal Depolarizing Shift (PDS)
• Ictal spread depends on failure of surround inhibition

Diagnosis

EEG:

• Most important test - shows epileptiform discharges (spikes/sharp waves)
• Only ~2% of non-epileptics show epileptiform activity; up to 90% of epileptics do
• Specific patterns: 3 Hz spike-wave (absence), hypsarrhythmia (infantile spasms), polyspike-wave (JME)

Neuroimaging:

• MRI brain - preferred; detects structural lesions in ~85% of intractable epilepsy
• CT scan for emergencies (hemorrhage, acute structural lesions)

Blood tests: Glucose, electrolytes, CBC, LFTs, renal function

Treatment

Antiseizure Medications (ASMs):

• Start with monotherapy; increase dose before switching
• ~60% achieve seizure freedom with first drug
• ~30% are drug-resistant (failure of 2 adequate ASM trials)

Drug-resistant Epilepsy Options:

• Epilepsy surgery (temporal lobectomy) - most effective for temporal lobe epilepsy
• Vagus nerve stimulation (VNS)
• Responsive neurostimulator (RNS)
• Ketogenic diet

Discontinuation: Consider after 2 seizure-free years with normal EEG and MRI

Status Epilepticus

• Seizure lasting >5 minutes or ≥2 seizures without recovery
• Management: Lorazepam IV → Phenytoin/Levetiracetam → General anesthesia (refractory)

STROKE - 10 Marks

Definition

Epidemiology

• Leading cause of adult disability worldwide
• 2nd leading cause of death globally
• ~750,000 new strokes/year in the US
• Mortality ~15%; only ~1/3 regain full function
• Recurrence rate ~10%/year after first stroke

Classification

Ischemic Stroke Subtypes (TOAST):

1. Large artery atherosclerosis - carotid/MCA stenosis
2. Cardioembolic - AF, valvular disease, MI (AF = 5-fold stroke risk)
3. Small vessel (lacunar) - penetrating artery disease
4. Other determined etiology
5. Cryptogenic - ~30% of cases

Risk Factors

• Modifiable: Hypertension (#1), atrial fibrillation, smoking, diabetes, dyslipidemia, obesity, carotid stenosis
• Non-modifiable: Age, sex (male), family history, race
• Cardiac conditions causing embolism: AF, mitral stenosis, mechanical valves, recent MI, left ventricular thrombus, infective endocarditis

Clinical Features

• MCA territory (most common): Contralateral hemiplegia + hemisensory loss, aphasia (dominant), neglect (non-dominant), homonymous hemianopia
• ACA territory: Leg > arm weakness, personality change
• PCA territory: Homonymous hemianopia, visual agnosia
• Posterior circulation (PICA - Wallenberg syndrome): Ipsilateral facial sensory loss, contralateral body sensory loss, dysphagia, vertigo, Horner's syndrome
• Lacunar syndromes: Pure motor hemiplegia, pure sensory, ataxic hemiparesis

Investigations

• Non-contrast CT brain - immediate; rules out hemorrhage (hyperdense area = bleed)
• MRI DWI - most sensitive for early ischemic stroke
• CT/MR Angiography - large vessel occlusion detection
• ECG + Cardiac monitoring ≥48 hours - detect AF (arrhythmias in up to 20% post-stroke)
• Troponin, Echo - cardioembolic workup
• Carotid Doppler - stenosis assessment
• Blood: CBC, coagulation, glucose, lipids

Management

Acute Ischemic Stroke:

• ABC - airway, oxygen if SpO₂ <94%
• Keep head of bed >30° (aspiration prevention)
• IV Alteplase (tPA): Within 4.5 hours of onset
  • Dose: 0.9 mg/kg (max 90 mg); 10% as bolus, rest over 60 min
  • Exclusions: BP >185/110, active bleeding, recent surgery, prior ICH, INR >1.7, glucose <50 or >400
• Endovascular Thrombectomy: For large vessel occlusion (ICA/proximal MCA)
  • Window: up to 6 hours (selected patients up to 24 hours with perfusion-diffusion mismatch)

Blood Pressure Management:

• Do NOT aggressively lower BP in acute stroke (impairs penumbral perfusion)
• Only treat if SBP consistently >220 mmHg or DBP >120 mmHg (in non-thrombolysis patients)
• Optimal post-stroke BP: SBP 160-200 mmHg, DBP 70-110 mmHg in first 48-72 hours

Antiplatelet Therapy:

• Aspirin 81-325 mg/day - start after excluding hemorrhage
• Clopidogrel or Aspirin + dipyridamole (Aggrenox) - superior to aspirin alone for secondary prevention
• Avoid dual antiplatelet (aspirin + clopidogrel) long-term - increases hemorrhage risk

Anticoagulation:

• Warfarin / DOACs for cardioembolic stroke with AF
• Target INR 2.0-3.0 with warfarin

Secondary Prevention

• BP control (most important modifiable factor)
• Statins (regardless of baseline LDL)
• Antiplatelet agents / anticoagulation as appropriate
• Smoking cessation, diabetes control, lifestyle modification
• Carotid endarterectomy if stenosis >70% (symptomatic)

Complications

• Cerebral edema (peaks day 3-5) - malignant MCA infarct
• Hemorrhagic transformation
• Aspiration pneumonia (mortality 15-25% in stroke)
• DVT/PE, UTI, pressure sores
• Post-stroke seizures - up to 60% recurrence risk within 1 year in severe strokes
• Post-stroke depression