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Wednesday, August 13, 2025

Epilepsy


Introduction

Epilepsy is a chronic neurological disorder characterized by a predisposition to generate recurrent, unprovoked seizures due to abnormal, excessive, or synchronous neuronal activity in the brain. It is one of the most common serious neurological conditions, affecting people of all ages.

The diagnosis requires at least two unprovoked seizures occurring >24 hours apart, or one unprovoked seizure with a high probability of recurrence (≥60% over 10 years) due to an underlying brain condition. Epilepsy can have diverse etiologies, multiple seizure types, and a wide range of comorbidities.

Epidemiology

  • Global prevalence: ~50 million people worldwide.

  • Incidence: 40–70 per 100,000 population/year in high-income countries; higher in low-income countries.

  • Age distribution: Peaks in childhood and in older adults (>60 years).

  • Gender: Slightly more common in males in some regions, but overall similar prevalence.

Etiology

Epilepsy can result from a wide range of structural, genetic, metabolic, immune, infectious, or unknown causes.

1. Structural

  • Stroke (most common in older adults)

  • Traumatic brain injury

  • Brain tumors

  • Cortical dysplasias

  • Hippocampal sclerosis

2. Genetic

  • Mutations in ion channel genes (e.g., SCN1A in Dravet syndrome)

  • Inherited epileptic syndromes

3. Infectious

  • Neurocysticercosis

  • Viral encephalitis

  • Meningitis

  • HIV-related CNS infections

4. Metabolic

  • Hypoglycemia, hyponatremia, hypocalcemia

  • Mitochondrial disorders

5. Immune

  • Autoimmune encephalitis (e.g., anti-NMDA receptor encephalitis)

6. Unknown (Idiopathic)

  • No identifiable structural or metabolic cause

Pathophysiology

Seizures result from:

  1. Hyperexcitability – Increased tendency of neurons to fire action potentials.

  2. Hypersynchrony – Abnormal synchronization of neuronal firing.

  3. Neurotransmitter imbalance:

    • Excess excitatory glutamate activity.

    • Reduced inhibitory GABAergic activity.

  4. Ion channel dysfunction – Abnormal sodium, potassium, or calcium channel activity.

Classification

The International League Against Epilepsy (ILAE) 2017 classification:

1. Focal Onset Seizures

  • Start in one hemisphere.

  • Aware (formerly simple partial) or Impaired awareness (formerly complex partial).

  • May evolve to bilateral tonic–clonic seizures.

2. Generalized Onset Seizures

  • Involve both hemispheres at onset.

  • Types:

    • Tonic–clonic

    • Absence

    • Myoclonic

    • Tonic

    • Clonic

    • Atonic

3. Unknown Onset Seizures

  • When onset is not witnessed or unclear.

Clinical Features

  • Motor symptoms: tonic (stiffening), clonic (jerking), myoclonic jerks, automatisms.

  • Sensory symptoms: visual flashes, auditory hallucinations, paresthesias.

  • Autonomic symptoms: tachycardia, flushing, sweating.

  • Cognitive/psychic symptoms: déjà vu, fear, confusion.

  • Postictal state: confusion, headache, focal weakness (Todd’s paralysis).

Diagnosis

Diagnosis is clinical, supported by investigations.

History and Examination

  • Detailed description of events (eyewitness account crucial).

  • Precipitating factors: sleep deprivation, alcohol, flashing lights.

  • Past neurological history.

Investigations

  • EEG: Detects epileptiform discharges; may identify seizure type.

  • MRI brain: Preferred to detect structural lesions.

  • Blood tests: Glucose, electrolytes, calcium, renal/liver function.

  • Lumbar puncture: If CNS infection suspected.

  • Video-EEG monitoring: For refractory cases and presurgical evaluation.

Management

Goals: Seizure control, prevention of recurrence, minimization of drug side effects, and improvement in quality of life.

1. General Measures

  • Identify and avoid seizure triggers.

  • Education on medication adherence.

  • Safety precautions: no swimming alone, avoid driving until seizure-free for the legally required period.

2. Pharmacologic Treatment

Choice of drug depends on seizure type, age, sex, comorbidities, and drug interactions.

First-line Drugs by Seizure Type

Focal Onset Seizures

  • Carbamazepine: Start 200 mg twice daily, titrate to 600–1200 mg/day.

  • Lamotrigine: Start 25 mg/day, increase gradually to 100–400 mg/day.

  • Levetiracetam: Start 500 mg twice daily, increase to 1000–3000 mg/day.

Generalized Tonic–Clonic Seizures

  • Valproic acid: Start 10–15 mg/kg/day, increase to 30–60 mg/kg/day.

  • Lamotrigine or Levetiracetam if valproic acid contraindicated.

Absence Seizures

  • Ethosuximide: 250 mg twice daily, increase to 20 mg/kg/day.

  • Valproic acid if coexisting with generalized tonic–clonic seizures.

Myoclonic Seizures

  • Valproic acid

  • Levetiracetam

  • Topiramate: Start 25–50 mg/day, increase to 200–400 mg/day.

Second-line and Adjunctive Agents

  • Topiramate

  • Zonisamide

  • Clobazam

  • Perampanel

  • Lacosamide

Drug Principles

  • Start with monotherapy; titrate to effective dose.

  • If ineffective or poorly tolerated, switch to another monotherapy.

  • Add-on therapy for refractory epilepsy.

  • Monitor for side effects (e.g., hepatotoxicity with valproic acid, rash with lamotrigine, hyponatremia with carbamazepine).

3. Non-Pharmacologic Treatments

  • Epilepsy surgery: For drug-resistant focal epilepsy (e.g., anterior temporal lobectomy for temporal lobe epilepsy).

  • Vagus nerve stimulation: Implanted device to reduce seizure frequency.

  • Ketogenic diet: High-fat, low-carbohydrate diet effective in some pediatric epilepsies.

Status Epilepticus

Medical emergency defined as seizure >5 minutes or recurrent seizures without recovery.

  • First-line: IV lorazepam or diazepam.

  • Second-line: IV phenytoin, valproate, or levetiracetam.

  • Refractory: General anesthesia with midazolam, propofol, or pentobarbital.

Prognosis

  • About 60–70% of patients achieve good seizure control with medication.

  • Some epilepsy syndromes remit with age; others are lifelong.

  • Risk factors for poor prognosis: symptomatic etiology, abnormal neurological exam, frequent seizures before treatment.

Complications

  • Physical injury during seizures.

  • Sudden unexpected death in epilepsy (SUDEP).

  • Cognitive impairment.

  • Psychosocial difficulties.

Patient Education

  • Importance of strict medication adherence.

  • Avoid triggers (sleep deprivation, alcohol).

  • Inform friends/family on seizure first aid.

  • Driving and occupational safety restrictions.




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