Epilepsy & Seizure Disorders

Detailed Overview

Epilepsy is classified by seizure type (focal vs. generalized) and etiology (structural, genetic, infectious, metabolic, immune, or unknown). The condition imposes a heavy burden due to the unpredictability of seizures, risk of bodily injury, and psychosocial stigma. Accurate diagnosis with EEG and imaging is essential to select the correct anti-seizure medication (ASM).

Epidemiology & Demographics

Affects ~1% of the global population. Bimodal age distribution: peaks in early childhood (genetic/developmental causes) and older adults >65 years (stroke/tumors).

Etiological Mechanism

In children: genetic mutations (e.g., SCN1A in Dravet syndrome), cortical dysplasia, hypoxic-ischemic encephalopathy. In adults: ischemic stroke, traumatic brain injury, CNS tumors, CNS infections (neurocysticercosis, HSV encephalitis).

Primary Causes

Mesial temporal sclerosis, prior stroke, glioblastoma, viral encephalitis, genetic channelopathies.

• Prior brain insult: Traumatic brain injury, CNS infection, or stroke.
• Family history: Having a first-degree relative with idiopathic epilepsy.
• Dementia: Neurodegenerative diseases like Alzheimer's increase risk in the elderly.

Epileptogenesis occurs when the delicate balance between excitatory (Glutamate) and inhibitory (GABA) neurotransmission in the cortex is disrupted. This can result from altered ion channel function (e.g., mutated voltage-gated sodium channels causing prolonged depolarization), loss of inhibitory interneurons following a brain injury, or aberrant synaptic reorganization (e.g., mossy fiber sprouting in the hippocampus). A seizure initiates when a group of hyperexcitable neurons (seizure focus) fire synchronously in high-frequency bursts (paroxysmal depolarizing shift). If this local discharge overcomes surround inhibition, it propagates via cortical networks to cause a focal seizure, or spreads rapidly to both hemispheres (via thalamocortical pathways) resulting in a generalized seizure.

Characteristic Clinical Presentation

• Focal aware seizure (Aura): Sensory (e.g., olfactory hallucination), autonomic, or motor symptoms without loss of consciousness.
• Focal impaired awareness seizure: Altered consciousness, staring, and automatisms (lip-smacking, picking at clothes).
• Generalized tonic-clonic seizure: Sudden loss of consciousness, body stiffening (tonic phase), followed by rhythmic jerking (clonic phase), and post-ictal confusion.
• Absence seizure: Brief (10-20 seconds) episodes of staring and unresponsiveness, common in children.

Physical Examination Signs

• Post-ictal state (confusion, lethargy, focal Todd's paralysis lasting hours).
• Tongue biting (especially lateral tongue injuries).
• Urinary or fecal incontinence during the event.

• SUDEP (Sudden Unexpected Death in Epilepsy): Fatal complication, most common in poorly controlled generalized tonic-clonic seizures.
• Status Epilepticus: Medical emergency risking permanent neuronal damage.
• Physical injury: Fractures, head trauma, or burns occurring during a seizure.

Diagnostic Criteria & Guidelines

At least two unprovoked seizures occurring >24 hours apart; OR one unprovoked seizure with a probability of further seizures >60% over 10 years (e.g., structural lesion on MRI or epileptiform discharges on EEG); OR diagnosis of an epilepsy syndrome.

Differential Diagnosis

• Syncope (vasovagal or cardiogenic)
• Psychogenic Non-Epileptic Seizures (PNES)
• Transient Ischemic Attack (TIA)
• Complicated migraine

Laboratory Tests & Biomarkers

• Serum Prolactin: Transiently elevated immediately after a generalized tonic-clonic seizure (used rarely to distinguish from PNES).
• Basic Labs / Tox Screen: Normal. Used to rule out provoked seizures (hypoglycemia, hyponatremia, drug intoxication).

Imaging Modalities & Findings

• Brain MRI (Epilepsy Protocol): May show mesial temporal sclerosis (hippocampal atrophy/T2 hyperintensity), focal cortical dysplasia, or tumors.
• Electroencephalogram (EEG): Interictal epileptiform discharges (spikes, sharp waves). Normal EEG does not rule out epilepsy.

• Single unprovoked seizure
  Does not meet criteria for epilepsy; ~40% chance of recurrence.
• Controlled Epilepsy
  Diagnosed epilepsy but seizure-free on medication.
• Drug-Resistant Epilepsy
  Failure of adequate trials of two tolerated and appropriately chosen ASM schedules.
• Status Epilepticus
  Continuous clinical or electrographic seizure lasting >= 5 mins, or recurrent without return to baseline.

Second-Line & Adjunctive Therapy

Add-on therapy for drug-resistant cases: Lacosamide, Clobazam, Brivaracetam, or Perampanel. Ketogenic diet (primarily in children).

Surgical & Procedural Management

For focal, drug-resistant epilepsy: Surgical resection of the seizure focus (e.g., anterior temporal lobectomy, highly curative). Neuromodulation: Vagus Nerve Stimulation (VNS), Responsive Neurostimulation (RNS), or Deep Brain Stimulation (DBS).

Recommended Lifestyle Changes

• Strict medication adherence; missed doses are the leading cause of breakthrough seizures.
• Avoid sleep deprivation and excessive alcohol consumption.
• Driving restrictions per local law (often 3-6 months seizure-free required).

Patient Counseling & Advice

Educate family on seizure first aid: gently roll patient on their side, cushion the head, do not put anything in the mouth, and time the seizure. Call 911 if it lasts > 5 minutes.

Follow-Up & Monitoring Schedule

Regular neurology visits. Monitor ASM levels (e.g., for Phenytoin, Valproate) and check CBC/LFTs for specific drug toxicities.

Preventive Strategies

Prevention of traumatic brain injury (helmets, seatbelts). Good prenatal and perinatal care.

About 60-70% of patients achieve seizure freedom with the first or second ASM. 30% develop drug-resistant epilepsy.