Epilepsy: Complete Clinical Overview

Definition

1. Classification (ILAE 2017)

2. Clinical Features

A. Generalized Onset Seizures

• May be preceded by a prodrome (hours of irritability, depression) or myoclonic jerks on awakening
• Tonic phase (10-20 seconds): sudden loss of consciousness, fall, tonic stiffening, jaw clenching with lateral tongue bite, piercing cry, cyanosis, dilated unreactive pupils, bladder emptying
• Clonic phase (~30 seconds): rhythmic flexor spasms, autonomic activation (hypertension, tachycardia, salivation, sweating), apnea continues
• Postictal phase: deep coma, then confusion, agitation, drowsiness for minutes to hours; pulsatile headache on waking; no memory of the event

• Sudden onset, abrupt offset (seconds) - no postictal state
• Blank stare, cessation of activity, simple automatisms
• EEG: characteristic 3-Hz generalized spike-and-wave discharge
• Provoked by hyperventilation; multiple per day possible
• Remit by adolescence in ~60% of cases

B. Focal Onset Seizures

• Motor: contralateral clonic jerking, tonic posturing, Todd paralysis post-ictally
• Sensory: contralateral tingling, numbness (somatosensory cortex); visual phenomena (occipital) - sparks, flashes, colors (red most common), or formed hallucinations (temporal-occipital junction)
• Auditory: buzzing, roaring, or voices (superior temporal gyrus)
• Visceral/Autonomic: epigastric rising sensation (most frequent aura - temporal lobe origin), palpitations
• Psychic: déjà vu, jamais vu, fear, euphoria, depersonalization

• Aura followed by behavioral arrest
• Automatisms: lip smacking, chewing, hand fumbling, ambulation
• Post-ictal confusion and fatigue (key distinguishing feature from absence)
• Typically 1-2 minutes duration

C. Age-Related Distribution

3. Causes / Etiology

• Neonates: hypoxic-ischemic encephalopathy, metabolic, intracranial hemorrhage, infections
• Infants/children: febrile seizures, genetic syndromes (West, Dravet, Lennox-Gastaut)
• Adolescents: idiopathic generalized epilepsies (JME, childhood absence)
• Adults: structural causes (trauma, tumor, stroke, mesial temporal sclerosis)
• Elderly: stroke (most common), neurodegenerative disease, tumor

4. Diagnosis

History and Examination

• Detailed eyewitness account of the event (onset, duration, movements, postictal state)
• Personal/family history of seizures, febrile convulsions, birth injury
• Precipitants: sleep deprivation, alcohol, fever, photosensitivity, drugs
• Full neurological examination

Investigations

• Most helpful laboratory test for epilepsy
• Epileptiform activity (spikes and sharp waves) - the only EEG finding with strong correlation to epilepsy
  • Present in ~90% of epilepsy patients (depending on recording circumstances) but in only ~2% without epilepsy
• Normal interictal EEG does NOT exclude epilepsy
• Minor nonspecific abnormalities do NOT confirm epilepsy
• Absence seizures: diagnostic 3-Hz spike-and-wave; provoked by hyperventilation
• Video-EEG monitoring: gold standard - records ictal event simultaneously with clinical behavior; distinguishes epileptic from non-epileptic (psychogenic) spells
• Activation techniques: sleep deprivation, hyperventilation, photic stimulation (photoparoxysmal response)

• MRI brain is the modality of choice (superior to CT) - detects mesial temporal sclerosis, cortical dysplasia, tumors, vascular malformations
• CT brain for acute settings (intracranial hemorrhage, trauma)
• [18F]FDG-PET: interictal hypometabolism at the seizure focus; useful in pre-surgical evaluation when MRI is normal
• Ictal SPECT (SISCOM): injected at seizure onset - shows ictal hyperperfusion; complementary to PET in pre-surgical evaluation

• CBC, glucose, electrolytes (Na, Ca, Mg), renal and liver function, toxicology screen
• Consider amino acid screen in neonates/infants

5. Treatment

General Principles

• Treatment is usually initiated after two unprovoked seizures
• Monotherapy preferred - start low, titrate slowly
• Serum drug levels guide compliance and toxicity; trough levels (pre-morning dose) are most consistent
• Higher serum concentrations needed for focal seizures than generalized ones

Antiseizure Drug (ASD) Selection by Seizure Type

Key Drug Notes

• Valproate: broad-spectrum; avoid in women of childbearing age (teratogenic - 20% serious adverse outcomes); monitor LFTs
• Carbamazepine: first-line focal; enzyme inducer; check for HLA-B*1502 (Stevens-Johnson risk in Asian patients)
• Lamotrigine: broad-spectrum; safest in pregnancy (1% serious adverse outcomes); slow titration to avoid rash
• Levetiracetam: broad-spectrum; renal dosing; behavioral side effects (irritability)
• Phenytoin: narrow therapeutic index; zero-order kinetics; gingival hyperplasia, hirsutism, nystagmus; available IV for acute use
• Ethosuximide: absence seizures only

Non-Pharmacological Treatment

• Indicated for drug-refractory focal epilepsy (failure of 2 adequate AED trials)
• Pre-surgical evaluation: history, neuropsychological testing, video-EEG, high-resolution MRI, FDG-PET, ictal SPECT (SISCOM), depth EEG recordings
• Temporal lobectomy for mesial temporal lobe epilepsy - best outcomes (60-80% seizure-free)
• Hemispherectomy, corpus callosotomy for selected generalized syndromes

• Adjunctive therapy for drug-resistant epilepsy when surgery is not feasible
• Reduces seizure frequency by 50% in ~50% of patients

• High-fat, low-carbohydrate diet; particularly effective in children and Dravet syndrome
• Produces ketosis, which reduces seizure susceptibility

• Closed-loop cortical stimulation; detects and aborts seizures
• For patients with drug-resistant focal epilepsy

Special Situations

1. Benzodiazepine IV (lorazepam/diazepam) - first-line
2. Phenytoin/fosphenytoin or Levetiracetam IV - second-line
3. Anesthetic agents (propofol, midazolam infusion) - refractory status

Summary Framework

EPILEPSY
├── CAUSES (ILAE 6 categories)
│   ├── Structural (tumor, stroke, dysplasia, trauma)
│   ├── Genetic (channelopathies, SCN1A, GABA receptor genes)
│   ├── Infectious (NCC, encephalitis)
│   ├── Metabolic (electrolytes, glucose, organ failure)
│   ├── Immune (anti-NMDAR, LGI1, Rasmussen)
│   └── Unknown
├── CLINICAL FEATURES
│   ├── Focal (aware/impaired awareness → temporal, frontal lobe)
│   └── Generalized (tonic-clonic, absence, myoclonic)
├── DIAGNOSIS
│   ├── EEG (epileptiform spikes; video-EEG gold standard)
│   ├── MRI brain (structural lesion)
│   └── Bloods, PET/SPECT (pre-surgical)
└── TREATMENT
    ├── Pharmacological (ASD - matched to seizure type)
    ├── Surgical (temporal lobectomy for refractory focal)
    ├── VNS / RNS / DBS
    └── Ketogenic diet