Generalized epilepsy in childhood

Symptomatic or cryptogenic generalized epilepsy syndromes

• Epidemiology & Etiologies
  • West Syndrome (Infantile Spasms): Onset 3–12 months; strongly associated with Tuberous Sclerosis Complex (TSC), perinatal HIE, and cortical dysplasias.
  • Lennox-Gastaut Syndrome (LGS): Onset 2–7 years; commonly secondary to evolved West syndrome, CNS infection, trauma, or structural brain lesions.
  • Dravet Syndrome: Onset <1 year; >80% due to loss-of-function SCN1A gene mutations.
• Clinical Features
  • West Syndrome Triad:
    • Epileptic spasms: Brief flexor/extensor contractions occurring in clusters (especially upon waking).
    • Developmental regression: Loss of social smile, visual tracking, and motor milestones.
    • Hypsarrhythmia on EEG.
  • Lennox-Gastaut Syndrome Triad:
    • Multiple refractory seizure types: Atonic “drop attacks” (high fall/trauma risk), tonic seizures (in sleep), and atypical absence.
    • Cognitive dysfunction: Severe intellectual disability and behavioral issues.
    • Slow spike-and-wave EEG pattern.
  • Dravet Syndrome: Prolonged febrile/afebrile hemiclonic seizures triggered by temperature elevation (fever, warm baths); progresses to refractory myoclonus and ataxia.
• Diagnostic Workup
  • Initial / Confirmatory Test: Video-EEG
    • West: Hypsarrhythmia (high-voltage, disorganized, chaotic background with multifocal spikes).
    • LGS: Slow generalized spike-and-wave (<2.5 Hz) during wakefulness; paroxysmal fast activity in non-REM sleep.
  • Neuroimaging: Brain MRI (Epilepsy Protocol): Identifies cortical malformations, stroke, subependymal nodules, or cortical tubers.
  • Genetic/Metabolic Testing: Microarray, epilepsy gene panels (SCN1A, TSC1/2), serum/CSF amino acids, and urine organic acids if MRI is non-diagnostic.
• Differential Diagnosis
  • Benign Myoclonus of Early Infancy: Normal development, occurs only when awake, completely normal EEG.
  • Sandifer Syndrome: Paroxysmal dystonic arching/head turning secondary to GERD; normal EEG.
  • Childhood Absence Epilepsy (CAE): Normal cognition, provoked by hyperventilation, 3-Hz spike-and-wave EEG, treated with ethosuximide.
  • Juvenile Myoclonic Epilepsy (JME): Morning myoclonic jerks in adolescents, 4–6 Hz polyspike-and-wave EEG, lifelong response to valproate.
• Management
  • West Syndrome:
    • First-line (standard): High-dose ACTH (IM) or oral prednisolone.
    • First-line (if TSC-associated): Vigabatrin (monitor for irreversible visual field constriction).
  • Lennox-Gastaut Syndrome (LGS):
    • First-line: Valproic acid + adjunctive Lamotrigine or Clobazam.
    • Second-line/Adjunctive: Rufinamide (specifically targets atonic drop attacks), Cannabidiol (CBD), Topiramate, or Felbamate (requires CBC/LFT monitoring for aplastic anemia/liver failure).
    • Refractory / Surgical: Ketogenic diet, Vagus Nerve Stimulation (VNS), and Corpus callosotomy (prevents atonic drop attack injuries).
  • Critical Contraindication: Avoid Na+ channel blockers (phenytoin, carbamazepine) in Dravet syndrome and myoclonic epilepsies (exacerbates seizures and risks status epilepticus).
• Complications
  • Head/Facial Trauma: Secondary to sudden drop attacks (requires protective helmet therapy).
  • Status Epilepticus & Non-Convulsive Status Epilepticus (NCSE).
  • Sudden Unexpected Death in Epilepsy (SUDEP).
  • Severe long-term cognitive and developmental disability.
  • Drug-Induced Toxicities: Vigabatrin-induced permanent visual field defects; Felbamate-induced aplastic anemia and acute hepatic necrosis.