Makindo Medical Notes

Related Subjects: |Status Epilepticus (Epilepsy) |Coma management |Lorazepam |Phenytoin |Levetiracetam |Epilepsy - General Management |First Seizure |Epilepsy in Pregnancy |Febrile seizures

Introduction

Lennox-Gastaut Syndrome (LGS) is a rare and severe form of childhood-onset epilepsy characterized by multiple types of seizures, intellectual disability, and specific EEG findings. It accounts for approximately 2-5% of all childhood epilepsies and is one of the most challenging epileptic syndromes to treat.

Etiology

• Often has an identifiable cause, but in many cases, it remains idiopathic (unknown origin).
• Possible causes include:
  • Structural brain abnormalities: Cortical dysplasia, congenital brain malformations.
  • Genetic factors: Mutations in genes such as SCN1A, CHD2, among others.
  • Perinatal injuries: Hypoxic-ischemic encephalopathy during birth.
  • Central nervous system infections: Meningitis, encephalitis.
  • Metabolic disorders: Disorders of metabolism affecting brain function.
  • Tuberous sclerosis complex: A genetic disorder causing benign tumors in the brain.
  • Head trauma: Severe brain injuries can precipitate LGS.

Associations

• Frequently associated with developmental delays and behavioral problems.
• May coexist with other neurological disorders such as autism spectrum disorder.
• High risk of cognitive impairment over time due to ongoing seizures and underlying brain dysfunction.

Clinical Features

• Onset typically between 3 and 5 years of age, but can range from infancy to adolescence.
• Characterized by multiple seizure types, including:
  • Atonic seizures ("drop attacks"): Sudden loss of muscle tone causing falls.
  • Tonic seizures: Sudden stiffening of muscles, often during sleep.
  • Atypical absence seizures: Brief lapses in consciousness with minimal motor signs.
  • Myoclonic seizures: Brief, shock-like jerks of muscles.
  • Generalized tonic-clonic seizures: Convulsions with loss of consciousness.
• Seizures are frequent and often resistant to treatment.
• Non-convulsive status epilepticus may occur, characterized by prolonged episodes of reduced awareness or confusion.
• Slow intellectual development or regression of cognitive abilities.
• Behavioral issues such as hyperactivity, aggression, or autistic features.

Diagnostic Investigations

• Electroencephalogram (EEG):
  • Shows characteristic generalized slow (<3 Hz) spike-and-wave discharges.
  • Paroxysmal fast activity during sleep.
• Magnetic Resonance Imaging (MRI):
  • Performed to identify structural brain abnormalities.
  • Can reveal lesions, cortical dysplasia, or other anomalies.
• Genetic Testing:
  • May be indicated to identify genetic mutations contributing to LGS.
• Metabolic and Other Laboratory Tests:
  • To rule out metabolic disorders or infections.

Management

• Antiepileptic Drugs (AEDs):
  • First-line medications:
    • Valproate (sodium valproate): Broad-spectrum efficacy.
    • Lamotrigine: Often used in combination with valproate.
    • Topiramate: Effective for multiple seizure types.
    • Clobazam: A benzodiazepine that can reduce seizure frequency.
    • Rufinamide: Specifically approved for LGS.
  • Adjunctive medications:
    • Felbamate: Effective but with significant potential side effects; used cautiously.
    • Cannabidiol (CBD): Approved for use in LGS in some countries.
  • AEDs often need to be used in combination due to refractory seizures.
• Ketogenic Diet:
  • A high-fat, low-carbohydrate diet that can reduce seizure frequency in some patients.
  • Requires strict medical supervision.
• Vagus Nerve Stimulation (VNS):
  • A device implanted under the skin that sends electrical impulses to the vagus nerve.
  • Can help reduce seizure frequency and intensity.
• Surgical Options:
  • Corpus Callosotomy:
    • Surgical procedure that severs connections between the two cerebral hemispheres.
    • Effective in reducing atonic seizures and drop attacks.
  • Resective Surgery:
    • Considered if a focal lesion is identified as the seizure source.
• Behavioral and Educational Support:
  • Special education programs tailored to the child's needs.
  • Behavioral therapy to manage behavioral issues.
• Family Support and Counseling:
  • Essential for managing the psychosocial impact on the family.

Prognosis

• Overall prognosis is guarded due to:
  • Refractory nature of seizures despite multiple treatments.
  • Progressive cognitive impairment and developmental delays.
  • Increased risk of injury due to frequent falls from atonic seizures.
  • Higher mortality rate compared to other epileptic syndromes, partly due to sudden unexpected death in epilepsy (SUDEP).
• Early diagnosis and comprehensive management can improve quality of life.

Conclusion

Lennox-Gastaut Syndrome is a complex and severe epilepsy syndrome requiring a multidisciplinary approach for management. Advances in medical therapies and supportive interventions offer hope for better seizure control and improved developmental outcomes.