Dravet Syndrome and LGS Resource Library

From Merritt’s Neurology, 14th edition:

Lennox-Gastaut Syndrome

The term Lennox-Gastaut syndrome (LGS) is often improperly used as a synonym for symptomatic generalized epilepsy, but like other age-dependent epileptic encephalopathies, such as West syndrome, LGS is defined by the presence of specific seizure types and EEG features. The etiology is variable. LGS can occur in the context of acquired brain injury, pathogenic genetic variants, and/or MCD. Age of onset is between 3 and 5 years of age. The core seizure types include tonic seizures (the hallmark of LGS), especially arising out of sleep, atonic seizures (drop attacks), and atypical absences. The EEG is poorly organized and shows diffuse, usually frontally predominant, slow (2-2.5 Hz) spike and wave during wakefulness and bursts of generalized paroxysmal fast activity during non–rapid eye movement sleep. Ictal EEG of the atypical absences is characterized by a prolonged runs of the slow spike-and-wave complex described earlier. Atonic seizures associated with a generalized spike- or polyspike-wave and tonic seizures manifest with diffuse fast activity (10-20 Hz) accompanying electrodecrement. In patients who evolve to LGS from WS (approximately 20% of LGS), the tonic component and corresponding electrodecrement of epileptic spasms may become progressively prolonged, morphing into tonic seizures over time.

Dravet Syndrome

Variants in SCN1A were originally identified in genetic epilepsy with febrile seizures plus families, but SCN1A was subsequently discovered to be the major gene for Dravet syndrome (DS), accounting for >85% of cases. SCN1A encodes a voltage-gated sodium channel important for inhibitory interneuron function. DS has an onset between 3 and 8 months (peak at 6 mo) and presents with bouts of status epilepticus with hemiclonic or generalized clonic or tonic-clonic seizures most often triggered by increased temperature. Typically, even a mild increase in body temperature due to fever, hot weather, or hot bath can be a triggering factor. These episodes become frequent over time and, between 1 and 4 years, other seizure types appear, including myoclonic jerks, atypical absences, and focal impaired awareness seizures. The EEG is usually normal at onset but progresses to generalized, focal, and multifocal abnormalities. Photosensitivity is present early in approximately 40% of patients. The occurrence of sudden unexplained death in epilepsy is relatively high. From the second year of life, children demonstrate variable neurologic impairment, such as ataxia and corticospinal tract dysfunction, as well as behavioral disturbances, and learning disabilities. Seizure frequency tends to stabilize or decrease after 5 years, but developmental outcomes remain severe.