Long-term course of Dravet syndrome: A study from an epilepsy center in Japan

Objective This study attempted to clarify the long-term course of Dravet syndrome (DS). Methods Sixty-four patients diagnosed with DS (44 with typical DS, and 20 with atypical DS) were studied. The long-term outcomes of clinical seizures, electroencephalographic findings, neuropsychological findings, and social situation were analyzed. The follow-up period ranged from 11 to 34years 5months (median 24years). Results At the last visit, the ages ranged from 19years to 45years (median 30years). Fifty-nine patients continued to have generalized tonic-clonic seizures (GTCS). Status epilepticus and unilateral seizures were not observed and myoclonic seizures, atypical absence seizures, and photosensitive seizures were resolved in most patients. The frequency of complex partial seizures was equally low, with five patients at presentation and six patients at the last visit, respectively. Five patients achieved seizure remission (seizure-free for 1year or longer). Only 1 of 44 patients with typical DS had seizure remission, whereas 4 of 20 patients with atypical DS remitted, with a statistically significant difference between the two phenotypes (p=0.03). Intellectual disability was found in all patients; especially, severe intellectual disability was prevalent. Patients with atypical DS tended to have milder intellectual disability compared to those with typical DS (p=0.0283). Occipital alpha rhythm in the basic activity was associated with milder intellectual disability (p=0.0085). The freedom from seizures correlated with appearance of occipital alpha rhythms (p=0.0008) and disappearance of epileptic discharges (p=0.0004). Two patients with GTCS died. Mutations of the neuronal voltage-gated sodium channel alpha subunit type 1 gene were detected at a high frequency (33 of 36 patients examined). Seizure remission was found only in the missense mutation group. Significance The long-term seizure and intellectual outcomes are extremely poor in patients with typical DS compared to those with atypical DS. Epilepsy phenotype may influence long-term course of DS.