Dravet syndrome: Early electroclinical findings and long‐term outcome in adolescents and adults

Abstract

To describe the outcome of Dravet syndrome (DS) in adolescents and adults we conducted a longitudinal retrospective study of two independent cohorts of 34 adolescents (group 1) and 50 adults (group 2). In both cohorts, we collected information about genetic mutation, and semiology of seizures at onset and during disease course.At the last evaluation, we considered the following features: epilepsy (distinguishing myoclonic/complete and nonmyoclonic/incomplete phenotype), neurologic signs, intellectual disability (ID), and behavioral disorders. Moreover, in both cohorts, we performed a correlation analysis between early characteristics of the disease and the outcome of DS with regard to seizure persistence, ID, behavioral disorder, and neurologic impairment at last evaluation. Group 1 includes 22 adolescents with complete form of DS and 12 with incomplete form; group 2 includes 35 adults with complete form and 15 with incomplete form. The seizures persisted in 73.6% of adolescents and in 80% of adults, but epilepsy severity progressively decreased through age.Seizure persistence correlated with the complete phenotype and with the occurrence of reflex seizures. At last evaluation, ID was moderate or severe in 70.5% of adolescents and in 80% of adults. The most severe cognitive and motor impairment was observed in patients with persisting seizures. The severity of cognition, language, and neurologic impairment at last evaluation correlated statistically with the complete phenotype. The study confirms that the global outcome of DS is poor in most cases, albeit epilepsy severity decreases throughout adulthood. The improvement of epilepsy throughout ages is not associated with improvement in intellectual abilities and motor skills; this confirms that the unfavorable outcome is not a pure consequence of epilepsy. K E Y W O R D Sadolescents and adults, complete Dravet syndrome, developmental and epileptic encephalopathy, longterm outcome, myoclonic phenotype, reflex seizures S50 | DARRA et Al.

Clinical Spectrum and Comorbidities of Dravet Syndrome in Taiwan 

“…Because there was no statistically signi cant difference between language, ambulation or seizure characteristics for those with and without vaccine-related seizures, the vaccination should not be withheld in patient with DS, and all clinicians should provide families with proper information before administering vaccination. In previous literatures, seizure frequency may decrease with age, which was independent of their SCN1A mutation type [12][13][14][15]. We also found a tendency of decreasing seizure frequency with age, although this did not reach statistical signi cance.…”

“…We also found a tendency of decreasing seizure frequency with age, although this did not reach statistical signi cance. In other study, in adolescence and adult groups with DS, fever sensitivity persisted but had less in uence [14].…”

“…Not all patients with DS from Taiwan were enrolled in the present study. In addition, the most common seizure pattern in adolescents and adults was generalized tonic-clonic, and mostly nocturnal and in cluster [14,36]. However, in our study, we did not record the serial seizure changes.…”

A systematic review of adults with Dravet syndrome

“…In 2019, a study conducted by Darra et al showed 70.5 % of 22 adolescents with "complete forms" (i.e., myoclonic phenotype) had moderate or severe ID, whereas the same level of ID was seen in more than 80 % of the 35 adults with the complete phenotype. They also noted that the most cognitive impairment was observed in DS adults with the most persisting seizures [67].…”

Families driven drug development and clinical trials: a pilot study in Dravet Syndrome to delineate what really matters

“…Several additional features are frequently reported: eating and sleep disorders, gait deterioration, dysautonomia, and a higher predisposition to infections [9][10][11]. The long-term outcome of individuals with Dravet syndrome remains poor [12][13][14][15]. This syndrome is considered as the archetype of developmental and epileptic encephalopathy (DEE) [16].…”