Adaptive behaviour in adolescents and adults with Dravet syndrome.

AIM: To explore the feasibility of using an adaptive behaviour profile (ABP) assessment generated from a well-known measure-the Vineland Adaptive Behavior Scales, Second Edition (VABS-II)-as an instrument for outcome measures in adolescents and adults with Dravet syndrome. METHOD: We administered the VABS-II to 35 adolescents and adults with Dravet syndrome (15 males; mean age 24 years, SD 8 years, range: 12-46 years) and collected epilepsy history and neurological features at the time of assessment. We conducted a cross-sectional analysis of VABS-II raw scores and performed cluster analysis to identify different subgroups. We then explored possible relationships between clinical and epilepsy features, ABPs, and age. RESULTS: Most participants obtained the minimum standard scores in the various VABS-II subdomains, while the raw score analysis outlined interindividual and intraindividual differences among skills. We found two subpopulations: one with a 'lower' ABP and one with a 'higher' ABP, corresponding respectively to individuals in whom myoclonic seizures or generalized spike-and-wave activity were present ('complete phenotype') or absent ('incomplete phenotype') on electroencephalography. INTERPRETATION: This study further delineates the natural history of Dravet syndrome. The assessment of an ABP through the VABS-II raw score analysis provides a means by which to illustrate profiles of adaptive behaviour in adolescents and adults with Dravet syndrome but shows limitations related to poor sensitivity in measuring fine clinical details. There is a need for new and more specific tools to monitor patients with developmental and epileptic encephalopathies. WHAT THIS PAPER ADDS: Most adults with Dravet syndrome obtained the minimum standard scores in the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) subdomains. The VABS-II raw score analysis showed interindividual and intraindividual variability. Individuals with myoclonic seizures and/or generalized spike-and-wave activity on electroencephalography showed a worse adaptive behaviour profile.

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

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.

Cognitive development in Dravet syndrome: a retrospective, multicenter study of 26 patients.

PURPOSE: To clarify the role of epilepsy and genetic background in determining the cognitive outcome of patients with Dravet syndrome. METHODS: In this retrospective study, we reviewed the clinical history and cognitive development of 26 patients who had been followed with standardized evaluations since seizure onset. The cognitive outcome was quantified as differential general quotient (dGQ) between ages 12 and 60 months. Statistical analysis correlated the dGQ with genotype and epilepsy course. KEY FINDINGS: Epilepsy started at the mean age of 5.6 months. All patients experienced prolonged convulsive seizures, whereas absences and myoclonus were reported in 17. Cognitive outcome was poor in almost all patients; the mean dGQ was 33 points, varying from 6-77 points. The analysis of individual cognitive profiles identified seven patients in whom the dGQ was <20 points; the main clinical characteristic in this subset of patients was lack of early absences and myoclonus. The statistical analysis of the whole series failed to reveal significant differences in cognitive outcome with regard to the presence of SCN1A mutations and their type. In particular, mutation-carrier patients with the best cognitive outcome harbored either missense or truncating mutations. SIGNIFICANCE: Dravet syndrome encompasses different epileptic and cognitive phenotypes that probably result from both genetic and epigenetic factors. In this series, early appearance of myoclonus and absences was associated with the worst cognitive outcome.

Multicenter prospective longitudinal study in 34 patients with Dravet syndrome: Neuropsychological development in the first six years of life.

The objective of this study was to identify developmental trajectories of developmental/behavioral phenotypes and possibly their relationship to epilepsy and genotype by analyzing developmental and behavioral features collected prospectively and longitudinally in a cohort of patients with Dravet syndrome (DS). Thirty-four patients from seven Italian tertiary pediatric neurology centers were enrolled in the study. All patients were examined for the SCN1A gene mutation and prospectively assessed from the first years of life with repeated full clinical observations including neurological and developmental examinations. Subjects were found to follow three neurodevelopmental trajectories. In the first group (16 patients), an initial and usually mild decline was observed between the second and the third year of life, specifically concerning visuomotor abilities, later progressing towards global involvement of all abilities. The second group (12 patients) showed an earlier onset of global developmental impairment, progressing towards a generally worse outcome. The third group of only two patients ended up with a normal neurodevelopmental quotient, but with behavioral and linguistic problems. The remaining four patients were not classifiable due to a lack of critical assessments just before developmental decline. The neurodevelopmental trajectories described in this study suggest a differential contribution of neurobiological and genetic factors. The profile of the first group, which included the largest fraction of patients, suggests that in the initial phase of the disease, visuomotor defects might play a major role in determining developmental decline. Early diagnosis of milder cases with initial visuomotor impairment may therefore provide new tools for a more accurate habilitation strategy.

Temporal lobe epilepsy in children: electroclinical study of 77 cases.

PURPOSE: Temporal lobe epilepsy (TLE) is probably more difficult to recognize in children than in adults. In fact, ictal symptoms in children are less stereotyped and less obvious, and the neuropathological substrate is more heterogeneous than in adults. The aim of this study is to examine the relationships between etiology, age at onset and electroclinical findings in 77 children with TLE, 32 of whom were surgically treated. METHODS: Electroclinical study including video-EEG recording of seizures in 77 children with TLE. The investigation focused on the first five initial ictal symptoms. RESULTS: Age at onset was less than 3 years in 39 cases, between 3 and 6 years in 17 cases and older than 6 years in 21 cases. Auras also occurred in younger children but were more common after the age of 6 years. A peculiar initial ictal semiology consisted in staring with arrest, lip cyanosis, and very slight oral automatisms. In some cases, EEG recordings documented seizures starting independently on both temporal lobes. Based on electroclinical and neuroradiological features, we recognized three subgroups: symptomatic TLE due to cortical malformations or nonevolutive tumors, TLE with mesial temporal sclerosis, and cryptogenic TLE. CONCLUSIONS: A correct electroclinical and neuroradiological approach allows in several cases early recognition of TLE even when onset is earlier than the age of 6 years. A correct definition of the localization relies primarily on video-EEG recording of the seizures, possibly repeated during follow up in cases lacking obvious neuroradiological correlation.