Objective: Dravet syndrome (DS) is a drug-resistant, infantile onset epilepsy syndrome with multiple seizure types and developmental delay. In recently published randomized controlled trials, fenfluramine (FFA) proved to be safe and effective in DS. Methods: DS patients were treated with FFA in the Zogenix Early Access Program at four Italian pediatric epilepsy centers. FFA was administered as add-on, twice daily at an initial dose of 0.2 mg/kg/d up to 0.7 mg/kg/d. Seizures were recorded in a diary. Adverse events and cardiac safety (with Doppler echocardiography) were investigated every 3 to 6 months. Results: Fifty-two patients were enrolled, with a median age of 8.6 years (interquartile range [IQR] = 4.1-13.9). Forty-five (86.5%) patients completed the efficacy analysis. The median follow-up was 9.0 months (IQR = 3.2-9.5). At last follow-up visit, there was a 77.4% median reduction in convulsive seizures. Thirty-two patients (71.1%) had a ≥50% reduction of convulsive seizures, 24 (53.3%) had a ≥75% reduction, and five (11.1%) were seizure-free. The most common adverse event was decreased appetite (n = 7, 13.4%). No echocardiographic signs of cardiac valvulopathy or pulmonary hypertension were observed. There was no correlation between type of genetic variants and response to FFA. Significance: In this real-world study, FFA provided a clinically meaningful reduction in convulsive seizure frequency in the majority of patients with DS and was well tolerated.

Electric source imaging (ESI) estimates the cortical generator of the electroencephalography (EEG) signals recorded with scalp electrodes. ESI has gained increasing interest for the presurgical evaluation of patients with drug-resistant focal epilepsy. In spite of a standardised analysis pipeline, several aspects tailored to the individual patient involve subjective decisions of the expert performing the analysis, such as the selection of the analysed signals (interictal epileptiform discharges and seizures, identification of the onset epoch and time-point of the analysis). Our goal was to investigate the inter-analyser agreement of ESI in presurgical evaluations of epilepsy, using the same software and analysis pipeline. Six experts, of whom five had no previous experience in ESI, independently performed interictal and ictal ESI of 25 consecutive patients (17 temporal, 8 extratemporal) who underwent presurgical evaluation. The overall agreement among experts for the ESI methods was substantial (AC1 = 0.65; 95% CI: 0.59–0.71), and there was no significant difference between the methods. Our results suggest that using a standardised analysis pipeline, newly trained experts reach similar ESI solutions, calling for more standardisation in this emerging clinical application in neuroimaging.

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.

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