Summary 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.

Results: Age at onset ranged from 1.1 to 8.6 years, and was earlier in children with more than one seizure. Autonomic seizures followed a stereotypical onset and progression. Emesis, pallor, or flushing was almost always among the first symptoms that usually culminated in vomiting (77.4% of patients). More than half (55%) of seizures were longer than 30 min but these did not appear to affect remission and number of seizures. Interictal EEG showed great variability, with 79.5% of patients showing spikes of variable localizations and evolution over time; 16.1% had background abnormalities only, and 5.4% had consistently normal EEG studies. Onsets in five ictal EEGs were posterior or anterior-left or right. On neuropsychological testing, IQ and subtests of Wechsler Intelligence Scale for Children-Revised (WISC-R) were within normal limits, although some minor statistically significant differences were found in arithmetic, comprehension, and picture arrangement in comparison with controls. Cumulative probability of recurrence was 57.6%, 45.6%, 35.1%, and 11.7% at 6, 12, 24, and 36 months, respectively, after the first seizure. Thirty-four (58.6%) of 59 patients treated with antiepileptic drugs continued having seizures before ultimate remission. Discussion: PS is a uniform childhood susceptibility to autonomic seizures that is related to early age of development and with excellent prognosis with regard to seizure remission and neuropsychological development.

Summary Objective PCDH19‐related epilepsy is an epileptic syndrome with infantile onset, characterized by clustered and fever‐induced seizures, often associated with intellectual disability (ID) and autistic features. The aim of this study was to analyze a large cohort of patients with PCDH19‐related epilepsy and better define the epileptic phenotype, genotype‐phenotype correlations, and related outcome‐predicting factors. Methods We retrospectively collected genetic, clinical, and electroencephalogram (EEG) data of 61 patients with PCDH19‐related epilepsy followed at 15 epilepsy centers. All consecutively performed EEGs were analyzed, totaling 551. We considered as outcome measures the development of ID, autistic spectrum disorder (ASD), and seizure persistence. The analyzed variables were the following: gender, age at onset, age at study, genetic variant, fever sensitivity, seizure type, cluster occurrence, status epilepticus, EEG abnormalities, and cognitive and behavioral disorders. Receiver operating characteristic curve analysis was performed to evaluate the age at which seizures might decrease in frequency. Results At last follow‐up (median = 12 years, range = 1.9‐42.1 years), 48 patients (78.7%) had annual seizures/clusters, 13 patients (21.3%) had monthly to weekly seizures, and 12 patients (19.7%) were seizure‐free for ≥2 years. Receiver operating characteristic analysis showed a significant decrease of seizure frequency after the age of 10.5 years (sensitivity = 81.0%, specificity = 70.0%). Thirty‐six patients (59.0%) had ID and behavioral disturbances. ASD was present in 31 patients. An earlier age at epilepsy onset emerged as the only predictive factor for ID (P = 0.047) and ASD (P = 0.014). Conversely, age at onset was not a predictive factor for seizure outcome (P = 0.124). Significance We found that earlier age at epilepsy onset is related to a significant risk for ID and ASD. Furthermore, long‐term follow‐up showed that after the age of 10 years, seizures decrease in frequency and cognitive and behavioral disturbances remain the primary clinical problems.