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CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy. Ganaxolone, a neuroactive steroid, reduces the frequency of major motor seizures in children with CDD. This analysis explored the effect of ganaxolone on non-seizure outcomes. Children (2–19 years) with genetically confirmed CDD and ≥ 16 major motor seizures per month were enrolled in a double-blind randomized placebo-controlled trial. Ganaxolone or placebo was administered three times daily for 17 weeks. Behaviour was measured with the Anxiety, Depression and Mood Scale (ADAMS), daytime sleepiness with the Child Health Sleep Questionnaire, and quality of life with the Quality of Life Inventory-Disability (QI-Disability) scale. Scores were compared using ANOVA, adjusted for age, sex, number of anti-seizure mediations, baseline 28-day major motor seizure frequency, baseline developmental skills, and behaviour, sleep or quality of life scores. 101 children with CDD (39 clinical sites, 8 countries) were randomized. Median (IQR) age was 6 (3–10) years, 79.2 % were female, and 50 received ganaxolone. After 17 weeks of treatment, Manic/Hyperactive scores (mean difference 1.27, 95%CI –2.38,-0.16) and Compulsive Behaviour scores (mean difference 0.58, 95%CI -1.14,-0.01) were lower (improved) in the ganaxolone group compared with the placebo group. Daytime sleepiness scores were similar between groups. The total change in QOL score for children in the ganaxolone group was 2.6 points (95%CI -1.74,7.02) higher (improved) than in the placebo group but without statistical significance. Along with better seizure control, children who received ganaxolone had improved behavioural scores in select domains compared to placebo. • Ganaxolone is a new anti-seizure medication for CDKL5 deficiency disorder. • Compared to the placebo group, children receiving ganaxolone had less hyperactive and compulsive behaviours. - There were nonsignificant, mild improvements in quality of life in the ganaxolone group. - Daytime sleepiness was similar in the placebo and ganaxolone groups. [ABSTRACT FROM AUTHOR]

Purpose: Dup15q syndrome is a rare genetic disease with a fairly nonspecific phenotype, clinical heterogeneity, and a wide spectrum of severity. However, no formal characterization has been attempted to select clusters of symptoms, signs and instrumental tests, to be used in the differential diagnosis with other neurodevelopmental disorders. Thus, our purpose was to identify symptoms, signs and instrumental findings, singly or in various combinations, favoring the early diagnosis of the Dup15q syndrome and the indication for genetic testing.Methods: 25 patients with Dup15q syndrome and 25 age and sex matched controls with other neurodevelopmental disorders were the study population. Patients' history, clinical and instrumental assessment were examined by five expert child neurologists blind to the genetic diagnosis. Each rater was asked to make the diagnosis in three subsequent steps: 1. Revision of the medical records; 2. Examination of the videorecorded clinical findings; 3. Assessment of the instrumental tests. Inter-rater agreement was measured with the Kendall's coefficient of concordance) and the Kappa statistic. Sensitivity, specificity and predictive values for symptoms, signs and instrumental findings, singly or in various combinations, were measured.Results: The Kendall's coefficient for the diagnosis of Dup15q syndrome was 0.43 at step 1 was 0.43, at step 2 was 0.42, at step 3. Patients with past feeding difficulties, hypotonia during the neonatal period, and epilepsy had >80 % probability of having the Dup15q syndrome.Conclusion: Feeding difficulties, hypotonia and epilepsy, though unspecific, can be used as signals of Dup15q syndrome and focused search of genetic abnormalities. [ABSTRACT FROM AUTHOR]

Purpose: Absence Status epilepticus (AS) is a form of Non Convulsive Status Epilepticus defined as a prolonged, generalized and non-convulsive seizure, with an altered content of consciousness. We aim to describe a group of healthy children, who presented recurrent and unprovoked de novo AS as the only manifestation of their epilepsy, with an excellent response to antiepileptic drugs.Method: We retrospectively reviewed the electroclinical and genetic features of 13 pediatric patients, referring to our epilepsy centers from 2005 to 2019, on the following criteria: (1) regular psychomotor development, (2) one or more unprovoked AS as the only epileptic manifestation, (3) normal blood testing, (4) normal neuroimaging, (5) EEG recording, (6) available follow-up (1-14 years).Results: Patients are 7 females and 6 males, aged 7-22, with a mean age at AS onset of 9,3 years. All of them started an antiepileptic therapy, with an excellent response to Valproic Acid (VPA) or Ethosuximide (ETS). 5 patients did not start the therapy immediately after the first AS and they presented recurrent AS (from 2 to 4 episodes). 10 of them performed aCGH, karyotype, NGS panel or Whole Exome Sequencing.Conclusions: We suggest that de novo AS may be a well-defined age-related and self-limited epilepsy syndrome, with a good prognosis and excellent response to therapy, but it comes with a high risk of relapsing if not adequately treated with antiepileptic drugs. [ABSTRACT FROM AUTHOR]

Preoperative evaluation, by means of intracerebral electrodes, in patients presenting with symptomatic drug resistant epilepsy, provides an opportunity to explore the S1 area in depth. We studied 7 pediatric patients with drug resistant epilepsy. Intracerebral electrodes were implanted in frontal, temporal and parietal lobes at different sites, depending on seizure types. SEPs were recorded to median and tibial nerve stimulation from the intracerebral electrode contacts referred to the earlobe ipsilateral to the stimulation. The analysis was addressed to the electrode contacts where an inversion of SEP component polarity was observed. A part from the median nerve N20 origin from the anterior bank of the postcentral gyrus, in 3 patients having electrode contacts close to medial surface of the parietal lobe, an inversion of polarity of the tibial nerve P40 component was observed. This is the first study demonstrating the origin of the tibial nerve P40 component from the medial surface of the S1 area by using intracerebral SEP recording. [ABSTRACT FROM AUTHOR]

Abstract: Background: Rett syndrome is a severe neurodevelopmental disorder affecting almost exclusively females. Among Rett clinical variants, the early-onset seizure variant describes girls with early onset epilepsy and it is caused by mutations in CDKL5. Methods: Four previously reported girls and five new cases with CDKL5 mutation, ranging from 14months to 13years, were evaluated by two clinical geneticists, classified using a severity score system based on the evaluation of 22 different clinical signs and compared with 128 classic Rett and 25 Zappella variant MECP2-mutated patients, evaluated by the same clinical geneticists. Clinical features were compared with previously described CDKL5 mutated patients. Both the statistical and the descriptive approach have been used to delineate clinical diagnostic criteria. Results: All girls present epilepsy with onset varying from 10days to 3months. Patients may present different type of seizures both at onset and during the whole course of the disease; multiple seizure types may also occur in the same individual. After treatment with antiepileptic drugs patients may experience a short seizure-free period but epilepsy progressively relapses. Typical stereotypic hand movements severely affecting the ability to grasp are present. Psychomotor development is severely impaired. In the majority of cases head circumference is within the normal range both at birth and at the time of clinical examination. Conclusion: For the practical clinical approach we propose to use six necessary and eight supportive diagnostic criteria. Epilepsy with onset between the first week and 5months of life, hand stereotypies, as well as severe hypotonia, are included among the necessary criteria. [Copyright &y& Elsevier]