SUMMARYPurpose: The aim of the study was to evaluate the outcome of status epilepticus (SE) in children and to define predictors for morbidity, mortality, and SE recurrence. Methods: The study included 302 children (age 2 months to less than 18 years; mean age ± SD 4.7 ± 4.2 years) with 489 episodes of SE. Etiology, treatment, and clinical and electroencephalography (EEG) features of SE and their impact on the outcome were analyzed. The outcome was classified into three categories: unchanged neurologic status, neurologic consequences, and lethal outcome. Univariate and multivariate Cox hazard regression analyses were used to define predictors of mortality, morbidity, and SE recurrence. Key Findings: Neurologic status was unchanged in 235 children (77.8%) and neurologic consequences occurred in 39 patients (12.9%); case-fatality ratio was 9.3% and recurrence rate was 21%. Mortality was related to progressive encephalopathy, preexisting neurologic abnormalities, specific EEG findings, and generalized convulsive type of SE. Neurologic consequences were associated with younger age, progressive encephalopathy, duration of SE >24 h, prior epilepsy, and specific EEG findings. Multivariate analyses showed that etiology of SE and prior neurologic abnormalities were independent predictors of mortality, whereas younger age, etiology, and very long duration of SE were predictors of morbidity. Significance: Outcome of SE in children is favorable in most of the cases, but mortality and morbidity rates are still high. Etiology and prior neurologic abnormalities were the main predictors of mortality, whereas the main predictor of morbidity was underlying etiology.

SUMMARYObjective: Evaluation of efficacy of vigabatrin as the first drug in infants with previously untreated infantile spasms (IS) and reporting the long-term outcome. Methods: We analyzed a cohort of 180 infants with infantile spasms treated with vigabatrin as the first drug. Following initial evaluation and a 48-h basal period for counting the spasms, vigabatrin was administered using the same protocol in all. After 14 days all infants were assessed for therapeutic response (primary outcome). Psychomotor development was evaluated by a psychologist and neurologist prior to the initiation of treatment and during the follow-up. Seizure outcomes were followed prospectively, by seizure types and epilepsy syndromes. Long-term (secondary) outcomes included neurologic status, occurrence of late epilepsy, and developmental/cognitive status. Results: Vigabatrin terminated the spasms in 101 patients (56.9%) at a mean period of 5 days. Patients with normal psychomotor development prior to the onset of spasms responded best. After follow-up of 2.4 to 18.9 years (mean 10.64; standard deviation [SD] 4.40), 38.1% of responders, treated with vigabatrin, had severe neurologic dysfunction, 42% had epilepsy, and 42.2% had unfavorable intellectual outcome. The group with symptomatic etiology and abnormal neurologic status at presentation demonstrated a significantly worse prognosis and a more unfavorable outcome than cryptogenic or idiopathic cases (85.1% and 81.6% versus 14.9% and 0%-p = 0.001). Idiopathic patients treated with vigabatrin were all intellectually normal, except the youngest patient who had borderline cognitive function. Significance: The most important prognostic factors were the underlying etiology and preexisting developmental profile. Long-term outcome in the patients treated with vigabatrin was similar to the outcome in patients treated with adrenocorticotropic hormone (ACTH) or corticosteroids, as reported in earlier studies. The long-term prognosis of idiopathic cases treated with vigabatrin was favorable.

SUMMARYObjective: Rett syndrome is an X-linked dominant neurodevelopmental disorder caused by mutations in the MECP2 gene, and characterized by cognitive and communicative regression, loss of hand use, and midline hand stereotypies. Epilepsy is a core symptom, but literature is controversial regarding genotype-phenotype correlation. Analysis of data from a large cohort should overcome this shortcoming. Methods: Data from the Rett Syndrome Networked Database on 1,248 female patients were included. Data on phenotypic and genotypic parameters, age of onset, severity of epilepsy, and type of seizures were collected. Statistical analysis was done using the IBM SPSS Version 21 software, logistic regression, and Kaplan-Meier survival curves. Results: Epilepsy was present in 68.1% of the patients, with uncontrolled seizures in 32.6% of the patients with epilepsy. Mean age of onset of epilepsy was 4.68 AE (standard deviation) 3.5 years. Younger age of onset was correlated to severity of epilepsy (Spearman correlation r = 0.668, p < 0.01). Patients with late truncating deletions had lower prevalence of epilepsy. Compared to them, the p.R133C mutation, associated with a milder Rett phenotype, increased the risk for epilepsy (odds ratio [OR] 2.46, confidence interval [CI] 95% 1.3-4.66), but not for severe epilepsy. The p.R255X mutation conferred an increased risk for epilepsy (OR 2.07, CI 95% 1.2-3.59) as well as for severe epilepsy (OR 3.4, CI 95% 1.6-7.3). The p.T158M and p.C306C mutations relatively increased the risk for severe epilepsy (OR 3.09 and 2.69, CI 95% 1.48-6.4 and 1.19-6.05, respectively), but not for epilepsy occurrence.

Rett spectrum disorder is a progressive neurological disease and the most common genetic cause of intellectual disability in females. MECP2 is the major causative gene. In addition, CDKL5 and FOXG1 mutations have been reported in Rett patients, especially with the atypical presentation. Each gene and different mutations within each gene contribute to variability in clinical presentation, and several groups worldwide performed genotype-phenotype correlation studies using cohorts of patients with classic and atypical forms of Rett spectrum disorder. The Rett Networked Database is a unified registry of clinical and molecular data of Rett patients, and it is currently one of the largest Rett registries worldwide with several hundred records provided by Rett expert clinicians from 13 countries. Collected data revealed that the majority of MECP2-mutated patients present with the classic form, the majority of CDKL5-mutated patients with the early-onset seizure variant, and the majority of FOXG1-mutated patients with the congenital form. A computation of severity scores further revealed significant differences between groups of patients and correlation with mutation types. The highly detailed phenotypic information contained in the Rett Networked Database allows the grouping of patients presenting specific clinical and genetic characteristics for studies by the Rett community and beyond. These data will also serve for the development of clinical trials involving homogeneous groups of patients.

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Mothers giving care to children with RTT are at high risk of severe depression and lower HRQoL scores of domains that reflect mental well-being. Results of this study can help in planning subsequent interventions directed at families dealing with Rett syndrome.

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Rett syndrome (RTT) is a neurodevelopmental disorder with one principal phenotype and several distinct, atypical variants (Zappella, early seizure onset and congenital variants). Mutations in MECP2 are found in most cases of classic RTT but at least two additional genes, CDKL5 and FOXG1, can underlie some (usually variant) cases. There is only limited correlation between genotype and phenotype. The Rett Networked Database (http://www.rettdatabasenetwork.org/) has been established to share clinical and genetic information. Through an "adaptor" process of data harmonization, a set of 293 clinical items and 16 genetic items was generated; 62 clinical and 7 genetic items constitute the core dataset; 23 clinical items contain longitudinal information. The database contains information on 1838 patients from 11 countries (December 2011), with or without mutations in known genes. These numbers can expand indefinitely. Data are entered by a clinician in each center who supervises accuracy. This network was constructed to make available pooled international data for the study of RTT natural history and genotype-phenotype correlation and to indicate the proportion of patients with specific clinical features and mutations. We expect that the network will serve for the recruitment of patients into clinical trials and for developing quality measures to drive up standards of medical management.