Children and adolescents with epilepsy in rehabilitation centers: A French prospective transversal study.

INTRODUCTION: The reason why some children and adolescent with epilepsy (CAWE) still challenge the "inclusive" educative policy needs to be explored. METHODS/PATIENTS: We conducted a transversal study in French medical, social, and educative rehab centers (MSERCs) dedicated to CAWE to describe the profile of 263 centers-involved (CI)-CAWE. Centers-involved CAWE were prospectively followed from September 2012 to August 2013. Medical, social, and educative rehab centers were dichotomized according to their care-provider agreement (i.e., CAWE of "moderate" (M) vs. "severe" (S) conditions). Clinical factors known to impact clinical outcome and quality of life (QoL) in epilepsy and four disabling conditions at risk to impact school life (i.e., cognitive and psychiatric/behavioral disorders, risk of physical hazards (i.e., refractory seizures with unpredictable loss of tone and/or awareness), and one or more seizure/week) were evaluated. The electronic chart of the French collaborative database (namely GRENAT) was used for data collection allowing comparison with the profile of 731 "normally integrated and schooled" (NIS)-CAWE extracted from GRENAT and matching for generation (i.e., born between 1988 and 2006). RESULTS: Centers-involved CAWE's profile was found, after adjustment, to be associated with clinical factors and disabling conditions reflecting the poorest clinical outcome and health-related quality of life (HR-QoL) (all p < 0.001). A cutoff of two disabilities/child highly discriminated NIS-CAWE vs. CI-CAWE. Centers-involved CAWE of S-MSERCs were the most severe (all p < 0.001), and the type of cognitive disability (i.e., intellectual disability (ID) vs. specific learning disorders (SLD)) highly paralleled the types of MSERCs (S vs. M). Using a parent-informant questionnaire, the number of disabilities/child was found to correlate with both the evaluation of the impact of epilepsy (r = 0.47, p < 0.001) and the HR-QoL (r = 0.37, p < 0.001). A satisfactory social life was reported (83.8%) even after S vs. M dichotomization (77.2% vs. 94.7%; p < 0.001). CONCLUSION: Multiple disabilities rather than epilepsy per se challenge the inclusive educative policy. Evaluation of disabilities could be the missing bridge to optimize this policy and understand its limits.

Prediction and detection of human epileptic seizures based on SIFT-MS chemometric data.

Although epilepsy is considered a public health issue, the burden imposed by the unpredictability of seizures is mainly borne by the patients. Predicting seizures based on electroencephalography has had mixed success, and the idiosyncratic character of epilepsy makes a single method of detection or prediction for all patients almost impossible. To address this problem, we demonstrate herein that epileptic seizures can not only be detected by global chemometric analysis of data from selected ion flow tube mass spectrometry but also that a simple mathematical model makes it possible to predict these seizures (by up to 4 h 37 min in advance with 92% and 75% of samples correctly classified in training and leave-one-out-cross-validation, respectively). These findings should stimulate the development of non-invasive applications (e.g., electronic nose) for different types of epilepsy and thereby decrease of the unpredictability of epileptic seizures.

Dogs demonstrate the existence of an epileptic seizure odour in humans.

Although different studies have shown that diseases such as breast or lung cancer are associated with specific bodily odours, no study has yet tested the possibility that epileptic seizures may be reflected in an olfactory profile, probably because there is a large variety of seizure types. The question is whether a "seizure-odour", that would be transversal to individuals and types of seizures, exists. This would be a pre requisite for potential anticipation, either by electronic systems (e.g., e-noses) or trained dogs. The aim of the present study therefore was to test whether trained dogs, as demonstrated for cancer or diabetes, may discriminate a general epileptic seizure odor (different from body odours of the same person in other contexts and common to different persons). The results were very clear: all dogs discriminated the seizure odour. The sensitivity and specificity obtained were amongst the highest shown up to now for discrimination of diseases. This constitutes a first proof that, despite the variety of seizures and individual odours, seizures are associated with olfactory characteristics. These results open a large field of research on the odour signature of seizures. Further studies will aim to look at potential applications in terms of anticipation of seizures.

Genotype-phenotype correlations to aid in the prognosis of individuals with uncommon 20q13.33 subtelomere deletions: a collaborative study on behalf of the 'association des Cytogénéticiens de langue Française'.

The identification of subtelomeric rearrangements as a cause of mental retardation has made a considerable contribution to diagnosing patients with mental retardation. It is remarkable that for certain subtelomeric regions, deletions have hardly ever been reported so far. All the laboratories from the 'Association des Cytogénéticiens de Langue Française' were surveyed for cases where an abnormality of the subtelomere FISH analysis had been ascertained. Among 1511 cases referred owing to unexplained mental retardation, 115 (7.6%) patients showed a clinically significant subtelomeric abnormality. We report the clinical features and the molecular cytogenetic delineation of isolated de novo deletions on 20q13.33 in two cases. Detailed mapping was performed by micro-array CGH in one patient and confirmed by FISH in the two patients. We compare our data with the only three patients reported in the literature. Both patients shared a deleted region of approximately 1.33 Mb including 40 genes, with a 324 kb difference between the two patients. Haploinsufficiency for CHRNA4 and ARFGAP1 may have contributed towards a severe phenotype. In addition, the data in all patients suggest that haploinsufficiency for SOX18 may not cause the hypotrichosis-lymphedema-telangiectasia syndrome, or causes milder disease. Our study gives important information by defining the size of imbalance and better predicting the phenotype. Two clinically distinct phenotypes may be drawn, a mild mental retardation or a more complex and severe phenotype, according to the presence or absence of the CHRNA4 and ARFGAP1 genes respectively.

Screening of subtle copy number changes in Aicardi syndrome patients with a high resolution X chromosome array-CGH.

Aicardi syndrome (AIC) is an uncommon neurodevelopmental disorder affecting almost exclusively females. Chief features include infantile spasms, corpus callosal agenesis, and chorioretinal abnormalities. AIC is a sporadic disorder and hypothesized to be caused by heterozygous mutations in an X-linked gene but up to now without any defined candidate region on the X chromosome. Array based comparative genomic hybridisation (array-CGH) has become the method of choice for the detection of microdeletions and microduplications at high resolution. In this study, for the first time, 18 AIC patients were analyzed with a full coverage X chromosomal BAC arrays at a theoretical resolution of 82 kb. Copy number changes were validated by real-time quantitation (qPCR). No disease associated aberrations were identified. For such conditions as AIC, in which there are no familial cases, additional patients should be studied in order to identify rare cases with submicroscopic abnormalities, and to pursue a positional candidate gene approach.