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.

Cognitive outcome after left functional hemispherectomy on dominant hemisphere in patients with Rasmussen encephalitis: beyond the myth of aphasia. Patient series.

BACKGROUND: Rasmussen encephalitis is a rare chronic neurological pathology frequently treated with functional hemispherectomy (or hemispherotomy). This surgical procedure frees patients of their severe epilepsy associated with the disease but may induce cognitive disorders and notably language alterations after disconnection of the left hemisphere. OBSERVATIONS: The authors describe longitudinally 3 cases of female patients with Rasmussen encephalitis who underwent left hemispherotomy in childhood and benefited from a favorable cognitive outcome. In the first patient, the hemispherotomy occurred at a young age, and the recovery of language and cognitive abilities was rapid and efficient. The second patient benefited from the surgery later in childhood. In addition, she presented a reorganization of language and memory functions that seem to have been at the expense of nonverbal ones. The third patient was a teenager during surgery. She benefited from a more partial cognitive recovery with persistent disorders several years after the surgery. LESSONS: Recovery of cognitive functions, including language, occurs after left hemispherotomy, even when performed late in childhood. Therefore, the surgery should be considered as early as possible to promote intercognitive reorganization.

Long-Term Follow-Up of Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy.

In 2009, cerebral adrenoleukodystrophy (c-ALD) became the first brain disease to be treated with lentiviral (LV)-based hematopoietic stem cell gene therapy with the ABCD1 gene in four boys (P1-P4) who had demyelinating lesions expected to be lethal in the short term and no bone marrow donor. We report the clinical and magnetic resonance imaging (MRI) follow-up over a mean of 8.8 years posttransplant. In parallel, vector genome copies, expression of transgenic ALD protein (ALDP), and viral integration sites were determined in peripheral blood cells. Prior to transplant, the four patients had a normal or near normal neurocognitive status but gadolinium-enhanced demyelination in various brain regions. Gadolinium diffusion disappeared during the first year posttransplant. P3 kept a near normal status until 8.3 years of follow-up, but P1, P2, and P4 showed major cognitive degradation around 9, 28, and 60 months posttransplant. Neurological status and demyelination stabilized until last evaluation in P2, but deteriorated in both P1 at 10 years and P4 at 3 years posttransplant. The proportion of myeloid and lymphoid cells expressing transgenic ALDP decreased by half within 5 years then stabilized around 5% to 10%. Integration site analysis revealed a durable polyclonal distribution of genetically corrected hematopoietic cells. No adverse effects were observed. The long-term arrest of demyelination at MRI and persistence of transduced hematopoietic progenitors support that LV gene therapy may be a safe and durable treatment of c-ALD. However, the neurological degradation observed in three out of four patients mitigates the benefit of this therapy, calling for an earlier intervention, more potent vectors, and additional therapeutic strategies.