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Abstract: Although status epilepticus (SE) affects the course of Dravet syndrome (DS), it rarely alters dramatically psychomotor outcome. We report an unusual pattern in 3 patients who following refractory SE lasting respectively 2, 7 and 12h experienced persistent and severe cognitive and motor deterioration. We compared these patients to published data and to personal experience in Necker hospital, to find links between severe outcome and clinical features such as treatment or duration of refractory SE. The key point was that anoxoischemic-like lesions appeared on MRI although cardiovascular function had remained stable. Therefore, neither hemodynamic failure, nor abnormalities of cardiac rhythm could explain the lesions and neurological worsening. For theoretical reasons the responsibility of therapy common for the 3 patients, e.g., barbiturates was suspected. [Copyright &y& Elsevier]

Chromosomal rearrangements are found in a subset of patients with autism. Duplications involving loci associated with behavioural disturbances constitute an especially good candidate mechanism. The Williams-Beuren critical region (WBCR), located at 7q11.23, is commonly deleted in Williams-Beuren microdeletion syndrome (WBS). However, only four patients with a duplication of the WBCR have been reported to date. Here, 206 patients with autism spectrum disorders were screened for the WBCR duplication by quantitative microsatellite analysis and multiple ligation-dependent probe amplification. One male patient with a de novo interstitial duplication of the entire WBCR of paternal origin was identified. The patient had autistic disorder, severe language delay and mental retardation, with mild dysmorphism. The present report concerns the first patient with autistic disorder and a WBCR duplication. This observation indicates that the 7q11.23 duplication could be involved in complex clinical phenotypes, ranging from developmental or language delay to mental retardation and autism. [ABSTRACT FROM AUTHOR]

Filamin-A-interacting protein 1 (FILIP1) is a structural protein that is involved in neuronal and muscle function and integrity and interacts with FLNa and FLNc. Pathogenic variants in filamin-encoding genes have been linked to neurological disorders (FLNA) and muscle diseases characterized by myofibrillar perturbations (FLNC), but human diseases associated with FILIP1 variants have not yet been described. Here, we report on five patients from four unrelated consanguineous families with homozygous FILIP1 variants (two nonsense and two missense). Functional studies indicated altered stability of the FILIP1 protein carrying the p.[Pro1133Leu] variant. Patients exhibit a broad spectrum of neurological symptoms including brain malformations, neurodevelopmental delay, muscle weakness and pathology, and dysmorphic features. Electron and immunofluorescence microscopy on the muscle biopsy derived from the patient harbouring the homozygous p.[Pro1133Leu] missense variant revealed core-like zones of myofibrillar disintegration, autophagic vacuoles and accumulation of FLNc. Proteomic studies on the fibroblasts derived from the same patient showed dysregulation of a variety of proteins including FLNc and alpha-B-crystallin, a finding (confirmed by immunofluorescence) which is in line with the manifestation of symptoms associated with the syndromic phenotype of FILIP1opathy. The combined findings of this study show that the loss of functional FILIP1 leads to a recessive disorder characterized by neurological and muscular manifestations as well as dysmorphic features accompanied by perturbed proteostasis and myopathology. [ABSTRACT FROM AUTHOR]

Abstract: Background: According to recent reports, herpes simplex virus type 1 (HSV-1) induces bronchopneumonitis (BPn) in immunocompetent patients undergoing prolonged mechanical ventilation (MV), whose respiratory functions deteriorate with a poor outcome. HSV-1 BPn is associated with HSV symptomatic or symptomless reactivation in the oropharynx. Objectives: We sought to systematically and genetically characterize HSV-1 strains isolated from immunocompetent patients receiving prolonged MV and to characterize the genetic relationship of strains sequentially isolated from oropharyngeal samples (OPS) and broncho-alveolar liquids (BAL) to determine the natural course of HSV BPn. Study design: In this molecular epidemiological study, microsatellite technology was used to determine genetic relationships between 211 HSV-1 strains isolated from OPS and/or BAL from 106 patients receiving MV. Results: Microsatellite haplotypes of HSV-1 strains sequentially isolated from the same individual were identical, and HSV-1 isolates from the lung were genetically indistinguishable from strains isolated from the oral cavity. Each patient was characterized by their own HSV-1 microsatellite haplotype, and no nosocomial transmission of strains between patients was observed. Conclusion: Our results demonstrate that, in patients who receive MV, the HSV-1 pulmonary infection results from the reactivation of genetically related HSV-1 in the oropharynx, which progressively infects the lower respiratory tract. [Copyright &y& Elsevier]