Introduzione: la pratica filosofica come relazione integrale.

Succinate dehydrogenase-deficient leukoencephalopathy is a complex II-related mitochondrial disorder for which the clinical phenotype, neuroimaging pattern, and genetic findings have not been comprehensively reviewed. Nineteen individuals with succinate dehydrogenase deficiency-related leukoencephalopathy were reviewed for neuroradiological, clinical, and genetic findings as part of institutional review board-approved studies at Children's National Health System (Washington, DC) and VU University Medical Center (Amsterdam, the Netherlands). All individuals had signal abnormalities in the central corticospinal tracts and spinal cord where imaging was available. Other typical findings were involvement of the cerebral hemispheric white matter with sparing of the U fibers, the corpus callosum with sparing of the outer blades, the basis pontis, middle cerebellar peduncles, and cerebellar white matter, and elevated succinate on magnetic resonance spectroscopy (MRS). The thalamus was involved in most studies, with a predilection for the anterior nucleus, pulvinar, and geniculate bodies. Clinically, infantile onset neurological regression with partial recovery and subsequent stabilization was typical. All individuals had mutations in SDHA, SDHB, or SDHAF1, or proven biochemical defect. Succinate dehydrogenase deficiency is a rare leukoencephalopathy, for which improved recognition by magnetic resonance imaging (MRI) in combination with advanced sequencing technologies allows noninvasive diagnostic confirmation. The MRI pattern is characterized by cerebral hemispheric white matter abnormalities with sparing of the U fibers, corpus callosum involvement with sparing of the outer blades, and involvement of corticospinal tracts, thalami, and spinal cord. In individuals with infantile regression and this pattern of MRI abnormalities, the differential diagnosis should include succinate dehydrogenase deficiency, in particular if MRS shows elevated succinat

Randomized clinical trial of first‐line genome sequencing in pediatric white matter disorders

Genome sequencing (GS) is promising for unsolved leukodystrophies, but its efficacy has not been prospectively studied.A prospective time-delayed cross-over design trial of GS to assess the efficacy of GS as a first-line diagnostic tool for genetic white matter disorders took place between 12/01/2015 - 09/27/2017. Patients were randomized to receive GS immediately with concurrent standard of care (SoC) testing, or to receive SoC testing for four months followed by GS.34 individuals were assessed at interim review. The genetic origin of two patient's leukoencephalopathy was resolved before randomization. Nine patients stratified to the immediate intervention group and 23 patients to the delayed-GS arm. The efficacy of GS was significant relative to SoC in the Immediate (5 of 9 [56%] vs. 0 of 9 [0%]; Wild-Seber