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Mitochondria are cytoplasmic organelles having a fundamental role in the regulation of neural stem cell (NSC) fate during neural development and maintenance. During embryonic and adult neurogenesis, NSCs undergo a metabolic switch from glycolytic to oxidative phosphorylation with a rise in mitochondrial DNA (mtDNA) content, changes in mitochondria shape and size, and a physiological augmentation of mitochondrial reactive oxygen species which together drive NSCs to proliferate and differentiate. Genetic and epigenetic modifications of proteins involved in cellular differentiation (Mechanistic Target of Rapamycin), proliferation (Wingless-type), and hypoxia (Mitogen-activated protein kinase)–and all connected by the common key regulatory factor Hypoxia Inducible Factor-1A–are deemed to be responsible for the metabolic shift and, consequently, NSC fate in physiological and pathological conditions. Both primary mitochondrial dysfunction due to mutations in nuclear DNA or mtDNA or secondary mitochondrial dysfunction in oxidative phosphorylation (OXPHOS) metabolism, mitochondrial dynamics, and organelle interplay pathways can contribute to the development of neurodevelopmental or progressive neurodegenerative disorders. This review analyses the physiology and pathology of neural development starting from the available in vitro and in vivo models and highlights the current knowledge concerning key mitochondrial pathways involved in this process. [ABSTRACT FROM AUTHOR]

Abstract: Congenital Cataracts with Facial Dysmorphisms and Neuropathy (CCFDN) is a complex autosomal recessive disorder characterized by bilateral congenital cataracts, developmental delay, peripheral; hypo-demyelinating neuropathy, mild facial dysmorphisms, and other rare signs. Cerebral and spinal cord atrophy is the main neuroimaging finding but other less common abnormalities have been previously described. We describe progressive focal lesions of supratentorial white matter in a 10-year-old boy affected by CCFDN. Other etiologies have been excluded and these lesions can be considered a new finding of the disease. We discuss a possible demyelinating mechanism affecting both peripheral and central myelin. [Copyright &y& Elsevier]

FHL1 is a member of the four-and-a half-LIM (FHL) domain protein family and it is highly expressed in adult human skeletal muscle. It is believed to participate in sarcomere assembly, muscle growth and differentiation, and in the biomechanical stress responses. Mutations in FHL1 gene have been associated with different myopathies, including reducing body myopathy, scapuloperoneal (SP) myopathy, X-linked myopathy with postural muscle atrophy, rigid spine syndrome (RSS), and Emery-Dreifuss muscular dystrophy. In 2008, we identified a missense mutation in the second LIM domain of FHL1 (c.365 G>C, p.W122S) in a family with SP myopathy. We have generated a knock-in mouse model harboring the c.365 G>C Fhl1 mutation and have investigated the effects of this mutation at pre-symptomatic, phenotypic-onset, and late-stage of the disease, in hemizygous males and heterozygous females mice. Survival was comparable in mutant and wild-type animals. Adult hemizygous males mice showed a slowly progressive phenotype similar to human patients with relatively late-onset muscle weakness. In particular, we observed reduced forelimb strength and exercise capacity. Western blot analysis showed absence of FHL1 protein in muscle of hemizygous males at advanced stages. This animal model may help to elucidate the role of FHL1 in skeletal muscle and the pathomechanism of FHL1 mutations in X-linked dominant scapuloperoneal myopathy. [Copyright &y& Elsevier]

Aim To describe a spectrum of intracerebral large artery disease in Aicardi-Goutières syndrome (AGS) associated with mutations in the AGS5 gene SAMHD1. Method We used clinical and radiological description and molecular analysis. Results Five individuals (three males, two females) were identified as having biallelic mutations in SAMHD1 and a cerebral arteriopathy in association with peripheral vessel involvement resulting in chilblains and ischaemic ulceration. The cerebral vasculopathy was primarily occlusive in three patients (with terminal carotid occlusion and basal collaterals reminiscent of moyamoya syndrome) and aneurysmal in two. Three of the five patients experienced intracerebral haemorrhage, which was fatal in two individuals. Post-mortem examination of one patient suggested that the arteriopathy was inflammatory in origin. Interpretation Mutations in SAMHD1 are associated with a cerebral vasculopathy which is likely to have an inflammatory aetiology. A similar disease has not been observed in patients with mutations in AGS1 to AGS4, suggesting a particular role for SAMHD1 in vascular homeostasis. Our report raises important questions about the management of patients with mutations in SAMHD1. [ABSTRACT FROM AUTHOR]

The present controlled study aims to evaluate topiramate (TPM) effect on total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein, very low-density lipoprotein, apolipoproteins A1, B and lipoprotein (a). Seventy patients in evolving age suffering from various types of epilepsy, treated with TPM, (age range: 6 months–22 years) were evaluated before and after 12 months of treatment and compared with 110 sex- and age-matched subjects. At baseline, no significant difference was present between controls and children treated with TPM. After a year, the BMI did not show significant change in adults and remained into respective growth curve. No significant difference in lipids and lipoproteins neither between first and second evaluation nor between patients and controls was found. Some intra-group variation has been noticed: whilst controls maintained similar levels, the 70 patients on TPM monotherapy showed a slight decrease in TC, triglycerides and HDL. These fluctuations, however, occurred in the normal range so neither dietary nor pharmacological treatment of hyperlipidaemia after a year of TPM was necessary. [ABSTRACT FROM AUTHOR]

The aim of the present study was to assess serum lipid levels before and after treatment with oxcarbazepine (OXC) in children with epilepsy. We measured total cholesterol (TC), triglycerides (TGs) and high-density lipoprotein cholesterol (HDL-C) in 28 patients whereas only TC levels in 11 patients, during baseline period and at 3 months after the beginning of therapy with OXC. During baseline period, median values were: 4.38 mmol/l (IQR = 4.12–5.03) for TC levels, 1.72 mmol/l (IQR = 1.42–2.01) for HDL-C levels and 1.54 mmol/l (IQR = 1.29–1.96) for TGs levels. At 3 months, median values were: 4.38 mmol/l (4.10–4.95) for TC levels ( P < 0.05), 1.57 mmol/l (1.34–1.93) for HDL-C levels ( P < 0.005) and 1.8 mmol/l (1.23–2.34) for TGs levels ( P < 0.05). Median serum lipid levels remained in the normal range, despite an increasing-trend at 3 months of treatment with OXC. Further studies are necessary to confirm these results. [ABSTRACT FROM AUTHOR]