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Background and purpose: Changes of brain structure and function have been described in peripheral neuropathies. The aim of our study was to systematically investigate possible modifications of major large‐scale brain networks using resting‐state functional magnetic resonance imaging (RS‐fMRI) in Charcot–Marie–Tooth disease type 1A (CMT1A) patients. Methods: In this cross‐sectional study, 3‐T MRI brain scans were acquired of right‐handed genetically confirmed CMT1A patients and age‐ and sex‐comparable healthy controls. Patients also underwent clinical and electrophysiological examinations assessing neurological impairment. RS‐fMRI data were analysed using a seed‐based approach, with 32 different seeds sampling the main hubs of default mode, sensorimotor, visual, salience (SN), dorsal attention, frontoparietal, language and cerebellar networks. Between‐group differences in terms of functional connectivity (FC) with the explored seeds were tested voxelwise, correcting for local grey matter density to account for possible structural abnormalities, whilst the relationship between FC modifications and neurological impairment was investigated using robust correlation analyses. Results: Eighteen CMT1A patients (34.0 ± 11.4 years; M/F 11/7) were enrolled, along with 20 healthy controls (30.1 ± 10.2 years; M/F 11/9). In the CMT group compared to controls, clusters of increased FC with the visual cortex (P = 0.001), SN (P < 6 × 10−4), dorsal attention network (P < 8 × 10−5) and language network (P < 7 × 10–4) were found, along with a single cluster of reduced FC with the visual cortex in the left lentiform nucleus (P = 10–6). A significant correlation emerged between neurophysiological impairment and increased FC with right temporal language areas (r = 0.655, P = 0.006), along with an association between walking ability and increased FC with the left supramarginal gyrus (SN) (r = 0.620, P = 0.006). Conclusions: Our data show evidence of diffuse functional reorganization involving multiple large‐scale networks in the CMT1A brain, independent of structural modifications and partially correlating with peripheral nerve damage and functional impairment. [ABSTRACT FROM AUTHOR]

Mutations in COL1A1 and COL1A2 genes, encoding the α1 and α2 chain of type I collagen, respectively, are responsible for the vast majority of cases of osteogenesis imperfecta (OI) (95% of patients with a definite clinical diagnosis). We have investigated 22 OI patients, representing a heterogeneous phenotypic range, at the biochemical and molecular level. A causal mutation in either type I collagen gene was identified in 20 of them: no recurrent mutation was found in unrelated subjects; 15 out of 20 mutations had not been reported previously. In two patients, we could not find any causative mutation in either type I collagen gene, after extensive genomic DNA sequencing. Failure of COL1A1/COL1A2 mutation screening may be due, in a few cases, to further clinical heterogeneity, i.e. additional non-collagenous disease loci are presumably involved in OI types beyond the traditional Sillence’s classification. [ABSTRACT FROM AUTHOR]

Background: Spasticity in multiple sclerosis (MS) results from an imbalance of inputs from descending pathways to the spinal motor circuits, as well as from a damage of the corticospinal tract (CST)., Objectives: To assess CST impairment in MS patients with and without spasticity and to evaluate its evolution under Sativex ® treatment., Methods: Ten MS patients with spasticity ("cases") underwent clinical (EDSS, 9-hole Peg, Ashworth scale, Timed 25-Foot Walk, and NRS for spasticity), MRI (CST fractional anisotropy [FA]), and electrophysiological (central motor conduction time [CMCT] and H/M ratio) evaluations at baseline and after 12 months. We selected 20 MS patients without spasticity as control group at baseline., Results: At baseline, cases showed a lower CST FA (0.492±0.045 vs 0.543±0.047; P=.01) and a higher CMCT (P=.001) compared to the control group. No correlations were found between clinical, electrophysiological, and MRI features. After 12 months, cases showed a decrease in non-prevalent degree of impairment (PDI) side FA (0.502±0.023 vs 0.516±0.033; P=.01) without differences for electrophysiological features compared to baseline. Treatment with Sativex ® resulted in a reduction of NRS for spasticity (P=.01)., Conclusions: We confirm the presence of CST impairment in MS patients with spasticity. We did not identify structural/electrophysiological correlates that could explain Sativex ® clinical effect., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)