Functional Connectivity Networks in Asymptomatic and Symptomatic DYT1 Carriers.

BACKGROUND: DYT1 mutation is characterized by focal to generalized dystonia and incomplete penetrance. To explore the complex perturbations in the different neural networks and the mutual interactions among them, we studied symptomatic and asymptomatic DTY1 mutation carriers by resting-state functional MRI. METHODS: A total of 7 symptomatic DYT1, 10 asymptomatic DYT1, and 26 healthy controls were considered. Resting-state functional MRI (Oxford Centre for Functional MRI of the Brain) [FMRIB] Software Library) (FSL) MELODIC, dual regression, (as a toolbox of FSL, with Nets is referred to "networks") (FSLNets) (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/FSLNets) was performed on 9 resting-state neural networks. RESULTS: DYT1 mutation signature (symptomatic DYT1 and asymptomatic DYT1) was characterized by increased connectivity in the dorsal attention network and in the left fronto-parietal network. Functional correlates of symptomatic DYT1 patients (symptomatic DYT1 vs healthy controls) showed increased connectivity in the sensorimotor network. DISCUSSION: This study argues that DYT1 dystonia is a network disorder, with crucial nodes in sensory-motor integration of posterior parietal structures. A better characterization of cortical networks involved in dystonia is crucial for possible neurophysiological therapeutic interventions. © 2016 International Parkinson and Movement Disorder Society.

Disulfiram neuropathy: two cases of distal axonopathy.

BACKGROUND: Disulfiram may cause a peripheral neuropathy that is considered dose- and duration-of-exposure-related. Axonal degeneration has been described as a pathological hallmark of disulfiram toxicity, but experiments have reported a primary toxic effect of the molecule on Schwann cells and myelin. CASE REPORTS: Case 1: At the end of two months of treatment with disulfiram 250 mg/day, a 31-year-old woman complained of weakness in distal segments of the lower limbs associated with burning dysesthesias, numbness and pain in the soles of the feet and the legs below the knees; bilateral walking steppage, reduction in foot strength, absence of ankle jerk and knee tendon reflexes, and tactile stocking pin-pick and vibratory sensory impairment in the lower limbs below the knee. Disulfiram was discontinued and she recovered partially over three months. Case 2: After one month of treatment with disulfiram 1600 mg/day, a 27-year-old man reported walking impairment, distal lower limb weakness and paresthesias. He had unsteady gait with bilateral steppage and foot drop, absence of ankle jerks and overall sensation impairment below the knee. Disulfiram was discontinued and nine months later there was almost complete recovery of motor deficits, only minor motor weakness in distal leg muscles, and no dysesthesia, sensation deficits or areflexia. In both of them clinical and neurophysiological patterns were indicative of a distal axonopathy. DISCUSSION The mechanisms by which disulfiram cause injury in human nerves are unclear, though may involve carbon disulfide. The discrepancy between experimental and clinical observations is still unexplained. CONCLUSION: We report two cases of disulfiram axonal toxicity and the partial response following discontinuation of the drug.