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Background: Cervical dystonia (CD) is a form of isolated focal dystonia typically associated to abnormal head, neck, and shoulder movements and postures. The complexity of the clinical presentation limits the investigation of its pathophysiological mechanisms, and the neural networks associated to specific motor manifestations are still the object of debate. Objectives: We investigated the morphometric properties of white matter fibers in CD and explored the networks associated with motor symptoms, while regressing out nonmotor scores. Methods: Nineteen patients affected by CD and 21 healthy controls underwent diffusion‐weighted magnetic resonance imaging. We performed fixel‐based analysis, a novel method evaluating fiber orientation within specific fiber bundles, and compared fiber morphometric properties between groups. Moreover, we correlated fiber morphometry with the severity of motor symptoms in patients. Results: Compared to controls, patients exhibited decreased white matter fibers in the right striatum. Motor symptom severity negatively correlated with white matter fibers passing through inferior parietal areas and the head representation area of the motor cortex. Conclusions: Abnormal white matter integrity at the basal ganglia level may affect several functional networks involved, for instance, in motor preparation and execution, visuomotor coordination, and multimodal integration. This may result in progressive maladaptive plasticity, culminating in overt symptoms of dystonia. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Abnormal sensory processing, including temporal discrimination threshold, has been described in various dystonic syndromes.Objective: To investigate visual sensory processing in DYT-SGCE and identify its structural correlates.Methods: DYT-SGCE patients without DBS (DYT-SGCE-non-DBS) and with DBS (DYT-SGCE-DBS) were compared to healthy volunteers in three tasks: a temporal discrimination threshold, a movement orientation discrimination, and movement speed discrimination. Response times attributed to accumulation of sensory visual information were computationally modelized, with μ parameter indicating sensory mean growth rate. We also identified the structural correlates of behavioral performance for temporal discrimination threshold.Results: Twenty-four DYT-SGCE-non-DBS, 13 DYT-SGCE-DBS, and 25 healthy volunteers were included in the study. In DYT-SGCE-DBS, the discrimination threshold was higher in the temporal discrimination threshold (P = 0.024), with no difference among the groups in other tasks. The sensory mean growth rate (μ) was lower in DYT-SGCE in all three tasks (P < 0.01), reflecting a slower rate of sensory accumulation for the visual information in these patients independent of DBS. Structural imaging analysis showed a thicker left primary visual cortex (P = 0.001) in DYT-SGCE-non-DBS compared to healthy volunteers, which also correlated with lower μ in temporal discrimination threshold (P = 0.029). In DYT-SGCE-non-DBS, myoclonus severity also correlated with a lower μ in the temporal discrimination threshold task (P = 0.048) and with thicker V1 on the left (P = 0.022).Conclusion: In DYT-SGCE, we showed an alteration of the visual sensory processing in the temporal discrimination threshold that correlated with myoclonus severity and structural changes in the primary visual cortex. © 2019 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

We aimed to analyse the response to rituximab in a cohort of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients with associated disorders. We conducted a clinical and electrophysiological retrospective monocentric study in 28 CIDP patients. Response to rituximab was defined as (a) a five‐point increase in the Medical Research Council sum score or a one‐point decrease in the Overall Neuropathy Limitations Scale score, compared to the score at the first rituximab infusion, or (b) the discontinuation of, or reduced need for, the last treatments before rituximab initiation. Twenty‐one patients (75%) were responders to rituximab. The median time before response was 6 months (1‐10 months). Only two patients needed to be treated again during a median follow‐up of 2.0 years (0.75‐9 years). Interestingly, the response rate was good in patients with associated autoimmune disease (5/8) and similar to the response rate observed in patients with a haematological disease (16/20) (P = 0.63). A shorter disease duration was associated with a better clinical response to rituximab (odds ratio 0.81, P = 0.025) and the response rate was better (P = 0.05) in common forms (83.3%) than in sensory forms (42.9%). No major adverse events were recorded. Rituximab is efficacious in CIDP patients with haematological or autoimmune disease. It improves clinical response and decreases dependence on first‐line treatments. [ABSTRACT FROM AUTHOR]

Background: Mutations in TUBB4A are associated with a wide phenotypic spectrum including generalized dystonia with whispering dysphonia (DYT‐TUBB4A). Methods: We report the case of a 44‐year‐old patient with DYT‐TUBB4A with a clinical presentation of disabling progressive dystonia, with a prominent laryngeal, cervical and facial involvement. Results: Bipallidal deep brain stimulation (DBS) resulted in a 55% reduction of dystonia severity assessed by the Burke–Fahn−Marsden scale score 6 months after surgery. The effect was obvious on the cervical and facial components of dystonia. Conclusion: We suggest that bipallidal DBS should be considered in patients with disabling dystonia related to TUBB4A variants. [ABSTRACT FROM AUTHOR]

Background and Purpose Methods Results Conclusions Myoclonus dystonia due to a pathogenic variant in SGCE (MYC/DYT‐SGCE) is a rare condition involving a motor phenotype associating myoclonus and dystonia. Dysfunction within the networks relying on the cortex, cerebellum, and basal ganglia was presumed to underpin the clinical manifestations. However, the microarchitectural abnormalities within these structures and related pathways are unknown. Here, we investigated the microarchitectural brain abnormalities related to the motor phenotype in MYC/DYT‐SGCE.We used neurite orientation dispersion and density imaging, a multicompartment tissue model of diffusion neuroimaging, to compare microarchitectural neurite organization in MYC/DYT‐SGCE patients and healthy volunteers (HVs). Neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF) were derived and correlated with the severity of motor symptoms. Fractional anisotropy (FA) and mean diffusivity (MD) derived from the diffusion tensor approach were also analyzed. In addition, we studied the pathways that correlated with motor symptom severity using tractography analysis.Eighteen MYC/DYT‐SGCE patients and 24 HVs were analyzed. MYC/DYT‐SGCE patients showed an increase of ODI and a decrease of FA within their motor cerebellum. More severe dystonia was associated with lower ODI and NDI and higher FA within motor cerebellar cortex, as well as with lower NDI and higher ISOVF and MD within the corticopontocerebellar and spinocerebellar pathways. No association was found between myoclonus severity and diffusion parameters.In MYC/DYT‐SGCE, we found microstructural reorganization of the motor cerebellum. Structural change in the cerebellar afferent pathways that relay inputs from the spinal cord and the cerebral cortex were specifically associated with the severity of dystonia. [ABSTRACT FROM AUTHOR]

Two 18-unsaturated progesterone derivatives, 18-vinylprogesterone (18-VP) and 18-ethynylprogesterone (18-EP) have proved to be potent inhibitors of the bovine cytochrome P-45011β, the enzyme involved in the last steps of aldosterone biosynthesis [Delorme, C., Piffeteau, A., Viger, A. & Marquet, A. (1995) Eur. J. Biochem. 232, 247–256]. In the present study, we demonstrate that these two compounds exhibit the characteristics of mechanism-based inactivators of this enzyme. Inactivation followed pseudo-first-order and saturation kinetics. The kinetic parameters of inactivation were ki = 0.11 min-1 and Ki = 4 µM for 18-VP and ki =0.12 min-1 and 22 µM for 18-EP Inactivation of P-45011β activity was strictly dependent on the presence of NADPH. Protection by the substrate deoxycorticosterone was observed, demonstrating a selective modification at the substrate-binding site. With radiolabeled 18-VP, inactivation was shown to be irreversible with a stoichiometry of 1.4 tool bound [3H]18-VP/mol inactivated cytochrome P-45011β SDS/PAGE analysis of the [3H]18-VP—inactivated enzyme showed that, under conditions preventing heme dissociation, the P-45011β band was labeled, while no labeling of the apoprotein was observed under denaturating conditions. Furthermore, the loss of catalytic activity could be correlated with the destruction of the P-450 chromophore evaluated by the Fe11-CO versus Fe11 difference spectra. These arguments led us to propose that 18-vinylprogesterone inactivates cytochrome P-45011β by heme destruction rather than by protein modification. [ABSTRACT FROM AUTHOR]