Fixel-Based Analysis Reveals Whole-Brain White Matter Abnormalities in Cervical Dystonia.

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.

How does Tourette syndrome impact adolescents' daily living? A text mining study.

Tourette syndrome is a neurodevelopmental disease in which clinical manifestations are essentially present during childhood and adolescence, corresponding to one of the critical development phases. However, its consequences on the daily lives of young patients have been insufficiently investigated. Here, we aimed to investigate this using a statistical text mining approach, allowing for the analysis of a large volume of free textual data. Sixty-two adolescents with Tourette syndrome participated in an interview in which they discussed their daily life (i) in school, (ii) at home, and (iii) with strangers, (iv) the aspect of Tourette syndrome which caused the most difficulty, and (v) their thoughts regarding their future as adults. Following data pre-processing, these corpora were analyzed separately using the IRAMUTEQ software through factorial correspondence analysis to identify the most commonly recurring topics of each corpus, and their relations with clinical features. The main difficulty corpus was directly related to comorbidities of Tourette syndrome. Daily life at home was correlated with executive functioning. Difficulties at school were related to a higher severity of tics. Thoughts regarding future daily life were worst for the youngest patients and were correlated with executive functioning and a higher depression score. Taken altogether, our results highlighted that social stigma was a pervasive topic among our corpora. From a clinical standpoint, tic severity was especially related to difficulties at school, while comorbidities had a high impact on social daily living and cost for managing both tics and symptoms of comorbidities. TRIAL REGISTRATION: clinicaltrials.gov/ct2/show/NCT04179435.

Acute cerebellar ataxia and myoclonus with or without opsoclonus: a para-infectious syndrome associated with COVID-19.

BACKGROUND AND PURPOSE: Patients with COVID-19 can have central or peripheral neurological manifestations. METHODS: The cases of two patients with acute cerebellar ataxia and myoclonus associated with COVID-19 are reported (with Video S1) and five previously reported patients are discussed. RESULTS: Acute cerebellar ataxia and myoclonus started between 10 days and 6 weeks after the first manifestations of COVID-19. Opsoclonus or ocular flutter was present in four patients. Patients were treated with intravenous immunoglobulins and/or steroids except for one patient, resulting in a striking improvement within a week. CONCLUSION: Acute cerebellar ataxia and myoclonus with or without opsoclonus belongs to the wide spectrum of neurological manifestations associated with COVID-19. It is important to recognize this possible manifestation since early treatment allows for rapid recovery.

Visual sensory processing is altered in myoclonus dystonia.

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.

Association of abnormal explicit sense of agency with cerebellar impairment in myoclonus-dystonia.

Non-motor aspects in dystonia are now well recognized. The sense of agency, which refers to the experience of controlling one's own actions, has been scarcely studied in dystonia, even though its disturbances can contribute to movement disorders. Among various brain structures, the cerebral cortex, the cerebellum, and the basal ganglia are involved in shaping the sense of agency. In myoclonus dystonia, resulting from a dysfunction of the motor network, an altered sense of agency may contribute to the clinical phenotype of the condition. In this study, we compared the explicit and implicit sense of agency in patients with myoclonus dystonia caused by a pathogenic variant of SGCE (DYT-SGCE) and control participants. We utilized behavioural tasks to assess the sense of agency and performed neuroimaging analyses, including structural, resting-state functional connectivity, and dynamic causal modelling, to explore the relevant brain regions involved in the sense of agency. Additionally, we examined the relationship between behavioural performance, symptom severity, and neuroimaging findings. We compared 19 patients with DYT-SGCE and 24 healthy volunteers. Our findings revealed that patients with myoclonus-dystonia exhibited a specific impairment in explicit sense of agency, particularly when implicit motor learning was involved. However, their implicit sense of agency remained intact. These patients also displayed grey-matter abnormalities in the motor cerebellum, as well as increased functional connectivity between the cerebellum and pre-supplementary motor area. Dynamic causal modelling analysis further identified reduced inhibitory effects of the cerebellum on the pre-supplementary motor area, decreased excitatory effects of the pre-supplementary motor area on the cerebellum, and increased self-inhibition within the pre-supplementary motor area. Importantly, both cerebellar grey-matter alterations and functional connectivity abnormalities between the cerebellum and pre-supplementary motor area were found to correlate with explicit sense of agency impairment. Increased self-inhibition within the pre-supplementary motor area was associated with less severe myoclonus symptoms. These findings highlight the disruption of higher-level cognitive processes in patients with myoclonus-dystonia, further expanding the spectrum of neurological and psychiatric dysfunction already identified in this disorder.

Non-Motor Symptoms and Quality of Life in Patients with PRRT2-Related Paroxysmal Kinesigenic Dyskinesia.

Background: Monoallelic pathogenic variants of PRRT2 often result in paroxysmal kinesigenic dyskinesia (PKD). Little is known about health-related quality of life (HrQoL), non-motor manifestations, self-esteem, and stigma in patients with PKD. Objectives: We investigated non-motor symptoms and how they related to HrQoL in a genetically homogeneous group of PRRT2-PKD patients. We paid special attention to perceived stigmatization and self-esteem. Methods: We prospectively enrolled 21 consecutive PKD patients with a pathogenic variant of PRRT2, and 21 healthy controls matched for age and sex. They were evaluated with dedicated standardized tests for non-motor symptoms, HrQoL, anxiety, depression, stigma, self-esteem, sleep, fatigue, pain, and psychological well-being. Results: Patients reported an alteration of the physical aspects of HrQoL, regardless of the presence of residual paroxysmal episodes. Non-motor manifestations were frequent, and were an important determinant of the alteration of HrQoL. In addition, patients perceived a higher level of stigmatization which positively correlated with a delay in diagnosis (ρ = 0.615, P = 0.003) and the fear of being judged (ρ = 0.452, P = 0.04), but not with the presence of paroxysmal episodes (ρ = 0.203, P = 0.379). Conclusions: Our findings have important implications for care givers concerning patient management and medical education about paroxysmal dyskinesia. PRRT2-PKD patients should be screened for non-motor disorders in routine care. A long history of misdiagnosis may play a role in the high level of perceived stigmatization. Improving knowledge about diagnostic clues suggestive of PKD is mandatory.

Somatotopy of cervical dystonia in motor-cerebellar networks: Evidence from resting state fMRI.

INTRODUCTION: Cervical dystonia is the most frequent form of isolated focal dystonia. It is often associated with a dysfunction in brain networks, mostly affecting the basal ganglia, the cerebellum, and the somatosensory cortex. However, it is unclear if such a dysfunction is somato-specific to the brain areas containing the representation of the affected body part, and may thereby account for the focal expression of cervical dystonia. In this study, we investigated resting state functional connectivity in the areas within the motor cortex and the cerebellum containing affected and non-affected body representations in cervical dystonia patients. METHODS: Eighteen patients affected by cervical dystonia and 21 healthy controls had resting state fMRI. The functional connectivity between the motor cortex and the cerebellum, as well as their corresponding measures of gray matter volume and cortical thickness, were compared between groups. We performed seed-based analyses, selecting the different body representation areas in the precentral gyrus as seed regions, and all cerebellar areas as target regions. RESULTS: Compared to controls, patients exhibited increased functional connectivity between the bilateral trunk representation area of the motor cortex and the cerebellar vermis 6 and 7b, respectively. These functional abnormalities did not correlate with structural changes or symptom severity. CONCLUSIONS: Our findings indicate that the abnormal function of the motor network is somato-specific to the areas encompassing the neck representation. Functional abnormalities in discrete relevant areas of the motor network could thus contribute to the focal expression of CD.

Long-term effect of apomorphine infusion in advanced Parkinson's disease: a real-life study.

Long-term effects of continuous subcutaneous apomorphine infusion (CSAI) on health-related quality of life (HRQoL) and predictors of CSAI discontinuation are poorly known. Data from consecutive advanced Parkinson's disease patients treated in routine care were retrospectively collected over 24 months after CSAI initiation, with a focus on the 39-item Parkinson's disease questionnaire (PDQ-39). We determined predictors of CSAI discontinuation and HRQoL improvement using multiple regression analysis. Of the 110 subjects evaluated over a 2-year period, 35% discontinued CSAI. Of those who continued treatment, HRQoL remained stable with a sustained reduction in motor fluctuations. The observed effect on dyskinesias was mild and transient. Of note, patients with preexisting impulse control disorders showed an overall good tolerability. PDQ-39 was the only baseline predictor of HRQoL improvement after 2 years of treatment. The presence of dyskinesias, poorer psychological status, shorter disease duration, male sex, and worse OFF state were predictors of discontinuation. Best candidates for CSAI are patients with: (i) poor baseline HRQoL and (ii) marked motor fluctuations.

Dissociation in reactive and proactive inhibitory control in Myoclonus dystonia.

Myoclonus-dystonia (MD) is a syndrome characterized by myoclonus of subcortical origin and dystonia, frequently associated with psychiatric comorbidities. The motor and psychiatric phenotypes of this syndrome likely result from cortico-striato-thamalo-cerebellar-cortical pathway dysfunction. We hypothesized that reactive and proactive inhibitory control may be altered in these patients. Using the Stop Signal Task, we assessed reactive and proactive inhibitory control in MD patients with (n = 12) and without (n = 21) deep brain stimulation of the globus pallidus interna and compared their performance to matched healthy controls (n = 24). Reactive inhibition was considered as the ability to stop an already initiated action and measured using the stop signal reaction time. Proactive inhibition was assessed through the influence of several consecutive GO or STOP trials on decreased response time or inhibitory process facilitation. The proactive inhibition was solely impaired in unoperated MD patients. Patients with deep brain stimulation showed impairment in reactive inhibition, independent of presence of obsessive-compulsive disorders. This impairment in reactive inhibitory control correlated with intrinsic severity of myoclonus (i.e. pre-operative score). The results point to a dissociation in reactive and proactive inhibitory control in MD patients with and without deep brain stimulation of the globus pallidus interna.