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BACKGROUND Local injections of botulinum toxin type A have been used to treat essential head detremor but have not been extensively studied in randomized trials. METHODS In a multicenter, double-blind, randomized trial, we assigned, in a 1:1 ratio, adult patients with essential or isolated head tremor to receive botulinum toxin type A or placebo. Botulinum toxin or placebo was injected under electromyographic guidance into each splenius capitis muscle on the day of randomization (day 0) and during week 12. The primary outcome was improvement by at least 2 points on the Clinical Global Impression of Change (CGI) scale at week 6 after the second injection (week 18 after randomization). The CGI scale was used to record the patient's assessment of the degree of improvement or worsening of head tremor since baseline; scores range from 3 (very much improved) to -3 (very much worse). Secondary outcomes included changes in tremor characteristics from baseline to weeks 6, 12, and 24. RESULTS A total of 120 patients were enrolled; 3 patients were excluded during screening, and 117 patients were randomly assigned to receive botulinum toxin (62 patients) or placebo (55 patients) and were included in the intention-to-treat analysis. Twelve patients in the botulinum toxin group and 2 patients in the placebo group did not receive injections during week 12. The primary outcome - improvement by at least 2 points on the CGI scale at week 18 - was met by 31% of the patients in the botulinum toxin group as compared with 9% of those in the placebo group (relative risk, 3.37; 95% confidence interval, 1.35 to 8.42; P=0.009). Analyses of secondary outcomes at 6 and 12 weeks but not at 24 weeks were generally supportive of the primary-outcome analysis. Adverse events occurred in approximately half the patients in the botulinum toxin group and included head and neck pain, posterior cervical weakness, and dysphagia. CONCLUSIONS Injection of botulinum toxin into each splenius capitis muscle on day 0 and during week 12 was more effective than placebo in reducing the severity of isolated or essential head tremor at 18 weeks but not at 24 weeks, when the effects of injection might be expected to wane, and was associated with adverse events. (Funded by the French Ministry of Health; Btx-HT ClinicalTrials.gov number, NCT02555982. [ABSTRACT FROM AUTHOR]

Background: SCA27B caused by FGF14 intronic heterozygous GAA expansions with at least 250 repeats accounts for 10-60% of cases with unresolved cerebellar ataxia. We aimed to assess the size and frequency of FGF14 expanded alleles in individuals with cerebellar ataxia as compared with controls and to characterize genetic and clinical variability., Methods: We sized this repeat in 1876 individuals from France sampled for research purposes in this cross-sectional study: 845 index cases with cerebellar ataxia and 324 affected relatives, 475 controls, as well as 119 cases with spastic paraplegia, and 113 with familial essential tremor., Findings: A higher frequency of expanded allele carriers in index cases with ataxia was significant only above 300 GAA repeats (10.1%, n = 85) compared with controls (1.1%, n = 5) (p < 0.0001) whereas GAA 250-299 alleles were detected in 1.7% of both groups. Eight of 14 index cases with GAA 250-299 repeats had other causal pathogenic variants (4/14) and/or discordance of co-segregation (5/14), arguing against GAA causality. We compared the clinical signs in 127 GAA ≥300 carriers to cases with non-expanded GAA ataxia resulting in defining a key phenotype triad: onset after 45 years, downbeat nystagmus, episodic ataxic features including diplopia; and a frequent absence of dysarthria. All maternally transmitted alleles above 100 GAA were unstable with a median expansion of +18 repeats per generation (r 2  = 0.44; p < 0.0001). In comparison, paternally transmitted alleles above 100 GAA mostly decreased in size (-15 GAA (r 2  = 0.63; p < 0.0001)), resulting in the transmission bias observed in SCA27B pedigrees., Interpretation: SCA27B diagnosis must consider both the phenotype and GAA expansion size. In carriers of GAA 250-299 repeats, the absence of documented familial transmission and a presentation deviating from the key SCA27B phenotype, should prompt the search for an alternative cause. Affected fathers have a reduced risk of having affected children, which has potential implications for genetic counseling., Funding: This work was supported by the Fondation pour la Recherche Médicale, grant number 13338 to JLM, the Association Connaître les Syndrome Cérébelleux - France (to GS) and by the European Union's Horizon 2020 research and innovation program under grant agreement No 779257 ("SOLVE-RD" to GS). DP holds a Fellowship award from the Canadian Institutes of Health Research (CIHR). SK received a grant (01GM1905C) from the Federal Ministry of Education and Research, Germany, through the TreatHSP network. This work was supported by the Australian Government National Health and Medical Research Council grants (GNT2001513 and MRFF2007677) to MB and PJL., Competing Interests: Declaration of interests MA received consulting fees from Reata pharmaceuticals, Merz, AbbVie, Orkyn, Ever Pharma, Ipsen; honoraria from Reata pharmaceuticals, Merz, AbbVie, Orkyn, Ever Pharma, Ipsen and participated on an advisory board for Reata Pharmaceuticals. ILB received grants from Pfizer, Fondation Plan Alzheimer, JPND/ANR, Alector; consulting fees from Prevail Therapeutics, Alector, JEITO and participated on an advisory board of Prevail Therapeutics. CM reveived financial support for attending meetings and travel from Nutricia and participated on an advisory board of Medesis Pharma society. BD had public funding contracts for Clinical Research: Contrat de Recherche Clinique (CRC) 2021 (APHP), CRC 2023 (APHP) and Agence Régionale de Santé (ARS); received honoraria from MERZ, IPSEN Pharma, LVL Medical; received support for attending meetings from MERZ Pharma, ADELIA; participated on an advisory board of MERZ, ORION Pharma and received equipment from MERZ. SF received support for participation in national and international meetings from Alnylam. MB received honoraria for thesis examinations; is member of Australian Academy of Health and Medical Sciences Australian Learned Academies Data Internetworking Network (ALADIN) Project Steering Committee; Australian Academy of Health and Medical Sciences Reports Committee; Clinical Genomics Advisory Committee, Kinghorn Sequencing Center; Gen V Scientific Advisory Committee, Murdoch Children's Research Institute; Viertel Foundation Medical Advisory Board; Australian Academy of Health and Medical Sciences Reports Committee; Present American Epilepsy Society Basic Sciences Committee; Gen V Bioresource Genetics Working Group. AD received grants from Biogen, WAVELIFE, ROCHE, TRIPLET Therapeutics, NIH RO1 (National Institute of Health), National Hospital Clinical Research Program; consulting fees from Wavelife science, ROCHE, TRIPLET Therapeutics, Pfizer, ASKBIO, Genome Quebec, VICO therapeutics; participated on an advisory board for REATA; is the president of the Société Francophone de Neurogénétique., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Impostor syndrome is a psychological condition that inhibits individuals' ability to recognize their achievements such that they fear being exposed as forgers. It is common in medical students, particularly in the early stages of clerkship training while transitioning from preclinical to clinical training. This cross-sectional study assessed the prevalence and associated factors of the imposter phenomenon among medical clinical students using the Clance Impostor Phenomenon Scale (CIPS), focusing on sociodemographic characteristics, mental health status, and occurrence of the impostor phenomenon. Out of 228 undergraduate clinical-year medical students, 108 (47.4%) reported experiencing the impostor phenomenon. The results from the multivariable analysis showed that high levels of stress (adjusted odds ratio = 2.315; 95% confidence interval = 1.105-4.853), anxiety (6.462; 1.374-30.392), and depression (4.219; 1.448-12.290) were significantly associated with an increased risk of experiencing the impostor phenomenon. We found no difference between participants in the early or later years of clerkship training. The study highlights the prevalence of impostor syndrome among medical students and its link to mental health issues. Addressing this issue through education, mentorship, systemic problem solving, normalizing failure, and monitoring and treating mental health issues could help students reach and realize their full educational and professional potential.

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., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Cervical dystonia is a neurological disorder characterized by involuntary muscle contractions and abnormal postures of the head and neck. Botulinum neurotoxin injection is the first-line treatment. Imaging determination of the cervical segments involved (lower or upper according to the torticollis-torticaput [COL-CAP] Classification) is an aid in determining the muscles to be injected. We aimed to clarify the impact of dystonia on posture and rotational movement of cervical vertebrae in the transverse plane., Methods: A comparative study was conducted in a movement disorders department. Ten people with cervical dystonia and 10 matched healthy subjects (without cervical dystonia) were recruited. 3-D images of posture and cervical range of motion in axial rotation in the sitting position were recorded by using a cone-beam CT scanner. Range of rotational motion of the upper cervical spine from the occipital bone to fourth cervical vertebra was measured and compared between the two groups., Findings: The head posture analysis showed that the total cervical spine position was more significantly distant from the neutral position for people with dystonia than healthy subjects (p = 0.007). The rotational range of motion of the cervical spine was significantly lower in cervical dystonia participants than in healthy subjects for the total (p = 0.026) and for upper cervical spine (p = 0.004)., Interpretation: We demonstrated, by means of cone-beam CT, that the disorganization of movements due to cervical dystonia affected the upper cervical spine and mostly the atlantoaxial joint. The involvement of rotator muscles at this cervical level should be considered more in treatments., Competing Interests: Declaration of Competing Interest The authors have stated explicitly that there are no conflicts of interest in connection with this work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study compares two methods to quantify the amplitude and frequency of head movements in patients with head tremor: one based on video-based motion analysis, and the other using a miniature wireless inertial magnetic motion unit (IMMU). Concomitant with the clinical assessment of head tremor severity, head linear displacements in the frontal plane and head angular displacements in three dimensions were obtained simultaneously in forty-nine patients using one video camera and an IMMU in three experimental conditions while sitting (at rest, counting backward, and with arms extended). Head tremor amplitude was quantified along/around each axis, and head tremor frequency was analyzed in the frequency and time-frequency domains. Correlation analysis investigated the association between the clinical severity of head tremor and head linear and angular displacements. Our results showed better sensitivity of the IMMU compared to a 2D video camera to detect changes of tremor amplitude according to examination conditions, and better agreement with clinical measures. The frequency of head tremor calculated from video data in the frequency domain was higher than that obtained using time-frequency analysis and those calculated from the IMMU data. This study provides strong experimental evidence in favor of using an IMMU to quantify the amplitude and time-frequency oscillatory features of head tremor, especially in medical conditions.

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Plantar flexion of toe dystonia is very painful and leads to difficulties in walking. The objective of this study was to investigate the effect of incobotulinum toxin A (Xeomin) in the treatment of this type of dystonia in parkinsonian patients, using a randomized, double blind, placebo-controlled trial., Methods: 45 parkinsonian patients with painful dystonic plantar flexion of toes were injected either with incobotulinum toxin A (Btx group), or with placebo in two muscle targets: the Flexor digitorum longus and the Flexor digitorum brevis. Three groups were compared: the first group received placebo in the Flexor digitorum longus and 100UI of Btx in the Flexor digitorum brevis (n = 16); the second group received 100 UI of Btx in the Flexor digitorum longus and placebo in the Flexor digitorum brevis (n = 13); and the third group, 2 injections of placebo (n = 16). The patients were injected in the same way twice with an interval of 3 months. The primary endpoint was measured six weeks after injections with the Clinical Global Impression (CGI) of change. Dystonia severity and associated pain were also assessed., Results: Mean CGI was improved in the Btx group compared to the placebo group (P = 0.039). A significant reduction of pain and dystonia severity were observed in patients treated with Btx compared to baseline but no improvement was noted when compared to placebo group. No difference of efficacy was highlighted between the two injection sites., Conclusions: Btx injections are effective for improving clinical state of parkinsonian patients with plantar flexion of toe dystonia., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Focal dystonia has been associated with deficient processing of sense of effort cues. However, corresponding studies are lacking in cervical dystonia (CD). We hypothesized that dystonic muscle activity would perturb neck force control based on sense of effort cues., Methods: Neck extension force control was investigated in 18 CD patients with different clinical features (7 with and 11 without retrocollis) and in 19 control subjects. Subjects performed force-matching and force-maintaining tasks at 5% and 20% of maximum voluntary contraction (MVC). Three task conditions were tested: i) with visual force feedback, ii) without visual feedback (requiring use of sense of effort), iii) without visual feedback, but with neck extensor muscle vibration (modifying muscle afferent cues). Trapezius muscle activity was recorded using electromyography (EMG)., Results: CD patients did not differ in task performance from healthy subjects when using visual feedback (ANOVA, p>0.7). In contrast, when relying on sense of effort cues (without visual feedback, 5% MVC), force control was impaired in patients without retrocollis (p = 0.006), but not in patients with retrocollis (p>0.2). Compared to controls, muscle vibration without visual feedback significantly affected performance in patients with retrocollis (p<0.001), but not in patients without retrocollis. Extensor EMG during rest, included as covariate in ANOVA, explained these group differences., Conclusion: This study shows that muscle afferent feedback biases sense of effort cues when controlling neck forces in patients with CD. The bias acts on peripheral or central sense of effort cues depending on whether the task involves dystonic muscles. This may explain why patients with retrocollis more accurately matched isometric neck extension forces. This highlights the need to consider clinical features (pattern of dystonic muscles) when evaluating sensorimotor integration in CD., Competing Interests: LC reports grants from Université Pierre et Marie Curie, Paris VI, outside the submitted work. SS reports personal fees from Allergan, personal fees from Ipsen, personal fees from Merz-Pharma, outside the submitted work. VG has nothing to disclose. SM reports grants from Fondation Paul Bennetot, outside the submitted work. MV reports grants from INSERM, grants from APHP, grants from APTES, grants from France Parkinson, grants from AMADYS, personal fees from Movement Disorders Society, outside the submitted work; and Member of the advisory board for Merz and Medtronic. PGL reports grants from Gloria and Jacques Gosweiler Foundation, outside the submitted work and owns shares in Aggero MedTech AB, a company commercializing a measurement instrument for spasticity. In addition, PGL and MAM have patented a method for measurement of manual dexterity (EP2659835A1). JPB reports personal fees from MERZ-PHARMA, personal fees from IPSEN, grants from AMADYS, grants from AFREK, outside the submitted work. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Background: The effectiveness of retraining therapy (RT) for writer's cramp is difficult to predict and its determinants are unknown. Methods: We examined factors potentially predicting improved legibility after RT in patients with writer's cramp (WC). We reviewed the files of 693 WC patients treated with RT from 1995 to 2009. Standardized assessments were made both at baseline and after 2 months of RT in 305 patients. The effect of RT on legibility was evaluated by using the handwriting subscore of the Burke-Fahn-Marsden (BFM) disability scale. Initial and final handwriting samples were blindly scored in random order. Associations between WC patterns and changes in legibility were identified by uni- and multivariable analyses. Results: Legibility improved by ≥1 point in the BFM handwriting subscore in 93 patients (31%). WC patients who improved were more likely to have synergic dystonic patterns involving the wrist and forearm (60% vs. 40%; P  = 0.03) and less likely to have flexion of fingers F3 to F5 (19% vs. 81%; P  = 0.017). Outcome was not related to gender, age, or dystonia duration. Our results confirm that retraining therapy could improve legibility in patients with writer's cramp. Conclusions: The pattern of writer's cramp can help to identify patients who are most likely to benefit from retraining therapy, regardless of age, gender, and disease duration.