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Surround inhibition, a neural mechanism relevant for skilled motor behavior, has been shown to be deficient in the affected primary motor cortex (M1) in patients with focal hand dystonia (FHD). Even in unilateral FHD, however, electrophysiological and neuroimaging studies have provided evidence for bilateral M1 abnormalities. Clinically, the presence of mirror dystonia, dystonic posturing when the opposite hand is moved, also suggests abnormal interhemispheric interaction. To assess whether a loss of inter-hemispheric inhibition (IHI) may contribute to the reduced surround inhibition, IHI towards the affected or dominant M1 was examined in 13 patients with FHD (seven patients with and six patients without mirror dystonia, all affected on the right hand) and 12 right-handed, age-matched healthy controls (CON group). IHI was tested at rest and during three different phases of a right index finger movement in a synergistic, as well as in a neighboring, relaxed muscle. There was a trend for a selective loss of IHI between the homologous surrounding muscles in the phase 50 ms before electromyogram onset in patients with FHD. Post hoc analysis revealed that this effect was due to a loss of IHI in the patients with FHD with mirror dystonia, while patients without mirror dystonia did not show any difference in IHI modulation compared with healthy controls. We conclude that mirror dystonia may be due to impaired IHI towards neighboring muscles before movement onset. However, IHI does not seem to play a major role in the general pathophysiology of FHD. [ABSTRACT FROM AUTHOR]

A mounting body of research points to cerebrovascular dysfunction as a fundamental element in the pathophysiology of Parkinson's disease (PD). In the current feasibility study, blood-oxygen-level-dependent (BOLD) MRI was used to measure cerebrovascular reactivity (CVR) in response to hypercapnia in 26 PD patients and 16 healthy controls (HC), and aimed to find a multivariate pattern specific to PD. Whole-brain maps of CVR amplitude (i.e., magnitude of response to CO 2 ) and latency (i.e., time to reach maximum amplitude) were computed, which were further analyzed using scaled sub-profile model principal component analysis (SSM-PCA) with leave-one-out cross-validation. A meaningful pattern based on CVR latency was identified, which was named the PD CVR pattern (PD-CVRP). This pattern was characterized by relatively increased latency in basal ganglia, sensorimotor cortex, supplementary motor area, thalamus and visual cortex, as well as decreased latency in the cerebral white matter, relative to HC. There were no significant associations with clinical measures, though sample size may have limited our ability to detect significant associations. In summary, the PD-CVRP highlights the importance of cerebrovascular dysfunction in PD, and may be a potential biomarker for future clinical research and practice., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Pirio Richardson has received honoraria for lectures from the International Parkinson’s Disease and Movement Disorders Society and the American Academy of Neurology. Dr. Pirio Richardson serves on the Scientific Advisory Boards for private foundations including the Benign Essential Blepharospasm Research Foundation and the Dystonia Medical Research Foundation. She has received royalties from Springer. The remaining authors declare they have no competing financial interests.

Introduction: The Control Network Neuromodulation to Enhance Cognitive Training in Complex Traumatic Brain Injury (CONNECT-TBI) study is an ongoing randomized, double-blinded, sham-controlled multisite clinical trial to determine the enhancing effects of noninvasive neuromodulation when paired with cognitive training in military participants (Veterans and active duty) with mild TBI. Attention Process Training-III (APT-III) was selected for its strong evidence base, manualized procedures, and computerized program. However, many aspects of APT-III that make it ideal for personalization make it less ideal for reliable implementation across participants, clinicians/technicians, and sites. The purpose of this feature article is to highlight APT-III procedures that require additional standardization for reliable administration across participants and sites., Materials and Methods: Ten studies using APT-III were reviewed for methodology of APT-III administration. The manual was also scrutinized; aspects of administration that involved clinical decision-making, subjectivity, flexibility, and/or that were identified by the APT-III developers as areas in need of "empirical evaluation" were flagged by clinicians. Literature and manual review findings were presented to the team for discussion and solution-finding. The authors created and refined a standardized process that would allow participants to move through APT-III training, including task movement algorithms and new materials drafts. Refining of algorithms and drafts continued until there was a consensus from team members., Results: Many gray areas were identified, but we will limit our reporting to focus on (1) dosage, (2) adaptation, (3) metacognitive strategy instruction, and (4) goal attainment scaling. We present APT-III manual details, literature review findings, and CONNECT-TBI decisions and materials for each of these areas of focus., Conclusions: We have highlighted some of the major gray areas of APT-III administration so that fellow researchers can understand the need to take similar steps in clinical trials using APT-III. We provide examples of our standardization process and resultant rules and materials. Our algorithm, based on prior studies using the APT-III and our own iterative adjustments, allows for adjustment of the difficulty and speed of the training tasks (but within certain parameters) in order to achieve the best balance between individualization and consistency across participants and sites. We provide an example of a workflow and reporting process for future studies., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Background: Prior studies have indicated that female individuals outnumber male individuals for certain types of dystonia. Few studies have addressed factors impacting these sex differences or their potential biological mechanisms., Objectives: To evaluate factors underlying sex differences in the dystonias and explore potential mechanisms for these differences., Methods: Data from individuals with various types of dystonia were analyzed in relation to sex. Data came from two different sources. One source was the Dystonia Coalition database, which contains predominantly idiopathic adult-onset focal and segmental dystonias. The second source was the MDSGene database, which contains predominantly early-onset monogenic dystonias., Results: The 3222 individuals from the Dystonia Coalition included 71% female participants and 29% male participants for an overall female-to-male ratio (F:M) of 2.4. This ratio varied according to body region affected and whether dystonia was task-specific. The female predominance was age-dependent. Sex did not have a significant impact on co-existing tremor, geste antagoniste, depression or anxiety. In the 1377 individuals from the MDSGene database, female participants outnumbered male participants for some genes (GNAL, GCH1, and ANO3) but not for other genes (THAP1, TH, and TOR1A)., Conclusions: These results are in keeping with prior studies that have indicated female individuals outnumber male individuals for both adult-onset idiopathic and early onset monogenic dystonias. These results extend prior observations by revealing that sex ratios depend on the type of dystonia, age, and underlying genetics., (© 2024 International Parkinson and Movement Disorder Society.)

Background: A better understanding of pain in adult-onset idiopathic dystonia (AOID) is needed to implement effective therapeutic strategies., Objective: To develop a new rating instrument for pain in AOID and validate it in cervical dystonia (CD)., Methods: Development and validation of the Pain in Dystonia Scale (PIDS) comprised three phases. In phase 1, international experts and participants with AOID generated and evaluated the preliminary items for content validity. In phase 2, the PIDS was drafted and revised by the experts, followed by cognitive interviews to ensure self-administration suitability. In phase 3, the PIDS psychometric properties were assessed in 85 participants with CD and retested in 40 participants., Results: The final version of PIDS evaluates pain severity (by body-part), functional impact, and external modulating factors. Test-retest reliability showed a high-correlation coefficient for the total score (0.9, P < 0.001), and intraclass correlation coefficients were 0.7 or higher for all items in all body-parts subscores. The overall PIDS severity score showed high internal consistency (Cronbach's α, 0.9). Convergent validity analysis revealed a strong correlation between the PIDS severity score and the Toronto Western Spasmodic Torticollis Rating Scale pain subscale (0.8, P < 0.001) and the Brief Pain Inventory-short form items related to pain at time of the assessment (0.7, P < 0.001) and impact of pain on daily functioning (0.7, P < 0.001)., Conclusion: The PIDS is the first specific questionnaire developed to evaluate pain in all patients with AOID, here, demonstrating high-level psychometric properties in people with CD. Future work will validate PIDS in other forms of AOID. © 2023 International Parkinson and Movement Disorder Society., (© 2023 International Parkinson and Movement Disorder Society.)

Background: Cerebrovascular dysfunction in Parkinson's disease (PD) is heterogeneous and may contribute to disease pathophysiology or progression. There is a need to understand the mechanisms by which cerebrovascular dysfunction is altered in participants with PD., Objectives: The objective of this study is to test the hypothesis that participants with PD exhibit a significant reduction in the ability of the cerebral vessels to dilate in response to vasoactive challenges relative to healthy controls (HC)., Methods: The current study uses a vasodilatory challenge while participants undergo functional magnetic resonance imaging to quantify the amplitude and delay of cerebrovascular reactivity in participants with PD relative to age and sex-matched HC. An analysis of covariance was used to evaluate differences in cerebrovascular reactivity amplitude and latency between PD participants and HC., Results: A significant main effect of group was observed for whole-brain cerebrovascular reactivity amplitude (F (1, 28)  = 4.38, p = 0.046, Hedge's g = 0.73) and latency (F (1, 28)  = 16.35, p < 0.001, Hedge's g = 1.42). Participants with PD exhibited reduced whole-brain amplitude and increased latencies in cerebrovascular reactivity relative to HC. The evaluation of regional effects indicates that the largest effects were observed in the cuneus, precuneus, and parietal regions., Conclusions: PD participants exhibited reduced and delayed cerebrovascular reactivity. This dysfunction may play an important role in chronic hypoxia, neuroinflammation, and protein aggregation, mechanisms that could lead to disease progression. Cerebrovascular reactivity may serve as an important biomarker and target for future interventions. © 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.)

Objective: To investigate the subjective phenomenon and the neural underpinnings of tics compared with voluntary movements in patients with tic disorders., Methods: We recorded electroencephalographic and electromyographic data while subjects completed a Libet clock paradigm. Patients and healthy volunteers reported the times of W (willing to move) and M (movement occurrence) while performing voluntary movements. This was repeated only for the patients for the tics., Results: In the patients, W and M times preceding voluntary movements and tics did not significantly differ from voluntary movements of healthy volunteers. The Bereitschaftspotentials in the patients were similar to healthy volunteers. Tics were only assessable for 7 patients due to artifacts. Two subjects did not show Bereitschaftspotentials, and they reported the lowest levels of tic voluntariness. 5 subjects did not show beta band event-related desynchronization before tics., Conclusions: For patients, the sense of volition for tics is similar to that of their voluntary movements which is similar to normal. Patients showed dissociations between the Bereitschaftspotential and beta desynchronization for tics, with 5/7 showing normal Bereitschaftspotentials and 2/7 showing desynchronization. The absence of desynchronization may suggest attempts to suppress tics., Significance: This physiology shows a difference for most tics compared with normal movements., (Published by Elsevier B.V.)

Objective: Hippocampal atrophy is an indicator of emerging dementia in PD, though it is unclear whether cerebral spinal fluid (CSF) Abeta-42, t-tau, or alpha-syn predict hippocampal subfield atrophy in a de novo cohort of PD patients. To examine whether levels of CSF alpha-synuclein (alpha-syn), beta-amyloid 1-42 (Abeta-42) , or total-tau (t-tau) are associated with hippocampal subfield volumes over time., Methods: We identified a subset of Parkinson's Progression Markers Initiative (PPMI) de novo PD patients with longitudinal T1-weighted imaging (baseline plus at least two additional visits across 12, 24, and 48 months) and CSF biomarkers available at baseline. We performed cross-sectional, regression, and linear mixed model analyses to evaluate the baseline and longitudinal CSF biomarkers, hippocampal subfields, and cognition. A false discovery rate (FDR) was used to correct for multiple comparisons., Results: 88 PD-CN and 21 PD-MCI had high quality longitudinal data. PD-MCI patients exhibited reduced bilateral CA1 volumes relative to PD-CN, though there were no significant differences in CSF biomarkers between these groups. Relationships between CSF biomarkers and hippocampal subfields changed over time, with a general pattern that lower CSF Abeta-42, higher t-tau and higher alpha-syn were associated with smaller hippocampal subfields, primarily in the right hemisphere., Conclusion: We replicated prior reports that demonstrated reduced CA1 volumes in PD-MCI in a de novo PD cohort. CSF biomarkers were associated with individual subfields, with evidence that the increased CSF t-tau was associated with smaller subiculum volumes at baseline and over time, though there was no clear indication that the subfields associated with cognition (CA1 and HATA) were associated with CSF biomarkers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: Several scales have been proposed to clinically evaluate the Motor Severity of Blepharospasm (BSP) but information about their measurement properties as a multicenter instrument is limited., Objective: To compare the measurement properties of four clinical scales in rating the severity of BSP in a large sample of patients from multiple sites., Methods: The Burke-Fahn-Marsden Scale (BFMS), the Global Dystonia Severity Rating Scale (GDRS), the Jankovic Rating Scale (JRS), and the Blepharospasm Severity Rating Scale (BSRS) were administered to 211 patients across 10 sites who were also requested to self-complete the Blepharospasm Disability Index (BDI). Measurement properties to be assessed included inter-/intra-observer agreement, item-to-total correlation, internal consistency, floor and ceiling effect, convergent/discriminant validity, and adherence to the distribution of BDI., Results: The BFMS had unsatisfactory measurement properties, the GDRS had acceptable reliability but other properties could not be completely testable; the JRS had satisfactory measurement properties but the scale did not accurately reflect the distribution of disability parameter (BDI) in the sample, and the BSRS had satisfactory measurement properties and also showed the best adherence to the distribution of BDI in the assessed sample., Conclusion: The comparison of the measurement properties of four rating scales to assess the motor state of the BSP in a large sample of patients from multiple sites showed that the GDRS should be used to simultaneously assess BSP and dystonia in other body parts, while the JRS (easier to use) and BSRS (better to discriminate severity) should be used to assess BSP alone., Competing Interests: The authors declare that there are no conflicts of interest relevant to this work. This work was supported in part by NIH grant NS119831 and NIH grants to The Dystonia Coalition (NS065701, TR001456, NS116025) which is part of the National Institutes of Health (NIH) Rare Disease Clinical Research Network (RDCRN), supported by the Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Science (NCATS), and the National Institute of Neurological Diseases and Stroke (NINDS)., (© 2022 International Parkinson and Movement Disorder Society.)

Background: Head tremor (HT) is a common feature of cervical dystonia (CD), usually quantified by subjective observation. Technological developments offer alternatives for measuring HT severity that are objective and amenable to automation., Objectives: Our objectives were to develop CMOR (Computational Motor Objective Rater; a computer vision-based software system) to quantify oscillatory and directional aspects of HT from video recordings during a clinical examination and to test its convergent validity with clinical rating scales., Methods: For 93 participants with isolated CD and HT enrolled by the Dystonia Coalition, we analyzed video recordings from an examination segment in which participants were instructed to let their head drift to its most comfortable dystonic position. We evaluated peak power, frequency, and directional dominance, and used Spearman's correlation to measure the agreement between CMOR and clinical ratings., Results: Power averaged 0.90 (SD 1.80) deg 2 /Hz, and peak frequency 1.95 (SD 0.94) Hz. The dominant HT axis was pitch (antero/retrocollis) for 50%, roll (laterocollis) for 6%, and yaw (torticollis) for 44% of participants. One-sided t-tests showed substantial contributions from the secondary (t = 18.17, p < 0.0001) and tertiary (t = 12.89, p < 0.0001) HT axes. CMOR's HT severity measure positively correlated with the HT item on the Toronto Western Spasmodic Torticollis Rating Scale-2 (Spearman's rho = 0.54, p < 0.001)., Conclusions: We demonstrate a new objective method to measure HT severity that requires only conventional video recordings, quantifies the complexities of HT in CD, and exhibits convergent validity with clinical severity ratings., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The dystonias are phenotypically and etiologically heterogenous disorders. Many proposals and a consensus recommendation have been provided for the diagnosis and classification of the dystonias, but these recommendations serve only as general guidelines. Current diagnosis and classification may still depend on clinical judgment causing different opinions., Objective: To delineate clinical features used by movement disorder specialists in the diagnosis and classification of isolated focal cervical dystonia, and to develop recommendations for a more consistent approach to classification according to anatomical regions involved., Methods: Cross-sectional data for subjects diagnosed with isolated dystonia were acquired from the Dystonia Coalition, an international, multicenter collaborative research network. Data from many movement disorder specialists were evaluated to determine how diagnoses of cervical dystonia related to their recorded examinations. Cases were included if they were given a diagnosis of focal cervical dystonia. Cases were also included if they had dystonia of the neck on exam, but were given an alternative diagnosis such as segmental dystonia., Results: Among 2916 subjects with isolated dystonia, 1258 were diagnosed with focal cervical dystonia. Among these 1258 cases, 28.3% had dystonia outside of the neck region. Regions involved outside of the neck included the shoulder, larynx, and sometimes other regions. Analysis of the results pointed to several factors that may influence specialists' use of current diagnostic guidelines for making a diagnosis of isolated focal cervical dystonia including varied interpretations of involvement of nearby regions (shoulder, larynx, platysma), severity of dystonia across different regions, and occurrence of tremor in different regions., Conclusions: Although focal cervical dystonia is the most common type of dystonia, a high percentage of subjects given this diagnosis had dystonia outside of the neck region. This observation points to the need for more specific guidelines for defining this common disorder. Such guidelines are proposed here., Competing Interests: This work was supported by grants to The Dystonia Coalition (NS065701, TR001456, NS116025) which is part of the National Institutes of Health (NIH) Rare Disease Clinical Research Network (RDCRN), supported by the Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Science (NCATS), and the National Institute of Neurological Diseases and Stroke (NINDS). TD also was supported in part by training grant NINDS T32‐NS007480 at Emory University. The authors have no conflicts of interest to report., (© 2021 International Parkinson and Movement Disorder Society.)

Background and Purpose: Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. The aims of this study were: (i) to develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; and (ii) to evaluate whether presence of tremor associated with dystonia influences model predictions of spread., Methods: Adult-onset isolated dystonia participants with focal onset from the Dystonia Coalition Natural History Project database were included. We developed two prediction models, one with dystonia as sole disease manifestation ("dystonia-only") and one accepting dystonia OR tremor in any body part as disease manifestations ("dystonia OR tremor"). Demographic and clinical predictors were selected based on previous evidence, clinical plausibility of association with spread, or both. We used logistic regressions and evaluated model discrimination and calibration. Internal validation was carried out based on bootstrapping., Results: Both predictive models showed an area under the curve of 0.65 (95% confidence intervals 0.62-0.70 and 0.62-0.69, respectively) and good calibration after internal validation. In both models, onset of dystonia in body regions other than the neck, older age, depression and history of neck trauma were predictors of spread., Conclusions: This predictive modeling of spread in adult-onset isolated dystonia based on accessible predictors (demographic and clinical) can be easily implemented to inform individuals' risk of spread. Because tremor did not influence prediction of spread, our results support the argument that tremor is a part of the dystonia syndrome, and not an independent or coincidental disorder., (© 2021 European Academy of Neurology.)

Background: Several monogenic causes for isolated dystonia have been identified, but they collectively account for only a small proportion of cases. Two genome-wide association studies have reported a few potential dystonia risk loci; but conclusions have been limited by small sample sizes, partial coverage of genetic variants, or poor reproducibility., Objective: To identify robust genetic variants and loci in a large multicenter cervical dystonia cohort using a genome-wide approach., Methods: We performed a genome-wide association study using cervical dystonia samples from the Dystonia Coalition. Logistic and linear regressions, including age, sex, and population structure as covariates, were employed to assess variant- and gene-based genetic associations with disease status and age at onset. We also performed a replication study for an identified genome-wide significant signal., Results: After quality control, 919 cervical dystonia patients compared with 1491 controls of European ancestry were included in the analyses. We identified one genome-wide significant variant (rs2219975, chromosome 3, upstream of COL8A1, P-value 3.04 × 10 -8 ). The association was not replicated in a newly genotyped sample of 473 cervical dystonia cases and 481 controls. Gene-based analysis identified DENND1A to be significantly associated with cervical dystonia (P-value 1.23 × 10 -6 ). One low-frequency variant was associated with lower age-at-onset (16.4 ± 2.9 years, P-value = 3.07 × 10 -8 , minor allele frequency = 0.01), located within the GABBR2 gene on chromosome 9 (rs147331823)., Conclusion: The genetic underpinnings of cervical dystonia are complex and likely consist of multiple distinct variants of small effect sizes. Larger sample sizes may be needed to provide sufficient statistical power to address the presumably multi-genic etiology of cervical dystonia. © 2021 International Parkinson and Movement Disorder Society., (© 2021 International Parkinson and Movement Disorder Society.)

Objective: The goal of this study is to better characterize the phenotypic heterogeneity of oromandibular dystonia (OMD) for the purpose of facilitating early diagnosis. Methods: First, we provide a comprehensive summary of the literature encompassing 1,121 cases. Next, we describe the clinical features of 727 OMD subjects enrolled by the Dystonia Coalition (DC), an international multicenter cohort. Finally, we summarize clinical features and treatment outcomes from cross-sectional analysis of 172 OMD subjects from two expert centers. Results: In all cohorts, typical age at onset was in the 50s and 70% of cases were female. The Dystonia Coalition cohort revealed perioral musculature was involved most commonly (85%), followed by jaw (61%) and tongue (17%). OMD more commonly appeared as part of a segmental dystonia (43%), and less commonly focal (39%) or generalized (10%). OMD was found to be associated with impaired quality of life, independent of disease severity. On average, social anxiety (LSA score: 33 ± 28) was more common than depression (BDI II score: 9.7 ± 7.8). In the expert center cohorts, botulinum toxin injections improved symptom severity by more than 50% in ~80% of subjects, regardless of etiology. Conclusions: This comprehensive description of OMD cases has revealed novel insights into the most common OMD phenotypes, pattern of dystonia distribution, associated psychiatric disturbances, and effect on QoL. We hope these findings will improve clinical recognition to aid in timely diagnosis and inform treatment strategies., Competing Interests: HJ has active or recent grant support from the US government (National Institutes of Health), private philanthropic organizations (Cure Dystonia Now), and industry (Retrophin, Inc.; Revance Therapeutics, Inc.). HJ has also served on advisory boards or as a consultant for Allergan Inc., CoA Therapeutics, Cavion Therapeutics, EnePharmaceuticals, Ipsen, and Retrophin Inc. He has received honoraria or stipends for lectures or administrative work from the American Academy of Neurology, the American Neurological Association, the Dystonia Medical Research Foundation, the International Neurotoxin Society, and the International Parkinsons Disease and Movement Disorders Society. HJ serves on the Scientific Advisory Boards for several private foundations including the Benign Essential Blepharospasm Research Foundation, Cure Dystonia Now, the Dystonia Medical Research Foundation, the Tourette Association of America, and Tyler's Hope for a Cure. He also is principle investigator for the Dystonia Coalition, which has received the majority of its support through the NIH (grants NS116025, NS065701 from the National Institutes of Neurological Disorders and Stroke TR 001456 from the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences). The Dystonia Coalition has received additional material or administrative support from industry sponsors (Allergan Inc. and Merz Pharmaceuticals) as well as private foundations (The Benign Essential Blepharospasm Foundation, Cure Dystonia Now, the Dystonia Medical Research Foundation, and the National Spasmodic Dysphonia Association). SF has received honoraria from Lundbeck, Sunovion, Biogen, Acadia, Impel, Acorda, and CereSpir. He has received grant support from Medtronics, Boston Scientific, Biohaven, Impax, Lilly, US World Meds, Sunovion Therapeutics, Vaccinex, Voyager, Jazz Pharmaceuticals, CHDI Foundation, Michael J. Fox Foundation, NIH (U10 NS077366), Parkinson Foundation. He has received royalties from Demos, Blackwell Futura, Springer for textbooks, Uptodate. SN receives grant support from NIH including NS107281 (JP), NS103957 (JP and TU), TR00135609 (HJ), and the Dystonia Medical Research Foundation. JP has received research funding from National Institutes of Health NS075321, NS103957, NS107281, NS092865, U10NS077384, NS097437, U54NS116025, U19 NS110456, AG050263, AG-64937, NS097799, NS075527, ES029524, NS109487, R61 AT010753 (NCATS, NINDS, NIA), Department of Defense (DOD W81XWH-217-1-0393), Michael J Fox Foundation, Barnes-Jewish Hospital Foundation (Elliot Stein Family Fund and Parkinson disease research fund), American Parkinson Disease Association (APDA) Advanced Research Center at Washington University, Greater St. Louis Chapter of the APDA, Paula and Rodger Riney Fund, Jo Oertli Fund, Huntington Disease Society of America, Murphy Fund, and CHDI. I have received honoraria from CHDI, Huntington Disease Study Group, Parkinson Study Group, Beth Israel Hospital (Harvard group), U Pennsylvania, Stanford U. He also is co-director for the Dystonia Coalition, which has received the majority of its support through the NIH (grants NS116025, NS065701 from the National Institutes of Neurological Disorders and Stroke TR 001456 from the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences). JP serves as Director of Medical and Scientific Advisory Committee of the Dystonia Medical Research Foundation, Chair of the Scientific Advisory Committee of the Parkinson Study Group, Chair of the Standards Committee of the Huntington Study Group, member of the Scientific Advisory Board of the APDA, Chair of the Scientific and Publication Committee for ENROLL-HD, and member of the Education Committee of the Huntington Study Group. JP has provided medical legal consultation to Wood, Cooper and Peterson, LLC and to Simmons and Simmons LLP. TB is supported by the German Research Foundation (SFB 936 and FOR 2698), the German federal research ministry (BMBF) through the Dystonia Translational Research and Therapy Consortium (DysTract) (Grant No. 01GM1514A) and the Innovationsausschuss of the Gemeinsamer Bundesausschuss (Translate NAMSE, structural support for the Lübeck Center for Rare Diseases). He receives honoraria from Merz Pharmaceuticals, Allergan and Ipsen Pharma. He is member of the advisory boards of Merz Pharmaceuticals, Allergan and Ipsen Pharma and receives consultancies from Merz Pharmaceuticals and Allergan. ER served on scientific advisory boards for Orkyn, Aguettant, Merz-Pharma; received honoraria for speeches from Orkyn, Aguettant, Merz-Pharma, Everpharma, International Parkinson and Movement disorders Society; received research support from Merz-Pharma, Orkyn, Aguettant, Elivie, Ipsen, Everpharma, Fondation Desmarest, AMADYS, Fonds de Dotation Brou de Laurière, Agence Nationale de la Recherche; received travel grant from Vitalair, PEPS development, Aguettant, Merz-Pharma, Ipsen, Merck, Orkyn, Elivie, Adelia Medical, Dystonia Medical Research Foundation, International Parkinson and Movement disorders Society, European Academy of Neurology, International Association of Parkinsonism and Related Disorders. JJ has received research/training funding from AbbVie Inc; Acadia Pharmaceuticals; Allergan, Inc; Biotek; Cerevel Therapeutics; CHDI Foundation; Dystonia Coalition; Emalex Biosciences, Inc; F. Hoffmann-La Roche Ltd; Huntington Study Group; Medtronic Neuromodulation; Merz Pharmaceuticals; Michael J Fox Foundation for Parkinson Research; National Institutes of Health; Neuraly, Inc.; Neurocrine Biosciences; Parkinsons Foundation; Parkinson Study Group; Prilenia Therapeutics; Revance Therapeutics, Inc; Teva Pharmaceutical Industries Ltd. JJ has served as a consultant for Aeon BioPharma; Nuvelution Pharma, Inc; Teva Pharmaceutical Industries Ltd. JJ has received royalties from Cambridge; Elsevier; Medlink: Neurology; Lippincott Williams and Wilkins; Wiley-Blackwell. Editorial boards: Expert Review of Neurotherapeutics; Medlink; Neurology in Clinical Practice; The Botulinum Journal; PeerJ; Therapeutic Advances in Neurological Disorders; Neurotherapeutics; Toxins; Tremor and Other Hyperkinetic Movements; Journal of Parkinsons Disease; UpToDate. ML has received research funding from the Dystonia Medical Research Foundation and Benign Essential Research Foundation. RB is a member of DSC and associated funding for this project. He is director of Botulinum Toxin Clinic and 45% of his effort is performing botulinum toxin injections. FC has received scholarship money from University of Sydney and Honorary from Abbvie. VF receives a salary from NSW Health, has received unrestricted research grants from the Michael J Fox Foundation, Abbvie and Merz, is on Advisory Boards and/or has received travel grants from Abbvie, Allergan, Cavion, Ipsen, Merz, Praxis, Seqirus, Stada, Teva and UCB, and receives royalties from Health Press Ltd. SPi has received funding through the Dystonia Coalition sub-award to University of New Mexico (U54TR18020). AB has received research funding from Merz Pharmaceutical and Allergan. He has also served as a consultant to Allergan. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Scorr, Factor, Parra, Kaye, Paniello, Norris, Perlmutter, Bäumer, Usnich, Berman, Mailly, Roze, Vidailhet, Jankovic, LeDoux, Barbano, Chang, Fung, Pirio Richardson, Blitzer and Jinnah.)

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal postures, repetitive movements, or both. Research in dystonia has been challenged by several factors. First, dystonia is uncommon. Dystonia is not a single disorder but a family of heterogenous disorders with varied clinical manifestations and different causes. The different subtypes may be seen by providers in different clinical specialties including neurology, ophthalmology, otolaryngology, and others. These issues have made it difficult for any single center to recruit large numbers of subjects with specific types of dystonia for research studies in a timely manner. The Dystonia Coalition is a consortium of investigators that was established to address these challenges. Since 2009, the Dystonia Coalition has encouraged collaboration by engaging 56 sites across North America, Europe, Asia, and Australia. Its emphasis on collaboration has facilitated establishment of international consensus for the definition and classification of all dystonias, diagnostic criteria for specific subtypes of dystonia, standardized evaluation strategies, development of clinimetrically sound measurement tools, and large multicenter studies that document the phenotypic heterogeneity and evolution of specific types of dystonia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kilic-Berkmen, Wright, Perlmutter, Comella, Hallett, Teller, Pirio Richardson, Peterson, Cruchaga, Lungu and Jinnah.)

Objective: To assess the clinical manifestations and predictors of different types of tremors in individuals with different types of isolated dystonia., Methods: Clinical manifestations of tremor were assessed in a multicenter, international cross-sectional, cohort study of 2,362 individuals with all types of isolated dystonia (focal, segmental, multifocal, and generalized) recruited through the Dystonia Coalition., Results: Methodical and standardized assessments of all participants in this cohort revealed the overall prevalence of any type of tremor was 53.3%. The prevalence of dystonic tremor varied from 36.9% to 48.4%, depending on criteria used to define it. To identify the factors associated with tremors in dystonia, the data were analyzed by generalized linear modeling and cluster analyses. Generalized linear modeling indicated 2 of the strongest factors associated with tremor included body region affected by dystonia and recruitment center. Tremor was also associated with severity of dystonia and duration of dystonia, but not with sex or race. The cluster analysis distinguished 8 subgroups within the whole cohort; defined largely by body region with dystonia, and secondarily by other clinical characteristics., Conclusion: The large number of cases evaluated by an international team of movement disorder experts facilitated the dissection of several important factors that influence the apparent prevalence and phenomenology of tremor in dystonia. These results are valuable for understanding the many differences reported in prior studies, and for guiding future studies of the nosology of tremor and dystonia., (© 2020 American Academy of Neurology.)

Schizophrenic patients often do not have the sense that they direct their own movements or author their own thoughts (passivity phenomena). As willing must precede movement to be causal and thus generate the sense of agency, it is possible that the timing between the senses of willing and movement is shortened in schizophrenia. We tested the subjective perception of this time interval in patients with schizophrenia using a method based on Libet's paradigm, in which subjects specify a time W - the time of willing a movement - and a time M - the time that movement occurred. Patients with schizophrenia and healthy volunteers made voluntary movements at times of their own choice while looking at a fast-rotating clock on a computer screen and reported when their movements were willed and made. We recorded surface electromyography to determine the time of actual movement, and electroencephalography to record brain potentials associated with movement. Results showed a significantly reduced interval between the reported M and W in patients with respect to the healthy volunteers ( p < 0.05). Specifically, patients did not report a significant difference in the timing of W at 19 ms prior to movement onset and M at 7.4 ms prior to movement onset ( p > 0.05), while the control group experienced a time W at 100 ms prior to movement onset and this differed significantly from their time M at 19 ms prior to movement onset ( p < 0.01). These results suggest that patients with schizophrenia do have an altered timing of awareness of action - or an impaired judgment of the sequence of events - and that this might be etiologic in the development of the abnormal sense of agency., (Copyright © 2020 Pirio Richardson, Triggiani, Matsuhashi, Voon, Peckham, Nahab, Mari and Hallett.)

Sensorimotor synchronization (SMS) is frequently dependent on coordination of excitatory and inhibitory activity across hemispheres, as well as the cognitive control over environmental distractors. However, the timing (motor planning versus execution) and cortical regions involved in these processes remain actively debated. Functional magnetic resonance imaging data were therefore analyzed from 34 strongly right-handed healthy adults performing a cued (to initiate motor planning) SMS task with either their right or left hand (motor execution phase) based on spatially congruent or incongruent visual stimuli. Behavioral effects of incongruent stimuli were limited to the first stimulus. Functionally, greater activation was observed in left sensorimotor cortex (SMC) and right cerebellar Lobule V for congruent versus incongruent stimuli. A negative blood-oxygen level dependent response, a putative marker of neural inhibition, was present in bilateral SMC, right supplemental motor area (SMA) and bilateral cerebellar Lobule V during the motor planning, but not execution phase. The magnitude of the inhibitory response was greater in right cortical regions and cerebellar Lobule V. Homologue connectivity was associated with inhibitory activity in the right SMA, suggesting that individual differences in intrinsic connectivity may mediate transcallosal inhibition. In summary, results suggest increased inhibition (i.e., greater negative BOLD response) within the right relative to left hemisphere, which was released once motor programs were executed. Both task and intrinsic functional connectivity results highlight a critical role of the left SMA in interhemispheric inhibition and motor planning., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction : Dystonia consists of involuntary movements, abnormal posturing, and pain. In adults, dystonia presents in a particular region of the body and causes significant disability due to pain as well as impairment in activities of daily living and employment. The current gold standard treatment, botulinum toxin (BoNT), has limitations - painful, frequent injections due to 'wearing off' of treatment effect; expense; and expected side effects like swallowing difficulty and weakness. There is a clear therapeutic gap in our current treatment options for dystonia and also a clear need for an effective novel treatment. Testing any novel treatment is complicated because most adults with focal dystonia are treated with BoNT. Areas covered : This review focuses on establishing the need for novel therapeutics. It also suggests potential leads from preclinical studies; and, discusses the issue of clinical trial readiness in the dystonia field. Expert opinion : Identifying a novel therapeutic intervention for dystonia patients faces two major challenges. The first is acknowledging the therapeutic gap that currently exists. Second, shifting some of our research aims in dystonia to clinical trial readiness is imperative if we are to be ready to test novel therapeutic agents.

Background: A challenge confronting the United States is delivery of quality specialty healthcare to citizens living in rural areas., Introduction: The Veterans Administration (VA) developed a large national telehealth network to address 5.2 million rural veterans. New Mexico's Albuquerque VA Neurology Service developed a teleneurology program for their rural veterans. This article analyzes our first 1,100 teleneurology patient visits., Materials and Methods: Veterans living in remote areas of New Mexico, southern Colorado, eastern Arizona, and western Texas were offered follow-up teleneurology care at 16 rural VA community-based outpatient clinics (CBOCs) following an initial evaluation at the Albuquerque VA neurology outpatient clinic. Surveys were sent after all teleneurology visits focused on quality of care, ease of communication, satisfaction, and staff's ability to deliver same quality care as in person. Problems encountered, differences between face-to-face clinics and teleneurology, and cost savings were examined., Results: Regarding the 701 (64%) returned surveys, we found 90% perceived they received good care, 91% felt there was good communication, 88% liked the convenience, and 87% reported they desired to continue teleneurology care. Ninety-six percent reported saving time, money, or both through CBOC visits instead of driving to Albuquerque., Discussion: All providers felt that they could deliver excellent care through teleneurology. We found emergency room visits for neurologic problems was similar for both groups., Conclusions: Our rural veteran patients and neurology staff overwhelmingly found high quality patient care can be delivered via teleneurology for a variety of chronic neurologic problems and was comparable to care delivered in neurology face-to-face clinics.

Background and Purpose: The feasibility, safety, and efficacy of a high-intensity multimodal exercise program (aerobic, strengthening, and balance training) have not been well vetted in persons with Parkinson disease (PD). Thus, the primary aim was to determine whether a high-intensity multimodal exercise boot camp (HIBC) was both feasible and safe in persons with PD. The secondary aim was to determine whether the program would produce greater benefit than a usual care, low-intensity exercise program (UC). An exploratory aim was to determine whether these programs affected putative disease-modifying mechanisms., Methods: Twenty-seven participants (19 men and 8 women) were randomized into 8 weeks of either the HIBC or UC supervised by physical therapists. For feasibility, participation, and meeting, Centers for Disease Control and Prevention (CDC) exercise guidelines were assessed. For safety, adverse events were monitored. For efficacy, the following outcome domains were assessed before and after participation: balance, motor activity, endurance and fatigue, strength, mental health, and quality of life. For disease-modifying mechanisms, circulating brain-derived neurotrophic factor (BDNF) and its genotype, superoxide dismutase, and cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-10) were monitored., Results: The HIBC was better at attaining CDC guidelines (P = 0.013) and spent more minutes in higher-intensity exercise per week (P < 0.001). There were no differences in adverse events (P = 0.419). The HIBC experienced significant improvements in 7/31 outcomes versus 3/31 in the UC arm. BDNF improved significantly for both groups from pre- to posttests (Ps ≤ 0.041) and an improved anti-inflammatory was observed for both groups., Discussion and Conclusions: A high-intensity multimodal exercise boot camp was feasible and safe in persons with PD. Compared with usual care, there were no differences in adverse events. Moreover, the high-intensity multimodal exercise program produced more improvement across more domains than usual care. Our results also suggest a possible link between improvement in outcomes and an improved anti-inflammatory milieu.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A244).

Dystonia, which causes intermittent or sustained abnormal postures and movements, can present in a focal or a generalized manner. In the limbs, focal dystonia can occur in either the upper or lower limbs and may be task-specific causing abnormal motor performance for only a specific task, such as in writer's cramp, runner's dystonia, or musician's dystonia. Focal limb dystonia can be non-task-specific and may, in some circumstances, be associated with parkinsonian disorders. The true prevalence of focal limb dystonia is not known and is likely currently underestimated, leaving a knowledge gap and an opportunity for future research. The pathophysiology of focal limb dystonia shares some commonalities with other dystonias with a loss of inhibition in the central nervous system and a loss of the normal regulation of plasticity, called homeostatic plasticity. Functional imaging studies revealed abnormalities in several anatomical networks that involve the cortex, basal ganglia, and cerebellum. Further studies should focus on distinguishing cause from effect in both physiology and imaging studies to permit focus on most relevant biological correlates of dystonia. There is no specific therapy for the treatment of limb dystonia given the variability in presentation, but off-label botulinum toxin therapy is often applied to focal limb and task-specific dystonia. Various rehabilitation techniques have been applied and rehabilitation interventions may improve outcomes, but small sample size and lack of direct comparisons between methods to evaluate comparative efficacy limit conclusions. Finally, non-invasive and invasive therapeutic modalities have been explored in small studies with design limitations that do not yet clearly provide direction for larger clinical trials that could support new clinical therapies. Given these gaps in our clinical, pathophysiologic, and therapeutic knowledge, we have identified priorities for future research including: the development of diagnostic criteria for limb dystonia, more precise phenotypic characterization and innovative clinical trial design that considers clinical heterogeneity, and limited available number of participants.

Objective: To determine the frequency of medication use in patients with dystonia enrolled in an international biorepository study., Methods: In a cross-sectional analysis, we included 2,026 participants enrolled at 37 sites in the United States, Canada, Europe, and Australia through Project 1 of the Dystonia Coalition, an international biorepository study. The primary aim was to assess the frequency of medication classes recommended for treating patients with dystonia, and the secondary aim was to compare characteristics (disease type, age, sex, duration of disease, comorbid conditions, severity)., Results: Querying the database for the presence of any medication for dystonia used (includes both injectable and oral therapy), we found 73% using medications (n = 1,488) and 27% using no dystonia medications (n = 538). Furthermore, 61% of the total sample used botulinum toxin (BoNT) therapy alone or in combination. Differences were found in medication use patterns by dystonia type, with the lowest oral medication use in focal dystonia and highest use in generalized dystonia; by region, with highest BoNT therapy rate reported in Italy and the lowest in the Northeast region of the United States; and by focal dystonia subtype, with highest BoNT therapy alone in blepharospasm and spasmodic dysphonia (49%) and lowest in other cranial dystonia (32%)., Conclusions: The majority of patients with dystonia enrolled in the Dystonia Coalition Project 1 were using medications to treat their dystonia. Overall, a complex picture of medication use patterns emerged, with factors such as region, disease duration, type of dystonia, disease severity, and psychiatric comorbidities all playing a significant role., (© 2017 American Academy of Neurology.)

Background: Recruitment for clinical trials is a major challenge. Movement disorders, which do not have associated diagnostic laboratory tests, may be especially prone to inaccuracy in coding. Our objective was to evaluate the accuracy of diagnostic codes such as cervical dystonia (CD) and PD in an electronic medical record., Methods: Retrospective chart review was performed to confirm the ICD-9 diagnoses of PD, CD and diabetes mellitus type 2 (DM-2), using published clinical diagnostic criteria (PD, CD) and hemoglobin A1c ≥ 6.5 (DM-2)., Results: 421 charts (n=129, n=142, n=150 for PD, CD and DM-2, respectively) were reviewed. The accuracy rate was different between all diseases examined with an overall p<0.001. In post hoc pairwise comparisons, the accuracy of DM-2 diagnosis by ICD-9 (96.6%) was greater than CD (88.0%) and both greater than PD (55.0%) (p≤0.003)., Conclusions: Using an electronic medical record based screening of clinically diagnosed diseases such as CD may be more accurate than previously thought and may identify potential clinical trial participants even without confirmatory lab tests available., Competing Interests: Financial Disclosures: Funding Sources and Conflict of Interest: The authors declare that there are no conflicts of interest relevant to this work. Financial Disclosures for the previous 12 months: The authors declare that there are no additional disclosures to report.

Objective: This study aims to understand whether the enhanced dPMI, seen in writer's cramp patients previously, extends to other populations of focal dystonia patients (e.g. cervical dystonia) as an endophenotypic marker., Methods: We studied 9 healthy subjects and 9 patients with CD. dPMI was tested by applying conditioning transcranial magnetic stimulation to the left dorsal premotor cortex and then a test pulse to the ipsilateral motor cortex at an interval of 6ms. We also looked at the duration of the cortical silent period (CSP)-a measure of cortical excitability., Results: CD patients had enhanced dPMI at rest (mean 57.0%, SD 16.2) in contrast to healthy volunteers (mean 124.1%, SD 35.7) (p<0.001). CSP latencies (in ms) in CD patients (mean 108.0, SD 33.1) were significantly shorter than in healthy volunteers (mean 159.1, SD 55.2) (p<0.05)., Conclusions: CD patients showed enhanced dPMI in a hand muscle-distant from their affected body part-similar to writer's cramp patients. This enhanced inhibition was independent of disease severity and neck posture. This suggests that enhanced dPMI may be an endophenotypic marker of dystonia., Significance: The abnormal dorsal premotor-motor connection in cervical dystonia is a potential novel and important avenue for therapeutic targeting., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Dystonia is characterized by abnormal posturing due to sustained muscle contraction, which leads to pain and significant disability. New therapeutic targets are needed in this disorder. The objective of this randomized, sham-controlled, blinded exploratory study is to identify a specific motor system target for non-invasive neuromodulation and to evaluate this target in terms of safety and tolerability in the cervical dystonia (CD) population. Eight CD subjects were given 15-minute sessions of low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (MC), dorsal premotor cortex (dPM), supplementary motor area (SMA), anterior cingulate cortex (ACC) and a sham condition with each session separated by at least two days. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score was rated in a blinded fashion immediately pre- and post-intervention. Secondary outcomes included physiology and tolerability ratings. The mean change in TWSTRS severity score by site was 0.25 ± 1.7 (ACC), -2.9 ± 3.4 (dPM), -3.0 ± 4.8 (MC), -0.5 ± 1.1 (SHAM), and -1.5 ± 3.2 (SMA) with negative numbers indicating improvement in symptom control. TWSTRS scores decreased from Session 1 (15.1 ± 5.1) to Session 5 (11.0 ± 7.6). The treatment was tolerable and safe. Physiology data were acquired on 6 of 8 subjects and showed no change over time. These results suggest rTMS can modulate CD symptoms. Both dPM and MC are areas to be targeted in further rTMS studies. The improvement in TWSTRS scores over time with multiple rTMS sessions deserves further evaluation.

The authors hypothesized that a deficient premotor-motor inhibitory network contributes to the unwanted involuntary movements in dystonia. The authors studied nine controls and nine patients with writer's cramp (WC). Dorsal premotor-motor cortical inhibition (dPMI) was tested by applying conditioning transcranial magnetic stimulation (TMS) to the dorsal premotor cortex and then a test pulse to the ipsilateral motor cortex at an interval of 6 ms. The authors used an H-reflex in flexor carpi radialis paired with TMS over the premotor cortex to assess for spinal cord excitability change. Finally, the authors interrupted a choice reaction time task with TMS over dorsal premotor cortex to assess performance in a nondystonic task. The results showed that WC patients exhibited dPMI at rest (88.5%, the ratio of conditioned to unconditioned test pulse), in contrast to controls, who did not show dPMI (109.6%) (P = 0.0198). This difference between patients and controls persisted during contraction (100% vs. 112%) and pen-holding (95.6% vs. 111%). The H-reflex in the arm was not modulated by the premotor cortex stimulation. The WC patients made more errors, and the error rate improved with TMS over the premotor cortex. These results suggest that abnormal premotor-motor interactions may play a role in the pathophysiology of focal dystonia. The dPMI was not modulated by task in either group, but was constantly greater in the patients. The significance of the increased inhibition is likely to be compensatory. It appears to be a robust finding and, in combination with other features, could be further explored as a biomarker., (© 2014 International Parkinson and Movement Disorder Society.)

Background: The prevalence of Parkinson disease (PD) varies by geographic location and ethnicity, but has never been studied among the Navajo., Methods: Period prevalence was calculated using the number of people diagnosed with PD in the Shiprock Service Unit Indian Health Service database during 1995-1999, 2000-2004, and 2005-2009 as the numerator, and the number seen for any reason as the denominator. Age-standardized rates were calculated using the 2000 US population., Results: During 2005-2009, 126 people were seen with PD (crude prevalence = 203.7/100,000 population). The age-adjusted rate was 335.9 (95% C. I. 277.8-394.0) overall, 438.5 (95% C.I. 336.5-540.5) in men and 259.7 (95% C.I. 192.8-326.7; p = 0.004) in women. The adjusted rate increased with age: 788.8 (95% C.I. 652.0-925.7) for age 40 and above to 1964.9 (95% C.I. 1613.7-2316.1) for age 60 and above. Adjusted rates were 246.6 (95% C.I. 187.2-306.0) in 1995-1999 and 284.7 (95% C.I. 227.0-342.4) in 2000-2004., Conclusion: Parkinson disease appears common among the Navajo. Estimates increased with age and time, and were higher in men. In-person interviews are needed to confirm these estimates, and to determine incidence, quality of care, and risk factors for PD among the Navajo.

In the motor system, one specific movement is generated, and, simultaneously, other possible movements are suppressed; a process called surround inhibition. Focal hand dystonia (FHD) is a movement disorder characterized by a loss of surround inhibition. In order to explain the deficit in surround inhibition induced by volitional movement in FHD patients, we examined the inhibitory circuit activated by afferent stimulation at "long latency". We studied 14 patients (age 48.9+/-13.2 years, 3 females, 11 males) with idiopathic task-related FHD. To measure long-latency afferent inhibition (LAI), transcranial magnetic stimulation (TMS) was applied to the affected hemisphere for FHD patients and to the dominant hemisphere for 17 healthy volunteers. Motor evoked potentials (MEPs) were recorded over abductor digiti minimi (ADM) and first dorsal interosseous (FDI) during rest and during voluntary phasic flexion of the second digit. Subjects were given electrical stimulation to either their fifth digit (homotopic to ADM, heterotopic to FDI) or their second digit (heterotopic to FDI, homotopic to ADM) at twice sensory perceptual threshold 180 ms prior to TMS application. Additionally, F-waves were recorded from ADM. At rest, we found a significant decrease in ADM MEP amplitudes with both homotopic and heterotopic stimulation compared to the corresponding non-stimulated trials. There was a trend toward less LAI in FHD patients. During movement, LAI was significantly decreased in both patients and controls. There was no significant group effect. The results for LAI in FDI were similar to those from ADM. F-wave area in ADM was greater during movement for both homo- and heterotopic stimulation. We found no difference in F-wave area between patients and healthy volunteers. Our results indicate that LAI is unlikely to be an underlying mechanism that contributes to the generation of normal surround inhibition in healthy volunteers or in the disruption of surround inhibition in FHD.

We describe a case of psychogenic palatal tremor. The diagnosis was supported by clinical criteria and neurophysiological testing, including frequency analysis and jerk-locked back-averaging. We discuss the differential diagnosis of palatal tremor as well as the role of neurophysiological testing in the diagnosis of psychogenic movement disorders., (Copyright (c) 2005 Movement Disorder Society.)

During individual finger movement, two opposite phenomena occur at the level of the central nervous system that could affect other intrinsic hand muscle representations, unintentional co-activation, and surround inhibition (SI). At rest, excitability in the motor cortex (M1) is inhibited at about 20 ms after electric stimulation of a peripheral nerve [short-latency afferent inhibition (SAI)]. We sought to determine whether SAI changes during selective index finger movement. Effects were measured by the response to transcranial magnetic stimulation in two functionally distinct target muscles of the hand [abductor digiti minimi muscle (ADM), first dorsal interosseus muscle (FDI)]. An increase in SAI in the ADM during index finger movement compared to at rest could help explain the genesis of SI. Electrical stimulation was applied to either the little finger (homotopic for ADM, heterotopic for FDI) or the index finger (heterotopic for ADM, homotopic for FDI). During index finger movement, homotopic SAI was present only in the ADM, and the effect of peripheral stimulation was greater when there was less co-activation. Heterotopic SAI found at rest disappeared with movement. We conclude that during movement, homotopic SAI on the muscle in the surround of the intended movement may contribute to SI.

In a retrospective chart review, we identified 35 patients with medically refractory epilepsy (MRE) who had been converted from polypharmacy to monotherapy and maintained on monotherapy for at least 12 months. None of the 35 patients had worsening of their seizure frequency after the conversion to monotherapy. Fourteen of the 35 patients (40%) became seizure-free. Nine of 35 patients (26%) had a 50% reduction in seizure frequency. Five of 35 patients (14%) had a 75% reduction in seizure frequency. Twenty-eight (80%) of 35 patients participated in a quality-of-life questionnaire. Quality of life was rated as better on monotherapy as compared with polypharmacy in a number of domains: memory loss, concern over medication long-term effects, difficulty in taking the medications, trouble with leisure time activities, and overall state of health. This improvement reached statistical significance. Conversion to monotherapy in patients with MRE may be successful in achieving a reduction in seizure frequency and an improvement in quality-of-life parameters. A prospective, randomized trial is necessary to validate these findings.