Journal of Clinical Movement Disorders is the first fully open access clinical journal dedicated to the study of the etiology, diagnosis, evaluation and ...

Isolated focal dystonias are a group of disorders with diverse symptomatology but unknown pathophysiology. Although recent neuroimaging studies demonstrated regional changes in brain connectivity, it remains unclear whether focal dystonia may be considered a disorder of abnormal networks. We examined topology as well as the global and local features of large-scale functional brain networks across different forms of isolated focal dystonia, including patients with task-specific (TSD) and nontask-specific (NTSD) dystonias. Compared with healthy participants, all patients showed altered network architecture characterized by abnormal expansion or shrinkage of neural communities, such as breakdown of basal ganglia–cerebellar community, loss of a pivotal region of information transfer (hub) in the premotor cortex, and pronounced connectivity reduction within the sensorimotor and frontoparietal regions. TSD were further characterized by significant connectivity changes in the primary sensorimotor and inferior parietal cortices and abnormal hub formation in insula and superior temporal cortex, whereas NTSD exhibited abnormal strength and number of regional connections. We suggest that isolated focal dystonias likely represent a disorder of large-scale functional networks, where abnormal regional interactions contribute to network-wide functional alterations and may underline the pathophysiology of isolated focal dystonia. Distinct symptomatology in TSD and NTSD may be linked to disorder-specific network aberrations.

Therapeutic strategies in dystonia have evolved considerably in the past few decades. Three major treatment modalities include oral medications, botulinum toxin injections and surgical therapies, particularly deep brain stimulation. Although there has been a tremendous interest in the later two modalities, there are relatively few recent reviews of oral treatment. We review the medical treatment of dystonia, focusing on three major neurotransmitter systems: cholinergic, GABAergic and dopaminergic. We also provide a practical guide to medication selection, therapeutic strategy and unmet needs.

Dystonic storm is a frightening hyperkinetic movement disorder emergency. Marked, rapid exacerbation of dystonia requires prompt intervention and admission to the intensive care unit. Clinical features of dystonic storm include fever, tachycardia, tachypnea, hypertension, sweating and autonomic instability, often progressing to bulbar dysfunction with dysarthria, dysphagia and respiratory failure. It is critical to recognize early and differentiate dystonic storm from other hyperkinetic movement disorder emergencies. Dystonic storm usually occurs in patients with known dystonia, such as DYT1 dystonia, Wilson’s disease and dystonic cerebral palsy. Triggers such as infection or medication adjustment are present in about one-third of all events. Due to the significant morbidity and mortality of this disorder, we propose a management algorithm that divides decision making into two periods: the first 24 h, and the next 2–4 weeks. During the first 24 h, supportive therapy should be initiated, and appropriate patients should be identified early as candidates for pallidal deep brain stimulation or intrathecal baclofen. Management in the next 2–4 weeks aims at symptomatic dystonia control and supportive therapies.

Spinal-generated movement disorders (SGMDs) include spinal segmental myoclonus, propriospinal myoclonus, orthostatic tremor, secondary paroxysmal dyskinesias, stiff person syndrome and its variants, movements in brain death, and painful legs-moving toes syndrome. In this paper, we review the relevant anatomy and physiology of SGMDs, characterize and demonstrate their clinical features, and present a practical approach to the diagnosis and management of these unusual disorders.

Background: As gene‐targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial‐ready cohorts is limited.Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD‐linked variants; (2) provide harmonized and quality‐controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD.Methods: We conducted a worldwide, systematic online survey to collect individual‐level data on individuals with PD‐linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ‐1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed.Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ‐1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published.Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD‐linked variants; (2) provide harmonized and quality‐controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene‐targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.