Cause Of Dystonia Research Articles

Preterm birth is associated with dystonic features and reduced cortical parvalbumin immunoreactivity in mice.

Preterm birth is a common cause of dystonia. Though dystonia is often associated with striatal dysfunction after neonatal brain injury, cortical dysfunction may best predict dystonia following preterm birth. Furthermore, abnormal sensorimotor cortex inhibition is associated with genetic and idiopathic dystonias. To investigate cortical dysfunction and dystonia following preterm birth, we developed a new model of preterm birth in mice. We induced preterm birth in C57BL/6J mice at embryonic day 18.3, ~24 h early. Leg adduction variability and amplitude, metrics we have shown distinguish between dystonia from spasticity during gait in people with CP, were quantified from gait videos of mice. Parvalbumin-positive interneurons, the largest population of cortical inhibitory interneurons, were quantified in the sensorimotor cortex and striatum. Mice born preterm demonstrate increased leg adduction amplitude and variability during gait, suggestive of clinically observed dystonic gait features. Mice born preterm also demonstrate fewer parvalbumin-positive interneurons and reduced parvalbumin immunoreactivity in the sensorimotor cortex, but not the striatum, suggesting dysfunction of cortical inhibition. These data may suggest an association between cortical dysfunction and dystonic gait features following preterm birth. We propose that our novel mouse model of preterm birth can be used to study this association. Mouse models of true preterm birth are valuable for studying clinical complications of prematurity. Mice born preterm demonstrate increased leg adduction amplitude and variability during gait, suggestive of clinically observed dystonic gait features. Mice born preterm demonstrate fewer parvalbumin-positive interneurons and reduced parvalbumin immunoreactivity in the sensorimotor cortex, suggesting dysfunction of cortical inhibition. Mice born preterm do not demonstrate changes in parvalbumin immunoreactivity in the striatum. Cortical dysfunction may be associated with dystonic gait features following preterm birth.

Role of Botulinum Toxin in Treatment of Secondary Dystonia: A Case Series and Overview of Literature.

Dystonia can present in primary and secondary forms, depending on co-occurring symptoms and syndromic associations. In contrast to primary dystonia, secondary forms of dystonia are often associated with lesions in the putamen or globus pallidus. Such disorders are commonly neurodegenerative or neurometabolic conditions which produce varied neurologic as well as systemic manifestations other than dystonia. Chemo-denervation with botulinum toxin has been successfully used for focal or segmental dystonia. However, studies evaluating the effect of BoNT therapy on patients with secondary dystonia are sparse, given the heterogeneity in etiology and presentation. We present a series of patients with secondary dystonia who were managed with botulinum toxin therapy. Patients included in this series had a confirmed neurometabolic cause of dystonia. A total of 14 patients, with ages ranging from 17 to 36 years, with disorders including Wilson's disease, pantothenate kinase-associated neurodegeneration (PKAN), Niemann-Pick disease type C (NPC), glutaric aciduria type 1, Sanfilippo syndrome (Mucopolysaccharidosis Type IIIb), and GM2 gangliosidosis (Sandhoff disease) are presented. Most patients experienced a mild to moderate improvement in treated dystonia with benefits ranging from 6 to 12 weeks, with the median length of the benefits lasting approximately eight weeks, without any significant adverse effects. Although the secondary causes of dystonia are complex and diverse, our presented data and the available reports of the use of botulinum toxin support the conclusion that chemo-denervation plays an important role in symptom alleviation.

Genetic analysis of IRF2BPL in a Taiwanese dystonia cohort: The genotype and phenotype correlation.

IRF2BPL mutation has been associated with a rare neurodevelopmental disorder with abnormal movements, including dystonia. However, the role of IRF2BPL in dystonia remains elusive. We aimed to investigate IRF2BPL mutations in a Taiwanese dystonia cohort. A total of 300 unrelated patients with molecularly unassigned isolated (n = 256) or combined dystonia (n = 44) were enrolled between January 2015 and July 2023. The IRF2BPL variants were analyzed based on whole exome sequencing. The in silico prediction of the identified potential pathogenic variant was performed to predict its pathogenicity. We also compared the clinical and genetic features to previous literature reports. We identified one adolescent patient carrying a de novo heterozygous pathogenic variant of IRF2BPL, c.379C>T (p.Gln127Ter), who presented with generalized dystonia, developmental regression, and epilepsy (0.33% of our dystonia cohort). This variant resides within the polyglutamine (poly Q) domain before the first PEST sequence block of the IRF2BPL protein, remarkably truncating the protein structure. Combined with other patients with IRF2BPL mutations in the literature (n = 60), patients with variants in the poly Q domain have a higher rate of nonsense mutations (p < 0.001) and epilepsy (p = 0.008) than patients with variants in other domains. Furthermore, as our index patient, carriers with substitutions before the first PEST sequence block have significantly older age of onset (p < 0.01) and higher non-epilepsy symptoms, including generalized dystonia (p = 0.003), and ataxia (p = 0.003). IRF2BPL mutation is a rare cause of dystonia in our population. Mutations in different domains of IRF2BPL exhibit different phenotypes.

The role of genetics in the treatment of dystonia with deep brain stimulation: Systematic review and Meta-analysis

BackgroundDystonia is a movement disorder characterized by sustained or intermittent muscle contractions that lead to involuntary postures or repetitive movements. Genetic mutations are being increasingly recognized as a cause of dystonia. Deep brain stimulation (DBS) is one of the limited treatment options available. However, there are varying reports on its efficacy in genetic dystonias. This systematic review of the characteristics of genetic dystonias treated with DBS and their outcomes aims to aid in the evaluation of eligibility for such treatment. MethodsWe performed a PUBMED search of all papers related to genetic dystonias and DBS up until April 2022. In addition to performing a systematic review, we also performed a meta-analysis to assess the role of the mutation on DBS response. We included cases that had a confirmed genetic mutation and DBS along with pre-and post-operative BFMDRS. ResultsNinety-one reports met our inclusion criteria and from them, 235 cases were analyzed. Based on our analysis DYT-TOR1A dystonia had the best evidence for DBS response and Rapid-Onset Dystonia Parkinsonism was among the least responsive to DBS. ConclusionWhile our report supports the role of genetics in DBS selection and response, it is limited by the rarity of the individual genetic conditions, the reliance on case reports and case series, and the limited ability to obtain genetic testing on a large scale in real-time as opposed to retrospectively as in many cases.

Dissecting genetic architecture of rare dystonia: genetic, molecular and clinical insights

BackgroundDystonia is one of the most common movement disorders. To date, the genetic causes of dystonia in populations of European descent have been extensively studied. However, other populations, particularly those...

Broadening the clinical spectrum: molecular mechanisms and new phenotypes of ANO3-dystonia.

Anoctamin 3 (ANO3) belongs to a family of transmembrane proteins that form phospholipid scramblases and ion channels. A large number of ANO3 variants were identified as the cause of craniocervical dystonia, but the underlying pathogenic mechanisms remain obscure. It was suggested that ANO3 variants may dysregulate intracellular Ca2+ signalling, as variants in other Ca2+ regulating proteins like hippocalcin were also identified as a cause of dystonia. In this study, we conducted a comprehensive evaluation of the clinical, radiological and molecular characteristics of four individuals from four families who carried heterozygous variants in ANO3. The median age at follow-up was 6.6 years (ranging from 3.8 to 8.7 years). Three individuals presented with hypotonia and motor developmental delay. Two patients exhibited generalized progressive dystonia, while one patient presented with paroxysmal dystonia. Additionally, another patient exhibited early dyskinetic encephalopathy. One patient underwent bipallidal deep brain stimulation (DBS) and showed a mild but noteworthy response, while another patient is currently being considered for DBS treatment. Neuroimaging analysis of brain MRI studies did not reveal any specific abnormalities. The molecular spectrum included two novel ANO3 variants (V561L and S116L) and two previously reported ANO3 variants (A599D and S651N). As anoctamins are suggested to affect intracellular Ca2+ signals, we compared Ca2+ signalling and activation of ion channels in cells expressing wild-type ANO3 and cells expressing anoctamin variants. Novel V561L and S116L variants were compared with previously reported A599D and S651N variants and with wild-type ANO3 expressed in fibroblasts isolated from patients or when overexpressed in HEK293 cells. We identified ANO3 as a Ca2+-activated phospholipid scramblase that also conducts ions. Impaired Ca2+ signalling and compromised activation of Ca2+-dependent K+ channels were detected in cells expressing ANO3 variants. In the brain striatal cells of affected patients, impaired activation of KCa3.1 channels due to compromised Ca2+ signals may lead to depolarized membrane voltage and neuronal hyperexcitability and may also lead to reduced cellular viability, as shown in the present study. In conclusion, our study reveals the association between ANO3 variants and paroxysmal dystonia, representing the first reported link between these variants and this specific dystonic phenotype. We demonstrate that ANO3 functions as a Ca2+-activated phospholipid scramblase and ion channel; cells expressing ANO3 variants exhibit impaired Ca2+ signalling and compromised activation of Ca2+-dependent K+ channels. These findings provide a mechanism for the observed clinical manifestations and highlight the importance of ANO3 for neuronal excitability and cellular viability.

Novel Genetic and Phenotypic Expansion in GOSR2-Related Progressive Myoclonus Epilepsy.

Biallelic variants in the Golgi SNAP receptor complex member 2 gene (GOSR2) have been reported in progressive myoclonus epilepsy with neurodegeneration. Typical clinical features include ataxia and areflexia during early childhood, followed by seizures, scoliosis, dysarthria, and myoclonus. Here, we report two novel patients from unrelated families with a GOSR2-related disorder and novel genetic and clinical findings. The first patient, a male compound heterozygous for the GOSR2 splice site variant c.336+1G>A and the novel c.364G>A,p.Glu122Lys missense variant showed global developmental delay and seizures at the age of 2 years, followed by myoclonus at the age of 8 years with partial response to clonazepam. The second patient, a female homozygous for the GOSR2 founder variant p.Gly144Trp, showed only mild fine motor developmental delay and generalized tonic-clonic seizures triggered by infections during adolescence, with seizure remission on levetiracetam. The associated movement disorder progressed atypically slowly during adolescence compared to its usual speed, from initial intention tremor and myoclonus to ataxia, hyporeflexia, dysmetria, and dystonia. These findings expand the genotype-phenotype spectrum of GOSR2-related disorders and suggest that GOSR2 should be included in the consideration of monogenetic causes of dystonia, global developmental delay, and seizures.

A Child with KMT2B-Related Acute-Onset Dystonia: Clinical Pointers to Molecular Diagnosis

Abstract Dystonia is common extrapyramidal presentation of neurological problems in childhood. The causes could range from infectious, autoimmune, drug-induced, or genetic in origin. Genetic causes are rare in origin but could masquerade the common causes. Recently, KMT2B-related dystonia has been identified as a common genetic cause of dystonia in childhood. We present a case of a 3.5-year-old with 18 months of follow-up, who was diagnosed with KMT2B-related dystonia and managed with antidystonia drugs to an acceptable level where she could perform her day-to-day work with ease. Here, we highlight certain clinical pointers of the disease and the need of special genetic test in diagnosing such cases. We also tabulated the three previously reported Indian cases and compared their parameter with ours.

Parkinson's Disease with Intolerable Painful Dystonia: Classification and Therapeutic Choices of Pain in Parkinson' Disease

Disabling painful dystonia is one of the most burdensome symptoms that a patient with Parkinson's disease (PD) experiences. How do we treat disabling painful dystonia in PD? In this review, classification and mechanisms of pain and their management in PD especially for dystonia-related pain are described. Moreover, painful bilateral dystonic foot spasm is also an important development to be considered in the early stage of the disease. Recent classification of pain in PD does not involve this symptom, partly because this symptom is relatively unobserved due to early initiation of treatment in PD patients. Treatment options for dystonia-related pain are diverse and are necessarily contingent on the cause of dystonia in PD. Reducing L-dopa and other drugs is useful for patients with on-dystonia and dyskinesia-related pain in PD. Increasing L-dopa and other drugs are better for early morning dystonia and off-period dystonia-related pain in PD. Finally, as severe and troublesome painful dystonia is often challenging to treat, continuous dopaminergic stimulation such as treatment with levodopa-carbidopa intestinal gel is considered effective for these symptoms.

A Clinical and Integrated Genetic Study of Isolated and Combined Dystonia in Taiwan

Dystonia is a clinically and genetically heterogeneous movement disorder. However, genetic causes of dystonia remain largely unknown in Asian subjects. To address this, we applied an integrated two-step approach that included gene dosage analysis and a next-generation sequencing panel containing 72 known genes causative for dystonia and related movement disorders to 318 Taiwanese patients with isolated or combined dystonia. Whole-genome sequencing was performed for one multiplex family with no known causative variant. The panel confirmed the genetic diagnosis in 40 probands (12.6%). A genetic diagnosis was more likely with juvenile onset compared with adult onset (24.2% vs 10.8%; P=0.03) and those with combined features, especially with myoclonus, compared with isolated dystonia (35.3% vs 10.5%; P=0.004). The most common causative genes were SGCE followed by GCH1, TH, CACNA1B, PRRT2, MR1, CIZ1, PLA2G6, and PRKN. Genetic causes were identified from single cases in TOR1A, TUBB4A, THAP1, ATP1A3, ANO3, GNAL, KMT2B, SLC6A3, ADCY5, CYP27A1, PANK2, C19orf12, and SPG11. The whole-genome sequencing analysis identified a novel intragenic deletion in OPHN1 in a multiplex family with X-linked dystonia and intellectual delay. Our findings delineate the genetic architecture and clinical spectrum of dystonia-causing pathogenic variants in an Asian population.

Genetic diagnosis of basal ganglia disease in childhood.

To correlate clinical, radiological, and biochemical features with genetic findings in children with bilateral basal ganglia lesions of unknown aetiology, and propose a diagnostic algorithm for early recognition. Children with basal ganglia disease were recruited in a 2-year prospective multicentre study for clinical, biomarker, and genetic studies. Radiological pattern recognition was examined by hierarchical clustering analysis. We identified 22 genetic conditions in 30 out of 62 paediatric patients (37 males, 25females; mean age at onset 2y, SD 3; range 0-10y; mean age at assessment 11y, range 1-25y) through gene panels (n=11), whole-exome sequencing (n=13), and mitochondrial DNA (mtDNA) sequencing (n=6). Genetic aetiologies included mitochondrial diseases (57%), Aicardi-Goutières syndrome (20%), and monogenic causes of dystonia and/or epilepsy (17%) mimicking Leigh syndrome. Radiological abnormalities included T2-hyperintense lesions (n=26) and lesions caused by calcium or manganese mineralization (n=9). Three clusters were identified: the pallidal, neostriatal, and striatal, plus the last including mtDNA defects in the oxidative phosphorylation system with prominent brain atrophy. Mitochondrial biomarkers showed poor sensitivity and specificity in children with mitochondrial disease, whereas interferon signature was observed in all patients with patients with Aicardi-Goutières syndrome. Combined whole-exome and mtDNA sequencing allowed the identification of several genetic conditions affecting basal ganglia metabolism. We propose a diagnostic algorithm which prioritizes early use of next-generation sequencing on the basis of three clusters of basal ganglia lesions.

Collagen VI Regulates Motor Circuit Plasticity and Motor Performance by Cannabinoid Modulation.

Collagen VI is a key component of muscle basement membranes, and genetic variants can cause monogenic muscular dystrophies. Conversely, human genetic studies recently implicated collagen VI in central nervous system function, with variants causing the movement disorder dystonia. To elucidate the neurophysiological role of collagen VI, we generated mice with a truncation of the dystonia-related collagen α3 VI (COL6A3) C-terminal domain (CTD). These Col6a3CTT mice showed a recessive dystonia-like phenotype in both sexes. We found that COL6A3 interacts with the cannabinoid receptor 1 (CB1R) complex in a CTD-dependent manner. Col6a3CTT mice of both sexes have impaired homeostasis of excitatory input to the basal pontine nuclei (BPN), a motor control hub with dense COL6A3 expression, consistent with deficient endocannabinoid (eCB) signaling. Aberrant synaptic input in the BPN was normalized by a CB1R agonist, and motor performance in Col6a3CTT mice of both sexes was improved by CB1R agonist treatment. Our findings identify a readily therapeutically addressable synaptic mechanism for motor control.SIGNIFICANCE STATEMENT Dystonia is a movement disorder characterized by involuntary movements. We previously identified genetic variants affecting a specific domain of the COL6A3 protein as a cause of dystonia. Here, we created mice lacking the affected domain and observed an analogous movement disorder. Using a protein interaction screen, we found that the affected COL6A3 domain mediates an interaction with the cannabinoid receptor 1 (CB1R). Concordantly, our COL6A3-deficient mice showed a deficit in synaptic plasticity linked to a deficit in cannabinoid signaling. Pharmacological cannabinoid augmentation rescued the motor impairment of the mice. Thus, cannabinoid augmentation could be a promising avenue for treating dystonia, and we have identified a possible molecular mechanism mediating this.

A Novel Heterozygous ANO3 Mutation in a Child Presenting Tremor with Dystonia and Review of the Literature

AbstractMutations in ANO3 have recently been identified as an autosomal dominant cause of dystonia (dystonia-24). Since then, the phenotypic spectrum has also been extended in children. Here, we reported a case of a 10-year-old Turkish girl child patient with a novel variant (NM_001313726: c.221dupA, p.Tyr74*), who exhibited tremor with mild dystonia. This report expands the phenotype caused by ANO3 variants and reveals an essential clinical aspect for patients and medical staff.

Novel insights into the pathogenesis of DYT1 dystonia from induced patient-derived neurons.

Novel insights into the pathogenesis of DYT1 dystonia from induced patient-derived neurons.

An unusual presentation of encephalitis which mimicked generalised tetanus

Movement disorders are frequent mimickers of more severe neurological presentations, whenever it is diagnosed one should suspect a central nervous system infection as an underlying cause. A 11 year old girl presented in casuality with intermittent generalised muscle spasm, clear sensorium, trismus and risus sardonicus. Initially managed as a case of tetanus, rapid resolution of spasms made suspicion of encephalitis as underlying cause of dystonia which mimicked tetanus. Blood investigation and CSF analysis were normal. CECT brain showed hyper dense lesions bilateral temporal lobes suggestive of viral encephalitis. Child was managed with intravenous acyclovir and dexamethasone after which child improved considerably. Acute dystonia is a close mimicker of tetanus. Any patient presenting with new onset movement disorder should be investigated for central nervous system infection even though it has been reported as a rare cause for the same.

Movement disorders in 2020: clinical trials, genetic discoveries, and COVID-19

Movement disorders in 2020: clinical trials, genetic discoveries, and COVID-19

Mutational spectrum of GNAL, THAP1 and TOR1A genes in isolated dystonia: study in a population from Spain and systematic literature review.

We aimed to investigate the prevalence of TOR1A, GNAL and THAP1 variants as the cause of dystonia in a cohort of Spanish patients with isolated dystonia and in the literature. A population of 2028 subjects (including 1053 patients with different subtypes of isolated dystonia and 975 healthy controls) from southern and central Spain was included. The genes TOR1A, THAP1 and GNAL were screened using a combination of high-resolution melting analysis and direct DNA resequencing. In addition, an extensive literature search to identify original articles (published before 10 August 2020) reporting mutations in TOR1A, THAP1 or GNAL associated to dystonia was performed. Pathogenic or likely pathogenic variants in TOR1A, THAP1 and GNAL were identified in 0.48%, 0.57% and 0.29% of our patients, respectively. Five patients carried the variation p.Glu303del in TOR1A. A very rare variant in GNAL (p.Ser238Asn) was found as a putative risk factor for dystonia. In the literature, variations in TOR1A, THAP1 and GNAL accounted for about 6%, 1.8% and 1.1% of published dystonia patients, respectively. There is a different genetic contribution to dystonia of these three genes in our patients (about 1.3% of patients) and in the literature (about 3.6% of patients), probably due the high proportion of adult-onset cases in our cohort. As regards age at onset, site of dystonia onset, and final distribution, in our population there is a clear differentiation between DYT-TOR1A and DYT-GNAL, with DYT-THAP1 likely to be an intermediate phenotype.

Editorial introductions

Current Opinion in Neurology was launched in 1988. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of neurology is divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Stéphane LehéricyStéphane LehéricyStéphane Lehéricy is Professor of Neuroradiology in the Salpêtrière hospital (PUPH), France. He has completed his PhD in basic neuroscience studying the pathophysiology of Alzheimer's disease (Yves Agid, Inserm, Paris, France), a post-doc in functional neuroimaging at SHFJ-CEA (Denis Le Bihan, Orsay, France). He spent about three years at the Centre for Magnetic Resonance Research, University of Minnesota, Minneapolis, USA (Kamil Ugurbil) studying basal ganglia function using high field MRI. Together with Pr Marie Vidailhet, Prof. Lehericy is co-head of the research team ‘Movement, Investigations and Therapeutics’ at Paris Brain Institute (ICM – Institut Cerveau Moelle, France). He also heads the Centre for NeuroImaging Research (CENIR), the ICM imaging platform and the Department of Neuroradiology of the Salpêtrière hospital. Dr Lehericy's scientific interest is in the study of the physiology of motor control and pathophysiology of movement disorders (focus on Parkinson's disease), neuroimaging and data analysis. His focus is on the functional organisation of the human motor system. He has contributed to the understanding of the functional and anatomical circuitry of the basal ganglia and of network dysfunction in movement disorders and particularly Parkinson's disease using multimodal MRI. Nutan SharmaNutan SharmaNutan Sharma, MD PhD, established the Dystonia Center for comprehensive care of patients with dystonia with sites at both Massachusetts General Hospital and Brigham and Woman's Hospital. The Center integrates information obtained from the systematic examination and treatment of patients with research regarding the pathophysiology of dystonia. Dr Sharma is the Principal Investigator of the Clinical Core of an NIH-funded P01 grant, “Molecular Etiology of Early Onset Torsion Dystonia’. The P01 supports: (1) systematic clinical evaluation as part of a longitudinal study of the natural history of dystonia; (2) collection of families with dystonia, obtaining both DNA and systematic clinical examination data, to help identify as yet unidentified dystonia causing genes. This work has led to the identification of mutations in GNAL as a cause of dystonia and contributed to the characterization of the phenotypic spectrum and response to treatment associated with KMT2B and ADCY5 mutations; (3) fMRI studies to evaluate white matter microstructure in those with focal dystonia. The genetic studies are in collaboration with Dr Laurie Ozelius. Dr Sharma is also a member of the Collaborative Center for the study of X-linked Dystonia-Parkinsonism (XDP). The XDP Center serves to fund research and medical care for those with XDP. The objectives of the Center include: (1) Identification and enrollment of patients with XDP and their families, including DNA isolation, generation of lymphoblast, fibroblast and iPS cell lines and (2) laboratory research that is conducted both at MGH and by other investigators, at various institutions throughout the world, who are invited to apply for funding that is then reviewed by a scientific advisory board. Dr Sharma established a natural history study protocol, with quantitative, cost-effective bedside measures that provide sensitivity and specificity in monitoring the course of XDP. Dr Sharma received her MD and PhD from the State University of New York at Stony Brook, USA. After completing a neurology residency at Yale University, USA, she completed a fellowship in movement disorders at Massachusetts General Hospital. She has received many grants for her work from research organizations including the NIH, the National Parkinson's Foundation and the Congressionally Directed Medical Research Program.

ANO3 Mutations in Chinese Dystonia: A Genetic Screening Study Using Next-Generation Sequencing.

Background: Dystonia-24 (DYT24) is a monogenic autosomal dominant dystonia caused by mutations in the gene ANO3, which has shown phenotypic and genotypic heterogeneity according to previous reports.Objective: To screen and identify ANO3 mutations in a cohort of patients with dystonia in China and to expand the spectrum of DYT24.Methods: This study screened ANO3 mutations in 187 Chinese dystonia patients using next-generation sequencing (NGS). In silico investigations were conducted in detected ANO3 variants and co-segregation analysis was carried out if applicable. The effects of identified variants were classified according to the standards and guidelines of the American College of Medical Genetics and Genomics (ACMG).Results: Four different variants were identified in four unrelated dystonia patients, including three missense variants [c.1789G>C (p.V600L), c.182A>C (p.E61A), c.787A>G (p.M263V)] and one splice site change (c.1714-3T>C). The novel missense mutation c.1798G>C (p.V600L), identified in a teenaged girl with generalized dystonia, showed high pathogenicity and was classified as “likely pathogenic” according to ACMG guidelines. Of note, she responded well to deep brain stimulation.Conclusion: Our study helps expand the mutational and clinical spectrum of DYT24 due to ANO3 mutations by further reporting four variants. Rare ANO3 variants appear to represent an uncommon cause of dystonia in China.

Mental health outcomes in children with acquired dystonia after basal ganglia stroke and associations with cognitive and motor outcomes

ABSTRACT Pediatric arterial ischemic stroke involving the basal ganglia and/or thalamus is one of the most common causes of dystonia in children. Dystonia is a movement disorder in which excessive, involuntary muscle contractions result in twisting or repetitive movements, and abnormal posturing. The basal ganglia have been implicated in mood functioning and difficulties in these domains have been noted in adults with dystonia, yet little is currently known about these outcomes in children with dystonia following stroke. The objective of this study was to explore mental health outcomes in children with basal ganglia stroke and to determine whether children with post-stroke dystonia experience additional mental health difficulties. We also examined associations between mental health, cognitive, and motor outcomes. Participants were 75 children with stroke involving the basal ganglia and/or thalamus (dystonia n = 24, no dystonia n = 51). Results supported the presence of greater levels of anxiety and depression symptoms in children with post-stroke dystonia after stroke relative to those with similar patterns of stroke, but no dystonia. There were no significant associations between motor, cognitive, and mental health outcomes in children with post-stroke dystonia aside from depression and behavioral regulation. Motor and cognitive outcome were significantly associated in the stroke only group. These findings suggest maladaptive reorganization after stroke may contribute to motor, cognitive, and mental health outcomes in children with post-stroke dystonia, and that these outcomes are independent from one another.