Search

Deep brain stimulation (DBS) of the internal globus pallidus (GPi) is a recognized treatment for medication‐refractory dystonia. Problems in executive functions and social cognition can be part of dystonia phenotypes. The impact of pallidal DBS on cognition appears limited, but not all cognitive domains have been investigated yet. In the present study, we compare cognition before and after GPi DBS. Seventeen patients with dystonia of various aetiology completed pre‐ and post‐DBS assessment (mean age 51 years; range 20–70 years). Neuropsychological assessment covered intelligence, verbal memory, attention and processing speed, executive functioning, social cognition, language and a depression questionnaire. Pre‐DBS scores were compared with a healthy control group matched for age, gender and education, or with normative data. Patients were of average intelligence but performed significantly poorer than healthy peers on tests for planning and for information processing speed. Otherwise, they were cognitively unimpaired, including social cognition. DBS did not change the baseline neuropsychological scores. We confirmed previous reports of executive dysfunctions in adult dystonia patients with no significant influence of DBS on cognitive functioning in these patients. Pre‐DBS neuropsychological assessments appear useful as they support clinicians in counselling their patients. Decisions about post‐DBS neuropsychological evaluations should be made on a case‐by‐case basis. [ABSTRACT FROM AUTHOR]

Paediatric movement disorders (PMDs) comprise a large group of disorders (tics, myoclonus, tremor, dystonia, chorea, Parkinsonism, ataxia), often with mixed phenotypes. Determination of the underlying aetiology can be difficult given the broad differential diagnosis and the complexity of the genotype–phenotype relationships. This can make the diagnostic process time‐consuming and difficult. In this overview, we present a diagnostic approach for PMDs, with emphasis on genetic causes. This approach can serve as a framework to lead the clinician through the diagnostic process in eight consecutive steps, including recognition of the different movement disorders, identification of a clinical syndrome, consideration of acquired causes, genetic testing including next‐generation sequencing, post‐sequencing phenotyping, and interpretation of test results. The aim of this approach is to increase the recognition and diagnostic yield in PMDs. What this paper adds: An up‐to‐date description and diagnostic framework for testing of paediatric movement disorders is presented.The framework helps to determine which patients will benefit from next‐generation sequencing. What this paper adds: An up‐to‐date description and diagnostic framework for testing of paediatric movement disorders is presented.The framework helps to determine which patients will benefit from next‐generation sequencing. [ABSTRACT FROM AUTHOR]

Stereotactic lesioning of the bilateral globus pallidus (GPi) was one of the first surgical treatments for medication‐refractory dystonia but has largely been abandoned in clinical practice after the introduction of deep brain stimulation (DBS). However, some patients with dystonia are not eligible for DBS. Therefore, we reviewed the efficacy, safety, and sustainability of bilateral pallidotomy by conducting a systematic review of individual patient data (IPD). Guidelines of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses and IPD were followed. In May 2020, Medline, Embase, Web of Science, and Cochrane Library were searched for studies reporting on outcome of bilateral pallidotomy for dystonia. If available, IPD were collected. In this systematic review, 100 patients from 33 articles were evaluated. Adverse events were reported in 20 patients (20%), of which 8 were permanent (8%). Pre‐and postoperative Burke‐Fahn‐Marsden Dystonia Rating Movement Scale scores were available for 53 patients. A clinically relevant improvement (>20%) of this score was found in 42 of 53 patients (79%). Twenty‐five patients with status dystonicus (SD) were described. In all but 2 the SD resolved after bilateral pallidotomy. Seven patients experienced a relapse of SD. Median‐reported follow‐up was 12 months (n = 83; range: 2–180 months). Based on the current literature, bilateral pallidotomy is an effective and relatively safe procedure for certain types of dystonia, particularly in medication‐refractory SD. Although due to publication bias the underreporting of negative outcomes is very likely, bilateral pallidotomy is a reasonable alternative to DBS in selected dystonia patients. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: DYT6 dystonia can have an unpredictable clinical course and the result of deep brain stimulation (DBS) of the internal part of the globus pallidus (GPi) is known to be less robust than in other forms of autosomal dominant dystonia. Patients who had previous stereotactic surgery with insufficient clinical benefit form a particular challenge with very limited other treatment options available. Case Report: A pediatric DYT6 patient unexpectedly deteriorated to status dystonicus 1 year after GPi DBS implantation with good initial clinical response. After repositioning the DBS electrodes the status dystonicus resolved. Discussion: This case study demonstrates that medication-resistant status dystonicus in DYT6 dystonia can be reversed by relocation of pallidal electrodes. This case highlights that repositioning of DBS electrodes may be considered in patients with status dystonicus, especially when the electrode position is not optimal, even after an initial clinical response to DBS. [ABSTRACT FROM AUTHOR]

Introduction: Dystonia-deafness syndrome is a distinct clinical presentation within the dystonia-spectrum. Although several genetic and acquired causes have been reported, etiology remains unknown in the majority of patients.Objectives: To describe two patients with dystonia-deafness syndrome due to a beta-actin gene mutation.Methods: We report on disease course, genetic testing, and management of 2 patients, mother and daughter, presenting with dystonia-deafness syndrome.Results: After exclusion of known dystonia-deafness syndrome causes, whole-exome sequencing revealed a beta-actin gene mutation (p.Arg183Trp) in both patients. Although beta-actin gene mutations are generally associated with developmental Baraitser-Winter syndrome, dystonia-deafness syndrome has been reported once in identical twin brothers. Bilateral GPi-DBS led to a significant decrease of dystonia and regain of independency in our patients.Conclusion: The p.Arg183Trp mutation in the beta-actin gene is associated with the clinical presentation of dystonia-deafness syndrome, even with only minimal or no developmental abnormalities of Baraitser-Winter syndrome. GPi-DBS should be considered to ameliorate the invalidating dystonia in these patients. © 2016 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Ramsay Hunt syndrome (progressive myoclonus ataxia) is a descriptive diagnosis characterized by myoclonus, ataxia, and infrequent seizures. Often the etiology cannot be determined. Recently, a mutation in the GOSR2 gene (c.430G>T, p.Gly144Trp) was reported in 6 patients with childhood-onset progressive ataxia and myoclonus. Methods We evaluated 5 patients with cortical myoclonus, ataxia, and areflexia. Results All 5 patients had the same homozygous mutation in GOSR2. Here we present their clinical and neurophysiological data. Our patients (aged 7-26 years) all originated from the northern Netherlands and showed a remarkably homogeneous phenotype. Myoclonus and ataxia were relentlessly progressive over the years. Electromyography revealed signs of sensory neuronopathy or anterior horn cell involvement, or both, in all patients with absent reflexes. Conclusions Based on the presented phenotype, we would advise movement disorder specialists to consider mutation analysis of GOSR2 in patients with Ramsay Hunt syndrome, especially when they also have areflexia. © 2013 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

The article presents a case study of a young Dutch boy with hyperkinetic movements that closely resembles chorea. The historical background of the condition of the boy is discussed. It is concluded that hyperkinetic movements in a young person with GOSR2 mutation can mimic chorea which has been classified by the panel expert in a video presented.

Objective: Dystonic storm is a rare but life threatening condition. DBS or radiofrequency lesioning have been used in severe cases, however, there is no agreement on the optimal target. Patients who had already previous basal ganglia surgery pose a particular challenge with limited treatment options available. Methods: An 11-year-old boy with pallidal DBS for treatment of DYT-6 positive generalized dystonia since 2 years developed severe dystonic storm. After implantation of DBS electrodes at age 9 his condition had improved for more than 2 years. Upon the occurrence of dystonic storm, re-programing of DBS could not ameliorate the severe status dystonicus. Only sedation with high dose benzodiazepines, baclofen, gabapentin and trihexyphenidyl resulted in transient improvement. Results: The BMFDR motor score on admission was 138. MRI imaging showed positioning of the DBS electrodes in the globus pallidus internus (GPi), however, more lateral and posterior than at the usual target. It was decided to reimplant the GPi electrodes and to implant thalamic Vim electrodes in addition. Early postoperatively this resulted in marked and immediate improvement of dystonic storm (BMFDRS 100,5). At 12-month follow-up, there was remarkable benefit and the patient could walk and attend school without medication. Conclusion: Dystonic storm may develop despite periods of beneficial response to pallidal DBS for several years. If electrodes are no optimally placed in the posteroventral lateral GPi, repositioning should be considered, which might not only abate status dystonicus, but also provide lasting benefits. [ABSTRACT FROM AUTHOR]

Cerebral palsy (CP) is the most common cause of motor disability in children. The largest group of children with CP present with spasticity. Dystonia is estimated to be present in approximately 15% of children with CP, referred to as dyskinetic CP. Still, dystonia in CP remains underdiagnosed. Dystonia and spasticity can occur together in a subgroup of children with CP as well. Dystonia is characterized by fluctuating hypertonia and involuntary movement and postures. Dystonia in children with CP can interfere with motor function, caregiving and comfort. It is important to recognize dystonia in children with CP as specific treatment is indicated. In this paper we describe three cases of children with dystonia in CP and we review the pharmacological treatment options for dystonia in CP and the surgical options including intrathecal baclofen pump and deep brain stimulation.

Objectives: The majority of people with suspected genetic dystonia remain undiagnosed after maximal investigation, implying that a number of causative genes have not yet been recognized. We aimed to investigate this paucity of diagnoses., Methods: We undertook weighted burden analysis of whole-exome sequencing (WES) data from 138 individuals with unresolved generalized dystonia of suspected genetic etiology, followed by additional case-finding from international databases, first for the gene implicated by the burden analysis (VPS16), and then for other functionally related genes. Electron microscopy was performed on patient-derived cells., Results: Analysis revealed a significant burden for VPS16 (Fisher's exact test p value, 6.9 × 10 9 ). VPS16 encodes a subunit of the homotypic fusion and vacuole protein sorting (HOPS) complex, which plays a key role in autophagosome-lysosome fusion. A total of 18 individuals harboring heterozygous loss-of-function VPS16 variants, and one with a microdeletion, were identified. These individuals experienced early onset progressive dystonia with predominant cervical, bulbar, orofacial, and upper limb involvement. Some patients had a more complex phenotype with additional neuropsychiatric and/or developmental comorbidities. We also identified biallelic loss-of-function variants in VPS41, another HOPS-complex encoding gene, in an individual with infantile-onset generalized dystonia. Electron microscopy of patient-derived lymphocytes and fibroblasts from both patients with VPS16 and VPS41 showed vacuolar abnormalities suggestive of impaired lysosomal function., Interpretation: Our study strongly supports a role for HOPS complex dysfunction in the pathogenesis of dystonia, although variants in different subunits display different phenotypic and inheritance characteristics. ANN NEUROL 2020;88:867-877., (© 2020 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Deep brain stimulation (DBS) is a treatment which uses high-frequency electric stimulation to suppress pathological brain activity. DBS has been applied for over 30 years now, particularly in patients with severe movement disorders, such as Parkinson's disease, dystonia and tremor. Although there is clearly scientific evidence for the effectiveness of DBS in these three movement disorders, the effect size of the treatment remains limited. Furthermore, DBS is not curative and can only be applied in a select subset of patients. In this article, we discuss the key indications and contraindications for DBS, and the outcomes achieved when it is applied in the aforementioned movement disorders. We discuss the most notable controversies and new developments in the field of deep brain stimulation, in order to offer referrers and fellow healthcare professionals an accessible introduction to this mode of therapy.

Background: Genetic disorders causing dystonia show great heterogeneity. Recent studies have suggested that next-generation sequencing techniques such as gene panel analysis can be effective in diagnosing heterogeneous conditions. The objective of this study was to investigate whether dystonia patients with a suspected genetic cause could benefit from the use of gene panel analysis., Methods: In this post hoc study, we describe gene panel analysis results of 61 dystonia patients (mean age, 31 years; 72% young onset) in our tertiary referral center. The panel covered 94 dystonia-associated genes. As comparison with a historic cohort was not possible because of the rapidly growing list of dystonia genes, we compared the diagnostic workup with and without gene panel analysis in the same patients. The workup without gene panel analysis (control group) included theoretical diagnostic strategies formulated by independent experts in the field, based on detailed case descriptions. The primary outcome measure was diagnostic yield; secondary measures were cost and duration of diagnostic workup., Results: Workup with gene panel analysis led to a confirmed molecular diagnosis in 14.8%, versus 7.4% in the control group (P = 0.096). In the control group, on average 3 genes/case were requested. The mean costs were lower in the gene panel analysis group (€1822/case) than in the controls (€2660/case). The duration of the workup was considerably shorter with gene panel analysis (28 vs 102 days)., Conclusions: Gene panel analysis facilitates molecular diagnosis in complex cases of dystonia, with a good diagnostic yield (14.8%), a quicker diagnostic workup, and lower costs, representing a major improvement for patients and their families. © 2016 International Parkinson and Movement Disorder Society., (© 2017 International Parkinson and Movement Disorder Society.)