Moving across disorders: A cross-sectional study of cognition in early onset ataxia and dystonia.

BACKGROUND: Early onset ataxia (EOA) and Early Onset Dystonia (EOD) are movement disorders developing in young people (age <25 per definition). These disorders result from dysfunctional networks involving the cerebellum and basal ganglia. As these structures are also important for cognition, cognitive deficits can be expected in EOA and EOD. EOA and EOD sometimes co-occur, but in those cases the predominant phenotype is determining. A pending question is whether predominantly EOA and EOD have different profiles of cognitive impairment. OBJECTIVES: We investigated whether cognitive functions were impaired in patients with either predominant EOA or predominant EOD and whether cognitive profiles differed between both patient groups. METHODS: The sample consisted of 26 EOA and 26 EOD patients with varying etiology but similar duration and severity of the disorder. Patient samples were compared to a group of 26 healthy controls, all matched on age and gender. All participants underwent neuropsychological testing for verbal intelligence, memory, working memory, attention/cognitive speed, executive functions, emotion recognition and language. RESULTS: EOA and EOD patients both performed significantly worse than healthy controls on tests of verbal intelligence, working memory and executive functions. Additionally, attention/cognitive speed and emotion recognition were impaired in the EOA group. Compared to EOD, EOA patients performed worse on attention/cognitive speed and verbal intelligence. CONCLUSIONS: Our results show overall similar profiles of cognitive deficits in both patient groups, but deficits were more pronounced in the patients with EOA. This suggests that more severe cognitive impairment is related to more severe cerebellar network dysfunction.

Negative Myoclonus: Neurophysiological Study and Clinical Impact in Progressive Myoclonus Ataxia.

INTRODUCTION: Negative myoclonus (NM) is an involuntary movement caused by a sudden interruption of muscular activity, resulting in gait problems and falls. OBJECTIVE: To establish frequency, clinical impact, and neurophysiology of NM in progressive myoclonus ataxia (PMA) patients. METHODS: Clinical, neurophysiological, and genetic data of 14 PMA individuals from University Medical Centre Groningen (UMCG) Expertise Center Movement Disorder Groningen were retrospectively collected. Neurophysiological examination included video-electromyography-accelerometry assessment in all patients and electroencephalography (EEG) examination in 13 individuals. Jerk-locked (or silent period-locked) back-averaging and cortico-muscular coherence (CMC) analysis aided the classification of myoclonus. RESULTS: NM was present in 6 (NM+) and absent in 8 (NM-) PMA patients. NM+ individuals have more frequent falls (100% vs. 37.5%) and higher scores on the Gross Motor Function Classification System (GMFCS) (4.3 ±0.74 vs. 2.5 ±1.2) than NM- individuals. Genetic background of NM+ included GOSR2 and SEMA6B, while that of NM- included ATM, KCNC3, NUS1, STPBN2, and GOSR2. NM was frequently preceded by positive myoclonus (PM) and silent-period length was between 88 and 194 ms. EEG epileptiform discharges were associated with NM in 2 cases. PM was classified as cortical in 5 NM+ and 2 NM- through EEG inspection, jerk-locked back-averaging, or CMC analysis. DISCUSSION: Neurophysiological examination is crucial for detecting NM that could be missed on clinical examination due to a preceding PM. Evidence points to a cortical origin of NM, an association with more severe motor phenotype, and suggests the presence of genetic disorders causing either a PMA or progressive myoclonus epilepsy, rather than pure PMA phenotype. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Efficacy of Hypnosis and Catalepsy Induction in Functional Neurological Disorders.

BACKGROUND: Patients with Functional Neurological Disorder (FND) experience complex patterns of motor and/or sensory symptoms. Treatment studies of psychological interventions are promising but limited. OBJECTIVES: The aim of the current pilot study is to investigate the effect of treatment consisting of a combination of hypnosis and catalepsy induction on FND symptom severity. METHODS: A within-subject waiting list-control design was used with 46 patients diagnosed with FND. The treatment consisted of 10 sessions. The primary outcome measure was FND symptom severity (The Psychogenic Movement Disorder Rating Scale; PMDRS). The secondary outcome measures were psychological distress and quality of life. RESULTS: The repeated measures (RM) ANOVA for the PMDRS as outcome measure revealed a significant effect for time with a large effect size (η2 = 0.679). Pairwise comparisons indicated that the effect of time in the treatment period was significant for the measure of FND symptom severity, whereas the waiting list period was not. The effect remained stable even at 8 weeks post treatment. As for the additional measurement, general psychological distress and quality of life, no statistically significant differences between individual time points were found. CONCLUSIONS: This pilot study showed that eight sessions of treatment consisting of a combination of hypnosis and catalepsy induction was effective in reducing FND symptom severity. Some explanations and limitations are provided in the paper as well as several avenues of future research.

Global Perceptions and Utilization of Clinical Neurophysiology in Movement Disorders.

BACKGROUND: Clinical neurophysiology (CNP) involves the use of neurophysiological techniques to make an accurate clinical diagnosis, to quantify the severity, and to measure the treatment response. Despite several studies showing CNP to be a useful diagnostic tool in Movement Disorders (MD), its more widespread utilization in clinical practice has been limited. OBJECTIVES: To better understand the current availability, global perceptions, and challenges for implementation of diagnostic CNP in the clinical practice of MD. METHODS: The International Parkinson and Movement Disorders Society (IPMDS) formed a Task Force on CNP. The Task Force distributed an online survey via email to all the members of the IPMDS between August 5 and 30, 2021. Descriptive statistics were used for analysis of the survey results. Some results are presented by IPMDS geographical sections namely PanAmerican (PAS), European (ES), African (AFR), Asian and Oceanian (AOS). RESULTS: Four hundred and ninety-one IPMDS members (52% males), from 196 countries, responded. The majority of responders from the AFR (65%) and PAS (63%) sections had no formal training in diagnostic CNP (40% for AOS and 37% for ES). The most commonly used techniques are electroencephalography (EEG) (72%) followed by surface EMG (71%). The majority of responders think that CNP is somewhat valuable or very valuable in the assessment of MD. All the sections identified "lack of training" as one of the biggest challenges for diagnostic CNP studies in MD. CONCLUSIONS: CNP is perceived to be a useful diagnostic tool in MD. Several challenges were identified that prevent widespread utilization of CNP in MD.

Moving on with (social) cognition in idiopathic cervical dystonia.

OBJECTIVE: Cervical dystonia (CD) is a movement disorder characterized by involuntary muscle contractions causing sustained twisting movements and abnormal postures of the neck and head. Assumed affected neuronal regions are the cortico-striatal-thalamo-cortical circuits, which are also involved in cognitive functioning. Indeed, impairments in different cognitive domains have been found in CD patients. However, to date studies have only investigated a limited range of cognitive functions within the same sample. In particular, social cognition (SC) is often missing from study designs. Hence, we aimed to evaluate a broad range of cognitive functions including SC in CD patients. METHOD: In the present study 20 idiopathic CD patients and 40 age-, gender-, and IQ-matched healthy controls (HCs) were assessed with tests for non-SC (verbal memory, psychomotor speed, and executive functions) as well as for SC (emotion recognition, Theory of Mind (ToM), and empathy). RESULTS: CD patients scored on average significantly lower than HC on tests for non-SC, but did not show impairments on any of the tests for SC. CONCLUSIONS: The current study showed impairments in non-SC in CD, but intact social cognitive functions. These results underline the importance of recognizing non-motor symptoms in idiopathic CD patients, but emphasize a focus on identifying strengths and weaknesses in cognitive functioning as these influence daily life activities.

A Critical Appraisal of the Whack-a-Mole and Swivel Chair Signs in the Diagnosis of Functional Movement Disorders.

BACKGROUND: The demonstration of positive signs during neurological examination is a cornerstone of the diagnosis of functional movement disorders, however, the available data supporting the diagnostic value of some of these signs is limited. OBJECTIVES: To determine the diagnostic value (sensitivity and specificity) of the "whack-a-mole" (WAM) and "swivel chair" (SC) tests in patients with functional movement disorders (FMD). METHODS: We enrolled patients with functional and organic movements in the WAM test if they exhibited tremor, dystonia, myoclonus, chorea, or tics. For the SC test, patients with a gait disorder as their primary impairment were recruited. Two blinded movement disorder specialists rated the presence of these signs in edited videos. RESULTS: Inclusion criteria were met by 42 patients with FMD and 65 patients with organic movement disorders. Both tests demonstrated high specificity (means, 78% and 96%), but their sensitivity was low (means, 52% and 37%). Interobserver agreement for the WAM sign was 0.77 in the FMD group, against 0.28 in patients with organic movement disorders, whereas Movement Disorders Clinical Practice for Review Only for the SC sign was 0.69 in both groups. CONCLUSIONS: The present study indicates that physicians must be cautious in the application and interpretation of these clinical signs in the diagnosis of functional movement disorders, and they should be carefully considered and used as necessary.

Deep brain stimulation in dystonia: The added value of neuropsychological assessments.

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.

The Muddle of Myoclonus: Many Guises, 2 Disciplines, Consensus Needed.

Myoclonus is often approached in different ways by epileptologists and movement disorder specialists, leading to confusion in the literature. Multiplicity and inconsistency over the past 2 centuries resulted in a lack of precision and ambiguity of the terminology. We show that this is a current problem in which one phenomenon has been described with many terms and vice versa. Of more importance, we discuss the conceptualization of myoclonus from perspectives of both fields and focus on the borderland that exists, especially in the spectrum of cortical and epileptic myoclonus. By giving 2 examples, we illustrate the conundrum: the spectrum of progressive myoclonus epilepsies and progressive myoclonic ataxias and "cortical tremor" observed in familial cortical myoclonic tremor with epilepsy or familial adult myoclonic epilepsy. We attempt to facilitate to bridge these subspecialties and form the base for a uniform understanding to take this issue forward toward future classifications, discussions, and scientific research.

Early onset ataxia with comorbid myoclonus and epilepsy: A disease spectrum with shared molecular pathways and cortico-thalamo-cerebellar network involvement.

OBJECTIVES: Early onset ataxia (EOA) concerns a heterogeneous disease group, often presenting with other comorbid phenotypes such as myoclonus and epilepsy. Due to genetic and phenotypic heterogeneity, it can be difficult to identify the underlying gene defect from the clinical symptoms. The pathological mechanisms underlying comorbid EOA phenotypes remain largely unknown. The aim of this study is to investigate the key pathological mechanisms in EOA with myoclonus and/or epilepsy. METHODS: For 154 EOA-genes we investigated (1) the associated phenotype (2) reported anatomical neuroimaging abnormalities, and (3) functionally enriched biological pathways through in silico analysis. We assessed the validity of our in silico results by outcome comparison to a clinical EOA-cohort (80 patients, 31 genes). RESULTS: EOA associated gene mutations cause a spectrum of disorders, including myoclonic and epileptic phenotypes. Cerebellar imaging abnormalities were observed in 73-86% (cohort and in silico respectively) of EOA-genes independently of phenotypic comorbidity. EOA phenotypes with comorbid myoclonus and myoclonus/epilepsy were specifically associated with abnormalities in the cerebello-thalamo-cortical network. EOA, myoclonus and epilepsy genes shared enriched pathways involved in neurotransmission and neurodevelopment both in the in silico and clinical genes. EOA gene subgroups with myoclonus and epilepsy showed specific enrichment for lysosomal and lipid processes. CONCLUSIONS: The investigated EOA phenotypes revealed predominantly cerebellar abnormalities, with thalamo-cortical abnormalities in the mixed phenotypes, suggesting anatomical network involvement in EOA pathogenesis. The studied phenotypes exhibit a shared biomolecular pathogenesis, with some specific phenotype-dependent pathways. Mutations in EOA, epilepsy and myoclonus associated genes can all cause heterogeneous ataxia phenotypes, which supports exome sequencing with a movement disorder panel over conventional single gene panel testing in the clinical setting.

New developments in diagnostics and treatment of adult-onset focal dystonia.

PURPOSE OF REVIEW: The aim of this review is to showcase the recent developments in the field of diagnosis and treatment of adult-onset focal dystonia. RECENT FINDINGS: Accurate phenotyping of focal dystonia is essential in the process of finding an underlying cause, including acquired, genetic, and idiopathic causes. Motor symptoms as well as the associated nonmotor symptoms and their detrimental impact on quality of life have received increased interest over the last years. The diagnostic process is complicated by the steadily increasing numbers of newly discovered genes associated with dystonia. Recent efforts have been aimed at further developing recommendations and algorithms to aid in diagnosis and in navigating the use of diagnostic tools. In terms of treatment, research on DBS is advancing towards a better understanding of the most effective stimulation locations within the globus pallidus. Moreover, with the introduction of the LFP-recording devices, the search continues for an accurate electrophysiological biomarker for dystonia. SUMMARY: Accurate phenotyping and (sub)classification of patients with dystonia is important for improving diagnosis, subsequent treatment effect and population-based study outcomes in research. Medical practitioners should be attentive to the presence of nonmotor symptoms in dystonia.

Muscular and kinematic features in speed skaters indicate a task-specific dystonia.

OBJECTIVE: Skater's cramp is a movement disorder in speed skaters. We investigated whether affected skaters matched the disease profile of task-specific dystonia, specifically whether there was evidence of maladaptive muscle activity occurring simultaneously with aberrant movements (jerking). We further examined different skating intensities, positing no change would be more indicative of task-specific dystonia. METHODS: We analyzed video, kinematic and muscle activity in 14 affected skaters. We measured the angular velocity and electromyographic activity of normalized speed skating strokes using one dimensional statistical non-parametric mapping. Skaters were matched with comparably skilled controls, and filled out a bespoke clinical questionnaire. RESULTS: Skaters' impacted leg showed over-activation in the peroneus longus, tibialis anterior and gastrocnemius that coincided with higher foot movement compared to their healthy leg and controls. This pattern persisted regardless of skating intensity. Clinical features indicated it was task-specific and painless with common trigger factors including stress, equipment change, and falling. CONCLUSIONS: We showed aberrant muscular and kinematic activity in a movement disorder in speed skaters indicative of task-specific dystonia. SIGNIFICANCE: Understanding skater's cramp as a task-specific dystonia could reduce the damage that misdiagnosis and unsuccessful invasive operations have caused. Our quantitative method has value in testing future treatment efficacy.

Functional neurological disorder is a feminist issue.

Functional neurological disorder (FND) is a common and disabling disorder, often misunderstood by clinicians. Although viewed sceptically by some, FND is a diagnosis that can be made accurately, based on positive clinical signs, with clinical features that have remained stable for over 100 years. Despite some progress in the last decade, people with FND continue to suffer subtle and overt forms of discrimination by clinicians, researchers and the public. There is abundant evidence that disorders perceived as primarily affecting women are neglected in healthcare and medical research, and the course of FND mirrors this neglect. We outline the reasons why FND is a feminist issue, incorporating historical and contemporary clinical, research and social perspectives. We call for parity for FND in medical education, research and clinical service development so that people affected by FND can receive the care they need.

Isolated Cervical Dystonia: Diagnosis and Classification.

This document presents a consensus on the diagnosis and classification of isolated cervical dystonia (iCD) with a review of proposed terminology. The International Parkinson and Movement Disorder Society Dystonia Study Group convened a panel of experts to review the main clinical and diagnostic issues related to iCD and to arrive at a consensus on diagnostic criteria and classification. These criteria are intended for use in clinical research, but also may be used to guide clinical practice. The benchmark is expert clinical observation and evaluation. The criteria aim to systematize the use of terminology as well as the diagnostic process, to make it reproducible across centers and applicable by expert and non-expert clinicians. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations, which are incorporated into the current criteria. Three iCD presentations are described in some detail: idiopathic (focal or segmental) iCD, genetic iCD, and acquired iCD. The relationship between iCD and isolated head tremor is also reviewed. Recognition of idiopathic iCD has two levels of certainty, definite or probable, supported by specific diagnostic criteria. Although a probable diagnosis is appropriate for clinical practice, a higher diagnostic level may be required for specific research studies. The consensus retains elements proven valuable in previous criteria and omits aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of iCD expands, these criteria will need continuous revision to accommodate new advances. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Early Onset Dystonia: Complaints about Executive Functioning, Depression and Anxiety.

Early Onset Dystonia (EOD) is thought to result from basal ganglia dysfunction, structures also involved in non-motor functions, like regulation of behavior, mood and anxiety. Problems in these domains have been found in proxy-reports but not yet in self-reports of EOD patients. The main questions are whether proxy-reports differ from those of patients and how problems relate to everyday social functioning. Subjective complaints about executive problems (BRIEF) and symptoms of depression and anxiety (CBCL) were obtained through a cross-sectional questionnaire study conducted on 45 EOD patients. Scores were in the normal range in patients and proxies. Proxy-rated behavior regulation was correlated with the estimated number of friends and quality of relations. Proxy-reported scores of depression correlated with the quality of relations and were higher than self-reports of adolescent/young adult patients. EOD patients and proxies do not seem to experience problematic regulation of behavior, mood and anxiety. Still, our study revealed two important aspects: (1) all measures were related to the estimated quality of relations with others, relating questionnaires to everyday social functioning; (2) proxies reported more symptoms of depression than patients. This may indicate overestimation by proxies or higher sensitivity of proxies to these symptoms, implying underestimation of problems by patients.

Gut Microbiome Composition in Dystonia Patients.

Dystonia is a movement disorder in which patients have involuntary abnormal movements or postures. Non-motor symptoms, such as psychiatric symptoms, sleep problems and fatigue, are common. We hypothesise that the gut microbiome might play a role in the pathophysiology of the (non-)motor symptoms in dystonia via the gut-brain axis. This exploratory study investigates the composition of the gut microbiome in dystonia patients compared to healthy controls. Furthermore, the abundance of neuro-active metabolic pathways, which might be implicated in the (non-)motor symptoms, was investigated. We performed both metagenomic and 16S rRNA sequencing on the stool samples of three subtypes of dystonia (27 cervical dystonia, 20 dopa-responsive dystonia and 24 myoclonus-dystonia patients) and 25 controls. While microbiome alpha and beta diversity was not different between dystonia patients and controls, dystonia patients had higher abundances of Ruminococcus torques and Dorea formicigenerans, and a lower abundance of Butyrivibrio crossotus compared to controls. For those with dystonia, non-motor symptoms and the levels of neurotransmitters in plasma explained the variance in the gut microbiome composition. Several neuro-active metabolic pathways, especially tryptophan degradation, were less abundant in the dystonia patients compared to controls. This suggest that the gut-brain axis might be involved in the pathophysiology of dystonia. Further studies are necessary to confirm our preliminary findings.

A Screening Tool to Quickly Identify Movement Disorders in Patients with Inborn Errors of Metabolism.

BACKGROUND: Movement disorders are frequent in patients with inborn errors of metabolism (IEMs) but poorly recognized, particularly by nonmovement disorder specialists. We propose an easy-to-use clinical screening tool to help recognize movement disorders. OBJECTIVE: The aim is to develop a user-friendly rapid screening tool for nonmovement disorder specialists to detect moderate and severe movement disorders in patients aged ≥4 years with IEMs. METHODS: Videos of 55 patients with different IEMs were scored by experienced movement disorder specialists (n = 12). Inter-rater agreements were determined on the presence and subtype of the movement disorder. Based on ranking and consensus, items were chosen to be incorporated into the screening tool. RESULTS: A movement disorder was rated as present in 80% of the patients, with a moderate inter-rater agreement (κ =0.420, P < 0.001) on the presence of a movement disorder. When considering only moderate and severe movement disorders, the inter-rater agreement increased to almost perfect (κ = 0.900, P < 0.001). Dystonia was most frequently scored (27.3%) as the dominant phenotype. Treatment was mainly suggested for patients with moderate or severe movement disorders. Walking, observations of the arms, and drawing a spiral were found to be the most informative tasks and were included in the screening tool. CONCLUSIONS: We designed a screening tool to recognize movement disorders in patients with IEMs. We propose that this screening tool can contribute to select patients who should be referred to a movement disorder specialist for further evaluation and, if necessary, treatment of the movement disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.