Dystonic Symptoms Research Articles

Dysphagia and Muscle Weakness Secondary to Botulinum Toxin Type A Treatment of Cervical Dystonia: A Drug Class Analysis of Prescribing Information.

The first-line management of cervical dystonia (CD) symptoms is intramuscular injection of botulinum toxin type A (BoNTA). However, a comparison of safety among BoNTAs is difficult because, per regulatory authorities, units of BoNTA activity are not interchangeable. Dysphagia and muscle weakness are widely considered two key adverse events to monitor closely in the treatment of CD. This integrated analysis compared the safety of BoNTAs approved for CD in the US by evaluating relationships between the incidence of dysphagia and muscle weakness in prescribing information and the core neurotoxin content. Coefficients The coefficients of determination (R2) and trendlines were estimated via regression-based lines of best fit. Adverse drug reaction (ADR) rates were strongly correlated with core neurotoxin amounts for conventional BoNTAs (slope coefficients: dysphagia = 0.048, R2 = 0.74; muscle weakness = 0.096, R2 = 0.82). The published ADR rates at approved doses for conventional BoNTAs were higher compared with DaxibotulinumtoxinA (DAXI; DAXXIFY®, Revance Therapeutics, Inc., Nashville, TN, USA) by core neurotoxin content. The use of a core neurotoxin amount was found to be an effective method for comparing the safety of BoNTA products. Current clinical trials suggest that DAXI, a novel BoNTA formulation, provides a potentially wider safety margin compared with other approved BoNTAs for CD. The lower amount of core neurotoxin administered at approved doses compared with conventional BoNTAs may explain low on-target ADRs like muscle weakness, whereas reduced diffusion from the injection site is thought to be responsible for low off-target ADRs like dysphagia.

Striatal cholinergic transmission in an inducible transgenic mouse model of paroxysmal non-kinesiogenic dyskinesia

Altered interaction between striatonigral dopaminergic (DA) inputs and local acetylcholine (ACh) in striatum has long been hypothesized to play a central role in the pathophysiology of dystonia and dyskinesia. Indeed, previous research using several genetic mouse models of human isolated dystonia identified a shared endophenotype with paradoxical excitation of striatal cholinergic interneuron (ChIs) activity in response to activation of dopamine D2 receptors (D2R). These mouse models lack a dystonic motor phenotype, which leaves a critical gap in comprehending the role of DA and ACh transmission in the manifestations of dystonia. To tackle this question, we used a combination of ex vivo slice physiology and in vivo monitoring of striatal ACh dynamics in the inducible, phenotypically penetrant, transgenic mouse model of paroxysmal non-kinesiogenic dyskinesia (PNKD), an animal with both dystonic and dyskinetic features. We found that, similarly to genetic models of isolated dystonia, the PNKD mouse displays D2R-induced paradoxical excitation of ChI firing in ex vivo striatal brain slices. In vivo, caffeine triggers dystonic symptoms while reversing the D2R-mediated excitation of ChIs and desynchronizing ACh release in PNKD mice. In WT littermate controls, caffeine stimulates spontaneous locomotion through a similar but reversed mechanism involving an excitatory switch of the D2R control of ChI activity, associated with enhanced synchronization of ACh release. These observations suggest that the “paradoxical excitation” of cholinergic interneurons described in isolated dystonia models could represent a compensatory or protective mechanism that prevents manifestation of movement abnormalities and that phenotypic dystonia is possible only when this is absent. These findings also suggest that D2Rs may play an important role in synchronizing the ChI network leading to rhythmic ACh release during heightened movement states. Dysfunction of this interaction and corresponding desynchrony of ACh release may contribute to aberrant movements.

Clinical and physiological characteristics of tremor in a large cohort of focal and segmental dystonia

ObjectiveTremor is a frequent co-occurring feature in patients with dystonia, especially in focal and segmental dystonia. Clinical studies have shown that tremor is more commonly observed when dystonia spreads to contiguous body regions. However, there is insufficient characterization of tremor physiology in focal and segmental forms of dystonia. We aimed to ascertain the characteristics of tremor presenting in these specific subtypes.MethodsWe enrolled dystonia patients with head and arm tremors presenting to our center. We categorized these participants as focal and segmental dystonia following the Movement Disorders Society guidelines. We recorded the frequency, amplitude, rhythmicity, burst duration, and discharge pattern on accelerometer and electromyography recordings. We compared the physiology of tremors in focal vs. segmental dystonia. We determined whether the physiology was affected by clinical features such as demographics, age at onset, dystonia duration, alcohol responsiveness, family history, and botulinum toxin responsiveness.Results72 patients, mainly focal cervical dystonia and focal cervical + arm or cranial dystonia (segmental) were enrolled. In the analysis of the head tremor recordings (n = 66; frequency range 3–6.5 Hz), we found that focal vs. segmental dystonia comparisons revealed a significantly lower frequency (mean ± standard deviation; 4.0 ± 0.9 Hz vs. 4.7 ± 1.0 Hz; p = 0.02), lower amplitude (0.004 ± 0.008 g2/Hz vs. 0.006 ± 0.008 g2/Hz; p = 0.03) and longer muscle burst durations (111.1 ± 40.4 ms vs. 91.5 ± 24 ms; p = 0.04). In the analysis of arm tremor recordings (n = 31; frequency range 3.5–7 Hz), we found focal vs. segmental dystonia comparison revealed a lower amplitude (0.04 ± 0.07 g2/Hz vs. 0.06 ± 0.06 g2/Hz; p = 0.045). In the stepwise regression analysis, the age at evaluation (β - 0.44; p = 0.006) and age at onset (β - 0.61; p = 0.005) significantly predicted the head tremor frequency whereas the alcohol responsiveness tended to predict the amplitude of the head tremor (β - 0.5; p = 0.04) and the arm tremor (β - 0.6; p = 0.02).ConclusionOur study found that the physiological characteristics of tremor in focal and segmental dystonia are somewhat distinct, suggesting that the spread of dystonia symptoms from one body region to another may have a bearing on the physiology of co-occurring tremor. The frequency of head tremors in younger participants was observed to be higher compared to older participants. The head and arm tremor tended be less severe in patients reporting alcohol responsiveness.

Striato-pallidal oscillatory connectivity correlates with symptom severity in dystonia patients

Dystonia is a hyperkinetic movement disorder that has been associated with an imbalance towards the direct pathway between striatum and internal pallidum, but the neuronal underpinnings of this abnormal basal ganglia pathway activity remain unknown. Here, we report invasive recordings from ten dystonia patients via deep brain stimulation electrodes that allow for parallel recordings of several basal ganglia nuclei, namely the striatum, external and internal pallidum, that all displayed activity in the low frequency band (3–12 Hz). In addition to a correlation with low-frequency activity in the internal pallidum (R = 0.88, P = 0.001), we demonstrate that dystonic symptoms correlate specifically with low-frequency coupling between striatum and internal pallidum (R = 0.75, P = 0.009). This points towards a pathophysiological role of the direct striato-pallidal pathway in dystonia that is conveyed via coupling in the enhanced low-frequency band. Our study provides a mechanistic insight into the pathophysiology of dystonia by revealing a link between symptom severity and frequency-specific coupling of distinct basal ganglia pathways.

Early onset primary torsion dystonia with DYT1 positive in an 8-Year-old child: a case report

Apart from tremor, primary clinical symptom of primary torsion dystonia (PTD) is dystonia. No history or evidence of neuronal degeneration or acquired origin are present. Out of the seven different loci reported for PTD, only two genes have been identified. This case is being presented with a diagnosis of PTD. The patient, an 8-year-old boy from non-consanguineous parents, had problem in walking for one year, mostly in his left leg and had trouble using his left hand to pick up objects. He had dystonia in the left upper and lower limbs, had intact sensory function with intact cranial nerve function. All his laboratory tests were normal including brain imaging; nevertheless, genetic testing revealed DYT1 was positive. BIRDEM Med J 2024; 14(3): 158-160

Chronic Cocaine Use and Parkinson's Disease: An Interpretative Model.

Over the years, the growing "epidemic" spread of cocaine use represents a crucial public health and social problem worldwide. According to the 2023 World Drug Report, 0.4% of the world's population aged 15 to 64 report using cocaine; this number corresponds to approximately 24.6 million cocaine users worldwide and approximately 1 million subjects with cocaine use disorder (CUD). While we specifically know the short-term side effects induced by cocaine, unfortunately, we currently do not have exhaustive information about the medium/long-term side effects of the substance on the body. The scientific literature progressively highlights that the chronic use of cocaine is related to an increase in cardio- and cerebrovascular risk and probably to a greater incidence of psychomotor symptoms and neurodegenerative processes. Several studies have highlighted an increased risk of antipsychotic-induced extrapyramidal symptoms (EPSs) in patients with psychotic spectrum disorders comorbid with psychostimulant abuse. EPSs include movement dysfunction such as dystonia, akathisia, tardive dyskinesia, and characteristic symptoms of Parkinsonism such as rigidity, bradykinesia, and tremor. In the present paper, we propose a model of interpretation of the neurobiological mechanisms underlying the hypothesized increased vulnerability in chronic cocaine abusers to neurodegenerative disorders with psychomotor symptoms. Specifically, we supposed that the chronic administration of cocaine produces significant neurobiological changes, causing a complex dysregulation of various neurotransmitter systems, mainly affecting subcortical structures and the dopaminergic pathways. We believe that a better understanding of these cellular and molecular mechanisms involved in cocaine-induced neuropsychotoxicity may have helpful clinical implications and provide targets for therapeutic intervention.

Pallidal Versus Subthalamic Deep-Brain Stimulation for Generalized Isolated Dystonia: A Retrospective Study.

Objectives: Deep-brain stimulation (DBS) has been used for the treatment of medically refractory dystonia with excellent results. In this study, we compared in detail the therapeutic advantages of two DBS targets for generalized isolated dystonia. Methods: In this retrospective study, we recruited 29 patients with generalized isolated dystonia who had undergone DBS treatment targeting either the globus pallidus interna (GPi) or the subthalamic nucleus (STN) in the Department of Functional Neurosurgery at Tiantan Hospital, Beijing, China, between January 2016 and December 2021. The movement and disability subscales of the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) were used to assess the severity of their dystonic symptoms and their activities of daily living, respectively. SF-36 was used to evaluate the patients' health-related quality of life. Results: The percentage improvement in the BFMDRS-M score at 6 months relative to the baseline score was clearly higher in the STN group (63.91%) than in the GPi group (38.36%). At the 3-, 6-, and 12-month follow-ups, the percentage improvement in arm symptoms was significantly higher after DBS of the STN (70.64%, 80.66%, and 76.89%, respectively) than after stimulation of the GPi (36.75%, 34.21%, and 38.47%, respectively). At 12 months after surgery, patient quality of life had improved on all SF-36 subscales in both groups. Conclusions: STN-DBS may have more advantages than GPi-DBS in patients with obvious arm dystonia. STN-DBS had a better clinical effect than GPi-DBS within 6 months after surgery.

Exome Sequence Analysis to Characterize Undiagnosed Family Segregating Motor Impairment and Dystonia.

Background: Hypermanganesemia with dystonia 1 (HMNDYT1) is a rare genetic disorder characterized by elevated blood manganese levels. This condition is associated with polycythemia, motor neurodegeneration with extrapyramidal features, and hepatic dysfunction, which can progress to cirrhosis in some patients. Materials and Methods: In this study, a consanguineous Saudi family with two affected individuals exhibiting symptoms of severe motor impairment, spastic paraparesis, postural instability, and dystonia was studied. Clinical and radiographic evaluations were conducted on the affected individuals. Whole exome sequencing (WES) was performed to diagnose the disease and to determine the causative variant underlying the phenotype. Moreover, Sanger sequencing was used for validation and segregation analysis of the identified variant. Bioinformatics tools were utilized to predict the pathogenicity of candidate variants based on ACMG criteria. Results: Exome sequencing detected a recurrent homozygous missense variant (c.266T>C; p.L89P) in exon 1 of the SLC30A10 gene. Sanger sequencing was employed to validate the segregation of the discovered variant in all available family members. Bioinformatics tools predicted that the variant is potentially pathogenic. Moreover, conservation analysis showed that the variant is highly conserved in vertebrates. Conclusions: This study shows that exome sequencing is instrumental in diagnosing undiagnosed neurodevelopmental disorders. Moreover, this study expands the mutation spectrum of SLC30A10 in distinct populations.

Principal Variables Analysis for Non-Gaussian Data

Principal variables analysis (PVA) is a technique for selecting a subset of variables that capture as much of the information in a dataset as possible. Existing approaches for PVA are based on the Pearson correlation matrix, which is not well-suited to describing the relationships between non-Gaussian variables. We propose a generalized approach to PVA enabling the use of different types of correlation, and we explore using Spearman, Gaussian copula, and polychoric correlations as alternatives to Pearson correlation. We compare performance in simulation studies varying the form of the true multivariate distribution over a range of possibilities. Our results show that on continuous non-Gaussian data, using generalized PVA with Gaussian copula or Spearman correlations provides a major improvement in performance compared to Pearson. On ordinal data, generalized PVA with polychoric correlations outperforms the rest by a wide margin. We apply generalized PVA to a dataset of 102 clinical variables measured on individuals with X-linked dystonia parkinsonism (XDP), a neurodegenerative disorder involving symptoms of both dystonia and parkinsonism. We find that using different types of correlation yields substantively different sets of principal variables; for example, parkinsonism-related metrics appear more explanatory than dystonia-related metrics on the observed data. Supplementary materials for this article are available online.

Video-based diagnosis support system for pianists with Musician's dystonia.

Musician's dystonia is a task-specific movement disorder that deteriorates fine motor control of skilled movements in musical performance. Although this disorder threatens professional careers, its diagnosis is challenging for clinicians who have no specialized knowledge of musical performance. To support diagnostic evaluation, the present study proposes a novel approach using a machine learning-based algorithm to identify the symptomatic movements of Musician's dystonia. We propose an algorithm that identifies the dystonic movements using the anomaly detection method with an autoencoder trained with the hand kinematics of healthy pianists. A unique feature of the algorithm is that it requires only the video image of the hand, which can be derived by a commercially available camera. We also measured the hand biomechanical functions to assess the contribution of peripheral factors and improve the identification of dystonic symptoms. The proposed algorithm successfully identified Musician's dystonia with an accuracy and specificity of 90% based only on video footages of the hands. In addition, we identified the degradation of biomechanical functions involved in controlling multiple fingers, which is not specific to musical performance. By contrast, there were no dystonia-specific malfunctions of hand biomechanics, including the strength and agility of individual digits. These findings demonstrate the effectiveness of the present technique in aiding in the accurate diagnosis of Musician's dystonia.

Does botulinum toxin affect psycho-social aspects in dystonia?

Dystonia is a movement disorder in which sustained muscle contractions give rise to abnormal postures or involuntary movements. It is a disabling and disfiguring disorder that affects activities of daily living and gives people a bizarre appearance often associated with psychological morbidity, embarrassment and social avoidance. Intramuscular injection of botulinum toxin (BoNT) is the most effective treatment for motor symptoms in focal dystonia, but little is known about its impact on the psycho-social dimension. The main aim of this study was to evaluate psycho-social changes in patients with focal dystonia after starting BoNT treatment using self-reported scales. The Beck Depression Inventory (BDI-II), the 36-Item Short Form Health Survey (SF-36), the Body Uneasiness Test (BUT), the State-Trait Anxiety Inventory (STAI) and the Visual Analogue Scale (VAS) assessing body self-image, satisfaction with physical aspects, social avoidance, self-reported depression, and self-distress were completed by 11 patients with dystonia and 9 patients with hyperhidrosis as a control group before BoNT (T0). VAS was then performed after four weeks (T1) to assess whether BoNT induced changes in the psychosocial dimension. Our results showed that only depressive symptoms and rumination about body defects improved in patients with dystonia after BoNT treatment, while improvement in self-distress and satisfaction with physical aspects was also found in hyperhidrosis. Individuals with hyperhidrosis experience poorer psychological well-being and suffer from higher levels of distress compared to dystonic patients. This suggests that individuals with this disabling condition are more vulnerable to social impact than dystonic patients.

Engaging dystonia networks with subthalamic stimulation.

Deep brain stimulation is a viable and efficacious treatment option for dystonia. While the internal pallidum serves as the primary target, more recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its complex surroundings have not been studied in depth. Indeed, multiple historical targets that have been used for surgical treatment of dystonia are directly adjacent to the STN. Further, multiple types of dystonia exist, and outcomes are variable, suggesting that not all types would profit maximally from the exact same target. Therefore, a thorough investigation of the neural substrates underlying effects on dystonia symptoms is warranted. Here, we analyze a multi-center cohort of isolated dystonia patients with subthalamic implantations (N = 58) and relate their stimulation sites to improvement of appendicular and cervical symptoms as well as blepharospasm. Stimulation of the ventral oral posterior nucleus of thalamus and surrounding regions was associated with improvement in cervical dystonia, while stimulation of the dorsolateral STN was associated with improvement in limb dystonia and blepharospasm. This dissociation was also evident for structural connectivity, where the cerebellothalamic, corticospinal and pallidosubthalamic tracts were associated with improvement of cervical dystonia, while hyperdirect and subthalamopallidal pathways were associated with alleviation of limb dystonia and blepharospasm. Importantly, a single well-placed electrode may reach the three optimal target sites. On the level of functional networks, improvement of limb dystonia was correlated with connectivity to the corresponding somatotopic regions in primary motor cortex, while alleviation of cervical dystonia was correlated with connectivity to the recently described 'action-mode' network that involves supplementary motor and premotor cortex. Our findings suggest that different types of dystonia symptoms are modulated via distinct networks. Namely, appendicular dystonia and blepharospasm are improved with modulation of the basal ganglia, and, in particular, the subthalamic circuitry, including projections from the primary motor cortex. In contrast, cervical dystonia was more responsive when engaging the cerebello-thalamo-cortical circuit, including direct stimulation of ventral thalamic nuclei. These findings may inform DBS targeting and image-based programming strategies for patient-specific treatment of dystonia.

Neurosurgical and pharmacological management of dystonia.

Dystonia characterizes a group of neurological movement disorders characterized by abnormal muscle movements, often with repetitive or sustained contraction resulting in abnormal posturing. Different types of dystonia present based on the affected body regions and play a prominent role in determining the potential efficacy of a given intervention. For most patients afflicted with these disorders, an exact cause is rarely identified, so treatment mainly focuses on symptomatic alleviation. Pharmacological agents, such as oral anticholinergic administration and botulinum toxin injection, play a major role in the initial treatment of patients. In more severe and/or refractory cases, focal areas for neurosurgical intervention are identified and targeted to improve quality of life. Deep brain stimulation (DBS) targets these anatomical locations to minimize dystonia symptoms. Surgical ablation procedures and peripheral denervation surgeries also offer potential treatment to patients who do not respond to DBS. These management options grant providers and patients the ability to weigh the benefits and risks for each individual patient profile. This review article explores these pharmacological and neurosurgical management modalities for dystonia, providing a comprehensive assessment of each of their benefits and shortcomings.

Understanding Anxiety in Cervical Dystonia: An Imaging Study.

Anxiety may precede motor symptoms in cervical dystonia (CD) and is associated with an earlier onset of dystonia. Our understanding of anxiety in CD is inadequate. To investigate brain networks associated with anxiety in CD. Twenty-six subjects with idiopathic CD underwent MRI Brain without contrast. Correlational tractography was derived using Diffusion MRI connectometry. Quantitative Anisotropy (QA) was used in deterministic diffusion fiber tracking. Correlational tractography was then used to correlate QA with State-Trait Anxiety Inventory (STAI) state (STAI-S) and trait (STAI-T) subscales. Connectometry analysis showed direct correlation between state anxiety and QA in tracts from amygdala to thalamus/ pulvinar bilaterally, and trait anxiety and QA in tracts from amygdala to motor cortex, sensorimotor cortex and parietal association area bilaterally (FDR ≤0.05). Our efforts to map anxiety to brain networks in CD highlight the role of the amygdala in the pathophysiology of anxiety in CD.

Superior cerebellar peduncle deep brain stimulation for cerebral palsy.

Patients with coexisting spastic cerebral palsy (CP) and dystonia have limited treatment options. In this study, the authors aimed to evaluate the efficacy of deep brain stimulation (DBS) targeting the superior cerebellar peduncles (SCPs) in adults with CP. Five patients with CP and medically refractory dystonia and spasticity underwent SCP DBS. Assessments included the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), modified Ashworth scale (mAS), and tests of cognition, mental status, and quality of life preoperatively and at 3, 6, and 12 months postoperatively (in both DBS ON and OFF states, double blinded). Active contacts and fiber bundles were examined. Four patients completed follow-up. The BFMDRS motor score decreased from 74 to 52 at 12 months postoperatively (30%, p = 0.008). The mean mAS score indicated significant spasticity reduction (from 2.9 ± 0.9 to 1.9 ± 0.6 after 12 months, p = 0.0454). Quality of life improved (p < 0.01), while cognition remained unaffected. Active contacts were found within the dentato-rubro-thalamic tract, with variable efficiency in decussating and nondecussating portions. In this pilot trial, SCP DBS showed promise as a well-tolerated treatment for CP, improving dystonic symptoms, spasticity, quality of life, and functional capacities. However, caution is needed when interpreting the results given the small sample size and heterogeneous motor outcomes.

Pallidal deep brain stimulation for patients with myoclonus-dystonia without SGCE mutations.

Pallidal deep brain stimulation (GPi-DBS) is effective for treating myoclonus and dystonia caused by SGCE mutations (DYT-SGCE, DYT11). However, it is unknown whether GPi-DBS is effective for the treatment of myoclonus-dystonia which is not associated with the SGCE gene mutations. In this study, we investigated the efficacy of GPi-DBS in treating myoclonus-dystonia in SGCE mutation-negative cases. Three patients with myoclonus-dystonia without SGCE mutations who underwent GPi-DBS were evaluated preoperatively and 6months postoperatively using the Unified Myoclonus Rating Scale (UMRS) and Fahn-Marsden Dystonia Rating Scale (FMDRS) for myoclonus and dystonia, respectively. In two of the three patients, myoclonus was more evident during action. Myoclonus was predominant at rest in the other patient, and he was unaware of his dystonia symptoms. The results were compared with those of the four DYT-SGCE cases. The mean UMRS score in patients with myoclonus-dystonia without SGCE mutations improved from 61.7 to 33.7 pre- and postoperatively, respectively, and the mean FMDRS score improved from 7.2 to 4.5. However, the degree of improvement in myoclonus-dystonia in patients without SGCE mutations was inferior to that in patients with DYT-SGCE (the UMRS score improved by 45% and 69%, respectively). GPi-DBS is effective for treating myoclonus-dystonia in patients with and without SGCE mutations. GPi-DBS should be considered as a treatment option for myoclonus-dystonia without SGCE mutations.

1137 Prospective, Multicenter, International Registry of Deep Brain Stimulation for Dystonia: A Sub-analysis of Cervical Dystonia Patients

INTRODUCTION: Management of dystonia using Deep Brain Stimulation (DBS) is a well-established therapeutic approach. However, optimal DBS target sites in patients with cervical (focal) versus generalized dystonia are thought to diverge and be specific for particular connections (Horn 2022). DBS devices equipped with capabilities such as directionality and Multiple Independent Current Control (MICC) may offer potential for improved clinical outcomes. METHODS: This is a sub-analysis of patients with focal (cervical) dystonia only or cervical dystonia in the context of segmental or generalized dystonia assessed as part of a prospective, multicenter, international dystonia registry (NCT02686125). All patients receive an MICC-based, directional DBS system (Vercise, Boston Scientific). Patients are followed up to 3-years (post-implant). Several study assessments are being collected to evaluate their dystonia symptoms (e.g., TWSTRS), quality of life, and overall satisfaction. Adverse Events are also collected. RESULTS: A total of 43-patients (mean age 56.9-years, 58% females) with focal (cervical) dystonia only and 83 patients (mean 41.95-years, 61% females) with cervical dystonia in context of segmental or generalized dystonia have been evaluated. Both groups reported significant improvement in overall TWSTRS scores – however the extent varied. In the cervical-only cohort, a 19.9-point improvement was noted at 6-months (n = 25) and sustained up to 1-year (23.2-point improvement, n = 20). In those with cervical dystonia within frame of segmental or generalized dystonia, a 9.7-point and 7.3-point improvement in overall TWSTRS scores was noted at 6- (n = 50) and 12-months (n = 38), respectively. Updated data will be reported. CONCLUSIONS: This registry represents the first comprehensive, large-scale collection of real-world outcomes associated with dystonia patients implanted with a directional DBS system capable of MICC. Preliminary results demonstrate significant improvement in patients with cervical dystonia (alone or in context of segmental or generalized dystonia) following DBS.

ε-sarcoglycan myoclonus-dystonia—overview of neurophysiological, behavioral, and imaging characteristics

Myoclonus-Dystonia is a rare, neurological movement disorder, clinically characterized by myoclonic jerks and dystonic symptoms, such as cervical dystonia and writer’s cramp. Psychiatric symptoms, like anxiety, depression, and addiction, are frequently reported. Monogenic Myoclonus-Dystonia is mostly caused by pathogenic variants in the ε-sarcoglycan gene, which is among other regions highly expressed in the cerebellum. The current pharmacological treatment is not satisfactory. Neurophysiological and imaging studies in this patient population are scarce with partly heterogeneous results and sometimes important limitations. However, some studies point towards subcortical alterations, e.g., of the cerebellum and its connections. Further studies addressing previous limitations are important for a better understanding of the underlying pathology of Myoclonus-Dystonia and might build a bridge for the development of future treatment.

Spatiotemporal patterns of throwing muscle synergies in yips-affected baseball players

“Yips” are involuntary movements that interfere with the automatic execution of sports movements. However, how the coordination among the various muscles necessary for sports movements is impaired in athletes with yips remains to be fully understood. This study aimed to assess whether muscle synergy analysis through non-negative matrix factorization (NMF) could identify impaired spatiotemporal muscle coordination in baseball players with throwing yips. Twenty-two college baseball players, including 12 with and 10 without yips symptoms participated in the study. Electromyographic activity was recorded from 13 ipsilateral upper extremity muscles during full-effort throwing. Muscle synergies were extracted through NMF. Cluster analysis was conducted to identify any common spatiotemporal patterns of muscle synergies in players with yips. Whether individual players with yips showed deviations in spatiotemporal patterns of muscle synergies compared with control players was also investigated. Four muscle synergies were extracted for each player, but none were specific to the yips group. However, a more detailed analysis of individual players revealed that two of the three players who presented dystonic symptoms during the experiment exhibited specific patterns that differed from those in control players. By contrast, each player whose symptoms were not reproduced during the experiment presented spatiotemporal patterns of muscle synergies similar to those of the control group. The results of this study indicate no common spatiotemporal pattern of muscle synergies specific to the yips group. Furthermore, these results suggest that the spatiotemporal pattern of muscle synergies in baseball throwing motion is not impaired in situations where symptoms are not reproduced even if the players have yips symptoms. However, muscle synergy analysis can identify the characteristics of muscle coordination of players who exhibit dystonic movements. These findings can be useful in developing personalized therapeutic strategies based on individual characteristics of yips symptoms.

Editorial: Exploring dystonia symptoms through animal models and patient studies

Editorial: Exploring dystonia symptoms through animal models and patient studies