Severity Of Dystonia Research Articles

The role of osteopathic manipulative treatment for dystonia: a literature review.

Dystonia is a movement disorder that causes involuntary muscle contractions leading to abnormal movements and postures, such as twisting. Dystonia is the third most common movement disorder in the United States, with as many as 250,000 people affected. Because of its complexity, dystonia presents a significant challenge in terms of management and treatment. Despite limited research, osteopathic manipulative treatment (OMT) has been considered as an adjunctive treatment due to its inexpensive and noninvasive nature, as opposed to other modalities such as botulinum toxin injections, deep brain stimulation (DBS), and transcranial magnetic stimulation, which are often expensive and inaccessible. OMT treatments performed in case studies and series such as balanced ligamentous tension/articular ligamentous strain (BLT/ALS), muscle energy (ME), high-velocity low-amplitude (HVLA), and myofascial release (MFR) have shown reduction of pain and muscle hypertonicity, including in patients with dystonia. The studies reviewed in this paper provide a snapshot of the literature regarding the current evidence of OMT's role for dystonia. A medical reference librarian conducted a thorough literature search across multiple databases including PubMed and Google Scholar to find articles relevant to the use of OMT for dystonia. The search employed a combination of Medical Subject Headings (MeSH) terms and keywords related to osteopathic medicine and dystonia to ensure precise retrieval of relevant articles within the last 20 years. Despite limited research on the topic, all four relevant reports found in the literature were selected for review. Of the four relevant reports, case series and studies highlighted the potential benefits of OMT in managing dystonia, particularly cervical dystonia and foot dystonia. OMT has shown promising results addressing pain, stiffness, and impaired motor function. In cases of foot dystonia in Parkinson's disease, OMT has helped improve gait and reduce pain by targeting somatic dysfunctions (SDs) associated with dystonia, such as abnormalities in foot progression angle (FPA) and musculoskeletal imbalances. Also, OMT has been found to alleviate symptoms of cervical dystonia, including tremors, muscle spasms, and neck stiffness. These interventions performed in case studies and series led to improvements in gait biomechanics in foot dystonia and overall symptom severity in patients with cervical dystonia. Currently, botulinum toxin, oral medications, physical therapy, and rehabilitation are commonly utilized in managing dystonia. The studies reviewed in this paper suggest that these treatments may lead to improvements in pain and muscle hypertonicity in patients with dystonia. It is important to investigate whether factors such as the type of dystonia (eg, focal vs. segmental) and its underlying cause (eg, idiopathic, trauma, infection, autoimmune, medication side effects) influence treatment outcomes. Further research is recommended to explore the role of OMT in managing dystonia.

External Factors Modulating Pain and Pain-Related Functional Impairment in Cervical Dystonia.

Little is known about factors modulating pain and pain-related functional impairment in isolated cervical dystonia (CD). The aim was to assess the prevalence and interrelationship between pain-modulating factors and pain-related determinants of functional impairment and quality of life in CD. We analyzed pain-aggravating and pain-relieving external factors, the degree of pain-related functional impact on routine activities, and the relationship between these and pain severity, using cross-sectional data collected using the Pain in Dystonia Scale (PIDS) from 85 participants with CD. Pairwise correlation analyses and age- and sex-adjusted linear regression models estimated the relationship between pain-modulating factors and pain severity, and the impact of pain severity, dystonia severity, and psychiatric symptoms on pain-related functional impairment and disease-specific quality of life (measured using the Craniocervical Dystonia Questionnaire-24). Stress and prolonged fixed position were the most frequent and impacting pain triggers, with women reporting larger impact. The average impact of pain-relieving factors was lower than that of pain triggers. Physical exercise and social gatherings were the most impacted activities by pain in CD. The intensity of external modulating factors was a predictor of pain severity. Severity of pain, CD, and psychiatric symptoms independently predicted pain-related functional impairment, whereas quality of life was predicted by pain severity, pain-related functional impairment, and psychiatric symptom severity, but not dystonia severity. The PIDS provides insight into external modulation and functional impact of pain in CD. The pattern of external modulation of pain in CD is in line with a multifactorial modulation and complex physiology.

Brain metabolic response to repetitive transcranial magnetic stimulation to lesion network in cervical dystonia

BackgroundA previous study identified a brain network underlying cervical dystonia (CD) based on causal brain lesions. This network was shown to be abnormal in idiopathic CD and aligned with connections mediating treatment response to deep brain stimulation, suggesting generalizability across etiologies and relevance for treatment. The main nodes of this network were located in the deep cerebellar structures and somatosensory cortex (S1), the latter of which can be easily reached via non-invasive brain stimulation. To date, there are no studies testing brain stimulation to networks identified using lesion network mapping. ObjectivesTo assess target engagement by stimulating the S1 and testing the brain's acute metabolic response to repetitive transcranial magnetic stimulation in CD patients and healthy controls. MethodsThirteen CD patients and 14 controls received a single session of continuous theta burst (cTBS) and sham to the right S1. Changes in regional brain glucose metabolism were measured using [18F]FDG-PET. ResultscTBS increased metabolism at the stimulation site in CD (P = 0.03) but not in controls (P = 0.15; group difference P = 0.01). In subcortical regions, cTBS increased metabolism in the brainstem in CD only (PFDR = 0.04). The remote activation was positively associated with dystonia severity and efficacy of sensory trick phenomenon in CD patients. ConclusionsOur results provide further evidence of abnormal sensory system function in CD and show that a single session of S1 cTBS is sufficient to induce measurable changes in brain glucose metabolism. These findings support target engagement, motivating therapeutic trials of cTBS to the S1 in CD.

Microstructure of the cerebellum and its afferent pathways underpins dystonia in myoclonus dystonia.

Myoclonus dystonia due to a pathogenic variant in SGCE (MYC/DYT-SGCE) is a rare condition involving a motor phenotype associating myoclonus and dystonia. Dysfunction within the networks relying on the cortex, cerebellum, and basal ganglia was presumed to underpin the clinical manifestations. However, the microarchitectural abnormalities within these structures and related pathways are unknown. Here, we investigated the microarchitectural brain abnormalities related to the motor phenotype in MYC/DYT-SGCE. We used neurite orientation dispersion and density imaging, a multicompartment tissue model of diffusion neuroimaging, to compare microarchitectural neurite organization in MYC/DYT-SGCE patients and healthy volunteers (HVs). Neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF) were derived and correlated with the severity of motor symptoms. Fractional anisotropy (FA) and mean diffusivity (MD) derived from the diffusion tensor approach were also analyzed. In addition, we studied the pathways that correlated with motor symptom severity using tractography analysis. Eighteen MYC/DYT-SGCE patients and 24 HVs were analyzed. MYC/DYT-SGCE patients showed an increase of ODI and a decrease of FA within their motor cerebellum. More severe dystonia was associated with lower ODI and NDI and higher FA within motor cerebellar cortex, as well as with lower NDI and higher ISOVF and MD within the corticopontocerebellar and spinocerebellar pathways. No association was found between myoclonus severity and diffusion parameters. In MYC/DYT-SGCE, we found microstructural reorganization of the motor cerebellum. Structural change in the cerebellar afferent pathways that relay inputs from the spinal cord and the cerebral cortex were specifically associated with the severity of dystonia.

Prevalence of Myofascial Trigger Points in Isolated Idiopathic Cervical Dystonia: A Possible Contributor to Pain, Movement and Disability.

Myofascial trigger points (TrPs) are hypersensitive points located in a tight band of muscle that, when palpated, produce not only local pain but also referred (distant) pain. The role of TrPs in patients with cervical dystonia (CD) has not been investigated. To identify the presence of TrPs in patients with isolated idiopathic CD and their association with pain. Thirty-one patients (74.2% women; age: 61.2 years, SD: 10.1 years) participated. TrPs were explored in the sternocleidomastoid, upper trapezius, splenius capitis, levator scapulae, anterior scalene, suboccipital, and infraspinatus muscles. Clinical features of CD were documented as well as the presence of pain. The severity of dystonia and its consequences were assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). The mean number of TrPs for each patient was 12 (SD:3), with no differences between patients with pain (n = 20) and those without pain (n = 11). Active TrPs were only found in patients with pain (mean: 7.5, SD:4). Latent TrPs were found in both groups but were more prevalent (P < 0.001) in patients without pain (mean: 11, SD:3.5) than in those with pain (mean: 5, SD:3.5). The number of active TrPs or latent TrPs was positively associated with the TWSTRS disability subscale and the TWSTRS total score. The number of active, but not latent, TrPs was associated with worse scores on the TWSTRS pain subscale. Active TrPs were present in patients with CD reporting pain, while latent TrPs were present in all CD patients, irrespective of their pain status. The numbers of active/latent TrPs were associated with disability. TrPs could act as pain generators in CD and also contribute to the involuntary muscle contractions characteristic of dystonia.

Kinematic upper limb analysis outperforms electromyography at grading the severity of dystonia in children with cerebral palsy

BackgroundSeverity of dyskinesia in children with cerebral palsy is often assessed using observation-based clinical tools. Instrumented methods to objectively measure dyskinesia have been proposed to improve assessment accuracy and reliability. Here, we investigated the technique and movement features that were most suitable to objectively measure the severity of dystonia in children with cerebral palsy. MethodsA prospective observational study was conducted with 12 participants with cerebral palsy with a predominant motor type of dyskinesia, spasticity, or mixed dyskinesia/spasticity who had upper limb involvement (mean age: 12.6 years, range: 6.7–18.2 years). Kinematic and electromyography data were collected bilaterally during three upper limb tasks. Spearman rank correlations of kinematic or electromyography features were calculated against dystonia severity, quantified by the Dyskinesia Impairment Scale. FindingsKinematic features were more influential compared to electromyography features at grading the severity of dystonia in children with cerebral palsy. Kinematic measures quantifying jerkiness of volitional movement during an upper limb task with a reaching component performed best (|rs| = 0.78–0.9, p < 0.001). InterpretationThis study provides guidance on the types of data, features of movement, and activity protocols that instrumented methods should focus on when objectively measuring the severity of dystonia in children with cerebral palsy.

Efficacy of Oral Trihexyphenidyl Plus Clonazepam Versus Trihexyphenidyl for the Treatment of Dystonia in Children With Dystonic Cerebral Palsy: An Open-Label Randomized Controlled Trial

BackgroundTrihexyphenidyl and clonazepam are commonly used to treat dystonia in children with cerebral palsy (CP). However, there is a notable gap in the literature when it comes to studies that combine these first-line agents for the management of dystonia. MethodsThis open-label, randomized controlled trial aimed to compare the efficacy of adding oral clonazepam to trihexyphenidyl (THP + CLZ) versus using trihexyphenidyl alone (THP) in reducing the severity of dystonia, as measured by the Barry-Albright Dystonia (BAD) score. The study was conducted over a 12-week therapy period in children with dystonic CP aged two to 14 years. ResultsEach group enrolled 51 participants. The THP + CLZ group showed significantly better improvement in dystonia severity at 12 weeks compared with the THP group alone (−4.5 ± 2.9 vs −3.4 ± 1.7, P = 0.02). Furthermore, the THP + CLZ group exhibited superior improvement in the severity of choreoathetosis, upper limb function, pain perception by the child, and quality of life, with P values of 0.02, 0.009, 0.01, and 0.01, respectively. The number of participants experiencing treatment-emergent adverse events was comparable in both groups (P = 0.67). Importantly, none of the participants in any of the groups reported any serious adverse events. ConclusionA combination of oral THP + CLZ proves to be more efficacious than using THP alone for the treatment of dystonic CP in children aged two to 14 years in terms of reducing the severity of dystonia.

Actigraph-based quantification of sleep in children with dystonia undergoing deep brain stimulation.

Dystonia is among the most common pediatric movement disorders and can manifest with a range of debilitating symptoms, including sleep disruptions. The duration and quality of sleep are strongly associated with quality of life in these individuals and could serve as biomarkers of dystonia severity and the efficacy of interventions such as deep brain stimulation (DBS). Thus, this study investigated sleep duration and its relationship to disease severity and DBS response in pediatric dystonia. Actigraphs (wearable three-axis accelerometers) were used to record multiday sleep data in 22 children with dystonia, including 6 patients before and after DBS implantation, and age- and sex- matched healthy controls. Data were preprocessed, and metrics of sleep duration and quality were extracted. Repeated-measures statistical analyses were used. Children with dystonia slept less than typically developing children (p = 0.009), and shorter sleep duration showed trending correlation with worse dystonia severity (r = -0.421, p = 0.073). Of 4 patients who underwent DBS and had good-quality data, 1 demonstrated significantly improved sleep (p < 0.001) postoperatively. Reduction in dystonia severity strongly correlated with increased sleep duration after DBS implantation (r = -0.965, p = 0.035). Sleep disturbances are an underrecognized marker of pediatric dystonia severity, as well as the effectiveness of interventions such as DBS. They can serve as objective biomarkers of disease burden and symptom progression after treatment.

A Case Study of Korean Medicine Treatment in a Patient Complaining of Generalized Dystonia

We report a case of generalized dystonia that developed from oromandibular dystonia and improved following Korean medicine treatment. The patient was hospitalized for 18 days and treated with herbal medicine, mainly Hyeongbangsabaek-san and Soyangbowi-tang, acupuncture, electroacupuncture, pharmacopuncture, cupping, and moxibustion. To evaluate the clinical effects of the treatment, we used the Unified Dystonia Rating Scale (UDRS) and Global Dystonia Severity Rating Scale (GDS) and checked dyskinesia occurrence in a diary recorded by the patient’s guardian. After 18 days of hospitalization, the UDRS for the trunk, upper extremities, and lower face improved by more than 50%, and the GDS for the whole region, except the larynx and lower face, also improved. In addition, the maximum duration of dystonia decreased from 6 hours to 3 hours, and the pain and numbness associated with dystonia disappeared. This case suggests that Korean medicine treatment is effective in treating generalized dystonia.

Zolpidem improves task-specific dystonia: A randomized clinical trial integrating exploratory transcranial magnetic stimulation and [18F] FDG-PET imaging

BackgroundTask-specific dystonia (TSFD) is a disabling movement disorder. Effective treatment options are currently limited. Zolpidem was reported to improve primary focal and generalized dystonia in a proportion of patients. The mechanisms underlying its therapeutic effects have not yet been investigated. MethodsWe conducted a randomized, double-blind, placebo-controlled, crossover trial of single-dose zolpidem in 24 patients with TSFD. Patients were clinically assessed using Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Writers' Cramp Rating Scale (WCRS), and Visual Analogue Scale (VAS), before and after receiving placebo and zolpidem. Transcranial magnetic stimulation was conducted on placebo and zolpidem to compare corticospinal excitability – active and resting motor thresholds (AMT and RMT), resting and active input/output curves and intracortical excitability - cortical silent period (CSP), short-interval intracortical inhibition curve (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). Eight patients underwent brain FDG-PET imaging on zolpidem and placebo. ResultsZolpidem treatment improved TSFD. Zolpidem compared to placebo flattened rest and active input/output curves, reduced ICF and was associated with hypometabolism in the right cerebellum and hypermetabolism in the left inferior parietal lobule and left cingulum. Correlations were found between changes in dystonia severity on WCRS and changes in active input/output curve and in brain metabolism, respectively. Patients with lower RMT, and higher rest and active input/output curves exhibited better response to zolpidem compared to placebo. ConclusionsZolpidem improved TSFD by reducing corticomotor output and influencing crucial nodes in higher-order sensory and motor networks.

POLR3A-related disorders: From spastic ataxia to generalised dystonia and long-term efficacy of deep brain stimulation.

While biallelic POLR3A loss-of-function variants are traditionally linked to hypomyelinating leukodystrophy, patients with a specific splice variant c.1909+22G>A manifest as adolescent-onset spastic ataxia without overt leukodystrophy. In this study, we reported eight new cases, POLR3A-related disorder with c.1909+22 variant. One of these patients showed expanded phenotypic spectrum of generalised dystonia and her sister remained asymptomatic except for hypodontia. Two patients with dystonic arm tremor responded to deep brain stimulation. In our systemic literature review, we found that POLR3A-related disorder with c.1909+22 variant has attenuated disease severity but frequency of dystonia and upper limb tremor did not differ among genotypes.

Severity of Antipsychotic-Induced Cervical Dystonia Assessed by the Algorithm-Based Rating System.

Severity of Antipsychotic-Induced Cervical Dystonia Assessed by the Algorithm-Based Rating System.

The relationship between manual ability, dystonia and choreoathetosis severity and upper limb movement patterns during reaching and grasping in children and young adults with dyskinetic cerebral palsy

IntroductionImpaired upper limb movements are a key feature in dyskinetic cerebral palsy (CP). However, information on how specific movement patterns relate to manual ability, performance and underlying movement disorders is lacking. Insight in these associations may contribute to targeted upper limb management in dyskinetic CP. This study aimed to explore associations between deviant upper limb movement patterns and (1) manual ability, (2) severity of dystonia/choreoathetosis, and (3) movement time/trajectory deviation during reaching and grasping. Participants/methodsParticipants underwent three-dimensional upper limb analysis during reaching forwards (RF), reaching sideways (RS) and reach-and-grasp vertical (RGV) as well as clinical assessment. Canonical correlation and regression analysis with statistical parametric mapping were used to explore associations between clinical/performance parameters and movement patterns (mean and variability). ResultsThirty individuals with dyskinetic CP participated (mean age 16±5 y; 20 girls). Lower manual ability was related to higher variability in wrist flexion/extension during RF and RS early in the reaching cycle (p < 0.05). Higher dystonia severity was associated with higher mean wrist flexion (40–82 % of the reaching cycle; p = 0.004) and higher variability in wrist flexion/extension (31–75 %; p < 0.001) and deviation (2–14 %; p = 0.007/60–73 %; p = 0.006) during RF. Choreoathetosis severity was associated with higher elbow pro/supination variability (12–19 %; p = 0.009) during RGV. Trajectory deviation was associated with wrist and elbow movement variability (p < 0.05). ConclusionCurrent novel analysis of upper limb movement patterns and respective timings allows to detect joint angles and periods in the movement cycle wherein associations with clinical parameters occur. These associations are not present at each joint level, nor during the full movement cycle. This knowledge should be considered for individualized treatment strategies.

Effects of onabotulinum toxin type A injections in patients with Meige's syndrome.

Meige's syndrome is a type of facial dystonia characterized by the simultaneous occurrence of blepharospasm and oromandibular dystonia. Although botulinum toxin type A (OBTA) injections are the standard treatment, evidence of their effectiveness and safety in this scenario is still lacking. Our research aimed to evaluate the improvement and occurrence of side effects following injections of onabotulinum toxin type A (OBTA) in patients with Meige's syndrome. Patients with Meige's syndrome undergoing botulinum toxin injections were enrolled in this study. We assessed dystonia intensity before and 14 days after OBTA injection using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) to measure the response of symptoms in the eyes (blepharospasm) and mouth (oromandibular dystonia). Other variables, such as dosage, side effects, and demographic data, were also recorded. The study included 41 participants, with a mean age of 67.7 years and a female-to-male ratio of 3.5:1. The mean BFMDRS score before the injections was 8.89, and after 14 days, it was 2.88. The most reported side effect was ptosis, with a 7.3% incidence. OBTA significantly reduced dystonia severity (p < 0.0001). The clinical response for the blepharospasm component was superior to the oromandibular dystonia component. Our results support that OBTA seems to be an effective and safe therapeutic option for treating Meige's syndrome. The effect of OBTA was more pronounced in the treatment of blepharospasm than in oromandibular dystonia.

Very Early Levodopa May Prevent Self-Injury in Lesch-Nyhan Disease

BackgroundIn Lesch-Nyhan disease (LND), early dopamine deficiency is thought to contribute to dystonia and self-injury, gradually developing over the first years of life. Previous attempts to restore dopamine levels in older patients have been unsuccessful. Based on the hypothesis that very early dopamine replacement can prevent full phenotypic development, we treated three patients with LND from infancy with levodopa. MethodsLevodopa/carbidopa (4:1) was started at age 11 to 13 months, aiming at escalating to 5 to 6 mg/kg levodopa per day. Follow-up focused on dystonia severity and whether self-injury occurred. In addition, the literature was reviewed to delineate the age at onset of self-injury for all reported cases to date. ResultsDuring long-term follow-up, self-injury appears to have been prevented in two patients (now aged 14 and 15.5 years), as their HPRT1 gene mutations had been invariably associated with self-injury before. Future self-injury is unlikely, as only 1.1% of 264 published cases had self-injury onset later in life than these patients’ current ages. The third patient started self-injury at age 1.5 years, while on a substantially lower levodopa dose. A clear effect of levodopa on dystonia could not be determined. ConclusionsOur observations suggest that levodopa, given early enough and sufficiently dosed, might be able to prevent self-injury in LND. Therefore, levodopa could be considered in patients with LND as early as possible, at least before the self-injury appears. Further research is needed to establish very early levodopa as an effective treatment strategy in LND, and to optimize timing and dosing.

Tremor in cervical dystonia.

Cervical dystonia (CD) is the most common form of focal dystonia encountered in the clinic. Approximately one-third of CD patients have co-existing tremor in the head and hands. Assessment of tremor as regular or irregular in context of its oscillation trajectory, frequency, and amplitude is a major clinical challenge and can confound the diagnosis of CD. The misdiagnosis may lead to therapeutic failures, poor quality of life, and poor utilization of medical and financial resources. We analyzed the largest cohort of CD patients (n = 3117) available to date, collected from 37 movement disorder centers in North America, Europe, and Asia. We used machine learning to determine what clinical features from clinician reports predicted the presence of tremor as well as its regular or irregular appearance. Out of 3,117 CD patients, 1,367 had neck tremor. The neck tremor was interpreted as irregular in 1,022, regular in 345, and mixed (both irregular and regular) in 442. A feature importance analysis determined that greater severity of CD, longer disease duration, and older age, in descending order, predicted the presence of neck tremor. The probability of neck tremor was reduced if the dystonia affected other body parts in addition to the neck. We also found a significantly heightened risk for developing neck tremor in women. An additional feature importance analysis indicated that increased severity of dystonia affecting other body parts, severity of CD, and prolonged disease duration was associated with a lower likelihood of regular neck tremor while increased age predicted a higher likelihood. Machine learning recognized the most relevant clinical features that can predict concurrent neck tremor and its irregularity in a large multi-center dystonia cohort. These results may facilitate a more accurate description of neck tremor and improved care path in CD.

Pallidal multifractal complexity is a new potential physiomarker of dystonia

ObjectiveLow-frequency 4–12 Hz pallidal oscillations are being considered as potential physiomarkers for dystonia. We suggest investigating the multifractal properties of pallidal activity as an additional marker. MethodsWe employed local field potentials (LFP) recordings from 23 patients with dystonia who were undergoing deep brain stimulation (DBS) surgery to explore the connection between disease severity and the multifractal characteristics of pallidal activity. Furthermore, we performed an analysis of LFP recordings from four patients, following the externalization of DBS lead electrodes, to investigate the impact of DBS and neck muscle vibration on multifractal parameters. ResultsGreater dystonia severity exhibited a correlation with a narrower multifractal spectrum width but higher multifractal spectral asymmetry. Both GPi DBS and muscle vibration in dystonia patients expanded the multifractal spectrum width while restoring multifractal spectral symmetry. Notably, the threshold peak intensities for an increase in multifractal spectrum width substantially overlapped with the optimal volume of tissue activated. A broader multifractal spectrum during DBS corresponded to more favorable clinical outcomes. ConclusionsMultifractal properties of pallidal neuronal activity serve as indicators of neural dysfunction in dystonia. SignificanceThese findings suggest the potential of utilizing multifractal characteristics as predictive factors for the DBS outcome in dystonia.

Effect of Thalamic versus Pallidal Deep Brain Stimulation on Head Tremor in Dystonic and Essential Tremor Patients-A Retrospective Video-Blinded Study.

Head tremor is common in dystonia syndromes and difficult to treat. Deep brain stimulation (DBS) is a therapeutic option in medically-refractory cases. In most DBS-centers, the globus pallidus internus (GPi) is targeted in patients with predominant dystonia and the ventrointermediate nucleus of the thalamus (Vim) in predominant tremor. The aim of the study was to evaluate the effect of GPi- versus Vim-DBS in dystonic or essential head tremor. All patients with dystonia or essential tremor (ET) (n = 381) who underwent DBS surgery at our institution between 1999 and 2020 were screened for head tremor in our database according to predefined selection criteria. Of the 33 patients meeting inclusion criteria tremor and dystonia severity were assessed at baseline, short- (mean 10 months) and long-term follow-up (41 months) by two blinded video-raters. Twenty-two patients with dystonic head tremor received either GPi- (n = 12) or Vim-stimulation (n = 10), according to the prevailing clinical phenotype. These two groups were compared with 11 patients with ET, treated with Vim-stimulation. The reduction in head tremor from baseline to short- and long-term follow-up was 60-70% and did not differ significantly between the three groups. GPi-DBS effectively and sustainably reduced head tremor in idiopathic dystonia. The effect was comparable to the effect of Vim-DBS on head tremor in dystonia patients with predominant limb tremor and to the effect of Vim-DBS on head tremor in ET.

Application of deep brain stimulation for the treatment of childhood-onset dystonia in patients with MEPAN syndrome.

Mitochondrial Enoyl CoA Reductase Protein-Associated Neurodegeneration (MEPAN) syndrome is a rare inherited metabolic condition caused by MECR gene mutations. This gene encodes a protein essential for fatty acid synthesis, and defects cause progressively worsening childhood-onset dystonia, optic atrophy, and basal ganglia abnormalities. Deep brain stimulation (DBS) has shown mixed improvement in other childhood-onset dystonia conditions. To the best of our knowledge, DBS has not been investigated as a treatment for dystonia in patients with MEPAN syndrome. Two children with MEPAN were identified as possible DBS candidates due to severe generalized dystonia unresponsive to pharmacotherapy. Temporary depth electrodes were placed in six locations bilaterally and tested during a 6-day hospitalization to determine the best locations for permanent electrode placement. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Barry-Albright Dystonia Scale (BADS) were used for preoperative and postoperative testing to quantitatively assess dystonia severity changes. Patient 1 had permanent electrodes placed at the globus pallidus internus (GPi) and pedunculopontine nucleus (PPN). Patient 2 had permanent electrodes placed at the GPi and ventralis intermedius nucleus of the thalamus (VIM). Both patients successfully underwent DBS placement with no perioperative complications and significant improvement in their BFMDRS score. Patient 2 also demonstrated improvement in the BADS. We demonstrated a novel application of DBS in MEPAN syndrome patients with childhood-onset dystonia. These patients showed clinically significant improvements in dystonia following DBS, indicating that DBS can be considered for dystonia in patients with rare metabolic disorders that currently have no other proven treatment options.

Incobotulinum Toxin-A in Professional Musicians with Focal Task-Specific Dystonia: A Double Blind, Placebo Controlled, Cross-Over Study.

Musician's focal task-specific dystonia is a complex disorder of fine motor control, with incomplete understanding of its etiology. There have been relatively few trials of botulinum toxin in upper limb task-specific dystonia, and prior studies have yielded variable results, leading to skepticism regarding the utility of this approach in elite performers. We conducted a double-blind, placebo-controlled, randomized, cross-over study of incobotulinum toxin-A in 21 professional musicians with focal upper extremity task-specific dystonia affecting performance on their instrument, using a novel paradigm of initial injections followed by booster injections at two- and four-week intervals. The primary outcome measure was the change in blinded dystonia rating of the active arm by two expert raters using a Clinical Global Impression numeric scale at week 8 compared to enrollment. 19 men and 2 women with musicians' dystonia were enrolled over a six-year period. Nineteen patients completed the study. Analysis of the primary outcome measure in comparison to baseline revealed a change in dystonia severity of P = 0.04 and an improvement in overall musical performance of P = 0.027. No clinically significant weakness was observed, and neutralizing antibodies to toxin were not found. Despite its small sample size, our study demonstrated a statistically significant benefit of incobotulinum toxin-A injections as a treatment for musicians' task-specific dystonia. Tailoring the use of toxin with booster injections allowed refinement of dosing strategy and outcomes, with benefits that were meaningful to patients clearly visible on videotaped evaluations. In addition to its application to musicians' dystonia, this approach may have relevance to optimize application of botulinum toxin in other forms of focal dystonia such as blepharospasm, cervical dystonia, writer's cramp, and spasmodic dysphonia.