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Oromandibular dystonia (OMD) is an isolated focal dystonia that affects the muscles of the jaw, lower face and tongue. It is a rare disorder but is associated with significant impairment in quality of life. Treatment with oral medications has not been successful. Surgical interventions, such as deep brain stimulation, may be of benefit but have not been adequately evaluated. Currently, botulinum toxin (BoNT) injections are regarded as the treatment of choice for OMD. However, the evidence supporting this is not available. Most studies are open label, observational studies, longitudinal clinical experience, case reports or retrospective analysis. From the available studies, OMD is responsive to appropriately targeted BoNT injections. Jaw closing dystonia responds the most robustly. Jaw opening dystonia is more complex to inject, but clinical experience is consistent with benefit. Lingual dystonia is the most difficult because injections into tongue muscles frequently give rise to dysphagia. More controlled studies are required to establish BoNT as an effective treatment for OMD. [ABSTRACT FROM AUTHOR]

Background Numerous studies have established botulinum toxin (BoNT) to be safe and effective for the treatment of cervical dystonia (CD). Despite its well-documented efficacy, there has been growing awareness that a significant proportion of CD patients discontinue therapy. The reasons for discontinuation are only partly understood. Methods This summary describes longitudinal studies that provided information regarding the proportions of patients discontinuing BoNT therapy, and the reasons for discontinuing therapy. The data come predominantly from un-blinded long-term follow-up studies, registry studies, and patient-based surveys. Results All types of longitudinal studies provide strong evidence that BoNT is both safe and effective in the treatment of CD for many years. Overall, approximately one third of CD patients discontinue BoNT. The most common reason for discontinuing therapy is lack of benefit, often described as primary or secondary non-response. The apparent lack of response is only rarely related to true immune-mediated resistance to BoNT. Other reasons for discontinuing include side effects, inconvenience, cost, or other reasons. Discussion Although BoNT is safe and effective in the treatment of the majority of patients with CD, approximately one third discontinue. The increasing awareness of a significant proportion of patients who discontinue should encourage further efforts to optimize administration of BoNT, to improve BoNT preparations to extend duration or reduce side effects, to develop add-on therapies that may mitigate swings in symptom severity, or develop entirely novel treatment approaches. [ABSTRACT FROM AUTHOR]

Introduction: Dystonia is a rare disorder that has undergone extensive scientific investigation leading to a transformation of understanding over the past century.Methods: This manuscript was prepared through a review of relevant literature for each topic.Results: Historically dystonia was considered the manifestation of psychiatric disorders. Subsequently, investigations have firmly established this as a neurological disorder. Though electrophysiological and imaging, dystonia is thought to arise from a loss inhibition of motor programs, defective sensorimotor integration and abnormal plasticity. The genetic studies in dystonia have revealed the hereditary nature of many forms of familial dystonia. Treatment of dystonia has focused primarily on botulinum toxin for focal and segmental dystonia and deep brain stimulation of the globus pallidus interna for generalized and medically refractory focal dystonia.Conclusion: The progress in dystonia in the past century has revised the concepts of this disorder, increased knowledge of genetics and underlying pathophysiology, and provides new therapeutic targets. To promote future research the development of diagnostic criteria, biomarkers and validated rating scales for each form of dystonia is essential. [ABSTRACT FROM AUTHOR]

Restless legs syndrome (RLS) is a common disorder diagnosed by the clinical characteristics of restlessness in the legs associated often with abnormal sensations that start at rest and are improved by activity, occurring with a diurnal pattern of worsened symptoms at night and improvement in the morning. RLS is the cause of impaired quality of life in those more severely afflicted. Treatment of RLS has undergone considerable change over the last few years. Several classes of medications have demonstrated efficacy, including the dopaminergic agents and the alpha-2-delta ligands. Levodopa was the first dopaminergic agent found to be successful. However, chronic use of levodopa is frequently associated with augmentation that is defined as an earlier occurrence of symptoms frequently associated with worsening severity and sometimes spread to other body areas. The direct dopamine agonists, including ropinirole, pramipexole, and rotigotine patch, are also effective, although side effects, including daytime sleepiness, impulse control disorders, and augmentation, may limit usefulness. The alpha-2-delta ligands, including gabapentin, gabapentin enacarbil, and pregabalin, are effective for RLS without known occurrence of augmentation or impulse control disorders, although sedation and dizziness can occur. Other agents, including the opioids and clonazepam do not have sufficient evidence to recommend them as treatment for RLS, although in an individual patient, they may provide benefit. [ABSTRACT FROM AUTHOR]

With advances in the understanding of the pathophysiology of dystonia, novel therapeutics are being developed. Such therapies will require clinical investigation ranging from exploratory studies to examine safety, tolerability, dosage selection, and preliminary efficacy to confirmatory studies to evaluate efficacy definitively. As dystonia is a rare and complex disorder with clinical and etiological heterogeneity, clinical trials will require careful consideration of the trial design, including enrollment criteria, concomitant medication use, and outcome measures. Given the complexities of designing and implementing efficient clinical trials, it is important for clinicians and statisticians to collaborate closely throughout the clinical development process and that each has a basic understanding of both the clinical and statistical issues that must be addressed. To facilitate designing appropriate clinical trials in this field, we review important general clinical trial and regulatory principles, and discuss the critical components of trials with an emphasis on considerations specific to dystonia. Additionally, we discuss designs used in early exploratory, late exploratory, and confirmatory phases, including adaptive designs. [ABSTRACT FROM AUTHOR]

Abstract: Objective: IncobotulinumtoxinA differs from available formulations in that it does not have accessory proteins. IncobotulinumtoxinA has previously shown non-inferiority to onabotulinumtoxinA for the treatment of CD with a 1:1 dosing regimen. The objective of this study was to compare the safety and efficacy of incobotulinumtoxinA (120U, 240U; Merz Pharmaceuticals) to placebo in subjects with cervical dystonia (CD). Methods: This was a prospective, double-blind, randomized, placebo-controlled, multicenter clinical trial in botulinum toxin-treated or toxin-naïve CD patients. The primary outcome measure was change from baseline to Week 4 on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total score. Adverse events (AEs) also were evaluated. Results: Participants (N=233) were mostly women (66%), a mean of 52.8yearsold, who had CD for a mean of 51.9months. Of those, 39% were toxin-naïve. IncobotulinumtoxinA significantly improved TWSTRS-Total scores from baseline to Week 4 compared to placebo (placebo=−2.2; 120U=−9.9, and 240U=−10.9; 240U vs. placebo p<0.001 and 120U vs. placebo p<0.001). This effect persisted through to the end of the study. The most frequently reported AEs in the incobotulinumtoxinA groups were dysphagia, neck pain, and muscular weakness which were generally mild. Interpretation: IncobotulinumtoxinA (at doses of 120U or 240U) is a safe and effective treatment for CD in previously-treated as well as toxin-naïve subjects. [Copyright &y& Elsevier]

Abstract: The majority of studies on the effects of botulinum toxin in blepharospasm patients have been small or unblinded. Our large-scale, multicenter, randomized clinical trial on the efficacy and safety of botulinum toxin (Dysport®; 40, 80, and 120 units/eye) versus placebo in bilateral benign essential blepharospasm (BEB) supported the high efficacy and good safety profile of Dysport®, with improvement in functional impairment, reduced frequency and intensity of facial spasms, and fewer withdrawals through lack of efficacy in the active treatment group compared with controls. The best balance of sustained efficacy and favorable safety profile was provided by 80 units of Dysport®/eye in this study. [Copyright &y& Elsevier]

Anxiety is present in 30–40% of patients with cervical dystonia (CD). It has been ascribed to a direct effect of the state of motor symptoms on related pain, disability, and disfigurement. Accordingly, any reported benefit of botulinum toxin (BoNT) on anxiety is thought to be secondary to its effect on the same. We sought to evaluate the distinctive impact of botulinum toxin (BoNT) on anxiety in cervical dystonia (CD). In this prospective observational study, 60 participants with idiopathic isolated CD were recruited from clinic. We assessed motor and anxiety burden using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) parts I-III and State-Trait Anxiety Inventory (STAI). Assessments were done at time of BoNT (baseline) and at 6 weeks post-injection. STAI and motor severity TWSTRS scores poorly correlated at the baseline visit (rho = −0.30, p = 0.411). Both, motor TWSTRS (M difference = −1.46, p < 0.024) and STAI (M difference = −10.37, p = 0.007) improved from baseline to 6 weeks (peak effect). The change in motor TWSTRS poorly correlated with change in anxiety scores from baseline visit to 6 weeks (rho = −0.14, p > 0.999). Of these measures of anxiety, improvement in STAI-T had the largest effect size (rank biserial = 0.52). BoNT improves both motor severity and anxiety in CD. Poor correlation between motor severity and anxiety at both the time of injection and during the time of peak effect, and improvement in trait anxiety suggests that BoNT has a direct beneficial effect on anxiety. • Botulinum toxin improves anxiety and motor severity at 6 weeks in cervical dystonia. • Anxiety and motor severity demonstrate weak correlation at the time of injection and at 6 weeks. • Change in anxiety poorly correlates with change in motor severity at 6 weeks. • The effect size of improvement for trait anxiety is greater than state anxiety. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic blepharospasm is a clinically heterogeneous dystonia also characterized by non motor symptoms.Methods: We used a k-means cluster analysis to assess 188 patients with idiopathic blepharospasm in order to identify relatively homogeneous subpopulations of patients, using a set of motor and psychiatric variables to generate the cluster solution.Results: Blepharospasm patients reached higher scores on scales assessing depressive- and anxiety-related disorders than healthy/disease controls. Cluster analysis suggested the existence of three groups of patients that differed by type of spasms, overall motor severity, and presence/severity of psychiatric problems. The greater severity of motor symptoms was observed in Group 1, the least severity in Group 3, while the severity of blepharospasm in Group 2 was between that observed in Groups 1 and 3. The three motor subtypes also differed by psychiatric features: the lowest severity of psychiatric symptoms was observed in the group with least severe motor symptoms (group 3), while the highest psychiatric severity scores were observed in group 2 that carried intermediate motor severity rather than in the group with more severe motor symptoms (group 1). The three groups did not differ by disease duration, age of onset, sex or other clinical features.Conclusions: The present study suggests that blepharospasm patients may be classified in different subtypes according to the type of spasms, overall motor severity and presence/severity of depressive symptoms and anxiety. [ABSTRACT FROM AUTHOR]

Abstract: Background: Little is known about sleep disturbances in cervical dystonia (CD), particularly the relationship to motoric symptoms. It is critical to clarify these points given the impact on quality of life. Methods: Primary CD patients receiving botulinum toxin (BoNT) injections and age- and gender- matched healthy controls were included. In both groups, sleep quality and daytime sleepiness were assessed. In CD, these assessments were repeated following BoNT injections. CD severity, mood symptoms, and health impact of CD were also assessed. Results: 54 CD patients and 55 controls were included. Impaired sleep quality was more frequent in CD compared to controls (t = 4.82, p < 0.0005), even when controlling for the effects of depression, anxiety, and benzodiazepineuse (F = 5.62, p = 0.020). Excessive daytime sleepiness was not significantly different between groups (t = 1.67, p = 0.1). 48 patients received BoNT and returned for follow-up. There was no improvement in sleep quality (t = 0.834, p = 0.41) or daytime somnolence (t = 1.77, p = 0.083) despite improvement in CD severity (t = 4.77, p < 0.0005) with BoNT. There was a small improvement in health impact (t = 2.10, p = 0.04). Conclusion: Sleep quality was more impaired in CD patients, compared to healthy subjects, and did not improve following BoNT treatment, despite a robust improvement in CD severity. This dichotomy suggests that sleep aberrations in CD require separate focus for effective treatment and cannot be viewed as secondary complications of the motor elements of this condition. [Copyright &y& Elsevier]

Abstract: One factor, which may contribute to slowed movement in dystonia, is impairment in controlling the voluntary rate of motor output. This study examined the ability of patients with focal hand dystonia to rapidly turn force on and off at the wrist and elbow joints. Dystonic patients were slower than controls in rapidly turning on force from rest at both joints, passively relaxing force and rapidly reversing force output from a steady-state flexion contraction. Adding a preload did not improve the ability of dystonic subjects to rapidly turn on force. These results support the idea that dystonia is a disorder of impaired motor cortical activation, possibly due to basal ganglia dysfunction. [Copyright &y& Elsevier]

Background: There are no widely accepted criteria to aid the physician in diagnosing BSP.Objective: To validate recently proposed diagnostic criteria for blepharospasm in a larger and geographically diverse population and to develop a screening system for blepharospasm.Methods: Video-recordings from 211 blepharospasm patients and 166 healthy/disease controls were examined by 8 raters. Agreement for presence of orbicularis oculi spasms, sensory trick, and increased blinking was measured by k statistics. Inability to voluntarily suppress the spasms was asked by the examiner but not captured in the video. Patients/controls were also requested to fill a self-administered questionnaire addressing relevant blepharospasm clinical aspects. The diagnosis at each site was the gold standard for sensitivity/specificity.Results: All the study items yielded satisfactory inter/intra-observer agreement. Combination of items rather than each item alone reached satisfactory sensitivity/specificity. The combined algorithm started with recognition of spasms followed by sensory trick. In the absence of a sensory trick, including "increased blinking" or "inability to voluntarily suppress the spasms" or both items yielded 88-92% sensitivity and 79-83% specificity. No single question of the questionnaire yielded high sensitivity/specificity. Serial application of the questionnaire to our blepharospasm and control subjects and subsequent clinical examination of subjects screening positive by the validated diagnostic algorithms yielded 78-81% sensitivity and 83-91% specificity.Conclusion: These results support the use of proposed diagnostic criteria in multi-ethnic, multi-center cohorts. We also propose a case-finding procedure to screen blepharospasm in a given population with less effort than would be required by examination of all subjects. [ABSTRACT FROM AUTHOR]

A large and ever-growing number of medications can induce various movement disorders. Drug-induced movement disorders are disabling but are often under-recognised and inappropriately managed. In particular, second generation antipsychotics, like first generation agents, are associated with potentially debilitating side-effects, most notably tardive syndromes and parkinsonism, as well as potentially fatal acute syndromes. Appropriate, evidence-based management is essential as these drugs are being prescribed to a growing population vulnerable to these side-effects, including children and elderly people. Prevention of the development of drug-induced movement disorders is an important consideration when prescribing medications that can induce movement disorders. Recent developments in diagnosis, such as the use of dopamine transporter imaging for drug-induced parkinsonism, and treatment, with the approval of valbenazine and deutetrabenazine, the first drugs indicated for tardive syndromes, have improved outcomes for many patients with drug-induced movement disorders. Future research should focus on development of safer antipsychotics and specific therapies for the different tardive syndromes and the treatment of drug-induced parkinsonism. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the minimal clinically important change (MCIC) after treatment in cervical dystonia patients using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS).Methods: Changes in the TWSTRS from an observational study of abobotulinumtoxinA in the routine management of cervical dystonia (NCT01314365) were analyzed using the Patient Global Impression of Change (PGIC) as anchor.Results: For the overall population (N = 304, baseline TWSTRS-Total score 43.4 ± 19.4), the MCIC for the TWSTRS Total score was -11.9 (95%CI: -13.9, -10.0; p < 0.0001). However, thresholds ranged from -3.2 to -18.0 dependent on baseline severity. TWSTRS-Total scores improved linearly by 3 points for every one-point PGIC increase. There was similar linearity between the graded PGIC categories and TWSTRS subscale scores (severity, disability, and pain).Conclusions: A 3-point change is the minimal clinically important change after treatment using TWSTRS as endpoint with higher cutoffs for greater baseline disease severity. For an average trial population (TWSTRS-total: 40-45), a 12-point decrease is clinically meaningful. [ABSTRACT FROM AUTHOR]

Background The ANCHOR-CD prospective observational registry study evaluated the effectiveness of abobotulinumtoxinA in adult idiopathic cervical dystonia (CD) in clinical practice. Methods Adults with CD were eligible. Treating physicians determined abobotulinumtoxinA dose and treatment interval. The primary endpoint was patient response rate (Toronto Western Spasmodic Torticollis Rating Scale [TWSTRS] score reduction ≥ 25% and Patient Global Impression of Change [PGIC] score of + 2 or + 3 at Week 4 of Cycle 1). Results 350 patients enrolled (75% women; mean age 59 ± 13.6 years; 27.4% botulinum neurotoxin-naive) and 347 received at least 1 treatment. The median abobotulinumtoxinA dose for Cycle 1 was 500 Units. At Week 4, the responder rate was 30.6% (n = 304) and the TWSTRS total score decreased 27.4% from baseline. PGIC of at least “Much improved” was documented in 43.6% of patients and maintained in Cycles 2 through 4 (43.3%, 48.9%, and 52.8%, respectively). A total of 39 adverse events (31 study drug-related) were reported in 17 patients (5%); the most common were dysphagia (n = 6), muscle weakness (n = 4), and neck pain (n = 3). Conclusion This study confirmed the beneficial effect of abobotulinumtoxinA on CD in routine clinical practice as measured by improvements in TWSTRS and PGIC. No new safety concerns were identified. [ABSTRACT FROM AUTHOR]

Background We developed a novel secured web-based dystonia video repository for the Dystonia Coalition, part of the Rare Disease Clinical Research network funded by the Office of Rare Diseases Research and the National Institute of Neurological Disorders and Stroke. A critical component of phenotypic data collection for all projects of the Dystonia Coalition includes a standardized video of each participant. We now describe our method for collecting, serving and securing these videos that is widely applicable to other studies. Methods Each recruiting site uploads standardized videos to a centralized secured server for processing to permit website posting. The streaming technology used to view the videos from the website does not allow downloading of video files. With appropriate institutional review board approval and agreement with the hosting institution, users can search and view selected videos on the website using customizable, permissions-based access that maintains security yet facilitates research and quality control. Results This approach provides a convenient platform for researchers across institutions to evaluate and analyze shared video data. We have applied this methodology for quality control, confirmation of diagnoses, validation of rating scales, and implementation of new research projects. Conclusions We believe our system can be a model for similar projects that require access to common video resources. [ABSTRACT FROM AUTHOR]

Background The Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy (CD PROBE; NCT00836017) is a prospective, observational, multicenter, real-world registry designed to assess the safety, effectiveness, and treatment utilization following multiple treatments of onabotulinumtoxinA. Methods Subjects were naïve to botulinum toxin, new to practice, or had not received toxin in ≥ 16 weeks if in a clinical trial. Dosages and treatment intervals varied due to the real-world design. Descriptive and inferential statistics evaluated changes over 3 treatments. Results 1046 subjects enrolled. Subjects were 74.4% female, 63.5% toxin-naïve, mean age 58.0 ± 14.7 years. The mean dose over 2481 treatment sessions was 189.8 ± 87.1 U, with average treatment intervals of 14.6 and 15.1 weeks. The mean Toronto Western Spasmodic Torticollis Rating Scale Total score in subjects who completed all assessments (n = 479) decreased from 39.2 at baseline to 27.1 at final visit ( P < .0001). A high percentage of physicians reported improvement in Clinician Global Impression of Change after initial assessment; this significantly increased at final assessment (n = 479, 91.2% vs 95.0%; P < .0001). Similarly, a high percentage of subjects reported improvement in Patient Global Impression of Change after initial assessment, which significantly increased at final assessment (n = 470, 83.0% vs 91.7%; P < .0001). Significant reductions in all Cervical Dystonia Impact Profile-58 scores were observed (n = 407). Overall, 26.2% of subjects reported adverse events, including muscular weakness (7.0%) and dysphagia (6.4%). Conclusions Results indicate robust improvement in clinical ratings and excellent tolerability following onabotulinumtoxinA treatment of CD. [ABSTRACT FROM AUTHOR]

Typically, botulinum toxin injections for blepharospasm or cervical dystonia (CD) are administered at approximately 3-month intervals, reflecting concerns that shorter intervals might increase the risk of adverse events (AEs) and development of neutralizing antibodies. These post-hoc analyses investigated flexible incobotulinumtoxinA (Xeomin®) injection intervals (6–20 weeks) in patients with blepharospasm or CD. Patients received up to 6 injections at intervals ≥ 6 weeks, as determined by physician assessment upon patient request. The blepharospasm study permitted flexible doses (≤ 50 U/eye). The CD study employed fixed dosing using incobotulinumtoxinA 120 U, 240 U, or placebo for the first treatment followed by subsequent randomization to 120 U or 240 U for the extension period. Standard safety assessments were performed. Intervals < 12 weeks were employed in 207 of 461 (44.9%) treatment cycles for blepharospasm and in 369 of 821 (44.9%) treatment cycles for CD. The most frequent AEs were eyelid ptosis and dry eyes in patients treated for blepharospasm, and dysphagia and neck pain in patients with CD. AE frequency and severity were similar for intervals < 12 weeks and ≥ 12 weeks in both studies. In conclusion, repeated incobotulinumtoxinA injections employing flexible intervals (6–20 weeks) per patients' needs were well tolerated. No additional safety concerns were observed with < 12-week intervals compared with ≥ 12-week intervals. [ABSTRACT FROM AUTHOR]

Summary: Background: In models of dopaminergic neuronal loss, the dopamine agonist pramipexole has exhibited neuroprotective properties. The Pramipexole On Underlying Disease (PROUD) study was designed to identify whether early versus delayed pramipexole initiation has clinical and neuroimaging benefits in patients with Parkinson's disease (PD). Methods: Between May 24, 2006, and April 22, 2009, at 98 centres, we recruited patients with PD diagnosed within 2 years and aged 30–79 years. We randomly assigned eligible patients (ratio 1:1), by a centralised, computerised randomisation schedule, to receive double-blind either placebo or pramipexole (1·5 mg a day) and followed them up for 15 months. At 9 months, or as early as 6 months if considered necessary, placebo recipients were assigned to pramipexole. In a neuroimaging substudy, striatal dopamine-transporter binding was assessed by SPECT. All patients, investigators, and independent raters were masked to study treatment. The primary endpoint was the 15-month change from baseline in total score on the unified Parkinson's disease rating scale (UPDRS). This trial is registered with ClinicalTrials.gov, number NCT00321854. Findings: Of 535 patients, 261 were randomly assigned to receive pramipexole and 274 to receive placebo. At 15 months (n=411), adjusted mean change in UPDRS total score showed no significant difference between early and delayed pramipexole (−0·4 points, 95% CI −2·2 to 1·4, p=0·65). 62 patients in the early pramipexole group and 61 patients in the delayed pramipexole group were included in the neuroimaging substudy, for which the adjusted mean 15-month change in striatal 123I-FP-CIT binding was −15·1% (SE 2·1) for early and −14·6% (2·0) for delayed pramipexole (difference −0·5 percentage points, 95% CI −5·4 to 4·4, p=0·84). Overall, 180 (81%) of patients given early pramipexole and 179 (84%) patients given delayed pramipexole reported adverse events (most frequently nausea), and 22 (10%) patients in the early pramipexole group and 17 (8%) in the delayed pramipexole group had serious events, two of which (hallucinations and orthostatic hypotension) were deemed related to study drug. Interpretation: By clinical and neuroimaging measures, pramipexole showed little evidence differentiating 15-month usage from usage delayed for 6–9 months. The results do not support the hypothesis that pramipexole has disease-modifying effects. Funding: Boehringer Ingelheim GmbH. [Copyright &y& Elsevier]

Abstract: This is a review on the use of injections of botulinum toxin for the treatment of focal dystonias. Disorders covered include cranial dystonia, cervical dystonia, spasmodic dysphonia, and focal hand dystonia. Considered are clinical aspects, alternative treatment strategies and principles of use of botulinum toxin injections. [Copyright &y& Elsevier]

Abstract: Objective: This study evaluated whether changes in the electromygraphic (EMG) pattern during rapid point-to-point movements in individuals diagnosed with PD can: (1) distinguish PD subjects from healthy subjects and (2) determine if differences in the EMG pattern reflect disease severity in PD. Methods: Three groups of 10 PD subjects and 10 age/sex-matched healthy subjects performed rapid 72° point-to-point elbow flexion movements. PD subjects were divided, a priori, into three groups based upon off medication motor UPDRS score. Results: Measures related to the EMG pattern distinguished all PD subjects and 9 out of 10 healthy subjects, resulting in 100% sensitivity. Further, significant correlations were shown between EMG measures and the motor UPDRS score. After 30 months, the one healthy subject whose EMG pattern was abnormal was reexamined. The EMG measures remained abnormal and the motor UPDRS score went from 0 to 10. Parkinson’s disease was diagnosed. Conclusion: Measures related to the variability of the EMG pattern during rapid point-to-point movements provide neurophysiological measures that objectively distinguish PD subjects from healthy subjects. These measures also correlate with disease severity. Significance: EMG measures may provide a non-invasive measure that is sensitive and specific for identifying individuals with PD. [Copyright &y& Elsevier]