Search Results (30)

There is limited published guidance available to help less experienced practitioners assess and manage shoulder conditions, including spasticity, after acquired central nervous system (CNS) lesions. To address this gap, 11 spasticity and dystonia experts convened in a 2023 meeting to build on existing guidance, provide consensus on best treatment practice, and develop expert recommendations to guide the diagnosis and treatment of complications of shoulder conditions following CNS lesions. Presentations by each expert on diagnosis and management were followed by discussion; consensus on assessment and treatment practices was identified and recommendations developed. The expert panel recommended an assessment approach structured using the following components: patient history, including interpretation of reported symptoms; observation of postures and pain responses; clinical examination with targeted tests for specific signs; diagnostic tests; and assessment of upper limb impairment, activity limitations, and participation restrictions. This assessment process and the recommended measures recognize the importance of identifying shoulder involvement in upper limb spasticity as part of the diagnostic process in shoulder conditions following CNS lesions. These recommendations provide a practical approach to diagnosis and treatment for clinicians who are less experienced in evaluating and treating such conditions, simplifying otherwise complicated clinical scenarios. Full article

Background: Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder due to mutations in the ATM gene. Given the residual kinase activity and the type of ATM mutation, its clinical spectrum varies from a severe classic phenotype to a variant atypical form. Material and methods: This study included 28 patients belonging to four big Bulgarian Muslim pedigrees with tremor and dystonia. Whole-exome sequencing was performed in seven affected individuals from two unrelated pedigrees, followed by Sanger sequencing of the coding sequences and exon–intron borders of the ATM gene. Results: Twenty-four of the affected individuals were homozygous for c.8147T>C (p.Val2716Ala) in ATM, while four of the affected individuals were compound heterozygous. The targeted Sanger sequencing along the ATM gene revealed as a second mutation in three of the patients the splice-site variant c.4909+1G>A and in one patient a synonymous pathogenic variant with a splicing effect, c.3576G>A, p.Lys1192. The age at onset in our group varied between 14 days and 40 years. The main symptoms were dystonia and tremor, more prominent in the upper limbs and the neck, and dystonic dysarthria and dysphagia. The clinical course was very slowly progressive. Brain imaging was normal in the majority of the patients. Conclusion: Clinical features due to mutations in the ATM gene can be very broad. The disease may appear as dystonia, especially of early onset, without frank cerebellar involvement and also normal cerebral imaging. A-T should be considered in all patients with unexplained, even mild movement disorders and elevated α fetoprotein. Full article

Focal limb dystonias (FLDs) are abnormal postures and muscle contractions in an arm or leg that can occur in the setting of specific activities or without any stimulus. This pathology can have a profound impact on quality of life and potentially limit work in those whose dystonias are brought on by activities related to their occupations. Botulinum toxin (BoNT) is approved for use in the United States by the Food and Drug Administration for several indications, including cervical dystonia and blepharospasm, but not for FLD. Despite this limitation, BoNT is frequently used clinically for FLD, generally with individualized dosing based on patient need and clinician expertise. Various methods exist for targeting treatment to the specific affected muscles and assessing the benefit of treatment. Small clinical trials have demonstrated the efficacy of BoNT, but larger controlled studies are needed. Full article

Background: Runner’s dystonia (RD), a rare task-specific lower-limb dystonia affecting high-mileage runners, presents as abnormal lower-extremity muscle contractions during running. Treatment of RD is challenging and often confounded by significant diagnostic delays due to overlapping symptomatology with other conditions. This case series examines the relationship between stiff knee gait RD and musculoskeletal (MSK) knee pathology. Methods: Eight RD cases, evaluated at the NIH Movement Disorders Clinic since 2018, were retrospectively reviewed. Patients underwent neurological, biomechanical, and MSK evaluations, including 3D motion analysis, surface electromyography, and knee ultrasound. Therapeutic interventions, including botulinum neurotoxin (BoNT) injections, were assessed. Results: Seven patients demonstrated stiff knee gait subtypes, with all having ipsilateral and/or contralateral knee effusions or tendinopathies. Three patients who received MSK interventions (e.g., aspiration, corticosteroid injections) combined with BoNT therapy experienced significant symptom improvement. One patient with isolated foot dystonia displayed different biomechanical patterns without knee pathology. Conclusions: RD patients with stiff knee gait often exhibit knee pathology, most likely due to altered biomechanics and running history. Addressing both issues is essential for optimizing treatment outcomes, reducing pain, and improving function, especially since pain can trigger dystonia. Future research should determine the ideal sequence of interventions for RD patients with MSK issues to develop effective, personalized treatment algorithms. Full article

Since its first approval by the Food and Drug Administration in 1989 for strabismus, botulinum toxin indications of use have been widely expanded. Due to its anticholinergic properties, this toxin is currently approved in adult patients for the treatment of a wide range of neuromuscular, otolaryngologic, orthopedic, gastrointestinal, and urologic disorders. Approved pediatric indications of use include the treatment of blepharospasm associated with dystonia, strabismus, lower-limb spasticity, focal spasticity in patients with cerebral palsy, and neurogenic detrusor overactivity. Alongside these approved indications, botulinum toxin is extensively used off-label. Although several clinical studies have shown that botulinum toxin is effective and well-tolerated in children, uncertainties persist regarding its long-term effects on growth and appropriate dosing in this population. As such, further research is needed to better define the botulinum toxin risk–benefit profile and expand approved uses in pediatrics. This narrative review aimed to provide a broad overview of the evidence concerning the clinical effectiveness and safety of BoNT with respect to its principal authorized and non-authorized pediatric therapeutic indications, as well as to describe perspectives on its future use in children. Full article

Chorea is a hyperkinetic movement disorder, accompanied by dystonia, myoclonus, tics, stereotypies, and tremors. It is characterized by excessive, purposeless movements that are distressing, irregularly timed, and randomly distributed. Chorea can be present in many diseases, such as hereditary, metabolic disturbance, drug-induced, and functional disorders, and, rarely, genetic, autoimmune, and infectious diseases. Primary myelofibrosis (PMF) is a myeloproliferative neoplasm that leads to ineffective clonal hematopoiesis, fibrous tissue deposits in the bone marrow, extramedullary hematopoiesis, and splenomegaly. In rare cases, following uncertain pathological mechanisms, it can present with chorea, particularly affecting the limbs, head, and orofaciolingual muscles. We present a case of a male patient with evolving PMF over several years who was admitted for progressive cognitive impairment and generalized involuntary movement disorder. We also present a review of all cases of myeloproliferative disorders presenting with chorea published in the last 40 years. Full article

Fatty acid hydroxylase-associated neurodegeneration (FAHN/SPG35) is caused by pathogenic variants in FA2H and has been linked to a continuum of specific motor and non-motor neurological symptoms, leading to progressive disability. As an ultra-rare disease, its mutational spectrum has not been fully elucidated. Here, we present the prototypical workup of a novel FA2H variant, including clinical and in silico validation. An 18-year-old male patient presented with a history of childhood-onset progressive cognitive impairment, as well as progressive gait disturbance and lower extremity muscle cramps from the age of 15. Additional symptoms included exotropia, dystonia, and limb ataxia. Trio exome sequencing revealed a novel homozygous c.75C>G (p.Cys25Trp) missense variant in the FA2H gene, which was located in the cytochrome b5 heme-binding domain. Evolutionary conservation, prediction models, and structural protein modeling indicated a pathogenic loss of function. Brain imaging showed characteristic features, thus fulfilling the complete multisystem neurodegenerative phenotype of FAHN/SPG35. In summary, we here present a novel FA2H variant and provide prototypical clinical findings and structural analyses underpinning its pathogenicity. Full article

Tryptophan hydroxylase 2 (TPH2) is the key and rate-limited enzyme of serotonin (5-HT) synthesis in the brain. The C1473G mutation in the Tph2 gene results in a two-fold decrease in enzyme activity in the mouse brain. The lethal yellow (A^Y) mutation in the Raly-Agouti locus results in the overexpression of the Agouti gene in the brain and causes obesity and depressive-like behavior in mice. Herein, the possible influences of these mutations and their combination on body mass, behavior, brain 5-HT and melanocortin systems in mice of the B6-1473CC/aa. B6-1473CC/A^Ya, B6-1473GG/aa are investigated. B6-1473GG/A^Ya genotypes were studied. The 1473G and A^Y alleles increase the activity of TPH2 and the expression of the Agouti gene, respectively, but they do not alter 5-HT and 5-HIAA levels or the expression of the genes Tph2, Maoa, Slc6a4, Htr1a, Htr2a, Mc3r and Mc4r in the brain. The 1473G allele attenuates weight gain and depressive-like immobility in the forced swim test, while the A^Y allele increases body weight gain and depressive-like immobility. The combination of these alleles results in hind limb dystonia in the B6-1473GG/A^Ya mice. This is the first evidence for the interaction between the C1473G and A^Y mutations. Full article

The pooled incidences of treatment-emergent adverse events (TEAEs) were examined by indication using the integrated clinical database of Merz-sponsored, placebo-controlled, or repeat-dose studies of incobotulinumtoxinA in adults with cervical dystonia, blepharospasm, limb spasticity, sialorrhea, or essential tremor of the upper limb. Overall incidences of TEAEs, serious TEAEs, TEAEs leading to discontinuation, fatal TEAEs, TEAEs of special interest (TEAESIs; indicating possible toxin spread), and treatment-related (TR) events were determined for incobotulinumtoxinA and placebo after a single injection and for repeated dose cycles of incobotulinumtoxinA. The most frequent events after a single dose of incobotulinumtoxinA are summarized. After a single cycle, incidences of overall TEAEs were similar between incobotulinumtoxinA and the placebo in most indications, although between-indication differences were observed. Few TEAEs led to incobotulinumtoxinA discontinuation; there were no fatal TEAEs with incobotulinumtoxinA. In general, repeated cycles did not increase the incidence of any event. The most frequent TR-TEAEs were indication-dependent, including dysphagia for indications affecting the head or neck. The TR-TEAESIs across all indications were most commonly muscular weakness, dysphagia and dry mouth. Overall, the results of this pooled analysis support and extend the favorable safety and tolerability profile of incobotulinumtoxinA for the treatment of adult neurological disorders established by individual clinical studies. Full article

By blocking the release of neurotransmitters, botulinum toxin A (BoNT-A) is an effective treatment for muscle over-activity and pain in stroke patients. BoNT-A has also been reported to increase passive range of motion (p-ROM), the decrease of which is mainly due to muscle shortening (i.e., muscle contracture). Although the mechanism of action of BoNT-A on p-ROM is far from understood, pain relief may be hypothesized to play a role. To test this hypothesis, a retrospective investigation of p-ROM and pain was conducted in post-stroke patients treated with BoNT-A for upper limb hypertonia. Among 70 stroke patients enrolled in the study, muscle tone (Modified Ashworth Scale), pathological postures, p-ROM, and pain during p-ROM assessment (Numeric Rating Scale, NRS) were investigated in elbow flexors (48 patients) and in finger flexors (64 patients), just before and 3–6 weeks after BoNT-A treatment. Before BoNT-A treatment, pathological postures of elbow flexion were found in all patients but one. A decreased elbow p-ROM was found in 18 patients (38%). Patients with decreased p-ROM had higher pain-NRS scores (5.08 ± 1.96, with a pain score ≥8 in 11% of cases) than patients with normal p-ROM (0.57 ± 1.36) (p < 0.001). Similarly, pathological postures of finger flexion were found in all patients but two. A decreased finger p-ROM was found in 14 patients (22%). Pain was more intense in the 14 patients with decreased p-ROM (8.43 ± 1.74, with a pain score ≥ 8 in 86% of cases) than in the 50 patients with normal p-ROM (0.98 ± 1.89) (p < 0.001). After BoNT-A treatment, muscle tone, pathological postures, and pain decreased in both elbow and finger flexors. In contrast, p-ROM increased only in finger flexors. The study discusses that pain plays a pivotal role in the increase in p-ROM observed after BoNT-A treatment. Full article

Xeomin^® is a commercial formulation of botulinum neurotoxin type A (BoNT/A) clinically authorized for treating neurological disorders, such as blepharospasm, cervical dystonia, limb spasticity, and sialorrhea. We have previously demonstrated that spinal injection of laboratory purified 150 kDa BoNT/A in paraplegic mice, after undergoing traumatic spinal cord injury (SCI), was able to reduce excitotoxic phenomena, glial scar, inflammation, and the development of neuropathic pain and facilitate regeneration and motor recovery. In the present study, as proof of concept in view of a possible clinical application, we studied the efficacy of Xeomin^® in the same preclinical SCI model in which we highlighted the positive effects of lab-purified BoNT/A. Data comparison shows that Xeomin^® induces similar pharmacological and therapeutic effects, albeit with less efficacy, to lab-purified BoNT/A. This difference, which can be improved by adjusting the dose, can be attributable to the different formulation and pharmacodynamics. Although the mechanism by which Xeomin^® and laboratory purified BoNT/A induce functional improvement in paraplegic mice is still far from being understood, these results open a possible new scenario in treatment of SCI and are a stimulus for further research. Full article

Tremor is part of the phenomenological spectrum of dystonia. Treatments available for tremor in dystonia are oral medications (OM), botulinum neurotoxin (BoNT), and brain surgery (deep brain stimulation or thalamotomy). There is limited knowledge regarding the outcome of different treatment options, and evidence is especially scarce for the tremor of the upper limbs occurring in people with dystonia. In this single-center retrospective study, we evaluated the outcome of different treatments in a cohort of people with upper limb dystonic tremors. Demographic, clinical, and treatment data were analyzed. Dropout rates and side effects were specifically assessed, as well as the 7-point patient-completed clinical global impression scale (p-CGI-S, 1: very much improved; 7: very much worse) as outcome measures. A total of 47 subjects (46.8% female) with dystonic tremor, tremor associated with dystonia, or task-specific tremor were included, with a median age at onset of 58 years (7–86). A total of 31 subjects were treated with OM, 31 with BoNT, and 7 with surgery. Dropout rates with OM were 74.2% due to either lack of efficacy (n = 10) or side effects (n = 13). A total of 7 patients treated with BoNT (22.6%) had mild weakness, causing dropout in 2. P-CGI-S was ≤3 (improvement) in 39% with OM, compared to 92% with BoNT and 100% with surgery. These findings suggest good symptom control of the tremor of the upper limb in dystonia with BoNT and surgery, with higher rates of dropout and side effects with OM. Randomized controlled studies are needed to confirm our findings and provide further insight into better selecting suitable patients for BoNT or brain surgery. Full article

Background—Movement patterns in dyskinetic cerebral palsy (DCP) are characterized by abnormal postures and involuntary movements. Current evaluation tools in DCP are subjective and time-consuming. Sensors could yield objective information on pathological patterns in DCP, but their reliability has not yet been evaluated. The objectives of this study were to evaluate (i) reliability and (ii) discriminative ability of sensor parameters. Methods—Inertial measurement units were placed on the arm, forearm, and hand of individuals with and without DCP while performing reach-forward, reach-and-grasp-vertical, and reach-sideways tasks. Intra-class correlation coefficients (ICC) were calculated for reliability, and Mann–Whitney U-tests for between-group differences. Results—Twenty-two extremities of individuals with DCP (mean age 16.7 y) and twenty individuals without DCP (mean age 17.2 y) were evaluated. ICC values for all sensor parameters except jerk and sample entropy ranged from 0.50 to 0.98 during reach forwards/sideways and from 0.40 to 0.95 during reach-and-grasp vertical. Jerk and maximal acceleration/angular velocity were significantly higher for the DCP group in comparison with peers. Conclusions—This study was the first to assess the reliability of sensor parameters in individuals with DCP, reporting high between- and within-session reliability for the majority of the sensor parameters. These findings suggest that pathological movements of individuals with DCP can be reliably captured using a selection of sensor parameters. Full article

This review provides an up-to-date literature account on the efficacy of Botulinum toxin treatment for common motor disorders of Parkinson Disease. The reviewed disorders include the common motor disorders in PD such as tremor, focal foot dystonia, rigidity and freezing of gait (FOG). In the area of Parkinson tremor, two newly described evaluation/injection techniques (Yale method in USA and Western University method in Canada) offer efficacy with low incidence of hand and finger weakness as side effects. Blinded studies conducted on foot dystonia of PD indicate that botulinum toxin injections into toe flexors are efficacious in alleviating this form of dystonia. Small, blinded studies suggest improvement of Parkinson rigidity after botulinum toxin injection; proof of this claim, however, requires information from larger, blinded clinical trials. In FOG, the improvement reported in open label studies could not be substantiated in blinded investigations. However, there is room for further controlled studies that include the proximal lower limb muscles in the injection plan and/or use higher doses of the injected toxin for this indication. Full article

Factors associated with neurotoxin treatments in children with cerebral palsy (CP) are poorly studied. We developed and externally validated a prediction model to identify the prognostic phenotype of children with CP who require neurotoxin injections. We conducted a longitudinal, international, multicenter, double-blind descriptive study of 165 children with CP (mean age 16.5 ± 1.2 years, range 12–18 years) with and without neurotoxin treatments. We collected functional and clinical data from 2005 to 2020, entered them into the BTX-PredictMed machine-learning model, and followed the guidelines, “Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis”. In the univariate analysis, neuromuscular scoliosis (p = 0.0014), equines foot (p < 0.001) and type of etiology (prenatal > peri/postnatal causes, p = 0.05) were linked with neurotoxin treatments. In the multivariate analysis, upper limbs (p < 0.001) and trunk muscle tone disorders (p = 0.02), the presence of spasticity (p = 0.01), dystonia (p = 0.004), and hip dysplasia (p = 0.005) were strongly associated with neurotoxin injections; and the average accuracy, sensitivity, and specificity was 75%. These results have helped us identify, with good accuracy, the clinical features of prognostic phenotypes of subjects likely to require neurotoxin injections. Full article