Parkinsonism and dystonia: Clinical spectrum and diagnostic clues

The links between the two archetypical basal ganglia disorders, dystonia and parkinsonism, are manifold and stem from clinical observations, imaging studies, animal models and genetics. The combination of both, i.e. the syndrome of dystonia-parkinsonism, is not uncommonly seen in movement disorders clinics and has a myriad of different underlying aetiologies, upon which treatment and prognosis depend. Based on a comprehensive literature review, we delineate the clinical spectrum of disorders presenting with dystonia-parkinsonism. The clinical approach depends primarily on the age at onset, associated neurological or systemic symptoms and neuroimaging. The tempo of disease progression, and the response to L-dopa are further important clues to tailor diagnostic approaches that may encompass dopamine transporter imaging, CSF analysis and, last but not least, genetic testing. Later in life, sporadic neurodegenerative conditions are the most frequent cause, but the younger the patient, the more likely the cause is unravelled by the recent advances of molecular genetics that are focus of this review. Here, knowledge of the associated phenotypic spectrum is key to guide genetic testing and interpretation of test results. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna

A survey of falls in people with dystonia.

ObjectiveDystonia is a chronic and sometimes progressive neurological disorder causing abnormalities in movement and function. We conducted a preliminary survey to investigate whether people with dystonia experience falls and to identify contributing factors to falls in this population.MethodsAn online survey of people with dystonia was conducted in November 2015. Respondents were asked to complete demographic information, three questionnaires (the Falls Self-Efficacy Scale International [FES-I], the Activities-based Balance Confidence Scale [ABC] and the Functional Disability Questionnaire [FDQ]), and to report any falls sustained during the previous 6 months.ResultsThirty-nine percent of the 122 respondents reported falling in the previous 6 months and 65% of fallers were diagnosed with dystonia not affecting the lower limbs. Fallers reported lower falls self-efficacy and balance confidence with higher functional disability. Both falling scales correlated with self-reported functional disability. Linear regression analysis for falls prediction revealed the variables FES-I and FDQ accounted for almost 30% of the falls in this dystonia population.ConclusionThis survey indicates that fear of falling and balance confidence are impaired in people with dystonia, possibly impacting on function and falls. Further investigation into balance, function and falls in this population is required

Continuous Subcutaneous Foslevodopa/Foscarbidopa in Parkinson’s Disease: Safety and Efficacy Results From a 12-Month, Single-Arm, Open-Label, Phase 3 Study

\ua9 2023, The Author(s). Introduction: Foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs for the treatment of Parkinson’s disease (PD), is administered as a 24-hour/day continuous subcutaneous infusion (CSCI) with a single infusion site. The efficacy and safety of foslevodopa/foscarbidopa versus oral immediate-release LD/CD was previously demonstrated in patients with PD in a 12-week, randomized, double-blind, phase 3 trial (NCT04380142). We report the results of a separate 52-week, open-label, phase 3 registrational trial (NCT03781167) that evaluated the safety/tolerability and efficacy of 24-hour/day foslevodopa/foscarbidopa CSCI in patients with advanced PD. Methods: Male and female patients with levodopa-responsive PD and ≥ 2.5 hours of “Off” time/day received 24-hour/day foslevodopa/foscarbidopa CSCI at individually optimized therapeutic doses (approximately 700–4250 mg of LD per 24 hours) for 52 weeks. The primary endpoint was safety/tolerability. Secondary endpoints included changes from baseline in normalized “Off” and “On” time, percentage of patients reporting morning akinesia, Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Parkinson’s Disease Sleep Scale–2 (PDSS-2), 39-item Parkinson’s Disease Questionnaire (PDQ-39), and EuroQol 5-dimension questionnaire (EQ-5D-5L). Results: Of 244 enrolled patients, 107 discontinued, and 137 completed treatment. Infusion site events were the most common adverse events (AEs). AEs were mostly nonserious (25.8% of patients reported serious AEs) and mild/moderate in severity. At week 52, “On” time without troublesome dyskinesia and “Off” time were improved from baseline (mean [standard deviation (SD)] change in normalized “On” time without troublesome dyskinesia, 3.8 [3.3] hours; normalized “Off” time, −3.5 [3.1] hours). The percentage of patients experiencing morning akinesia dropped from 77.7% at baseline to 27.8% at week 52. Sleep quality (PDSS-2) and quality of life (PDQ-39 and EQ-5D-5L) also improved. Conclusion: Foslevodopa/foscarbidopa has the potential to provide a safe and efficacious, individualized, 24-hour/day, nonsurgical alternative for patients with PD. Trial Registration Number: ClinicalTrials.gov identifier NCT03781167

Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination.

Abstract OBJECTIVE: We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination. METHODS: We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients. RESULTS: The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10\u2009mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of 652 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077). CONCLUSION: Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation

Leg muscle power is enhanced by training in people with Parkinson's disease: A randomized controlled trial

Objective: To determine the effects of leg muscle power training in people with Parkinsons disease. Design: Randomized controlled trial. Setting: University laboratory (outcome measures and experimental intervention), community (control intervention). Subjects: Community-dwelling people with Parkinsons disease. Interventions: Leg muscle power training using pneumatic variable resistance equipment (experimental) was compared with low intensity sham exercise (control). Both groups exercised twice weekly for 12 weeks. Main measures: Primary outcomes were peak power of four leg muscle groups. Secondary outcomes were measures of muscle strength, mobility, balance and falls. Results: Exercise adherence was high in both groups. Leg muscle power was significantly better in the experimental group than the control group in all four primary outcome measures at 12 weeks after adjusting for baseline values: leg extensors (57.9 watts, 95% confidence interval (CI) 22.0-93.7, p = 0.002); knee flexors (29.6 watts, 95% CI 7.4-51.8, p = 0.01); hip flexors (68.1 watts, 95% CI 19.6-116.5, p = 0.007); and hip abductors (37.4 watts, 95% CI 19.9-54.9, p < 0.001). The experimental group performed significantly better on tests of leg muscle strength (p < 0.001 to 0.07) and showed trends toward better performance in the Timed Up and Go (p = 0.13) and choice stepping reaction time (p = 0.11). There was a non-significant reduction in the rate of falls in the experimental group compared with the control group (incidence rate ratio 0.84, p = 0.76). Conclusions: This programme significantly improved muscle power in all trained muscle groups. © The Author(s) 2013

Validation of Fear of Falling and Balance Confidence Assessment Scales in Persons with Dystonia

© 2017 Academy of Neurologic Physical Therapy, APTA. Background and Purpose: Falls are problematic for people living with neurological disorders and a fear of falling can impact on actual falls. Fear of falling is commonly assessed using the Falls Self-Efficacy Scale International (FES-I) or the Activities-specific Balance Confidence (ABC) Scale. These scales can predict risk of falling. We aimed to validate the FES-I and the ABC in persons with dystonia. Methods: We conducted an online survey of people with dystonia, collecting information on demographics, 6-month falls history, dystonia disability, and the FES-I and ABC scales. Scales were validated for structural validity and internal consistency. We also examined goodness-of-fit, convergent validity, and predictive validity, and determined cutoff scores for predicting falls risk. Results: Survey responses (n = 122) showed that both FES-I and ABC scales have high internal validity and convergent validity with the Functional Disability Questionnaire in persons with dystonia. Each scale examines a single factor, fear of falling (FES-I) and balance confidence (ABC). At least one fall was reported by 39% of participants; the cutoff value for falls risk was found to be 29.5 and 71.3 for the FES-I and the ABC respectively. Discussion and Conclusions: The FES-I and the ABC scales are valid scales to examine fear of falling and balance confidence in persons with dystonia. Fear of falling is high and balance confidence is low and both are worse in those with dystonia who have previously fallen. Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A182)

Head and trunk stability during gait before and after levodopa intake in Parkinson's disease subtypes

Introduction: People with Parkinson's disease (PD) can be classified into tremor dominant (TD) and postural instability and gait difficulty (PIGD) subtypes; the latter group having more impaired gait and increased fall risk. While there is some evidence that anti-parkinsonian medication, levodopa, might not improve balance and gait control or reduce fall risk in the PIGD subtype, it is unclear whether the levodopa dosage intake affects gait stability. To address these issues, this study used accelerometry to compare gait stability: (i) during before and after levodopa intake between non-PIGD and PIGD subtypes; (ii) between individuals who took less or >750 mg of levodopa/day. Methods: In 15 non-PIGD (Combination of 13 TD patients and 2 classified as indeterminate subtype) and 23 PIGD participants of similar mean (SD) age ((63.0 (7.6) versus 62.6 (10.0) years, respectively)) and disease-duration (8.9 (8.9) versus 11.3 (4.6) years, respectively), head and trunk stability during gait was examined using anteroposterior, vertical and mediolateral acceleration harmonic ratios (HRs). Participants were assessed before and after a levodopa dose, during typical “off” and “on” periods, respectively. Results: Two-way analyses of variance (group × medication status) revealed that compared to the non-PIGD subgroup, the PIGD subgroup showed significantly worse head stability (lower anteroposterior HR) in the “off” state, and significantly worse pelvis stability (significantly lower mediolateral and vertical HRs) in the “on” state (p < 0.05 for both). Levodopa was effective in treating most of the disease-related impairments (not bradykinesia) in both groups, (p < 0.05) but improved gait stability (lowered pelvis mediolateral and vertical HRs) only in people with the non-PIGD subtype (p < 0.05) and those taking <750 mg of levodopa/day (p < 0.05). Conclusions: People with the PD PIGD subtype exhibit impaired gait stability that is not improved and frequently worsened by levodopa. New non-pharmaceutical approaches, technological (e.g. cueing) or exercise-based (e.g. balance training) are required to improve or compensate for mediolateral gait instability in this subtype and ultimately prevent falls

A cross-sectional study of walking, balance and upper limb assessment scales in people with cervical dystonia.

Cervical dystonia (CD) is a neurological movement disorder causing the neck to move involuntarily away from the neutral position. CD is a network disorder, involving multiple brain areas and, therefore, may impair movement in parts of the body other than the neck. This study used clinical assessments to investigate walking, balance and upper limb function (UL) in people with CD; the reliability of scoring these assessments and examined for relationship between CD severity, usual exercise and clinical assessments. We conducted a prospective observational cohort study of participants with isolated, focal, idiopathic CD. Participants were assessed by experienced physiotherapists and completed three questionnaires and eight clinical assessments of fear of falling, balance confidence, walking, balance, UL function and usual exercise. Results were compared to published data from healthy adults and other neurological populations. Twenty-two people with mild to moderate CD participated. Fear of falling, gross UL function and usual exercise were worse in people with CD compared with healthy adults, while walking, balance and distal UL function were similar to healthy populations. All assessments were reliably performed by physiotherapists, and we found no correlations between the severity of dystonia or usual exercise and performance on the physical assessments. Routine performance of clinical assessment of walking and balance are likely not required in people with mild to moderate CD; however, fear of falling and gross upper limb function should be assessed to determine any problems which may be amenable to therapy

Transitional Care for Young People with Neurological Disorders: A Scoping Review with A Focus on Patients with Movement Disorders

Childhood‐onset movement disorders represent a heterogenous group of conditions. Given the complexity of these disorders, the transition of care from pediatric to adult medicine is an important consideration. We performed a scoping review of the literature on transitional care in chronic neurological disease, exploring key transitional issues and proposed transitional care models. Our aim was to describe the current knowledge and gaps about the transition process of young adults with chronic neurological disorders, paying special attention to childhood onset movement disorders. A total of 64 articles were included in the qualitative synthesis; 56 articles reported on transitional care issues, and 8 articles reported on transitional care models. Only 2 articles included patients with movement disorders. The following 4 main transitional issues were identified following synthesis of the available literature: (1) inadequate preparation for the transition process, (2) inappropriate and inconsistent transition practices, (3) inadequate adult services, and (4) heightened emotional response surrounding transition. Of the reported transitional care models, multidisciplinary ambulatory care was the most common approach. In studies evaluating patient‐related outcomes, positive health, educational, and vocational outcomes were found. The available literature provides insights on issues that can arise during transition that should be addressed to improve patient and caregiver comfort and satisfaction with care. Further research is needed to evaluate how transitional care programs affect outcomes and their cost effectiveness. More studies are required to determine the needs and outcomes specific to patients with childhood onset movement disorders