Effects of physiotherapy and home-based training in parkinsonian syndromes: protocol for a randomised controlled trial (MobilityAPP).

INTRODUCTION: Gait and mobility impairment are pivotal signs of parkinsonism, and they are particularly severe in atypical parkinsonian disorders including multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). A pilot study demonstrated a significant improvement of gait in patients with MSA of parkinsonian type (MSA-P) after physiotherapy and matching home-based exercise, as reflected by sensor-based gait parameters. In this study, we aim to investigate whether a gait-focused physiotherapy (GPT) and matching home-based exercise lead to a greater improvement of gait performance compared with a standard physiotherapy/home-based exercise programme (standard physiotherapy, SPT). METHODS AND ANALYSIS: This protocol was deployed to evaluate the effects of a GPT versus an active control undergoing SPT and matching home-based exercise with regard to laboratory gait parameters, physical activity measures and clinical scales in patients with Parkinson's disease (PD), MSA-P and PSP. The primary outcomes of the trial are sensor-based laboratory gait parameters, while the secondary outcome measures comprise real-world derived parameters, clinical rating scales and patient questionnaires. We aim to enrol 48 patients per disease group into this double-blind, randomised-controlled trial. The study starts with a 1 week wearable sensor-based monitoring of physical activity. After randomisation, patients undergo a 2 week daily inpatient physiotherapy, followed by 5 week matching unsupervised home-based training. A 1 week physical activity monitoring is repeated during the last week of intervention. ETHICS AND DISSEMINATION: This study, registered as 'Mobility in Atypical Parkinsonism: a Trial of Physiotherapy (Mobility_APP)' at clinicaltrials.gov (NCT04608604), received ethics approval by local committees of the involved centres. The patient's recruitment takes place at the Movement Disorders Units of Innsbruck (Austria), Erlangen (Germany), Lausanne (Switzerland), Luxembourg (Luxembourg) and Bolzano (Italy). The data resulting from this project will be submitted to peer-reviewed journals, presented at international congresses and made publicly available at the end of the trial. TRIAL REGISTRATION NUMBER: NCT04608604.

Physiotherapy improves motor function in patients with the Parkinson variant of multiple system atrophy: A prospective trial.

BACKGROUND AND OBJECTIVES: Gait impairment and reduced mobility are disabling symptoms of multiple system atrophy. While physiotherapy is increasingly recognized as a valuable supplement to pharmacotherapy for patients with Parkinson's disease, data on the efficacy of physiotherapy for multiple system atrophy are lacking. This study aimed to explore the feasibility of two consecutive exercise-based interventions in patients with multiple system atrophy. SUBJECTS AND METHODS: We included 10 patients with the parkinsonian variant of multiple system atrophy and 10 patients with Parkinson's disease, matched for gender and Hoehn & Yahr stage (≤3). Interventions consisted of a five-day inpatient physiotherapy program followed by a five-week unsupervised home-based exercise program. Outcomes included instrumented gait analysis, patient questionnaires, clinical rating scales and physical tests. Patients were examined at baseline, after the first inpatient treatment and again after the home-based intervention. Additionally, a structured telephone interview was performed immediately after the second intervention period. RESULTS: Both patient groups exhibited a similar improvement of gait after the interventions, as measured by instrumented gait analysis. These effects reached their maximum level after inpatient physiotherapy and remained stable following the home-based exercise program. Patient questionnaires also showed improvements after the interventions, but motor clinical rating scales did not. CONCLUSION: Our pilot results suggest that a short-term bout of physiotherapy is feasible, safe and improves gait performance in patients with multiple system atrophy. This highlights the potential of physiotherapy for this disabling condition where pharmacotherapy typically achieves poor effects. The present findings warrant a larger controlled study.

Feedback Facility-Assisted Balance Training in a Patient With Multiple System Atrophy: A Case Presentation.

Multiple system atrophy is a rare neurodegenerative disease with a poor prognosis. Furthermore, there are no pharmacological or notable rehabilitation strategies available to prevent the worsening of the disease. This case presentation assessed the outcome of feedback facility-assisted balance training in combination with physical therapy in a 61-year-old man. The patient participated in 30 training sessions over 6 weeks for 30 minutes each that involved balance training. His static and dynamic balance abilities were improved on the Berg Balance Scale, Trunk Impairment Scale, Functional Independence Measure, and Functional Reach. Although this patient's gait speed and muscle strength did not show improvement after training, feedback facility-assisted balance training might be a potential strategy to help reduce the rate of symptom deterioration in patients with multiple system atrophy. LEVEL OF EVIDENCE: V.

Modulation of Cerebellar-Cortical Connections in Multiple System Atrophy Type C by Cerebellar Repetitive Transcranial Magnetic Stimulation.

OBJECTIVE: This study aims at modulating the altered cerebellar-cortical interactions in patients with multiple system atrophy-cerebellar subtype (MSA-C) by using cerebellar repetitive transcranial magnetic stimulation (rTMS). We hypothesized that cerebellar modulation by low-frequency rTMS can resolve the abnormal cortical excitability in multiple system atrophy cerebellar subtype. MATERIALS AND METHODS: We studied detailed effects of rTMS of the cerebellum on reaction time (RT) and short-latency afferent inhibition (SAI) response in MSA-C group, Alzheimer Disease (AD) group, and a control group of healthy individuals. The RT and SAI responses were measured before and after 1 Hz cerebellar rTMS in all groups. The study was conducted in the neurophysiology laboratory in Hacettepe University Hospital. RESULTS: Our results indicated that motor cortex disinhibition was predominant in patients with AD and MSA-C. In AD and control groups, there were no changes in SAI after rTMS. However, after application of rTMS over the cerebellum in MSA-C patients, the pathological disinhibition and RT results showed an improvement compared to their previous results. CONCLUSION: Our study highlights that cerebellar rTMS impairs abnormal cerebellar-cortical inhibitory connections in case of MSA-C.

Principal component analysis for ataxic gait using a triaxial accelerometer.

BACKGROUND: It is quite difficult to evaluate ataxic gait quantitatively in clinical practice. The aim of this study was to analyze the characteristics of ataxic gait using a triaxial accelerometer and to develop a novel biomarker of integrated gate parameters for ataxic gait. METHODS: Sixty-one patients with spinocerebellar ataxia (SCA) or multiple system atrophy with predominant cerebellar ataxia (MSA-C) and 57 healthy control subjects were enrolled. The subjects were instructed to walk 10 m for a total of 12 times on a flat floor at their usual walking speed with a triaxial accelerometer attached to their back. Gait velocity, cadence, step length, step regularity, step symmetry, and degree of body sway were evaluated. Principal component analysis (PCA) was used to analyze the multivariate gait parameters. The Scale for the Assessment and Rating of Ataxia (SARA) was evaluated on the same day of the 10-m walk trial. RESULTS: PCA divided the gait parameters into four principal components in the controls and into two principal components in the patients. The four principal components in the controls were similar to those found in earlier studies. The second principal component in the patients had relevant factor loading values for gait velocity, step length, regularity, and symmetry in addition to the degree of body sway in the medio-lateral direction. The second principal component score (PCS) in the patients was significantly correlated with disease duration and the SARA score of gait (ρ = -0.363, p = 0.004; ρ = -0.574, p < 0.001, respectively). CONCLUSIONS: PCA revealed the main component of ataxic gait. The PCS of the main component was significantly different between the patients and controls, and it was well correlated with disease duration and the SARA score of gait in the patients. We propose that this score provides a novel method to assess the severity of ataxic gait quantitatively using a triaxial accelerometer.

Role of intestinal peptides and the autonomic nervous system in postprandial hypotension in patients with multiple system atrophy.

Postprandial hypotension (PPH) is a major clinical problem in patients with autonomic failure such as that observed in multiple system atrophy (MSA). The pathophysiology of PPH remains unclear, although autonomic dysfunction and gastrointestinal vasoactive peptides have been suspected to participate in its pathogenesis. We measured blood pressure and plasma levels of glucose, insulin, noradrenaline, neurotensin, glucagon-like peptide (GLP)-1 and GLP-2 before and after meal ingestion in 24 patients with MSA to reveal the roles of the autonomic nervous system and gastrointestinal vasoactive peptides in PPH. We performed a second meal-ingestion test by administering acarbose to evaluate the effects of acarbose (an α-glucosidase inhibitor) on PPH and vasoactive peptides in 14 patients with MSA and PPH. We also evaluated blood pressure responses to the head-up tilt test and heart rate variability in all the patients. Severities of PPH and orthostatic hypotension were significantly correlated. Patients with PPH had significantly worse orthostatic hypotension and lower heart rate variability than those without PPH. Postprandial GLP-1 secretion was higher in patients with PPH than in those without PPH. No significant differences were observed in the postprandial increases in plasma levels of glucose, insulin, noradrenaline, neurotensin or GLP-2. Acarbose significantly attenuated postprandial hypotension and tended to decrease GLP-2 secretion. Our results indicate that autonomic failure is involved in the pathogenesis of PPH and confirm that acarbose has a preventive effect against PPH in patients with MSA. Decreased postprandial secretion of GLP-2, which increases intestinal blood pooling, may attenuate PPH in patients with MSA.

The impact of resistance training on balance and functional ability of a patient with multiple system atrophy.

PURPOSE: This case study documents the impact of a resistance-training program on a female patient with Multiple System Atrophy (MSA). CASE DESCRIPTION: A 68-year-old female with a 2-year history of MSA was referred to physical therapy with a history of falls, increasing loss of balance and rapidly progressing lower body Parkinson's like dysfunction. Examination included range of motion, muscle strength, motor control, ambulation with and without assistive device, and determination of postural hypotension. Functional Reach (FR), Timed Up and Go (TUG), timed single limb stance (SLS), and the Performance Oriented Mobility Assessment (POMA) assessed safety, balance, and fall risk. Hypokinesia and festinating gait were observed during ambulation. Transfers sit to stand were functional, but with compromised safety. Impairments of muscle performance were found at ankle, knee, and hip. The patient wanted to be able to live at home to care for herself and disabled spouse. Low to moderate intensity, lower extremity resistance training was added (twice weekly) to an existing program of balance and flexibility exercises. OUTCOMES: Clinically meaningful gains were achieved in all functional measures, and the patient performed SLS for 10 seconds when previously unable. More importantly, she achieved her goal of remaining at home with her spouse. DISCUSSION: The addition of resistance training to an existing program of balance and flexibility exercises did not cause any adverse effects and appears to have led to improvements in balance and functional ability.

Case report: Tai Chi and Parkinsonism.

BACKGROUND AND PURPOSE: To describe the effects of an eight-week Tai Chi class on two patients: one with Parkinson's disease, the other with multiple system atrophy. METHOD AND RESULTS: Both patients demonstrated improved scores on the Activities-specific Balance Confidence Scale and the Functional Reach Test. One subject also demonstrated improved scores for the Timed Up and Go test. Both subjects reported subjective improvements in balance and balance awareness. CONCLUSIONS: Tai Chi may be a viable option for improving balance in patients with mild Parkinsonism.

Occupational therapy in multiple system atrophy: a pilot randomized controlled trial.

There is some evidence that rehabilitation therapies may be useful in progressive neurological conditions, but this usefulness has not been studied in multiple system atrophy (MSA) to date. The aim of this small pilot study was to identify the feasibility of a larger randomized controlled trial of occupational therapy and to report preliminary data on the impact of occupational therapy on disability, mood, and health-related quality of life in patients with MSA. Patient groups were comparable for age, gender distribution, type of MSA, and severity. The active occupational therapy intervention group experienced a significant reduction of Unified Parkinson's Disease Rating Scale (total score and Activities of Daily Living [ADL] section), and PDQ-39 scores (total scores and ADL subsection). An occupational therapy program may improve functional abilities in patients with mild to moderate MSA. A larger multicenter study is needed.

[A case of multiple system atrophy treated with erythropoietin]. / Przypadek zaniku wieloukladowego leczony erytropoetyna.

The patient, a women aged 52, with a three-year history of treatment for arterial hypotension, was admitted to hospital because of progressing worsening of symptoms. The whole clinical syndrome made possible the recognition of multiple system atrophy as the cause of her symptoms. In view of failures in previous treatment it was decided to give her erythropoietin injections for four weeks. The treatment led to improvement of her status. The authors discuss the probable action mechanism of erythropoietin in this case.