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.

[Cognitive impairment in multiple system atrophy - exclusion criteria or an integral part of the clinical picture?] / Kognitivnye narusheniya pri mul'tisistemnoi atrofii ­ kriterii isklyucheniya ili neot"emlemaya chast' klinicheskoi kartiny?

Multiple system atrophy (MSA) is a severe, orphan disease characterized by a steady increase in symptoms of parkinsonism, cerebellar disorders, and autonomic failure. In addition to autonomic failure, which is considered the defining symptom of this type of atypical parkinsonism, there are a range of other non-motor clinical manifestations, such as sleep disorders, pain syndrome, anxiety-depressive disorders, cognitive impairment (CI). CI, especially severe CI, has long been considered as a distinctive feature of MCA. Recently, there have been many clinical studies with pathomorphological or neuroimaging confirmation, indicating a high prevalence of cognitive disorders in MCA. In this article, we discuss the pathogenetic mechanisms of the development of MCA and CI in MCA, as well as the range of clinical manifestations of cognitive dysfunction.

Clinical value of video oculomotor evaluation in the differential diagnosis of multiple system atrophy and Parkinson's disease.

BACKGROUND: Multiple system atrophy (MSA) is a neurodegenerative disease that progresses rapidly and has a poor prognosis. This study aimed to assess the value of video oculomotor evaluation (VOE) in the differential diagnosis of MSA and Parkinson's disease (PD). METHODS: In total, 28 patients with MSA, 31 patients with PD, and 30 age- and sex-matched healthy controls (HC) were screened and included in this study. The evaluation consisted of a gaze-holding test, smooth pursuit eye movement (SPEM), random saccade, and optokinetic nystagmus (OKN). RESULTS: The MSA and PD groups had more abnormalities and decreased SPEM gain than the HC group (64.29%, 35.48%, 10%, p < .001). The SPEM gain in the MSA group was significantly lower than that in the PD group at specific frequencies. Patients with MSA and PD showed prolonged latencies in all saccade directions compared with those with HC. However, the two diseases had no significant differences in the saccade parameters. The OKN gain gradually decreased from the HC to the PD and the MSA groups (p < .05). Compared with the PD group, the gain in the MSA group was further decreased in the OKN test at 30°/s (Left, p = .010; Right p = .016). Receiver operating characteristic curves showed that the combination of oculomotor parameters with age and course of disease could aid in the differential diagnosis of patients with MSA and PD, with a sensitivity of 89.29% and a specificity of 70.97%. CONCLUSIONS: The combination of oculomotor parameters and clinical data may aid in the differential diagnosis of MSA and PD. Furthermore, VOE is vital in the identification of neurodegenerative diseases.

[Neuropathology of the Neurodegenerative Diseases].

A definite diagnosis of neurodegenerative diseases is required for neuropathological examination during an autopsy. Each neurodegenerative disease has specific vulnerable regions and affected systems (system degeneration), and is typified by an accumulation of abnormal protein with the formation of characteristic morphological aggregates in the nerve and glial cells, called proteinopathy. The most common neurodegenerative diseases are tauopathy, such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick's disease (PiD); α-synucleinopathy, including multiple system atrophy (MSA); and TAR DNA-binding protein of 43 kDa (TDP-43) proteinopathy, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). PSP and CBD show characteristic tau-positive astrocytic inclusions known as tufted astrocytes and astrocytic plaques, respectively. PiD shows tau-positive neuronal inclusions termed Pick bodies. MSA is characterized by α-synuclein-positive oligodendroglial inclusions, called glial cytoplasmic inclusions. ALS- and FTLD-TDP show TDP-43-positive neuronal inclusions, such as skein-like and round inclusions. Huntington's disease shows polyglutamine-positive neuronal inclusions, and Creutzfeldt-Jakob disease shows diffuse deposition of granular prions in the neuropil. The atypical proteins in these diseases have abnormal conformational properties. A comprehensive comparison of the clinical findings and neuropathological observations, including neuroanatomy and images acquired during life, is important to improve the sensitivity of clinical diagnosis.

Revisiting the relevance of Hirano bodies in neurodegenerative diseases.

AIMS: Hirano bodies (HBs) are eosinophilic pathological structures with two morphological phenotypes commonly found in the hippocampal CA1 region in Alzheimer's disease (AD). This study evaluated the prevalence and distribution of HBs in AD and other neurodegenerative diseases. METHODS: This cross-sectional study systematically evaluated HBs in a cohort of 193 cases with major neurodegenerative diseases, including AD (n = 91), Lewy body disease (LBD, n = 87), progressive supranuclear palsy (PSP, n = 36), multiple system atrophy (MSA, n = 14) and controls (n = 26). The prevalence, number and morphology of HBs in the stratum lacunosum (HBL) and CA1 pyramidal cell layer were examined. In addition, we investigated the presence of HBs in five additional hippocampal subregions. RESULTS: The morphological types of HBs in CA1 were divided into three, including a newly discovered type, and were evaluated separately, with their morphology confirmed in three dimensions: (1) classic rod-shaped HB (CHB), (2) balloon-shaped HB (BHB) and the newly described (3) string-shaped HB (SHB). The prevalence of each HB type differed between disease groups: Compared with controls, for CHB in AD, AD + LBD, PSP and corticobasal degeneration, for BHB in AD + LBD and PSP, and SHB in AD + LBD and PSP were significantly increased. Regression analysis showed that CHBs were independently associated with higher Braak NFT stage, BHBs with LBD and TDP-43 pathology, SHBs with higher Braak NFT stage, PSP and argyrophilic grain disease and HBLs with MSA. CONCLUSIONS: This study demonstrates that HBs are associated with diverse neurodegenerative diseases and shows that morphological types appear distinctively in various conditions.

The potential of phosphorylated α-synuclein as a biomarker for the diagnosis and monitoring of multiple system atrophy.

INTRODUCTION: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by the presence of glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-Syn). Accurate diagnosis and monitoring of MSA present significant challenges, which can lead to potential misdiagnosis and inappropriate treatment. Biomarkers play a crucial role in improving the accuracy of MSA diagnosis, and phosphorylated α-synuclein (p-syn) has emerged as a promising biomarker for aiding in diagnosis and disease monitoring. METHODS: A literature search was conducted on PubMed, Scopus, and Google Scholar using specific keywords and MeSH terms without imposing a time limit. Inclusion criteria comprised various study designs including experimental studies, case-control studies, and cohort studies published only in English, while conference abstracts and unpublished sources were excluded. RESULTS: Increased levels of p-syn have been observed in various samples from MSA patients, such as red blood cells, cerebrospinal fluid, oral mucosal cells, skin, and colon biopsies, highlighting their diagnostic potential. The α-Syn RT-QuIC assay has shown sensitivity in diagnosing MSA and tracking its progression. Meta-analyses and multicenter investigations have confirmed the diagnostic value of p-syn in cerebrospinal fluid, demonstrating high specificity and sensitivity in distinguishing MSA from other neurodegenerative diseases. Moreover, combining p-syn with other biomarkers has further improved the diagnostic accuracy of MSA. CONCLUSION: The p-syn stands out as a promising biomarker for MSA. It is found in oligodendrocytes and shows a correlation with disease severity and progression. However, further research and validation studies are necessary to establish p-syn as a reliable biomarker for MSA. If proven, p-syn could significantly contribute to early diagnosis, disease monitoring, and assessing treatment response.

Low and high-order topological disruption of functional networks in multiple system atrophy with freezing of gait: A resting-state study.

OBJECTIVE: Freezing of gait (FOG), a specific survival-threatening gait impairment, needs to be urgently explored in patients with multiple system atrophy (MSA), which is characterized by rapid progression and death within 10 years of symptom onset. The objective of this study was to explore the topological organisation of both low- and high-order functional networks in patients with MAS and FOG. METHOD: Low-order functional connectivity (LOFC) and high-order functional connectivity FC (HOFC) networks were calculated and further analysed using the graph theory approach in 24 patients with MSA without FOG, 20 patients with FOG, and 25 healthy controls. The relationship between brain activity and the severity of freezing symptoms was investigated in patients with FOG. RESULTS: Regarding global topological properties, patients with FOG exhibited alterations in the whole-brain network, dorsal attention network (DAN), frontoparietal network (FPN), and default network (DMN), compared with patients without FOG. At the node level, patients with FOG showed decreased nodal centralities in sensorimotor network (SMN), DAN, ventral attention network (VAN), FPN, limbic regions, hippocampal network and basal ganglia network (BG), and increased nodal centralities in the FPN, DMN, visual network (VIN) and, cerebellar network. The nodal centralities of the right inferior frontal sulcus, left lateral amygdala and left nucleus accumbens (NAC) were negatively correlated with the FOG severity. CONCLUSION: This study identified a disrupted topology of functional interactions at both low and high levels with extensive alterations in topological properties in MSA patients with FOG, especially those associated with damage to the FPN. These findings offer new insights into the dysfunctional mechanisms of complex networks and suggest potential neuroimaging biomarkers for FOG in patients with MSA.

Transcriptomic insights into multiple system atrophy from a PLP-α-synuclein transgenic mouse model.

Multiple system atrophy (MSA) is a rare, neurodegenerative disorder with rapid motor and non-motor symptom progression. MSA is characterized by protein aggregations of α-synuclein found in the cytoplasm of oligodendrocytes. Despite this pathological hallmark, there is still little known about the cause of this disease, resulting in poor treatment options and quality of life post-diagnosis. In this study, we investigated differentially expressed genes (DEGs) via RNA-sequencing of brain samples from a validated PLP-α-synuclein transgenic mouse model, identifying a total of 40 DEGs in the PLP group compared to wild-type (WT), with top detected genes being Gm15446, Mcm6, Aldh7a1 and Gm3435. We observed a significant enrichment of immune pathways and endothelial cell genes among the upregulated genes, whereas downregulated genes were significantly enriched for oligodendrocyte and neuronal genes. We then calculated possible overlap of these DEGs with previously profiled human MSA RNA, resulting in the identification of significant downregulation of the Tsr2 gene. Identifying key gene expression profiles specific to MSA patients is crucial to further understanding the cause, and possible prevention, of this rapidly progressive neurodegenerative disorder.

Skin Biopsy Detection of Phosphorylated α-Synuclein in Patients With Synucleinopathies.

Importance: Finding a reliable diagnostic biomarker for the disorders collectively known as synucleinopathies (Parkinson disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA], and pure autonomic failure [PAF]) is an urgent unmet need. Immunohistochemical detection of cutaneous phosphorylated α-synuclein may be a sensitive and specific clinical test for the diagnosis of synucleinopathies. Objective: To evaluate the positivity rate of cutaneous α-synuclein deposition in patients with PD, DLB, MSA, and PAF. Design, Setting, and Participants: This blinded, 30-site, cross-sectional study of academic and community-based neurology practices conducted from February 2021 through March 2023 included patients aged 40 to 99 years with a clinical diagnosis of PD, DLB, MSA, or PAF based on clinical consensus criteria and confirmed by an expert review panel and control participants aged 40 to 99 years with no history of examination findings or symptoms suggestive of a synucleinopathy or neurodegenerative disease. All participants completed detailed neurologic examinations and disease-specific questionnaires and underwent skin biopsy for detection of phosphorylated α-synuclein. An expert review panel blinded to pathologic data determined the final participant diagnosis. Exposure: Skin biopsy for detection of phosphorylated α-synuclein. Main Outcomes: Rates of detection of cutaneous α-synuclein in patients with PD, MSA, DLB, and PAF and controls without synucleinopathy. Results: Of 428 enrolled participants, 343 were included in the primary analysis (mean [SD] age, 69.5 [9.1] years; 175 [51.0%] male); 223 met the consensus criteria for a synucleinopathy and 120 met criteria as controls after expert panel review. The proportions of individuals with cutaneous phosphorylated α-synuclein detected by skin biopsy were 92.7% (89 of 96) with PD, 98.2% (54 of 55) with MSA, 96.0% (48 of 50) with DLB, and 100% (22 of 22) with PAF; 3.3% (4 of 120) of controls had cutaneous phosphorylated α-synuclein detected. Conclusions and Relevance: In this cross-sectional study, a high proportion of individuals meeting clinical consensus criteria for PD, DLB, MSA, and PAF had phosphorylated α-synuclein detected by skin biopsy. Further research is needed in unselected clinical populations to externally validate the findings and fully characterize the potential role of skin biopsy detection of phosphorylated α-synuclein in clinical care.

Clinical Characteristics and Outcomes in Young-Onset Multiple System Atrophy.

BACKGROUND: Young-onset multiple system atrophy (YOMSA) is defined as the onset of multiple system atrophy (MSA) before the age of 40 years old. YOMSA is rare and there is much uncertainty of the phenotype and natural history in patients with YOMSA. OBJECTIVE: The objective is to evaluate the characteristics and disease course of patients with YOMSA. METHODS: We retrospectively reviewed medical records of patients with MSA who were evaluated at all Mayo Clinic sites from 1998 to 2021. We identified patients with YOMSA and evaluated clinical characteristics, autonomic function testing results, and disease course. RESULTS: Of 1496 patients with a diagnosis of clinically probable or clinically established MSA, 20 patients had YOMSA. The median age of onset was 39.1 (interquartile range [IQR] = 37.1, 40.1) years; 13 patients (65%) were male. MSA-parkinsonism was the most common subtype (65%). The median duration of symptom onset to YOMSA diagnosis was 4.9 (IQR = 3.7, 9) years. At the time of medical record review, 17 patients were deceased with a median survival of 8.3 (IQR = 7, 10.9) years. Univariate analysis showed that initial onset of autonomic failure predicted unfavorable survival (hazard ratio = 2.89, P = 0.04) compared to those who presented with motor impairment only at onset. At the time of YOMSA diagnosis, composite autonomic severity score was available in 19 patients with a median of 5 (IQR = 4, 6.5). CONCLUSIONS: YOMSA resembles MSA in most aspects including phenotype and prognosis, although the diagnosis is usually delayed. The presence of autonomic failure at symptom onset may be a poor predictor for survival.

Multiple system atrophy: an update and emerging directions of biomarkers and clinical trials.

Multiple system atrophy is a rare, debilitating, adult-onset neurodegenerative disorder that manifests clinically as a diverse combination of parkinsonism, cerebellar ataxia, and autonomic dysfunction. It is pathologically characterized by oligodendroglial cytoplasmic inclusions containing abnormally aggregated α-synuclein. According to the updated Movement Disorder Society diagnostic criteria for multiple system atrophy, the diagnosis of clinically established multiple system atrophy requires the manifestation of autonomic dysfunction in combination with poorly levo-dopa responsive parkinsonism and/or cerebellar syndrome. Although symptomatic management of multiple system atrophy can substantially improve quality of life, therapeutic benefits are often limited, ephemeral, and they fail to modify the disease progression and eradicate underlying causes. Consequently, effective breakthrough treatments that target the causes of disease are needed. Numerous preclinical and clinical studies are currently focusing on a set of hallmarks of neurodegenerative diseases to slow or halt the progression of multiple system atrophy: pathological protein aggregation, synaptic dysfunction, aberrant proteostasis, neuronal inflammation, and neuronal cell death. Meanwhile, specific biomarkers and measurements with higher specificity and sensitivity are being developed for the diagnosis of multiple system atrophy, particularly for early detection of the disease. More intriguingly, a growing number of new disease-modifying candidates, which can be used to design multi-targeted, personalized treatment in patients, are being investigated, notwithstanding the failure of most previous attempts.

Stochastic Optical Reconstruction Microscopy Imaging of Multiple System Atrophy Inclusions Suggests Stepwise α-Synuclein Aggregation.

BACKGROUND: The architecture and composition of glial (GCI) and neuronal (NCI) α-synuclein inclusions observed in multiple system atrophy (MSA) remain to be precisely defined to better understand the disease. METHODS: Here, we used stochastic optical reconstruction microscopy (STORM) to characterize the nanoscale organization of glial (GCI) and neuronal (NCI) α-synuclein inclusions in cryopreserved brain sections from MSA patients. RESULTS: STORM revealed a dense cross-linked internal structure of α-synuclein in all GCI and NCI. The internal architecture of hyperphosphorylated α-synuclein (p-αSyn) inclusions was similar in glial and neuronal cells, suggesting a common aggregation mechanism. A similar sequence of p-αSyn stepwise intracellular aggregation was defined in oligodendrocytes and neurons, starting from the perinuclear area and growing inside the cells. Consistent with this hypothesis, we found a higher mitochondrial density in GCI and NCI compared to oligodendrocytes and neurons from unaffected donors (P < 0.01), suggesting an active recruitment of the organelles during the aggregation process. CONCLUSIONS: These first STORM images of GCI and NCI suggest stepwise α-synuclein aggregation in MSA. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Associations of sleep-related variables with reverse dipping patterns of blood pressure in α-synucleinopathies.

INTRODUCTION: The reverse dipping blood pressure (BP) pattern is very common in α-synucleinopathies. We aimed to explore the associations of sleep-related variables with abnormal BP circadian rhythms in Parkinson's disease (PD) and multiple system atrophy (MSA). METHODS: A total of 126 patients, 76 with PD and 50 with MSA, were included. All participants underwent ambulatory BP monitoring and full-night polysomnography (PSG). We analyzed abnormal dipping patterns and sleep-related parameters, including moderate to severe obstructive sleep apnea (OSA), rapid eye movement behavior disorder (RBD), average oxygen saturation (SaO2%), lowest SaO2%, duration of SaO2% <90%, and apnea-hypopnea index (AHI). Binary logistic regression was performed to explore the associations between paraclinical variables, sleep-related variables, and reverse dipping patterns. RESULTS: Reverse dipping patterns were predominant in patients with PD (58.5 %) and MSA (68.0 %). Patients with MSA had higher AHI, RBD, and lower average SaO2% than those with PD. Taking both diseases together as a whole group of α-synucleinopathies, logistic regression analysis indicates the Hoehn-Yahr stage (odds ratio [OR] = 2.00 for reverse systolic and 2.34 for reverse diastolic dipping patterns), moderate to severe OSA (OR = 2.71 for reverse systolic and 2.53 for reverse diastolic dipping patterns), average SaO2% (OR = 1.35 for reverse systolic dipping patterns), and male sex (OR = 2.70 for reverse diastolic dipping patterns) were independently associated with reverse dipping patterns. CONCLUSIONS: Reverse dipping patterns were common in patients with PD and MSA. Hoehn-Yahr stage, moderate to severe OSA, average SaO2%, and male sex were associated with reverse dipping patterns in α-synucleinopathy.

Putaminal T1/T2-weighted ratio is increased in PSP compared to PD and healthy controls, a multi-cohort study.

INTRODUCTION: Differentiating Parkinson's disease (PD) from progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is a common clinical problem. We aimed to apply the T1-/T2-weighted ratio imaging technique, based on standard clinical MRI, to reveal differences in neurodegeneration in three large cohorts. METHODS: Three cohorts, with a total of 405 participants (269 PD, 44 PSP, 38 MSA, 54 controls), were combined and T1/T2-weighted ratio image analyses were carried out. A combination of automatic segmentation and atlas-based ROI were used in this study. The cohorts were combined using the ComBat batch correction procedure. RESULTS: Group differences were found in the putamen (p = 0.040), with higher T1/T2-weighted ratio in this region in PSP compared to PD and healthy controls (p-values 0.010 and 0.007 respectively). Using putaminal T1/T2-weighted ratio for diagnostic separation, a fair performance was found in separating PSP from healthy controls, with an area under the receiver operating characteristic curve of 0.701. CONCLUSION: Different patterns of T1/T2-weighted ratio, reflecting differences in underlying pathophysiology, were found between the groups. Since T1/T2-weighted ratio can be applied to standard clinical MRI sequences to allow more quantitative analyses, this seems to be a promising biomarker for diagnostics and treatment evaluation of parkinsonian disorders for clinical trials.

[Recent clinical advances in hereditary spinocerebellar degeneration].

Spinocerebellar degeneration (SCD) is a neurodegenerative disorder characterized by cerebellar ataxia and other multisystem manifestations, such as Parkinsonism and pyramidal tract symptoms. No effective treatment is available for SCD. Approximately one-third of the cases of SCD are inherited, and the remaining two-third are sporadic, including multiple system atrophy. This article provides an overview of hereditary SCD, its clinical features, recent treatment advances, biomarkers, role of genomic medicine, and future treatment prospects.

Recent Advances in Clinical Trials in Multiple System Atrophy.

PURPOSE OF REVIEW: This review summarizes previous and ongoing neuroprotection trials in multiple system atrophy (MSA), a rare and fatal neurodegenerative disease characterized by parkinsonism, cerebellar, and autonomic dysfunction. It also describes the preclinical therapeutic pipeline and provides some considerations relevant to successfully conducting clinical trials in MSA, i.e., diagnosis, endpoints, and trial design. RECENT FINDINGS: Over 30 compounds have been tested in clinical trials in MSA. While this illustrates a strong treatment pipeline, only two have reached their primary endpoint. Ongoing clinical trials primarily focus on targeting α-synuclein, the neuropathological hallmark of MSA being α-synuclein-bearing glial cytoplasmic inclusions. The mostly negative trial outcomes highlight the importance of better understanding underlying disease mechanisms and improving preclinical models. Together with efforts to refine clinical measurement tools, innovative statistical methods, and developments in biomarker research, this will enhance the design of future neuroprotection trials in MSA and the likelihood of positive outcomes.

Reliability of the unified multiple system atrophy rating scale using the telephone.

OBJECTIVE: The unified multiple system atrophy rating scale (UMSARS) was used to evaluate various symptoms of multiple system atrophy (MSA). And UMSARS part 1 was originally developed for use in interviews, but the need for telemedicine is increasing in COVID-19 pandemic. The purpose of this study is to evaluate the reliability of the UMSARS part 1 telephone survey. METHODS: Thirty-two MSA patients took the UMSARS part 1 face-to-face, followed by two more telephone evaluations. Intraclass correlation coefficients (ICC) and Cronbach's alpha (α) coefficients were calculated, and the inter-rater reliability was determined. At the same time, we asked about the problems in COVID-19 pandemic. RESULTS: The study participants included 15 men and 17 women with mean age of 67.1 years (SD, 8.3). For the total UMSARS part 1 score, the inter-rater ICC and Cronbach's α coefficient were 0.89 to 0.92, and 0.84 to 0.87, respectively. More than half of the items had a relatively high ICC. Cronbach's α coefficients were more than 0.7 for all items. Changes that occurred in COVID-19 pandemic included reduced outings and lack of rehabilitation in about half of the cases. CONCLUSION: The UMSARS part 1 has high inter-rater reliability and internal consistency. Evaluation of subjective symptoms showed that some variability could occur. In addition, there was concern about the influence of lack of rehabilitation due to COVID-19 pandemic.