Multiple System Atrophy and Progressive Supranuclear Palsy in Persian Population: A Retrospective Cross-sectional Study

Multiple System Atrophy and Progressive Supranuclear Palsy in Persian Population: A Retrospective Cross-sectional Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Multiple System Atrophy and Progressive Supranuclear Palsy in Persian Population: A Retrospective Cross-sectional Study Mehri Salari, Kamran Rezaei, Mohammad Javad Qalamzan, Sara Sadeghzadeh, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6526460/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are neurodegenerative disorders with distinct demographic and clinical profiles. In Middle Eastern countries, limited data exist on their demographic features and clinical manifestations. Objectives This study describes MSA and PSP patients in a Persian cross-sectional study. Methods This cross-sectional study was retrospectively conducted using medical records of patients diagnosed with MSA or PSP between January 2019 and January 2025, based on the MDS diagnostic criteria components at the initial diagnosis. Results A total of 106 MSA and 108 PSP patients were included. MSA-C (23.58%), MSA-P (60.37%), and unclassified (16.03%) were the subgroups of MSA in this project. PSP subtypes were PSP-P (72.22%), PSP-RS (26.85%), and PSP-PAGF (0.92%). The PSP group had a significantly higher age of participants in this study (71.82 ± 7.46 vs 68.85 ± 8.66). The male/female fraction was significantly higher in patients with PSP compared to the MSA group (70.37%/29.62% vs 45.28%/54.71%, p -value < 0.001). Following a comparison of common symptoms, the onset of disease before age 70 years when Parkinsonism is the symptom of onset was significantly more frequent in MSA, whereas onset after 70 years was more frequent in PSP (p < 0.05). Urinary problems were more significant in the MSA group (70.0%) compared to the PSP cases (52.9%, p -value < 0.05). Conclusion Describing demographic and clinical presentations of MSA and PSP patients in a Middle Eastern population would enhance our understanding of the characteristics of these disorders in this region. Multiple System Atrophy Progressive Supranuclear Palsy Parkinsonism Persian Figures Figure 1 INTRODUCTION Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are neurodegenerative conditions classified under the spectrum of atypical Parkinsonian syndromes ( 1 – 3 ). While both conditions share clinical features with Parkinson's disease (PD), such as bradykinesia, rigidity, and postural instability, they are distinguished by their distinct pathological mechanisms, clinical presentations, and disease progression ( 4 – 6 ). Multiple System Atrophy (MSA) is a sporadic, adult-onset disorder characterized by the presence of α-synuclein-positive glial cytoplasmic inclusions (GCIs), which predominantly affect oligodendrocytes and lead to widespread neurodegeneration ( 7 ). MSA is categorized into two clinical subtypes: MSA-P, characterized by predominant Parkinsonian features, and MSA-C, characterized by predominant cerebellar ataxia. Autonomic dysfunction is a hallmark of MSA and often aids in differentiating it from PD ( 8 , 9 ). The disease progresses rapidly, with a median survival of 6–10 years from symptom onset, and no disease-modifying therapies are currently available ( 10 ). Progressive Supranuclear Palsy (PSP) is a tauopathy characterized by the accumulation of hyperphosphorylated tau protein in neurons and glia, particularly in the basal ganglia, brainstem, and cortex ( 11 ). The most common clinical variant, Richardson's syndrome (PSP-RS), presents with early postural instability, vertical supranuclear gaze palsy, and cognitive dysfunction ( 1 ). Other forms, like PSP-parkinsonism (PSP-P), can resemble PD in the initial phases but generally show a limited response to levodopa treatment. ( 12 , 13 ). Other subtypes of PSP, including PSP-corticobasal syndrome (PSP-CBS), with parkinsonism, apraxia, cortical sensory loss, and other CBS-like symptoms, PSP-frontal (PSP-F) with predominant behavioral symptoms and less often motor onset, PSP-speech/language (PSP-SL), with initial symptoms such as progressive non-fluent speech aphasia and apraxia), and PSP-postural instability (PSP-PI), presenting initially with severe postural instability comprise a lower frequency of PSP patients compared to previously mentioned subtypes ( 14 ). PSP is associated with significant morbidity, including falls, dysphagia, and pseudobulbar affect, and has a median survival of 5–7 years ( 11 , 15 ). The diagnostic criteria established by the Movement Disorder Society (MDS) for both MSA and PSP would help differentiate between these two conditions ( 13 , 16 ). Both disorders can present with parkinsonism, postural instability, and early fall, making initial diagnosis difficult ( 3 , 8 ). Additionally, autonomic dysfunction, while more prominent in MSA, can also occur in PSP, further complicating the diagnostic process ( 17 ). Neuroimaging findings, such as midbrain atrophy in PSP, and putaminal slit sign and/or hot cross bun sign in MSA, provide valuable diagnostic clues, but these features may not be evident in the early stages of the disease ( 11 , 18 ), sometimes resulting in diagnostic challenges. Recent studies have significantly advanced our understanding of how MSA and PSP manifest across diverse ethnic populations, revealing notable differences in demographic and clinical presentations ( 5 , 19 , 20 ). There is a notable scarcity of comprehensive studies investigating the demographic and clinical features of MSA and PSP in Middle Eastern countries, limiting insights into their prevalence, phenotypic variations, and disease progression in these populations. The present paper is designed to study the clinical features of Persian MSA and PSP patients. It expands our knowledge of these conditions in this country, further providing a valuable source of information regarding the status of MSA and PSP in Middle Eastern ethnic groups. METHODS Study Design This study used the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline as a checklist ( 21 ). This study used a dataset containing demographic, clinical features, and imaging findings, retrospectively collected from patients diagnosed with MSA and PSP following examination by a Movement Disorders Specialist at a referral movement disorders Centre in Tehran from January 2019 to January 2025. Retrospective data were collected from the clinic's medical records by three investigators under the supervision of a movement disorders specialist. Patients and Participants We conducted a retrospective investigation of the medical records of patients who were referred to our movement disorders clinic between January 2019 and January 2025. A total of 111 patients diagnosed with Multiple System Atrophy (MSA) and 123 patients diagnosed with Progressive Supranuclear Palsy (PSP) were initially identified. Informed consent was taken from the patients before participation in the study. Patients were included in the final analysis if they met the following inclusion criteria: ( 1 ) Diagnosed with MSA or PSP according to the referring physician's assessment at the time of the initial consultation. The diagnosis was performed by a movement disorders specialist based on the clinical judgment and criteria provided by MDS ( 13 , 16 ), and ( 2 ) Sufficient data were available in their medical records from the first medical consultation (initial diagnosis) to assess the presence or absence of each component of the relevant MDS diagnostic criteria for MSA ( 16 ) and PSP ( 13 ). Patients were excluded if their medical records were incomplete regarding the features assessed by the MDS criteria. The MDS criteria ( 16 ) were used for the subgroup assignment of MSA patients into the following subgrouping systems: ( 1 ) Clinically established MSA, clinically probable MSA, and possible prodromal MSA regarding the establishment of the diagnosis, and ( 2 ) MSA with predominant Parkinsonism (MSA-P) and MSA with predominant cerebellar signs (MSA-C). If a patient could not meet the criteria to fall into MSA-P or MSA-C subgroups, it was considered “unclassified”. In addition, the MDS criteria ( 13 ) were used to assign PSP patients into subgroups: PSP with predominant Parkinsonism (PSP-P), PSP-Richardson's syndrome (PSP-RS), and PSP-Pure akinesia with gait freezing (PSP-PAGF). Data was extracted from the medical records included patient demographics (age, sex, age at onset, duration from initiation of the symptoms to first diagnosis), presenting symptoms, and neurological examination findings presented in the MDS criteria ( 13 , 16 ). Statistical Analysis and Software Statistical analysis was performed using Python version 3 within the Anaconda application. Data was organized and manipulated using the Pandas library. Descriptive statistics (means, standard deviations, frequencies, and percentages) were used to summarize patient characteristics and the frequency of each component of the MDS criteria. Patients with missing data were excluded from the analysis. The chi-square test, t-test, and Mann-Whitney’s U test were used for comparison analysis using the SciPy library. Data visualization was performed using Matplotlib and Seaborn libraries. A p -value of less than 0.05 was considered statistically significant for all analyses. RESULTS Number of participants in each group and subgroup There were 125 and 139 patients diagnosed with MSA and PSP in the period of this study, respectively. After filtering the available records based on the inclusion criteria, a total number of 106 patients with MSA and 108 patients with PSP participated in this retrospective cross-sectional (Table 1 ). The fifty excluded patients, who were related to the retrospective data, had an incomplete medical record. MSA patients were classified into clinically established (21, 19.81%), clinically probable (70, 66.03%), and possible prodromal MSA (15, 14.15%). In the MSA group, 25 (23.58%) had MSA-C, 64 (60.37%) had MSA-P, and 17 (16.03%) were unclassified. PSP subgroups included 78 (72.22%) with PSP-P, 29 (26.85%) with PSP-RS, and one (0.92%) with PSP-PAGF. Table 1 Demographic Features of the MSA and PSP patients. Age, age at onset, and duration are by years and were compared using t-test. The sex variable is compared using the Mann Whitney U-test. Variable MSA (n = 106) PSP (n = 108) P -value Sex 0.000 Male 48 (45.28%) 76 (70.37%) Female 58 (54.71%) 32 (29.62%) Age (Mean ± SD) 68.85 ± 8.66 71.82 ± 7.46 0.008 Age at onset (Mean ± SD) 65.09 ± 8.67 67.01 ± 7.47 0.084 Duration (Mean ± SD) 3.74 ± 3.37 4.75 ± 3.35 0.030 Parkinsonism as SOO (n) 100 (94.34%) 85 (78.70%) 0.001 Parkinsonism as SOO; Age (Mean ± SD) 68.60 ± 8.38 72.48 ± 7.80 0.003 Parkinsonism as SOO; Age at onset (Mean ± SD) 64.78 ± 8.41 67.68 ± 7.65 0.031 Parkinsonism as SOO; Duration (Mean ± SD) 3.80 ± 3.46 4.71 ± 3.57 0.043 Urinary problems (n) 74 (70.0%) 60 (52.9%) 0.017 Speech problems (n) 34 (33.0%) 49 (43.5%) 0.143 Note : MSA: Multiple system atrophy, PSP: Progressive supranuclear palsy, SD: Standard deviation, SOO: Symptom of onset. Comparison of MSA and PSP groups As shown in Table 1 , the male/female proportion was significantly higher in PSP than in MSA patients (2.37 vs 0.82, P -value = 0.000). In addition, the mean age of the PSP group was significantly higher than the MSA group (71.82 ± 7.46 vs 68.85 ± 8.66, P -value = 0.008). The same was true for the mean duration of the disease (4.75 ± 3.35 for PSP, vs 3.74 ± 3.37 for MSA, P -value = 0.030), but the mean of age at onset was not significantly different in the MSA (65.09 ± 8.67) and PSP (67.01 ± 7.47) subjects ( Supplementary Fig. 1) . The age of patients presenting with Parkinsonism as a symptom of onset was significantly higher in PSP cases (68.60 ± 8.38 vs 72.48 ± 7.80, P -value = 0.003, Table 1 ). There were no significant differences in the duration and age of onset of patients with parkinsonism as a presenting symptom of onset in both groups. Looking at this significant difference in age, we decided to compare parkinsonism as a symptom of onset in patients aged < 70 years and those aged ≥ 70 years. In the subgroup with patients younger than 70 years, MSA patients presented significantly more with parkinsonism as the symptom of onset (50.0% vs 27.78%, Chi-square statistic = 94.65, P -value = 0.000). Moreover, this was reversed in patients aged 70 years and older, where the PSP group showed significantly higher rates (44.34% vs 50.93%, Chi-square statistic = 94.62, P -value = 0.000). Supplementary Fig. 2 represents the distribution of age across the patients with Parkinsonism as a symptom of onset in this study. As expected, the rate of urinary problems was significantly higher in the MSA (70.0%) compared to the PSP (52.9%, P -value = 0.017) group (Table 1 ). In contrast, there was no significant difference in the rate of speech problems between these two groups. MSA clinical subgroups The information provided in Table 2 and Table 3 describes the clinical and imaging features in MSA clinical subgroups. In a method of categorization, the MSA patients were divided into clinically established MSA, clinically probable MSA, and possible prodromal MSA using the consensus MDS criteria ( 16 ). Orthostatic hypotension, constipation, urinary problems, parkinsonism, and REM sleep behavioral disorder (RBD) were the most prominent clinical presentations. Table 2 Demographic, clinical, and imaging features of diagnosis establishment subgroups in the MSA patients (n = 106). Clinically established MSA Clinically probable MSA Possible prodromal MSA Number of cases 21 (19.81%) 70 (66.03%) 15 (14.15%) Age 69.04 ± 8.91 68.67 ± 8.93 69.46 ± 7.40 Age at onset 66.14 ± 8.42 64.24 ± 8.42 67.60 ± 7.69 Duration 2.90 ± 1.86 4.41 ± 1.80 1.80 ± 1.01 Urinary problems 21 (100%) 53 (75.7%) 0 (0%) Orthostatic hypotension 12 (57.14%) 22 (31.42%) 0 (0%) Poorly L-dopa responsive parkinsonism 16 (76.19%) 0 (0%) 2 (13.33%) Bradykinesia/ Rigidity 12 (57.14%) 47 (67.14%) 11 (73.33%) Postural Instability 15 (71.42%) 39 (55.71%) 6 (40%) Moderate to severe postural Instability within 3 years 15 (71.42%) 9 (12.85%) 3 (20%) Resting tremor 10 (47.61%) 33 (47.14%) 8 (53.33%) Craniocervical dystonia 1 (4.76%) 1 (1.42%) 0 Severe speech impairment within 3 years of motor onset 7 (33.33%) 23 (32.85%) 4 (26.66%) Severe dysphagia within 3 years of motor onset 2 (9.52%) 16 (22.85%) 3 (20%) Jerky myoclonic postural or kinetic tremor 8 (38.09%) 17 (24.28%) 5 (33.33%) Postural deformities 7 (33.33%) 5 (7.14%) 2 (13.33%) Inspiratory sighs 2 (9.52%) 7 (10%) 0 Pathologic laughter or crying 3 (14.28%) 1 (1.42%) 1 (6.66%) RBD 11 (52.38%) 31 (44.28%) 6 (40%) Cold discolored hands and feet 3 (14.28%) 4 (5.71%) 0 Stridor 0 5 (7.14%) 1 (6.66%) Constipation 15 (71.42%) 35 (50%) 8 (53.33%) Gait ataxia 15 (71.42%) 29 (41.42%) 0 Limb ataxia 5 (23.80%) 2 (2.85%) 0 Oculomotor features 4 (19.04%) 3 (4.28%) 0 Cerebellar dysarthria 1 (4.76%) 1 (1.42%) 0 Cognitive decline 9 (42.85%) 26 (37.14%) 2 (13.33%) Hallucination 6 (28.57%) 14 (20%) 2 (13.33%) MRI features (n = 89) 18 58 13 HCB sign 4 (22.22%) 4 (6.89%) 0 (0.0%) Atrophy of MCP 3 (15.78%) 6 (10.34%) 1 (7.69%) Atrophy of Putamen (and signal decrease on iron-sensitive sequences) 1 (5.55%) 5 (8.62%) 1 (7.69%) Atrophy of pons 5 (27.77%) 8 (13.79%) 2 (15.38%) Atrophy of cerebellum 7 (38.88%) 20 (34.48%) 2 (15.38%) Note : RBD: REM sleep behavioral disorder, HCB sign: Hot cross bun sign, MCP: Middle cerebellar peduncle. Table 3 Demographic, clinical, and imaging features of clinical subgroups in the MSA patients (n = 106). MSA-C MSA-P P -value (MSA-C vs MSA-P Unclassified Number of cases 25 (23.58%) 64 (60.37%) 17 (16.03%) Age 70.60 ± 8.93 68.68 ± 8.36 0.344 62.64 ± 8.81 Age at onset 66.44 ± 8.80 65.21 ± 8.59 0.551 62.64 ± 8.81 Duration 4.16 ± 3.72 3.43 ± 2.56 0.299 4.29 ± 5.21 Urinary problems 19 (76.0%) 42 (65.62%) 0.349 13 (76.47%) Orthostatic hypotension 9 (36.0%) 23 (35.93%) 1.000 2 (11.76%) Poorly L-dopa responsive parkinsonism 6 (24.0%) 10 (15.62%) 0.361 2 (11.76%) Bradykinesia/ Rigidity 8 (32.0%) 52 (81.25%) 0.000 10 (58.82%) Postural Instability 15 (60.0%) 34 (53.12%) 0.564 10 (58.82%) Moderate to severe postural Instability within 3 years 10 (40.0%) 14 (21.87%) 0.086 3 (17.64%) Resting tremor 5 (20.0%) 39 (60.93%) 0.001 7 (41.17%) Craniocervical dystonia 0 2 (3.12%) 0.384 0 Severe speech impairment within 3 years of motor onset 6 (24.0%) 21 (32.81%) 0.422 7 (41.17%) Severe dysphagia within 3 years of motor onset 3 (12.0%) 16 (25%) 0.183 2 (11.76%) Jerky myoclonic postural or kinetic tremor 6 (24.0%) 17 (26.56%) 0.810 7 (41.17%) Postural deformities 5 (20.0%) 8 (12.5%) 0.375 1 (5.88%) Inspiratory sighs 3 (12.0%) 4 (6.25%) 0.373 2 (11.76%) Pathologic laughter or crying 0 4 (6.25%) 0.208 1 (5.88%) RBD 11 (44.0%) 32 (50%) 0.616 5 (29.41%) Cold discolored hands and feet 1 (4.0%) 4 (6.25%) 0.689 2 (11.76%) Stridor 3 (12.0%) 2 (3.12%) 0.107 1 (5.88%) Constipation 16 (64.0%) 35 (54.68%) 0.430 7 (41.17%) Gait ataxia 24 (96.0%) 10 (15.62%) 0.000 10 (58.82%) Limb ataxia 4 (16.0%) 2 (3.12%) 0.031 1 (5.88%) Oculomotor features 4 (16.0%) 3 (4.68%) 0.078 0 Cerebellar dysarthria 1 (4.0%) 1 (1.56%) 0.499 0 Cognitive decline 8 (32.0%) 22 (34.37%) 0.837 7 (41.17%) Hallucination 6 (24.0%) 13 (20.31%) 0.709 3 (17.64%) MRI features (n = 89) 25 64 - - HCB sign 3 (12.0%) 5 (7.81%) - - Atrophy of MCP 4 (16.0%) 6 (9.37%) - - Atrophy of Putamen (and signal decrease on iron-sensitive sequences) 2 (8.0%) 5 (7.81%) - - Atrophy of pons 4 (16.0%) 11 (17.18%) - - Atrophy of cerebellum 10 (40.0%) 19 (29.68%) - - Note : MSA - C &P: Multiple system atrophy – cerebellar type and Parkinsonian type, RBD: REM sleep behavioral disorder, HCB sign: Hot cross bun sign, MCP: Middle cerebellar peduncle. The illustrative distribution of MSA-C and MAS-P patients across clinical establishment subgroups of MSA is presented in Supplementary Fig. 3 . Resting tremor and bradykinesia were significantly more present in MSA-P patients, whereas limb and gait ataxia were more prominent in MSA-C cases. Other clinical features did not show significant differences in the two subgroups (Table 2 and Table 3 ). PSP clinical subgroups As shown in Table 4 , PSP-P constitutes a higher percentage of the PSP patients in this study. Vertical gaze palsy (VPG), slowed vertical velocity saccades, falling (particularly within the past 3 years), parkinsonism, urinary and speech problems, and frontal, cognitive, and psychiatric problems were most prominent in these patients. VPG and weight loss were significantly more prominent in the PSP-RS group, while parkinsonism was significantly more present in the PSP-P patients. The Hummingbird sign was the most prominent MRI feature. The Morning Glory sign was relatively less frequent in the PSP-RS group (Fig. 1 ). Table 4 Demographic, clinical, and imaging features of PSP-RS and PSP-P patients (There was only one patient with PSP-PAGF) PSP-P (n = 78) PSP-RS (n = 29) P -value Age 72.51 ± 7.88 70.41 ± 5.72 0.193 Age at onset 67.56 ± 7.69 66.10 ± 6.30 0.363 Duration 4.85 ± 3.65 4.34 ± 2.40 0.484 VGP 38 (48.71%) 21 (72.41%) 0.030 Slow velocity of vertical saccades 50 (64.10%) 19 (65.51%) 0.896 Frequent macro square wave jerks or eyelid opening apraxia 18 (23.07%) 3 (10.34%) 0.144 Repeated unprovoked falling within 3 years 51 (65.38%) 23 (79.31%) 0.169 Positive pull test 50 (64.10%) 23 (79.31%) 0.136 Progressive gait freezing within 3 years 30 (38.46%) 15 (51.72%) 0.220 Parkinsonism, akinetic-rigid, predominantly axial 78 (100%) 7 (24.13%) 0.000 Luria 25 (32.05%) 8 (27.58%) 0.661 Speech/language disorder 34 (43.58%) 15 (51.72%) 0.457 Frontal cognitive/behavioral presentation 40 (51.28%) 10 (34.48%) 0.124 Corticobasal syndrome 6 (7.69%) 3 (10.34%) 0.667 Levodopa-resistance 0 (0.0%) 7 (24.13%) 0.000 Hypokinetic or spastic dysarthria 9 (11.53%) 4 (13.79%) 0.757 Dysphagia 21 (26.92%) 13 (44.82%) 0.079 Photophobia 0 (0.0%) 0 (0.0%) - Predominant midbrain atrophy or hypometabolism 10 (12.82%) 4 (13.79%) 0.900 Blurry or doubled vision 8 (10.25%) 3 (10.34%) 0.995 Sleep difficulties 38 (48.71%) 15 (51.72%) 0.786 Drooling or sialorrhea 5 (6.41%) 3 (10.34%) 0.498 Urinary urgency or incontinence 41 (52.56%) 19 (65.51%) 0.234 Constipation 26 (33.33%) 10 (34.48%) 0.915 Depression or anxiety 49 (62.82%) 15 (51.72%) 0.302 Hyperphagia and change in food preferences 1 (1.28%) 1 (3.44%) 0.473 Weight loss (with possible malnutrition) 5 (6.41%) 6 (20.68%) 0.032 Nonfluent agrammatic variant of primary progressive aphasia 6 (7.69%) 2 (6.89%) 0.896 progressive apraxia of speech 12 (15.38%) 2 (6.89%) 0.252 Apathy 28 (35.89%) 10 (34.48%) 0.896 Impulsivity, disinhibition, or perseveration 22 (28.20%) 10 (34.48%) 0.533 Limb myoclonus 7 (8.97%) 2 (6.89%) 0.737 Limb dystonia 1 (1.28%) 2 (6.89%) 0.123 MRI features (n = 83) 63 20 Morning glory sign 15 (23.80%) 1 (5.0%) - Hummingbird sign 20 (31.74%) 7 (35.0%) - Note : PSP – P, RS, & PAGF: Progressive supranuclear palsy – Parkinsonism, Richardson syndrome, and Pure akinesia with gait freezing, VGP: Vertical gaze palsy DISCUSSION MSA studies The MDS criteria for diagnosing MSA serve as a valuable tool for clinicians to differentiate these patients from possible differential diagnoses ( 2 , 16 ). These criteria consist of motor, non-motor, and imaging features found to be more differentiative in the diagnosis of MSA ( 16 ), and it was utilized in our study to describe the clinical features of these patients. Non-motor features are important constituents of the diagnosis and scaling of severity in patients with MSA ( 22 – 24 ). In general, it is believed that non-motor features significantly increase in severity during the first two years of the disease course in these patients ( 22 ). Moreover, orthostatic hypotension is considered as a common key component of MSA ( 25 ). The risk of fatigue (Odds ratio (OR) = 2.806, 95% CI = 1.253–6.286 in a study by Zhang et al.( 26 )) and cognitive decline (OR = 0.328,95% CI = 0.135–0.797 in a study by W. Li et al. ( 25 )) is suggested to be associated with this phenomenon. Our study found that although the frequency of orthostatic hypotension in clinically established MSA patients is close to that in a recent multi-center cohort of Chinese patients (~ 60.0%) ( 25 ), this was not compatible with other clinical groups in our study. Meanwhile, the mentioned Chinese study did not directly clarify the level of clinical establishment of the diagnosis ( 25 ) -i.e., clinically established, probable, or possible prodromal—and if their subjects were clinically established patients, this is more compatible with the same group in our study. A notable feature of patients with MSA that has gained attention in recent cohort studies is the presence of RBD. It was a prominent finding in our study, involving almost half of all clinical MSA subgroups. This phenomenon is, however, a common finding in many α-synucleinopathies such as Parkinson’s disease ( 27 , 28 ). In a recent single-center study in Korea, one-fifth of the patients with RBD were related to the MSA group, while more than half of them were diagnosed with Parkison’s disease ( 27 ). The next component of MSA that has recently attracted attention in some cohort studies is cognitive decline. Although cognitive decline is not a key component of MSA patients, it has attracted increasing attention in recent studies ( 29 ). A cohort study conducted by Sambati et al. on Italian MSA patients reported that almost 60% of patients showed a cognitive decline at the baseline evaluation, and 10% of them had established dementia ( 30 ). Our study on Persian patients revealed that almost one-third of individuals in each MSA clinical group had cognitive decline, which is a considerably lower rate compared to the Italian cohort. It is important to note that the diagnosis of MSA in the Italian cohort was based on the international consensus criteria and the absence of non-supporting features except dementia (based on the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria), and the cognitive evaluation was performed using a battery of cognitive evaluation tests comprehensively assessing different domains of cognitive function ( 30 ). Moving to differences between MSA-P and MSA-C, a European cohort study highlighted the significant differences between MSA-C and MSA-P patients ( 31 ). The study found that aside from rigidity, bradykinesia, resting tremor, and gait freezing were notably more pronounced in MSA-P cases, and cerebellar signs were equally significant but more prominent in MSA-C cases, they did not identify any other clinical findings that were significantly more common in either subgroup ( 31 ). This is compatible with our findings, where there were no other significant differences in the clinical components of MDS criteria for MSA patients between MSA-C and MSA-P, except those related to parkinsonism and cerebellar signs. It is important to note that the patients discussed in this paper were evaluated during their first medical consultation, and the data presented pertains specifically to this initial evaluation. According to a study by Starhof et al., the rates of clinical components of MDS criteria for MSA patients can vary across different follow-up phases of the disease ( 32 ). Although our patients had different durations of the symptoms at entry, it is possible that many of the variables observed in our study may experience a significantly increased rate of occurrence in the future. PSP studies The present paper assessed the MDS criteria ( 13 ) in Persian patients diagnosed with PSP. This is an important topic, filling a fraction of the gap in our knowledge regarding the characteristics of different ethnic groups with PSP across the world. An important finding of our paper is that despite an estimated higher prevalence of PSP-RS in most of the studies ( 33 ), PSP-P had a higher frequency of PSP subgroups in our study. Regarding this matter, in a recently published study on multi-ethnic PSP patients in Malaysia, it was shown that of 104 PSP patients who participated in the project, 48.1% were PSP-RS, 37.5% were PSP-P, and 10.6% of cases were diagnosed with PSP-PAGF ( 34 ). Ethnic and genetic variations may play a crucial role in this clinical diversity. As confirmed in recent studies on large PSP cohort patients, higher Magnetic Resonance Parkinsonism Index (MRPI; midsagittal area of the pons/midbrain ratio multiplied by the middle cerebellar peduncle width/superior cerebellar peduncle width ratio) plays a helpful role in early distinguishing of PSP patients compared to other atypical Parkinsonism disorders ( 35 ). This emphasizes the importance of imaging findings in these patients, however, as shown in our paper, the frequency of typical imaging findings in PSP patients is relatively low, and clinical manifestations described in the MDS criteria ( 13 ) still play a crucial role in the early differentiation of PSP from other atypical Parkinsonism disorders. The present paper provided a thorough clinical view of PSP patients, highlighting the distribution of MDS criteria features ( 13 ) in Persian PSP patients. Additional insights into our findings Despite the criteria for diagnosis of MSA and PSP patients, emphasizing the ocular motor manifestations, non-motor features (e.g., RBD, orthostatic hypotension, urinary dysfunction), and imaging findings, in some instances there might be challenges in distinguishing MSA from PSP ( 23 ). Generally, in clinical settings where specific complex laboratory analyses such as seed amplification assay and serum neurofilament examinations -introduced recently as potential ways of diagnosis ( 7 , 36 , 37 )- are not readily accessible, distinguishing between MSA and PSP can present significant challenges ( 38 ). This challenge is more sensible knowing that up to one-third of patients with MSA may represent non-motor symptoms prior to motor manifestations ( 19 ). These non-motor symptoms may include urinary problems and RBD (i.e., frequent symptoms in both MSA and PSP) in more than two-thirds of these cases, potentially challenging the diagnosis ( 19 ). Expanding our knowledge of clinical presentations of MSA and PSP across different ethnic groups may help clinicians obtain a better insight when facing these patients. Our study found urinary problems and RBD are common symptoms in patients with PSP. In our study, the age at onset (with a cut-off of 70 years) of patients with parkinsonism as the initial motor manifestation showed a significant way of distinguishing MSA from PSP in Persian patients. An interesting study regarding the utility of clinical presentations in differentiating MSA from PSP is conducted by Wiblin et al. ( 39 ), showing that even in signs and symptoms that are commonly presented in both disorders, the time of onset may play a helpful role in diagnosis. They showed that although both MSA and PSP patients remarkably show episodes of falling, it is important to note that episodes of falling start much earlier in the disease course of PSP patients (a median of 18.5 months before diagnosis, compared to the median of one month before diagnosis in MSA cases) ( 39 ). Their findings suggested that the time of onset of symptoms may play an important role in distinguishing these patients when facing clinical diagnostic challenges. MRI findings, a component of MDS criteria for diagnosis of MSA and PSP ( 13 , 16 ), are a helpful way to surpass the challenges in the diagnosis of PSP and MSA ( 4 , 35 ). However, as shown in our paper, the MRI signs described in the diagnostic criteria are not prominent findings in these patients, and only up to one-third of these patients showed at least one of these signs. Although atrophy of pons is more prominent in MSA-C, in our study nearly the same fraction of MSA-C and MSA-P patients presented this sign ( 40 ). Studies also reported that MSA-P presents higher rates of putaminal atrophy compared to the MAS-C ( 40 ), but the present paper revealed that there was little difference between the two MSA subtypes regarding this MRI finding. The frequency of other MRI findings of MSA in the present paper was compatible with the literature ( 40 ). Compared to our study, the rate of cerebellar atrophy (84.9%) and the hot cross bun sign (24.5%) were relatively higher in a cohort of another Asian country, India ( 41 ). This was probably due to differences in the duration of the symptoms of onset at entry, which was approximately 4.34 ± 3.04 years in the Indian cohort ( 41 ) compared to 3.74 ± 3.37 years in our study. Our paper also studied the rate of the Hummingbird sign and Morning Glory sign in Persian PSP patients. These two signs are reported with different sensitivities and specificities across the literature ( 40 ). Studies revealed that the Hummingbird sign has 97%-100% specificity but a relatively lower sensitivity of 35%-57% for the diagnosis of PSP ( 42 , 43 ). There could be different rates of presentation of the mentioned MRI signs in settings with different durations of disease onset of PSP (like our study). A study by Sjöström et al. recently suggested putaminal T1/T2-weighted MRI ratio has the potential to distinguish between PSP, MSA, Parkinson’s disease, and healthy control. ( 38 ). They showed this ratio at cerebellar white matter was significantly higher in PSP patients compared to MSA patients with area under the receiver operating characteristic curve of 0.62 ( 38 ). The shortfall of information on the phenotypical description of MSA and PSP patients in Middle Eastern countries, Iran in particular, was another key factor in conducting the present research paper. Research on the demographic and clinical characteristics of MSA and PSP remains scarce in West Asia and the Middle East compared to other Asian countries like India, where more studies have provided data on the disease presentation ( 41 , 44 ). In general, Indian PSP patients present more with the PSP-RS subtype, and the mean age at onset of the Indian patients is around 64 years ( 44 ), which is slightly lower compared to our Persian cross-sectional study with a mean age at onset of 67 years. Regarding the MSA patients in Indian studies, MSA-P showed a slightly higher fraction of the total Indian MSA patients in a cohort (29 MSA-P, vs 25 MSA-C) ( 45 ). In our Persian cross-sectional study, MSA-P comprised a remarkably higher fraction of MSA patients (64 MSA-P, vs 25 MSA-C). In addition, the differences between MRI findings in Indian and Persian MSA patients were discussed earlier. Further investigations in similar ethnic groups may provide valuable insights into the clinical presentations of MSA and PSP patients in this region. Declarations CONFLICT OF INTEREST There were no conflicts of interest or funding sources for this article. ACKNOWLEDGEMENT None. DATA AVAILABILITY STATEMENT The data used in this study will be available upon request. AUTHOR ROLES (1) Research Project: A. Conception, B. Organization, C. Execution, D. Validation, E. Data analysis, F. Visualization, G. Data Acquisition; (2) Manuscript: A. Writing of the First Draft, B. Review and Critique. M.S.: 1A, 1B, 1C, 1D, 2B K.R.: 1C, 1E, 1G, 1F, 2A, 2B M.Q.: 1C, 1G, 2A S.S.: 1C, 1G F.H.: 1C, 1G M.G.: 1G M.E.: 1C, 1D, 2B FUNDING SOURCES AND CONFLICT OF INTEREST No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. FINANCIAL DISCLOSURES FOR THE PREVIOUS 12 MONTHS The authors declare that there are no additional disclosures to report. STATEMENT REGARDING ETHICAL CONDUCT AND INFORMED CONSENT We hereby confirm that the present study conforms to the ethical standards and guidelines of the journal. Patient consent was obtained for this research. ETHICAL COMPLIANCE STATEMENT We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. The present paper is also approved by the ethics committee of Shahid Beheshti University of Medical Sciences. References Lee S, Kim H, Kim R, Jin B, Kim S, Woo KA et al (2025) Application of elastic net for clinical outcome prediction and classification in progressive supranuclear palsy: A multicenter cohort study. 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Saudi J Anaesth 13(Suppl 1):S31–s4 Zhang L, Hou Y, Cao B, Wei Q, Ou R, Liu K et al (2022) Longitudinal evolution of motor and non-motor symptoms in early-stage multiple system atrophy: a 2-year prospective cohort study. BMC Med 20(1):446 Eschlböck S, Kiss G, Krismer F, Fanciulli A, Kaindlstorfer C, Raccagni C et al (2021) Urodynamic Evaluation in Multiple System Atrophy: A Retrospective Cohort Study. Mov Disord Clin Pract 8(7):1052–1060 Sakakibara R, Panicker J, Simeoni S, Uchiyama T, Yamamoto T, Tateno F et al (2019) Bladder dysfunction as the initial presentation of multiple system atrophy: a prospective cohort study. Clin Auton Res 29(6):627–631 Li W, Ding Y, Zhao Z, Zhang X, Guan A, Tang L et al (2025) Orthostatic hypotension is involved in cognitive impairment in patients with multiple system atrophy: a multi-center cohort study in China. J Neurol 272(3):186 Zhang L, Cao B, Hou Y, Gu X, Wei QQ, Ou R et al (2022) Fatigue in Patients With Multiple System Atrophy: A Prospective Cohort Study. Neurology 98(1):e73–e82 Byun JI, Sunwoo JS, Shin YW, Shin JW, Kim TJ, Jun JS et al (2025) Clinical characteristics and phenoconversion in isolated REM sleep behavior disorder: a prospective single-center study in Korea, compared with Montreal cohort. J Clin Sleep Med 21(1):81–88 Zhang L, Hou Y, Li C, Wei Q, Ou R, Liu K et al (2023) Longitudinal evolution of sleep disturbances in early multiple system atrophy: a 2-year prospective cohort study. BMC Med 21(1):454 Eschlböck S, Delazer M, Krismer F, Bodner T, Fanciulli A, Heim B et al (2020) Cognition in multiple system atrophy: a single-center cohort study. Ann Clin Transl Neurol 7(2):219–228 Sambati L, Calandra-Buonaura G, Giannini G, Cani I, Provini F, Poda R et al (2020) Cognitive Profile and Its Evolution in a Cohort of Multiple System Atrophy Patients. Front Neurol 11:537360 Wenning GK, Geser F, Krismer F, Seppi K, Duerr S, Boesch S et al (2013) The natural history of multiple system atrophy: a prospective European cohort study. Lancet Neurol 12(3):264–274 Starhof C, Korbo L, Lassen CF, Winge K, Friis S (2016) Clinical Features in a Danish Population-Based Cohort of Probable Multiple System Atrophy Patients. Neuroepidemiology 46(4):261–267 Swallow DM, Zheng CS, Counsell CE (2022) Systematic review of prevalence studies of progressive supranuclear palsy and corticobasal syndrome. Mov Disorders Clin Pract 9(5):604–613 Lim SY, Dy Closas AMF, Tan AH, Lim JL, Tan YJ, Vijayanathan Y et al (2023) New insights from a multi-ethnic Asian progressive supranuclear palsy cohort. Parkinsonism Relat Disord 108:105296 Nigro S, Antonini A, Vaillancourt DE, Seppi K, Ceravolo R, Strafella AP et al (2020) Automated MRI Classification in Progressive Supranuclear Palsy: A Large International Cohort Study. Mov Disord 35(6):976–983 Liu M, Cai Y, Pan J, Wang T, Li Y, Yu Q et al (2024) Serum neurofilament light chain as a diagnostic and prognostic biomarker in multiple system atrophy: a prospective cohort study. J Neurol 272(1):74 Chen Y, Wang Y, Tao Q, Lu P, Meng F, Zhuang L et al (2024) Diagnostic value of isolated plasma biomarkers and its combination in neurodegenerative dementias: A multicenter cohort study. Clin Chim Acta 558:118784 Sjöström H, van Westen D, Hall S, Tjerkaski J, Westman E, Muehlboeck S et al (2024) Putaminal T1/T2-weighted ratio is increased in PSP compared to PD and healthy controls, a multi-cohort study. Parkinsonism Relat Disord 121:106047 Wiblin L, Durcan R, Galna B, Lee M, Burn D (2019) Clinical Milestones Preceding the Diagnosis of Multiple System Atrophy and Progressive Supranuclear Palsy: A Retrospective Cohort Study. J Mov Disord 12(3):177–183 Aludin S, Schmill L-PA (eds) (2021) MRI signs of Parkinson’s disease and atypical parkinsonism. RöFo-Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren. Georg Thieme Verlag KG Pradhan S, Tandon R (2017) Relevance of non-specific MRI features in multiple system atrophy. Clin Neurol Neurosurg 159:29–33 Mueller C, Hussl A, Krismer F, Heim B, Mahlknecht P, Nocker M et al (2018) The diagnostic accuracy of the hummingbird and morning glory sign in patients with neurodegenerative parkinsonism. Parkinsonism Relat Disord 54:90–94 Mangesius S, Hussl A, Krismer F, Mahlknecht P, Reiter E, Tagwercher S et al (2018) MR planimetry in neurodegenerative parkinsonism yields high diagnostic accuracy for PSP. Parkinsonism Relat Disord 46:47–55 Raju S, Shetty K, Sahoo L, Paramanandam V, Iyer JM, Bowmick S et al (2025) Progressive Supranuclear Palsy in India: Past, Present, and Future. Ann Indian Acad Neurol 28(1):17–25 Seniaray N, Verma R, Ranjan R, Belho E, Mahajan H (2021) Comprehensive Functional Evaluation of the Spectrum of Multi-System Atrophy with 18F-FDG PET/CT and 99mTc TRODAT-1 SPECT: 5 Year's Experience from a Tertiary Care Center. Ann Indian Acad Neurol 24(4):490–494 Additional Declarations No competing interests reported. Supplementary Files SupplementaryFigure1.pdf SupplementaryFigure2.pdf SupplementaryFigure3.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6526460","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":451951006,"identity":"2daf77c0-a34b-4d37-a5a1-0e024c71ff50","order_by":0,"name":"Mehri Salari","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mehri","middleName":"","lastName":"Salari","suffix":""},{"id":451951007,"identity":"2391afaf-64b8-4424-857e-f24843af49a2","order_by":1,"name":"Kamran 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frequency of clinical features in MSA and PSP subtypes.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6526460/v1/facff093dbd978aa7fb9c588.jpg"},{"id":83023207,"identity":"0c676724-9ae9-4da8-bb0e-874757194efd","added_by":"auto","created_at":"2025-05-19 07:54:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1989305,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6526460/v1/4cb04b32-ae33-4a77-91b7-fb7dd0c8999d.pdf"},{"id":82349335,"identity":"e03f4514-99bc-4338-bf6d-184efae5f864","added_by":"auto","created_at":"2025-05-09 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11:02:46","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":49128,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6526460/v1/6420dab01f0b40314a0d4150.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Multiple System Atrophy and Progressive Supranuclear Palsy in Persian Population: A Retrospective Cross-sectional Study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eMultiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are neurodegenerative conditions classified under the spectrum of atypical Parkinsonian syndromes (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). While both conditions share clinical features with Parkinson's disease (PD), such as bradykinesia, rigidity, and postural instability, they are distinguished by their distinct pathological mechanisms, clinical presentations, and disease progression (\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMultiple System Atrophy (MSA) is a sporadic, adult-onset disorder characterized by the presence of α-synuclein-positive glial cytoplasmic inclusions (GCIs), which predominantly affect oligodendrocytes and lead to widespread neurodegeneration (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). MSA is categorized into two clinical subtypes: MSA-P, characterized by predominant Parkinsonian features, and MSA-C, characterized by predominant cerebellar ataxia. Autonomic dysfunction is a hallmark of MSA and often aids in differentiating it from PD (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). The disease progresses rapidly, with a median survival of 6\u0026ndash;10 years from symptom onset, and no disease-modifying therapies are currently available (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eProgressive Supranuclear Palsy (PSP) is a tauopathy characterized by the accumulation of hyperphosphorylated tau protein in neurons and glia, particularly in the basal ganglia, brainstem, and cortex (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). The most common clinical variant, Richardson's syndrome (PSP-RS), presents with early postural instability, vertical supranuclear gaze palsy, and cognitive dysfunction (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Other forms, like PSP-parkinsonism (PSP-P), can resemble PD in the initial phases but generally show a limited response to levodopa treatment. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Other subtypes of PSP, including PSP-corticobasal syndrome (PSP-CBS), with parkinsonism, apraxia, cortical sensory loss, and other CBS-like symptoms, PSP-frontal (PSP-F) with predominant behavioral symptoms and less often motor onset, PSP-speech/language (PSP-SL), with initial symptoms such as progressive non-fluent speech aphasia and apraxia), and PSP-postural instability (PSP-PI), presenting initially with severe postural instability comprise a lower frequency of PSP patients compared to previously mentioned subtypes (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). PSP is associated with significant morbidity, including falls, dysphagia, and pseudobulbar affect, and has a median survival of 5\u0026ndash;7 years (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe diagnostic criteria established by the Movement Disorder Society (MDS) for both MSA and PSP would help differentiate between these two conditions (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Both disorders can present with parkinsonism, postural instability, and early fall, making initial diagnosis difficult (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Additionally, autonomic dysfunction, while more prominent in MSA, can also occur in PSP, further complicating the diagnostic process (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Neuroimaging findings, such as midbrain atrophy in PSP, and putaminal slit sign and/or hot cross bun sign in MSA, provide valuable diagnostic clues, but these features may not be evident in the early stages of the disease (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), sometimes resulting in diagnostic challenges.\u003c/p\u003e \u003cp\u003eRecent studies have significantly advanced our understanding of how MSA and PSP manifest across diverse ethnic populations, revealing notable differences in demographic and clinical presentations (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). There is a notable scarcity of comprehensive studies investigating the demographic and clinical features of MSA and PSP in Middle Eastern countries, limiting insights into their prevalence, phenotypic variations, and disease progression in these populations. The present paper is designed to study the clinical features of Persian MSA and PSP patients. It expands our knowledge of these conditions in this country, further providing a valuable source of information regarding the status of MSA and PSP in Middle Eastern ethnic groups.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis study used the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline as a checklist (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). This study used a dataset containing demographic, clinical features, and imaging findings, retrospectively collected from patients diagnosed with MSA and PSP following examination by a Movement Disorders Specialist at a referral movement disorders Centre in Tehran from January 2019 to January 2025. Retrospective data were collected from the clinic's medical records by three investigators under the supervision of a movement disorders specialist.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePatients and Participants\u003c/h3\u003e\n\u003cp\u003eWe conducted a retrospective investigation of the medical records of patients who were referred to our movement disorders clinic between January 2019 and January 2025. A total of 111 patients diagnosed with Multiple System Atrophy (MSA) and 123 patients diagnosed with Progressive Supranuclear Palsy (PSP) were initially identified. Informed consent was taken from the patients before participation in the study. Patients were included in the final analysis if they met the following inclusion criteria: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Diagnosed with MSA or PSP according to the referring physician's assessment at the time of the initial consultation. The diagnosis was performed by a movement disorders specialist based on the clinical judgment and criteria provided by MDS (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), and (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Sufficient data were available in their medical records from the first medical consultation (initial diagnosis) to assess the presence or absence of each component of the relevant MDS diagnostic criteria for MSA (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) and PSP (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePatients were excluded if their medical records were incomplete regarding the features assessed by the MDS criteria.\u003c/p\u003e \u003cp\u003eThe MDS criteria (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) were used for the subgroup assignment of MSA patients into the following subgrouping systems: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Clinically established MSA, clinically probable MSA, and possible prodromal MSA regarding the establishment of the diagnosis, and (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) MSA with predominant Parkinsonism (MSA-P) and MSA with predominant cerebellar signs (MSA-C). If a patient could not meet the criteria to fall into MSA-P or MSA-C subgroups, it was considered \u0026ldquo;unclassified\u0026rdquo;.\u003c/p\u003e \u003cp\u003eIn addition, the MDS criteria (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) were used to assign PSP patients into subgroups: PSP with predominant Parkinsonism (PSP-P), PSP-Richardson's syndrome (PSP-RS), and PSP-Pure akinesia with gait freezing (PSP-PAGF).\u003c/p\u003e \u003cp\u003eData was extracted from the medical records included patient demographics (age, sex, age at onset, duration from initiation of the symptoms to first diagnosis), presenting symptoms, and neurological examination findings presented in the MDS criteria (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eStatistical Analysis and Software\u003c/h3\u003e\n\u003cp\u003eStatistical analysis was performed using Python version 3 within the Anaconda application. Data was organized and manipulated using the Pandas library. Descriptive statistics (means, standard deviations, frequencies, and percentages) were used to summarize patient characteristics and the frequency of each component of the MDS criteria. Patients with missing data were excluded from the analysis.\u003c/p\u003e \u003cp\u003eThe chi-square test, t-test, and Mann-Whitney\u0026rsquo;s U test were used for comparison analysis using the SciPy library. Data visualization was performed using Matplotlib and Seaborn libraries. A \u003cem\u003ep\u003c/em\u003e-value of less than 0.05 was considered statistically significant for all analyses.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eNumber of participants in each group and subgroup\u003c/h2\u003e \u003cp\u003eThere were 125 and 139 patients diagnosed with MSA and PSP in the period of this study, respectively. After filtering the available records based on the inclusion criteria, a total number of 106 patients with MSA and 108 patients with PSP participated in this retrospective cross-sectional (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The fifty excluded patients, who were related to the retrospective data, had an incomplete medical record. MSA patients were classified into clinically established (21, 19.81%), clinically probable (70, 66.03%), and possible prodromal MSA (15, 14.15%). In the MSA group, 25 (23.58%) had MSA-C, 64 (60.37%) had MSA-P, and 17 (16.03%) were unclassified. PSP subgroups included 78 (72.22%) with PSP-P, 29 (26.85%) with PSP-RS, and one (0.92%) with PSP-PAGF.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic Features of the MSA and PSP patients. Age, age at onset, and duration are by years and were compared using t-test. The sex variable is compared using the Mann Whitney U-test.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMSA (n\u0026thinsp;=\u0026thinsp;106)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePSP (n\u0026thinsp;=\u0026thinsp;108)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e48 (45.28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e76 (70.37%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e58 (54.71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32 (29.62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e68.85\u0026thinsp;\u0026plusmn;\u0026thinsp;8.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e71.82\u0026thinsp;\u0026plusmn;\u0026thinsp;7.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at onset (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65.09\u0026thinsp;\u0026plusmn;\u0026thinsp;8.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e67.01\u0026thinsp;\u0026plusmn;\u0026thinsp;7.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.084\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.74\u0026thinsp;\u0026plusmn;\u0026thinsp;3.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.75\u0026thinsp;\u0026plusmn;\u0026thinsp;3.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.030\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParkinsonism as SOO (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e100 (94.34%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e85 (78.70%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParkinsonism as SOO; Age (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e68.60\u0026thinsp;\u0026plusmn;\u0026thinsp;8.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e72.48\u0026thinsp;\u0026plusmn;\u0026thinsp;7.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParkinsonism as SOO; Age at onset (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e64.78\u0026thinsp;\u0026plusmn;\u0026thinsp;8.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e67.68\u0026thinsp;\u0026plusmn;\u0026thinsp;7.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParkinsonism as SOO; Duration (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.80\u0026thinsp;\u0026plusmn;\u0026thinsp;3.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.71\u0026thinsp;\u0026plusmn;\u0026thinsp;3.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.043\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary problems (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e74 (70.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60 (52.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpeech problems (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34 (33.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e49 (43.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.143\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003eNote\u003c/b\u003e: MSA: Multiple system atrophy, PSP: Progressive supranuclear palsy, SD: Standard deviation, SOO: Symptom of onset.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eComparison of MSA and PSP groups\u003c/h2\u003e \u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the male/female proportion was significantly higher in PSP than in MSA patients (2.37 vs 0.82, \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;=\u0026thinsp;0.000). In addition, the mean age of the PSP group was significantly higher than the MSA group (71.82\u0026thinsp;\u0026plusmn;\u0026thinsp;7.46 vs 68.85\u0026thinsp;\u0026plusmn;\u0026thinsp;8.66, \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;=\u0026thinsp;0.008). The same was true for the mean duration of the disease (4.75\u0026thinsp;\u0026plusmn;\u0026thinsp;3.35 for PSP, vs 3.74\u0026thinsp;\u0026plusmn;\u0026thinsp;3.37 for MSA, \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;=\u0026thinsp;0.030), but the mean of age at onset was not significantly different in the MSA (65.09\u0026thinsp;\u0026plusmn;\u0026thinsp;8.67) and PSP (67.01\u0026thinsp;\u0026plusmn;\u0026thinsp;7.47) subjects (\u003cb\u003eSupplementary Fig.\u0026nbsp;1)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eThe age of patients presenting with Parkinsonism as a symptom of onset was significantly higher in PSP cases (68.60\u0026thinsp;\u0026plusmn;\u0026thinsp;8.38 vs 72.48\u0026thinsp;\u0026plusmn;\u0026thinsp;7.80, \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;=\u0026thinsp;0.003, Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). There were no significant differences in the duration and age of onset of patients with parkinsonism as a presenting symptom of onset in both groups. Looking at this significant difference in age, we decided to compare parkinsonism as a symptom of onset in patients aged\u0026thinsp;\u0026lt;\u0026thinsp;70 years and those aged\u0026thinsp;\u0026ge;\u0026thinsp;70 years. In the subgroup with patients younger than 70 years, MSA patients presented significantly more with parkinsonism as the symptom of onset (50.0% vs 27.78%, Chi-square statistic\u0026thinsp;=\u0026thinsp;94.65, \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;=\u0026thinsp;0.000). Moreover, this was reversed in patients aged 70 years and older, where the PSP group showed significantly higher rates (44.34% vs 50.93%, Chi-square statistic\u0026thinsp;=\u0026thinsp;94.62, \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;=\u0026thinsp;0.000). \u003cb\u003eSupplementary Fig.\u0026nbsp;2\u003c/b\u003e represents the distribution of age across the patients with Parkinsonism as a symptom of onset in this study.\u003c/p\u003e \u003cp\u003eAs expected, the rate of urinary problems was significantly higher in the MSA (70.0%) compared to the PSP (52.9%, \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;=\u0026thinsp;0.017) group (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In contrast, there was no significant difference in the rate of speech problems between these two groups.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMSA clinical subgroups\u003c/h3\u003e\n\u003cp\u003eThe information provided in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e describes the clinical and imaging features in MSA clinical subgroups. In a method of categorization, the MSA patients were divided into clinically established MSA, clinically probable MSA, and possible prodromal MSA using the consensus MDS criteria (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Orthostatic hypotension, constipation, urinary problems, parkinsonism, and REM sleep behavioral disorder (RBD) were the most prominent clinical presentations.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic, clinical, and imaging features of diagnosis establishment subgroups in the MSA patients (n\u0026thinsp;=\u0026thinsp;106).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eClinically established MSA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eClinically probable MSA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePossible prodromal MSA\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of cases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (19.81%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70 (66.03%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (14.15%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69.04\u0026thinsp;\u0026plusmn;\u0026thinsp;8.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.67\u0026thinsp;\u0026plusmn;\u0026thinsp;8.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e69.46\u0026thinsp;\u0026plusmn;\u0026thinsp;7.40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at onset\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.14\u0026thinsp;\u0026plusmn;\u0026thinsp;8.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.24\u0026thinsp;\u0026plusmn;\u0026thinsp;8.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67.60\u0026thinsp;\u0026plusmn;\u0026thinsp;7.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.90\u0026thinsp;\u0026plusmn;\u0026thinsp;1.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary problems\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (75.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrthostatic hypotension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (57.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (31.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePoorly L-dopa responsive parkinsonism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (76.19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (13.33%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBradykinesia/ Rigidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (57.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47 (67.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (73.33%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostural Instability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (71.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (55.71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (40%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate to severe postural Instability within 3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (71.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (12.85%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (20%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResting tremor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (47.61%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (47.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (53.33%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCraniocervical dystonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (4.76%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere speech impairment within 3 years of motor onset\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (33.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (32.85%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (26.66%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere dysphagia within 3 years of motor onset\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (9.52%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (22.85%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (20%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJerky myoclonic postural or kinetic tremor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (38.09%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (24.28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (33.33%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostural deformities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (33.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (7.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (13.33%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInspiratory sighs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (9.52%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathologic laughter or crying\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (14.28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (6.66%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRBD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (52.38%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (44.28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (40%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCold discolored hands and feet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (14.28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (5.71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStridor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (7.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (6.66%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConstipation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (71.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (53.33%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGait ataxia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (71.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (41.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLimb ataxia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (23.80%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2.85%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOculomotor features\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (19.04%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (4.28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebellar dysarthria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (4.76%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCognitive decline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (42.85%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (37.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (13.33%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHallucination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (28.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (13.33%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMRI features (n\u0026thinsp;=\u0026thinsp;89)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHCB sign\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (22.22%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (6.89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrophy of MCP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (15.78%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (10.34%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (7.69%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrophy of Putamen (and signal decrease on iron-sensitive sequences)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (8.62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (7.69%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrophy of pons\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (27.77%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (13.79%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (15.38%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrophy of cerebellum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (38.88%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (34.48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (15.38%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003eNote\u003c/b\u003e: RBD: REM sleep behavioral disorder, HCB sign: Hot cross bun sign, MCP: Middle cerebellar peduncle.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic, clinical, and imaging features of clinical subgroups in the MSA patients (n\u0026thinsp;=\u0026thinsp;106).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMSA-C\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMSA-P\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value \u003cem\u003e(MSA-C vs MSA-P\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUnclassified\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of cases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (23.58%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64 (60.37%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17 (16.03%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.60\u0026thinsp;\u0026plusmn;\u0026thinsp;8.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.68\u0026thinsp;\u0026plusmn;\u0026thinsp;8.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.344\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e62.64\u0026thinsp;\u0026plusmn;\u0026thinsp;8.81\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at onset\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.44\u0026thinsp;\u0026plusmn;\u0026thinsp;8.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65.21\u0026thinsp;\u0026plusmn;\u0026thinsp;8.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.551\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e62.64\u0026thinsp;\u0026plusmn;\u0026thinsp;8.81\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.16\u0026thinsp;\u0026plusmn;\u0026thinsp;3.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.43\u0026thinsp;\u0026plusmn;\u0026thinsp;2.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.299\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.29\u0026thinsp;\u0026plusmn;\u0026thinsp;5.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary problems\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (76.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (65.62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.349\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (76.47%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrthostatic hypotension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (36.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (35.93%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (11.76%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePoorly L-dopa responsive parkinsonism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (24.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (15.62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.361\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (11.76%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBradykinesia/ Rigidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (32.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (81.25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (58.82%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostural Instability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (53.12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.564\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (58.82%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate to severe postural Instability within 3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (40.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (21.87%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.086\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (17.64%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResting tremor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (60.93%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (41.17%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCraniocervical dystonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (3.12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.384\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere speech impairment within 3 years of motor onset\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (24.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (32.81%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.422\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (41.17%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere dysphagia within 3 years of motor onset\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (12.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.183\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (11.76%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJerky myoclonic postural or kinetic tremor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (24.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (26.56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.810\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (41.17%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostural deformities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.375\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (5.88%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInspiratory sighs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (12.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (6.25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.373\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (11.76%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathologic laughter or crying\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (6.25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.208\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (5.88%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRBD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (44.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.616\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (29.41%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCold discolored hands and feet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (6.25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.689\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (11.76%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStridor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (12.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (3.12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.107\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (5.88%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConstipation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (64.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (54.68%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.430\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (41.17%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGait ataxia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (96.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (15.62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (58.82%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLimb ataxia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (16.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (3.12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.031\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (5.88%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOculomotor features\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (16.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (4.68%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebellar dysarthria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.499\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCognitive decline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (32.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (34.37%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.837\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (41.17%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHallucination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (24.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (20.31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.709\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (17.64%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMRI features (n\u0026thinsp;=\u0026thinsp;89)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHCB sign\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (12.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (7.81%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrophy of MCP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (16.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (9.37%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrophy of Putamen (and signal decrease on iron-sensitive sequences)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (8.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (7.81%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrophy of pons\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (16.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (17.18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrophy of cerebellum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (40.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (29.68%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cb\u003eNote\u003c/b\u003e: MSA - C \u0026amp;P: Multiple system atrophy \u0026ndash; cerebellar type and Parkinsonian type, RBD: REM sleep behavioral disorder, HCB sign: Hot cross bun sign, MCP: Middle cerebellar peduncle.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe illustrative distribution of MSA-C and MAS-P patients across clinical establishment subgroups of MSA is presented in \u003cb\u003eSupplementary Fig.\u0026nbsp;3\u003c/b\u003e. Resting tremor and bradykinesia were significantly more present in MSA-P patients, whereas limb and gait ataxia were more prominent in MSA-C cases. Other clinical features did not show significant differences in the two subgroups (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003ePSP clinical subgroups\u003c/h3\u003e\n\u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, PSP-P constitutes a higher percentage of the PSP patients in this study. Vertical gaze palsy (VPG), slowed vertical velocity saccades, falling (particularly within the past 3 years), parkinsonism, urinary and speech problems, and frontal, cognitive, and psychiatric problems were most prominent in these patients. VPG and weight loss were significantly more prominent in the PSP-RS group, while parkinsonism was significantly more present in the PSP-P patients. The Hummingbird sign was the most prominent MRI feature. The Morning Glory sign was relatively less frequent in the PSP-RS group (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic, clinical, and imaging features of PSP-RS and PSP-P patients (There was only one patient with PSP-PAGF)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePSP-P (n\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePSP-RS (n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72.51\u0026thinsp;\u0026plusmn;\u0026thinsp;7.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.41\u0026thinsp;\u0026plusmn;\u0026thinsp;5.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.193\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at onset\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67.56\u0026thinsp;\u0026plusmn;\u0026thinsp;7.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.10\u0026thinsp;\u0026plusmn;\u0026thinsp;6.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.363\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.85\u0026thinsp;\u0026plusmn;\u0026thinsp;3.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.34\u0026thinsp;\u0026plusmn;\u0026thinsp;2.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.484\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVGP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (48.71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (72.41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.030\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSlow velocity of vertical saccades\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (64.10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (65.51%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.896\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrequent macro square wave jerks or eyelid opening apraxia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (23.07%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (10.34%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.144\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRepeated unprovoked falling within 3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (65.38%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (79.31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.169\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive pull test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (64.10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (79.31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.136\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgressive gait freezing within 3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (38.46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (51.72%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.220\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParkinsonism, akinetic-rigid, predominantly axial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (24.13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (32.05%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (27.58%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.661\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpeech/language disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (43.58%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (51.72%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.457\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrontal cognitive/behavioral presentation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (51.28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (34.48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.124\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticobasal syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (7.69%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (10.34%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.667\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevodopa-resistance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (24.13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypokinetic or spastic dysarthria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (11.53%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (13.79%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.757\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDysphagia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (26.92%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (44.82%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.079\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhotophobia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePredominant midbrain atrophy or hypometabolism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (12.82%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (13.79%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.900\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlurry or doubled vision\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (10.25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (10.34%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.995\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSleep difficulties\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (48.71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (51.72%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.786\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrooling or sialorrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (6.41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (10.34%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.498\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary urgency or incontinence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (52.56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (65.51%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.234\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConstipation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (33.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (34.48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.915\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDepression or anxiety\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (62.82%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (51.72%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.302\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperphagia and change in food preferences\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.473\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight loss (with possible malnutrition)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (6.41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (20.68%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.032\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNonfluent agrammatic variant of primary progressive aphasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (7.69%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (6.89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.896\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eprogressive apraxia of speech\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (15.38%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (6.89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.252\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (35.89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (34.48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.896\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImpulsivity, disinhibition, or perseveration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (28.20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (34.48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.533\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLimb myoclonus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (8.97%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (6.89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.737\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLimb dystonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (6.89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.123\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMRI features (n\u0026thinsp;=\u0026thinsp;83)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMorning glory sign\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (23.80%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (5.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHummingbird sign\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (31.74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (35.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003eNote\u003c/b\u003e: PSP \u0026ndash; P, RS, \u0026amp; PAGF: Progressive supranuclear palsy \u0026ndash; Parkinsonism, Richardson syndrome, and Pure akinesia with gait freezing, VGP: Vertical gaze palsy\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eMSA studies\u003c/h2\u003e \u003cp\u003eThe MDS criteria for diagnosing MSA serve as a valuable tool for clinicians to differentiate these patients from possible differential diagnoses (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). These criteria consist of motor, non-motor, and imaging features found to be more differentiative in the diagnosis of MSA (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), and it was utilized in our study to describe the clinical features of these patients.\u003c/p\u003e \u003cp\u003eNon-motor features are important constituents of the diagnosis and scaling of severity in patients with MSA (\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). In general, it is believed that non-motor features significantly increase in severity during the first two years of the disease course in these patients (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Moreover, orthostatic hypotension is considered as a common key component of MSA (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). The risk of fatigue (Odds ratio (OR)\u0026thinsp;=\u0026thinsp;2.806, 95% CI\u0026thinsp;=\u0026thinsp;1.253\u0026ndash;6.286 in a study by Zhang et al.(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e)) and cognitive decline (OR\u0026thinsp;=\u0026thinsp;0.328,95% CI\u0026thinsp;=\u0026thinsp;0.135\u0026ndash;0.797 in a study by W. Li et al. (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e)) is suggested to be associated with this phenomenon. Our study found that although the frequency of orthostatic hypotension in clinically established MSA patients is close to that in a recent multi-center cohort of Chinese patients (~\u0026thinsp;60.0%) (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), this was not compatible with other clinical groups in our study. Meanwhile, the mentioned Chinese study did not directly clarify the level of clinical establishment of the diagnosis (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) -i.e., clinically established, probable, or possible prodromal\u0026mdash;and if their subjects were clinically established patients, this is more compatible with the same group in our study.\u003c/p\u003e \u003cp\u003eA notable feature of patients with MSA that has gained attention in recent cohort studies is the presence of RBD. It was a prominent finding in our study, involving almost half of all clinical MSA subgroups. This phenomenon is, however, a common finding in many α-synucleinopathies such as Parkinson\u0026rsquo;s disease (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). In a recent single-center study in Korea, one-fifth of the patients with RBD were related to the MSA group, while more than half of them were diagnosed with Parkison\u0026rsquo;s disease (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe next component of MSA that has recently attracted attention in some cohort studies is cognitive decline. Although cognitive decline is not a key component of MSA patients, it has attracted increasing attention in recent studies (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). A cohort study conducted by Sambati et al. on Italian MSA patients reported that almost 60% of patients showed a cognitive decline at the baseline evaluation, and 10% of them had established dementia (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Our study on Persian patients revealed that almost one-third of individuals in each MSA clinical group had cognitive decline, which is a considerably lower rate compared to the Italian cohort. It is important to note that the diagnosis of MSA in the Italian cohort was based on the international consensus criteria and the absence of non-supporting features except dementia (based on the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria), and the cognitive evaluation was performed using a battery of cognitive evaluation tests comprehensively assessing different domains of cognitive function (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMoving to differences between MSA-P and MSA-C, a European cohort study highlighted the significant differences between MSA-C and MSA-P patients (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). The study found that aside from rigidity, bradykinesia, resting tremor, and gait freezing were notably more pronounced in MSA-P cases, and cerebellar signs were equally significant but more prominent in MSA-C cases, they did not identify any other clinical findings that were significantly more common in either subgroup (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). This is compatible with our findings, where there were no other significant differences in the clinical components of MDS criteria for MSA patients between MSA-C and MSA-P, except those related to parkinsonism and cerebellar signs.\u003c/p\u003e \u003cp\u003eIt is important to note that the patients discussed in this paper were evaluated during their first medical consultation, and the data presented pertains specifically to this initial evaluation. According to a study by Starhof et al., the rates of clinical components of MDS criteria for MSA patients can vary across different follow-up phases of the disease (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Although our patients had different durations of the symptoms at entry, it is possible that many of the variables observed in our study may experience a significantly increased rate of occurrence in the future.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePSP studies\u003c/h2\u003e \u003cp\u003eThe present paper assessed the MDS criteria (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) in Persian patients diagnosed with PSP. This is an important topic, filling a fraction of the gap in our knowledge regarding the characteristics of different ethnic groups with PSP across the world. An important finding of our paper is that despite an estimated higher prevalence of PSP-RS in most of the studies (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), PSP-P had a higher frequency of PSP subgroups in our study. Regarding this matter, in a recently published study on multi-ethnic PSP patients in Malaysia, it was shown that of 104 PSP patients who participated in the project, 48.1% were PSP-RS, 37.5% were PSP-P, and 10.6% of cases were diagnosed with PSP-PAGF (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). Ethnic and genetic variations may play a crucial role in this clinical diversity.\u003c/p\u003e \u003cp\u003eAs confirmed in recent studies on large PSP cohort patients, higher Magnetic Resonance Parkinsonism Index (MRPI; midsagittal area of the pons/midbrain ratio multiplied by the middle cerebellar peduncle width/superior cerebellar peduncle width ratio) plays a helpful role in early distinguishing of PSP patients compared to other atypical Parkinsonism disorders (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). This emphasizes the importance of imaging findings in these patients, however, as shown in our paper, the frequency of typical imaging findings in PSP patients is relatively low, and clinical manifestations described in the MDS criteria (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) still play a crucial role in the early differentiation of PSP from other atypical Parkinsonism disorders.\u003c/p\u003e \u003cp\u003eThe present paper provided a thorough clinical view of PSP patients, highlighting the distribution of MDS criteria features (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) in Persian PSP patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eAdditional insights into our findings\u003c/h2\u003e \u003cp\u003eDespite the criteria for diagnosis of MSA and PSP patients, emphasizing the ocular motor manifestations, non-motor features (e.g., RBD, orthostatic hypotension, urinary dysfunction), and imaging findings, in some instances there might be challenges in distinguishing MSA from PSP (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Generally, in clinical settings where specific complex laboratory analyses such as seed amplification assay and serum neurofilament examinations -introduced recently as potential ways of diagnosis (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e)- are not readily accessible, distinguishing between MSA and PSP can present significant challenges (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). This challenge is more sensible knowing that up to one-third of patients with MSA may represent non-motor symptoms prior to motor manifestations (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). These non-motor symptoms may include urinary problems and RBD (i.e., frequent symptoms in both MSA and PSP) in more than two-thirds of these cases, potentially challenging the diagnosis (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Expanding our knowledge of clinical presentations of MSA and PSP across different ethnic groups may help clinicians obtain a better insight when facing these patients. Our study found urinary problems and RBD are common symptoms in patients with PSP. In our study, the age at onset (with a cut-off of 70 years) of patients with parkinsonism as the initial motor manifestation showed a significant way of distinguishing MSA from PSP in Persian patients.\u003c/p\u003e \u003cp\u003eAn interesting study regarding the utility of clinical presentations in differentiating MSA from PSP is conducted by Wiblin et al. (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e), showing that even in signs and symptoms that are commonly presented in both disorders, the time of onset may play a helpful role in diagnosis. They showed that although both MSA and PSP patients remarkably show episodes of falling, it is important to note that episodes of falling start much earlier in the disease course of PSP patients (a median of 18.5 months before diagnosis, compared to the median of one month before diagnosis in MSA cases) (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). Their findings suggested that the time of onset of symptoms may play an important role in distinguishing these patients when facing clinical diagnostic challenges.\u003c/p\u003e \u003cp\u003eMRI findings, a component of MDS criteria for diagnosis of MSA and PSP (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), are a helpful way to surpass the challenges in the diagnosis of PSP and MSA (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). However, as shown in our paper, the MRI signs described in the diagnostic criteria are not prominent findings in these patients, and only up to one-third of these patients showed at least one of these signs. Although atrophy of pons is more prominent in MSA-C, in our study nearly the same fraction of MSA-C and MSA-P patients presented this sign (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). Studies also reported that MSA-P presents higher rates of putaminal atrophy compared to the MAS-C (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e), but the present paper revealed that there was little difference between the two MSA subtypes regarding this MRI finding. The frequency of other MRI findings of MSA in the present paper was compatible with the literature (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). Compared to our study, the rate of cerebellar atrophy (84.9%) and the hot cross bun sign (24.5%) were relatively higher in a cohort of another Asian country, India (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e). This was probably due to differences in the duration of the symptoms of onset at entry, which was approximately 4.34\u0026thinsp;\u0026plusmn;\u0026thinsp;3.04 years in the Indian cohort (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e) compared to 3.74\u0026thinsp;\u0026plusmn;\u0026thinsp;3.37 years in our study.\u003c/p\u003e \u003cp\u003eOur paper also studied the rate of the Hummingbird sign and Morning Glory sign in Persian PSP patients. These two signs are reported with different sensitivities and specificities across the literature (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). Studies revealed that the Hummingbird sign has 97%-100% specificity but a relatively lower sensitivity of 35%-57% for the diagnosis of PSP (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e). There could be different rates of presentation of the mentioned MRI signs in settings with different durations of disease onset of PSP (like our study). A study by Sj\u0026ouml;str\u0026ouml;m et al. recently suggested putaminal T1/T2-weighted MRI ratio has the potential to distinguish between PSP, MSA, Parkinson\u0026rsquo;s disease, and healthy control. (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). They showed this ratio at cerebellar white matter was significantly higher in PSP patients compared to MSA patients with area under the receiver operating characteristic curve of 0.62 (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe shortfall of information on the phenotypical description of MSA and PSP patients in Middle Eastern countries, Iran in particular, was another key factor in conducting the present research paper. Research on the demographic and clinical characteristics of MSA and PSP remains scarce in West Asia and the Middle East compared to other Asian countries like India, where more studies have provided data on the disease presentation (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e). In general, Indian PSP patients present more with the PSP-RS subtype, and the mean age at onset of the Indian patients is around 64 years (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e), which is slightly lower compared to our Persian cross-sectional study with a mean age at onset of 67 years. Regarding the MSA patients in Indian studies, MSA-P showed a slightly higher fraction of the total Indian MSA patients in a cohort (29 MSA-P, vs 25 MSA-C) (\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e). In our Persian cross-sectional study, MSA-P comprised a remarkably higher fraction of MSA patients (64 MSA-P, vs 25 MSA-C). In addition, the differences between MRI findings in Indian and Persian MSA patients were discussed earlier. Further investigations in similar ethnic groups may provide valuable insights into the clinical presentations of MSA and PSP patients in this region.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eCONFLICT OF INTEREST\u003c/p\u003e\n\u003cp\u003eThere were no conflicts of interest or funding sources for this article.\u003c/p\u003e\n\u003cp\u003eACKNOWLEDGEMENT\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003eDATA AVAILABILITY STATEMENT\u003c/p\u003e\n\u003cp\u003eThe data used in this study will be available upon request.\u003c/p\u003e\n\u003cp\u003eAUTHOR ROLES\u003c/p\u003e\n\u003cp\u003e(1) Research Project: A. Conception, B. Organization, C. Execution, D. Validation, E. Data analysis, F. Visualization, G. Data Acquisition; (2) Manuscript: A. Writing of the First Draft, B. Review and Critique.\u003c/p\u003e\n\u003cp\u003eM.S.: 1A, 1B, 1C, 1D, 2B\u003c/p\u003e\n\u003cp\u003eK.R.: 1C, 1E, 1G, 1F, 2A, 2B\u003c/p\u003e\n\u003cp\u003eM.Q.: 1C, 1G, 2A\u003c/p\u003e\n\u003cp\u003eS.S.: 1C, 1G\u003c/p\u003e\n\u003cp\u003eF.H.: 1C, 1G\u003c/p\u003e\n\u003cp\u003eM.G.: 1G\u003c/p\u003e\n\u003cp\u003eM.E.: 1C, 1D, 2B\u003c/p\u003e\n\u003cp\u003eFUNDING SOURCES AND CONFLICT OF INTEREST\u003c/p\u003e\n\u003cp\u003eNo specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work.\u003c/p\u003e\n\u003cp\u003eFINANCIAL DISCLOSURES FOR THE PREVIOUS 12 MONTHS\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no additional disclosures to report.\u003c/p\u003e\n\u003cp\u003eSTATEMENT REGARDING ETHICAL CONDUCT AND INFORMED CONSENT\u003c/p\u003e\n\u003cp\u003eWe hereby confirm that the present study conforms to the ethical standards and guidelines of the journal. Patient consent was obtained for this research.\u003c/p\u003e\n\u003cp\u003eETHICAL COMPLIANCE STATEMENT\u003c/p\u003e\n\u003cp\u003eWe confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. The present paper is also approved by the ethics committee of Shahid Beheshti University of Medical Sciences.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLee S, Kim H, Kim R, Jin B, Kim S, Woo KA et al (2025) Application of elastic net for clinical outcome prediction and classification in progressive supranuclear palsy: A multicenter cohort study. Parkinsonism Relat Disord 132:107301\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLieto M, Roca A, Bruzzese D, Antenora A, Alfieri G, Sacc\u0026agrave; F et al (2019) Longitudinal study of a cohort of MSA-C patients in South Italy: survival and clinical features. Neurol Sci 40(10):2105\u0026ndash;2109\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHirschbichler ST, Erro R, Ganos C, Stamelou M, Batla A, Balint B, Bhatia KP (2017) Atypical atypical parkinsonism: Critical appraisal of a cohort. 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Ann Indian Acad Neurol 28(1):17\u0026ndash;25\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSeniaray N, Verma R, Ranjan R, Belho E, Mahajan H (2021) Comprehensive Functional Evaluation of the Spectrum of Multi-System Atrophy with 18F-FDG PET/CT and 99mTc TRODAT-1 SPECT: 5 Year's Experience from a Tertiary Care Center. Ann Indian Acad Neurol 24(4):490\u0026ndash;494\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Multiple System Atrophy, Progressive Supranuclear Palsy, Parkinsonism, Persian","lastPublishedDoi":"10.21203/rs.3.rs-6526460/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6526460/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eProgressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are neurodegenerative disorders with distinct demographic and clinical profiles. In Middle Eastern countries, limited data exist on their demographic features and clinical manifestations.\u003c/p\u003e\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eThis study describes MSA and PSP patients in a Persian cross-sectional study.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis cross-sectional study was retrospectively conducted using medical records of patients diagnosed with MSA or PSP between January 2019 and January 2025, based on the MDS diagnostic criteria components at the initial diagnosis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 106 MSA and 108 PSP patients were included. MSA-C (23.58%), MSA-P (60.37%), and unclassified (16.03%) were the subgroups of MSA in this project. PSP subtypes were PSP-P (72.22%), PSP-RS (26.85%), and PSP-PAGF (0.92%). The PSP group had a significantly higher age of participants in this study (71.82\u0026thinsp;\u0026plusmn;\u0026thinsp;7.46 vs 68.85\u0026thinsp;\u0026plusmn;\u0026thinsp;8.66). The male/female fraction was significantly higher in patients with PSP compared to the MSA group (70.37%/29.62% vs 45.28%/54.71%, \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Following a comparison of common symptoms, the onset of disease before age 70 years when Parkinsonism is the symptom of onset was significantly more frequent in MSA, whereas onset after 70 years was more frequent in PSP (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Urinary problems were more significant in the MSA group (70.0%) compared to the PSP cases (52.9%, \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eDescribing demographic and clinical presentations of MSA and PSP patients in a Middle Eastern population would enhance our understanding of the characteristics of these disorders in this region.\u003c/p\u003e","manuscriptTitle":"Multiple System Atrophy and Progressive Supranuclear Palsy in Persian Population: A Retrospective Cross-sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-09 10:46:41","doi":"10.21203/rs.3.rs-6526460/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"891fe3f2-ee0b-4d4b-9772-4ecebfb56939","owner":[],"postedDate":"May 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-19T07:53:37+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-09 10:46:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6526460","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6526460","identity":"rs-6526460","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}