Multiple System Atrophy Of Cerebellar Type Research Articles

Retraction: Very late-onset Friedreich’s ataxia with rapid course mimicking as possible multiple system atrophy cerebellar type

Retraction: Very late-onset Friedreich’s ataxia with rapid course mimicking as possible multiple system atrophy cerebellar type

Scale for Ocular Motor Disorders in Ataxia (SODA) in Patients with Multiple System Atrophy.

A clinical scale fully dedicated to evaluating ocular motor abnormalities is required for now. We investigated the utility of a recently developed Scale for Ocular motor Disorders in Ataxia (SODA) in patients with multiple system atrophy (MSA). We prospectively assessed SODA in consecutive patients with MSA between August 2021 and August 2023 at the Korea University Medical Center. The results of the clinical exam-based SODA were compared with those measured using video-oculography (VOG-guided SODA). We also compared the findings with other established clinical scales targeting patients with MSA, including the Unified Multiple System Atrophy Rating Scale (UMSARS) I-II, Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor part (UPDRS-III), Scale for Assessment of Rating of Ataxia (SARA), Composite Autonomic Symptom Score-31 (COMPASS-31), and Composite Autonomic Severity Score (CASS). Twenty patients were enrolled in our study (17 with cerebellar-type MSA and three with Parkinson-type MSA). Scores ranged from 1 to 14 (median [interquartile range (IQR)] = 8 [5-10]). Among the subscales, saccades had a median score of 2.5 (IQR = 1-3), followed by ocular pursuit (1 [0-1]), nystagmus (1 [0-2]), saccadic intrusions (1 [0-1]), vestibulo-ocular reflex (VOR) (0.5 [0-1]), ocular alignment (0 [0-1]), and VOR cancellation (1 [0-1]). The clinical-exam-based SODA (p = 0.020) and VOG-guided SODA (p = 0.034) positively correlated with disease duration. No correlation was found between clinical exam-based SODA and other scales. Skew deviation, gaze-evoked nystagmus, VOR cancellation, and smooth pursuit had the highest precision among the items. Ocular misalignment and spontaneous and positional nystagmus were frequently false positive and were poorly detected with clinical exam-based SODA. Six patients with repeated evaluation exhibited higher scores, along with deterioration documented on other clinical scales. The SODA can reliably predict neurodegeneration as an additional clinical surrogate in MSA.

Evoked potential response in patients with idiopathic Parkinson’s disease and atypical parkinsonian syndromes: A comparative study

Patients with idiopathic Parkinson’s disease (IPD) and atypical parkinsonian syndromes (APSs) suffer from a range of disorders, especially in balance and locomotion, which necessitate visual, auditory, and somatosensory inputs. In this study, IPD patients, APS patients, and healthy controls (HCs) (n = 50 per group) underwent a series of assessments for visual evoked potentials (VEP), brainstem auditory evoked response (BAER), and short-latency somatosensory evoked potentials (SSEP). Results showed that VEP P100 latency was prolonged in multiple system atrophy-cerebellar type (MSA-C), multiple system atrophy-parkinsonian type (MSA-P), and corticobasal ganglionic degeneration (CBD) patients. The latency of peaks III and V was prolonged in IPD, MSA-C, dementia with Lewy bodies (DLB), and Parkinson’s disease dementia (PDD). BAER I-III and I-V interpeak latency were prolonged in IPD, DLB, and PDD, whereas BAER I-III, III-V, and I-V interpeak latencies were increased and the V/I amplitude ratio was decreased in MSA-C. The central sensory conduction time (N20-N13) was increased in MSA-P and MSA-C in SSEP. IPD patients had prolonged VEP P100 latency (P < 0.001), lower VEP N75-P100 amplitude (P < 0.001), prolonged BAER I, II, II, IV, V peak latencies (P < 0.001), I-III, I-V interpeak latencies (P < 0.001), lower BAER V/I amplitude ratio (P < 0.001), and prolonged SSEP N13, N20, central sensory conduction time (N20-N13) (P < 0.001) than HCs. IPD patients also had prolonged BAER I, II, II, IV, V peak latencies (P < 0.001), prolonged I-III, I-V interpeak latencies (P < 0.001), and shorter SSEP N13, N20, central sensory conduction time (N20-N13) (P < 0.001) than APS patients. Moreover, APS patients had prolonged VEP P100 and N145 latencies (P < 0.001) and decreased N75-N145 amplitude (P < 0.001) compared to HCs. APS patients also had prolonged BAER II, II, IV, V peak latencies (P < 0.001), prolonged I-III, III-V, I-V interpeak latencies (P < 0.001), decreased V/I amplitude ratio, and prolonged SSEP N13, N20, central sensory conduction time (N20-N13) (P < 0.001) than HCs. Postural instability and gait disorder (PIGD) IPD had significantly prolonged BAER III, V peak latencies (P < 0.05), and prolonged III-V interpeak latencies (P < 0.05) compared to tremor-dominant IPD. Overall, the IPD and APS patients had significant VEP, BAER, and SSEP abnormalities of demyelination and axonal variety in the visual, auditory, and somatosensory pathways. The changes were also correlated with the disease duration and severity. Although the diseases are predominantly motor disorders with significant non-motor components, these electrophysiological abnormalities might open a new avenue to assess the non-motor symptoms.

Cranial Nerve Thinning Distinguishes RFC1-Related Disorder from Other Late-Onset Ataxias.

RFC1-related disorder (RFC1/CANVAS) shares clinical features with other late-onset ataxias, such as spinocerebellar ataxias (SCA) and multiple system atrophy cerebellar type (MSA-C). Thinning of cranial nerves V (CNV) and VIII (CNVIII) has been reported in magnetic resonance imaging (MRI) scans of RFC1/CANVAS, but its specificity remains unclear. To assess the usefulness of CNV and CNVIII thinning to differentiate RFC1/CANVAS from SCA and MSA-C. Seventeen individuals with RFC1/CANVAS, 57 with SCA (types 2, 3 and 6), 11 with MSA-C and 15 healthy controls were enrolled. The Balanced Fast Field Echo sequence was used for assessment of cranial nerves. Images were reviewed by a neuroradiologist, who classified these nerves as atrophic or normal, and subsequently the CNV was segmented manually by an experienced neurologist. Both assessments were blinded to patient and clinical data. Non-parametric tests were used to assess between-group comparisons. Atrophy of CNV and CNVIII, both alone and in combination, was significantly more frequent in the RFC1/CANVAS group than in healthy controls and all other ataxia groups. Atrophy of CNV had the highest sensitivity (82%) and combined CNV and CNVIII atrophy had the best specificity (92%) for diagnosing RFC1/CANVAS. In the quantitative analyses, CNV was significantly thinner in the RFC1/CANVAS group relative to all other groups. The cutoff CNV diameter that best identified RFC1/CANVAS was ≤2.2 mm (AUC = 0.91; sensitivity 88.2%, specificity 95.6%). MRI evaluation of CNV and CNVIII using a dedicated sequence is an easy-to-use tool that helps to distinguish RFC1/CANVAS from SCA and MSA-C.

The clinical application value of brain 18F-FDG PET/CT in the diagnostics of Parkinsonian syndromes

Objective: To analyze the PET/CT imaging features of fluoride 18F-fluorodeoxyglucose (18F-FDG) in patients with various types of Parkinson's syndrome (PS), and to establish a "diagnostic tree" model of 18F-FDG PET/CT for PS. Methods: Data of patients with Parkinson's disease (PD), patients with multiple system atrophy cerebellar type (MSA-C), and patients with multiple system atrophy Parkinson's type (MSA-P)admitted to the Neurology Department of Huashan Hospital affiliated to Fudan University from January 2019 to December 2021. 18F-FDG PET/CT examination was conducted in all patients. Clinical and follow-up data was collected to determine clinical diagnosis. The specific patterns of brain glucose metabolism in patients with various types of Parkinsonism were observed and their utility in the differential diagnosis of the disease was analyzed. 18F-FDG PET/CT imaging"diagnostic tree"model was established and its value in the differential diagnosis of Parkinsonism was verified. Results: A total of 320 patients, 187 males and 133 females, aged (62±9) years, were enrolled in our study, including 80 PD, 90 PSP, 114 MSA-C and 36 MSA-P patients. The differential diagnostic features of cerebral glucose metabolism of Parkinsonism were as follows: the metabolism of putamen increased in PD patients, the metabolism of caudate nucleus, thalamus, midbrain, and frontal lobe decreased in PSP patients, the metabolism of cerebellum decreased in MSA-C patients, and the metabolism of putamen and cerebellum decreased in MSA-P patients. The sensitivity and specificity of the"diagnostic tree"model are 88.75% and 91.25% for PD diagnosis, 54.44% and 96.96% for PSP diagnosis, 87.72% and 86.41% for MSA-C diagnosis, and 55.56% and 91.55% for MSA-P diagnosis, respectively. It could correctly classify 75%(240/320) of patients. Conclusions: Characteristic metabolism patterns of brain in 18F-FDG PET/CT imaging is significant for the differential diagnosis of PD, PSP, MSA-C and MSA-P. The"diagnostic tree"model is valuable for clinical diagnosis.

A diagnostic clue in cerebellar-type multiple system atrophy: the hot cross bun sign.

A diagnostic clue in cerebellar-type multiple system atrophy: the hot cross bun sign.

Effects of cerebellar transcranial alternating current stimulation in cerebellar ataxia: study protocol for a randomised controlled trial.

Cerebellar ataxia (CA) is a movement disorder that can affect balance and gait, limb movement, oculomotor control, and cognition. Multiple system atrophy-cerebellar type (MSA-C) and spinocerebellar ataxia type 3 (SCA3) are the most common forms of CA, for which no effective treatment is currently available. Transcranial alternating current stimulation (tACS) is a non-invasive method of brain stimulation supposed to alter cortical excitability and brain electrical activity, modulating functional connectivity within the brain. The cerebellar tACS can modulate the cerebellar outflow and cerebellum-linked behavior and it is a proven safe technique for humans. Therefore, the aim of this study is to 1) examine whether cerebellar tACS improves ataxia severity and various non-motor symptoms in a homogeneous cohort of CA patients consisting of MSA-C and SCA3, 2) explore the time course of these effects, and 3) assess the safety and tolerance of cerebellar tACS in all participants. This is a 2-week, triple-blind, randomised, sham-controlled study. 164 patients (MSA-C: 84, SCA3: 80) will be recruited and randomly assigned to either active cerebellar tACS or sham cerebellar tACS, in a 1:1 ratio. Patients, investigators, and outcome assessors are unaware of treatment allocation. Cerebellar tACS (40 min, 2 mA, ramp-up and down periods of 10s each) will be delivered over 10 sessions, distributed in two groups of five consecutive days with a two-day break in between. Outcomes are assessed after the tenth stimulation (T1), and after 1 month (T2) and 3 months (T3). The primary outcome measure is the difference between the active and sham groups in the proportion of patients with an improvement of 1.5 points in the Scale for the Assessment and Rating of Ataxia (SARA) score after 2 weeks of treatment. In addition, effects on a variety of non-motor symptoms, quality of life, and autonomic nerve dysfunctions are assessed via relative scales. Gait imbalance, dysarthria, and finger dexterity are objectively valued via relative tools. Finally, functional magnetic resonance imaging is performed to explore the possible mechanism of treatment effects. The results of this study will inform whether repeated sessions of active cerebellar tACS benefit CA patients and whether this form of non-invasive stimulation might be a novel therapeutic approach to consider in a neuro-rehabilitation setting.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05557786; https://www.clinicaltrials.gov/ct2/show/NCT05557786.

Phosphorylated α-synuclein in skin Schwann cells: a new biomarker for multiple system atrophy.

Multiple system atrophy (MSA) is characterized by accumulation of phosphorylated α-synuclein (p-syn) as glial cytoplasmic inclusions in the brain and a specific biomarker for this disorder is urgently needed. We aimed at investigating if p-syn can also be detected in skin Remak non-myelinating Schwann cells (RSCs) as Schwann cell cytoplasmic inclusions (SCCi) and may represent a reliable clinical biomarker for MSA. This cross-sectional diagnostic study evaluated skin p-syn in 96 patients: 46 with probable MSA (29 with parkinsonism type MSA and 17 with cerebellar type MSA), 34 with Parkinson's disease (PD) and 16 with dementia with Lewy bodies (DLB). We also included 50 healthy control subjects. Patients were recruited from five different medical centres. P-syn aggregates in skin sections were stained by immunofluorescence, followed by analyses with confocal microscopy and immuno-electron microscopy. All analyses were performed in a blinded fashion. Overall, p-syn aggregates were found in 78% of MSA patients and 100% of patients with PD/DLB, whereas they could not be detected in controls. As for neuronal aggregates 78% of MSA patients were positive for p-syn in somatic neurons, whereas all PD/DLB patients were positive in autonomic neurons. When analysing the presence of p-syn in RSCs, 74% of MSA patients were positive, whereas no such SCCi could be observed in PD/DLB patients. Analyses by immuno-electron microscopy confirmed that SCCi were only found in cases with MSA and thus absent in those with PD/DLB. In conclusion, our findings demonstrate that (i) fibrillar p-syn in RSCs is a pathological hallmark of MSA and may be used as a specific and sensitive disease biomarker; (ii) in Lewy body synucleinopathies (PD/DLB) only neurons contain p-syn deposits; and (iii) the cell-specific deposition of p-syn in the skin thus mirrors that of the brain in many aspects and suggests that non-myelinated glial cells are also involved in the MSA pathogenesis.

An atypical course of a 71-year old man with right arm weakness and ataxia: Expert commentary

Dr Khemani and colleagues have presented a diagnostically challenging case of a sporadic, adult onset ataxia (SAOA) syndrome resembling Multiple System Atrophy cerebellar type (MSA-C), with an atypical presentation of focal amyotrophy, eventually diagnosed as spinocerebellar ataxia type 3 (SCA3) [ [1] Khemani P. Elliott M. Levine T. An Atypical Clinical Course of a 71-Year-Old Man with Right Arm Weakness and Ataxia. Parkinsonism Relat Disord, 2022 Abstract Full Text Full Text PDF Scopus (0) Google Scholar ]. The patient had presented elsewhere three years prior, with a Miller Fisher syndrome (MFS) associated with an elevated antiGQ1b antibody titer. However, as the patient had become wheelchair bound over the subsequent three years, the initial diagnosis of MFS is perhaps questionable. When evaluating ataxic disorders, it is important to establish the disease onset and course accurately. As the patient had a progressive cerebellar syndrome, the possible causes could be categorized broadly as: primary autoimmune (paraneoplastic or non-paraneoplastic); or neurodegenerative (sporadic or genetic). Primary autoimmune cerebellar ataxia encompassing paraneoplastic ataxia syndromes, and immune-mediated ataxias (gluten ataxia and anti-GAD65 ataxia) may present insidiously, with accumulating disability especially if timely and appropriate immunosuppressive therapies are not instituted [ [2] Hadjivassiliou M. Graus F. Honnorat J. Jarius S. Titulaer M. Manto M. Hoggard N. Sarrigiannis P. Mitoma H. Diagnostic criteria for primary autoimmune cerebellar ataxia-guidelines from an international task force on immune-mediated cerebellar ataxias. Cerebellum. 2020; 19: 605-610 Crossref PubMed Scopus (35) Google Scholar ].

Monocytohigh-density lipoprotein ratio has a high predictive value for the diagnosis of multiple system atrophy and the differentiation from Parkinson's disease.

Background and purposeInflammation is closely related to the pathogenesis of multiple system atrophy (MSA). As markers of inflammation, the monocyte to high-density lipoprotein ratio (MHR), neutrophil to lymphocyte ratio (NLR), and red cell distribution width to platelet ratio (RPR) have been proven to be associated with a large variety of diseases. The aim of this study was to explore the association between inflammatory markers (MHR, NLR, and RPR) and MSA, and the difference between MSA and Parkinson’s disease (PD) was further compared by these inflammatory markers.Materials and methodsThis study was divided into three groups: 47 patients with MSA, 125 patients with PD, and 124 healthy controls. The corresponding laboratory indicators of subjects were collected and analyzed to obtain MHR, NLR, and RPR values.ResultsCompared with healthy controls, the MHR, NLR, and RPR were higher in the MSA group (P < 0.05), and the MHR was higher in the MSA group than in the PD group (P < 0.001). Multivariate logistic regression analysis showed that MHR*10 (corrected OR = 1.312, 95% CI 1.093–1.575) and RPR*100 (corrected OR = 1.262, 95% CI 1.055–1.509) were positively correlated with the risk of MSA. The receiver operating characteristic (ROC) curve indicated that the areas under the curve (AUCs) of the MHR, NLR, and RPR for predicting MSA were 0.651 (95% CI 0.562–0.74; P < 0.05), 0.6 (95% CI 0.501–0.699; P < 0.05), and 0.612 (95% CI 0.516–0.708; P < 0.05), respectively. The AUC of MSA and PD predicted by the MHR was 0.727 (P < 0.001). When the cut-off value was 0.38, the sensitivity and specificity were 60 and 77%, respectively. Spearman correlation analysis showed that the MHR was significantly and positively correlated with the course of MSA cerebellar type (MSA-C) patients.ConclusionThere may be peripheral inflammation in patients with MSA. Compared with NLR and RPR, MHR has higher predictive value for the diagnosis and differential diagnosis of MSA.

Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study.

Despite recent progress in the field of genetics, sporadic late-onset (> 40years) cerebellar ataxia (SLOCA) etiology remains frequently elusive, while the optimal diagnostic workup still needs to be determined. We aimed to comprehensively describe the causes of SLOCA and to discuss the relevance of the investigations. We included 205 consecutive patients with SLOCA seen in our referral center. Patients were prospectively investigated using exhaustive clinical assessment, biochemical, genetic, electrophysiological, and imaging explorations. We established a diagnosis in 135 (66%) patients and reported 26 different causes for SLOCA, the most frequent being multiple system atrophy cerebellar type (MSA-C) (41%). Fifty-one patients (25%) had various causes of SLOCA including immune-mediated diseases such as multiple sclerosis or anti-GAD antibody-mediated ataxia; and other causes, such as alcoholic cerebellar degeneration, superficial siderosis, or Creutzfeldt-Jakob disease. We also identified 11 genetic causes in 20 patients, including SPG7 (n = 4), RFC1-associated CANVAS (n = 3), SLC20A2 (n = 3), very-late-onset Friedreich's ataxia (n = 2), FXTAS (n = 2), SCA3 (n = 1), SCA17 (n = 1), DRPLA (n = 1), MYORG (n = 1), MELAS (n = 1), and a mitochondriopathy (n = 1) that were less severe than MSA-C (p < 0.001). Remaining patients (34%) had idiopathic late-onset cerebellar ataxia which was less severe than MSA-C (p < 0.01). Our prospective study provides an exhaustive picture of the etiology of SLOCA and clues regarding yield of investigations and diagnostic workup. Based on our observations, we established a diagnostic algorithm for SLOCA.

Spinocerebellar ataxia type 8 in Russian patients

To assess the incidence of spinocerebellar ataxia type 8 (SCA8) in patients with progressive cerebellar ataxia and describe the clinical features of the SCA8 phenotype in Russian patients. Genotyping of CTA/CTG repeats in ATXN8OS gene was carried out in 411 patients with degenerative ataxias using fragment analysis. SCA types 1, 2, 3 and 6 as well as Friedreich's ataxia were preliminarily excluded. All patients underwent brain MRI study. Scale for the Assessment and Rating of Ataxia (SARA), and the Montreal Cognitive Assessment Scale (MoCA) to screen for cognitive impairment were used. Six patients with SCA8 (1.5%) were identified as carriers of the expansion in the ATXN8OS gene (91-152 CTA/CTG repeats). All cases were sporadic. Age of onset ranged from 14 to 42 years. All patients had slowly progressive cerebellar ataxia, oculomotor disturbances, dysarthria, pyramidal signs, and two patients had cognitive impairment. In one patient the clinical presentation corresponded to multiple system atrophy cerebellar type (ataxia, orthostatic hypotension, cerebellum and brainstem atrophy). Brain MRI study in all patients revealed cerebellar atrophy. SCA8 is a rare form of autosomal dominant ataxia with a predominance of the classical phenotype. All identified cases of SCA8 were sporadic, which should be taken into account when planning genetic testing in patients with spinocerebellar ataxia.

Head-impulse tests aid in differentiation of multiple system atrophy from Parkinson's disease.

The integrity of the vestibulo-ocular reflex (VOR) remains to be delineated in patients with parkinsonism. We aimed to define the findings of the VOR using head-impulse tests (HITs) and their differential diagnostic value in patients with Parkinson's disease (PD) and multiple system atrophy (MSA). From December 2019 to January 2021, 30 patients with PD and 23 patients with MSA (17 with cerebellar-type MSA and 6 with parkinsonian-type MSA) had a video-oculographic recording of HITs at two university hospitals in South Korea. Reversed (p = 0.034) and perverted (p = 0.015) catch-up saccades were more frequently observed in MSA than in PD during HITs. The gain difference between the ACs and the PCs were larger in MSA than in PD (p = 0.031), and positively correlated with the disease duration in patients with MSA (Spearman's coefficient = 0.512, p = 0.012). Multivariate logistic regression analysis showed that reversed (p = 0.044) and perverted (p = 0.039) catch-up saccades were more frequently associated with MSA than with PD during HITs. In conclusion, HITs aid in differentiation of MSA from PD, and may serve as a surrogate marker for the clinical decline.

Quantitative Evaluation of Cerebellar Function in Multiple System Atrophy with Transcranial Magnetic Stimulation.

Objective evaluation of cerebellar dysfunction in neurodegenerative disorders is often difficult because of other overlapping symptoms. Cerebellar inhibition (CBI) tested by dual-coil transcranial magnetic stimulation (TMS) is anticipated as a promising measure to estimate cerebellar function. Cerebellar TMS inhibits the primary motor cortex (M1), which can be measured as the decrease of motor evoked potential (MEP) elicited by a single-pulse TMS over the M1. This study was conducted to quantify cerebellar dysfunction using CBI in cerebellar type multiple system atrophy (MSA-C) patients. First, CBI was measured using MEP elicited from a hand muscle by stimulating the hand motor area of M1. The amount of CBI was defined as the degree of decrease in the MEP amplitude in the presence of cerebellar stimulation compared with the condition of M1 stimulation alone. Results of the MSA-C patients were compared with those of healthy volunteers. Correlation between amounts of CBI and a clinical scale of ataxia, the International Cooperative Ataxia Scale Rating (ICARS), was assessed. Healthy volunteers showed more inhibition than MSA-C patients. Moreover, ICARS showed that the CBI amount in the patients is correlated with the degree of ataxia significantly. Results suggest that CBI can be a good marker of disease progression in MSA-C patients.

The stimulator of interferon genes (STING) pathway is upregulated in striatal astrocytes of patients with multiple system atrophy

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by the accumulation of pathogenic phosphorylated α-synuclein in oligodendrocytes. In brains affected by MSA, severe astrogliosis is also observed, but its precise role in MSA pathogenesis remains largely unknown. Recently, the stimulator of interferon genes (STING) pathway and type I interferons, its downstream molecules, have been reported to be involved in the neurodegenerative process and to be activated in astrocytes. This study aimed to investigate the role of the STING pathway in the pathogenesis of MSA using postmortem brains. Samples used for immunohistochemical analysis included 6 cases of MSA parkinsonism type (MSA-P), 6 cases of MSA cerebellar type (MSA-C), and 7 age-matched controls. In MSA-P cases, astrocytes immunopositive for STING and TANK-binding kinase 1 (TBK1), its downstream molecule, were abundantly observed in the putamen and the substantia nigra. Moreover, these molecules colocalized with glial fibrillary acidic protein (GFAP) in reactive astrocytes, and the density of STING-positive astrocytes correlated with that of GFAP-positive reactive astrocytes in the brains of patients with MSA-P. These results suggest that the upregulated expression of STING pathway-related proteins in astrocytes and the subsequent inflammation may contribute to the pathogenesis in MSA-P and could provide novel therapeutic targets for the treatment of MSA.

Potential Fluid Biomarkers and a Prediction Model for Better Recognition Between Multiple System Atrophy-Cerebellar Type and Spinocerebellar Ataxia.

ObjectiveThis study screened potential fluid biomarkers and developed a prediction model based on the easily obtained information at initial inspection to identify ataxia patients more likely to have multiple system atrophy-cerebellar type (MSA-C).MethodsWe established a retrospective cohort with 125 ataxia patients from southwest China between April 2018 and June 2020. Demographic and laboratory variables obtained at the time of hospital admission were screened using Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression to construct a diagnosis score. The receiver operating characteristic (ROC) and decision curve analyses were performed to assess the accuracy and net benefit of the model. Also, independent validation using 25 additional ataxia patients was carried out to verify the model efficiency. Then the model was translated into a visual and operable web application using the R studio and Shiny package.ResultsFrom 47 indicators, five variables were selected and integrated into the prediction model, including the age of onset (AO), direct bilirubin (DBIL), aspartate aminotransferase (AST), eGFR, and synuclein-alpha. The prediction model exhibited an area under the curve (AUC) of 0.929 for the training cohort and an AUC of 0.917 for the testing cohort. The decision curve analysis (DCA) plot displayed a good net benefit for this model, and external validation confirmed its reliability. The model also was translated into a web application that is freely available to the public.ConclusionThe prediction model that was developed based on laboratory and demographic variables obtained from ataxia patients at admission to the hospital might help improve the ability to differentiate MSA-C from spinocerebellar ataxia clinically.

Swallowing Outcomes Following Voice Therapy in Multiple System Atrophy with Dysphagia: Comparison of Treatment Efficacy with Parkinson\u2019s Disease

Difficulties with speech and swallowing occur in patients with Parkinsonism. Lee Silverman Voice Treatment (LSVT) is proven as an effective treatment for speech and swallowing function in idiopathic Parkinson’s disease (IPD). The effect of LSVT on swallowing function in multiple system atrophy-cerebellar type (MSA-C) is unknown. We sought to determine LSVT’s effect on swallowing function in MSA-C patients compared to IPD patients. LSVT-LOUD was performed on 13 patients with Parkinsonism (6 IPD and 7 MSA-C). Maximum phonation time (MPT), voice intensity, Speech Handicap Index-15 (SHI-15), Swallowing-Quality of Life (SWAL-QOL), National Institutes of Health-swallowing safety scale (NIH-SSS), and videofluoroscopic dysphagia scale (VDS) before and after LSVT were analyzed and reevaluated three months after treatment. The IPD and MSA-C groups showed significant improvements in overall speech and swallowing measures after LSVT. In particular, pharyngeal phase score and total score of VDS improved significantly in both groups. A two-way repeated-measure ANOVA revealed a significant main effect for time in the MPT, voice intensity, NIH-SSS, pharyngeal phase score and total score of VDS, psychosocial subdomain of SHI-15, and SWAL-QOL. The MSA-C group experienced less overall improvement in swallowing function, but the two groups had an analogous pattern of improvement. In conclusion, LSVT is effective for enhancing swallowing function, particularly in the pharyngeal phase, in both IPD and MSA-C patients. This study demonstrated that LSVT elicits significant improvements in MSA-C patients. We deemed LSVT to be an effective treatment for IPD and MSA-C patients who suffer from dysphagia.

Short-Term Effect of Intensive Speech Therapy on Dysarthria in Patients With Sporadic Spinocerebellar Degeneration.

Purpose The aim of this study was to investigate a structured approach for effective speech therapy (ST) for dysarthria and speech-related quality of life in patients with sporadic spinocerebellar degeneration (SCD), including cerebellar-type multiple-system atrophy and cerebellar cortical atrophy. Method Twenty-two patients with SCD (cerebellar-type multiple system atrophy, 15 patients; cerebellar cortical atrophy, seven patients) who underwent intensive ST were examined. Dysarthria was evaluated using the Scale for Assessment and Rating of Ataxia Speech Dysfunction, Assessment of Motor Speech for Dysarthria Articulation, oral diadochokinesis (OD), and Voice Handicap Index-10 (VHI-10). Respiratory muscle strength (inspiratory and expiratory pressure) and respiratory-phonatory coordination (maximum phonation time) were measured. Cognitive function was evaluated using the Montréal Cognitive Assessment and the word fluency test. Mood was evaluated using the Hospital Anxiety and Depression Scale. The relationships between dysarthria scales (particularly, VHI-10) and clinical data were analyzed using stepwise regression. The differences in outcomes after intensive ST were analyzed using the Wilcoxon signed-rank test. The alpha level (p) for statistical significance was set at .0125 by Bonferroni correction. Results For both pre- and post-ST, the patient's OD (p = .002) and maximum phonation time (p = .002) significantly improved, except for Speech Dysfunction scores of the Scale for Assessment and Rating of Ataxia (p = .705) and the VHI-10 (p = .018). The Assessment of Motor Speech for Dysarthria Articulation, OD, and inspiratory pressure were identified as independent variables of VHI-10 (adjusted R 2 = .820) for speech-related quality of life; no correlations among the Montréal Cognitive Assessment, word fluency test, and Hospital Anxiety and Depression Scale scores were observed. Conclusion OD and VHI-10 showed improvements due to changes in speech function and respiratory-phonatory coordination, justifying intensive ST treatment for dysarthria in patients with SCD.

Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 Disease.

ObjectiveTo delineate the full phenotypic spectrum, discriminative features, piloting longitudinal progression data, and sample size calculations of replication factor complex subunit 1 (RFC1) repeat expansions, recently identified as causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS).MethodsMultimodal RFC1 repeat screening (PCR, Southern blot, whole-exome/genome sequencing–based approaches) combined with cross-sectional and longitudinal deep phenotyping in (1) cross-European cohort A (70 families) with ≥2 features of CANVAS or ataxia with chronic cough (ACC) and (2) Turkish cohort B (105 families) with unselected late-onset ataxia.ResultsPrevalence of RFC1 disease was 67% in cohort A, 14% in unselected cohort B, 68% in clinical CANVAS, and 100% in ACC. RFC1 disease was also identified in Western and Eastern Asian individuals and even by whole-exome sequencing. Visual compensation, sensory symptoms, and cough were strong positive discriminative predictors (>90%) against RFC1-negative patients. The phenotype across 70 RFC1-positive patients was mostly multisystemic (69%), including dysautonomia (62%) and bradykinesia (28%) (overlap with cerebellar-type multiple system atrophy [MSA-C]), postural instability (49%), slow vertical saccades (17%), and chorea or dystonia (11%). Ataxia progression was ≈1.3 Scale for the Assessment and Rating of Ataxia points per year (32 cross-sectional, 17 longitudinal assessments, follow-up ≤9 years [mean 3.1 years]) but also included early falls, variable nonlinear phases of MSA-C–like progression (SARA points 2.5–5.5 per year), and premature death. Treatment trials require 330 (1-year trial) and 132 (2-year trial) patients in total to detect 50% reduced progression.ConclusionsRFC1 disease is frequent and occurs across continents, with CANVAS and ACC as highly diagnostic phenotypes yet as variable, overlapping clusters along a continuous multisystemic disease spectrum, including MSA-C-overlap. Our natural history data help to inform future RFC1 treatment trials.Classification of EvidenceThis study provides Class II evidence that RFC1 repeat expansions are associated with CANVAS and ACC.

Amelioration of motor and nonmotor symptoms in cortical cerebellar atrophy and multiple system atrophy-cerebellar type by inpatient rehabilitation: a retrospective study.

Sporadic spinocerebellar degenerative diseases such as multiple system atrophy (cerebellar type) and cortical cerebellar atrophy typically present with cerebellar ataxia. Multiple system atrophy is characterized by ataxia, with parkinsonism, dysautonomia and neuropsychiatric symptoms, resulting in reduced quality of life. Effects of physical rehabilitation focused on motor symptoms with ataxia in nonmultiple system atrophy patients have been reported; however, without addressing concomitant nonmotor symptoms. Here, we examined the motor, nonmotor and quality of life effects of inpatient physical rehabilitation in 15 multiple systems atrophy and nine cortical cerebellar atrophy patients without dementia. Rehabilitation involved a 4-week hospitalization with physical, occupational and speech therapy. The following assessments were conducted at admission and discharge: the scale for the assessment and rating of ataxia for ataxia; Montreal cognitive assessment for cognition, hospital anxiety and depression scale for emotion and medical outcomes study short-form for health-related quality of life. Data were analyzed for statistical significance (P < 0.05) using the Wilcoxon signed-rank test. In patients with multiple system atrophy, rehabilitation significantly improved ataxia, cognition with mild cognitive impairment (73.3%) and health-related quality of life; however, patients with depression (86.7%) showed no improvement in emotional health and quality of life. Similar effects on motor and nonmotor symptoms were observed in patients with cortical cerebellar atrophy. This suggests that inpatient rehabilitation could not only improve motor and nonmotor functions, but also the quality of life in patients with spinocerebellar degenerative disease.