Variant Of Multiple System Atrophy Research Articles

Comparison of spontaneous brain activity in distinguishing the parkinsonian variant of multiple system atrophy from Parkinson's disease at an early stage

Comparison of spontaneous brain activity in distinguishing the parkinsonian variant of multiple system atrophy from Parkinson's disease at an early stage

Early Screening for the Parkinson Variant of Multiple System Atrophy: A 6-Item Score.

A 4-item score based on ≥2 features out of orthostatic hypotension, overactive bladder, urinary retention and postural instability was previously shown to early distinguish the Parkinson-variant of multiple system atrophy (MSA-P)from Parkinson's disease (PD) with 78% sensitivity and 86% specificity. To replicate and improve the 4-item MSA-P score. We retrospectively studied 161 patients with early parkinsonism [ie, ≤2 years disease duration or no postural instability, aged 64 (57; 68) years, 44% females] and a diagnosis of clinically established MSA-P (n = 38) or PD (n = 123) after ≥24 months follow-up. The 4-item MSA-P score had a 92% sensitivity and 78% specificity for a final MSA-P diagnosis. By including dopaminergic responsiveness and postural deformities into a 6-item score (range: 0-6), reaching ≥3 points at early disease identified MSA-P patients with 89% sensitivity and 98% specificity. The 6-item MSA-P score is a cost-effective tool to pinpoint individuals with early-stage MSA-P.

Multiple system atrophy with amyloid-β-predominant Alzheimer's disease neuropathologic change.

Multiple system atrophy is a neurodegenerative disease with α-synuclein pathology predominating in the striatonigral and olivopontocerebellar systems. Mixed pathologies are considered to be of low frequency and mostly comprise primary age-related tauopathy or low levels of Alzheimer's disease-related neuropathologic change. Therefore, the concomitant presence of different misfolded proteins in the same brain region is less likely in multiple system atrophy. During the neuropathological evaluation of 21 consecutive multiple system atrophy cases, we identified four cases exhibiting an unusual discrepancy between high Thal amyloid-β phase and low transentorhinal Braak neurofibrillary tangle stage. We mapped α-synuclein pathology, measured the size and number of glial cytoplasmic inclusions and compared the amyloid-β peptides between multiple system atrophy and Alzheimer's disease. In addition, we performed α-synuclein seeding assay from the affected putamen samples. We performed genetic testing for APOE, MAPT, PSEN1, PSEN2 and APP. We refer to the four multiple system atrophy cases with discrepancy between amyloid-β and tau pathology as 'amyloid-β-predominant Alzheimer's disease neuropathologic change-multiple system atrophy' to distinguish these from multiple system atrophy with primary age-related tauopathy or multiple system atrophy with typical Alzheimer's disease neuropathologic change. As most multiple system atrophy cases with mixed pathologies reported in the literature, these cases did not show a peculiar clinical or MRI profile. Three amyloid-β-predominant Alzheimer's disease neuropathologic change-multiple system atrophy cases were available for genetic testing, and all carried the APOE ɛ4 allele. The extent and severity of neuronal loss and α-synuclein pathology were not different compared with typical multiple system atrophy cases. Analysis of amyloid-β peptides revealed more premature amyloid-β plaques in amyloid-β-predominant Alzheimer's disease neuropathologic change-multiple system atrophy compared with Alzheimer's disease. α-Synuclein seeding amplification assay showed differences in the kinetics in two cases. This study highlights a rare mixed pathology variant of multiple system atrophy in which there is an anatomical meeting point of amyloid-β and α-synuclein, i.e. the striatum or cerebellum. Since biomarkers are entering clinical practice, these cases will be recognized, and the clinicians have to be informed that the prognosis is not necessarily different than in pure multiple system atrophy cases but that the effect of potential α-synuclein-based therapies might be influenced by the co-presence of amyloid-β in regions where α-synuclein also aggregates. We propose that mixed pathologies should be interpreted not only based on differences in the clinical phenotype but also on whether protein depositions regionally overlap, potentially leading to a different response to α-synuclein-targeted therapies.

Nature of Parkinsonian features in multiple system atrophy.

For this observational study, we evaluated the clinical profile of Parkinsonian features in multiple system atrophy (MSA), as there is no clarity about the specifics of these features in this disease compared to progressive supranuclear palsy (PSP) and Parkinson's disease (PD). Here, we selected 57 patients with MSA based on standard criteria and grouped them into two categories - Parkinsonian variant of MSA (MSA-P) and cerebellar variant of MSA (MSA-C). However, researchers did not distinguish among patients based on the nature of extrapyramidal syndrome or levodopa responsiveness. Then, we examined the patients at the time of their first visit to outpatient clinics or indoor wards and recorded and analyzed the specific extrapyramidal features or their variations. The extrapyramidal features including levodopa responsiveness were highly variable among MSA-C as well as MSA-P patients. A subset of patients presented with features resembling PSP (symmetry [56.1%], axial rigidity [52.6%], backward falls [28.1%], and down-gaze restriction [17.5%]), while others presented with features resembling PD (asymmetry [43.9%], tremors [71.9%], and peripheral rigidity [40.4%]). After grouping patients based on predominant extrapyramidal features, 36.8% of patients had PD-like, 19.3% had PSP-like, and 43.9 % had mixed presentation. Moreover, 86% of patients had a perceptible levodopa response, including a sustained response for more than six months in 64% of patients. Extrapyramidal features in MSA patients may be PD-like, PSP-like, or mixed. Moreover, an initial presentation resembling PSP or PD may be deceptive and one must follow it up for MSA.

The Frequency of Intermediate Alleles in Patients with Cerebellar Phenotypes.

Cerebellar syndromes are clinically and etiologically heterogeneous and can be classified as hereditary, neurodegenerative non-hereditary, or acquired. Few data are available on the frequency of each form in the clinical setting. Growing interest is emerging regarding the genetic forms caused by triplet repeat expansions. Alleles with repeat expansion lower than the pathological threshold, termed intermediate alleles (IAs), have been found to be associated with disease manifestation. In order to assess the relevance of IAs as a cause of cerebellar syndromes, we enrolled 66 unrelated Italian ataxic patients and described the distribution of the different etiology of their syndromes and the frequency of IAs. Each patient underwent complete clinical, hematological, and neurophysiological assessments, neuroimaging evaluations, and genetic tests for autosomal dominant cerebellar ataxia (SCA) and fragile X-associated tremor/ataxia syndrome (FXTAS). We identified the following diagnostic categories: 28% sporadic adult-onset ataxia, 18% cerebellar variant of multiple system atrophy, 9% acquired forms, 9% genetic forms with full-range expansion, and 12% cases with intermediate-range expansion. The IAs were six in the FMR1 gene, two in the gene responsible for SCA8, and one in the ATXN2 gene. The clinical phenotype of patients carrying the IAs resembles, in most of the cases, the one associated with full-range expansion. Our study provides an exhaustive description of the causes of cerebellar ataxia, estimating for the first time the frequency of IAs in SCAs- and FXTAS-associated genes. The high percentage of cases with IAs supports further screening among patients with cerebellar syndromes.

Functional connectome automatically differentiates multiple system atrophy (parkinsonian type) from idiopathic Parkinson's disease at early stages.

Differentiating the parkinsonian variant of multiple system atrophy (MSA-P) from idiopathic Parkinson's disease (IPD) is challenging, especially in the early stages. This study aimed to investigate differences and similarities in the brain functional connectomes of IPD and MSA-P patients and use machine learning methods to explore the diagnostic utility of these features. Resting-state fMRI data were acquired from 88 healthy controls, 76 MSA-P patients, and 53 IPD patients using a 3.0T scanner. The whole-brain functional connectome was constructed by thresholding the Pearson correlation matrices of 116 regions, and topological properties were evaluated through graph theory approaches. Connectome measurements were used as features in machine learning models (random forest [RF]/logistic regression [LR]/support vector machine) to distinguish IPD and MSA-P patients. Regarding graph metrics, early IPD and MSA-P patients shared network topological properties. Both patient groups showed functional connectivity disruptions within the cerebellum-basal ganglia-cortical network, but these disconnections were mainly in the cortico-thalamo-cerebellar circuits in MSA-P patients and the basal ganglia-thalamo-cortical circuits in IPD patients. Among the connectome parameters, t tests combined with the RF method identified 15 features, from which the LR classifier achieved the best diagnostic performance on the validation set (accuracy=92.31%, sensitivity=90.91%, specificity=93.33%, area under the receiver operating characteristic curve=0.89). MSA-P and IPD patients show similar whole-brain network topological alterations. MSA-P primarily affects cerebellar nodes, and IPD primarily affects basal ganglia nodes; both conditions disrupt the cerebellum-basal ganglia-cortical network. Moreover, functional connectome parameters showed outstanding value in the differential diagnosis of early MSA-P and IPD.

Effects of High Cervical Spinal Cord Stimulation on Gait Disturbance and Dysarthropneumophonia in Parkinson's Disease and Parkinson Variant of Multiple System Atrophy: A Case Series.

High cervical spinal cord stimulation (HCSCS) was found to have therapeutic effects on Parkinsonian gait disturbance. However, the results were inconsistent and confounded with symptoms of pain. This study aimed to reveal the gait and dysarthric effects of HCSCS in PD (Parkinson’s disease) and MSA-P (Parkinson variant of multiple system atrophy) patients without pain. Three PD and five MSA-P patients without painful comorbidities were assessed for gait performance and speech before SCS surgery and at 3- and 6-month follow-up. Stride length and the time spent in the Timed Up-and-Go task showed little change after HCSCS surgery. Overall voice quality (measured by dysphonia severity index) and perceptual speech intelligence improved significantly at 3 months, but improvements slightly diminished at 6 months postoperatively. Change in quality of life (measured by 8-item Parkinson’s disease questionnaire) was also notable at 3 months but narrowed over time following HCSCS. In conclusion, HCSCS showed therapeutic effects in improving the dysarthria but not gait disturbance in pain-free PD and MSA-P patients.

Multimodal striatal neuromarkers in distinguishing parkinsonian variant of multiple system atrophy from idiopathic Parkinson's disease.

To develop an automatic method of classification for parkinsonian variant of multiple system atrophy (MSA-P) and Idiopathic Parkinson's disease (IPD) in early to moderately advanced stages based on multimodal striatal alterations and identify the striatal neuromarkers for distinction. 77 IPD and 75 MSA-P patients underwent 3.0 T multimodal MRI comprising susceptibility-weighted imaging, resting-state functional magnetic resonance imaging, T1-weighted imaging, and diffusion tensor imaging. Iron-radiomic features, volumes, functional and diffusion scalars of bilateral 10 striatal subregions were calculated and provided to the support vector machine for classification RESULTS: A combination of iron-radiomic features, function, diffusion, and volumetric measures optimally distinguished IPD and MSA-P in the testing dataset (accuracy 0.911 and area under the receiver operating characteristic curves [AUC] 0.927). The diagnostic performance further improved when incorporating clinical variables into the multimodal model (accuracy 0.934 and AUC 0.953). The most crucial factor for classification was the functional activity of the left dorsolateral putamen. The machine learning algorithm applied to multimodal striatal dysfunction depicted dorsal striatum and supervening prefrontal lobe and cerebellar dysfunction through the frontostriatal and cerebello-striatal connections and facilitated accurate classification between IPD and MSA-P. The dorsolateral putamen was the most valuable neuromarker for the classification.

Characterization and diagnostic potential of R2* in early-stage progressive supranuclear palsy variants

IntroductionIron accumulation in subcortical brain nuclei has been shown to be differentially increased in atypical parkinsonian disorders. It is unclear whether the patterns of iron accumulation are consistent between variants of progressive supranuclear palsy (PSP) and their diagnostic utility in early to moderately advanced stages of the diseases. MethodsBrain iron content (R2*) was quantified using magnetic resonance imaging in patients clinically diagnosed as PSP – parkinsonism (PSP–P, n = 15), PSP – Richardson's syndrome (PSP-RS, n = 14), Parkinson's disease (PD, n = 15), or the parkinsonian variant of multiple system atrophy (MSA-P, n = 14) using established criteria, and healthy controls (HC). Disease duration was less than 5 years in all patients. The quantification of regional R2* was performed using a semi-automatized approach. ResultsSignificant group differences in R2*, primarily within the red nucleus and the substantia nigra, were identified between PSP, PD, MSA-P, and HC, but not between PSP-P and PSP-RS. However, distinct R2* correlation patterns across brain regions were observed for the different groups. Good classification performances (sensitivity and specificity >80%) were only obtained for PSP vs. HC. For all other comparisons, sensitivity and/or specificity was below <70%. ConclusionIron accumulation in subcortical brain nuclei has distinct correlated patterns in PSP-P and PSP-RS, which could be reflecting different pathophysiological mechanisms. Increased iron content in these nuclei appears to be a predictor for atypical parkinsonian disorders such as PSP and MSA. Further studies are required to reproduce this finding and elucidate the evolution of these patterns over the course of the disease.

Use of levodopa-carbidopa intestinal gel to treat patients with multiple system atrophy

BackgroundLevodopa-carbidopa intestinal gel (LCIG) is an effective treatment for late-stage Parkinson's disease (PD) but had not been evaluated in levodopa-responsive patients with the parkinsonian variant of multiple system atrophy (MSA-P) and motor fluctuations. We aimed to assess the safety of LCIG in MSA-P patients. MethodsIn a retrospective, single-center study, we analyzed clinical and treatment-related data for all patients with MSA-P or PD treated with LCIG between December 2004 and November 2017. Adverse events (AEs) were classified into three classes: AEs related to gastrointestinal effects or to the PEG-J procedure, AEs related to the device, and AEs related to the pharmacological effect of LCIG. Results7 MSA-P and 63 PD patients had been treated with LCIG for a median [interquartile range] period of 31 [16;43] and 19 [8;45] months, respectively. There were no significant intergroup differences in safety. Enteral nutrition was introduced at the same time as LCIG treatment in 4 (57%) MSA-P patients. In the MSA-P and PD groups, LCIG was associated with a better Global Clinical Impression score and discontinuation of oral anti-parkinsonian drugs (in 43% and 27% of cases, respectively). ConclusionsLCIG treatment is feasible in MSA-P patients with severe motor complications. The safety profile is similar to that seen in PD.

Automated Differentiation of Atypical Parkinsonian Syndromes Using Brain Iron Patterns in Susceptibility Weighted Imaging.

In recent studies, iron overload has been reported in atypical parkinsonian syndromes. The topographic patterns of iron distribution in deep brain nuclei vary by each subtype of parkinsonian syndrome, which is affected by underlying disease pathologies. In this study, we developed a novel framework that automatically analyzes the disease-specific patterns of iron accumulation using susceptibility weighted imaging (SWI). We constructed various machine learning models that can classify diseases using radiomic features extracted from SWI, representing distinctive iron distribution patterns for each disorder. Since radiomic features are sensitive to the region of interest, we used a combination of T1-weighted MRI and SWI to improve the segmentation of deep brain nuclei. Radiomics was applied to SWI from 34 patients with a parkinsonian variant of multiple system atrophy, 21 patients with cerebellar variant multiple system atrophy, 17 patients with progressive supranuclear palsy, and 56 patients with Parkinson’s disease. The machine learning classifiers that learn the radiomic features extracted from iron-reflected segmentation results produced an average area under receiver operating characteristic curve (AUC) of 0.8607 on the training data and 0.8489 on the testing data, which is superior to the conventional classifier with segmentation using only T1-weighted images. Our radiomic model based on the hybrid images is a promising tool for automatically differentiating atypical parkinsonian syndromes.

Multiple system atrophy variant with severe hippocampal pathology.

The striatonigral and olivopontocerebellar systems are known to be vulnerable in multiple system atrophy (MSA), showing neuronal loss, astrogliosis, and alpha‐synuclein‐immunoreactive inclusions. MSA patients who displayed abundant neuronal cytoplasmic inclusions (NCIs) in the regions other than the striatonigral or olivopontocerebellar system have occasionally been diagnosed with variants of MSA. In this study, we report clinical and pathologic findings of MSA patients characterized by prominent pathologic involvement of the hippocampus. We assessed 146 consecutively autopsied MSA patients. Semi‐quantitative analysis of anti‐alpha‐synuclein immunohistochemistry revealed that 12 of 146 patients (8.2%) had severe NCIs in two or more of the following areas: the hippocampal granule cells, cornu ammonis areas, parahippocampal gyrus, and amygdala. In contrast, the remaining 134 patients did not show severe NCIs in any of these regions. Patients with severe hippocampal involvement showed a higher representation of women (nine women/three men; Fisher's exact test, p = 0.0324), longer disease duration (13.1 ± 5.9 years; Mann–Whitney U‐test, p = 0.000157), higher prevalence of cognitive impairment (four patients; Fisher's exact test, p = 0.0222), and lower brain weight (1070.3 ± 168.6 g; Mann–Whitney U‐test, p = 0.00911) than other patients. The hippocampal granule cells and cornu ammonis area 1/subiculum almost always showed severe NCIs. The NCIs appeared to be ring‐shaped or neurofibrillary tangle‐like, fibrous configurations. Three of 12 patients also had dense, round‐shaped NCIs that were morphologically similar to pick bodies. The patients with Pick body‐like inclusions showed more severe atrophy of the medial temporal lobes and broader spreading of NCIs than those without. Immunohistochemistry for hyperphosphorylated tau and phosphorylated TDP‐43 revealed minimal aggregations in the hippocampus of the hippocampal MSA patients. Our observations suggest a pathological variant of MSA that is characterized by severe involvement of hippocampal neurons. This phenotype may reinforce the importance of neuronal alpha‐synucleinopathy in the pathogenesis of MSA.

Characterization and diagnostic potential of diffusion tractography in multiple system atrophy

IntroductionMicrostructural integrity of the middle cerebellar peduncle (MCP) and the putamen captured by diffusion-tensor imaging (DTI) is differentially affected in the parkinsonian and cerebellar variants of multiple system atrophy (MSA-P, MSA-C) compared to Parkinson's disease (PD). The current study applied DTI and tractography in order to 1) characterize the distribution of DTI metrics along the tracts of the MCP and from the putamen in MSA variants, and 2) evaluate the usefulness of combining these measures for the differential diagnosis of MSA-P against PD in the clinical setting. MethodsTwenty-nine MSA patients (MSA-C, n = 10; MSA-P, n = 19), with a mean disease duration of 2.8 ± 1.7 years, 19 PD patients, and 27 healthy controls (HC) were included in the study. Automatized tractography with a masking procedure was employed to isolate the MCP tracts. DTI measures along the tracts of the MCP and within the putamen were acquired and jointly used to classify MSA vs. PD, and MSA-P vs. PD. Putamen volume was additionally tested as classification feature in post hoc analyses. ResultsDTI measures within the MCP and putamen showed significant alterations in MSA variants compared to HC and PD. Classification accuracy for MSA vs. PD and MSA-P vs PD using diffusion measures was 91.7% and 89.5%, respectively. When replacing the putaminal DTI measure by a normalized measure of putamen volume classification accuracy improved to 95.8% and 94.7%, respectively. ConclusionMultimodal information from MCP tractography and putamen volume yields excellent diagnostic accuracy to discriminate between early-to-moderately advanced patients with MSA and PD.

A distinct neuromelanin magnetic resonance imaging pattern in parkinsonian multiple system atrophy

BackgroundParkinsonian variant of multiple system atrophy is a neurodegenerative disorder frequently misdiagnosed as Parkinson’s disease. No early imaging biomarkers currently differentiate these disorders.MethodsSimple visual imaging analysis of the substantia nigra and locus coeruleus in neuromelanin-sensitive magnetic resonance imaging and nigrosome 1 in susceptibility-weighted sequences was performed in thirty patients with parkinsonian variant of multiple system atrophy fulfilling possible/probable second consensus diagnostic criteria. The neuromelanin visual pattern was compared to patients with Parkinson’s disease with the same disease duration (n = 10) and healthy controls (n = 10). Substantia nigra semi-automated neuromelanin area/signal intensity was compared to the visual data.ResultsGroups were similar in age, sex, disease duration, and levodopa equivalent dose. Hoehn & Yahr stage was higher in parkinsonian multiple system atrophy patients, 69% of whom had normal neuromelanin size/signal, significantly different from Parkinson’s disease patients, and similar to controls. Nigrosome 1 signal was lost in 74% of parkinsonian multiple system atrophy patients. Semi-automated neuromelanin substantia nigra signal, but not area, measurements were able to differentiate groups.ConclusionsIn patients with parkinsonism, simple visual magnetic resonance imaging analysis showing normal neuromelanin substantia nigra and locus coeruleus, combined with nigrosome 1 loss, allowed the distinction of the parkinsonian variant of multiple system atrophy from Parkinson’s disease and healthy controls. This easy and widely available method was superior to semi-automated measurements in identifying specific imaging changes in substantia nigra and locus coeruleus.

MRI-Based Radiomics of Basal Nuclei in Differentiating Idiopathic Parkinson's Disease From Parkinsonian Variants of Multiple System Atrophy: A Susceptibility-Weighted Imaging Study.

ObjectivesTo investigate the value of MRI-based radiomic model based on the radiomic features of different basal nuclei in differentiating idiopathic Parkinson’s disease (IPD) from Parkinsonian variants of multiple system atrophy (MSA-P).MethodsRadiomics was applied to the 3T susceptibility- weighted imaging (SWI) from 102 MSA-P patients and 83 IPD patients (allocated to a training and a testing cohort, 7:3 ratio). The substantia nigra (SN), caudate nucleus (CN), putamen (PUT), globus pallidus (GP), red nucleus (RN), and subthalamic nucleus (STN) were manually segmented, and 396 features were extracted. After feature selection, support vector machine (SVM) was generated, and its predictive performance was calculated in both the training and testing cohorts using the area under receiver operating characteristic curve (AUC).ResultsSeven radiomic features were selected from the PUT, by which the SVM classifier achieved the best diagnostic performance with an AUC of 0.867 in the training cohort and an AUC of 0.862 in the testing cohort. Furthermore, the combined model, which incorporating part III of the Parkinson’s Disease Rating Scale (UPDRSIII) scores into radiomic features of the PUT, further improved the diagnostic performance. However, radiomic features extracted from RN, SN, GP, CN, and STN had moderate to poor diagnostic performance, with AUC values that ranged from 0.610 to 0.788 in the training cohort and 0.583 to 0.766 in the testing cohort.ConclusionRadiomic features derived from the PUT had optimal value in differentiating IPD from MSA-P. A combined radiomic model, which contained radiomic features of the PUT and UPDRSIII scores, further improved performance and may represent a promising tool for distinguishing between IPD and MSA-P.

Abnormalities of white matter differentiate the Parkinson variant of multiple system atrophy from Parkinson's disease

Objective: To identify objective markers between the Parkinson variant of multiple system atrophy (MSA-P) and Parkinson's disease (PD). Methods: Retrospective analysis was performed on 10 patients with MSA-P, 15 patients with PD, and 15 healthy control group during the period from August 2016 to February 2019 in Baoshan Branch of Shanghai First People's Hospital.We combined the novel tract based spatial statistics (TBSS) and region of interest (ROI) analyses for the first time to investigate three groups with diffusion tensor imaging. By TBSS, we performed pairwise comparisons of mean diffusivity and fractional anisotropy (FA) maps. The clusters with significant differences between MSA-P and PD were used as ROIs for further analyses. Results: FA values in the left anterior thalamic radiation(ATR) (ROI values were 0.371(0.287-0.535), 0.472(0.390-0.594), 0.473(0.388-0.555); P values were 0.008, 0.008) and left superior longitudinal fasciculus (SLF)(ROI values were 0.397(0.291-0.469), 0.456(0.338-0.560), 0.473(0.427-0.530); P values were 0.013,<0.001) were significantly decreased in MSA-P compared with PD or controls, and significantly correlated with clinical data((r =-0.807, P =0.005),(r =-0.455, P =0.022)). Conclusion: Our findings indicate the abnormalities of left ATR and left SLF as specific biomarkers for differential diagnosis.

Parkinson's disease or atypical parkinsonism? The importance of acoustic voice analysis in differential diagnosis of speech disorders.

IntroductionSpeech disorder is a common clinical manifestation in patients with Parkinson's disease and atypical parkinsonian syndromes and tends to occur before the onset of the axial parkinsonian symptoms. Due to parkinsonian features that overlap those of Parkinson's disease, the differentiation of voice and a speech disorder is a challenge for clinicians primarily in the early stage of the disease.MethodsSpeech samples were obtained from 116 subjects including 30 cases of Parkinson's disease, 30 cases of progressive supranuclear palsy, 30 cases of multiple system atrophy, and control group consisted of 26 subjects. Differential diagnosis of dysarthria subtypes was based on the quantitative, acoustic analysis of particular speech components. Additionally, Voice Handicap Index questionnaire was taken into account to differentiate the severity of voice impairment in the study groups.ResultsOur results showed significant differences in the distribution of acoustic parameters between Parkinson's disease and atypical parkinsonian syndromes. A mixed type of dysarthria with a combination of hypokinetic, spastic, and atactic features has been found in patients with atypical parkinsonism. In patients with the clinical diagnosis of the parkinsonian variant of multiple system atrophy, ataxic components of dysarthria were observed. Patients with PD presented pure hypokinetic dysarthria. Some parameters may be used as a marker for the diagnosis of the initial stage of PD. Voice impartment was significantly more frequent and severe in atypical parkinsonism than in Parkinson's disease.ConclusionAcoustic voice analysis is a very sensitive and noninvasive tool, provides objective information for the assessment of different speech components, has the specific potential to provide quantitative data essential for the improvement of the diagnostic process, and maybe a useful instrument in the differential diagnosis of parkinsonian syndromes.

Differences and Similarities Between the Parkinsonian Variant of Multiple System Atrophy and Parkinson Disease in the Natural History Study of the Synucleinopathies (4795)

Differences and Similarities Between the Parkinsonian Variant of Multiple System Atrophy and Parkinson Disease in the Natural History Study of the Synucleinopathies (4795)

Gray Matter Atrophy in Parkinson's Disease and the Parkinsonian Variant of Multiple System Atrophy: A Combined ROI- and Voxel-Based Morphometric Study

OBJECTIVES:Parkinson’s disease (PD) and the parkinsonian variant of multiple system atrophy (MSA-P) are distinct neurodegenerative disorders that share similar clinical features of parkinsonism. The morphological alterations of these diseases have yet to be understood. The purpose of this study was to evaluate gray matter atrophy in PD and MSA-P using regions of interest (ROI)-based measurements and voxel-based morphometry (VBM).METHODS:We studied 41 patients with PD, 20 patients with MSA-P, and 39 controls matched for age, sex, and handedness using an improved T1-weighted sequence that eased gray matter segmentation. The gray matter volumes were measured using ROI and VBM.RESULTS:ROI volumetric measurements showed significantly reduced bilateral putamen volumes in MSA-P patients compared with those in PD patients and controls (p<0.05), and the volumes of the bilateral caudate nucleus were significantly reduced in both MSA-P and PD patients compared with those in the controls (p<0.05). VBM analysis revealed multifocal cortical and subcortical atrophy in both MSA-P and PD patients, and the volumes of the cerebellum and temporal lobes were remarkably reduced in MSA-P patients compared with the volumes in PD patients (p<0.05).CONCLUSIONS:Both PD and MSA-P are associated with gray matter atrophy, which mainly involves the bilateral putamen, caudate nucleus, cerebellum, and temporal lobes. ROI and VBM can be used to identify these morphological alterations, and VBM is more sensitive and repeatable and less time-consuming, which may have potential diagnostic value.

Heightened risk of early vocal fold motion impairment onset and dysphagia in the parkinsonian variant of multiple system atrophy: a comparative study

ObjectiveWe compared differences in frequency and timing of onset of the following clinical events between the cerebellar and parkinsonian variants of multiple system atrophy (MSA-C and MSA-P, respectively): type of operation including tracheostomy and/or aspiration prevention surgery, vocal fold motion impairment (VFMI), sleep apnea (SA), introduction of mechanical ventilation (MV), and dysphagia. The risks of these events cooccurring with either MSA-C or MSA-P were compared. MethodsWe retrospectively assessed clinical outcomes only of patients with MSA who presented at the Department of Otolaryngology of the University of Tokyo Hospital between 2008 and 2018. The proportion and timing of onset events between MSA-C and MSA-P and risks of onset were compared using chi-square tests and Cox proportional hazard models adjusted for age, sex, and disease severity, respectively. ResultsWe identified 113 patients (median age: 60 years, 72 men [64%]). The frequency and timing of VFMI, SA, MV, dysphagia, and surgeries were 55 patients (49%) and 76 (95% CI 61–91) months after MSA onset, 85 (75%) and 41 (32–50), 36 (32%) and 100 (73–127), 77 (68%) and 43 (36–50), and 25 (22%) and 102 (84–120), respectively. Twenty-seven patients (24%) had MSA-P and higher risk of VFMI (p < .001), SA (p = .030), and dysphagia (p = .017) than did patients with MSA-C. ConclusionWhile MSA-P is less common, it may involve heightened risk of VFMI and dysphagia early onset. Thus, careful follow-up for VFMI, SA, and dysphagia may be needed for these patients. Criteria for Rating Diagnostic Accuracy StudiesClass II.