Diagnosis Of Multiple System Atrophy Research Articles

The utility of susceptibility-weighted imaging in the diagnosis of multiple system atrophy, cerebellar type

The utility of susceptibility-weighted imaging in the diagnosis of multiple system atrophy, cerebellar type

Advanced brain aging in multiple system atrophy compared to Parkinson’s disease

Multiple system atrophy (MSA) and Parkinson’s disease (PD) belong to alpha-synucleinopathy, but they have very different clinical courses and prognoses. An imaging biomarker that can differentiate between the two diseases early in the disease course is desirable for appropriate treatment. Neuroimaging-based brain age paradigm provides an individualized marker to differentiate aberrant brain aging patterns in neurodegenerative diseases. In this study, patients with MSA (N = 23), PD (N = 33), and healthy controls (N = 34; HC) were recruited. A deep learning approach was used to estimate brain-predicted age difference (PAD) of gray matter (GM) and white matter (WM) based on image features extracted from T1-weighted and diffusion-weighted magnetic resonance images, respectively. Spatial normative models of image features were utilized to quantify neuroanatomical impairments in patients, which were then used to estimate the contributions of image features to brain age measures. For PAD of GM (GM-PAD), patients with MSA had significantly older brain age (9.33 years) than those with PD (0.75 years; P = 0.002) and HC (-1.47 years; P < 0.001), and no significant difference was found between PD and HC (P = 1.000). For PAD of WM (WM-PAD), it was significantly greater in MSA (9.27 years) than that in PD (1.90 years; P = 0.037) and HC (-0.74 years; P < 0.001); there was no significant difference between PD and HC (P = 0.087). The most salient image features that contributed to PAD in MSA and PD were different. For GM, they were the orbitofrontal regions and the cuneus in MSA and PD, respectively, and for WM, they were the central corpus callosum and the uncinate fasciculus in MSA and PD, respectively. Our results demonstrated that MSA revealed significantly greater PAD than PD, which might be related to markedly different neuroanatomical contributions to brain aging. The image features with distinct contributions to brain aging might be of value in the differential diagnosis of MSA and PD.

Discrimination of MSA-P and MSA-C by RT-QuIC analysis of olfactory mucosa: the first assessment of assay reproducibility between two specialized laboratories

BackgroundDetection of the pathological and disease-associated alpha-synuclein (αSynD) in the brain is required to formulate the definitive diagnosis of multiple system atrophy (MSA) and Parkinson’s disease (PD). We recently showed that αSynD can be detected in the olfactory mucosa (OM) of MSA and PD patients. For this reason, we have performed the first interlaboratory study based on α-synuclein Real-Time Quaking-Induced Conversion (αSyn_RT-QuIC) analysis of OM samples collected from PD and MSA patients with the parkinsonian (MSA-P) and cerebellar (MSA-C) phenotypes.MethodsOM samples were prospectively collected from patients with a probable diagnosis of MSA-P (n = 20, mean disease duration 4.4 years), MSA-C (n = 10, mean disease duration 4 years), PD (n = 13, mean disease duration 8 years), and healthy control subjects (HS) (n = 11). Each sample was analyzed by αSyn_RT-QuIC in two independent specialized laboratories, one located in Italy (ITA-lab) and one located in the USA (USA-lab). Both laboratories have developed and used harmonized αSyn_RT-QuIC analytical procedures. Results were correlated with demographic and clinical data.ResultsThe αSyn_RT-QuIC analysis reached a 96% interrater agreement of results (IAR) between laboratories (Kappa = 0.93, 95% CI 0.83–1.00). In particular, αSyn_RT-QuIC seeding activity was found in the OM of 9/13 patients with PD (sensitivity 69%, IAR 100%) and 18/20 patients with MSA-P (sensitivity 90%, IAR 100%). Interestingly, samples collected from patients with MSA-C did not induce αSyn_RT-QuIC seeding activity, except for one subject in USA-lab. Therefore, we found that MSA-P and MSA-C induced opposite effects. Regardless of disease diagnosis, the αSyn_RT-QuIC seeding activity correlated with some clinical parameters, including the rigidity and postural instability.ConclusionsOur study provides evidence that OM-αSynD may serve as a novel biomarker for accurate clinical diagnoses of PD, MSA-P, and MSA-C. Moreover, αSyn_RT-QuIC represents a reliable assay that can distinguish patients with MSA-P from those with MSA-C, and may lead to significant advancements in patients stratification and selection for emerging pharmacological treatments and clinical trials.

Frequency of FMR1 Premutation Alleles in Patients with Undiagnosed Cerebellar Ataxia and Multiple System Atrophy in the Japanese Population.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder caused by FMR1 premutation expansion of CGG repeats. FXTAS can be misdiagnosed with many neurodegenerative disorders manifesting with cerebellar ataxias owing to their overlapping clinical and radiological features. The frequency of the FMR1 premutation allele in Japan has not been fully determined. Herein, we aimed to determine the frequency of FMR1 premutation alleles in Japanese patients with undiagnosed cerebellar ataxia and multiple system atrophy, using repeat-primed PCR in 186 patients with adult onset of undiagnosed cerebellar ataxia and 668 patients with multiple system atrophy, to identify expanded CGG repeats as well as to detect AGG interruptions within the expanded alleles. The size of expansions was estimated using fragment length analysis of PCR products obtained by conventional PCR employing a pair of unique primers flanking the repeat sequence. We identified FMR1 premutation alleles in three male patients. One patient revealed 84 repeat units with one AGG interruption and another patient showed 103 repeat units. Both had presented with sporadic cerebellar ataxia, giving an estimated frequency of 3.7% among Japanese male patients with sporadic cerebellar ataxia with age at onset above 50years. One patient with the clinical diagnosis of multiple system atrophy harbored 60 repeat units with four AGG interruptions. FMR1 intermediate alleles were observed in two males and one female among the multiple system atrophy patients. We found that genetic tests for FMR1 premutation should be considered in Japanese male patients with cerebellar ataxia with the age at onset above 50years.

Assembly of \u03b1-synuclein and neurodegeneration in the central nervous system of heterozygous\xa0M83 mice following the peripheral administration of \u03b1-synuclein seeds

Peripheral administration (oral, intranasal, intraperitoneal, intravenous) of assembled A53T α-synuclein induced synucleinopathy in heterozygous mice transgenic for human mutant A53T α-synuclein (line M83). The same was the case when cerebellar extracts from a case of multiple system atrophy with type II α-synuclein filaments were administered intraperitoneally, intravenously or intramuscularly. We observed abundant immunoreactivity for pS129 α-synuclein in nerve cells and severe motor impairment, resulting in hindlimb paralysis and shortened lifespan. Filaments immunoreactive for pS129 α-synuclein were in evidence. A 70% loss of motor neurons was present five months after an intraperitoneal injection of assembled A53T α-synuclein or cerebellar extract with type II α-synuclein filaments from an individual with a neuropathologically confirmed diagnosis of multiple system atrophy. Microglial cells changed from a predominantly ramified to a dystrophic appearance. Taken together, these findings establish a close relationship between the formation of α-synuclein inclusions in nerve cells and neurodegeneration, accompanied by a shift in microglial cell morphology. Propagation of α-synuclein inclusions depended on the characteristics of both seeds and transgenically expressed protein.

Magnetic resonance T1w/T2w ratio and voxel-based morphometry in multiple system atrophy

Diagnosis of multiple system atrophy (MSA) may be improved by using multimodal imaging approaches. We investigated the use of T1-weighted/T2-weighted (T1w/T2w) images ratio combined with voxel-based morphometry to evaluate brain tissue integrity in MSA compared to Parkinson’s disease (PD) and healthy controls (HC). Twenty-six patients with MSA, 43 patients with PD and 56 HC were enrolled. Whole brain voxel-based and local regional analyses were performed to evaluate gray and white matter (GM and WM) tissue integrity and mean regional values were used for patients classification using logistic regression. Increased mean regional values of T1w/T2w in bilateral putamen were detected in MSA-P compared to PD and HC. The combined use of regional GM and T1w/T2w values in the right and left putamen showed the highest accuracy in discriminating MSA-P from PD and good accuracy in discriminating MSA from PD and HC. A good accuracy was also found in discriminating MSA from PD and HC by either combining regional GM and T1w/T2w values in the cerebellum or regional WM and T1w/T2w in the cerebellum and brainstem. The T1w/T2w image ratio alone or combined with validated MRI parameters can be further considered as a potential candidate biomarker for differential diagnosis of MSA.

Parkinsonism and dysautonomia with anti-CV2/CRMP5 associated paraneoplastic neurological syndromes mimicking multiple system atrophy: a case report

BackgroundParaneoplastic neurological syndromes (PNSs) are broad-spectrum disorders that can affect any part of the nervous system varying in core symptoms. Onconeural antibodies, including Hu, Yo, Ri, anti-CV2, amphiphysin, Ma2, and Tr are well-characterized and commonly used for the diagnosis of definite PNS. Generally, anti-CV2 antibodies have usually been associated with cerebellar ataxia, chorea, peripheral and autonomic neuropathies, myelopathy, optic neuritis, and retinitis. However, Parkinsonism has not been reported as the core symptom in patients with anti-CV2 antibodies.Case presentationWe report a patient with anti-CV2 antibody manifested as Parkinsonism and autonomic dysfunction, which may lead to the diagnosis of multiple system atrophy with predominant Parkinsonism (MSA-P). A lumbar puncture examination was undergone to find a positive anti-CV2 antibody in cerebrospinal fluid. PET-CT showed no tumor. Immunotherapy was adopted and the symptoms were relieved for 5 months. However, with no evidence of tumor, he died after 8 months.ConclusionsOur findings indicate that PNS with anti-CV2 antibody can be shown as MSA-P mimic. Considering that MSA is a neurodegenerative disease with a poor prognosis, screening for other treatable or controllable factors like PNS presented in this case is necessary when encountering a rapid progressive MSA-mimic patient.

Glia Imaging Differentiates Multiple System Atrophy from Parkinson's Disease: A Positron Emission Tomography Study with [11 C]PBR28 and Machine Learning Analysis.

The clinical diagnosis of multiple system atrophy (MSA) is challenged by overlapping features with Parkinson's disease (PD) and late-onset ataxias. Additional biomarkers are needed to confirm MSA and to advance the understanding of pathophysiology. Positron emission tomography (PET) imaging of the translocator protein (TSPO), expressed by glia cells, has shown elevations in MSA. In this multicenter PET study, we assess the performance of TSPO imaging as a diagnostic marker for MSA. We analyzed [11 C]PBR28 binding to TSPO using imaging data of 66 patients with MSA and 24 patients with PD. Group comparisons were based on regional analysis of parametric images. The diagnostic readout included visual reading of PET images against clinical diagnosis and machine learning analyses. Sensitivity, specificity, and receiver operating curves were used to discriminate MSA from PD and cerebellar from parkinsonian variant MSA. We observed a conspicuous pattern of elevated regional [11 C]PBR28 binding to TSPO in MSA as compared with PD, with "hotspots" in the lentiform nucleus and cerebellar white matter. Visual reading discriminated MSA from PD with 100% specificity and 83% sensitivity. The machine learning approach improved sensitivity to 96%. We identified MSA subtype-specific TSPO binding patterns. We found a pattern of significantly increased regional glial TSPO binding in patients with MSA. Intriguingly, our data are in line with severe neuroinflammation in MSA. Glia imaging may have potential to support clinical MSA diagnosis and patient stratification in clinical trials on novel drug therapies for an α-synucleinopathy that remains strikingly incurable. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Individual voxel-based morphometry adjusting covariates in multiple system atrophy

IntroductionThis study aimed to evaluate whether novel individual voxel-based morphometry adjusting covariates (iVAC), such as age, sex, and total intracranial volume, could increase the accuracy of a diagnosis of multiple system atrophy (MSA) and enable the differentiation of MSA from Parkinson's disease (PD). MethodsWe included 53 MSA patients (MSA-C: 33, MSA-P: 20), 53 PD patients, and 189 healthy controls in this study. All participants underwent high-resolution T1-weighted imaging (WI) and T2-WI with a 3.0-T MRI scanner. We evaluated the occurrence of significant atrophic findings in the pons/middle cerebellar peduncle (MCP) and putamen on iVAC and compared these findings with characteristic changes on T2-WI. ResultsOn iVAC, abnormal findings were observed in the pons/MCP of 96.2% of MSA patients and in the putamen of 80% of MSA patients; however, on T2-WI, they were both observed at a frequency of 60.4% in MSA patients. On iVAC, all but one MSA-P patient (98.1%) showed significant atrophic changes in the pons/MCP or putamen. By contrast, 69.8% of patients with MSA showed abnormal signal changes in the pons/MCP or putamen on T2-WI. iVAC yielded 95.0% sensitivity and 96.2% specificity for differentiating MSA-P from PD. ConclusioniVAC enabled us to recognize the morphological characteristics of MSA visually and with high accuracy compared to T2-WI, indicating that iVAC is a potential diagnostic screening tool for MSA.

Urodynamic Evaluation in Multiple System Atrophy: A Retrospective Cohort Study.

ABSTRACTBackgroundUrological dysfunction in patients with multiple system atrophy (MSA) is one of the main manifestations of autonomic failure. Urodynamic examination is clinically relevant since underlying pathophysiology of lower urinary tract (LUT) dysfunction can be variable.ObjectiveEvaluation of the pathophysiology of urological symptoms and exploration of differences in urodynamic patterns of LUT dysfunction between MSA‐P and MSA‐C.MethodsRetrospective study of patients with possible and probable MSA who were referred for urodynamic studies between 2004 and 2019. Demographic data, medical history, physical examination and urodynamic studies assessing storage and voiding dysfunction were obtained.ResultsSeventy‐four patients were included in this study (MSA‐P 64.9% n = 48; median age 62.5 (IQR 56.8–70) years). Detrusor overactivity during filling phase was noted in 58.1% (n = 43) of the patients. In the voiding phase, detrusor sphincter dyssynergia and detrusor underactivity were observed in 24.6% (n = 17) and in 62.1% (n = 41) of the patients, respectively. A postmicturition residual volume of over 100 ml was present in 71.4% (n = 50) of the patients. Comparison of MSA subtypes showed weaker detrusor contractility in MSA‐P compared to MSA‐C [pdetQmax 26.2 vs. 34.4 cmH20, P = 0.04]. In 56.2% (n = 41) of patients pathophysiology of LUT dysfunction was deemed to be neurogenic and consistent with the diagnosis of MSA. In 35.6% (n = 26) urodynamic pattern suggested other urological co‐morbidities.ConclusionUrodynamic evaluation is an important tool to analyze the pattern of LUT dysfunction in MSA. Impaired detrusor contractility was seen more in MSA‐P which needs to be investigated in further studies.

The differential diagnostic value of a battery of oculomotor evaluation in Parkinson's Disease and Multiple System Atrophy.

IntroductionClinical diagnosis of Parkinsonism is still challenging, and the diagnostic biomarkers of Multiple System Atrophy (MSA) are scarce. This study aimed to investigate the diagnostic value of the combined eye movement tests in patients with Parkinson's disease (PD) and those with MSA.MethodsWe enrolled 96 PD patients, 33 MSA patients (18 with MSA‐P and 15 with MSA‐C), and 40 healthy controls who had their horizontal ocular movements measured. The multiple‐step pattern of memory‐guided saccade (MGS), the hypometria/hypermetria of the reflexive saccade, the abnormal saccade in smooth pursuit movement (SPM), gaze‐evoked nystagmus, and square‐wave jerks in gaze‐holding test were qualitatively analyzed. The reflexive saccadic parameters and gain of SPM were also quantitatively analyzed.ResultsThe MGS test showed that patients with either diagnosis had a significantly higher incidence of multiple‐step pattern compared with controls (68.6%, 65.2%, and versus. 2.5%, p < .05, in PD, MSA, versus. controls, respectively). The reflexive saccade test showed that MSA patients showing a prominent higher incidence of the abnormal saccade (63.6%, both hypometria and hypermetria) than that of PD patients and controls (33.3%, 7.5%, respectively, hypometria) (p < .05). The SPM test showed PD patients had mildly decreased gain among whom 28.1% presenting “saccade intrusions”; and that MSA patients had the significant decreased gain with 51.5% presenting “catch‐up saccades”(p < .05). Only MSA patients showed gaze‐evoked nystagmus (24.2%), square‐wave jerks (6.1%) in gaze‐holding test (p < .05).ConclusionsA panel of eye movements tests may help to differentiate PD from MSA. The combined presence of hypometria and hypermetria in saccadic eye movement, the impaired gain of smooth pursuit movement with “catch‐up saccades,” gaze‐evoked nystagmus, square‐wave jerks in gaze‐holding test, and multiple‐step pattern in MGS may provide clues to the diagnosis of MSA.

Early atypical signs and insula hypometabolism predict survival in multiple system atrophy

ObjectiveWe aim to search for predictors of survival among clinical and brain 18F-FDG positron emission tomography (PET) metabolic features in our cohort of patients with multiple system atrophy (MSA).MethodsWe included...

Laboratory-Supported Multiple System Atrophy beyond Autonomic Function Testing and Imaging: A Systematic Review by the MoDiMSA Study Group.

Neuroimaging has been used to support a diagnosis of possible multiple system atrophy (MSA). Only blood pressure changes upon standing are included in the second consensus criteria but other autonomic function tests (AFT) are also useful to diagnose widespread and progressive autonomic failure typical of MSA. Additional diagnostic tools are of interest to improve accuracy of MSA diagnosis. To assess the utility of diagnostic tools beyond brain imaging and AFT in enhancing a laboratory-supported diagnosis of MSA to support the upcoming revision of the consensus criteria. The International Parkinson and Movement Disorders Society MSA Study Group (MoDiMSA) performed a systematic review of original papers on biomarkers, sleep studies, genetic, neuroendocrine, neurophysiological, neuropsychological and other tests including olfactory testing and acute levodopa challenge test published before August 2019. Evaluation of history of levodopa responsiveness and olfaction is useful in patients in whom MSA-parkinsonian subtype is suspected. Neuropsychological testing is useful to exclude dementia at time of diagnosis. Applicability of sphincter EMG is limited. When MSA-cerebellar subtype is suspected, a screening for the common causes of adult-onset progressive ataxia is useful, including spinocerebellar ataxias in selected patients. Diagnosing stridor and REM sleep behavior disorder is useful in both MSA subtypes. However, none of these tools are validated in large longitudinal cohorts of postmortem confirmed MSA cases. Despite limited evidence, additional laboratory work-up of patients with possible MSA beyond imaging and AFT should be considered to optimize the clinical diagnostic accuracy.

Cognitive Profile and Its Evolution in a Cohort of Multiple System Atrophy Patients

Introduction: Cognitive decline is not a characteristic feature of multiple system atrophy (MSA), but recent evidence suggests cognitive impairment as an integral part of the disease. We aim to describe the cognitive profile and its progression in a cohort of patients with MSA.Methods: We retrospectively selected patients referred to our department with a clinical diagnosis of MSA who were evaluated at least once a year during the course of the disease and underwent a comprehensive neuropsychological evaluation.Results: At the first evaluation (T0), 37 out of 60 patients (62%) were cognitively impaired, mainly (76%) in attention and executive functioning. Thirteen patients were impaired in one cognitive domain and 24 in more than one cognitive domain. Six out of the 24 had dementia. Twenty patients underwent a follow-up evaluation (T1) after a mean of 16.6 ± 9.3 months from the first evaluation (T0). Eight out of 20 patients were cognitively normal at both T0 and T1. Seven out of 12 patients presented with stable cognitive impairment at T1, while cognitive decline progressed in five patients. Patients with progression in cognitive decline performed significantly worse at T0 than cognitively stable patients. Education was significantly different between patients with and without cognitive impairment. No other differences in demographic and clinical variables and autonomic or sleep disturbances were found. Patients with dementia were older at disease onset and at T0 and had lower education and disease duration at T0 compared to those in other groups.Conclusions: In patients with MSA, we observed three different cognitive profiles: normal cognition, stable selective attention-executive deficits, and progressive cognitive deficits evolving to dementia. The detection of cognitive impairment in patients with suspected MSA suggests the need for comprehensive and longitudinal neuropsychological evaluation.

Application of bulbocavernosus reflex combined with anal sphincter electromyography in the diagnosis of MSA and PD

Background Multiple system atrophy (MSA) and Parkinson's disease (PD) are characterized by abnormal changes in the extrapyramidal system and autonomic nervous system. The two diseases are consistent in some clinical manifestations and few objective indicators for preclinical prediction. Method The value of anal sphincter electromyography (EAS-EMG) in the diagnosis of MSA has been recognized by researchers, while the bulbocavernosus reflex (BCR) has been found to be of great significance in the diagnosis of PD and MSA. In this study, the diagnostic value of BCR combined with EAS-EMG in patients with MSA and PD was further discussed. Results Forty-three patients with MSA, 120 patients with PD and 40 normal controls were recruited, and the BCR and EAS-EMG were evaluated. The average duration, average amplitude, percentage of polyphasic waves, satellite potential, phase pattern and amplitude of strong contraction were observed. The results showed that the abnormal rate of BCR in the control group was 0%, and the abnormal rate of EAS-EMG was 2.5%; these differences were statistically significant compared with the MSA group (BCR 90.9%, EAS-EMG 93.9%). For patients with PD, there were some significant differences in BCR and EAS-EMG between the control group and the PD group. Conclusion Our study revealed that BCR combined with EAS-EMG detection can provide an objective electrophysiological basis for the diagnosis of MSA and PD, which is beneficial for the early treatment of disease.

Automated Analysis of Diffusion-Weighted Magnetic Resonance Imaging for the Differential Diagnosis of Multiple System Atrophy from Parkinson's Disease.

ABSTRACTBackgroundManual region‐of‐interest analysis of putaminal and middle cerebellar peduncle diffusivity distinguishes patients with multiple system atrophy (MSA) and Parkinson's disease (PD) with high diagnostic accuracy. However, a recent meta‐analysis found substantial between‐study heterogeneity of diagnostic accuracy due to the lack of harmonized imaging protocols and standardized analyses pipelines.ObjectiveEvaluation of diagnostic accuracy of observer‐independent analysis of microstructural integrity as measured by diffusion‐tensor imaging in patients with MSA and PD.MethodsA total of 29 patients with MSA and 19 patients with PD (matched for age, gender, and disease duration) with 3 years of follow‐up were investigated with diffusion‐tensor imaging and T1‐weighted magnetic resonance imaging. Automated localization of relevant brain regions was obtained, and mean diffusivity and fractional anisotropy values were averaged within the regions of interest. The classification was performed using a C5.0 hierachical decision tree algorithm.ResultsMean diffusivity of the middle cerebellar peduncle and cerebellar gray and white matter compartment as well as the putamen were significantly increased in patients with MSA and showed superior effect sizes compared to the volumetric analysis of these regions. A classifier model identified mean diffusivity of the middle cerebellar peduncle and putamen as the most predictive parameters. Cross‐validation of the classification model yields a Cohen's κ and overall diagnostic accuracy of 0.823 and 0.914, respectively.ConclusionAnalysis of microstructural integrity within the middle cerebellar peduncle and putamen yielded a superior effect size compared to the volumetric measures, resulting in excellent diagnostic accuracy to discriminate patients with MSA from PD in the early to moderate disease stages. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Can Autonomic Testing and Imaging Contribute to the Early Diagnosis of Multiple System Atrophy? A Systematic Review and Recommendations by the Movement Disorder Society Multiple System Atrophy Study Group.

In the current consensus diagnostic criteria, the diagnosis of probable multiple system atrophy (MSA) is based solely on clinical findings, whereas neuroimaging findings are listed as aid for the diagnosis of possible MSA. There are overlapping phenotypes between MSA-parkinsonian type and Parkinson's disease, progressive supranuclear palsy, and dementia with Lewy bodies, and between MSA-cerebellar type and sporadic adult-onset ataxia resulting in a significant diagnostic delay and misdiagnosis of MSA during life. In light of an ongoing effort to revise the current consensus criteria for MSA, the Movement Disorders Society Multiple System Atrophy Study Group performed a systematic review of original articles published before August 2019. We included articles that studied at least 10 patients with MSA as well as participants with another disorder or control group for comparison purposes. MSA was defined by neuropathological confirmation, or as clinically probable, or clinically probable plus possible according to consensus diagnostic criteria. We discuss the pitfalls and benefits of each diagnostic test and provide specific recommendations on how to evaluate patients in whom MSA is suspected. This systematic review of relevant studies indicates that imaging and autonomic function tests significantly contribute to increasing the accuracy of a diagnosis of MSA.

Comparison of Neuropathological Characteristics between Multiple System Atrophy Cerebellar Type and Parkinsonian Type

Background: Multiple system atrophy (MSA) is a sporadic neurodegenerative disease characterized by various combinations of parkinsonism, cerebellar ataxia, autonomic dysfunction and pyramidal signs. Two clinical subtypes are recognized: MSA with predominant cerebellar ataxia (MSA-C) and MSA with predominant parkinsonism (MSA-P). The aim of this study was to compare pathological features between MSA-C and MSA-P.Methods: Two autopsy confirmed cases with MSA were included from the Pusan National University Hospital Brain Bank. Case 1 had been clinically diagnosed as MSA-C and case 2 as MSA-P. The severity of neuronal loss and gliosis as well as the glial and neuronal cytoplasmic inclusions were semiquantitatively assessed in both striatonigral and olivopontocerebellar regions. Based on the grading system, pathological phenotypes of MSA were classified as striatonigral degeneration (SND) predominant (SND type), olivopontocerebellar degeneration (OPC) predominant (OPC type), or equivalent SND and OPC pathology (SND=OPC type).Results: Both cases showed widespread and abundant α-synuclein positive glial cytoplasmic inclusions in association with neurodegenerative changes in striatonigral or olivopontocerebellar structures, leading to the primary pathological diagnosis of MSA. Primary age-related tauopathy was incidentally found but Lewy bodies were not in both cases. The pathological phenotypes of MSA were MSA-OPC type in case 1 and MSA-SND=OPC type in case 2.Conclusions: Our data suggest that clinical phenotypes of MSA reflect the pathological characteristics.

Sacral Reflex Characteristics of Patients with Multiple System Atrophy.

Objectives To observe and analyze the parameters of the sacral reflex and pudendal nerve somatosensory evoked potential (SSEP) in patients with multiple system atrophy (MSA) with respect to factors such as age, disease course, and subtype and provide evidence for the clinical diagnosis of MSA. Materials and Methods A total of 51 MSA patients and 30 healthy controls were selected from the First Affiliated Hospital of Wenzhou Medical University from May 2013 to November 2015. Electrophysiological sacral reflex detection and SSEP detection were performed using the Keypoint EMG/EP system. The extraction rate, latency, and amplitude of the sacral reflex and SSEP in the MSA group and control group were compared. Results The sacral reflex latency and amplitude in patients with MSA were statistically different from those of the healthy controls. The latency of sacral reflex increases with the prolongation of the disease course, and the amplitude and initiation rate decrease with the prolongation of the disease course. There was no significant difference in sacral reflex latency and amplitude between MSA patients of different ages and subtypes. There was no significant difference in the latency or amplitude of SSEP between the MSA group and healthy control group. Conclusions The latency of sacral reflex increases with the prolongation of the disease course, and the amplitude and extraction rate decrease with the prolongation of the disease course. There was no significant difference in the parameters of sacral reflex between young MSA patients and elderly patients. And there was no statistically significant difference between MSA-P subtypes and MSA-C subtypes. This trial is registered with ISRCTNCR2009041.

Orofacial dystonia and asssociated bulbar symptoms in multiple system atrophy: A blinded video analysis

BackgroundOrofacial dystonia (OFD) is considered a supporting feature for a diagnosis of Multiple System Atrophy (MSA). However, the association of OFD with other adjacent symptoms has not been explored. ObjectivesTo identify clinical characteristics of OFD and associated bulbar symptoms in MSA patients. MethodsIn this blinded trial, video clips of 24 MSA patients were reviewed by two movement disorder neurologists who rated the presence of OFD. Analysis was performed to determine correlations between the presence of OFD and clinical demographics as well as associated bulbar symptoms. ResultsThere were 14 patients with MSA-P and 10 patients with MSA-C. OFD was identified in seven patients (29.16%) and MSA-P as the majority (85.71%). Oromandibular dystonia (OMD) was hardly ever identified in isolation with the most frequent combination being OMD with upper facial dystonia, blepharospasm and platysma dystonia. All OMD patients had the jaw-closing subtype. Mean onset of OFD was 1.7 (SD = 0.5) years after the first symptom onset and 1.1 years (SD = 0.4) after the introduction of levodopa. Patients with OFD used significantly higher levodopa equivalent daily dosage (LEDD) than those without (p = 0.02). There were moderate correlations between the presence of OFD and LEDD (r = 0.458, p = 0.02), and dysarthria (r = 0.639, p = 0.001) while a strong correlation was demonstrated between the presence of OFD and dysphagia (r = 0.9, p < 0.001). ConclusionOFD is probably a manifestation of motor fluctuations in MSA and its presence is significantly associated with bulbar symptoms. Neurologists should inquire about dysphagia when encountering MSA patients with OFD for early recognition and appropriate management.