Parkinsonian Multiple System Atrophy Research Articles

Suprahyoid Tremor as an Early Feature of Multiple System Atrophy-Parkinsonism: A Case Report.

Suprahyoid Tremor as an Early Feature of Multiple System Atrophy-Parkinsonism: A Case Report.

Tilt-evoked, breathing-driven blood pressure oscillations: Independence from baroreflex-sympathoneural function

PurposeOrthostasis increases the variability of continuously recorded blood pressure (BP). Low-frequency (LF) BP oscillations (Mayer waves) in this setting are related to the vascular-sympathetic baroreflex. Mechanisms of increased high-frequency (HF) BP oscillations at the periodicity of respiration during orthostasis have received less research attention. A previously reported patient with post-neurosurgical orthostatic hypotension (OH) and vascular-sympathetic baroreflex failure had large tilt-evoked, breathing-driven BP oscillations, suggesting that such oscillations can occur independently of vascular-sympathetic baroreflex modulation. In the present study we assessed effects of orthostasis on BP variability in the frequency domain in patient cohorts with or without OH.MethodsPower spectral analysis of systolic BP variability was conducted on recordings from 73 research participants, 42 with neurogenic OH [13 pure autonomic failure, 14 Parkinson’s disease (PD) with OH, 12 parkinsonian multiple system atrophy, and 3 status post-brainstem neurosurgery] and 31 without OH (control group of 16 healthy volunteers and 15 patients with PD lacking OH), before, during, and after 5′ of head-up tilt at 90 degrees from horizontal. The data were log transformed for statistical testing.ResultsAcross all subjects, head-up tilting increased HF power of systolic BP variability (p = 0.001), without a difference between the neurogenic OH and control groups. LF power during orthostasis was higher in the control than in the OH groups (p = 0.009).ConclusionsThe results of this observational cohort study confirm those based on our case report and lead us to propose that even in the setting of vascular-sympathetic baroreflex failure orthostasis increases HF power of BP variability.

Planimetric and Volumetric Brainstem MRI Markers in Progressive Supranuclear Palsy, Multiple System Atrophy, and Corticobasal Syndrome. A Systematic Review and Meta-Analysis.

Various MRI markers-including midbrain and pons areas (Marea, Parea) and volumes (Mvol, Pvol), ratios (M/Parea, M/Pvol), and composite markers (magnetic resonance imaging Parkinsonism Indices 1,2; MRPI 1,2)-have been proposed as imaging markers of Richardson's syndrome (RS) and multiple system atrophy-Parkinsonism (MSA-P). A systematic review/meta-analysis of relevant studies aiming to compare the diagnostic accuracy of these imaging markers is lacking. Pubmed and Scopus were searched for studies with >10 patients (RS, MSA-P or CBS) and >10 controls with data on Marea, Parea, Mvol, Pvol, M/Parea, M/Pvol, MRPI 1, and MRPI 2. Cohen's d, as a measure of effect size, was calculated for all markers in RS, MSA-P, and CBS. Twenty-five studies on RS, five studies on MSA-P, and four studies on CBS were included. Midbrain area provided the greatest effect size for differentiating RS from controls (Cohen's d = -3.10; p < 0.001), followed by M/Parea and MRPI 1. MSA-P had decreased midbrain and pontine areas. Included studies exhibited high heterogeneity, whereas publication bias was low. Midbrain area is the optimal MRI marker for RS, and pons area is optimal for MSA-P. M/Parea and MRPIs produce smaller effect sizes for differentiating RS from controls.

The characteristic of nonmotor symptoms with different phenotypes and onsets in multiple system atrophy patients

ObjectivesThe characteristic of nonmotor symptoms in patients with multiple system atrophy (MSA) has varied among previous studies. The objective was to investigatethe nonmotor characteristics in MSA patients with different phenotypes, sex and different onset patterns. MethodsWe performed a retrospective review of 1492 MSA patients. All cases were evaluatedby neurologists and assessed with motormanifestations, nonmotor symptoms, auxiliary examinationand brain MRI scans. ResultsMultiple system atrophy–cerebellar ataxia (MSA-C) was the predominant phenotype in 998 patients. Average age of onset (56.8 ± 9.2 years) was earlier, the disease duration (2.4 ± 2.2 year) was shorter and brain MRI abnormalities (49.2 %) were more frequently in MSA-C (P < 0.001). Multiple system atrophy–parkinsonism (MSA-P) patients were more likely to have nonmotor symptoms. After adjusted significant parameters, urinary dysfunction (OR 1.441, 95 %CI = 1.067–1.946, P = 0.017), constipation (OR 1.482, 95 %CI = 1.113–1.973, P = 0.007), cognitive impairment (OR 1.509, 95 %CI = 1.074–2.121, P = 0.018) and drooling (OR 2.095, 95 %CI = 1.248–3.518, P = 0.005) were associated with the MSA-P phenotype. Males were more likely to have orthostatic hypotension, urinary dysfunction, sexual dysfunction, drooling and females in constipation and probable RBD. In different onset patterns, constipation (59.2 %) and probable RBD (28.4 %) were more frequently in autonomiconset pattern. ConclusionsMSA-C is the predominant phenotype in Chinese patients, while many nonmotor symptoms are more common in MSA-P phenotype. Patients with different sex and onset patterns have different nonmotor characteristics. The different clinical features identified could help the physician counseling of MSA patients more easily and more accurately.

The High Value of External Anal- and Urethral-Sphincter Electromyography in Differential Diagnosis with MSA-P, PD, and PSP.

It is a challenge to differentiate multiple system atrophy parkinsonism (MSA-P), Parkinson's disease (PD), and progressive supranuclear palsy (PSP). We aimed to explore the value of external anal-sphincter electromyography (EAS-EMG) and urethral-sphincter electromyography (US-EMG) in differential diagnosis with MSA-P, PD, and PSP. A total of 149 subjects, including 27 MSA-P, 100 PD, and 22 PSP, were recruited. The average duration and amplitude of motor unit potentials (MUPs), percentage of polyphasic MUPs, amplitude during strong contraction, and recruitment pattern during maximal voluntary contraction were recorded. The differences in EAS-EMG and US-EMG results between MSA-P, PD, and PSP were analyzed. In EAS-EMG examination, the average duration of MUPs of MSA-P was significantly longer than that of PD and PSP; the percentage of polyphasic MUPs and the ratio of simple phase and simple-mix phase of MSA-P and PSP were significantly higher than that of PD; the amplitude during strong contraction of MSA-P was significantly lower than that of PD. In US-EMG examination, the average duration of MUPs in male MSA-P was significantly longer than that in male PD and PSP; the ratio of simple phase and simple-mix phase in male MSA-P was significantly higher than that in male PD; there was no statistical difference in US-EMG indexes between male PD and PSP male. And because only one female PSP was examined, only female MSA-P and PD were compared, the average duration of MUPs in female MSA-P was significantly longer than that in female PD; the ratio of simple phase and simple-mix phase in female MSA-P was significantly higher than that in female PD. The average duration of MUPs and the ratio of the simple phase and simple-mix phase of EAS-EMG and US-EMG all can provide the basis for the differential diagnosis between MSA-P and PD. US-EMG can be used as a supplement to differentiate MSA-P from PD when EAS-EMG is limited. The only discriminating indicator between MSA-P and PSP seems to be the average duration of MUPs of EAS-EMG and US-EMG. There is still a lack of diagnostic electromyography indicators between PD and PSP.

Clinical outcomes and cognitive impairments between progressive supranuclear palsy and multiple system atrophy.

Both progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) belong to atypical parkinsonian syndromes. It is important to differentiate these diseases accurately. We compared clinical outcomes and cognitive impairments between PSP and MSA. Eighty-five MSA parkinsonism type (MSA-P) patients and 76 PSP patients participated in this research. The Montreal Cognitive Assessment (MoCA) and the mini-mental state examination (MMSE) evaluated cognitive function. MSA-P patients had a significantly higher incidence of dyskinesia, fall, urinary symptoms, and constipation, whereas patients with PSP had a higher incidence of tremor and salivation. MSA-P patients had higher MMSE and MoCA scores than PSP patients. The MMSE score showed a diagnostic cut-off score of 24.5 in PSP versus MSA-P. The MoCA score showed a diagnostic cut-off score of 20.5 in PSP versus MSA-P. In conclusion, patients with PSP had differences in the clinical outcomes and cognitive impairments compared with MSA-P patients. PSP patients had more severe cognitive deficits. The score of MMSE and MoCA could be used in distinguishing MSA-P from PSP.

Diffusion Magnetic Resonance Imaging Microstructural Abnormalities in Multiple System Atrophy: A Comprehensive Review.

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by autonomic failure, ataxia, and/or parkinsonism. Its prominent pathological alterations can be investigated using diffusion magnetic resonance imaging (dMRI), a technique that exploits the characteristics of water random motion inside brain tissue. The aim of this report was to review currently available literature on the application of dMRI in MSA and to describe microstructural abnormalities, diagnostic applications, and pathophysiological correlates. Sixty-four published studies involving microstructural investigation using dMRI in MSA were included. Widespread microstructural abnormalities of white matter were described, especially in the middle cerebellar peduncle, corticospinal tract, and hemispheric fibers. Gray matter degeneration was identified as well, with diffuse involvement of subcortical structures, especially in the putamina. Diagnostic applications of dMRI were mostly explored for the differential diagnosis between MSA parkinsonism and Parkinson's disease. Recently, machine learning algorithms for image processing and disease classification have demonstrated high diagnostic accuracy, showing potential for translation into clinical practice. To a lesser extent, clinical correlates of microstructural abnormalities have also been investigated, and abnormalities related to motor, ocular, and cognitive impairments were described. dMRI in MSA has contributed to in vivo identification of known pathological abnormalities. Translation into clinical practice of the latest advancements for the differential diagnosis between MSA and other forms of parkinsonism seems feasible. Current limitations involve the possibility of correctly diagnosing MSA in the very early stages, when the clinical diagnosis is most uncertain. Furthermore, pathophysiological correlates of microstructural abnormalities remain understudied. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dopamine transporter imaging in progressive supranuclear palsy: Severe but nonspecific to subtypes.

Previous studies with a limited sample size suggested more severe dopaminergic transporter (DAT) lesions in the striatum of progressive supranuclear palsy (PSP) than those in Parkinson's disease (PD) and multiple system atrophy-parkinsonism (MSA-P). However, few studies had taken various subtypes of PSP into consideration, making the reanalysis of DAT imaging in larger PSP cohort with various subtypes in need. To compare the dopaminergic lesion patterns of PSP with MSA-P and PD, and to explore the specific striatal subregional patterns of different PSP subtypes. 11 C-CFT positron emission tomography (PET) imaging was conducted in 83 PSP patients consisting of different subtypes, 61 patients with PD, 41 patients with MSA-P, and 43 healthy volunteers. Demographic and clinical data were compared by the chi-squared test or one-way analysis of variance. A generalized linear model was used to examine intergroup differences in tracer uptake values after adjusting for age, disease duration, and disease severity. Areas under the receiver operating characteristic curve were calculated to assess the diagnostic accuracy of subregional DAT binding patterns. The patients with PSP presented more severe DAT loss in the striatum than in PD and MSA-P, especially in caudate. In PSP, the subregional lesion was still more severe in putamen than in caudate, similar to that in PD and MSA-P. Among detailed subtypes, no significant difference was detected. The dopaminergic lesions were more severe in PSP, and no difference was detected among subtypes.

The Strengths and Obstacles in the Differential Diagnosis of Progressive Supranuclear Palsy-Parkinsonism Predominant (PSP-P) and Multiple System Atrophy (MSA) Using Magnetic Resonance Imaging (MRI) and Perfusion Single Photon Emission Computed Tomography (SPECT).

Multiple System Atrophy—Parkinsonism Predominant (MSA-P) and Progressive Supranuclear Palsy—Parkinsonism Predominant (PSP-P) are the clinical manifestations of atypical parkinsonism. Currently, there are no efficient in vivo methods available relating to neuroimaging or biochemical analysis in the examination of these entities. Among the advanced methods available, using positron emission tomography is constrained by high cost and low accessibility. In this study the authors examined patients with two types of atypical parkinsonism—MSA-P and PSP-P, which are difficult to differentiate, especially in the early years of their development. The aim of this study was to assess whether the examination of patients in the period following the early years (3–6-year duration of symptoms) could be enhanced by perfusion single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI) or evaluation of cognitive abilities. Extended examination using MRI and perfusion SPECT showed that the evaluation of the mesencephalon/pons ratio, mesencephalic volume decrease, the Magnetic Resonance Parkinsonism Index (MRPI) and frontal perfusion should be considered more feasible than screening cognitive evaluation in MSA-P and PSP-P with a 3–6-year duration of symptoms.

Long-standing multiple system atrophy-Parkinsonism with limbic and FTLD-type α-synuclein pathology.

Multiple system atrophy (MSA) is a sporadic neurodegenerative disease clinically marked by autonomic failure and variable degrees of parkinsonism and cerebellar ataxias. The average age of onset is in the sixth decade of life with a five-year survival, although fulminant and more benign courses have been described (1). The pathologic hallmark of MSA is abundant α-synuclein-positive protein aggregates within oligodendrocytes (glial cytoplasmic inclusions, GCI) and neurons (neuronal cytoplasmic inclusions, NCI, and neuronal nuclear inclusions, NNI). The density of GCIs has been correlated with disease duration and severity of neuronal loss (2). Here, we present an unusual case of MSA clinically characterized by rapid decline followed by a 20-year disease duration in a severely affected state. At autopsy, the brain showed severe gliosis and neuronal loss in a pattern characteristic of MSA. Additionally, there were atypical Pick body-like and ring-shaped α-synuclein inclusions, most prominent in limbic regions, consistent with a recently described subtype of MSA designated "atypical MSA" (3). Four different α-synuclein antibodies highlighted only scant α-synuclein-positive pathology; however, Gallyas and Campbell-Switzer silver stains identified additional GCIs most prominent in subcortical white matter. Interestingly, many of the α-synuclein-positive limbic inclusions were Gallyas-negative, while many of the Gallyas-positive inclusions were α-synuclein-negative (4). This observation of markedly disparate α-synuclein immunohistochemical versus Gallyas reactivity of MSA inclusions is unusual and could support the possibility that MSA inclusions have variable compositions, something which has been recently suggested (5).

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.

Co-registration Analysis of Fluorodopa and Fluorodeoxyglucose Positron Emission Tomography for Differentiating Multiple System Atrophy Parkinsonism Type From Parkinson's Disease.

It is difficult to differentiate between Parkinson's disease and multiple system atrophy parkinsonian subtype (MSA-P) because of the overlap of their signs and symptoms. Enormous efforts have been made to develop positron emission tomography (PET) imaging to differentiate these diseases. This study aimed to investigate the co-registration analysis of 18F-fluorodopa and 18F-flurodeoxyglucose PET images to visualize the difference between Parkinson's disease and MSA-P. We enrolled 29 Parkinson's disease patients, 28 MSA-P patients, and 10 healthy controls, who underwent both 18F-fluorodopa and 18F-flurodeoxyglucose PET scans. Patients with Parkinson's disease and MSA-P exhibited reduced bilateral striatal 18F-fluorodopa uptake (p < 0.05, vs. healthy controls). Both regional specific uptake ratio analysis and statistical parametric mapping analysis of 18F-flurodeoxyglucose PET revealed hypometabolism in the bilateral putamen of MSA-P patients and hypermetabolism in the bilateral putamen of Parkinson's disease patients. There was a significant positive correlation between 18F-flurodeoxyglucose uptake and 18F-fluorodopa uptake in the contralateral posterior putamen of MSA-P patients (rs = 0.558, p = 0.002). Both 18F-flurodeoxyglucose and 18F-fluorodopa PET images showed that the striatum was rabbit-shaped in the healthy control group segmentation analysis. A defective rabbit-shaped striatum was observed in the 18F-fluorodopa PET image of patients with Parkinson's disease and MSA-P. In the segmentation analysis of 18F-flurodeoxyglucose PET image, an intact rabbit-shaped striatum was observed in Parkinson's disease patients, whereas a defective rabbit-shaped striatum was observed in MSA-P patients. These findings suggest that there were significant differences in the co-registration analysis of 18F-flurodeoxyglucose and 18F-fluorodopa PET images, which could be used in the individual analysis to differentiate Parkinson's disease from MSA-P.

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.

Changes of Amide Proton Transfer Imaging in Multiple System Atrophy Parkinsonism Type.

Multiple system atrophy (MSA), an atypical parkinsonism of alpha-synucleinopathies, has no specific biomarker of diagnosis. According to different combinations of symptoms, MSA can be classified as parkinsonism-type MSA (MSA-P) and cerebellar-type MSA (MSA-C; Watanabe et al., 2018). Amide proton transfer (APT) imaging is by far the most studied chemical exchange saturation transfer imaging for its sensitivity to mobile protons and peptides in tissues. We hypothesize that APT imaging may be a feasible biomarker of MSA-P. Twenty MSA-P patients and 20 age-matched normal controls were enrolled in this study and underwent MR exams on a 3.0-T MR scanner. Magnetization transfer spectra at 3.5 ppm were acquired at two transverse slices of the head, including the midbrain and the basal ganglia. Mann–Whitney U test was used to compare the asymmetrical magnetization transfer ratio (MTRasym) difference between MSA-P patients and normal controls. The APT MTRasym values of MSA patients in the red nucleus (RN) (SN; P = 0.000), substantia nigra (P = 0.000), thalamus (P = 0.000), and putamen (P = 0.013) were significantly higher than those in normal controls. There was a negative correlation between APT MTRasym and the score of part III of the Unified Parkinson Disease Rating Scale (R = −0.338, P = 0.044) in the putamen, while there was a positive correlation between the APT MTRasym and the rate of motor symptom progression (R = 0.406, P = 0.017) in the RN. These findings suggest that APT MTRasym changes are found and may be of value in the diagnosis of MSA-P.

Differential Diagnosis of Multiple System Atrophy-Parkinsonism and Parkinson's Disease Using α-Synuclein and External Anal Sphincter Electromyography.

Background and aim: Discriminating multiple system atrophy-parkinsonism (MSA-P) from Parkinson's disease (PD) is challenging. We aimed to provide a new method to make an identification between MSA-P and PD by combining biofluid marker with electrophysiology marker.Methods: The XYCQ EV Enrichment KIT was applied to extract extracellular vesicles (EVs) from saliva. The levels of α-syn which included total α-syn (α- synTotal), phosphorylated-ser129 α-syn (α-synPS129) and oligomeric α-syn (α-synOlig) in EVs of saliva were tested by new developed Electrochemiluminescence (ECL) assays. We collected multi-motor unit potential (MUP) of all participants who conducted external anal sphincter electromyography (EAS-EMG). The duration, phase, amplitude and satellite potential of EAS-EMG were analyzed. The Receiver operator characteristic (ROC) curve was adopted to analyze the diagnostic utility of α-syn in EVs of saliva, EAS-EMG for MSA-P.Results: In EVs of saliva, the α-synTotal concentrations were lower in MSA-P than PD (P = 0.003). No significant difference was shown in α-synOlig and α-synPS129. α-synTotal 4.46 pg/ng distinguished MSA-P from PD with area under the curve (AUC) 0.804. Compared with PD, the duration, phase and satellite potential of EAS-EMG in MSA-P were increased (P = 0.002, 0.008, 0.001). There was no significant difference in amplitude. ROC curve showed that the duration (AUC: 0.780), phase (AUC: 0.751), and satellite potential (AUC: 0.809) had both diagnostic value for MSA-P. The combination of α-synTotal in salivary EVs and EAS-EMG (including duration, phase and satellite potential) could efficiently make a differentiation between MSA-P and PD with sensitivity of 100% and specificity of 86%. The AUC value was 0.901.Conclusion: The study suggested the combination of α-synTotal in salivary EVs and EAS-EMG could help efficiently distinguish MSA-P from PD.

Skin Biopsy May Help to Distinguish Multiple System Atrophy-Parkinsonism from Parkinson's Disease With Orthostatic Hypotension.

The differential diagnosis between multiple system atrophy parkinsonism type (MSA-P) and Parkinson's disease with orthostatic hypotension (PD+OH) is difficult because the 2 diseases have a similar clinical picture. The aim of this study is to distinguish MSA-P from PD+OH by immunostaining for abnormal phosphorylated α-synuclein at serine 129 (p-syn) in cutaneous nerves. We recruited 50 patients with parkinsonism and chronic orthostatic hypotension: 25 patients fulfilled the diagnostic criteria for MSA-P and 25 patients for PD+OH. The patients underwent a skin biopsy from the cervical area, thigh, and leg to analyze somatic and autonomic skin innervation and p-syn in skin nerves. Intraneural p-syn positivity was found in 72% of patients with MSA-P, mainly in distal skin sites. More important, p-syn deposits in MSA-P differed from PD+OH because they were mainly found in somatic fibers of subepidermal plexi, whereas scant autonomic fiber involvement was found in only 3 patients. All patients with PD+OH displayed widely distributed p-syn deposits in the autonomic skin fibers of proximal and distal skin sites, whereas somatic fibers were affected only slightly in 4 patients with PD+OH. Skin innervation mirrored p-syn deposits because somatic innervation was mainly reduced in MSA-P. Sympathetic innervation was damaged in PD+OH but fairly preserved in MSA-P. The p-syn in cutaneous nerves allows the differentiation of MSA-P from PD+OH; MSA-P mainly shows somatic fiber involvement with relatively preserved autonomic innervation; and by contrast, PD+OH displays prevalent abnormal p-syn deposits and denervation in autonomic postganglionic nerves. © 2020 International Parkinson and Movement Disorder Society.

A Case of Multiple System Atrophy-Parkinsonism Type (MSA-P) with Gait Disturbance and Posture Instability Treated with Korean Medicine

A Case of Multiple System Atrophy-Parkinsonism Type (MSA-P) with Gait Disturbance and Posture Instability Treated with Korean Medicine

Presynaptic Striatal Dopaminergic Function in Atypical Parkinsonism: A Metaanalysis of Imaging Studies.

Multiple-system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS) have signs and symptoms overlapping those of Parkinson disease (PD), complicating their clinical diagnosis. Although presynaptic dopaminergic brain imaging with PET and SPECT is clinically widely used for patients with suspected PD, the benefit of functional imaging in atypical parkinsonism syndromes remains unclear. We compared striatal presynaptic dopaminergic function in MSA parkinsonism variant (MSA-P), MSA cerebellar variant (MSA-C), PSP, CBS, and PD using combined quantitative data from all published studies. Methods: The PubMed database was searched from inception to August 2018 for the terms "dopamine" OR "dopaminergic" AND "PET" OR "SPECT" OR "SPET" and keywords related to PD, MSA, PSP, and CBS. In total, 1,711 publications were identified. PET or SPECT studies comparing patients with atypical parkinsonism to another diagnostic group (PD, MSA, PSP, or CBS) were included. Tracers for dopamine transporter (DAT), aromatic amino acid decarboxylase (AADC), or vesicular monoamine type 2 were investigated. Tracer binding data were extracted from the original articles. Heterogeneity of the data was examined using I2 statistics, and a random-effects model was used to summarize data. Hedges g was used as an estimator of effect size in group comparisons. Results are reported according to PRISMA guidelines. Results: Thirty-five studies (29 DAT, 6 AADC, no vesicular monoamine type 2 studies) with 356 MSA-P patients, 204 PSP patients, 79 CBS patients, and 62 MSA-C patients were included in the metaanalysis. Caudate nucleus and putamen DAT function was clearly lower in PSP than in PD (caudate: 34.1% difference, g = -1.08, 95% confidence interval [CI] = -1.52 to -0.64; putamen: 18.2%, g = -0.86, 95% CI = -1.50 to -0.21) and MSA-P (striatum: 31.4%, g = -0.70, 95% CI = -1.21 to -0.19) and was clearly lower in MSA-P than in MSA-C (striatum: 46.0%, g = 1.46, 95% CI = 0.23 to 2.68). Although not significant because of limited data, aromatic l-AADC results paralleled the DAT findings. Conclusion: Striatal presynaptic DAT function is clearly lower in PSP patients than in PD and MSA-P patients and is clearly lower in MSA-P patients than in MSA-C patients.

Efficacy of Parenteral Amantadine Therapy in the Treatment of Multiple System Atrophy With Predominant Parkinsonism

The aim of this study was to assess clinical response to a high-dose intravenous (IV) amantadine given for 5 consecutive days in patients with multiple system atrophy parkinsonism (MSA-P). Subjects with a diagnosis of MSA-P treated with IV amantadine were included. Patients' disease severity before and after therapy was evaluated using the Unified Multiple System Atrophy Rating Scale (UMSARS). Fourteen subjects (8 females) were included. In 10 subjects (71.4%), clinical improvement was noted. The UMSARS score after treatment decreased by 2 points (median [interquartile range, 0-3]) when compared with UMSARS score at baseline (P = 0.0020). Upon examining the walking parameter, a trend of improvement was shown (P = 0.0625) (range, 0-1 points). Neither specific demographic parameters nor occurrence of adverse effects was found to be a predictive factor for improvement. Adverse events were mild and transient except for one patient who experienced acute psychosis prompting treatment cessation, upon which psychosis resolved. Our preliminary data show that IV amantadine may be a safe and effective therapy in MSA-P. A double-blind placebo-controlled trial is needed to establish the true benefit of amantadine therapy.

Functional Variant rs3135500 in NOD2 Increases the Risk of Multiple System Atrophy in a Chinese Population.

Background: Given the overlap of clinical manifestations and pathological characteristics between Parkinson's disease (PD) and multiple system atrophy (MSA), we investigated the associations between five functional polymorphisms of nucleotide-binding oligomerization domain protein 2 (NOD2) which were associated with PD, and MSA in a Chinese population.Methods: A cohort of 431 MSA patients and 441 unrelated healthy controls (HCs) were included in the study. Five polymorphisms in NOD2, including P268S, R702W, G908R, 1007fs, and rs3135500, were genotyped. The mRNA expression of NOD2 in peripheral mononuclear cells (PBMCs) in 32 MSA patients were analyzed using RT-PCR, and the concentration of NOD2 and α-synuclein from plasma of 57 MSA patients were also measured by ELISA analysis.Results: No heterozygous or homozygous for R702W, G908R, and 1007fs were found in all the subjects. For rs3135500, differences in genotype distributions, dominant and additive genetic models, were found between MSA and HCs, and between MSA Parkinsonism (MSA-P) patients and HCs. Interestingly, patients carrying the “A” allele of rs3135500 had higher mRNA NOD2 level from PBMCs and NOD2 protein from plasma than patients without this allele (p = 0.028 and p = 0.036, respectively). In addition, we also found the concentration of NOD2 in plasma was positively correlated with the levels of NOD2 mRNA in PBMC and α-synuclein in plasma (R = 0.761 and 0.832, respectively).Conclusion: Our findings suggest that the rs3135500 variant in the NOD2 gene might increase the risk for MSA and might provide new evidence that inflammation mediated by NOD2 involved in the pathogenesis of MSA. Further association studies involving a larger number of participants, as well as functional studies, are needed to confirm our current findings.