Multiple System Atrophy Group Research Articles

Clinical value of video oculomotor evaluation in the differential diagnosis of multiple system atrophy and Parkinson's disease.

Multiple system atrophy (MSA) is a neurodegenerative disease that progresses rapidly and has a poor prognosis. This study aimed to assess the value of video oculomotor evaluation (VOE) in the differential diagnosis of MSA and Parkinson's disease (PD). In total, 28 patients with MSA, 31 patients with PD, and 30 age- and sex-matched healthy controls (HC) were screened and included in this study. The evaluation consisted of a gaze-holding test, smooth pursuit eye movement (SPEM), random saccade, and optokinetic nystagmus (OKN). The MSA and PD groups had more abnormalities and decreased SPEM gain than the HC group (64.29%, 35.48%, 10%, p<.001). The SPEM gain in the MSA group was significantly lower than that in the PD group at specific frequencies. Patients with MSA and PD showed prolonged latencies in all saccade directions compared with those with HC. However, the two diseases had no significant differences in the saccade parameters. The OKN gain gradually decreased from the HC to the PD and the MSA groups (p<.05). Compared with the PD group, the gain in the MSA group was further decreased in the OKN test at 30°/s (Left, p=.010; Right p=.016). Receiver operating characteristic curves showed that the combination of oculomotor parameters with age and course of disease could aid in the differential diagnosis of patients with MSA and PD, with a sensitivity of 89.29% and a specificity of 70.97%. The combination of oculomotor parameters and clinical data may aid in the differential diagnosis of MSA and PD. Furthermore, VOE is vital in the identification of neurodegenerative diseases.

Corneal confocal microscopy may help to distinguish Multiple System Atrophy from Parkinson’s disease

Multiple system atrophy (MSA) and Parkinson’s disease (PD) have clinical overlapping symptoms, which makes differential diagnosis difficult. Our research aimed to distinguish MSA from PD using corneal confocal microscopy (CCM), a noninvasive and objective test. The study included 63 PD patients, 30 MSA patients, and 31 healthy controls (HC). When recruiting PD and MSA, questionnaires were conducted on motor and non-motor functions, such as autonomic and cognitive functions. Participants underwent CCM to quantify the corneal nerve fibers. Corneal nerve fiber density (CNFD) and corneal nerve fiber length (CNFL) values in MSA are lower than PD (MSA vs. PD: CNFD, 20.68 ± 6.70 vs. 24.64 ± 6.43 no./mm2, p < 0.05; CNFL, 12.01 ± 3.25 vs. 14.17 ± 3.52 no./mm2, p < 0.05). In MSA + PD (combined), there is a negative correlation between CNFD and the Orthostatic Grading Scale (OGS) (r = −0.284, p = 0.007). Similarly, CNFD in the only MSA group was negatively correlated with the Unified Multiple System Atrophy Rating Scale I and II (r = −0.391, p = 0.044; r = −0.382, p = 0.049). CNFD and CNFL were inversely associated with MSA (CNFD: β = −0.071; OR, 0.932; 95% CI, 0.872 ~ 0.996; p = 0.038; CNFL: β = −0.135; OR, 0.874; 95% CI, 0.768–0.994; p = 0.040). Furthermore, we found the area under the receiver operating characteristic curve (ROC) of CNFL was the largest, 72.01%. The CCM could be an objective and sensitive biomarker to distinguish MSA from PD. It visually reflects a more severe degeneration in MSA compared to PD.

Multi-parametric radiomics of conventional T1 weighted and susceptibility-weighted imaging for differential diagnosis of idiopathic Parkinson’s disease and multiple system atrophy

ObjectivesThis study aims to investigate the potential of radiomics with multiple parameters from conventional T1 weighted imaging (T1WI) and susceptibility weighted imaging (SWI) in distinguishing between idiopathic Parkinson’s disease (PD) and multiple system atrophy (MSA).MethodsA total of 201 participants, including 57 patients with PD, 74 with MSA, and 70 healthy control (HCs) individuals, underwent T1WI and SWI scans. From the 12 subcortical nuclei (e.g. red nucleus, substantia nigra, subthalamic nucleus, putamen, globus pallidus, and caudate nucleus), 2640 radiomic features were extracted from both T1WI and SWI scans. Three classification models - logistic regression (LR), support vector machine (SVM), and light gradient boosting machine (LGBM) - were used to distinguish between MSA and PD, as well as among MSA, PD, and HC. These classifications were based on features extracted from T1WI, SWI, and a combination of T1WI and SWI. Five-fold cross-validation was used to evaluate the performance of the models with metrics such as sensitivity, specificity, accuracy, and area under the receiver operating curve (AUC). During each fold, the ANOVA and least absolute shrinkage and selection operator (LASSO) methods were used to identify the most relevant subset of features for the model training process.ResultsThe LGBM model trained by the features combination of T1WI and SWI exhibited the most outstanding differential performance in both the three-class classification task of MSA vs. PD vs. HC and the binary classification task of MSA vs. PD, with an accuracy of 0.814 and 0.854, and an AUC of 0.904 and 0.881, respectively. The texture-based differences (GLCM) of the SN and the shape-based differences of the GP were highly effective in discriminating between the three classes and two classes, respectively.ConclusionsRadiomic features combining T1WI and SWI can achieve a satisfactory differential diagnosis for PD, MSA, and HC groups, as well as for PD and MSA groups, thus providing a useful tool for clinical decision-making based on routine MRI sequences.

Update on [18F]ACI‐12589: a novel and promising PET tracer for a‐synuclein

AbstractBackgroundParkinson’s disease (PD) and other synucleinopathies, such as Multiple System Atrophy (MSA), involve a progressive accumulation of a‐synuclein (a‐syn) inclusions which correlate well with clinical manifestations. A PET agent capable of imaging specifically and selectively a‐syn inclusions could significantly improve differential diagnosis and clinical trials for drug candidates targeting a‐syn. Here, we report the preclinical and initial clinical characterization of [18F]ACI‐12589 in patients with different synucleinopathies.MethodLeveraging AC Immune’s proprietary small molecule Morphomer® library, compounds were optimized for affinity and specificity for pathological a‐syn as well as for selectivity versus frequent co‐pathologies, using autoradiography and radiobinding techniques. Based on these results [18F]ACI‐12589, was selected for initial clinical evaluation. PET scans were acquired for approximately 50 participants including idiopathic and genetic PD, MSA, Dementia with Lewy bodies (DLB) in addition to controls and cases from other neurodegenerative disorders (NDDs). Initial participants underwent 0‐90 min dynamic scans with arterial blood sampling allowing full kinetic modeling, while following scans were acquired as 60‐90 min static scans.ResultWhen tested on tissue sections, ACI‐12589 demonstrated a specific signal matching the distribution of pathological a‐syn. This target engagement was observed across a range of cases with different synucleinopathy diagnoses, but also in tissues from other NDDs, when a‐syn inclusions were present as co‐pathology. ACI‐12589 is selective in vitro versus frequent co‐pathologies such as amyloid‐b and Tau and has a clean off‐target profile, including for MAO‐A and B. Initial clinical data indicate that [18F]ACI‐12589 displayed substantial retention in MSA cases in expected disease‐affected brain areas based on clinical manifestations. When quantified, the signal in the cerebellar peduncles was clearly discriminating the MSA group from controls, synucleinopathy cases and other NDDs. In addition, this signal could not be blocked in vivo by the MAO‐B inhibitor Selegiline. Although to a lower level than in MSA cases, some signal retention was observed in different NDDs.Conclusion[18F]ACI‐12589 displays the preclinical and clinical characteristics deemed necessary to become a reliable and accurate PET radiotracer for the detection of a‐syn pathology in MSA. Additional evaluations of this tracer will focus on the longitudinal and early disease stage assessments.

The characteristics and alteration of peripheral immune function in patients with multiple system atrophy.

Multiple system atrophy (MSA) is a degenerative disease. Immune dysfunction found to play a crucial role in the pathogenesis of this disease in the literature, while the characteristics of peripheral immune function remain unclear. This study aimed to investigate the characteristics and alterations of peripheral immune function in patients with MSA. A case-control study was conducted between January 2021 to December 2022 at SanBo Brain Hospital, Capital Medical University, Beijing, China. A total of 74 participants were recruited, including 47 MSA patients and 27 non-MSA participants. Peripheral blood samples were collected from each participant. A total of 29 types of immune cells were measured using the flow cytometry analysis technology. Single-factor analysis and multiple-factor analysis (multiple linear regression models) were performed to determine the differences and risk factors in immune cells between the MSA and non-MSA groups. Alterations of the count or percentage of CD19+ B lymphocytes and CD3-CD56+ B lymphocytes in MSA patients were found in this study. The reductions of the count and percentage of CD19+ B lymphocytes were still robust after adjusting for variables of age, gender, body mass index, albumin, and hemoglobin. Furthermore, the reductions in the count and percentage of CD19+ B lymphocytes in the MSA patients were more significant in women and individuals aged 60 years old or above than in the non-MSA participants. Our findings suggested that MSA patients may be influenced by B lymphocytes, particularly CD19+ cells. Therefore, the reductions in immune cells should be considered in the diagnosis and treatment of MSA. Further studies are warranted to confirm and expand upon these findings.

Establishment and clinical application evaluations of a deep mining strategy of plasma proteomics based on nanomaterial protein coronas

Research on plasma proteomics has received extensive attention, because human plasma is an important sample for disease biomarker research due to its easy clinical accessibility and richness in biological information. Plasma samples contain a large number of leaked proteins from different tissues in the body, immune proteins and communication signal proteins. However, MS signal suppression from high-abundance proteins results in a large number of proteins that are present in low abundance in plasma not being detected by the LC-MS method. This situation makes it more difficult to study neurological diseases, where tissue sampling is difficult and body fluid samples such as plasma or cerebrospinal fluid are both affected by signal suppression. A large number of methods have been developed to deeply mine plasma proteomics information; however, their application limitations remain to some extent. Traditional immuno- or affinity-based depletion, fractionation and subproteome enrichment methods cannot meet the challenges of large clinical cohort applications due to limited time efficiency.In this study, a deep mining strategy of plasma proteomics was established by combing the protein corona formed by deep mining beads (DMB beads, hereafter referred to as magnetic covalent organic frameworks Fe3O4@TpPa-1), DIA-MS detection and the DIA-NN library searching method. By optimizing the enrichment step, mass spectrometry acquisition and data processing, the evaluation results of the deep mining strategy showed the following: depth, the strategy identified and quantified results of 2000+ proteins per plasma sample; stability, more than 87% of the enriched low-abundance proteins had CV < 20%; accuracy, good agreement between measured and theoretical values (1.81/2, 8.68/10, 38.36/50) for the gradient addition of E. coli proteins to a plasma sample; time efficiency, the processing time was reduced from >12h in the traditional method to <5h (incubation 30 min, washing 15 min, reductive/alkylation/digestion/desalting 4 h), and more importantly, 96 samples can be processed simultaneously in combination with the magnetic module of the automated device. The optimal strategy enables greater enrichment of neurological disease-related proteins, including SNCA and BDNF. Finally, the deep mining strategy was applied in a pilot study of multiple system atrophy (MSA) for biomarker discovery. The results showed that a total of 215 proteins were upregulated and 184 proteins were downregulated (p < 0.05) in the MSA group compared with the healthy control group. Eighteen proteins of these differentially expressed proteins were reported to be associated with neurological diseases or expressed specifically in brain tissue, 8 and 4 of which have reference concentrations of μg/L and ng/L, respectively. The alterations of ENPP2 and SLC2A1/Glut1 were reanalyzed by ELISA, further supporting the results of mass spectrometry. In conclusion, the results of the evaluation and application of the deep mining strategy showed promise for clinical research applications.

Video-oculographic Differences between Parkinson Disease and Multiple System Atrophy (P9-11.016)

<h3>Objective:</h3> With video-oculography (VOG), this study aimed to explore and compare visually-guided and self-paced volitional saccades in Parkinson’s disease (PD) and multiple system atrophy (MSA). <h3>Background:</h3> Saccades, rapid eye movements, are divided into two distinct types: reflexive and voluntary. Reflexive saccades are proceeded after a visual, auditory or somatosensory stimulus, while voluntary saccades require internally-generated drive. Each saccade is presumed to require separate neural systems. The voluntary saccades are mediated through higher centers, including frontal eye fields and basal ganglia, in addition to superior colliculus. Saccades are one of the most useful eye movements in the evaluation of the movement disorders. Voluntary saccades have been poorly investigated in PD and MSA. <h3>Design/Methods:</h3> We investigated visually guided reflexive and memory guided voluntary saccades by video-oculography in 39 PD and 15 MSA patients. There were no differences for age, sex, and UPDRS motor scores between PD and MSA patients. Two saccades were recorded sequentially, using an infrared eye tracking system (SMI, South Korea). <h3>Results:</h3> Comparison of visually-guided reflexive saccades between PD and MSA patients showed no difference in accuracy and peak velocity. In self-paced volitional saccades, PD patients produced significantly longer mean accuracy than MSA patients. Pause at the left eccentric position was consistently longer in both PD and MSA, with no statistical group difference. Volitional saccadic velocity was significantly slower than reflexive saccadic velocity in both groups. Self-paced saccadic accuracy was higher than reflexive saccadic accuracy only in PD, with significant difference. MSA patients did not show significant differences of accuracy between two saccades, although mean accuracy tended to be decreased in volitional saccades paradigm. <h3>Conclusions:</h3> In both PD and MSA patients, saccadic eye movements driven by memory-guided voluntary effort had much slower velocity, compared to visually-guided reflexive saccades. PD patients showed hypermetric volitional saccades, meanwhile MSA groups had no difference in accuracy between two saccades. <b>Disclosure:</b> Ms. Kim has nothing to disclose. Dr. Kim has nothing to disclose. Dr. Kim has nothing to disclose. Dr. Chang has nothing to disclose. Kee Duk Park has nothing to disclose. Dr. Yun has nothing to disclose.

Quick computer aided differential diagnostics based on repetitive finger tapping in Parkinson’s disease and atypical parkinsonisms

BackgroundParkinson's disease (PD) is the second most common neurodegenerative disorder whose prevalence rises with age, yet clinical diagnosis is still a challenging task due to similar manifestations of other neurodegenerative movement disorders. In untreated patients or those with unclear responses to medication, correct percentages of early diagnoses go as low as 26%. Technology has been used in various forms to facilitate discerning between persons with PD and healthy individuals, but much less work has been dedicated to separating PD and atypical parkinsonisms. MethodsA wearable system was developed based on inertial sensors that capture the movements of fingers during repetitive finger tapping. A k-nearest-neighbor classifier was used on features extracted from gyroscope recordings for quick aid in differential diagnostics, discerning patients with PD, progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and healthy controls (HC). ResultsThe overall classification accuracy achieved was 85.18% in the multiclass setup. MSA and HC groups were the easiest to discern (100%), while PSP was the most elusive diagnosis, as some patients were incorrectly assigned to MSA and HC groups. ConclusionsThe system shows potential for use as a tool for quick diagnostic aid, and in the era of big data, offers a means of standardization of data collection that could allow scientists to aggregate multi-center data for further research.

Value of electrophysiological indicators in differential diagnosis of parkinson's disease and multiple system atrophy

BackgroundWe evaluated the value of electrophysiological indicators by external anal sphincter electromyography (EAS-EMG), sympathetic skin response (SSR), R-R interval variation (RRIV), and Bulbocavernosus Reflex (BCR) in differential diagnosis of multiple system atrophy (MSA) and Parkinson’s disease (PD).MethodsA total of 41 patients with MSA and 32 patients with PD were enrolled. The electrophysiological changes of autonomic dysfunction were assessed with BCR, EAS-EMG, SSR, and RRIV, and the abnormal rate of each indicator was calculated. The diagnostic value of each indicator was analyzed with ROC curve.ResultsThe incidence rate of autonomic dysfunction in MSA group was significantly higher than that in PD group (p < 0.05). The abnormal rates of BCR and EAS-EMG indicators in MSA group were higher than those in PD group (p < 0.05). The abnormal rates of SSR and RRIV indicators in MSA group and PD group were high; however, there was no significant difference between MSA and PD groups (p > 0.05). The sensitivity of BCR combined with EAS-EMG indicators in differential diagnosis of MSA and PD were 92.3% in males and 86.7% in females, respectively, and the specificity was 72.7% in males and 90% in females, respectively.ConclusionsCombined analysis of BCR and EAS-EMG has high sensitivity and specificity for differential diagnosis of MSA and PD.

Non-motor symptoms in multiple system atrophy: A comparative study with Parkinson's disease and progressive supranuclear palsy.

Non-motor symptoms (NMS) are compulsory clinical features for the clinical diagnosis of multiple system atrophy (MSA), some of which precede motor symptoms onset. To date, few studies have systematically investigated NMS in MSA and the timing of presenting NMS as the disease progresses. Clinically, MSA is difficult to be differentiated from Parkinson's disease (PD) and progressive supranuclear palsy (PSP), and the differences in NMS between MSA and PD/PSP remain unclear. The aim of this study was to compare the burden of NMS between MSA and PD/PSP and to delineate the timing of NMS presentation relative to the onset of motor symptoms in MSA. A total of 61, 87, and 30 patients with MSA, PD, and PSP, respectively, were enrolled in this study. NMS was systematically assessed in all patients using the NMS scale (NMSS), and the onset of NMS relative to the onset of motor symptoms in MSA was investigated. MSA group had higher total NMSS scores (82.15 ± 46.10) than the PD (36.14 ± 30.78) and PSP (50.30 ± 55.05) groups (p < 0.001 overall). The number distribution pattern of the NMS was significantly different among the three parkinsonian disorders (p < 0.001 overall). In total, 85.2% of patients with MSA had more than 10 NMS, which was significantly higher than PD (28.7%) and PSP (33.3%). The frequency and scores of many NMSS subdomains and symptoms were higher in MSA than in PD and PSP (all p < 0.05). Multivariate logistic regression analysis revealed that patients with fainting, lack of motivation, swallowing, and loss of sexual interest could be attributed to MSA rather than PD or PSP, while patients with loss of concentration and forgetfulness were characteristic features of PD or PSP rather than MSA. REM-sleep behavior disorder (RBD), constipation, problems having sex, and loss of sexual interest preceded the motor symptoms onset of MSA by 2.81 ± 4.51, 1.54 ± 6.32, 1.35 ± 4.70, and 0.45 ± 3.61 years, respectively. The NMS spectrum in MSA differs from that of PD and PSP. Patients with MSA have a higher NMS burden than patients with PD or PSP. RBD, constipation, problems having sex, and loss of sexual interest may become early diagnostic clinical markers of MSA.

Adjustment for theAge- and Gender-Related Metabolic Changes Improves the Differential Diagnosis of Parkinsonism.

The online version contains supplementary material available at 10.1007/s43657-022-00079-6.

Combined regional T1w/T2w ratio and voxel-based morphometry in multiple system atrophy: A follow-up study.

Several MRI techniques have become available to support the early diagnosis of multiple system atrophy (MSA), but few longitudinal studies on both MSA variants have been performed, and there are no established MRI markers of disease progression. We aimed to characterize longitudinal brain changes in 26 patients with MSA (14 MSA-P and 12 MSA-C) over a 1-year follow-up period in terms of local tissue density and T1w/T2w ratio in a-priori regions, namely, bilateral putamen, cerebellar gray matter (GM), white matter (WM), and substantia nigra (SN). A significant GM density decrease was found in cerebellum and left putamen in the entire group (10.7 and 33.1% variation, respectively) and both MSA subtypes (MSA-C: 15.4 and 33.0% variation; MSA-P: 7.7 and 33.2%) and in right putamen in the entire group (19.8% variation) and patients with MSA-C (20.9% variation). A WM density decrease was found in the entire group (9.3% variation) and both subtypes in cerebellum-brainstem (MSA-C: 18.0% variation; MSA-P: 5% variation). The T1w/T2w ratio increase was found in the cerebellar and left putamen GM (6.6 and 24.9% variation), while a significant T1w/T2w ratio decrease was detected in SN in the entire MSA group (31% variation). We found a more progressive atrophy of the cerebellum in MSA-C with a similar progression of putaminal atrophy in the two variants. T1w/T2w ratio can be further studied as a potential marker of disease progression, possibly reflecting decreased neuronal density or iron accumulation.

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

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

Serotonin Transporter Imaging in Multiple System Atrophy and Parkinson's Disease.

Both Parkinson's disease (PD) and multiple system atrophy (MSA) exhibit degeneration of brainstem serotoninergic nuclei, affecting multiple subcortical and cortical serotoninergic projections. In MSA, medullary serotoninergic neuron pathology is well documented, but serotonin system changes throughout the rest of the brain are less well characterized. To use serotonin transporter [11 C]3-amino-4-(2-dimethylaminomethyl-phenylsulfaryl)-benzonitrile positron emission tomography (PET) to compare serotoninergic innervation in patients with MSA and PD. We performed serotonin transporter PET imaging in 18 patients with MSA, 23 patients with PD, and 16 healthy controls to explore differences in brainstem, subcortical, and cortical regions of interest. Patients with MSA showed lower serotonin transporter distribution volume ratios compared with patients with PD in the medulla, raphe pontis, ventral striatum, limbic cortex, and thalamic regions, but no differences in the dorsal striatal, ventral anterior cingulate, or total cortical regions. Controls showed greater cortical serotonin transporter binding compared with PD or MSA groups but lower serotonin transporter binding in the striatum and other relevant basal ganglia regions. There were no regional differences in binding between patients with MSA-parkinsonian subtype (n=8) and patients with MSA-cerebellar subtype (n=10). Serotonin transporter distribution volume ratios in multiple different regions of interest showed an inverse correlation with the severity of Movement Disorders Society Unified Parkinson's Disease Rating Scale motor score in patients with MSA but not patients with PD. Brainstem and some forebrain subcortical region serotoninergic deficits are more severe in MSA compared with PD and show an MSA-specific correlation with the severity of motor impairments. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Quantitative susceptibility mapping and blood neurofilament light chain differentiate between parkinsonian disorders.

ObjectivesWe employed quantitative susceptibility mapping (QSM) to assess iron deposition in parkinsonian disorders and explored whether combining QSM values and neurofilament light (NfL) chain levels can improve the accuracy of distinguishing Parkinson’s disease (PD) from multiple system atrophy (MSA) and progressive supranuclear palsy (PSP).Materials and methodsForty-seven patients with PD, 28 patients with MSA, 18 patients with PSP, and 28 healthy controls (HC) were enrolled, and QSM data were reconstructed. Susceptibility values in the bilateral globus pallidus (GP), putamen (PUT), caudate nucleus (CN), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN) were obtained. Plasma NfL levels of 47 PD, 18 MSA, and 14 PSP patients and 22 HC were measured by ultrasensitive Simoa technology.ResultsThe highest diagnostic accuracy distinguishing MSA from PD patients was observed with increased susceptibility values in CN (AUC: 0.740). The susceptibility values in RN yielded the highest diagnostic performance for distinguishing PSP from PD patients (AUC: 0.829). Plasma NfL levels were significantly higher in the MSA and PSP groups than in PD and HC groups. Combining the susceptibility values in the RN and plasma NfL levels improved the diagnostic performance for PSP vs. PD (AUC: 0.904), whereas plasma NfL levels had higher diagnostic accuracy for MSA vs. PD (AUC: 0.877).ConclusionThe exploratory study indicates different patterns of iron accumulation in deep gray matter nuclei in Parkinsonian disorders. Combining QSM values with NfL levels may be a promising biomarker for distinguishing PSP from PD, whereas plasma NfL may be a reliable biomarker for differentiating MSA from PD. QSM and NfL measures appeared to have low accuracy for separating PD from controls.

Evaluation of the visual system with visual evoked potential and optical coherence tomography in patients with idiopathic Parkinson's disease and withmultiple system atrophy.

In addition to motor findings, non-motor findings including alterations in visual acuity, decrease in blink reflex, and pupil reactivity cause the impaired quality of life in idiopathic Parkinson's disease (PD) and multiple system atrophy (MSA). Our study aimed to examine possible latency and amplitude changes in pattern visual evoked potentials (pVEP) along with retinal and macular changes in optical coherence tomography (OCT) in PD and MSA groups. We also intended to investigate whether any OCT parameters could be a biomarker for Parkinson's or MSA. Our study included 50 patients with PD, 15 with MSA, and 50 healthy control subjects. All patients in the study underwent neurological and ophthalmological examination and investigations of OCT to measure the retinal and macular thickness and pVEP to assess visual pathways. When PD, MSA, and control groups were compared, a significant difference was found in all retinal thickness values in average, nasal, and superior retinal nerve fiber thickness (pRNFL), and in all macular thickness values except nasal outer and inferior outer quadrants and in ganglion cell complex (GCC) thicknesses (p < 0.05). Moreover, a significant difference was found in N75, P100, and N145 latencies and N75-P100 amplitude (p < 0.05). The thickness of both pRNFL, inner and outer macular quadrants, was thinner in the MSA group than in PD but GCC thickness was thinner in PD group. The present study compared pVEP and OCT parameters in PD and MSA groups. It was concluded that pVEP and OCT examinations were of importance in that they were easily accessible, affordable, noninvasive biomarkers that might be used in early periods and progression of the disease and in follow-up.

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.

The "Black Straight-Line Sign" in the Putamen in Diffusion-Weighted Imaging: A Potential Diagnostic MRI Marker for Multiple System Atrophy.

Background and PurposeThe diagnosis of multiple system atrophy (MSA) remains challenging in clinical practice. This study investigated the value of hypointense signals in the putamen (“black straight-line sign”) in diffusion-weighted imaging (DWI) of brain MRI for distinguishing (MSA) from Parkinson's disease (PD).MethodsWe retrospectively enrolled 30 MSA patients, 30 PD patients, and 30 healthy controls who had undergone brain MRI between 2016 and 2020. Two readers independently assessed the signal intensity of the bilateral putamen on DWI. The putaminal hypointensity was scored using 4-point visual scales. Putaminal hypointensity and the presence of a “black straight-line sign” were statistically compared between MSA and PD or healthy controls.ResultsThe mean scores of putaminal hypointensity in DWI in the MSA group were significantly higher than in both the PD (U = 315.5, P = 0.034) and healthy control groups (U = 304.0, P = 0.022). Uni- or bilateral putaminal hypointensity in DWI with a score ≥2 was identified in 53.3% (16/30), 16.7% (5/30), and 13.3% (4/30) of MSA, PD, and healthy controls, respectively, with significant differences between MSA and PD (X2 = 8.864, P = 0.003) or healthy controls (X2 = 10.800, P = 0.001). Notably, the “black straight-line sign” of the putamen was observed in 16/30 (sensitivity 53.3%) patients with MSA, while it was absent in PD and healthy controls (specificity 100%). There were no significant differences for the presence of “black straight-line sign” in the MSA-P and MSA-C groups (X2 = 0.433, P = 0.510).ConclusionThe “black straight-line sign” of the putamen in DWI of head MRIs has the potential to serve as a diagnostic marker for distinguishing MSA from PD.

Decoding the dopamine transporter imaging for the differential diagnosis of parkinsonism using deep learning

PurposeThis work attempts to decode the discriminative information in dopamine transporter (DAT) imaging using deep learning for the differential diagnosis of parkinsonism.MethodsThis study involved 1017 subjects who underwent DAT PET imaging ([11C]CFT) including 43 healthy subjects and 974 parkinsonian patients with idiopathic Parkinson’s disease (IPD), multiple system atrophy (MSA) or progressive supranuclear palsy (PSP). We developed a 3D deep convolutional neural network to learn distinguishable DAT features for the differential diagnosis of parkinsonism. A full-gradient saliency map approach was employed to investigate the functional basis related to the decision mechanism of the network. Furthermore, deep-learning-guided radiomics features and quantitative analysis were compared with their conventional counterparts to further interpret the performance of deep learning.ResultsThe proposed network achieved area under the curve of 0.953 (sensitivity 87.7%, specificity 93.2%), 0.948 (sensitivity 93.7%, specificity 97.5%), and 0.900 (sensitivity 81.5%, specificity 93.7%) in the cross-validation, together with sensitivity of 90.7%, 84.1%, 78.6% and specificity of 88.4%, 97.5% 93.3% in the blind test for the differential diagnosis of IPD, MSA and PSP, respectively. The saliency map demonstrated the most contributed areas determining the diagnosis located at parkinsonism-related regions, e.g., putamen, caudate and midbrain. The deep-learning-guided binding ratios showed significant differences among IPD, MSA and PSP groups (P < 0.001), while the conventional putamen and caudate binding ratios had no significant difference between IPD and MSA (P = 0.24 and P = 0.30). Furthermore, compared to conventional radiomics features, there existed average above 78.1% more deep-learning-guided radiomics features that had significant differences among IPD, MSA and PSP.ConclusionThis study suggested the developed deep neural network can decode in-depth information from DAT and showed potential to assist the differential diagnosis of parkinsonism. The functional regions supporting the diagnosis decision were generally consistent with known parkinsonian pathology but provided more specific guidance for feature selection and quantitative analysis.

C9ORF72 repeat expansion is not associated with atypical parkinsonism in the Serbian population

These include, among others, two forms of atypical Parkinsonism, multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). This study aimed to assess the potential role of C9orf72 repeat expansions among Serbian patients diagnosed with MSA and PSP. Genomic DNA of 44 MSA patients, 73 PSP patients, and 96 controls was extracted from peripheral blood, and normal C9orf72 alleles were analyzed by standard quantitative fluorescence polymerase chain reaction (QF-PCR) and fragment analysis. Subsequently, for all samples presenting a single allele, repeat-primed PCR was performed with two different sets of primers to avoid a false-negative result. Thirty repeats were used as a pathogenic cut-off and 20-29 repeats for the intermediate alleles. No pathological C9orf72 expansions were detected in the MSA and PSP patients nor the control subjects. In the MSA group, the most common was the allele with 2 repeats, and the largest repeat number was 14. Among PSP patients, the most common allele also had 2 repeats, while the largest detected repeat size within the normal range was 17. Also, we identified one PSP patient that had an intermediate size allele (25 repeats). We did not find correlation between the number of repeats and disease onset, age at the time of examination, or disease duration in MSA or PSP patients. Regarding family history, in PSP the sum of both allele repeats numbers was higher in patients with positive family history than in sporadic cases. The results presented in this study are the first systematic assessment of C9orf72 allele sizes among patients diagnosed with MSA and PSP in the Serbian population. Although the potential role of intermediate C9orf72 repeats in neurodegenerative disorders is still to be elucidated, our results support the current knowledge that C9orf72 repeat expansions are not associated with MSA and PSP.