Dataset Information

Vagus Nerve Ultrasonography Helps Distinguish Multiple System Atrophy from Other Parkinsonian Syndromes.

ABSTRACT:

Background

Distinguishing multiple system atrophy from other parkinsonian syndromes is challenging.

Objectives

To evaluate vagus nerve ultrasonography for differentiating parkinsonian syndromes.

Methods

A single-center, cross-sectional, observational study assessed 85 consecutive adult patients with de novo parkinsonism between June 2020 and December 2022, using 12 MHz ultrasonography of the vagus nerve cross-sectional area.

Results

Bilateral vagus nerves were smaller in multiple system atrophy than in other parkinsonian syndromes. The area under the receiver operating characteristic curve for differentiating multiple system atrophy was 0.79 on the right side and 0.74 on the left. The cut-off values to diagnose multiple system atrophy were 0.71 and 0.86 mm² on the right and left sides, respectively, with sensitivities of 82.6% and 87.0%, specificities of 74.2% and 64.5%, positive predictive values of 54% and 47.6%, and negative predictive values of 92.0% and 93.0%.

Conclusions

Vagus nerve ultrasonography may differentiate multiple system atrophy from other parkinsonian syndromes.

SUBMITTER: Oura K

PROVIDER: S-EPMC10585973 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Vagus Nerve Ultrasonography Helps Distinguish Multiple System Atrophy from Other Parkinsonian Syndromes.

Oura Kazumasa K Yamaguchi Takashi T Nozaki Ryota R Taguchi Keita K Suzuki Yoshio Y Takahashi Kai K Takahashi Kenta K Iwaoka Kazuhiro K Takahashi Makoto M Itabashi Ryo R Maeda Tetsuya T

Movement disorders clinical practice 20230825 10

<h4>Background</h4>Distinguishing multiple system atrophy from other parkinsonian syndromes is challenging.<h4>Objectives</h4>To evaluate vagus nerve ultrasonography for differentiating parkinsonian syndromes.<h4>Methods</h4>A single-center, cross-sectional, observational study assessed 85 consecutive adult patients with de novo parkinsonism between June 2020 and December 2022, using 12 MHz ultrasonography of the vagus nerve cross-sectional area.<h4>Results</h4>Bilateral vagus nerves were smalle ...[more]

PMID: 37868925

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Project description:BackgroundParkinson's disease (PD) and multiple system atrophy (MSA) are two distinct α-synucleinopathies traditionally differentiated through clinical symptoms. Early diagnosis of MSA is problematic, and seed amplification assays (SAAs), such as real-time quaking-induced conversion (RT-QuIC), offer the potential to distinguish these diseases through their underlying α-synuclein (α-Syn) pathology and proteoforms. Currently, SAAs provide a binary result, signifying either the presence or absence of α-Syn seeds. To enhance the diagnostic potential and biological relevance of these assays, there is a pressing need to incorporate quantification and stratification of α-Syn proteoform-specific aggregation kinetics into current SAA pipelines.MethodsOptimal RT-QuIC assay conditions for α-Syn seeds extracted from PD and MSA patient brains were determined, and assay kinetics were assessed for α-Syn seeds from different pathologically relevant brain regions (medulla, substantia nigra, hippocampus, middle temporal gyrus, and cerebellum). The conformational profiles of disease- and region-specific α-Syn proteoforms were determined by subjecting the amplified reaction products to concentration-dependent proteolytic digestion with proteinase K.ResultsUsing our protocol, PD and MSA could be accurately delineated using proteoform-specific aggregation kinetics, including α-Syn aggregation rate, maximum relative fluorescence, the gradient of amplification, and core protofilament size. MSA cases yielded significantly higher values than PD cases across all four kinetic parameters in brain tissues, with the MSA-cerebellar phenotype having higher maximum relative fluorescence than the MSA-Parkinsonian phenotype. Statistical significance was maintained when the data were analysed regionally and when all regions were grouped.ConclusionsOur RT-QuIC protocol and analysis pipeline can distinguish between PD and MSA, and between MSA phenotypes. MSA α-Syn seeds induce faster propagation and exhibit higher aggregation kinetics than PD α-Syn, mirroring the biological differences observed in brain tissue. With further validation of these quantitative parameters, we propose that SAAs could advance from a yes/no diagnostic to a theranostic biomarker that could be utilised in developing therapeutics.

Project description:Multiple system atrophy (MSA) is a rare adult-onset neurodegenerative disease of unknown cause, with no effective therapeutic options, and no cure. Limited work to date has attempted to characterize the transcriptional changes associated with the disease, which presents as either predominating parkinsonian (MSA-P) or cerebellar (MSC-C) symptoms. We report here the results of RNA expression profiling of cerebellar white matter (CWM) tissue from two independent cohorts of MSA patients (n = 66) and healthy controls (HC; n = 66). RNA samples from bulk brain tissue and from oligodendrocytes obtained by laser capture microdissection (LCM) were sequenced. Differentially expressed genes (DEGs) were obtained and were examined before and after stratifying by MSA clinical sub-type. We detected the highest number of DEGs in the MSA-C group (n = 747) while only one gene was noted in MSA-P, highlighting the larger dysregulation of the transcriptome in the MSA-C CWM. Results from both bulk tissue and LCM analysis showed a downregulation of oligodendrocyte genes and an enrichment for myelination processes with a key role noted for the QKI gene. Additionally, we observed a significant upregulation of neuron-specific gene expression in MSA-C and enrichment for synaptic processes. A third cluster of genes was associated with the upregulation of astrocyte and endothelial genes, two cell types with a key role in inflammation processes. Finally, network analysis in MSA-C showed enrichment for β-amyloid related functional classes, including the known Alzheimer’s disease (AD) genes, APP and PSEN1. This is the largest RNA profiling study ever conducted on post-mortem brain tissue from MSA patients. We were able to define specific gene expression signatures for MSA-C highlighting the different stages of the complex neurodegenerative cascade of the disease that included alterations in several cell-specific transcriptional programs. Finally, several results suggest a common transcriptional dysregulation between MSA and AD-related genes despite the clinical and neuropathological distinctions between the two diseases.

Dataset Information

Vagus Nerve Ultrasonography Helps Distinguish Multiple System Atrophy from Other Parkinsonian Syndromes.

Background

Objectives

Methods

Results

Conclusions

Publications

Vagus Nerve Ultrasonography Helps Distinguish Multiple System Atrophy from Other Parkinsonian Syndromes.

Similar Datasets

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