Voxel-Based Meta-Analysis of Gray Matter Abnormalities in Multiple System Atrophy

Junyu Lin,Yanbing Hou,Xinran Xu,Jing Yang,Huifang Shang

doi:10.3389/fnagi.2020.591666

Abstract

Purpose: This study aimed to identify consistent gray matter volume (GMV) changes in the two subtypes of multiple system atrophy (MSA), including parkinsonism subtype (MSA-P), and cerebellar subtype (MSA-C), by conducting a voxel-wise meta-analysis of whole brain voxel-based morphometry (VBM) studies.Method: VBM studies comparing MSA-P or MSA-C and healthy controls (HCs) were systematically searched in the PubMed, Embase, and Web of Science published from 1974 to 20 October 2020. A quantitative meta-analysis of VBM studies on MSA-P or MSA-C was performed using the effect size-based signed differential mapping (ES-SDM) method separately. A complementary analysis was conducted using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) method, which allows a familywise error rate (FWE) correction for multiple comparisons of the results, for further validation of the results.Results: Ten studies were included in the meta-analysis of MSA-P subtype, comprising 136 MSA-P patients and 211 HCs. Five studies were included in the meta-analysis of MSA-C subtype, comprising 89 MSA-C patients and 134 HCs. Cerebellum atrophy was detected in both MSA-P and MSA-C, whereas basal ganglia atrophy was only detected in MSA-P. Cerebral cortex atrophy was detected in both subtypes, with predominant impairment of the superior temporal gyrus, inferior frontal gyrus, temporal pole, insula, and amygdala in MSA-P and predominant impairment of the superior temporal gyrus, middle temporal gyrus, fusiform gyrus, and lingual gyrus in MSA-C. Most of these results survived the FWE correction in the complementary analysis, except for the bilateral amygdala and the left caudate nucleus in MSA-P, and the right superior temporal gyrus and the right middle temporal gyrus in MSA-C. These findings remained robust in the jackknife sensitivity analysis, and no significant heterogeneity was detected.Conclusion: A different pattern of brain atrophy between MSA-P and MSA-C detected in the current study was in line with clinical manifestations and provided the evidence of the pathophysiology of the two subtypes of MSA.

Highlights

Multiple system atrophy (MSA) is a sporadic disorder characterized by autonomic dysfunction in combination with parkinsonism and/or cerebellar ataxia
Studies were excluded if (1) there were no healthy controls (HCs); (2) the stereotactic coordinates were not available, even if we contacted the authors to ask for help; (3) the results were only reported in regions of interest (ROIs) instead of in the whole brain; (4) MSA patients were studied as one group without distinguishing MSA is categorized into parkinsonism subtype (MSA-P) or MSA-C; and (5) the study was conducted in the same center as previously published using overlapping data
The current meta-analysis revealed a different pattern of gray matter volume (GMV) reduction between the two subtypes

Summary

Introduction

Multiple system atrophy (MSA) is a sporadic disorder characterized by autonomic dysfunction in combination with parkinsonism and/or cerebellar ataxia. A number of VBM studies have been conducted to explore the gray matter volume (GMV) differences between the MSA-P/MSA-C patients and the healthy controls (HCs) recently. Some studies found cerebellum atrophy in MSA-P (Minnerop et al, 2007; Chang et al, 2009; Tzarouchi et al, 2010; Kim et al, 2015; Planetta et al, 2015), whereas some other studies did not (Brenneis et al, 2003; Tir et al, 2009; Wang et al, 2011; Shigemoto et al, 2013; Dash et al, 2019). Some studies detected supratentorial GMV reduction in MSA-C (Brenneis et al, 2006; Minnerop et al, 2007; Chang et al, 2009), while some other studies detected GMV reduction limited to the cerebellum in MSA-C (Specht et al, 2005; Dash et al, 2019)

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