Prominent White Matter Involvement in Multiple System Atrophy of Cerebellar Type.

Jennifer Faber,Annika Spottke,Oliver Speck,Stefan Vielhaber,Ales Dudesek,Peter J Nestor,Christoph Kamm,Xueyan Jiang,Ilaria Giordano,Thomas Klockgether,Christine Kindler,Judith Machts,Lukas Scheef,Julio Acosta‐Cabronero,Emrah Düzel

doi:10.1002/mds.27987

Abstract

Sporadic degenerative ataxia patients fall into 2 major groups: multiple system atrophy with predominant cerebellar ataxia (MSA-C) and sporadic adult-onset ataxia (SAOA). Both groups have cerebellar volume loss, but little is known about the differential involvement of gray and white matter in MSA-C when compared with SAOA. The objective of this study was to identify structural differences of brain gray and white matter between both patient groups. We used magnetic resonance imaging to acquire T1-weighted images and diffusion tensor images from 12 MSA-C patients, 31 SAOA patients, and 55 healthy controls. Magnetic resonance imaging data were analyzed with voxel-based-morphometry, tract-based spatial statistics, and tractography-based regional diffusion tensor images analysis. Whole-brain and cerebellar-focused voxel-based-morphometry analysis showed gray matter volume loss in both patient groups when compared with healthy controls, specifically in the cerebellar areas subserving sensorimotor functions. When compared with controls, the SAOA and MSA-C patients showed white matter loss in the cerebellum, whereas brainstem white matter was reduced only in the MSA-C patients. The tract-based spatial statistics revealed reduced fractional anisotropy within the pons and cerebellum in the MSA-C patients both in comparison with the SAOA patients and healthy controls. In addition, tractography-based regional analysis showed reduced fractional anisotropy along the corticospinal tracts in MSA-C, but not SAOA. Although in our cohort extent and distribution of gray and white matter loss were similar between the MSA-C and SAOA patients, magnetic resonance imaging data showed prominent microstructural white matter involvement in the MSA-C patients that was not present in the SAOA patients. Our findings highlight the significance of microstructural white matter changes in the differentiation between both conditions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Highlights

Progressive ataxia frequently starts in adults without a familial background
multiple system atrophy with predominant cerebellar ataxia (MSA-C) patients, sporadic adult onset ataxia (SAOA) patients, and healthy controls did not differ with respect to age and sex distribution
Whole-brain voxel-based morphometry (VBM) did not reveal differences in gray or white matter volume between the multiple system atrophy (MSA)-C and SAOA patients, but the cerebellar gray and white matter of both patient groups were reduced when compared with healthy controls (Supporting Information Fig. 1)

Summary

Introduction

Progressive ataxia frequently starts in adults without a familial background. These patients may suffer from an acquired ataxia, such as alcoholic cerebellar degeneration or paraneoplastic cerebellar degeneration. The essential diagnostic feature of MSA is severe autonomic failure defined by orthostatic blood pressure drop of at least 30 mmHg systolic after standing from a recumbent position or urinary incontinence.[6] The second group of sporadic ataxia is clinically distinguished from MSA-C by the lasting absence of severe autonomic failure These patients have been designated as idiopathic late-onset cerebellar ataxia or sporadic adult onset ataxia (SAOA) of unknown etiology.[7,8] The few SAOA cases that have come to autopsy had degeneration restricted to the cerebellar cortex and inferior olives,[9,10] but it is not clear whether SAOA is a disease entity or rather a group of different conditions presenting with a uniform clinical syndrome of progressive cerebellar ataxia. Atrophy of the cerebellum and brainstem are common features of MSA-C and SAOA.[13,14,15,16,17,18,19,20,21,22] In addition, microstructural alterations of the white matter have been reported in previous studies in MSA-C patients.[21,22,23,24] We used multimodal imaging approach to assess structural alteration of the brain in a deeply phenotyped cohort of MSA-C and SAOA patients to identify magnetic resonance imaging (MRI) parameters that might help to differentiate both conditions

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