Altered white matter microarchitecture in amyotrophic lateral sclerosis: A voxel-based meta-analysis of diffusion tensor imaging.

Feifei Zhang,Jing Dai,Zhiyun Jia,Qiyong Gong,Guangxiang Chen,Huifang Shang,Manxi He

doi:10.1016/j.nicl.2018.04.005

Abstract

BackgroundThe results of recent diffusion tensor imaging (DTI) studies on amyotrophic lateral sclerosis (ALS) are inconclusive and controversial. We performed a voxel-based meta-analysis to identify a statistical consensus among published DTI studies of altered white matter (WM) microarchitecture in ALS.MethodsA systematic search was conducted for relevant studies that used voxel-wise analyses of WM microarchitecture in patients with ALS. Anisotropic effect size-signed differential mapping (AES-SDM) was applied to analyze fractional anisotropy (FA) differences between ALS patients and healthy controls. Meta-regression analysis was used to explore the effects of clinical characteristics on WM integrity in patients with ALS.ResultsA total of 14 studies with 16 datasets that included 396 patients and 360 healthy controls were identified. The pooled meta-analysis revealed that patients with ALS exhibited significant FA reductions in two clusters relative to healthy controls. The largest cluster exhibited a peak coordinate in the left corona radiata, extending to the body and splenium of the corpus callosum, left superior longitudinal fasciculus, posterior limb of the internal capsule, right corona radiata, and bilateral cingulate gyrus. The other cluster exhibited decreased FA in the right corticospinal tract that extended to the right cerebral peduncle. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score was positively correlated with the FA reduction in the left corona radiata. Mean age and illness duration were not linearly correlated with the FA reductions.ConclusionsThis study provides a thorough profile of WM microarchitecture alterations in patients with ALS and further evidence that the neuronal degeneration is not limited to the corticospinal tract but also includes extra-motor areas, which supports the view that ALS is a multisystem degenerative disorder that involves the white matter.

Highlights

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative, age-related and predominantly male disease that may result in the progressive loss of bulbar and limb function
In one study (Trojsi et al, 2015), the amyotrophic lateral sclerosis (ALS) patients were divided into 3 groups according to clinical stage, and these groups were compared with the same healthy controls
The largest cluster exhibited a peak coordinate in the left corona radiata that extended to the body and splenium of the CC, left superior longitudinal fasciculus, posterior limb of the internal capsule, right corona radiata, and bilateral cingulate gyrus

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative, age-related and predominantly male disease that may result in the progressive loss of bulbar and limb function. We performed a voxel-based meta-analysis to identify a statistical consensus among published DTI studies of altered white matter (WM) microarchitecture in ALS. The pooled meta-analysis revealed that patients with ALS exhibited significant FA reductions in two clusters relative to healthy controls. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score was positively correlated with the FA reduction in the left corona radiata. Conclusions: This study provides a thorough profile of WM microarchitecture alterations in patients with ALS and further evidence that the neuronal degeneration is not limited to the corticospinal tract and includes extra-motor areas, which supports the view that ALS is a multisystem degenerative disorder that involves the white matter

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