Early-stage volume losses in the corpus callosum and thalamus predict the progression of brain atrophy in patients with multiple sclerosis

Abstract

A method that can be used in the early stage of multiple sclerosis (MS) to predict the progression of brain volume loss (BVL) has not been fully established. Thus, to develop a method of predicting progressive BVL in patients with MS (pwMS), eighty-two consecutive Japanese pwMS—with either relapsing-remitting MS (86%) or secondary progressive MS (14%)—and 41 healthy controls were included in this longitudinal retrospective analysisover anobservational periodof approximately 3.5 years. Using a hierarchical cluster analysis with multivariate imaging data obtained by FreeSurfer analysis, we classified the pwMS into clusters. As a result, at baseline and follow-up, pwMS were cross-sectionally classified into three major clusters (Clusters 1, 2, and 3) in ascending order by disability and BVL. Among the patients included in Cluster 1 at baseline, approximately one-third of patients (12/52) transitioned into Cluster 2 at follow-up. The volumes of thecorpus callosum, the thalamus, and the whole brain excluding the ventricles were significantly decreased in the transition group compared with the nontransition group and were found to be the most important predictors of transition. Decreased volumes of thecorpus callosum and thalamus in the relatively early stage of MS may predict the development of BVL.

Brain volume loss in Japanese patients with multiple sclerosis is present in the early to middle stage of the disease

“…In our previous study, we utilised a hierarchical cluster analysis with multivariate imaging data obtained by FreeSurfer analysis and classified cross-sectionally patients with MS into three clusters (Clusters 1, 2, and 3) in ascending order by disability and BVL at baseline [ 28 ] and follow-up [ 22 ]. Among patients included in Cluster 1 at baseline, approximately one-third of patients transitioned into Cluster 2 at follow-up.…”

“…Among patients included in Cluster 1 at baseline, approximately one-third of patients transitioned into Cluster 2 at follow-up. Baseline volumes of the corpus callosum, thalamus, and whole brain, excluding the volume of the ventricles, were significantly reduced in the transition group when compared with those in the nontransition group and were identified as the most important predictors of transition [ 22 ]. Conversely, in the current study, we found that the rate of whole-brain atrophy could be easily obtained in routine clinical practice using icobrain ms, which could be another good prognostic predictor.…”

“…Eighty-two Japanese patients with MS were retrospectively recruited from the Department of Neurology at Tohoku Medical and Pharmaceutical University Hospital, Sendai, Japan, between 2017 and 2021, as previously described [ 22 ]. The inclusion criteria were as follows [ 1 ]: MS and/or CISs as defined by the 2017 revision of the McDonald criteria [ 2 , 23 ] age between 20 and 70 years.…”

“…Thereafter, we compared the prognoses between groups with higher and lower atrophy rates and similar disease durations. Herein, we evaluated the rate of whole-brain atrophy using ico brain ms in the same cohort as that in our previous study [ 22 ], which evaluated the regional brain volumes using FreeSurfer analysis. Although our previous study has revealed that baseline volumes of the thalamus and corpus callosum early in the disease stage can predict the progression of brain atrophy in MS, quantification of these regional brain volumes requires complex methods.…”

Normative modeling of thalamic nuclear volumes

“…It serves as a relay center for primary sensory input to the cortex, facilitates movement and motor functional processing, and participates in higher cortical functions such as arousal, executive function, learning, memory, emotion, motivation, language, and multisensory integration (Schmahmann 2003). The thalamus and, specifically, its component nuclei have been implicated in several neurological, neuropsychiatric, and neurodegenerative conditions including essential tremor, multiple sclerosis, epilepsy, obsessive-compulsive disorder, schizophrenia, chronic pain syndrome, Alzheimer’s disease, and frontotemporal dementia (Neudorfer et al 2024; Fujimori and Nakashima 2024; Burdette, Patra, and Johnson 2024; Yang et al 2024; Alemán-Gómez et al 2023; Wang et al 2023; Forno et al 2023; McKenna et al 2023; Bernstein et al 2021; Low et al 2019). Until recently, the thalamus has been considered as a “whole” in most neuroimaging studies.…”