Deep Grey Matter Injury in Multiple Sclerosis: A NAIMS Consensus Statement

Daniel Ontaneda; Praneeta C. Raza; Kedar R. Mahajan; Douglas L. Arnold; Michael G. Dwyer; Susan A. Gauthier; Douglas N. Greve; Daniel M. Harrison; Roland G. Henry; David K. B. Li; Caterina Mainero; Wayne Moore; Sridar Narayanan; Jiwon Oh; Raihaan Patel; Daniel Pelletier; Alexander Rauscher; William D. Rooney; Nancy L. Sicotte; Roger Tam; Daniel S. Reich; Christina J. Azevedo


Brain. 2021;144(7):1974-1984. 

In This Article

Abstract and Introduction


Although multiple sclerosis has traditionally been considered a white matter disease, extensive research documents the presence and importance of grey matter injury including cortical and deep regions. The deep grey matter exhibits a broad range of pathology and is uniquely suited to study the mechanisms and clinical relevance of tissue injury in multiple sclerosis using magnetic resonance techniques. Deep grey matter injury has been associated with clinical and cognitive disability.

Recently, MRI characterization of deep grey matter properties, such as thalamic volume, have been tested as potential clinical trial end points associated with neurodegenerative aspects of multiple sclerosis. Given this emerging area of interest and its potential clinical trial relevance, the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative held a workshop and reached consensus on imaging topics related to deep grey matter.

Herein, we review current knowledge regarding deep grey matter injury in multiple sclerosis from an imaging perspective, including insights from histopathology, image acquisition and post-processing for deep grey matter. We discuss the clinical relevance of deep grey matter injury and specific regions of interest within the deep grey matter. We highlight unanswered questions and propose future directions, with the aim of focusing research priorities towards better methods, analysis, and interpretation of results.


Multiple sclerosis has traditionally been viewed as a white matter disease, with focal lesions resulting in neuronal injury and tissue destruction.[1,2] However, detailed neuropathological examination also reveals extensive pathology in cortical and deep grey matter (DGM).[3] While the mechanisms of DGM injury vary across structures, the net effect of this pathology can be examined in vivo using MRI. Volume loss/atrophy of the thalamus and other DGM structures has been well-documented in multiple sclerosis using MRI and is clinically relevant.[4–9] The precise mechanisms of DGM loss remain to be fully elucidated and likely represent a complex interplay between the various aspects of pathology in multiple sclerosis.

Conventional MRI can be used to measure DGM volume and lesions. However, DGM lesions are best visualized at 7 T,[10,11] are more difficult to visualize at conventional field strengths, and have even been considered a red flag for a diagnosis of multiple sclerosis.[12] Advanced techniques, such as functional MRI (fMRI), diffusion tensor MRI, relaxometry and magnetic resonance (MR) spectroscopy, can quantify additional changes in DGM structures.[13–15] With recent advances in imaging, there is an opportunity to satisfy an unmet need to fully characterize DGM injury in multiple sclerosis and develop measures for use in clinical care and research. A better understanding of the mechanisms of DGM injury will provide fundamental knowledge about the pathophysiology of multiple sclerosis and may enable more efficient clinical trial design for neuroprotective therapies.