Spinal cord grey matter pathology in multiple sclerosis

Abstract

Background: Traditionally, Multiple Sclerosis (MS) has been considered to be a predominantly white matter (WM) disease. More recent studies have revealed considerable grey matter (GM) involvement in the brain. However there is a paucity of literature examining GM pathology in the spinal cord. Objectives and methods: We use human post-mortem material to explore various aspects of spinal cord GM pathology in MS including (i) the extent and pattern of spinal cord demyelination, (ii) the relative contributions of GM and WM volume loss to spinal cord atrophy, (iii) the extent of neuronal pathology within the spinal cord and (iv) the sensitivity of post-mortem MRI for detecting spinal cord GM plaques. Results: Within the spinal cord, GM demyelination is more extensive than WM demyelination with many lesions showing a novel morphological pattern whereby the plaque borders maintain a strict respect for the GM/WM boundary. Demyelination is more extensive in the spinal cord GM than in other brain regions examined. Post-mortem MR imaging at 4.7 Tesla is highly sensitive for detecting the spinal cord GM plaques. We demonstrate substantial neuronal loss in the spinal cord in MS, observing reductions in both interneuron and motoneuron numbers. This neuronal loss occurs predominantly within GM plaques. We also observe reductions in interneuron size, both within plaques and in the myelinated GM. Despite this, we find no evidence of spinal cord GM atrophy. Conclusions: This study represents the first detailed examination of spinal cord GM involvement in MS. We demonstrate substantial GM pathology in the spinal cord, further challenging the concept that MS is a predominantly WM disease. A greater understanding of this pathology may provide important insights into MS pathogenesis and mechanisms of disability in the disease