MS Research Supports Long-Term Targeting of Spinal Cord Demyelination

Photo Credit: Magicmine

Researchers discovered spinal cord lesions were strongly associated with clinical disease milestones even in later stages of MS.

Research presented at ACTRIMS Forum 2024 suggests that vasculature plays a primary role in spinal cord lesion formation, and physicians should target long-term demyelination in patients with MS.

MD/PhD candidate Alex David Waldman and a team of coinvestigators sought to clarify the factors contributing to spinal cord pathology in MS.

“Spinal cord pathology is a major determinant of irreversible disability in progressive multiple sclerosis,” Mr. Waldman and colleagues wrote. “Given the lack of consensus regarding the vascular and cerebrospinal fluid contributions to spinal cord pathology, we aimed to characterize the prevalence and topography of spinal cord demyelination in a large post-mortem cohort using immunohistochemistry (IHC), the gold standard method for lesion detection.”

Observing Lesions & Inflammatory Activity

Researchers examined tissue from the cervical, thoracic, and lumbar spine regions in 119 patients with MS. They used IHC to detect proteolipid protein and characterize CD38 expression. Using mixed models and permutation-based voxelwise analysis, Mr. Waldman and colleagues evaluated lesion prevalence and topography patterns.

The team reported spinal cord lesions in 76.5% of cases. Lesions predominantly affected the cervical spine and were inflammatory in 87.9% of cases.

“Topographically, lesions consistently affected the dorsal and lateral columns with relative sparing of subpial areas in a distribution mirroring the vascular network,” Mr. Waldman and colleagues noted.

In addition, spinal cord lesions showed a strong association with clinical disease milestones, such as time from onset to wheelchair use or death.

Targeting Demyelination

Mr. Waldman and colleagues concluded that demyelination is common, highly inflammatory, and biased toward the cervical spine.

The lesions’ topography and tendency to spare subpial areas demonstrate that vasculature plays a primary role in lesion pathogenesis. This suggests “short-range cell infiltration from the blood and signaling molecules in the perivascular space are involved in lesion development,” researchers wrote.

“These findings challenge the notion that end-stage progressive multiple sclerosis is ‘burnt out’ and that diffusible factors from the cerebrospinal fluid mediate an outside-in lesional gradient in the spinal cord,” Mr. Waldman and colleagues wrote. “Taken together, this study provides support for long-term targeting of inflammatory demyelination in the spinal cord and nominates vascular dysfunction as a potential target for new therapeutic approaches to limit irreversible disability.”