Critical spinal cord lesions associate with secondary progressive motor impairment in long-standing MS: A population-based case-control study

Abstract

Background: Progressive motor impairment anatomically attributable to prominent, focally atrophic lateral column spinal cord lesions (“critical lesions”) can be seen in multiple sclerosis (MS), for example, progressive hemiparetic MS. Objective: The aim of this study was to investigate whether similar spinal cord lesions are more frequent in long-standing MS patients with secondary progressive motor impairment (secondary progressive MS (SPMS)) versus those maintaining a relapsing-remitting course (relapsing-remitting MS (RRMS)). Methods: We retrospectively identified Olmsted County (MN, USA) residents on 31 December 2011 with (1) RRMS or SPMS for ⩾25 years, and (2) available brain and spine magnetic resonance imaging (MRI). A blinded neuroradiologist determined demyelinating lesion burden and presence of potential critical lesions (prominent focally atrophic spinal cord lateral column lesions). Results: In total, 32 patients were included: RRMS, 18; SPMS, 14. Median (range) disease duration (34 (27–53) vs. 39 (29–47) years) and relapse number (4 (1–10) vs. 3 (1–15)) were similar. In comparison to RRMS, SPMS patients more commonly showed potential critical spinal cord lesions (8/18 (44%) vs. 14/14 (100%)), higher spinal cord (median (range) 4 (1–7) vs. 7.5 (3–12)), and brain infratentorial (median (range) 1 (0–12) vs. 2.5 (1–13)) lesion number; p < 0.05. By multivariate analysis, only the presence of potential critical lesions independently associated with motor progression ( p = 0.02). Conclusion: Critical spinal cord lesions may be important contributors to motor progression in MS.

Multiple sclerosis lesions and atrophy in the spinal cord: Distribution across vertebral levels and correlation with disability

“…This is compatible with an MRI study investigating the cervical cord ( Kearney et al, 2015a ) and histological studies as SC lesions primarily reflect demyelination ( Nijeholt et al, 2001 ), whereas the underlying cause of SC atrophy is less clear ( Evangelou et al, 2005 , Petrova et al, 2018 ). On the other hand, studies exist that reported a more direct relation between SC lesions and atrophy ( Pravatà et al, 2019 , Sechi et al, 2021 ). Further, simply because both measures develop over time, as underlined by the high correlation with disease duration, we expected at least some degree of correlation.…”

Visual imaging as a predictor of neurodegeneration in experimental autoimmune demyelination and multiple sclerosis

“…While the murine EAE model does not have significant brain lesions, it causes demyelinating SC lesions with some animals developing hind-limb paralysis. The spinal cord is disproportionately affected in patients with progressive MS [ 39 ] and those with lateral cord lesions [ 40 ] and focal atrophy, termed “critical” [ 41 ], are due to axonal loss within the corticospinal tract leading to paraparesis. Our results show comparable T cell infiltration, demyelination, and axonal loss in SC white matter and optic nerve during peak of EAE (15 dpi), which was accompanied by a functional delay in VEPs.…”

Oligoclonal M bands and cervical spinal cord lesions predict early secondary progressive multiple sclerosis

“…However, cervical spinal cord involvement is also associated with marked brain cortical atrophy and in a reduction of the pyramidal and cerebellar tracts, which could further accelerate the neurodegenerative process ( 11 ). In fact, some observations provide strong evidence that SC injury, rather than diffuse symmetric injury to the brain's white matter, is the major contributor to motor progression in MS ( 12 ).…”