Spinal Cord Atrophy Predicts Progressive Disease in Relapsing Multiple Sclerosis

Abstract

Objective A major challenge in multiple sclerosis (MS) research is the understanding of silent progression and Progressive MS. Using a novel method to accurately capture upper cervical cord area from legacy brain MRI scans we aimed to study the role of spinal cord and brain atrophy for silent progression and conversion to secondary progressive disease (SPMS). Methods From a single‐center observational study, all RRMS (n = 360) and SPMS (n = 47) patients and 80 matched controls were evaluated. RRMS patient subsets who converted to SPMS (n = 54) or silently progressed (n = 159), respectively, during the 12‐year observation period were compared to clinically matched RRMS patients remaining RRMS (n = 54) or stable (n = 147), respectively. From brain MRI, we assessed the value of brain and spinal cord measures to predict silent progression and SPMS conversion. Results Patients who developed SPMS showed faster cord atrophy rates (−2.19%/yr) at least 4 years before conversion compared to their RRMS matches (−0.88%/yr, p < 0.001). Spinal cord atrophy rates decelerated after conversion (−1.63%/yr, p = 0.010) towards those of SPMS patients from study entry (−1.04%). Each 1% faster spinal cord atrophy rate was associated with 69% (p < 0.0001) and 53% (p < 0.0001) shorter time to silent progression and SPMS conversion, respectively. Interpretation Silent progression and conversion to secondary progressive disease are predominantly related to cervical cord atrophy. This atrophy is often present from the earliest disease stages and predicts the speed of silent progression and conversion to Progressive MS. Diagnosis of SPMS is rather a late recognition of this neurodegenerative process than a distinct disease phase. ANN NEUROL 2022;91:268–281

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

“…We speculate that non-dominant hand manual dexterity may be manipulated by complementary pathways including the visual and proprioceptive systems while the dominant hand may have more robust canonical input from the corticospinal tract without a dependency on other inputs. While this effect was only observed in patients with RRMS, these data are consistent with the observation that RRMS patients who developed progressive disease showed faster cervical SC atrophy rates at least four years before conversion to progressive disease compared to those that did not progress [ 44 ]. This emphasizes the need to monitor neurodegeneration early in the RRMS disease course as a driver of clinical disability.…”

Reply to “Spinal Cord Atrophy Is a Preclinical Marker of Progressive MS”

“…13 In their cross-sectional study, Zeydan et al assessed total cord area shortly after SPMS conversion at the C2, C7, and C2-C7 levels from T2-weighted clinical protocols. In contrast to our study, 14 they did not find differences between RRMS and SPMS patients at the high cervical cord level. 15 However, cord area at the C7 level discriminated between the two groups, suggesting that caudal levels were more sensitive to disability than those in the high cervical cord, an analysis not undertaken in our study.…”

Simultaneous assessment of regional distributions of atrophy across the neuraxis in MS patients

“…While both the CSA and SPM-BSC approaches showed consistent associations with clinical impairment scales (i.e. EDSS and MSSS), the voxel-based nature of the SPM-BSC approach showed not only that voxels at the C2-C3 level were associated with the degree of impairment, but that these clusters also included the cervical C1 segment, where associations were even stronger ( Bischof et al, 2022 ). Crucially, the extent of regional atrophy was overlapping with the identified cluster revealed by the correlations, indicating its clinical validity.…”

“…thalamus) ( Eshaghi et al, 2018 ) and cord atrophy ( Eden et al, 2019 , Valsasina et al, 2012 ), is a prominent component. Its accumulation over time is associated with the accrual of disability ( Geurts et al, 2012 ), and although present in patients throughout the course of MS it is more severe in progressive MS patients and those transitioning to a progressive form of the disease ( Bischof et al, 2022 , Casserly et al, 2018 , Fisniku et al, 2008 ). However, while the clinical eloquence of spinal involvement is recognized ( Ciccarelli et al, 2019 , Kearney et al, 2015b , Kearney et al, 2014 , Lukas et al, 2015 , Rocca et al, 2017 , Schlaeger et al, 2014 ), clinical trials typically report only on neuroimaging outcome measures above the foramen magnum, such as number of brain lesions and global brain volume changes.…”