Spinal cord atrophy significant predictor of silent progression in relapse-onset MS

WEST PALM BEACH, Fla. — Spinal cord atrophy appeared to predict silent progression in relapse-onset MS, according to results of a single-center observational study presented at ACTRIMS Forum.

“Understanding progressive disease is an important challenge in MS,” Antje Bischof, MD, of the department of neurology and institute of translational neurology at the University Hospital Münster in Germany, said during a presentation. “We know there are some patients who very early on in the disease already demonstrate disability worsening, and that is called silent progression. These patients need more aggressive treatment, and therefore it is very important to develop predictive biomarkers to be able to stratify these patients early on to more aggressive treatments.”

According to Bischof, among all radiographic measures, spinal cord atrophy has shown the strongest correlations with disability, in addition to allowing for stratification of patients who are relapsing from those who are progressing to secondary progressive disease.

In the current study, Bischof and colleagues sought to determine whether spinal cord and brain atrophy could predict silent clinical progression via a novel method to accurately capture upper cervical cord area from legacy brain MRI scans. They included 360 patients with relapsing remitting MS (RRMS), 47 with secondary progressive MS (SPMS) and 80 matched controls. They defined silent progression as onset of irreversible Expanded Disability Status Scale (EDSS) worsening based on three-strata, with confirmation over 12 months and independent from relapses. During the 12-year observation period, they compared 159 patients with RRMS who silently progressed with 147 clinically matched patients with RRMS who remained stable.

Further, Bischof and colleagues assessed previously published group assignments for silent progression based on disability worsening and relapse activity and including patients with RRMS and SPMS to avoid possible bias from splitting patients into RRMS/SPMS groups. They used brain MRI to examine the value of global and regional brain measures and spinal cord area at C1 vertebral (C1A) level for predicting silent clinical progression.

Survival analyses showed spinal cord atrophy most strongly predicted silent clinical progression, with a 1% faster spinal cord atrophy rate linked to 69% (P < .0001) shorter time to silent clinical progression. Ventricular enlargement represented the second strongest MRI metric and the strongest brain measure for predicting silent progression, with each 1% enlargement of the lateral ventricles linked to a 16% shorter time to silent clinical progression (P = .007). Sensitivity analyses that included patients with SPMS showed faster C1A atrophy rates among patients with silent clinical progression vs. those who remained stable, which excluded a potential bias resulting from RRMS/SPMS dichotomization.

“Silent progression and SPMS conversion are predominantly related to spinal cord atrophy, which also suggests that maybe the diagnosis of SPMS conversion or the course of relapsing in SPMS should maybe be redefined and reconsidered given that the neurodegenerative processes obviously start during the relapsing phase, and it is rather a continuum than a dichotomic disease course,” Bischof said.