Spinal cord atrophy predicted disease progression in people with relapsing multiple sclerosis (MS), a single-center observational study showed.
A 1% faster cervical cord atrophy rate was associated with 69% (P<0.0001) shorter time to silent clinical progression and a 53% (P<0.0001) shorter time to secondary progressive MS (SPMS) conversion, reported Antje Bischof, MD, of University Hospital Münster in Germany, at ACTRIMS Forum 2022, the annual meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.
"Relapse-free, insidious disability worsening -- termed silent progression -- can occur early in MS," Bischof said.
Predictive biomarkers could help stratify patients for treatment, she noted. "Among all radiographic measures, the spinal cord shows the strongest correlation with disability and discriminates progressive from relapsing-remitting subtypes," she added.
Bischof and colleagues evaluated 360 people with relapsing remitting disease (RRMS), 47 with SPMS, and 80 matched controls. RRMS patients who converted to SPMS or silently progressed during a 12-year observation period were compared with clinically matched RRMS patients who remained stable.
The researchers assessed global and regional brain measures and the upper cervical cord area at the C1 vertebral level (C1A) in scans acquired from a large prospective longitudinal cohort of MS patients.
Silent progression was defined as onset of irreversible Expanded Disability Status Scale (EDSS) worsening, confirmed over 12 months and independent from relapses. EDSS worsening was defined based on three strata: an increase by 1.5 if EDSS was 0, an increase by 1.0 if EDSS was 1.0-5.0, and an increase by 0.5 if EDSS was 5.5 or higher.
During the 12-year observation period, 147 people maintained stable RRMS, 159 people had silent progression, and 54 converted to SPMS.
Cervical cord atrophy at the C1 level was the strongest predictor of both silent clinical progression and SPMS conversion using survival analysis. Patients who developed SPMS showed faster cord atrophy rates (-2.19%/year) compared with their matched RRMS counterparts who remained stable (-0.88%/year).
The second strongest indicator of silent clinical progression was ventricular enlargement. Each 1% enlargement of the lateral ventricles was linked with a 16% shorter time to silent progression (P=0.007).
"Using a novel method to accurately capture C1A from legacy brain MRI scans, we show that silent clinical progression is predominantly associated with cervical cord atrophy," Bischof noted. "This atrophy is often present from the earliest disease stages and predicts the speed of silent progression."
More extensive findings from the study were published in Annals of Neurology. "Importantly, our findings challenge the traditional dichotomy of an RRMS and subsequent SPMS phenotype and suggest that relapse-onset MS should be considered a continuum stratified by early quantitative measures related to disability worsening, including spinal cord atrophy," the researchers wrote.
Disclosures
Bischof disclosed no relationships with industry.
Primary Source
Americas Committee for Treatment and Research in Multiple Sclerosis
Source Reference: Bischof A, et al "Spinal cord atrophy predicts silent progression in relapse-onset multiple sclerosis" ACTRIMS 2022; abstract CE2.2.
Secondary Source
Annals of Neurology
Source Reference: Bischof A, et al "Spinal cord atrophy predicts progressive disease in relapsing multiple sclerosis" Ann Neurol 2022; DOI: 10.1002/ana.26281.
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