Asymptomatic spinal cord lesions in Multiple Sclerosis: A systematic review and meta-analysis of subclinical disease activity

Background: Spinal cord lesions are common in Multiple Sclerosis (MS) and contribute to disability, but the frequency of new asymptomatic lesions during follow-up is uncertain. Objective: To review new asymptomatic spinal cord lesions (aSCLe), estimate the patient-level proportion developing at least one lesion, and assess isolated spinal cord activity without concomitant brain Magnetic Resonance Imaging (MRI) activity. Methods: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. PubMed, Scopus, and Web of Science were searched through May 1st, 2026 for studies reporting new aSCLe on follow-up MRI in clinically stable patients with MS (pwMS). According to the criteria used in original papers, MS stability was clinically defined most commonly as the absence of relapses, new neurological symptoms, and/or disability progression during the interval assessed; however, operational definitions varied across studies. The primary outcome was the patient-level proportion developing at least one new lesion. Comparable studies were pooled using a random-effects generalized linear mixed model (GLMM). Results: Nine studies were included in the qualitative synthesis and three in the meta-analysis (1637 patients). The pooled proportion developing at least one new asymptomatic spinal cord lesion was 13.0% (95% confidence interval 6.2–25.1; I² = 96.5%). In relapsing-remitting multiple sclerosis, the pooled estimate was 19.1% (95% confidence interval 13.2–26.7; I² = 79.1%). Isolated spinal cord activity was reported across studies but could not be pooled because of heterogeneous definitions and analytic units. Conclusions: Available evidence suggests that new asymptomatic spinal cord lesions may occur during clinically stable follow-up in a meaningful proportion of pwMS. Clinicians should recognize that spinal cord activity may be missed when surveillance relies on brain MRI alone. Standardized whole-cord protocols and patient-level reporting are needed to determine prognostic value and implications for treatment escalation.