Quantitative cervical cord MRI in spinal muscular atrophy: a sensitive imaging biomarker of disease evolution and treatment.

Background: Nusinersen is an approved disease-modifying therapy for spinal muscular atrophy (SMA), a rare neuromuscular disease characterized by degeneration of alpha motor neurons in the brainstem and spinal cord (SC), leading to progressive muscle atrophy and weakness. This exploratory study investigated the potential of quantitative SC magnetic resonance imaging (MRI) as a biomarker for monitoring treatment-related changes in pediatric and adult SMA patients treated with nusinersen at different disease stages.

Methods: Five pediatric and three adult SMA patients underwent clinical assessments, including the Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM), along with SC MRI at multiple time points (TPs) during nusinersen treatment. At each TP, total cross-sectional area (TCA), grey matter area (GM_area), and magnetization transfer saturation (MT_sat) were measured at multiple cervical SC levels.

Results: All pediatric patients showed a progressive increase in SC TCA and GM_area over time, paralleled by improvements in HFMSE and RULM scores. In contrast, adult patients exhibited stable SC MRI measures with modest functional gains. MT_sat values remained largely stable across time points, with a mild decrease observed at TP5. TCA and GM_area showed positive association trends with clinical scales.

Conclusion: Nusinersen showed beneficial effects in both adult and pediatric SMA patients, with more marked improvements in children. Quantitative SC MRI metrics, especially TCA and GM_area, reflected clinical trends and may serve as non-invasive biomarkers for monitoring treatment effects, pending validation in larger cohorts.