Significance of T2 lesions in multiple sclerosis: A 13‐year longitudinal study

Objective To evaluate the relation between T2 lesions and disease severity in relapsing‐remitting multiple sclerosis (MS). Methods This article describes a 13‐year longitudinal study in 30 patients. Results Patients were 36.3 ± 6.0 years old, had MS for 6.1 ± 5.8 years, Expanded Disability Status Scale was 2.2 ± 0.8, and brain parenchymal fraction (BPF) was 0.825 ± 0.015 at study entry. At last visit, Expanded Disability Status Scale was 4.4 ± 1.95, Multiple Sclerosis Functional Composite was −0.34 ± 1.7, and BPF was 0.774 ± 0.037. Baseline T2 lesion volume correlated with the BPF of the last visit ( r = −0.66; p < 0.0001), magnetization transfer ratio (MTR) in normal‐appearing brain tissue ( r = −0.52; p = 0.004), and lesion MTR ( r = −0.76; p < 0.0001). Change in T2 lesion volume in the first 2 years correlated with BPF of the last visit ( r = −0.40; p = 0.03), normal‐appearing brain tissue MTR ( r = −0.44; p = 0.015), lesion MTR ( r = −0.46; p = 0.018), Multiple Sclerosis Functional Composite scores ( r = −0.50; p = 0.005), and Paced Auditory Serial Addition Task scores ( r = −0.52; p = 0.003). Age was a significant covariate for clinical but not magnetic resonance imaging outcomes. Interpretation T2 lesions in relapsing‐remitting MS correlate strongly with brain tissue loss and brain tissue integrity 13 years later, and with clinical disease severity, though age significantly impacts the clinical correlation. The results provide direct evidence for the disability threshold hypothesis in MS and support monitoring T2 lesions in relapsing‐remitting MS. Ann Neurol 2006