How patients with neuromyelitis optica spectrum disease accumulate disability.

Abstract

Background: It is believed that patients with neuromyelitis optica spectrum disease acquire disability exclusively through relapses. However, the possibility of disability accumulation in the absence of relapses has also been suggested. We quantified irreversible disability accumulation in the presence and absence of relapses in neuromyelitis optica spectrum disease.

Methods: We identified patients with neuromyelitis optica spectrum disease in the MSBase registry. Disability-worsening events were required to be sustained until the end of follow-up. Worsening in the absence of relapses was validated through primary record review.

Results: Over 884 patient-years of follow-up, we identified 32 disability-worsening events in 31 patients. Notably, six events (18.7%) in five patients (1.9%) occurred in the absence of relapses. A positive association was identified between relapse trajectory and the hazard of disability worsening (hazard ratio (95% credible interval): 2.36 (1.61, 3.64)), and an inverse relationship with disability worsening occurring in the absence of relapses (0.41 (0.11, 1.47)).

Conclusion: Irreversible disability worsening was rare in this proactively treated cohort of neuromyelitis optica spectrum disease patients (3.6 events per 100 patient-years). However, almost 19% of worsening occurred in the absence of relapses, reassuringly in only 2% of patients. Our findings support relapses as the principal driver of disability in neuromyelitis optica spectrum disease while also providing evidence of relapse-independent disability worsening beyond identifiable comorbidities.