Biologic therapy and brain atrophy in neuromyelitis optica: a Japanese-German longitudinal MRI study

BACKGROUND: Differences in brain atrophy rates between patients with aquaporin-4 IgG-positive neuromyelitis optica spectrum disorder (AQP4Ab+NMOSD) and healthy controls (HCs), as well as the impact of biologic agents (BIO) on brain atrophy, have not been fully examined. METHODS: In total, 72 patients with AQP4Ab+NMOSD identified at Chiba University Hospital or in the Berlin Registry of Neuroimmunological Entities (Chiba, 63; Berlin, 9) and 52 age-matched and sex-matched HCs (Chiba, 47; Berlin, 5) were included. Only patients without relapses between the baseline and follow-up MRI scans were included. Regional brain volumes were normalised to the intracranial volume. Patients who continuously used BIOs or non-BIO preventive treatments between the two MRI scans were assigned to the BIO or non-BIO subgroups, respectively. We applied a longitudinal combined association test to correct for MRI scanner differences. RESULTS: Patient age and the interval between MRI scans did not differ between the groups. The NMOSD group exhibited a lower whole-brain volume than the HC group at follow-up (p<0.001) and a significantly higher whole-brain atrophy rate (p=0.009). Patients with smaller subcortical grey matter (SGM) volumes at follow-up MRI exhibited greater clinical disability (ρ = -0.27, p=0.022). In the BIO subgroup, early initiation of treatment (p=0.013) and a higher relative duration of BIO exposure (p=0.028) were associated with lower annualised SGM atrophy rates. CONCLUSIONS: This study suggested progressive silent brain atrophy in patients with AQP4Ab+NMOSD and that early BIO initiation might prevent the progression of brain atrophy.