Higher longitudinal brain white matter atrophy rate in aquaporin-4 IgG-positive NMOSD compared with healthy controls

Abstract

We aimed to compare longitudinal brain atrophy in patients with neuromyelitis optica spectrum disorder (NMOSD) with healthy controls (HCs). The atrophy rate in patients with anti-aquaporin-4 antibody-positive NMOSD (AQP4 + NMOSD) was compared with age-sex-matched HCs recruited from the Japanese Alzheimer's Disease Neuroimaging Initiative study and another study performed at Chiba University. Twenty-nine patients with AQP4 + NMOSD and 29 HCs were enrolled in the study. The time between magnetic resonance imaging (MRI) scans was longer in the AQP4 + NMOSD group compared with the HCs (median; 3.2 vs. 2.9 years, P = 0.009). The annualized normalized white matter volume (NWV) atrophy rate was higher in the AQP4 + NMOSD group compared with the HCs (median; 0.37 vs. - 0.14, P = 0.018). The maximum spinal cord lesion length negatively correlated with NWV at baseline MRI in patients with AQP4 + NMOSD (Spearman's rho = - 0.41, P = 0.027). The annualized NWV atrophy rate negatively correlated with the time between initiation of persistent prednisolone usage and baseline MRI in patients with AQP4 + NMOSD (Spearman's rho = - 0.43, P = 0.019). Patients with AQP4 + NMOSD had a greater annualized NWV atrophy rate than HCs. Suppressing disease activity may prevent brain atrophy in patients with AQP4 + NMOSD.

Figure 1

Flow chart and study design showing enrolment and age-sex-matching of patients with AQP4 + NMOSD and HCs. AQP4 + NMOSD anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders, HCs healthy controls. Chiba-HCs means another study performed in Chiba University by Shimizu et al.

Figure 2

Brain volume changes and disease duration in each patient with AQP4 + NMOSD. (A) NBV changes and disease durations. (B) NGV changes and disease durations. (C) NWV changes and disease durations. AQP4 + NMOSD anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders, NBV normalized brain volume, NGV normalized gray matter volume, NWV normalized white matter volume.

Figure 3

The percent brain volume changes between MRI-1 and MRI-2 in patients with AQP4 + NMOSD and HCs. (A) NBV changes and follow-up durations. (B) NGV changes and follow-up durations. (C) NWV changes and follow-up durations. The black dotted lines represent brain volume changes (in percentage) for each patient. The fitted average slopes in patients with AQP4 + NMOSD and HCs are shown by the black line. AQP4 + NMOSD anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders, HCs healthy controls, NBV normalized brain volume, NGV normalized gray matter volume, NWV normalized white matter volume.

Figure 4

Correlation between brain volumes and spinal lesion cord length in patients with AQP4 + NMOSD. (A) NBV changes and maximum spinal cord lesion length. (B) NGV changes and maximum spinal cord lesion length. (C) NWV changes and maximum spinal cord lesion length. AQP4 + NMOSD anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders, NBV normalized brain volume, NGV normalized gray matter volume, NWV normalized white matter volume.

Figure 5

Correlation between persistent prednisolone usage and the annualized NWV atrophy rate in patients with AQP4 + NMOSD. (A) The annualized NWV atrophy rates and persistent prednisolone usage durations at MRI-1. (B) The annualized NWV atrophy rates and persistent prednisolone usage durations at MRI-2. AQP4 + NMOSD anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders, NWV normalized white matter volume.