Brain volumetry and spinal cord imaging in patients with AQP4-IgG+ NMOSD-a systematic review and meta-analysis.

BACKGROUND

Magnetic resonance imaging (MRI) is often used to evaluate disease-related brain changes in patients with aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD).

OBJECTIVES

To use a meta-analysis for assessment of quantitative volumetric brain and spinal cord changes in patients with AQP4-IgG+ NMOSD and healthy participants.

DESIGN

We analyzed volume estimates of the brain, gray matter, white matter, thalamus, T2/FLAIR-brain lesions, as well as mean upper cervical cord area (MUCCA). Inclusion criteria included patients with AQP4-IgG+ NMOSD, MRI-based segmentation data, and matched healthy participants. Data from NMOSD patients with mixed/unknown serostatus or significant comorbidities were excluded.

DATA SOURCES: We searched MEDLINE through Pubmed for peer-reviewed articles published between 05/2006 (revised NMOSD diagnostic criteria) and 01/2025.

METHODS

Standardized mean differences and pooled effect sizes (Hedges' g) were determined with random-effects models, adjusting for duplicate reporting, outliers, and small study effects. Metaregressions were used to determine clinical associations.

RESULTS

Evidence of pooled data showed that whole brain volume (g = -0.61, 95% confidence interval (CI): -0.91 to -0.32, p < 0.001, N pat/con = 385/325, k = 11) and gray matter volume (g = -0.40, 95% CI: -0.72 to -0.09, p = 0.018, N pat/con = 259/267, k = 9) were significantly different between patients and healthy participants. Heterogeneity was moderate (τ² = 0.08 and τ² = 0.09, respectively). Moreover, we found a large effect for reduced MUCCA (g = -0.99, 95% CI: -1.59 to -0.39, p = 0.007, N pat/con = 189/162, k = 7) with moderate heterogeneity (τ² = 0.31). No conclusive evidence emerged for changes in thalamic or white matter volume. Bias analysis did not indicate that smaller studies affected effect sizes. A systematic review of voxel-based morphometry revealed that reduced gray matter volume was most likely in the bilateral thalamus (⩽69%) and occipital (44%), frontal (27%), and temporal cortices (27%).

CONCLUSION

AQP4-IgG+ NMOSD patients have specific global and local central nervous system volume reductions, potentially induced by astrocytic damage and demyelination. Volumetric outcomes may therefore inform MRI-guided disease monitoring and endpoints in clinical studies.

TRIAL REGISTRATION: PROSPERO (CRD42024493121). This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines.