A Case-Control Study on the Relationship Between Lesion Burden and Expanded Disability Status Scale in Aquaporin-4-Positive and Aquaporin-4-Negative Neuromyelitis Optica Spectrum Disorder Patients

Background: Although brain lesions are increasingly acknowledged as a crucial aspect of neuromyelitis optica spectrum disorder (NMOSD), their role in contributing to disability is not yet fully understood. The association between imaging characteristics and disability status holds significant clinical importance but remains underexplored due to the rarity of the disease and the limited available data. Objectives: To examine brain and spinal cord lesions in NMOSD and their relationship with the Expanded Disability Status Scale (EDSS), particularly focusing on variations of aquaporin-4 antibody status. Patients and Methods: This retrospective study analyzed patients with confirmed NMOSD from the multiple sclerosis (MS) Research Center’s neuromyelitis optica (NMO) dataset at Sina Hospital, Tehran. Demographic data, disease characteristics, EDSS scores, and aquaporin-4 (AQP4) antibody status were extracted from medical records. Brain and spinal MRIs (1.5 T) were reviewed to characterize T2/fluid attenuated inversion recovery (FLAIR) hyperintense lesions in predefined brain regions and assess spinal lesion length. Statistical analyses, including t-tests, analysis of variance (ANOVA), and chi-square tests, were performed to evaluate associations between brain lesions, AQP4 status, and EDSS. A general linear model was applied to control for spinal lesion length as a confounding factor. The significance level was considered 0.05. Results: From a total of 72 participants (male: N = 15 (20.5%), mean age = 33.38 ± 11.32), 36 (49.8%) patients were AQP4 positive. Also, 63% had T2/FLAIR hyperintense brain lesions, mainly located in the hemispheric white matter (44%) and the periependymal areas of the lateral ventricles (29%). There was a correlation between EDSS and the total number of brain lesions (P < 0.001) and with the length of cord lesions (P = 0.03). Patients who were aquaporin-4 positive showed moderate correlations between EDSS and lesions in the hemispheric white matter (P = 0.005) and the length of cord lesions (P < 0.001). Conversely, AQP4-negative patients demonstrated significant correlations with lesions in the corticospinal tract (P = 0.018) but not with the length of cord lesions. Conclusion: This study evaluated the relationship between T2/FLAIR hyperintense brain and spinal cord lesions and disability in NMOSD patients. The findings indicate that the total number of brain lesions is significantly correlated with EDSS, regardless of AQP4 status. However, lesion distribution and its impact on disability differ between AQP4-positive and AQP4-negative patients. In AQP4-positive cases, spinal cord lesion length and hemispheric white matter lesions were strongly associated with EDSS, while in AQP4-negative patients, corticospinal tract (CST) lesions showed a moderate correlation with disability. These results underscore the need to consider brain lesion burden in NMOSD disability assessment and highlight potential differences in disease mechanisms based on AQP4 status. The study’s limitations include variability in imaging protocols and the lack of advanced imaging techniques such as diffusion tensor imaging (DTI) and MR spectroscopy. Future research should focus on longitudinal assessments to clarify the role of brain lesion evolution in disability progression and explore advanced imaging biomarkers to refine prognostic models and personalized treatment strategies.