Radiological and histopathological analysis of diffusely abnormal white matter in chronic multiple sclerosis.

Abstract

Objective: To characterize DAWM in chronic MS through advanced MRI techniques and histopathological evaluation, and to compare it with NAWM and focal white matter lesions. Study Design: Retrospective Observational study. Setting: Bajwa Trauma Centre and Teaching Hospital, Sargodha. Period: 01-10-2024 to 01-04-2025. Methods: analyzed postmortem brain tissue from 20 formalin-fixed brain slices of 10 chronic MS patients using 0.7 T and 1.5 T MRI, combined with histological staining and immunohistochemistry. Quantitative MRI parameters (T1, T2, FA, ADC, MTR) and histological markers (axonal count, myelin density, gliosis, microglial activation) were assessed and correlated. Results: DAWM showed intermediate MRI and histopathological features between NAWM and focal lesions. T1 and T2 relaxation times were significantly elevated in DAWM, while FA and MTR were reduced (p < 0.001). Histologically, DAWM exhibited 40% fewer axons and 11% lower myelin content than NAWM, but less damage than focal lesions (66% axonal loss, 22% myelin reduction). Gliosis and microglial activity were pronounced in DAWM. Strong correlations were found between imaging metrics and histological markers (T1 with axonal loss, r = 0.82; FA with myelin density, r = –0.75). Conclusion: DAWM represents a unique and chronic degenerative component of MS, distinct from both NAWM and focal lesions. Its imaging and histological profiles suggest an ongoing, diffuse process of axonal and myelin loss, with implications for disease progression and disability. Incorporating DAWM analysis into MS diagnostics could improve monitoring and treatment strategies.