Diffusely abnormal white matter in multiple sclerosis.

Area of Science:

• Neuroimaging
• Neuropathology
• Multiple Sclerosis Research

Background:

• Multiple Sclerosis (MS) research has historically focused on focal lesions.
• Diffusely Abnormal White Matter (DAWM) is an understudied MRI abnormality present in at least 25% of MS patients.
• DAWM exhibits poorly defined boundaries and intermediate signal intensity on specific MRI sequences.

Purpose of the Study:

• To review the identification and characteristics of DAWM in MS.
• To summarize in vivo and postmortem findings related to DAWM.
• To discuss potential pathophysiological mechanisms underlying DAWM.

Main Methods:

• Review of existing MRI studies, including proton density and T2-weighted imaging.
• Analysis of histological data from postmortem studies.
• Comparison of advanced MRI metrics between DAWM, normal-appearing white matter (NAWM), and focal lesions.

Main Results:

• DAWM is present across all MS clinical phenotypes and associated with increased lesion volume and brain volume reduction in clinically isolated syndrome.
• Advanced MRI metrics show abnormalities in DAWM greater than NAWM but less than focal lesions, affecting myelin, axons, and water content.
• Histological studies indicate primary lipid abnormalities and some axonal damage in DAWM.

Conclusions:

• DAWM is a prevalent and potentially impactful finding in MS that warrants further investigation.
• Current imaging studies on DAWM are insufficient given its prevalence.
• Larger longitudinal and quantitative imaging studies are necessary to fully characterize DAWM's significance and microstructure.