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Cortical demyelination and diffuse white matter injury in multiple sclerosis
Alexandra Kutzelnigg1, Claudia F Lucchinetti, Christine Stadelmann
1Center for Brain Research, Medical University of Vienna, Vienna, Austria.
Brain : a Journal of Neurology
|October 19, 2005
Summary
Multiple sclerosis pathology involves focal white matter lesions and diffuse brain-wide inflammation. Chronic disease progression is linked to normal-appearing white matter injury and cortical demyelination.
Area of Science:
- Neuroscience
- Neuropathology
- Immunology
Background:
- Multiple sclerosis (MS) is characterized by focal demyelinated plaques in white matter, but these lesions do not fully account for clinical deficits.
- Global brain pathology, including normal-appearing white matter (NAWM) and cortex, is crucial for understanding MS progression.
Purpose of the Study:
- To analyze global brain pathology in multiple sclerosis (MS), focusing on NAWM and cortical changes.
- To investigate the relationship between focal lesions, diffuse white matter injury, and cortical pathology in different MS subtypes.
Main Methods:
- Quantitative morphological analysis of autopsy brain tissue from 52 MS patients (various subtypes) and 30 controls.
- Assessment of focal inflammatory demyelinating lesions, NAWM injury, cortical demyelination, and microglia activation.
Main Results:
- Active focal lesions were prominent in acute/relapsing MS.
- Diffuse NAWM injury and cortical demyelination characterized progressive MS subtypes.
- Global inflammation in the brain and meninges accompanied cortical and NAWM pathology, with minimal correlation to focal lesion load.
Conclusions:
- MS initiates as a focal CNS inflammatory disease, forming white matter plaques.
- Chronic MS involves accumulating diffuse brain-wide inflammation, leading to progressive axonal injury in NAWM and cortical demyelination.