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The longstanding MS lesion. A quantitative MRI and electron microscopic study
Abstract:
Important questions remain unanswered about the sequence of events leading to progressive and ultimately irreversible tissue damage in MS. This study was designed to investigate the pathological characteristics of, and function of, the blood-brain barrier within longstanding MS lesions using quantitative and Gd-DTPA enhanced MRI techniques. The ultrastructural appearances of postmortem lesions from a single, separate case of MS have been correlated with the MRI findings. Both MRI and ultrastructural analysis revealed considerable heterogeneity in the chronic lesions: some are 'closed' with no detectable extracellular water, but most are 'open' and show expansion of the extracellular space to as much as 87% of tissue area. This variable expansion probably results from differing degrees of axonal loss. Evidence of blood-brain barrier damage was found in only 17% of lesions, was less severe than that seen in acute lesions, and may result from repeated previous inflammatory insults. The findings imply progressive axonal loss in lesions as they age. It is possible that this loss is related to clinical progression of the disease.
Insights
Chronic multiple sclerosis (MS) lesions show significant tissue damage and extracellular space expansion, suggesting progressive axonal loss. This damage may correlate with long-term disease progression.
Area of Science:
- Neuroscience
- Pathology
- Radiology
Background:
- The sequence of events leading to irreversible tissue damage in multiple sclerosis (MS) remains unclear.
- Understanding chronic MS lesions is crucial for managing disease progression.
Purpose of the Study:
- To investigate the pathological characteristics of longstanding MS lesions.
- To assess blood-brain barrier function within chronic MS lesions using advanced MRI techniques.
Main Methods:
- Quantitative and Gadolinium-DTPA enhanced MRI techniques were employed.
- Ultrastructural analysis of postmortem MS lesions was correlated with MRI findings.
Main Results:
- Chronic MS lesions exhibit significant heterogeneity, with most showing expanded extracellular space (up to 87%).
- This expansion is likely due to varying degrees of axonal loss.
- Blood-brain barrier damage was observed in only 17% of lesions and was less severe than in acute lesions.
Conclusions:
- Progressive axonal loss occurs as MS lesions age.
- This age-related axonal loss may be linked to the clinical progression of multiple sclerosis.