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Multiple sclerosis. Pathology of recurrent lesions
J W Prineas1, R O Barnard, T Revesz
1Department of Veterans Affairs Medical Center, East Orange, New Jersey.
Abstract:
Recent autopsy studies suggest that remyelinated shadow plaques located in otherwise intact white matter are the outcome of a previous single episode of acute demyelination. In the present study, of 98 remyelinated plaques examined in 15 patients with multiple sclerosis who died between 27 days and 5 years after clinical onset, 15 showed evidence of a superimposed new demyelinating lesion. Inspection of old shadow plaques in a separate series of patients with subacute and long-standing multiple sclerosis revealed that such lesions sometimes exhibit punched-out areas of demyelination and gliosis similar in size and shape to fresh lesions located within or overlapping remyelinated shadow plaques. The findings support magnetic resonance imaging evidence that local recurrence may be as important or more important than progressive edge activity in determining plaque growth and the conversion of nascent lesions into classical demyelinated plaques. The findings also support experimental evidence that recurrent demyelination of the same area of white matter may be one of the factors underlying failed remyelination in multiple sclerosis.
Insights
Recurrent demyelination in multiple sclerosis (MS) white matter can cause new lesions within old plaques. This finding suggests repeated attacks, not just plaque edge growth, drive MS lesion development and failed remyelination.
Area of Science:
- Neuroscience
- Pathology
- Immunology
Background:
- Remyelinated shadow plaques in multiple sclerosis (MS) are thought to result from prior acute demyelination.
- Understanding the evolution of MS lesions is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the occurrence of new demyelination within pre-existing remyelinated plaques in multiple sclerosis (MS).
- To explore the role of recurrent demyelination in MS plaque progression and remyelination failure.
Main Methods:
- Autopsy examination of 98 remyelinated plaques from 15 multiple sclerosis (MS) patients.
- Histological analysis of shadow plaques in patients with varying disease durations.
- Comparison of fresh demyelinating lesions with areas within old shadow plaques.
Main Results:
- 15 out of 98 examined remyelinated plaques showed evidence of new demyelinating lesions.
- Old shadow plaques sometimes contained "punched-out" areas resembling fresh lesions.
- These findings align with MRI data suggesting local recurrence influences plaque growth.
Conclusions:
- Recurrent demyelination within the same white matter area is a significant factor in multiple sclerosis (MS) lesion development.
- Local lesion recurrence may be more critical than plaque edge activity in lesion expansion.
- Repeated demyelination may contribute to the failure of remyelination in MS.