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A comparison of the pathology of primary and secondary progressive multiple sclerosis
T Revesz1, D Kidd, A J Thompson
1Department of Neuropathology, Institute of Neurology, London, UK.
Abstract:
The dynamics of primary progressive multiple sclerosis differ from those of the more common secondary progressive form. The observation by MRI that the frequency of enhancement with gadolinium-DTPA, a marker for blood-brain barrier dysfunction, is significantly less in the primary progressive form, has led to the hypothesis that inflammation is less intense in this group. To test this, we have studied postmortem material from nine cases judged from a retrospective analysis of case notes to show clear clinical evidence of either primary progressive or secondary progressive disease. Five hundred and seventy-eight lesions were analysed. There was significantly more inflammation in secondary progressive multiple sclerosis (as judged by the frequency of perivascular cuffing and cellularity of the parenchyma) than in primary progressive disease. These observations have implications for therapeutic strategies in progressive multiple sclerosis.
Insights
Inflammation is less intense in primary progressive multiple sclerosis (PPMS) compared to secondary progressive multiple sclerosis (SPMS). Postmortem analysis of lesions revealed significantly lower inflammation markers in PPMS, impacting treatment strategies.
Area of Science:
- Neuroimmunology
- Neuropathology
- Multiple Sclerosis Research
Background:
- Primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS) exhibit distinct clinical dynamics.
- Magnetic resonance imaging (MRI) suggests reduced blood-brain barrier dysfunction in PPMS, hypothesizing lower inflammatory activity.
- Understanding inflammatory differences is crucial for targeted therapeutic strategies in progressive multiple sclerosis.
Purpose of the Study:
- To investigate and compare the inflammatory status of lesions in postmortem brain tissue from patients with PPMS and SPMS.
- To determine if reduced MRI enhancement in PPMS correlates with lower histopathological evidence of inflammation.
Main Methods:
- Retrospective clinical case note analysis to confirm disease type (PPMS vs. SPMS).
- Postmortem examination of brain tissue from nine patients (PPMS and SPMS).
- Histopathological analysis of 578 lesions, assessing perivascular cuffing and parenchymal cellularity as markers of inflammation.
Main Results:
- Significantly less inflammation was observed in primary progressive multiple sclerosis lesions compared to secondary progressive multiple sclerosis lesions.
- Histopathological findings included lower frequency of perivascular cuffing and reduced parenchymal cellularity in PPMS.
- These results support the hypothesis of less intense inflammation in PPMS.
Conclusions:
- The study provides histopathological evidence that inflammation is less pronounced in primary progressive multiple sclerosis than in secondary progressive multiple sclerosis.
- These findings have significant implications for developing differential therapeutic approaches for progressive multiple sclerosis subtypes.
- Targeting inflammation may require distinct strategies depending on the specific progressive MS disease course.