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Updated: Aug 16, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Blood-brain barrier alterations in both focal and diffuse abnormalities on postmortem MRI in multiple sclerosis
Catharina M P Vos1, Jeroen J G Geurts, Lisette Montagne
1Department of Pathology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
Abstract:
Postmortem MRI-guided tissue sampling significantly enhances the yield of MS lesions in autopsy material, but so far it is unknown whether abnormalities concur with blood-brain barrier alterations. Here we sampled MS lesions with focal and diffuse abnormalities (diffusely abnormal white matter; DAWM) on MRI; both were coupled to the presence of MS lesions upon neuropathological examination. Extravascular distribution of fibrinogen, indicating BBB disturbance, was observed in so-called (p)reactive lesions that reflect discrete areas of microglial activation without demyelination within an otherwise normal appearing white matter. Leakage became more extensive in active demyelinating MS lesions to chronic inactive lesions. An enlargement of the perivascular (Virchow-Robin) space containing infiltrated leukocytes was associated with both DAWM and focal abnormalities on postmortem MRI. This study shows for the first time that in MS brain changes in the vasculature take place not only in focal lesions but also in DAWM as detected by postmortem MRI.
Insights
Postmortem MRI reveals blood-brain barrier (BBB) disruptions in multiple sclerosis (MS) lesions, including diffusely abnormal white matter (DAWM). These vascular changes are present even in early MS, indicating widespread BBB involvement.
Area of Science:
- Neurology
- Neuroimaging
- Pathology
Background:
- Postmortem MRI enhances detection of multiple sclerosis (MS) lesions in autopsy tissue.
- The relationship between MRI-detected abnormalities and blood-brain barrier (BBB) integrity in MS is not fully understood.
Purpose of the Study:
- To investigate BBB alterations in MS lesions identified by postmortem MRI, including focal lesions and diffusely abnormal white matter (DAWM).
Main Methods:
- Postmortem MRI was used to guide tissue sampling of MS lesions.
- Neuropathological examination assessed demyelination, microglial activation, fibrinogen extravasation (indicating BBB leakage), and perivascular leukocyte infiltration.
Main Results:
- Fibrinogen extravasation, a marker of BBB disturbance, was found in (p)reactive lesions and active demyelinating MS lesions, increasing with lesion severity.
- Enlarged perivascular spaces with leukocyte infiltration were associated with both DAWM and focal MRI abnormalities.
- BBB changes were detected not only in focal MS lesions but also in DAWM.
Conclusions:
- Postmortem MRI-guided sampling confirms BBB alterations in various MS lesion types, including DAWM.
- Vascular pathology in MS is more widespread than previously recognized, extending to areas of diffusely abnormal white matter.
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