Diffuse Vascular Pathology and Blood-brain Barrier Disruption in the MS Spinal Cord
Marco Pisa1, Aimee Avery1, kiara Wild2, lovel lisac1, Paula Seghers1, Talal Salem1, Andrew Lockhart1, Monika Hofer3, Clara Limbaeck3, Gabriele De Luca1
1Nuffield Department of Clinical Neurosciences, University of Oxford, 2Oxford Medical School, University of Oxford, 3Neuropathology, Oxford University Hospital NHS Fundation Trust
Objective:
To characterise vascular pathology in the Multiple sclerosis (MS) spinal cord
Background:
MS pathology has traditionally focused on demyelinating lesions centred around venules. However, recent work highlights vascular changes beyond lesions as key factors in disease activity and neurodegeneration. The spinal cord is particularly relevant to disability in MS but little is known about vascular pathology in this region.
Design/Methods:

Spinal cord samples (cervical, thoracic, lumbar) from 46 MS and 20 controls were stained for haematoxylin/eosin, elastin Van-Giessen, and Luxol Fast-Blue. Systematic assessment of measures of small vessel disease included vascular thickness, perivascular space dilation, fibrosis, hyalinotic changes, and myelin pallor. Fibrinogen, a marker for blood-brain barrier integrity, was examined in a subset of 42 MS and 6 controls using quantitative and semiquantitative methods.

Results:

Controls showed age-related vascular thickening with hyalinotic and fibrotic changes, and perivascular space dilation. In non-lesional tissue, MS cases had 89% more vascular fibrosis (p=0.002) than controls. In non-lesional white matter, myelin pallor increased by 66% (p<0.001) in MS compared to controls with both groups showing a symmetrical topographical pattern of myelin pallor. Perivascular space dilation increased by 93% in white (p<0.001) and 82% in grey matter (p<0.001) compared to controls. Striking fibrinogen deposition was observed in non-lesional MS areas, both extracellularly and within hypertrophic astrocytes. Extracellular fibrinogen was over 200 times more common in MS (p<0.0001) and correlated with increased inflammation and faster rate to wheelchair dependency. Fibrinogen-positive astrocyte coverage increased by 247% and hypertrophy by 83% (both p<0.001), both correlating with age at wheelchair dependence. MS lesions showed a further increase in vascular fibrosis, extracellular and astrocytic fibrinogen compared to the surrounding non-lesional tissue (all p<0.001).

Conclusions:

These findings highlight that vascular abnormalities and blood-brain barrier leakage outside the paradigmatic demyelinated lesion are key features of MS spinal cord pathology and relate to inflammation and disease severity.

10.1212/WNL.0000000000211800
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.