The “central vein sign” in inflammatory demyelination: The role of fibrillar collagen type I

Abstract

Accumulating evidence corroborates the role of the "central vein sign" in the radiological diagnosis of multiple sclerosis (MS). Here, we report human magnetic resonance imaging (MRI) and corresponding pathological data that inflammation-dependent intracerebral remodeling of the vessel wall is directly associated with the prominence of intralesional veins on susceptibility-based MRI. In adult marmosets with experimental autoimmune encephalomyelitis, vessel-wall fibrosis was detected early in the demyelinating process, even in lesions <2 weeks old, though fibrosis was more evident after 6 weeks. Vascular remodeling consisted of both luminal enlargement and eccentric thickening of the perivascular space (fibrillar collagen type I deposition) and affected almost exclusively white matter, but not subpial cortical, lesions. The long-term effect of vessel remodeling in MS lesions is currently unknown, but it might potentially affect tissue repair. ANN NEUROL 2019;85:934-942 O n susceptibility-based magnetic resonance imaging (MRI), perivenular topography has been recently proposed to be specific to multiple sclerosis (MS)-related focal inflammatory demyelination, potentially facilitating a pathologically specific radiological diagnosis. 1,2 This is strictly related to the fact that the immunological events triggering the formation of demyelinated lesions in the white matter (WM) typically include blood-brain barrier (BBB) opening in small-to medium-sized parenchymal veins and subsequent infiltration of blood-derived scavenger and demyelinating cells. 3 However, reasons for central vein conspicuity on susceptibility-based MRI not only during the perivenular inflammatory phase at lesion onset, but also after restoration of the BBB in chronic lesions, remain unknown.View this article online at wileyonlinelibrary.com.

Ex vivo MR microscopy of a human brain with multiple sclerosis: Visualizing individual cells in tissue using intrinsic iron

“…Commensurate with this, a rim of collagen deposition is seen around some of the larger blood vessels in Sirius red staining, but not in the iron staining. This observation adds evidence that the dark signal is seen around blood vessels could be a result of water exclusion from collagen deposition, ( Absinta et al, 2019 ) short T 2 * relaxation times of macro-molecules. Vascular hypointensity is commonly seen within MS lesions in the lower-resolution in-vivo scans, and is referred to as the “central vein sign.” ( Lummel et al, 2011 ; Sati et al, 2016 ) It is possible that more subtle vascular remodeling outside lesions are visible in the high-resolution, highly sensitive MRM scans reported herein.…”

The “central vein sign” in patients with diagnostic “red flags” for multiple sclerosis: A prospective multicenter 3T study

“…2 In four patients diagnosed with a systemic inflammatory disorder with involvement of the CNS (patient ID 3, 17, 27, 30), the neurological manifestation was the first manifestation of the disease. Four patients who received a diagnosis of MS had a concomitant systemic inflammatory disorder ("history of SAD" in Table 2) potentially affecting the CNS (patient ID 6,7,10,22). Of note, none of these four patients harbored MS atypical clinical, laboratory, or imaging features at the level of the CNS.…”

“…2,5 The presence of a vein at the center of brain white matter (WM) lesions, the "central vein sign" (CVS), is a specific feature of MS and can now be depicted at clinical MRI field strength using specialized gradient-echo MRI sequences. [5][6][7] Several studies have shown how this promising imaging biomarker can differentiate MS from other disorders, including migraine, 8,9 cerebral The "central vein sign" in patients with diagnostic "red flags" for multiple sclerosis: A prospective multicenter 3T study small vessel disease, 10 neuromyelitis optica, 11 Susac syndrome, 12 and primary or secondary vasculitis of the CNS, showing similar WM lesions on MRI. 6 However, most prior studies are retrospective.…”

The central vein sign in multiple sclerosis patients with vascular comorbidities

“…5,6 On the contrary, inflammatory demyelinating WM lesions in MS develop around small parenchymal veins. 7 Previous studies have shown that subjects with MS have a higher proportion of lesions with a central vein compared to CSVD patients. 2,8,9 Vascular comorbidities are prevalent in MS and are associated with an increased MRI lesion burden and brain atrophy, as well as with clinical disability progression.…”