Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies

Abstract

ObjectivesIn multiple sclerosis (MS), magnetic resonance imaging (MRI) is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the “central vein sign”) improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS‐mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking. In a multicenter study, we assessed the frequency of perivenular lesions in MS versus systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS).MethodsIn 31 patients with inflammatory CNS vasculopathies and 52 with relapsing–remitting MS, 3‐dimensional T2*‐weighted and T2–fluid‐attenuated inversion recovery images were obtained during a single MRI acquisition after gadolinium injection. For each lesion, the central vein sign was evaluated according to consensus guidelines. For each patient, lesion count, volume, and brain location, as well as fulfillment of dissemination in space MRI criteria, were assessed.ResultsMS showed higher frequency of perivenular lesions (median = 88%) than did inflammatory CNS vasculopathies (14%), without overlap between groups or differences between 3T and 1.5T MRI. Among inflammatory vasculopathies, Behçet disease showed the highest median frequency of perivenular lesions (34%), followed by PACNS (14%), antiphospholipid syndromes (12%), Sjögren syndrome (11%), and systemic lupus erythematosus (0%). When a threshold of 50% perivenular lesions was applied, central vein sign discriminated MS from inflammatory vasculopathies with a diagnostic accuracy of 100%.InterpretationThe central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths. Ann Neurol 2018;83:283–294

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

“…1,2 Under normal conditions, parenchymal veins are visible on in vivo susceptibility-based MRI because of the paramagnetism of deoxyhemoglobin, which shortens T2* relaxation. Even though the perivenular nature of the demyelination process in MS and relative tendency to tissue fibrosis ("sclerosis") were reported in the earliest neuropathological descriptions of the disease, 14,15 these pathological features were not considered relevant in the diagnostic workflow until recently.…”

“…Even though the perivenular nature of the demyelination process in MS and relative tendency to tissue fibrosis ("sclerosis") were reported in the earliest neuropathological descriptions of the disease, 14,15 these pathological features were not considered relevant in the diagnostic workflow until recently. 1,2 Under normal conditions, parenchymal veins are visible on in vivo susceptibility-based MRI because of the paramagnetism of deoxyhemoglobin, which shortens T2* relaxation. In MS, the observed MRI prominence of intralesional veins can be further explained by both postinflammatory enlargement of the lumen (and the related higher content of deoxyhemoglobin) and perivenular fibrillar collagen-I deposition.…”

Magnetic resonance imaging diagnosis of demyelinating diseases: An update

“…1). [29][30][31] Callosal-septal interface lesions These intracallosal lesions spread perpendicularly to the ventricular wall (Fig. 1 Although this type of lesion is frequently (63%) seen in MS, 28 similar lesions can be seen in other diseases, such as NMOSD and ischemia, so the specificity of this type of lesion is not very high.…”

“…Veins running through MS lesions (central vein sign) are frequently seen on T2*-weighted images, susceptibility-weighted images and fluid-attenuated inversion recovery (FLAIR) T2*-weighted images (combined T2*weighted and FLAIR images), which could be useful for differentiation from diseases, such as NMOSD, cerebral small vessel disease, Susac syndrome, migraine and inflammatory vasculopathies (Behc ßet's disease, primary angitis of the central nervous system, antiphospholipid syndrome, Sj€ ogren's syndrome and systemic lupus erythematosus). [29][30][31] Callosal-septal interface lesions These intracallosal lesions spread perpendicularly to the ventricular wall ( Fig. 2).…”

The role of iron and myelin in orientation dependent R2* of white matter

“…Further correlation with clinical data 55 or biochemical data, such as serum ferritin levels 56 would be straightforward. Note also that 3D gradient echo MRI will likely become part of routine imaging protocols for MS, as it is required for the detection of the central vein sign as a diagnostic marker for MS. [57][58][59][60][61] Lastly, this approach may also be sensitive to diffuse WMwide remyelination rendered possible by future treatment approaches for MS, and may complement measures of remyelination in focal lesions using magnetization transfer imaging, 62 myelin water imaging, 28,63,64 or MR phase based approaches. 65,66 This work has some limitations.…”