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

Abstract

Objectives: In 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).

Methods: In 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.

Results: MS 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%.

Interpretation: The central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths. Ann Neurol 2018;83:283-294.

Figure 1

Frequency of perivenular lesions and topographical distribution of brain lesions in inflammatory vasculopathies and multiple sclerosis (MS). APS = antiphospholipid syndrome; PACNS = primary angiitis of the central nervous system; SLE = systemic lupus erythematosus.

Figure 2

Representative axial 3T FLAIR* images from individuals with relapsing–remitting multiple sclerosis (MS; 27‐year‐old woman), Sjögren disease (46‐year‐old woman), antiphospholipid antibody syndrome (APS; 37‐year‐old man), and systemic lupus erythematosus (SLE; 38‐year‐old woman). The central vein sign (arrows) is present in the majority of MS lesions but is not typical of white matter lesions in inflammatory vasculopathies. Boxes show magnified views of lesions in the 3 orthogonal planes for central vein assessment. [Color figure can be viewed at http://www.annalsofneurology.org]

Figure 3

Axial, sagittal, and coronal 3T FLAIR* images from individuals with relapsing–remitting multiple sclerosis (MS; 30‐year‐old woman; top) and Behçet disease (42‐year‐old woman; bottom), respectively. Perivenular MS‐like lesions (arrows) can be seen in Behçet disease. Magnified views of representative lesions are displayed in the boxes. [Color figure can be viewed at http://www.annalsofneurology.org]

Figure 4

Axial 3T FLAIR* images showing the presence of nonperivenular parenchymal lesions in 2 patients with primary angiitis of the central nervous system (PACNS). (A) Biopsy‐proven PACNS (57‐year‐old man; biopsy of the right frontal lobe and overlaying leptomeninges, asterisk). The histopathology shows the presence of a vasculocentric, transmural, multilayer inflammatory infiltrate (predominantly T lymphocytes) involving both the leptomeningeal and parenchymal arterioles. Scale bars: hematoxylin & eosin (H&E), 100 µm; CD3 (T lymphocytes), 250 µm; CD68 (macrophages), 100 µm; CD20 (B lymphocytes), 50 µm. (B) Imaging‐proven PACNS (48‐year‐old man). Vessel‐wall enhancement (arrows) of the left posterior and left middle cerebral artery is demonstrated using black‐blood arterial wall magnetic resonance imaging (MRI).

Figure 5

Representative axial 1.5T T2* echo‐planar images from individuals with relapsing–remitting multiple sclerosis (MS; 55‐year‐old and 24‐year‐old women), antiphospholipid antibody syndrome (APS; 51‐year‐old woman), and systemic lupus erythematosus (SLE; 40‐year‐old woman). The central vein sign (arrows) is present in the majority of MS lesions but is not typical of white matter lesions in inflammatory vasculopathies. Boxes show magnified views of lesions in the 3 orthogonal planes for central vein assessment. [Color figure can be viewed at http://www.annalsofneurology.org]