• Martina Absinta, Luisa Vuolo, Anuradha Rao, Govind Nair, Pascal Sati, Irene C M Cortese, Joan Ohayon, Kaylan Fenton, María I Reyes-Mantilla, Dragan Maric, Peter A Calabresi, John A Butman, Carlos A Pardo, and Daniel S Reich.
• From the Translational Neuroradiology Unit (M.A., L.V., A.R., G.N., P.S., D.S.R.), Neuroimmunology Clinic (I.C.M.C., J.O., K.F.), and Flow Cytometry Core Facility (D.M.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Neuroimaging Research Unit (M.A.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Department of Neurology and Radiology (L.V.), University of Florence, Italy; Department of Neurology (M.I.R.-M., P.A.C., C.A.P.), Johns Hopkins School of Medicine, Baltimore; and Diagnostic Radiology Department (J.A.B., D.S.R.), Clinical Center, NIH, Bethesda, MD.
• Neurology. 2015 Jul 7; 85 (1): 18-28.

ObjectiveTo determine the frequency and nature of leptomeningeal contrast enhancement in multiple sclerosis (MS) via in vivo 3-tesla postcontrast T2-weighted, fluid-attenuated inversion recovery (FLAIR) MRI and 7-tesla postmortem MRI-pathology correlation.MethodsBrain MRI, using the postcontrast T2-weighted, FLAIR technique, was prospectively collected in 299 MS cases and 37 age-matched neurologically healthy controls. Expert raters evaluated focal gadolinium enhancement in the leptomeningeal compartment. Two progressive MS cases came to autopsy after in vivo MRI characterization. Pathologic and immunohistochemical examination assessed the association of enhancement with leptomeningeal inflammation and adjacent cortical demyelination.ResultsFocal contrast enhancement was detected in the leptomeningeal compartment in 74 of 299 MS cases (25%) vs 1 of 37 neurologically healthy controls (2.7%; p = 0.001). Enhancement was nearly twice as frequent (p = 0.009) in progressive MS (39/118 cases, 33%) as in relapsing-remitting MS (35/181, 19%). Enhancing foci generally remained stable throughout the evaluation period (up to 5.5 years). Pathology showed perivascular lymphocytic and mononuclear infiltration in the enhancing areas in association with flanking subpial cortical demyelination.ConclusionLeptomeningeal contrast enhancement occurs frequently in MS and is a noninvasive, in vivo marker of inflammation and associated subpial demyelination. It might therefore enable testing of new treatments aimed at eliminating this inflammation and potentially arresting progressive MS.© 2015 American Academy of Neurology.

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