• Jan-Mendelt Tillema, Stephen D Weigand, Jay Mandrekar, Yunhong Shu, Claudia F Lucchinetti, Istvan Pirko, and John D Port.
• Department of Neurology, Mayo Clinic, Rochester, MN, USA.
• Mult. Scler. 2017 Jun 1; 23 (7): 973-981.

BackgroundThe relationship between cortical lesions (CLs) and white matter lesions (WMLs) in multiple sclerosis (MS) is poorly understood. Pathological studies support a topographical association between CLs and underlying subcortical WMLs and suggest CLs may play a role in both disease initiation and progression. We hypothesized that cortical MS lesions are physically connected to white matter MS lesions via axonal connections.ObjectiveTo assess the presence of CL-WML connectivity utilizing novel magnetic resonance imaging (MRI) methodology.MethodsIn all, 28 relapsing-remitting MS patients and 25 controls received 3 T MRI scans, including double inversion recovery (DIR) for CL detection coupled with diffusion tensor imaging (DTI). CL and WML maps were created, and DTI was used to calculate inter-lesional connectivity and volumetric connectivity indices.ResultsAll patients showed inter-lesional WML connectivity (median 76% of WMLs connected to another WML; interquartile range (IQR), 58%-88%). On average, 52% of detected CLs per patient were connected to at least one WML (IQR, 42%-71%). Volumetric connectivity analysis showed significantly elevated cortical lesion ratios in MS patients (median, 2.3; IQR, 1.6-3.3) compared to null MS and healthy control datasets ( p < 0.001).ConclusionThese findings provide strong evidence of inter-lesional connectivity between CLs and WMLs, supporting our hypothesis of intrinsic CL-WML connectivity.

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