Abstract Details

Title Cerebral leptomeningeal enhancement is common and associated with cortical and thalamic lesions in relapsing-remitting multiple sclerosis: A 7T MRI study

Topic Multiple Sclerosis

Presentation(s) S31 - MS and CNS Inflammatory Disease: Imaging (3:41 PM-3:52 PM)

Poster/Presentation
Number 002

Background Recent studies have shown cortical and deep grey demyelination/atrophy and meningeal inflammation in multiple sclerosis (MS); the latter is thought to underlie MRI-defined leptomeningeal enhancement (LME).

Objective To investigate LME prevalence and relationship to cortical/thalamic lesions in relapsing-remitting (RR) MS using 7T MRI.

Design/Methods 30 RRMS subjects [age 44.0±11.3 years (mean±SD), disease duration 12.6±9.6 years, Expanded Disability Status Scale (EDSS) score 2.0±1.4, 67% women, 93% (n=28) on disease-modifying treatment] and 15 age-/sex-matched healthy controls underwent gadolinium-enhanced 7T brain MRI using 3D-MP2RAGE and 3D-FLAIR sequences with 0.7 mm³ isotropic voxels. Ten-minute-delayed post-contrast 3D-FLAIR was evaluated for LME foci. Total brain white matter T1 hypointense and T2 hyperintense lesion volumes, cortical lesions (CLs) and thalamic lesions (TLs) were expert-quantified. Wilcoxon rank sum- and two-sample t-tests assessed group differences; Spearman’s correlations were also investigated.

Results

LME was found in 20/30 RRMS subjects (66.7%) vs. 1/15 controls (6.7%). LME-positive RRMS subjects had 2.8±1.5 [1-6] LME foci, longer disease duration (14.9±10.4 vs. 8.1±5.7 years, p=0.028), increased TL number (4.0±2.1 vs. 1.3±0.7, p<0.001) and volume (0.106±0.088 vs. 0.0067±0.013 ml, p<0.001), and increased CL number (21.5±12.6 vs. 5.5±5.0, p<0.001) and volume (0.80±1.13 vs 0.13±0.13 mL, p=0.016) vs. LME-negative subjects. LME “spread” morphology was associated with increased CL (p<0.001) and TL (p=0.06) number vs. “nodular only” morphology. LME foci number showed higher correlations with cortical (r_s=0.50, p=0.01) and thalamic (r_s=0.81, p<0.001) lesion volumes than with T1 (r_s=0.32, p=0.06) or T2 (r_s=0.34, p=0.09) lesion volumes. No MRI measures correlated with EDSS score (all p>0.05).

Conclusions

Cerebral LME is common in RRMS using 7T MRI and is more strongly associated with cortical/thalamic gray matter than with white matter lesion burden. These data suggest commonalities in the pathogenesis of MS-related gray matter disease, such as CSF-borne inflammation, given the proximity of these regions to the CSF compartment. LME may be a sign of such inflammation.

Authors/Disclosures
Jonathan D. Zurawski, MD (Brigham & Women's Hospital) PRESENTER	The institution of Dr. Zurawski has received research support from The Race to Erase MS Foundation. The institution of Dr. Zurawski has received research support from Novartis Pharmaceuticals. The institution of Dr. Zurawski has received research support from I-Mab Biopharma . The institution of Dr. Zurawski has received research support from Elizabeth A. Kremer MS Research Foundation. The institution of Dr. Zurawski has received research support from Novartis.
Shahamat Tauhid, MD (Brigham & Women's Hospital)	Dr. Tauhid has nothing to disclose.
Renxin Chu (Brigham & Women's Hospital)	Dr. Chu has nothing to disclose.
Fariha Khalid, MD (Brigham And Women's Hospital)	No disclosure on file
Brian C. Healy	The institution of Mr. Healy has received research support from Analysis Group. The institution of Mr. Healy has received research support from Bristol-Myers Squibb. The institution of Mr. Healy has received research support from Verily Life Sciences. The institution of Mr. Healy has received research support from Novartis. The institution of Mr. Healy has received research support from Merck Serono. The institution of Mr. Healy has received research support from Genzyme.
Howard L. Weiner, MD (Brigham and Women'S Hospital)	Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana Life Sciences. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for vTv Therapeutics. Dr. Weiner has stock in vTv Therapeutics. The institution of Dr. Weiner has received research support from National Institute of Health. The institution of Dr. Weiner has received research support from National MS Society. The institution of Dr. Weiner has received research support from Genzyme Corp. The institution of Dr. Weiner has received research support from Genentech, Inc. . The institution of Dr. Weiner has received research support from Verily Life Sciences LLC. The institution of Dr. Weiner has received research support from EMD Serono, Inc..
Rohit Bakshi, MD, FAAN	Dr. Bakshi has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Bakshi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. The institution of Dr. Bakshi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Neuroimaging. The institution of Dr. Bakshi has received research support from Bristol Myers Squibb. The institution of Dr. Bakshi has received research support from EMD Serono. The institution of Dr. Bakshi has received research support from Novartis.

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