Abstract Details

Title Choroid Plexus Enlargement in Multiple Sclerosis: Normative Trajectories, Clinical Correlates, and Genetic Associations

Topic Multiple Sclerosis

Presentation(s) P5 - Poster Session 5 (11:45 AM-12:45 PM)

Poster/Presentation
Number 19-003

Objective To define normative choroid plexus (ChP) volume trajectories across the healthy lifespan and compute z-scores in multiple sclerosis (MS) patients, evaluating associations with demographic, clinical, MRI, and genetic variables, including Human Leukocyte Antigen (HLA) and non-HLA polygenic risk scores (PRS).

Background The ChP regulates cerebrospinal fluid production and CNS homeostasis. In MS, ChP enlargement has been reported early in the disease course, but its normative trajectory and associations with MS-related features remain unclear.

Design/Methods This multicenter retrospective study included 461 healthy controls (HC) and 727 MS patients (age 18-70 years) who underwent 3T brain MRI and neurological assessment. ChP volumes were quantified using ASCHOPLEX, normalized for head size, modeled in HC to compute z-scores for MS patients, and correlated with demographic, clinical, MRI, and genetic data. PRSs were calculated based on established MS-associated susceptibility loci.

Results In HC, normalized ChP volume (NChPV) was predicted by normalized brain volume, lateral ventricle volume, and its squared term (R²=0.54), remaining stable until age 35, then increasing nonlinearly (p-FDR<0.002). MS patients had significantly higher NChPV z-scores than HC (p-FDR<0.001), independent of age or phenotype (p-FDR≥0.484). NChPV z-scores rose during the first five years after onset (p-FDR=0.012–0.015) before plateauing. Higher z-scores were associated with higher T2-hyperintense white matter lesion volume (β=0.012, p<0.001), higher Expanded Disability Status Scale (EDSS) score only in patients with EDSS score<3.0 (β=0.303, p=0.001), and higher HLA genetic burden (β=0.103, p=0.027). No significant association with other brain volumetric measures or non-HLA PRSs was found (p≥0.177).

Conclusions We provided normative ChP trajectories and found early, sustained NChPV enlargement in MS, associated with inflammatory lesion burden, HLA genetic risk, disease duration and disability in the earliest phases of the disease. The ChP may contribute to MS pathophysiology and its volumetric assessment may represent a non-invasive biomarker of MS susceptibility and neuroinflammation.

Authors/Disclosures
Paolo Preziosa (Ospedale San Raffaele) PRESENTER	Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
Gianluca Corazzolla, MD	Dr. Corazzolla has nothing to disclose.
Alessandro Meani	Alessandro Meani has nothing to disclose.
Monica Margoni	Monica Margoni has received research support from MAGNIMS. Monica Margoni has received research support from Merck-Serono. Monica Margoni has received research support from Sanofi-Genzyme.
Loredana Storelli	Loredana Storelli has nothing to disclose.
Elisabetta Pagani	Elisabetta Pagani has nothing to disclose.
Martina Rubin, MD (San Raffaele Hospital)	Dr. Rubin has nothing to disclose.
Ferdinando Clarelli	Dr. Clarelli has nothing to disclose.
Elisabetta Mascia	Elisabetta Mascia has nothing to disclose.
Melissa Sorosina	Melissa Sorosina has received research support from Italian Multiple Sclerosis Foundation. Melissa Sorosina has received research support from Italian Ministry of Health.
Federica Esposito	Federica Esposito has received personal compensation in the range of $0-$499 for serving as a Consultant for Merck. Federica Esposito has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Federica Esposito has received personal compensation in the range of $0-$499 for serving as a Consultant for Novartis. Federica Esposito has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Federica Esposito has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. The institution of Federica Esposito has received research support from Italian MS Society. The institution of Federica Esposito has received research support from Italian Ministry of Health. The institution of Federica Esposito has received research support from ERA Net. The institution of Federica Esposito has received research support from European Commission. Federica Esposito has received intellectual property interests from a discovery or technology relating to health care.
Maria A. Rocca (Neuroimaging Research Unit)	Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. The institution of Maria Assunta Rocca has received research support from MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi 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 Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.

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