Abstract Details

Title Exploring the Contribution of Cerebrovascular Risk Factors to Glymphatic System Impairment in Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) P8 - Poster Session 8 (11:45 AM-12:45 PM)

Poster/Presentation
Number 19-003

Objective To investigate whether choroid plexus (CP) volume and the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index, both markers of glymphatic system function, are influenced by cerebrovascular risk factors (cVRFs) in multiple sclerosis (MS).

Background cVRFs are associated with more severe brain damage and clinical disability in MS patients, possibly due to synergistic interactions with MS pathology. The glymphatic system, contributing to brain waste clearance, is impaired in both MS and cerebrovascular diseases.

Design/Methods We included 209 MS patients and 123 age- and sex-matched healthy controls (HC) who underwent cVRF assessment (i.e., smoking, hypertension, dyslipidemia, hyperglycemia, and obesity), neurological evaluation, and brain 3T MRI acquisition. CP volume was quantified using a deep learning-based approach on 3D T1-weighted MRI scans; DTI-ALPS was used to assess glymphatic system function.

Results At least one cVRF was present in 64% of MS patients and 41% of HC. MS patients with and without cVRFs showed no significant differences for disease duration, disability, clinical phenotype and treatment (p≥0.738). Compared to HC, MS patients showed significantly higher T2-hyperintense white matter (WM) lesion volume, lower global and regional brain volumes, and larger CP volumes (FDR-p≤0.003), regardless of cVRFs (FDR-p≥0.553). Both MS groups with and without cVRFs exhibited significantly lower DTI-ALPS index compared to their respective HC counterparts (FDR-p≤0.002), with the coexistence of MS and cVRFs resulting in a significantly greater DTI-ALPS index reduction (FDRp=0.013). Lower DTI-ALPS and higher nCPV correlated with higher T2-hyperintense WM lesion volume and lower brain volumes (FDR-p≤0.007), independently from cVRF presence (FDRp≥0.122).

Conclusions cVRFs may worsen glymphatic system dysfunction in MS, possibly contributing to aggravate neuroinflammation and neurodegeneration, amplifying brain damage accumulation. Our results support the importance of proactive cVRF management in MS care.

Authors/Disclosures
Tetsu Morozumi, PT (Ospedale San Raffaele S.r.l.) PRESENTER	Mr. Morozumi has nothing to disclose.
Martina Rubin, MD (San Raffaele Hospital)	Dr. Rubin has nothing to disclose.
Paolo Preziosa (Ospedale San Raffaele)	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.
Elisabetta Pagani	Elisabetta Pagani 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.
Matteo Albergoni, PT (Ospedale San Raffaele SRL (VAT: IT 07636600962))	Dr. Albergoni has nothing to disclose.
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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