Abstract Details

Title Glymphatic Impairment in Multiple Sclerosis: A New Pathological Mechanism Associated with Disease Burden

Topic Multiple Sclerosis

Presentation(s) S5 - COVID and MS Basic Science (5:18 PM-5:30 PM)

Poster/Presentation
Number 010

Background

Glymphatic system acts as a brain waste cleaner, avoiding the accumulation of proinflammatory and toxic molecules. Impaired glymphatic functioning may contribute to MS pathology. However, studies evaluating glymphatic system in MS are lacking.

Objective To assess glymphatic function in multiple sclerosis (MS) and to evaluate the association between glymphatic function, clinical disability, disease course, white (WM) and gray matter (GM) lesions and atrophy and WM microstructural damage.

Design/Methods We enrolled 71 MS patients (49 relapsing-remitting [RR]; 22 progressive [P]MS) and 32 matched healthy controls (HCs). Each subject underwent neurological and MRI assessment including T1 and T2 imaging, diffusion- and susceptibility weighted imaging and double inversion recovery. Glymphatic function was measured through the diffusion along perivascular space index (DTI-ALPS) by manually drawing regions of interest on brain areas where veins and paravascular spaces run perpendicular to lateral ventricles and fibres axis.

Results

MS patients showed lower DTI-ALPS vs HCs (estimated mean difference [EMD]: -0.09, p=0.01). RRMS and PMS patients displayed lower DTI-ALPS (EMD: -0.06, p=0.04 and EMD: -0.19, p=0.001, respectively) vs HCs with PMS showing lower DTI-ALPS vs RRMS (EMD: -0.09, p=0.03). Lower DTI-ALPS correlated with more severe clinical disability (r=-0.45, p=0.001) and longer disease duration (r=-0.37, p=0.004). DTI-ALPS progressively reduced over the first 4.13 years of disease course (r=-0.38, p=0.04) without further worsening thereafter. Lower DTI-ALPS was associated with cortical and deep GM atrophy (r=0.30, p=0.02 and r=0.42, p=0.003, respectively), reduced fractional anisotropy and increased mean diffusivity in normal-appearing WM (r=0.45, p=0.001 and r=-0.45, p=0.001) and higher WM and cortical lesion volume (r=-0.36, p=0.006).

Conclusions

Glymphatic system is impaired in MS, especially in PMS. Impaired glymphatic function correlated with more severe disability and MS-related MRI pathological processes reflecting both neurodegeneration and neuroinflammation. Therefore, glymphatic impairment may fuel MS pathological processes resulting in clinical disability.

Authors/Disclosures
Antonio Carotenuto PRESENTER	Mr. Carotenuto has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Merk, Novartis, Roche and Almirall. The institution of Mr. Carotenuto has received research support from ALMIRALL. The institution of Mr. Carotenuto has received research support from Carotenuto Antonio.
Laura Cacciaguerra, MD, PhD (Mayo Clinic)	Dr. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS Celgene. Dr. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIOMEDIA.
Elisabetta Pagani	No disclosure on file
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.
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 $5,000-$9,999 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.