Abstract Details

Title Cognitive Impairment Is Related to Glymphatic System Dysfunction in Pediatric Multiple Sclerosis

Topic Child Neurology and Developmental Neurology

Presentation(s) P6 - Poster Session 6 (8:00 AM-9:00 AM)

Poster/Presentation
Number 8-003

Objective To investigate whether the glymphatic system is already impaired in pediatric multiple sclerosis (MS) patients, stratified according to their cognitive status, compared to matched healthy controls (HC) and to assess its association with clinical disability and brain structural damage.

Background

Recent evidence suggests that the impairment of the glymphatic system is clinically relevant, and it has been described in adult subjects with aging and patients with several inflammatory, demyelinating and neurodegenerative diseases of the central nervous system, including MS.

Design/Methods

Sixty-five pediatric MS patients and 23 age- and sex-matched HC underwent neurological, neuropsychological and 3.0T MRI assessment, including conventional and diffusion tensor imaging. We calculated the diffusion along perivascular space (DTI-ALPS) index, a proxy of glymphatic function. Patients who scored below the 5th percentile of the normative sample on at least two different cognitive domain tests were classified as cognitively impaired (CI).

Results No significant differences in DTI-ALPS index were observed between HC and cognitively preserved (CP) pediatric MS patients (FDR-p=0.956). Compared to HC and CP patients, CI pediatric MS patients showed significantly lower DTI-ALPS index (FDR-p≤0.003). In HC, no associations were observed between DTI-ALPS index and normalized brain, cortical, thalamic volumes and normal-appearing (NA) WM values (FDR-p≥0.323). In pediatric MS patients, higher brain WM lesion volume (LV), higher NAWM mean diffusivity (MD) and lower normalized thalamic volume and NAWM fractional anisotropy were associated with a lower DTI-ALPS index (FDR-p≤0.015). Random forest selected lower DTI-ALPS index (Relative Importance [RI]=100%), higher T2-hyperintense WM LV (RI=67.7%) and higher NAWM MD values (RI=66.3%) as informative predictors of cognitive impairment (out-of-bag-AUC= 0.747).

Conclusions

An impairment of the glymphatic system was observed in pediatric MS and may contribute to the pathophysiology of the disease by promoting the accumulation of focal lesions and irreversible tissue loss, which may lead to cognitive impairment.

Authors/Disclosures
Monica Margoni PRESENTER	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.
Elisabetta Pagani	Elisabetta Pagani has nothing to disclose.
Alessandro Meani	Alessandro Meani 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.
Damiano Mistri, MSC (Università Vita-Salute San Raffaele)	Mr. Mistri has nothing to disclose.
Mor Gueye	No disclosure on file
Lucia Moiola, MD, PhD (Fondazione Centro San Raffaele)	Dr. Moiola has nothing to disclose.
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.
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.

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