Abstract Details

Title Neuromyelitis Optica as an In-Vivo Model of Glymphatic System Alterations: An MRI Study

Topic Autoimmune Neurology

Presentation(s) S3 - Autoimmune Neurology 1: Mechanisms of Disease, Clinical Practice (2:12 PM-2:24 PM)

Poster/Presentation
Number 007

Background The glymphatic system requires astrocytes endfeet to regulate blood, cerebrospinal and interstitial fluids exchange through the aquaporin-4 (AQP4) water channel. Since NMOSD is an autoimmune astrocytopathy targeting AQP4, glymphatic functioning could be altered in this disease.

Objective We aimed to assess whether patients with neuromyelitis optica spectrum disorders (NMOSD) have glymphatic functioning impairment and if such alterations are associated with clinical disability.

Design/Methods 34 NMOSD patients and 46 age- and sex-matched healthy controls (HC) from two independent cohorts (exploratory- and validation-dataset) underwent a standardized 3.0 T MRI protocol (T2-, T1-weighted sequences and diffusion tensor imaging). Susceptibility-weighted imaging (SWI) was also acquired in the exploratory-dataset. We evaluated perivascular space (PVS) enlargement and glymphatic system function by calculating the diffusion along perivascular space (DTI-ALPS) index. In the exploration-dataset, SWI was used to draw the regions of interest for DTI-ALPS calculation in areas having veins perpendicular to lateral ventricles. Between-group comparisons, partial correlations and regression models were run to assess associations between DTI-ALPS index, PVS scores, clinical and MRI variables.

Results The two datasets were similar for demographic and clinical features. In both, NMOSD patients had reduced DTI-ALPS index (p-values: 0.004-0.038). Patients also showed a higher frequency of severe PVS enlargement in the centrum semiovale (29.4 vs. 8.7%, p=0.040). Lower DTI-ALPS index, deep grey matter and cortical volumes predicted NMOSD diagnosis (R²=0.62). Lower DTI-ALPS index, higher number of myelitis, and higher T2-lesion volume associated with worse disability (R²=0.55). Higher PVS scores correlated with global brain and deep grey matter atrophy (r-values: -0.44, -0.36; p-values: 0.01-0.046).

Conclusions

We detected glymphatic system impairment in two independent cohorts of NMOSD patients. Reduced glymphatic functioning was associated with worse clinical disability, suggesting a direct correlation with the disease pathogenetic mechanism and its magnitude.

Authors/Disclosures
Laura Cacciaguerra, MD, PhD (Mayo Clinic) PRESENTER	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.
Antonio Carotenuto	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.
Elisabetta Pagani	No disclosure on file
Marta Radaelli (Hsr)	Marta Radaelli has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono. Marta Radaelli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Marta Radaelli has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Marta Radaelli has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Sanofi-Genzyme.
Vittorio Martinelli (S. Raffaele Hospital)	Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis, Biogen, Sanofi Genzyme, TEVA and Merck. Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck .
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.
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.