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Abstract Details

Local GM Demyelination and Remote Microstructural Damage in Connected WM Tracts both Contribute to Cortical Neurodegeneration in MS
Multiple Sclerosis
S31 - MS and CNS Inflammatory Disease: Imaging (4:14 PM-4:25 PM)
005

Neurodegeneration in MS has been related to local GM demyelination and inflammation together with connected WM tracts’ damage. However, their relative contribution to neurodegeneration is unknown.

To investigate the associations between cortical neurodegeneration and 1) local gray matter (GM) myelination and microglia density, and 2) remote white matter (WM) tract integrity in multiple sclerosis (MS) by combining postmortem MRI and histopathology.

Brain structural and diffusion-weighted postmortem in situ 3T MRI were obtained from 16 MS patients and 10 age- and sex-matched non-neurological controls (nNC). At subsequent autopsy, cortical regions were dissected from 6 standardized locations. Neuron density and volume, and axon density were determined as histopathological markers for cortical neurodegeneration, while myelin and microglia density were evaluated as markers for local GM damage. Using MRI, tissue blocks were matched to cortical AAL atlas regions and connected WM tract fractional anisotropy (FA), mean (MD), axial (AD) and radial (RD) diffusivities were determined as markers for remote damage. Using linear mixed model, between-group differences and within-group relations between neurodegeneration and local or remote damage were evaluated.

Compared to nNC, MS donors displayed significant axonal loss (p=0.003) and a trend to lower GM myelin density (p=0.107). In connected tracts, MS donors showed increased normal-appearing WM (NAWM) AD (p=0.013) and MD (p=0.037) and whole tract AD (p=0.018) compared to nNC. Axonal density was associated with myelin density in both nNC (β=0.63, p<0.001) and MS (β=0.61, p<0.001). In MS, axonal density was associated with NAWM AD, MD and RD (β=-0.41; β=-0.43; β=-0.42, p=0.03 for all) and whole tract MD (β=-0.36, p=0.041).

Cortical neurodegeneration, predominantly characterized by axonal loss, was observed in MS, and was associated with cortical demyelination and microstructural abnormalities in connected WM tracts. Both local GM damage and remote WM tract dysintegrity contribute to GM neurodegeneration in MS.

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.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
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.
No disclosure on file
No disclosure on file