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Abstract Details

Correspondence Among Gray Matter Damage and Neurotransmitter Maps Is Clinically Relevant in Multiple Sclerosis
Multiple Sclerosis
P10 - Poster Session 10 (8:00 AM-9:00 AM)
3-004

In multiple sclerosis (MS), clinically-relevant GM atrophy progresses in a non-random manner, possibly due to the preferential involvement of specific neurotransmitter networks, which has not been fully evaluated yet.

To investigate the associations among regional gray matter (GM) atrophy, neurotransmitter distributions and clinical manifestations in a large group of patients with multiple sclerosis (PwMS).

Brain 3.0 T MRI scans were acquired from 286 PwMS and 172 healthy controls (HC). Regional GM volume differences, cross-correlations between regional GM atrophy and nuclear imaging-derived neurotransmitter maps and their associations with disease duration, clinical disability, cognitive impairment, fatigue and depression were investigated using voxel-based morphometry and Juspace toolbox.

Compared to HC, PwMS showed a widespread cortico-subcortical GM atrophy being spatially correlated with serotonergic, dopaminergic, opioid, noradrenergic, cholinergic and glutamatergic maps (false discovery rate, [FDR]-p≤0.004). PwMS with a disease duration ≥5 vs <5 years had a significant GM atrophy in several deep GM, cortical and cerebellar regions being spatially correlated with a higher distribution of serotoninergic and dopaminergic receptors (FDR-p≤0.03). Compared to mildly-disabled PwMS, those with Expanded Disability Status Scale (EDSS)≥3.0 or ≥4.0 had significant cortical, subcortical and cerebellar atrophy, which was associated with serotonergic and dopaminergic maps (FDR-p≤0.04). A significant spatial correspondence with opioid and cholinergic maps was also found for PwMS with EDSS≥4.0 vs <4.0 (FDR-p≤0.04). Cognitively-impaired vs cognitively-preserved PwMS had a widespread GM atrophy being spatially correlated with serotonergic, dopaminergic, noradrenergic, cholinergic and glutamatergic maps (FDR-p≤0.04). PwMS with vs without fatigue had significant cortical, subcortical and cerebellar atrophy, which were associated with serotonergic, dopaminergic, opioid and glutamatergic maps (FDR-p≥0.07). No significant GM atrophy and associations with neurotransmitter maps were found according to depression.

GM atrophy in regions belonging to specific neurotransmitter systems may contribute to explain part of MS clinical manifestations, including locomotor disability, cognitive impairment and fatigue.

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.
Alessia Fiore, MD Dr. Fiore has nothing to disclose.
Nicolò Tedone, Other (San Raffaele hospital) Dr. Tedone 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.
Carmen Vizzino Carmen Vizzino has nothing to disclose.
Damiano Mistri, MSC (Università Vita-Salute San Raffaele) Mr. Mistri has nothing to disclose.
Mor Gueye, MD Dr. Gueye has nothing to disclose.
Maria Assunta 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.