Correspondence Among Gray Matter Damage and Neurotransmitter Maps Is Clinically Relevant in Multiple Sclerosis (P10-3.004)

<h3>Objective:</h3> 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). <h3>Background:</h3> 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. <h3>Design/Methods:</h3> 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. <h3>Results:</h3> 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 &lt;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 &lt;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. <h3>Conclusions:</h3> 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. <b>Disclosure:</b> 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. Dr. Fiore has nothing to disclose. Dr. Tedone has nothing to disclose. Monica Margoni has received research support from MAGNIMS. Carmen Vizzino has nothing to disclose. Damiano Mistri has nothing to disclose. Dr. Gueye has nothing to disclose. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. 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, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).