Contributions
Abstract: P569
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Multiple sclerosis (MS) is characterized by changes in functional and diffusion structural connectivity that worsen network information transmission. Attention and working memory mainly rely in the integrity of large-scale neural networks connecting frontal and parietal areas, however, damage mechanisms at this level are unknown.
Goals: To study the integrity and metabolic changes of the frontoparietal network through the combination of diffusion magnetic resonance imaging (MRI) and spectroscopy data of the superior longitudinal fasciculus, and their impact on cognition.
Methods: 129 MS patients and 33 healthy controls (HC) underwent an MRI session with diffusion-weighted and 3D-structural sequences. In 102 patients and 25 HC from this cohort, chemical shift imaging spectroscopy with a box of 78cm3 over the corpus callosum, including the cingulated, was also acquired. Frontoparietal network was reconstructed through probabilistic tractography and network integrity was analysed using graph theory metrics. Metabolic information in white matter included levels of N-acetylaspartate (NAA/Cr), as marker of neuroaxonal integrity, myo-inositol (mI/Cr), as marker of astrogliosis and mI/NAA ratios. Cognition was assessed with the Paced auditory serial addition test (PASAT) and the Symbol digit modalities test (SDMT). A mean z-score of both tests was obtained (zAttention).
Results: Thirty three patients were considered cognitively impaired (CI; zAttention below -1.5). A significant reduction of global efficiency, assortativity and clustering coefficient was observed in patients, especially in CI (p< 0.05). MS persons displayed decreased NAA/Cr, and increased mI/Cr and mI/NAA levels (p< 0.01). Metabolic changes were correlated with worse strength, transitivity, global efficiency and clustering coefficient of the network (r=0.37 to 0.51 for correlations with NAA/Cr, and r=-0.26 to -0.49 for correlations with mI/Cr and mI/NAA, p< 0.01).
Worse zAttention was correlated with decreased global efficiency, clustering coefficient and NAA/Cr (r=0.21 to 0.38, p< 0.05), and with increased mI/NAA levels (r=-0.29, p< 0.01). When these variables were included in a multiple regression model, cognitive worsening was mainly driven by the reduction of NAA/Cr (β=0.331, p< 0.01).
Conclusion: Astrogliosis and neuroaxonal damage impair frontoparietal network efficiency in MS. Worse attention performance is influenced by the reduction of neuroaxonal integrity of this network.
Disclosure:
ES received travel reimbursement from TEVA;
EMH, NB, JB, HP declare nothing to disclose;
MS received speaker honoraria from Genzyme and Novartis, and funding from the Generalitat de Catalunya (SLT002/16/00354);
NSV receives funding from the Spanish Government (Instituto de Salud Carlos III, Spain, and Fondo Europeo de Desarrollo Regional [FEDER, FI16/00251], and the Predoctoral Grant for Health Research);
EML received speaking honoraria from Biogen, Genzyme and Novartis, travel reimbursement from Roche, Sanofi-Genzyme and TEVA, and funding from the Spanish Government (Instituto de Salud Carlos III [CM13/00150; MV15/00012; JR16/00006]), Fundació Marató TV3 (20142030), GMSI (2016) and Fundació Cellex Barcelona;
YB: received speaking honoraria from Biogen, Novartis and Genzyme;
AS received compensation for consulting services and speaker honoraria from Bayer-Schering, Merck-Serono, Biogen-Idec, Sanofi-Aventis, TEVA and Novartis;
SL received speaker honoraria from Biogen Idec, Novartis, Teva, Genzyme and Merck, and research support from a Juan Rodes grant from the Instituto de Salud Carlos III (JR14/00016) and the Spanish Government (PI15/00587).
Funding: This work was funded by a Proyecto de Investigacion en Salud (FIS 2015. PI15/00587, SL, AS) integrated in the Plan Estatal de Investigación Científica y Técnica de Innovación I+D+I and co-funded by the Instituto de Salud Carlos III-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER, 'Otra manera de hacer Europa'); Red Española de Esclerosis Múltiple (REEM) (RD16/0015/0002, RD16/0015/0003, RD12/0032/0002, RD12/0060/01-02); TEVA SLU.
Abstract: P569
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Multiple sclerosis (MS) is characterized by changes in functional and diffusion structural connectivity that worsen network information transmission. Attention and working memory mainly rely in the integrity of large-scale neural networks connecting frontal and parietal areas, however, damage mechanisms at this level are unknown.
Goals: To study the integrity and metabolic changes of the frontoparietal network through the combination of diffusion magnetic resonance imaging (MRI) and spectroscopy data of the superior longitudinal fasciculus, and their impact on cognition.
Methods: 129 MS patients and 33 healthy controls (HC) underwent an MRI session with diffusion-weighted and 3D-structural sequences. In 102 patients and 25 HC from this cohort, chemical shift imaging spectroscopy with a box of 78cm3 over the corpus callosum, including the cingulated, was also acquired. Frontoparietal network was reconstructed through probabilistic tractography and network integrity was analysed using graph theory metrics. Metabolic information in white matter included levels of N-acetylaspartate (NAA/Cr), as marker of neuroaxonal integrity, myo-inositol (mI/Cr), as marker of astrogliosis and mI/NAA ratios. Cognition was assessed with the Paced auditory serial addition test (PASAT) and the Symbol digit modalities test (SDMT). A mean z-score of both tests was obtained (zAttention).
Results: Thirty three patients were considered cognitively impaired (CI; zAttention below -1.5). A significant reduction of global efficiency, assortativity and clustering coefficient was observed in patients, especially in CI (p< 0.05). MS persons displayed decreased NAA/Cr, and increased mI/Cr and mI/NAA levels (p< 0.01). Metabolic changes were correlated with worse strength, transitivity, global efficiency and clustering coefficient of the network (r=0.37 to 0.51 for correlations with NAA/Cr, and r=-0.26 to -0.49 for correlations with mI/Cr and mI/NAA, p< 0.01).
Worse zAttention was correlated with decreased global efficiency, clustering coefficient and NAA/Cr (r=0.21 to 0.38, p< 0.05), and with increased mI/NAA levels (r=-0.29, p< 0.01). When these variables were included in a multiple regression model, cognitive worsening was mainly driven by the reduction of NAA/Cr (β=0.331, p< 0.01).
Conclusion: Astrogliosis and neuroaxonal damage impair frontoparietal network efficiency in MS. Worse attention performance is influenced by the reduction of neuroaxonal integrity of this network.
Disclosure:
ES received travel reimbursement from TEVA;
EMH, NB, JB, HP declare nothing to disclose;
MS received speaker honoraria from Genzyme and Novartis, and funding from the Generalitat de Catalunya (SLT002/16/00354);
NSV receives funding from the Spanish Government (Instituto de Salud Carlos III, Spain, and Fondo Europeo de Desarrollo Regional [FEDER, FI16/00251], and the Predoctoral Grant for Health Research);
EML received speaking honoraria from Biogen, Genzyme and Novartis, travel reimbursement from Roche, Sanofi-Genzyme and TEVA, and funding from the Spanish Government (Instituto de Salud Carlos III [CM13/00150; MV15/00012; JR16/00006]), Fundació Marató TV3 (20142030), GMSI (2016) and Fundació Cellex Barcelona;
YB: received speaking honoraria from Biogen, Novartis and Genzyme;
AS received compensation for consulting services and speaker honoraria from Bayer-Schering, Merck-Serono, Biogen-Idec, Sanofi-Aventis, TEVA and Novartis;
SL received speaker honoraria from Biogen Idec, Novartis, Teva, Genzyme and Merck, and research support from a Juan Rodes grant from the Instituto de Salud Carlos III (JR14/00016) and the Spanish Government (PI15/00587).
Funding: This work was funded by a Proyecto de Investigacion en Salud (FIS 2015. PI15/00587, SL, AS) integrated in the Plan Estatal de Investigación Científica y Técnica de Innovación I+D+I and co-funded by the Instituto de Salud Carlos III-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER, 'Otra manera de hacer Europa'); Red Española de Esclerosis Múltiple (REEM) (RD16/0015/0002, RD16/0015/0003, RD12/0032/0002, RD12/0060/01-02); TEVA SLU.