Contributions
Abstract: P1069
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Introduction: In multiple sclerosis (MS), aberrations in structural connectivity (SC), which is based on the visualisation of the brain as a complex network, might impact on cognitive function. In particular, disruptions to crucial hierarchical structures may be especially deleterious. The rich club (RC) organisation reflects the brain network hierarchy: it is a key subnetwork made up of hubs, i.e. central, highly connected grey matter regions or 'nodes', and the strong associations existing between them.
Aims: To assess, in patients with a clinically isolated syndrome (CIS), 1) the pattern of SC changes, including those affecting the RC organisation, 2) the association between SC changes and cognitive function.
Methods: We included 19 patients (9 female; mean age 36±9 yrs.) within 3 months of the CIS and 12 healthy controls (HC) (8; 35±8). T1-, T2- and diffusion-weighted 3T images were acquired. Patients were scored on the symbol digit modalities test (SDMT). Multi-shell multi-tissue constrained spherical deconvolution was used to build structural connectomes. Metrics of network connectivity (nodal strength; clustering coefficient), and network efficiency (global/local efficiency) were obtained for 1) whole network, 2) RC subnetwork (RCsn), containing 9% of nodes with the highest average nodal strength and their connections, and 3) non-RC subnetwork (non-RCsn), containing the remainder of the nodes/connections. Linear regression models assessed differences between groups and the associations between network metrics and SDMT scores, adjusting for age, gender and lesion load.
Results: CIS patients showed lower nodal strength than HC in the whole network (adjusted difference: -6283, p< 0.01) and non-RCsn (-3629.7, p< 0.01), but not in the RCsn. In the whole network, only lower global efficiency implied worse SDMT scores (b=0.60, p=0.02). When the RCsn was analysed, lower global (b=0.69, p< 0.01) and local (b=0.64, p< 0.01) efficiency and clustering coefficient (b=0.62,
p< 0.01) were associated with worse SDMT performance. None of the non-RCsn metrics correlated with cognitive function.
Conclusions: Structural networks show lower connectivity in CIS patients than HC, mainly at the expense of disrupted peripheral connections, whereas the RC organisation is spared. Future longitudinal studies will address whether cognitive decline in MS appears as a consequence of a disrupted RC organisation, as suggested by the strong association between rich club connectivity and cognition.
Disclosure:
Ooi, Joshua: nothing to disclose.
Grussu, Francesco: Is funded by the Hoirzon2020-EU.3.1 CDS-QUAMRI grant (ref: 634541) and by the UCL CMIC Pump Priming Award.
Collorone, Sara: has a MAGNIMS-ECTRIMS fellowship.
Charalambous, Thalis: nothing to disclose.
Prados, Ferran: has a Guarantors of Brain fellowship.
Kanber, Baris: nothing to disclose.
Ourselin, Sebastien: nothing to disclose.
Toosy, Ahmed: has received speaker honoraria from Biomedia, Sereno Symposia International Foundation, Bayer and meeting expenses from Biogen Idec. He is the UK PI for two clinical trials sponsored by MEDDAY pharmaceutical company (MD1003 in optic neuropathy [MS-ON] and progressive MS [MS-SPI2]).
Gandini Wheeler-Kingshott, Claudia: receives research grants (PI and co-applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon2020, NIHR/MRC.
Ciccarelli, Olga: serves as a consultant for Genzyme, Teva, Roche, Biogen, Novartis and GE Healthcare.
Tur, Carmen: received an ECTRIMS post-doctoral research fellowship in 2015. She has also received honoraria and support for travelling from Teva and Ismar Healthcare.
Abstract: P1069
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Introduction: In multiple sclerosis (MS), aberrations in structural connectivity (SC), which is based on the visualisation of the brain as a complex network, might impact on cognitive function. In particular, disruptions to crucial hierarchical structures may be especially deleterious. The rich club (RC) organisation reflects the brain network hierarchy: it is a key subnetwork made up of hubs, i.e. central, highly connected grey matter regions or 'nodes', and the strong associations existing between them.
Aims: To assess, in patients with a clinically isolated syndrome (CIS), 1) the pattern of SC changes, including those affecting the RC organisation, 2) the association between SC changes and cognitive function.
Methods: We included 19 patients (9 female; mean age 36±9 yrs.) within 3 months of the CIS and 12 healthy controls (HC) (8; 35±8). T1-, T2- and diffusion-weighted 3T images were acquired. Patients were scored on the symbol digit modalities test (SDMT). Multi-shell multi-tissue constrained spherical deconvolution was used to build structural connectomes. Metrics of network connectivity (nodal strength; clustering coefficient), and network efficiency (global/local efficiency) were obtained for 1) whole network, 2) RC subnetwork (RCsn), containing 9% of nodes with the highest average nodal strength and their connections, and 3) non-RC subnetwork (non-RCsn), containing the remainder of the nodes/connections. Linear regression models assessed differences between groups and the associations between network metrics and SDMT scores, adjusting for age, gender and lesion load.
Results: CIS patients showed lower nodal strength than HC in the whole network (adjusted difference: -6283, p< 0.01) and non-RCsn (-3629.7, p< 0.01), but not in the RCsn. In the whole network, only lower global efficiency implied worse SDMT scores (b=0.60, p=0.02). When the RCsn was analysed, lower global (b=0.69, p< 0.01) and local (b=0.64, p< 0.01) efficiency and clustering coefficient (b=0.62,
p< 0.01) were associated with worse SDMT performance. None of the non-RCsn metrics correlated with cognitive function.
Conclusions: Structural networks show lower connectivity in CIS patients than HC, mainly at the expense of disrupted peripheral connections, whereas the RC organisation is spared. Future longitudinal studies will address whether cognitive decline in MS appears as a consequence of a disrupted RC organisation, as suggested by the strong association between rich club connectivity and cognition.
Disclosure:
Ooi, Joshua: nothing to disclose.
Grussu, Francesco: Is funded by the Hoirzon2020-EU.3.1 CDS-QUAMRI grant (ref: 634541) and by the UCL CMIC Pump Priming Award.
Collorone, Sara: has a MAGNIMS-ECTRIMS fellowship.
Charalambous, Thalis: nothing to disclose.
Prados, Ferran: has a Guarantors of Brain fellowship.
Kanber, Baris: nothing to disclose.
Ourselin, Sebastien: nothing to disclose.
Toosy, Ahmed: has received speaker honoraria from Biomedia, Sereno Symposia International Foundation, Bayer and meeting expenses from Biogen Idec. He is the UK PI for two clinical trials sponsored by MEDDAY pharmaceutical company (MD1003 in optic neuropathy [MS-ON] and progressive MS [MS-SPI2]).
Gandini Wheeler-Kingshott, Claudia: receives research grants (PI and co-applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon2020, NIHR/MRC.
Ciccarelli, Olga: serves as a consultant for Genzyme, Teva, Roche, Biogen, Novartis and GE Healthcare.
Tur, Carmen: received an ECTRIMS post-doctoral research fellowship in 2015. She has also received honoraria and support for travelling from Teva and Ismar Healthcare.