Contributions
Abstract: P508
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: THC:CBD is a second-line agent for the treatment of spasticity in MS with partial efficacy. Although THC:CBD mechanism of action is not completely understood, it may involve modulation of nociceptive as well as corticospinal pathways.
Goals: Aim of this study is to investigate brain networks connectivity changes on resting state (RS) functional MRI (fMRI) of MS patients treated with THC:CBD.
Methods: Based on statistical power calculation, we planned to include at least 12 MS patients eligible for treatment with THC:CBD oromucosal spray and followed at Verona University Hospital MS Center. Patients were evaluated at baseline before treatment start (T0) and after ≥4 weeks of THC:CBD treatment at a stable dose (T1). Clinical variables included the EDSS and the Numerical Rating Scale (NRS) for spasticity scores. THC:CBD response was defined as a ≥20% reduction on the NRS score at T1 compared to T0. Brain MRI was performed at T0 and T1 on a 1.5 T scanner, acquiring RS fMRI with a T2-weighted EPI sequence (TR=3000 ms, TE=50 ms, slice thickness=4 mm, ETL=57, 30 slices, 80 dynamics, time=240 s). Connectivity changes were compared before and after treatment in the whole group and according to response status, using functional connectivity toolbox (CONN, version 15.h). Each exam was first preprocessed using default CONN pipeline, then a second level group analysis step was applied. ROI-to-ROI and seed-to-voxel connectivity were evaluated.
Results: Between January and September 2014, 15 consecutive patients were enrolled in the study. Of these, 12 (7 males, 5 females) completed all the assessments and entered data analysis. Median age was 51 years (36-73), disease duration 21.5 years (10-37), EDSS score 6.0 (4.5-8.0), and baseline NRS score 8 (5-9). The clinical course was relapsing-remitting in 2 and secondary progressive in 10 patients. Seven patients (58.3%) resulted THC:CBD responders at T1. On fMRI analysis, we observed a significant association between THC:CBD therapy and global brain connectivity increase, decreased connectivity of motor areas, and bidirectional connectivity changes of the left cerebellum with a number of cortical areas. Connectivity increase at T1 was greater in responders than non-responders.
Conclusions: THC:CBD administration appears to increase overall brain connectivity of MS patients with spasticity, particularly in responders. Modulation of motor areas and cerebellum connectivity seems to play a prominent role in THC:CBD effect.
Disclosure:
Gajofatto Alberto: nothing to disclose.
Cordobi Nicolò: nothing to disclose.
Gobbin Francesca: nothing to disclose.
Calabrese Massimiliano: Advisory Board membership: Bayer-Shering, Genzyme, Biogen Idec. Payment for development of educational presentations including service on speakers bureaus: Biogen-Elan, Genzyme, TEVA, Bayer Schering, Travel/accommodation expenses covered or reimbursed: Novartis Pharma, Genzyme, Biogen idec, Merck Serono, Bayer-Schering, TEVA.
Barillari Marco: nothing to disclose.
Turatti Marco:nothing to disclose.
Benedetti Maria Donata: nothing to disclose
Abstract: P508
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: THC:CBD is a second-line agent for the treatment of spasticity in MS with partial efficacy. Although THC:CBD mechanism of action is not completely understood, it may involve modulation of nociceptive as well as corticospinal pathways.
Goals: Aim of this study is to investigate brain networks connectivity changes on resting state (RS) functional MRI (fMRI) of MS patients treated with THC:CBD.
Methods: Based on statistical power calculation, we planned to include at least 12 MS patients eligible for treatment with THC:CBD oromucosal spray and followed at Verona University Hospital MS Center. Patients were evaluated at baseline before treatment start (T0) and after ≥4 weeks of THC:CBD treatment at a stable dose (T1). Clinical variables included the EDSS and the Numerical Rating Scale (NRS) for spasticity scores. THC:CBD response was defined as a ≥20% reduction on the NRS score at T1 compared to T0. Brain MRI was performed at T0 and T1 on a 1.5 T scanner, acquiring RS fMRI with a T2-weighted EPI sequence (TR=3000 ms, TE=50 ms, slice thickness=4 mm, ETL=57, 30 slices, 80 dynamics, time=240 s). Connectivity changes were compared before and after treatment in the whole group and according to response status, using functional connectivity toolbox (CONN, version 15.h). Each exam was first preprocessed using default CONN pipeline, then a second level group analysis step was applied. ROI-to-ROI and seed-to-voxel connectivity were evaluated.
Results: Between January and September 2014, 15 consecutive patients were enrolled in the study. Of these, 12 (7 males, 5 females) completed all the assessments and entered data analysis. Median age was 51 years (36-73), disease duration 21.5 years (10-37), EDSS score 6.0 (4.5-8.0), and baseline NRS score 8 (5-9). The clinical course was relapsing-remitting in 2 and secondary progressive in 10 patients. Seven patients (58.3%) resulted THC:CBD responders at T1. On fMRI analysis, we observed a significant association between THC:CBD therapy and global brain connectivity increase, decreased connectivity of motor areas, and bidirectional connectivity changes of the left cerebellum with a number of cortical areas. Connectivity increase at T1 was greater in responders than non-responders.
Conclusions: THC:CBD administration appears to increase overall brain connectivity of MS patients with spasticity, particularly in responders. Modulation of motor areas and cerebellum connectivity seems to play a prominent role in THC:CBD effect.
Disclosure:
Gajofatto Alberto: nothing to disclose.
Cordobi Nicolò: nothing to disclose.
Gobbin Francesca: nothing to disclose.
Calabrese Massimiliano: Advisory Board membership: Bayer-Shering, Genzyme, Biogen Idec. Payment for development of educational presentations including service on speakers bureaus: Biogen-Elan, Genzyme, TEVA, Bayer Schering, Travel/accommodation expenses covered or reimbursed: Novartis Pharma, Genzyme, Biogen idec, Merck Serono, Bayer-Schering, TEVA.
Barillari Marco: nothing to disclose.
Turatti Marco:nothing to disclose.
Benedetti Maria Donata: nothing to disclose