Resting-state functional connectivity in multiple sclerosis patients receiving nabiximols for spasticity
Alberto Gajofatto 1 2, Nicolò Cardobi 3, Francesca Gobbin 3 4, Massimiliano Calabrese 3 4, Marco Turatti 4, Maria Donata Benedetti 4
- 1Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Piazzale L.A. Scuro 10, Verona, 37134, Italy. alberto.gajofatto@univr.it.
- 2Unit of Neurology, Regional Multiple Sclerosis Center, Borgo Roma Hospital, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. alberto.gajofatto@univr.it.
- 3Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Piazzale L.A. Scuro 10, Verona, 37134, Italy.
- 4Unit of Neurology, Regional Multiple Sclerosis Center, Borgo Roma Hospital, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
Affiliationer
Background: Nabiximols (Sativex®) is a cannabinoid approved for multiple sclerosis (MS)-related spasticity. Its mechanism of action is partially understood, and efficacy is variable.
Objective: To conduct an exploratory analysis of brain networks connectivity changes on resting state (RS) functional MRI (fMRI) of MS patients treated with nabiximols.
Methods: We identified a group of MS patients treated with Sativex® at Verona University Hospital, who underwent RS brain fMRI in the 4 weeks before (T0) and 4-8 weeks after (T1) treatment start. Sativex® response was defined as ≥ 20% spasticity Numerical Rating Scale score reduction at T1 vs. T0. Connectivity changes on fMRI were compared between T0 and T1 in the whole group and according to response status. ROI-to-ROI and seed-to-voxel connectivity were evaluated.
Results: Twelve MS patients (7 males) were eligible for the study. Seven patients (58.3%) resulted Sativex® responders at T1. On fMRI analysis, Sativex® exposure was associated with global brain connectivity increase (particularly in responders), decreased connectivity of motor areas, and bidirectional connectivity changes of the left cerebellum with a number of cortical areas.
Conclusions: Nabiximols administration is associated with brain connectivity increase of MS patients with spasticity. Modulation of sensorimotor cortical areas and cerebellum connectivity could play a role in nabiximols effect.