D Landi1, S Vollaro2, G Pellegrino2, D Mulas2, A Ghazaryan2, E Falato2, P Pasqualetti2, P M Rossini2, M M Filippi2. 1. Department of Neurology, Campus Bio-Medico University of Rome, via Alvaro del Portillo 200, Rome 00128, Italy. Electronic address: doriana.landi@gmail.com. 2. Department of Neurology, Campus Bio-Medico University of Rome, via Alvaro del Portillo 200, Rome 00128, Italy.
Abstract
OBJECTIVE: Fingolimod is an effective disease modifying therapy for multiple sclerosis (MS). Beyond its main action on peripheral lymphocytes, several noteworthy side effects have been demonstrated in vitro, among which modulation of neural excitability. Our aim was to explore cortical excitability in vivo in patients treated with fingolimod 0.5mg/day. METHODS: Paired-pulse TMS was applied on the left primary motor cortex in 13 patients affected by relapsing-remitting MS, the day before the first dose of fingolimod (T0) and 60days later (T1). Resting motor threshold, baseline motor evoked potentials, short interval intracortical inhibition (at 1, 3, 5ms) and intracortical facilitation (at 7, 9, 11 and 13ms) were estimated at T0 and T1. RESULTS: Intracortical facilitation was reduced at T1, without any changes in short interval intracortical inhibition. CONCLUSIONS: Fingolimod selectively reduced intracortical facilitation, which is mainly mediated by glutamate. SIGNIFICANCE: This is the first in vivo confirmation of the effects of fingolimod on glutamatergic drive in treated humans. Our results suggest a novel neuromodulatory activity of fingolimod with potential effect on glutamate-mediated excitotoxicity in vivo, as already seen in animal models.
OBJECTIVE:Fingolimod is an effective disease modifying therapy for multiple sclerosis (MS). Beyond its main action on peripheral lymphocytes, several noteworthy side effects have been demonstrated in vitro, among which modulation of neural excitability. Our aim was to explore cortical excitability in vivo in patients treated with fingolimod 0.5mg/day. METHODS: Paired-pulse TMS was applied on the left primary motor cortex in 13 patients affected by relapsing-remitting MS, the day before the first dose of fingolimod (T0) and 60days later (T1). Resting motor threshold, baseline motor evoked potentials, short interval intracortical inhibition (at 1, 3, 5ms) and intracortical facilitation (at 7, 9, 11 and 13ms) were estimated at T0 and T1. RESULTS: Intracortical facilitation was reduced at T1, without any changes in short interval intracortical inhibition. CONCLUSIONS:Fingolimod selectively reduced intracortical facilitation, which is mainly mediated by glutamate. SIGNIFICANCE: This is the first in vivo confirmation of the effects of fingolimod on glutamatergic drive in treated humans. Our results suggest a novel neuromodulatory activity of fingolimod with potential effect on glutamate-mediated excitotoxicity in vivo, as already seen in animal models.
Authors: Giovanni Pellegrino; Giorgio Arcara; Giovanni Di Pino; Cristina Turco; Matteo Maran; Luca Weis; Francesco Piccione; Hartwig Roman Siebner Journal: Hum Brain Mapp Date: 2019-03-10 Impact factor: 5.038
Authors: Giovanni Pellegrino; Matteo Maran; Cristina Turco; Luca Weis; Giovanni Di Pino; Francesco Piccione; Giorgio Arcara Journal: Neural Plast Date: 2018-01-11 Impact factor: 3.599
Authors: Giovanni Pellegrino; Giorgio Arcara; Anna Maria Cortese; Luca Weis; Silvia Di Tomasso; Gino Marioni; Stefano Masiero; Francesco Piccione Journal: Neuroimage Clin Date: 2019-11-12 Impact factor: 4.881