title: Oral fingolimod reduces glutamate-mediated intracortical excitability in relapsing-remitting multiple sclerosis.
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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Neurology, Campus Bio-Medico University of Rome, via Alvaro del Portillo 200, Rome 00128, Italy. Electronic address: doriana.landi@gmail.com.
authors.forename: D
authors.initials: D
authors.lastname: Landi
authors.affiliation: Department of Neurology, Campus Bio-Medico University of Rome, via Alvaro del Portillo 200, Rome 00128, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Vollaro
authors.affiliation: Department of Neurology, Campus Bio-Medico University of Rome, via Alvaro del Portillo 200, Rome 00128, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Pellegrino
authors.affiliation: Department of Neurology, Campus Bio-Medico University of Rome, via Alvaro del Portillo 200, Rome 00128, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Mulas
authors.affiliation: Department of Neurology, Campus Bio-Medico University of Rome, via Alvaro del Portillo 200, Rome 00128, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ghazaryan
authors.affiliation: Department of Neurology, Campus Bio-Medico University of Rome, via Alvaro del Portillo 200, Rome 00128, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Falato
authors.affiliation: Department of Neurology, Campus Bio-Medico University of Rome, via Alvaro del Portillo 200, Rome 00128, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Pasqualetti
authors.affiliation: Department of Neurology, Campus Bio-Medico University of Rome, via Alvaro del Portillo 200, Rome 00128, Italy.
authors.forename: P M
authors.initials: PM
authors.lastname: Rossini
authors.affiliation: Department of Neurology, Campus Bio-Medico University of Rome, via Alvaro del Portillo 200, Rome 00128, Italy.
authors.forename: M M
authors.initials: MM
authors.lastname: Filippi
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000818:Animals; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D005260:Female; D000068876:Fingolimod Hydrochloride; D018698:Glutamic Acid / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000187:drug effects* / Q000502:physiology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000503:physiopathology; D011409:Propylene Glycols / Q000008:administration & dosage*; D011446:Prospective Studies; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D050781:Transcranial Magnetic Stimulation / Q000379:methods
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D018698:Glutamic Acid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
keywords: Fingolimod; Glutamate; Intracortical facilitation; Motor cortex; Multiple sclerosis; Transcranial magnetic stimulation