title: Early effect of dalfampridine in patients with MS: A multi-instrumental approach to better investigate responsiveness.
abstract: BACKGROUND
  4-aminopyridine (4-AP) is a potassium-channel blocker able to enhance walking speed in MS improving the action potentials of demyelinated axons on which internodal potassium channels are exposed.
  
  
  OBJECTIVE
  to study early 4-AP effect with clinical, subjective, neurophysiological and neuroradiological tools.
  
  
  METHODS
  Clinical (Timed 25-Foot Walk - T25FW, Timed Up-And-Go - TUG), subjective (MS Walking Scale-12 - MSWS-12), neurophysiological (Motor Evoked Potentials - MEPs) and imaging (Diffusion Tensor Imaging - DTI) evaluations were performed before (T0) and after (T1) 14days of 4-AP treatment. MEPs were recorded from Abductor Hallucis of both legs. A Tract-Based-Spatial-Statistics (TBSS) was performed on DTI.
  
  
  RESULTS
  We found a significant difference between T0 and T1 for T25FW, TUG, MSWS-12 (p≤0.001) in the whole patients' sample (23 subjects, median EDSS 6.0) and decrease of Central Motor Conduction Time and increase of mean Amplitude (Amp) at T1 (p=0.008 and p=0.006). We also recorded a significant difference of T25FW, TUG, MSWS-12 and Amp in clinical responder (CR) patients (CR: amelioration >20% at T25FW). TBSS showed a significant Mean and Radial Diffusivity reduction in the corticospinal tracts (p<0.05) of the whole group of patients; this reduction was also found in the CR subgroup.
  
  
  CONCLUSIONS
  Neurophysiological and neuroradiological parameters were modified in MS patients treated with 4-AP, and most of them reported a subjective improvement of their motor performances after treatment. The use of clinical, subjective, neurophysiological and neuroradiological tools could help to better explore MS patients responsiveness to 4-AP.
authors.affiliation: Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy. Electronic address: laura.brambilla@istituto-besta.it.
authors.forename: L
authors.initials: L
authors.lastname: Brambilla
authors.affiliation: Department of Neurophysiology, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Rossi Sebastiano
authors.affiliation: Department of Neuroradiology, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Aquino
authors.affiliation: Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Torri Clerici
authors.affiliation: Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Brenna
authors.affiliation: Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy; University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Moscatelli
authors.affiliation: Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Frangiamore
authors.affiliation: Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Giovannetti
authors.affiliation: Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Antozzi
authors.affiliation: Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Mantegazza
authors.affiliation: Department of Neurophysiology, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Franceschetti
authors.affiliation: Department of Neuroradiology, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Bruzzone
authors.affiliation: Department of Neuroradiology, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Erbetta
authors.affiliation: Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Confalonieri
mesh_terms: D015761:4-Aminopyridine / Q000627:therapeutic use*; D000328:Adult; D056324:Diffusion Tensor Imaging; D019054:Evoked Potentials, Motor / Q000187:drug effects; D005080:Exercise Test; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D017063:Outcome Assessment, Health Care / Q000379:methods*; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D050781:Transcranial Magnetic Stimulation; D016138:Walking / Q000502:physiology
chemical_list: D026902:Potassium Channel Blockers; D015761:4-Aminopyridine
keywords: 4-Aminopyridine; Dalfampridine; Diffusion Tensor Imaging; Fampridine; Motor Evoked Potentials; Multiple Sclerosis; Subjective outcomes; Walking ability