L Brambilla1, D Rossi Sebastiano2, D Aquino3, V Torri Clerici4, G Brenna4, M Moscatelli5, R Frangiamore4, A M Giovannetti4, C Antozzi4, R Mantegazza4, S Franceschetti2, M G Bruzzone3, A Erbetta3, P Confalonieri4. 1. Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy. Electronic address: laura.brambilla@istituto-besta.it. 2. Department of Neurophysiology, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy. 3. Department of Neuroradiology, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy. 4. Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy. 5. 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.
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. CONCLUSION: 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.
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. CONCLUSION: 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: Ratthaporn Boonsuth; Rebecca S Samson; Carmen Tur; Marco Battiston; Francesco Grussu; Torben Schneider; Masami Yoneyama; Ferran Prados; Antrea Ttofalla; Sara Collorone; Rosa Cortese; Olga Ciccarelli; Claudia A M Gandini Wheeler-Kingshott; Marios C Yiannakas Journal: Front Neurol Date: 2021-11-25 Impact factor: 4.003