Early effect of dalfampridine in patients with MS: A multi-instrumental approach to better investigate responsiveness

• A multi-instrumental approach for evaluation of early responsivity of MS patients to treatment with 4-amynopiridine (4-AP)
• Walking speed, subjective view, motor evoked potentials, Diffusion Tensor Imaging (DTI) changes after 2 weeks of 4-AP therapy
• Dalfampridine improves motor central conduction and walking abilities, especially in patients more compromised at baseline
• Patients reported subjective improvement of motion after treatment, as evaluated by means of MSWS-12
• DTI showed changes in Medial and Radial Diffusivity after the treatment, possibly related to 4-AP mechanism of action
• Treatment with 4-AP should be continued in all patients who ameliorate in walking speed or refer a subjective benefit

Background4-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.Objectiveto study early 4-AP effect with clinical, subjective, neurophysiological and neuroradiological tools.MethodsClinical (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) 14 days of 4-AP treatment. MEPs were recorded from Abductor Hallucis of both legs. A Tract-Based-Spatial-Statistics (TBSS) was performed on DTI.ResultsWe 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.ConclusionNeurophysiological 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.