At the 12 days endpoint analysis, based on the electrophysiological evaluation, the group divided into responders and non-responders. 9 patients presented early amelioration of the MEP and CMCT latencies, whereas the other 6 showed no significant improvement. The following analysis, repeated measures ANOVA, was conducted only on the group of the responders (n=9).
3.1 Quality of life
Regarding the quality of life, a significant main effect of time was observed (Fig. 1), Wilks' Lambda = 0.033, F (3, 6) =58, p < 0.001.
When we examined the pairwise comparisons for statistic differences within groups per daily quality of life, we observed significant differences between quality of life at baseline and quality of life on day 12 (p < 0.001), between quality of life at baseline and quality of life on day 30 (p < 0.001), between quality of life at baseline and quality of life on day 90 (p < 0.001). Also, significant differences were observed between quality of life at day 5 and quality of life on day 12 (p < 0.001), between quality of life at day 5 and quality of life on day 30 (p < 0.001), between quality of life at day 5 and quality of life on day 90 (p < 0.001). Furthermore, significant differences were observed between quality of life at day 12 and quality of life on day 30 (p < 0.001) and between quality of life at day 12 and quality of life on day 90 (p = 0.003). The only non-significant differences observed were between quality of life baseline and quality of life at day 5 (p = 1) and between quality of life at day 30 and quality of life at day 90 (p = 1).
Fig. 1 The effect of fampridine on the level of the quality of life
3.2 Timed-25-Foot-Walk test
Analysing the Timed-25-Foot-Walk test results, a significant main effect of time was observed (Fig. 2), Wilks' Lambda = 0.011, F (4, 5) =112.621, p < 0.001.
When examining the pairwise comparisons for statistic differences within groups related to the Timed-25-Foot-Walk test, we observed significant differences between the time obtained by the patients at baseline and the time obtained on day 12 (p < 0.001), between time obtained at baseline and time obtained on day 30 (p < 0.001), between time obtained at baseline and time obtained on day 90 (p < 0.001). Also significant differences were observed between time obtained by the patients on the 25 Foot Walk test at day 5 and the time obtained on day 12 (p < 0.001), between time obtained at day 5 and time obtained on day 30 (p < 0.001), between time obtained at day 5 and time obtained on day 90 (p < 0.001). Significant differences were also observed between time obtained by the patients on the 25 Foot Walk test at day 12 and time obtained on day 30 (p < 0.001) and between time obtained at day 12 and time obtained on day 90 (p = 0.003). In addition, significant differences were also observed between time obtained by the patients on the 25 Foot Walk test on day 30 and time obtained on day 90 (p<0.001). The only non-significant differences observed were between the Timed-25-Foot-Walk test at baseline and Timed-25-Foot-Walk test at day 5 (p = 0.132).
Fig. 2 The effect of fampridine on the time obtained by the patients on the 25 Foot Walk test
3.3 The Central Motor Conduction Time (CMCT) from the right hemisphere
Regarding the Central Motor Conduction Time (CMCT) from the right hemisphere a non- significant main effect of time was observed (Fig 3), Wilks' Lambda = 0.202, F (4, 5) =4.931, p = 0.055.
However, when we examined the pairwise comparisons, to see if there is a statistical difference within groups dealing with the Central Motor Conduction Time (CMCT) from the right hemisphere, we observed significant differences between the CMCT at baseline and CMCT on day 5 (p = 0.035), between CMCT at baseline and CMCT on day 12 (p = 0.029), between CMCT at baseline and CMCT on day 90 (p = 0.03). Also, significant differences were observed between CMCT at day 30 and CMCT on day 90 (p = 0.005). Non-significant differences were observed between any other possible pair of time points where the CMCT was measured.
Fig. 3 The effect of fampridine on the time obtained by the patients on the Central Motor Conduction Time (CMCT) from the right hemisphere
3.4 The Central Motor Conduction Time (CMCT) from the left hemisphere
Analysis of CMCT from the left hemisphere revealed a significant main effect of time (Fig. 4), Wilks' Lambda = 0.130, F (4, 5) =8.387, p < 0.019.
During these next pairwise comparisons, we observed significant differences between the CMCT at baseline and CMCT on day 12 (p = 0.009), between CMCT at baseline and CMCT on day 90 (p = 0.037), between CMCT at day 5 and CMCT on day 12 (p = 0.031). Also, significant differences were observed between CMCT at day 30 and CMCT on day 90 (p = 0.004). Non-significant differences were observed between any other possible pair of time points where the CMCT was measured.
Fig. 4 The effect of fampridine on the time obtained by the patients on the Central Motor Conduction Time (CMCT) from the left hemisphere
3.5 The Central Motor Conduction Time (CMCT)
A significant main effect of time was observed, Wilks' Lambda = 0.106, F (4, 5) =10.556, p < 0.012.
During pairwise comparisons, investigating statistical differences within groups, significant differences between the CMCT at baseline and CMCT were visible on day 5 (p = 0.006), between CMCT at baseline and CMCT on day 12 (p = 0.014), between CMCT at baseline and CMCT on day 90 (p = 0.029). Also, significant differences were observed between CMCT at day 5 and CMCT at day 12 (p=0.040) and between CMCT at day 30 and CMCT on day 90 (p = 0.004). Non-significant differences were observed between any other possible pair of time points where the CMCT was measured. (Fig. 5)
Fig. 5 The effect of fampridine on the time obtained by the patients on the Central Motor Conduction Time (CMCT)
3.6 The Central Motor Conduction Time (CMCT) from the right and left hemisphere in the lower limbs
CMCT from the left hemisphere in the lower limbs showed a significant main effect of time (Fig. 6), Wilks' Lambda = 0.159, F (4, 5) =6.612, p = 0.031.
Significant differences between the CMCT at baseline and CMCT were visible on day 12 (p = 0.044) by the use of pairwise comparisons. Also, significant differences were observed between CMCT at day 30 and CMCT on day 90 (p = 0.011). Non-significant differences regarding the CMCT in the lower limbs from the left hemisphere were observed between any other possible pair of time points where the CMCT was measured.
Regarding the Central Motor Conduction Time (CMCT) from the right hemisphere in the lower limbs a significant main effect of time was observed, Wilks' Lambda = 0.162, F (4, 5) =6.458, p = 0.033.
When we examined the pairwise comparisons for statistical difference within groups related to the CMCT from the left hemisphere in the lower limbs, we observed significant differences only between CMCT at day 30 and CMCT on day 90 (p = 0.002).
Fig. 6 The effect of fampridine on the time obtained by the patients on the Central Motor Conduction Time (CMCT) from the left and right hemisphere in the lower limbs
3.7 The Central Motor Conduction Time (CMCT) from the right and left hemisphere in the upper limbs
Analysis of CMCT from the left hemisphere in the upper limbs revealed a significant main effect of time, Wilks' Lambda = 0.148, F (4, 5) =7.221, p = 0.026.
When we examined the pairwise comparisons for statistical difference within groups related to the CMCT from the left hemisphere in the upper limbs, we observed a statistically significant improvement between every time point in which this test was assessed (Fig. 7). Specifically, we found significant differences between CMCT at baseline and CMCT on day 5 (p = 0.039), CMCT at baseline and CMCT on day 12 (p = 0.003), CMCT at baseline and CMCT on day 30 (p = 0.001), CMCT at baseline and CMCT on day 90 (p < 0.001). Also, significant differences were observed between CMCT at day 5 and CMCT on day 12 (p = 0.001), CMCT on day 5 and CMCT on day 12 (p < 0.001), CMCT on day 5 and CMCT on day 90 (p < 0.001). Furthermore, significant differences were observed between CMCT at day 12 and CMCT on day 30 (p = 0.005), CMCT on day 12 and CMCT on day 90 (p = 0.001), CMCT on day 30 and CMCT on day 90 (p = 0.002).
Regarding the Central Motor Conduction Time (CMCT) from the right hemisphere in the upper limbs a significant main effect of time was observed, Wilks' Lambda = 0.074, F (4, 5) =15.595, p = 0.005.
Analysing in same manner the CMCT from the right hemisphere in the upper limbs, we observed a statistically significant improvement between every time point in which this test was assessed. Specifically, we found significant differences between CMCT at baseline and CMCT on day 5 (p = 0.001), CMCT at baseline and CMCT on day 12 (p < 0.001), CMCT at baseline and CMCT on day 30 (p < 0.001), CMCT at baseline and CMCT on day 90 (p < 0.001). Also, significant differences were observed between CMCT at day 5 and CMCT on day 12 (p < 0.001), CMCT on day 5 and CMCT on day 12 (p < 0.001), CMCT on day 5 and CMCT on day 90 (p < 0.001). Furthermore, significant differences were observed between CMCT at day 12 and CMCT on day 30 (p < 0.001), CMCT on day 12 and CMCT on day 90 (p < 0.001), CMCT on day 30 and CMCT on day 90 (p = 0.034).
Fig. 7 The effect of fampridine on the time obtained by the patients on the Central Motor Conduction Time (CMCT) from the left and right hemisphere in the upper limbs