Contributions
Abstract: P1266
Type: Poster Sessions
Abstract Category: Therapy - Tools for detecting therapeutic response
Introduction: Most patients with multiple sclerosis (MS) develop walking limitations during the disease. Only a subset of patients improves with oral fampridine, the only drug approved for this condition.
Objectives: Evaluate the effect of Fampridine on cortical excitability in MS patients with gait disability.
Aim: Investigate whether cortical excitability changes can serve as predictor of therapeutic response to Fampridine.
Methods: This prospective observational study enrolled adult MS patients with gait impairment (EDSS score range: 2.5-7) planned to receive Fampridine. Patients with contraindications to Fampridine or MEPs, recent relapse (< 3 months), recent modification of treatment (prior 6 months), or EDSS above 7 were excluded. Eligible patients had to have recordable Motor Evoked Potentials (MEPs) in at least one hand. They received Fampridine 10 mg twice daily for two weeks. Upon inclusion and 14 days after starting Fampridine, a neurologist (NR) blinded to the cortical excitability studies performed a neurological examination, timed 25-foot walk test (T25wt) and EDSS, while a neurologist (RA) blinded to the clinical evaluation performed cortical excitability studies to measure Resting Motor Threshold (rMT), Short-Interval Cortical Inhibition, Intracortical Facilitation (ICF), and Cortical Silent Period.
Results: Twenty patients were included (11 men; mean age=49). Thirteen had relapsing remitting MS, seven had progressive disease (EDSS 2.5-7). Mean improvement on T25wt (ΔT25wt) was 4.9 seconds (range 1.1-7.6). Eleven patients considered responders to Fampridine had 20% improvement compared to baseline. The treatment was tolerated well with no serious adverse effects.
At baseline, EDSS positively correlated only with rMT (0.567; p-value=0.009). At follow up after 14 days, significant enhancement of ICF15 was observed (139% versus 243%, p=0.018). ICF-10 was enhanced but did not reach statistical significance. A significant positive correlation was only found between ΔT25wt and rMT (p-value=0.0089).
Discussion and conclusions: Fampridine had significant modulatory effect of the cerebral cortex demonstrated by increased excitatory effect of paired-pulse TMS. This Glutamate enhancing effect reflects a decreased threshold of excitatory control rather than a change in GABA/Glutamate balance. rMT could help select patients with a favorable response to Fampridine.
Disclosure: This research was supported by an unrestricted grant from Biogen.
All authors have nothing to disclose.
Abstract: P1266
Type: Poster Sessions
Abstract Category: Therapy - Tools for detecting therapeutic response
Introduction: Most patients with multiple sclerosis (MS) develop walking limitations during the disease. Only a subset of patients improves with oral fampridine, the only drug approved for this condition.
Objectives: Evaluate the effect of Fampridine on cortical excitability in MS patients with gait disability.
Aim: Investigate whether cortical excitability changes can serve as predictor of therapeutic response to Fampridine.
Methods: This prospective observational study enrolled adult MS patients with gait impairment (EDSS score range: 2.5-7) planned to receive Fampridine. Patients with contraindications to Fampridine or MEPs, recent relapse (< 3 months), recent modification of treatment (prior 6 months), or EDSS above 7 were excluded. Eligible patients had to have recordable Motor Evoked Potentials (MEPs) in at least one hand. They received Fampridine 10 mg twice daily for two weeks. Upon inclusion and 14 days after starting Fampridine, a neurologist (NR) blinded to the cortical excitability studies performed a neurological examination, timed 25-foot walk test (T25wt) and EDSS, while a neurologist (RA) blinded to the clinical evaluation performed cortical excitability studies to measure Resting Motor Threshold (rMT), Short-Interval Cortical Inhibition, Intracortical Facilitation (ICF), and Cortical Silent Period.
Results: Twenty patients were included (11 men; mean age=49). Thirteen had relapsing remitting MS, seven had progressive disease (EDSS 2.5-7). Mean improvement on T25wt (ΔT25wt) was 4.9 seconds (range 1.1-7.6). Eleven patients considered responders to Fampridine had 20% improvement compared to baseline. The treatment was tolerated well with no serious adverse effects.
At baseline, EDSS positively correlated only with rMT (0.567; p-value=0.009). At follow up after 14 days, significant enhancement of ICF15 was observed (139% versus 243%, p=0.018). ICF-10 was enhanced but did not reach statistical significance. A significant positive correlation was only found between ΔT25wt and rMT (p-value=0.0089).
Discussion and conclusions: Fampridine had significant modulatory effect of the cerebral cortex demonstrated by increased excitatory effect of paired-pulse TMS. This Glutamate enhancing effect reflects a decreased threshold of excitatory control rather than a change in GABA/Glutamate balance. rMT could help select patients with a favorable response to Fampridine.
Disclosure: This research was supported by an unrestricted grant from Biogen.
All authors have nothing to disclose.