Long-term effects of prolonged-release fampridine in cognitive function, fatigue, mood and quality of life of MS patients: The IGNITE study

A Prospective, Observational, Cohort Study to Assess the Efficacy and Safety of Prolonged-Release Fampridine in Cognition, Fatigue, Depression, and Quality of Life in Multiple Sclerosis Patients: The FAMILY Study

“…These findings are consistent with a number of previous studies which also reported an improvement in PASAT after shortor long-term treatment with PR-FAM [17,24,26]. Studies utilizing the Symbol Digit Modalities Test (SDMT) further corroborate these results by demonstrating an improvement in visual processing speed after short-and longterm treatment with PR-FAM [28,30,44,45]. In contrast, some studies failed to demonstrate an impact of PR-FAM on cognitive function, as assessed either by PASAT or SDMT [24,27,31].…”

“…These observations were extended by another study demonstrating PR-FAM's positive effects on depressive symptoms over 2 years in a cohort of MS patients; of note, responsiveness in depression did not coincide with an improvement in ambulatory function [18]. On the contrary, no positive effect on depression was reported after 6 and 12 months of PR-FAM treatment in a recent real-life study also conducted within Greece [28]. Given that fatigue and depression are closely interrelated with a similar pathophysiological mechanism even being speculated within the context of MS, it is not surprising that a paralleled improvement was observed in both variables.…”

“…Apart from one randomized, placebo-controlled study describing PR-FAM's beneficial effects on different cognitive domains as well as on fatigue and depression over 2 years in a cohort of MS patients [18], most studies conducted so far, utilizing a randomized, placebo-controlled design, have failed to demonstrate fampridine's benefits in such non-walking outcomes [22][23][24][25]. On the other hand, a limited number of openlabel, uncontrolled studies have already described PR-FAM-induced improvements in fatigue, cognition, mood and overall QoL [4,17,19,[26][27][28][29][30][31]. Whereas these studies offer valuable information towards a possible role of PR-FAM on these functions, data remain unclear, with variabilities in study parameters, including study design, treatment algorithms and assessment protocols, do not allowing the drawing of univocal conclusions [32].…”

Cognitive Efficacy of Pharmacologic Treatments in Multiple Sclerosis: A Systematic Review

“…The other class III crossover RCT in 20 MS patients found no significant cognitive improvement during the 2-week treatment condition relative to the placebo condition [52]. Of the remaining seven class IV observational studies, six were positive [53][54][55][56][57][58].…”

Gonadotropin-Releasing Hormone (GnRH) Neuron Potassium Currents and Excitability in Both Sexes Exhibit Minimal Changes upon Removal of Negative Feedback

“…Voltage-gated potassium channels are widely recognized as regulators of excitability (Johnston et al, 2010) and have been targeted clinically. For example, blocking a fraction of potassium channels with 4-aminopyridine (4AP) increases the excitability of motor neurons in amyotropic lateral sclerosis and multiple sclerosis and provides relief from the symptoms of these diseases (Bakirtzis et al, 2018;Peikert et al, 2019). In many neurons, 4AP increases input resistance and diminishes the ability of voltage-gated potassium channels to blunt action potential firing and/or the membrane potential changes in response to synaptic inputs (Hoffman, 2013;DeFazio et al, 2019).…”