Why drugs fail in postpolio syndrome

Post-poliomyelitis syndrome (PPS) is defined as the development of new muscle weakness, atrophy, and prominent mid-day muscle fatigue, unrelated to any known cause, that develops 25 to 30 years after paralytic poliomyelitis.1 Despite suggestions that it is an age-related phenomenon due to attrition of joints and muscles in an aging population, when strictly defined, the new weakness in PPS reflects ongoing motor neuron deterioration.2 Based on previously proposed mechanisms,1 two controlled clinical trials have been conducted, one with prednisone to increase muscle strength and another with amantadine to decrease muscle fatigue.1 Both studies were negative. In this issue of Neurology , Trojan et al. report the third negative controlled study.3 This is also the first multicenter trial using pyridostigmine, an anticholinesterase drug that improves neuromuscular transmission. No benefit was noted in quality of life (primary endpoint) or in muscle strength and fatigue (secondary endpoints). This well-conducted study brings up a number of complexities …