How to design a therapeutic study in patients with the post-polio syndrome. Methodological concerns and status of present therapies

The innervation of muscles in patients with the post-polio syndrome (PPS) may differ from limb to limb or even within the same limb because of the segmental nature of the initial involvement and the varying degree of subsequent recovery. Consequently, the compensatory effort of the neighboring muscles varies even in the same limb. Clinicohistological studies have confirmed that in PPS the various muscle groups differ according to whether they were affected during the acute polio and have recovered (partially or completely), or whether they were clinically spared during the original disease, in spite of subclinical involvement. Because the impact of the late effects of polio is also variable in these muscle groups, the effect of therapies may be different not only from patient to patient and from limb to limb, but also from muscle to muscle within the same limb. These variables require careful statistical determination of the sample size at the design of a trial. Another problematic issue in the therapy of PPS is to define the end point of therapy. The two disabling PPS symptoms, excessive fatigue and new muscle weakness, can coexist. An experimental therapeutic design must focus separately on the fatigue, using validated fatigue scales, and on muscle weakness, using quantitative muscle testing. Another methodological concern is the placebo-controlled design. Patients with PPS, even those without depression, can be prone to a placebo effect; hence the need for controlled trials. Finally, the length of a trial remains unresolved because of the slow and unpredictable progression of PPS that varies from patient to patient. Until the natural history of PPS is defined, therapies aimed at arresting disease progression are not reliable.