After the acute poliomyelitis, remaining motor neurons send out sprouts to take over degenerated muscle fibers (collateral sprouting). This results in enlarged motor units, 5 to 10 times larger than normal. These new synapses never seem to fully stabilize (Wiechers 1988). With increasing time since the acute polio, neuromuscular transmission becomes more unstable with increasing jitter and blocking (Wiechers and Hubbell 1981), which is more frequent in muscles with new weakness (Ryniewicz et al 1990; Maselli et al 1992). Findings from SFEMG reveal that the largest motor units are more likely to become unstable (Cashman et al 1987a; Emeryk et al 1990). Muscle biopsy studies support the electrophysiologic pathophysiology. Over time, the number of angulated fibers is continually increased (Dalakas and Illa 1991). On average, 30 to 40 years after the acute poliomyelitis there is disintegration of the new terminal sprouts that formed after the acute infection (Dalakas 1988; Gordon et al 2004). This is followed by degeneration of axonal branches as demonstrated by small group atrophy on muscle biopsies (Drachman et al 1967; Cashman et al 1987a). Later, larger group atrophy may occasionally be seen, suggesting a drop out of motor neurons (Dalakas and Illa 1991). An increasing inability to activate muscles may also play a role in post-polio syndrome weakness (Beelen et al 2003). Gonzalez and colleagues reported that the CSF of persons with post-polio syndrome displayed a disease-specific and highly predictive differential expression of 5 distinct proteins: gelsolin, hemopexin, peptidylglycine alpha-amidating monooxygenase, glutathione synthetase, and kallikrein 6, respectively, compared to the controls, leading to the hypothesis that denervation in post-polio syndrome is a result of chronic intrathecal inflammation as expressed by the increase in inflammatory cytokines (Gonzalez et al 2009).