Because generalized fatigue is one of the most frequent manifestations of post-polio syndrome, many systemic diseases must be excluded. Most of these diseases can usually be excluded with blood tests and include hypo- and hyperthyroidism, anemia, leukemia and cancer, which cause an elevated erythrocyte sedimentation rate and other blood test abnormalities, liver failure, and kidney failure. Cardiac failure and sleep disorders also need to be excluded as causes of fatigue. Often in post-polio syndrome patients the creatinine kinase is mildly elevated (Jubelt and Cashman 1987; Nelson 1990; Windebank et al 1991; Waring and McLaurin 1992). In one study, elevated creatinine kinase levels were more likely to occur in those with progressive weakness (Windebank et al 1991), and markedly increased levels indicated muscle overuse (Peach 1990). Electrodiagnostic studies cannot differentiate patients with post-polio syndrome from asymptomatic post-polio patients (Cashman et al 1987; Jubelt and Drucker 1999). However, these studies are important to exclude other neuromuscular diseases (amyotrophic lateral sclerosis, radiculopathy, polyneuropathy, myasthenia gravis, and myopathies). In a comparative EMG analysis of muscle activity and assessment of muscle strength and fatigue after maximal isometric contraction during knee extension in post-polio patients, Correa and colleagues were able to show a decreased endurance on initial muscle contraction and during contraction 15 minutes after the initial maximal voluntary contraction, along with a muscle fatigue that was assessed through linear regression (Correa et al 2008). Imaging studies (eg, CT, MRI) are needed to exclude spine problems such as spondylosis and stenosis. Gonzalez and colleagues report that the CSF of persons with post-polio syndrome displayed a disease-specific and highly predictive (p=0.0017) differential expression of 5 distinct proteins: gelsolin, hemopexin, peptidylglycine alpha-amidating monooxygenase, glutathione synthetase, and kallikrein 6 in comparison with the control groups (Gonzalez et al 2009). An independent ELISA confirmed the increase of kallikrein 6, suggesting that these 5 proteins should be further evaluated as candidate biomarkers for the diagnosis and development of new therapies for post-polio syndrome patients.