Compound muscle action potential amplitude predicts the severity of cubital tunnel syndrome.Background: Cubital tunnel syndrome has a spectrum of presentations ranging from mild paresthesias to debilitating numbness and intrinsic atrophy. Commonly, the classification of severity relies on clinical symptoms and slowing of conduction velocity across the elbow. However, changes in compound muscle action potential (CMAP) amplitude more accurately reflect axonal loss. We hypothesized that CMAP amplitude would better predict functional impairment than conduction velocity alone.Methods: A retrospective cohort of patients who underwent a surgical procedure for cubital tunnel syndrome over a 5year period were included in the study. All patients had electrodiagnostic testing performed at our institution. Clinical and electrodiagnostic variables were recorded. The primary outcome was preoperative functional impairment, defined by grip and key pinch strength ratios. Multivariable regression identified which clinical and electrodiagnostic variables predicted preoperative functional impairment.Results: Eighty-three patients with a mean age of 57 years (75% male) were included in the study. The majority of patients (88%) had abnormal electrodiagnostic studies. Fifty-four percent had reduced CMAP amplitude, and 79% had slowing of conduction velocity across the elbow (recorded from the first dorsal interosseous). On bivariate analysis, older age and longer symptom duration were significantly associated (p < 0.05) with reduced CMAP amplitude and slowing of conduction velocity across the elbow, whereas body mass index (BMI), laterality, a primary surgical procedure compared with revision surgical procedure, Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire scores, and visual analog scale (VAS) scores for pain were not. Multivariable regression analysis demonstrated that reduced first dorsal interosseous CMAP amplitude independently predicted the loss of preoperative grip and key pinch strength and that slowed conduction velocity across the elbow did not. Conclusions:Reduced first dorsal interosseous amplitude predicted preoperative weakness in grip and key pinch strength, and isolated slowing of conduction velocity across the elbow did not. CMAP amplitude is a sensitive indicator of axonal loss and an important marker of the severity of cubital tunnel syndrome. It should be considered when counseling patients with regard to their prognosis and determining the necessity and timing of operative intervention.Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.Disclosure: There was no source of external funding for this study. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article

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Increased osteoclast-mediated bone resorption is characteristic of osteoporosis, malignant bone disease and inflammatory arthritis. Targeted deletion of Sirtuin1 (Sirt1), a key player in aging and metabolism, in osteoclasts results in increased osteoclast-mediated bone resorption in vivo, making it a potential novel therapeutic target to block bone resorption. Sirt1 activating compounds (STACs) were generated and were investigated in animal disease models and in humans however their mechanism of action was a source of controversy. We studied the effect of SRT2183 and SRT3025 on osteoclastogenesis in bone-marrow derived macrophages (BMMs) in vitro, and discovered that these STACs inhibit RANKL-induced osteoclast differentiation, fusion and resorptive capacity without affecting osteoclast survival. SRT2183 and SRT3025 activated AMPK, increased Sirt1 expression and decreased RelA/p65 lysine310 acetylation, critical for NF-κB activation, and an established Sirt1 target. However, inhibition of osteoclastogenesis by these STACs was also observed in BMMs derived from sirt1 knock out (sirt1-/-) mice lacking the Sirt1 protein, in which neither AMPK nor RelA/p65 lysine 310 acetylation was affected, confirming that these effects require Sirt1, but suggesting that Sirt1 is not essential for inhibition of osteoclastogenesis by these STACs under these conditions. In sirt1 null osteoclasts treated with SRT2183 or SRT3025 Sirt3 was found to be down-regulated. Our findings suggest that SRT2183 and SRT3025 activate Sirt1 and inhibit RANKL-induced osteoclastogenesis in vitro however under conditions of Sirt1 deficiency can affect Sirt3. As aging is associated with reduced Sirt1 level and activity, the influence of STACs on Sirt3 needs to be investigated in vivo in animal and human disease models of aging and osteoporosis.

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