Chronic Exertional Compartment Syndrome Caused by Functional Venous Outflow Obstruction.

OBJECTIVE: Investigate the theory that chronic exertional compartment syndrome (CECS) results from venous outflow obstruction due to functional muscular compression. Chronic exertional compartment syndrome occurs when increased pressure within a muscle compartment produces pain and/or neurologic symptoms. The exact etiology of CECS is unknown, leading to inconsistent diagnostic and treatment plans. STUDY DESIGN: Retrospective case series. SETTING: Private practice and sports medicine. PATIENTS: Two hundred eighty-four patients with exercise-induced lower leg pain. Twenty-two patients lost to follow-up. INTERVENTIONS: Leg vasculature was evaluated using stress computed tomography angiography (CTA) and MVP Flex to identify areas of functional venous compression. All patients then underwent targeted botulinum toxin treatment. Posttreatment follow-up imaging was performed using stress CTA in 197 patients. MAIN OUTCOME MEASURES: Presence of functional venous compression on stress CTA. Symptom reduction and normalization of venous flow after targeted botulinum toxin injections. RESULTS: Baseline imaging demonstrated CECS and functional venous obstruction with replication of symptoms in 260 of 284 patients [91.5% ± 3.2% (95% CI)]. Four weeks after treatment, 227 of 284 patients [79.9% ± 4.7% (95% CI)] described reduced/resolved symptoms with activity. One hundred fifty-five of the 197 patients [78.7% ± 5.7% (95% CI)] reimaged with stress CTA demonstrated resolved/reduced venous outflow obstruction. Twenty-two patients were lost to follow-up, and 35 patients had persistent symptoms. CONCLUSION: Chronic exertional compartment syndrome results from venous outflow obstruction due to functional muscular compression. Understanding the cause of CECS will allow the development of more precise and successful treatment plans. Based on our findings, treatment should be directed at the sites of venous compression.

Emerin induces nuclear breakage in Xenopus extract and early embryos.

Emerin is an inner nuclear membrane protein often mutated in Emery-Dreifuss muscular dystrophy. Because emerin has diverse roles in nuclear mechanics, cytoskeletal organization, and gene expression, it has been difficult to elucidate its contribution to nuclear structure and disease pathology. In this study, we investigated emerin's impact on nuclei assembled in Xenopus laevis egg extract, a simplified biochemical system that lacks potentially confounding cellular factors and activities. Notably, these extracts are transcriptionally inert and lack endogenous emerin and filamentous actin. Strikingly, emerin caused rupture of egg extract nuclei, dependent on the application of shear force. In egg extract, emerin localized to nonnuclear cytoplasmic membranes, and nuclear rupture was rescued by targeting emerin to the nucleus, disrupting its membrane association, or assembling nuclei with lamin A. Furthermore, emerin induced breakage of nuclei in early-stage X. laevis embryo extracts, and embryos microinjected with emerin were inviable, with ruptured nuclei. We propose that cytoplasmic membrane localization of emerin leads to rupture of nuclei that are more sensitive to mechanical perturbation, findings that may be relevant to early development and certain laminopathies.