{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:22:41Z","timestamp":1789024961435,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T00:00:00Z","timestamp":1468540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 3857\u201077570C"],"award-info":[{"award-number":["T32 3857\u201077570C"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Epilepsy is one of the most disabling symptoms of tuberous sclerosis complex (<jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>) and is a leading cause of morbidity and mortality in affected individuals. The relationship between systemic disease manifestations and the presence of epilepsy has not been thoroughly investigated. This study utilizes a multicenter <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content> Natural History Database including 1,816 individuals to test the hypothesis that systemic disease manifestations of <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content> are associated with epilepsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Univariate analysis was used to identify patient characteristics (e.g., age, gender, race, and <jats:italic><jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content><\/jats:italic> mutation status) associated with the presence of epilepsy. Individual logistic regression models were built to examine the association between epilepsy and each candidate systemic or neurologic disease variable, controlling for the patient characteristics found to be significant on univariate analysis. Finally, a multivariable logistic regression model was constructed, using the variables found to be significant on the individual analyses as well as the patient characteristics that were significant on univariate analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nearly 88% of our cohort had a history of epilepsy. After adjusting for age, gender, and <jats:italic><jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content><\/jats:italic> mutation status, multiple systemic disease manifestations including cardiac rhabdomyomas (odds ratio [<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>] 2.3, 95% confidence interval [<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>] 1.3\u20133.9, p = 0.002), retinal hamartomas (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 2.1, <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.0\u20134.3, p = 0.04), renal cysts (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 2.1, <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.3\u20133.4, p = 0.002), renal angiomyolipomas (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 3.0, <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.8\u20135.1, p &lt; 0.001), shagreen patches (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 1.7, <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.0\u20132.7, p = 0.04), and facial angiofibromas (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 1.7, <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.1\u20132.9, p = 0.03) were associated with a higher likelihood of epilepsy. In the multivariable logistic regression model, cardiac rhabdomyomas (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 1.9, <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.0\u20133.5, p = 0.04) remained significantly associated with the presence of epilepsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>The identification of systemic disease manifestations such as cardiac rhabdomyomas that confer a higher risk of epilepsy development in <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content> could contribute to disease prognostication and assist in the identification of individuals who may receive maximal benefit from potentially novel, targeted, preventative therapies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13467","type":"journal-article","created":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T09:56:57Z","timestamp":1468576617000},"page":"1443-1449","source":"Crossref","is-referenced-by-count":39,"title":["Systemic disease manifestations associated with epilepsy in tuberous sclerosis complex"],"prefix":"10.1111","volume":"57","author":[{"given":"Anna","family":"Jeong","sequence":"first","affiliation":[{"name":"Department of Neurology Washington University School of Medicine St. Louis Missouri U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine St. Louis Missouri U.S.A."},{"name":"Hope Center for Neurological Disorders Washington University School of Medicine St. Louis Missouri 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