Tuberous sclerosis complex and epilepsy: Recent developments and future challenges

Gregory L. Holmes, Carl E. Stafstrom, Scott C. Baraban, Edward Bertram, Patrick Bolton, Amy Brooks-Kayal, Harry T. Chugani, Douglas Coulter, Peter Crino, Nihal C. Delanerolle, Orrin Devinsky, Margaret Jacobs, Frances E. Jensen, Jaideep Kapur, Rustem Khazipov, Timo Kirchstein, John Lonsdale, Gary Mathern, James Riviello, Mustafa SahinTristan Sands, Raman Sankar, Paula Schauwecker, Kevin Staley, Delia Talos, Elizabeth Thiele, Nancy Taylor, Cheryl Dunigan, Vicky H. Whittemore

Research output: Contribution to journalReview article

Abstract

Tuberous sclerosis complex (TSC) is a congenital syndrome characterized by the widespread development of benign tumors in multiple organs, caused by mutations in one of the tumor suppressor genes, TSC1 or TSC2. About 80% of affected patients have a new mutation, and the remaining 20% have inherited a TSC gene mutation from a parent. The disorder affects approximately 1 in 6000 individuals. Cortical tubers are the neuropathological hallmark of TSC. The most common neurological manifestations of TSC are epilepsy, mental retardation, and autistic behavior. Epilepsy occurs in up to 80-90% of patients and is often intractable, with a poor response to anticonvulsant medications. While the molecular basis of TSC is well established, far less is known about the mechanisms of epilepsy in this disorder. In this article, we first summarize known clinical aspects of TSC with emphasis on its neurological features. Then, based on the molecular, pathological, immunohistochemical, neurochemical, and physiological properties of tubers in patients with TSC and in animal models, we discuss possible mechanisms of seizures and epileptogenesis in TSC. Finally, we provide an updated literature review and a consensus statement from the Tuberous Sclerosis Complex Working Group for future research into the mechanisms of epilepsy in TSC.

Original languageEnglish (US)
Pages (from-to)617-630
Number of pages14
JournalEpilepsia
Volume48
Issue number4
DOIs
StatePublished - Apr 1 2007

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Keywords

  • Epilepsy
  • Epileptogenesis
  • Tuber
  • Tuberous sclerosis complex

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Holmes, G. L., Stafstrom, C. E., Baraban, S. C., Bertram, E., Bolton, P., Brooks-Kayal, A., Chugani, H. T., Coulter, D., Crino, P., Delanerolle, N. C., Devinsky, O., Jacobs, M., Jensen, F. E., Kapur, J., Khazipov, R., Kirchstein, T., Lonsdale, J., Mathern, G., Riviello, J., ... Whittemore, V. H. (2007). Tuberous sclerosis complex and epilepsy: Recent developments and future challenges. Epilepsia, 48(4), 617-630. https://doi.org/10.1111/j.1528-1167.2007.01035.x