Tuberous sclerosis complex and epilepsy

Recent developments and future challenges

Gregory L. Holmes, Carl 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 Sahin & 9 others Tristan Sands, Raman Sankar, Paula Schauwecker, Kevin Staley, Delia Talos, Elizabeth Thiele, Nancy Taylor, Cheryl Dunigan, Vicky H. Whittemore

Research output: Contribution to journalArticle

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 2007
Externally publishedYes

Fingerprint

Tuberous Sclerosis
Epilepsy
Mutation
Neurologic Manifestations
Tumor Suppressor Genes
Intellectual Disability
Anticonvulsants
Consensus
Seizures
Animal Models

Keywords

  • Epilepsy
  • Epileptogenesis
  • Tuber
  • Tuberous sclerosis complex

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Holmes, G. L., Stafstrom, C., Baraban, S. C., Bertram, E., Bolton, P., Brooks-Kayal, A., ... 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

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

In: Epilepsia, Vol. 48, No. 4, 04.2007, p. 617-630.

Research output: Contribution to journalArticle

Holmes, GL, Stafstrom, C, Baraban, SC, Bertram, E, Bolton, P, Brooks-Kayal, A, Chugani, HT, Coulter, D, Crino, P, Delanerolle, NC, Devinsky, O, Jacobs, M, Jensen, FE, Kapur, J, Khazipov, R, Kirchstein, T, Lonsdale, J, Mathern, G, Riviello, J, Sahin, M, Sands, T, Sankar, R, Schauwecker, P, Staley, K, Talos, D, Thiele, E, Taylor, N, Dunigan, C & Whittemore, VH 2007, 'Tuberous sclerosis complex and epilepsy: Recent developments and future challenges', Epilepsia, vol. 48, no. 4, pp. 617-630. https://doi.org/10.1111/j.1528-1167.2007.01035.x
Holmes, Gregory L. ; Stafstrom, Carl ; Baraban, Scott C. ; Bertram, Edward ; Bolton, Patrick ; Brooks-Kayal, Amy ; Chugani, Harry T. ; Coulter, Douglas ; Crino, Peter ; Delanerolle, Nihal C. ; Devinsky, Orrin ; Jacobs, Margaret ; Jensen, Frances E. ; Kapur, Jaideep ; Khazipov, Rustem ; Kirchstein, Timo ; Lonsdale, John ; Mathern, Gary ; Riviello, James ; Sahin, Mustafa ; Sands, Tristan ; Sankar, Raman ; Schauwecker, Paula ; Staley, Kevin ; Talos, Delia ; Thiele, Elizabeth ; Taylor, Nancy ; Dunigan, Cheryl ; Whittemore, Vicky H. / Tuberous sclerosis complex and epilepsy : Recent developments and future challenges. In: Epilepsia. 2007 ; Vol. 48, No. 4. pp. 617-630.
@article{d47567fcabc44a3c9627657ea87bd2f3,
title = "Tuberous sclerosis complex and epilepsy: Recent developments and future challenges",
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.",
keywords = "Epilepsy, Epileptogenesis, Tuber, Tuberous sclerosis complex",
author = "Holmes, {Gregory L.} and Carl Stafstrom and Baraban, {Scott C.} and Edward Bertram and Patrick Bolton and Amy Brooks-Kayal and Chugani, {Harry T.} and Douglas Coulter and Peter Crino and Delanerolle, {Nihal C.} and Orrin Devinsky and Margaret Jacobs and Jensen, {Frances E.} and Jaideep Kapur and Rustem Khazipov and Timo Kirchstein and John Lonsdale and Gary Mathern and James Riviello and Mustafa Sahin and Tristan Sands and Raman Sankar and Paula Schauwecker and Kevin Staley and Delia Talos and Elizabeth Thiele and Nancy Taylor and Cheryl Dunigan and Whittemore, {Vicky H.}",
year = "2007",
month = "4",
doi = "10.1111/j.1528-1167.2007.01035.x",
language = "English (US)",
volume = "48",
pages = "617--630",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Tuberous sclerosis complex and epilepsy

T2 - Recent developments and future challenges

AU - Holmes, Gregory L.

AU - Stafstrom, Carl

AU - Baraban, Scott C.

AU - Bertram, Edward

AU - Bolton, Patrick

AU - Brooks-Kayal, Amy

AU - Chugani, Harry T.

AU - Coulter, Douglas

AU - Crino, Peter

AU - Delanerolle, Nihal C.

AU - Devinsky, Orrin

AU - Jacobs, Margaret

AU - Jensen, Frances E.

AU - Kapur, Jaideep

AU - Khazipov, Rustem

AU - Kirchstein, Timo

AU - Lonsdale, John

AU - Mathern, Gary

AU - Riviello, James

AU - Sahin, Mustafa

AU - Sands, Tristan

AU - Sankar, Raman

AU - Schauwecker, Paula

AU - Staley, Kevin

AU - Talos, Delia

AU - Thiele, Elizabeth

AU - Taylor, Nancy

AU - Dunigan, Cheryl

AU - Whittemore, Vicky H.

PY - 2007/4

Y1 - 2007/4

N2 - 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.

AB - 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.

KW - Epilepsy

KW - Epileptogenesis

KW - Tuber

KW - Tuberous sclerosis complex

UR - http://www.scopus.com/inward/record.url?scp=34247164656&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247164656&partnerID=8YFLogxK

U2 - 10.1111/j.1528-1167.2007.01035.x

DO - 10.1111/j.1528-1167.2007.01035.x

M3 - Article

VL - 48

SP - 617

EP - 630

JO - Epilepsia

JF - Epilepsia

SN - 0013-9580

IS - 4

ER -