Topical Review: Intractable Seizures in Tuberous Sclerosis Complex: From Molecular Pathogenesis to the Rationale for Treatment

Curatolo, Paolo; Bombardieri, Roberta; Verdecchia, Magda; Seri, Stefano

doi:10.1177/08830738050200040901

Cited by 80 publications

(38 citation statements)

References 33 publications

(3 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Its CNS manifestations, especially cortical tubers, are considered most disabling . Seizures occur in the first years of life in approximately 80% of patients with TSC (Curatolo & Verdecchia, 2003;Curatolo et al, 2005). Involvement of cortical tubers and/or perituberal zones in epileptogenesis is demonstrated by the excellent outcome following surgical removal of cortical tubers, with a high percentage of patients rendered seizure-free (Romanelli et al, 2004;Weiner et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Tuberous sclerosis: A primary pathology of astrocytes?

Sosunov

Weiner

et al. 2008

Epilepsia

View full text Add to dashboard Cite

SUMMARYPurpose: Cortical tubers are epileptogenic lesions in patients with tuberous sclerosis complex (TSC). Giant cells and dysplastic neurons are pathological hallmarks of cortical tubers. Severe astrogliosis, which is invariably present in tubers, has attracted much less attention. We hypothesize that the development of astrogliosis in cortical tubers constitutes a primary pathology of astrocytes and is directly related to TSC 1/2 mutations. Methods: To begin to test this hypothesis, we performed immunohistochemical and electron microscopic analysis of brain tuber tissue resected from epileptic TSC patients. We compared alterations in tuber astrocytes to those found in other acute and chronic human epilepsy pathologies. Results: We found that astrogliosis in tubers is comprised of a mixture of "gliotic" and "reactive" astrocytes. The majority of tuber astrocytes are "gliotic" astrocytes that are morphologically and immunophenotypically similar to astrocytes in areas of gliosis in hippocampal sclerosis (HS). However, specific immunostaining features differentiate TSC gliosis from HS gliosis. "Reactive" tuber astrocytes are large-sized, vimentin positive cells in the vicinity of giant cells that show activation of the mammalian target of rapamycin (mTOR) pathway, consistent with mutated TSC gene function. These cells resemble acutely reactive human astrocytes seen in tissue resected from depth electrode implantation patients. Oligodendrocytes and NG2 expressing glial cells do not have any detectable alterations within tubers. Conclusion: We conclude that astrocytes are the type of glial cell selectively impacted in cortical tuber pathology. We propose that tubers may be dynamic lesions, with progression of astrocytes over time from "reactive" to "gliotic." Tuber astrogliosis in TSC may represent a genetic "model" of gliosis that is phenotypically similar to gliosis seen in acquired human pathologies.

show abstract

Section: Introductionmentioning

confidence: 99%

Tuberous sclerosis: A primary pathology of astrocytes?

Sosunov

Weiner

et al. 2008

Epilepsia

View full text Add to dashboard Cite

show abstract

“…Starting in infancy, patients with TSC develop increasing seizure frequency and severity. 35 In fact, 25%-50% of patients with TSC develop refractory epilepsy. 35,36 Given the medically refractory nature of the epilepsy, surgery should be considered for such cases.…”

Section: Tscmentioning

confidence: 99%

“…35 In fact, 25%-50% of patients with TSC develop refractory epilepsy. 35,36 Given the medically refractory nature of the epilepsy, surgery should be considered for such cases. The outcome of surgery is dependent on accurate presurgical assessment to guide resection of the epileptogenic tuber.…”

Section: Tscmentioning

confidence: 99%

[¹⁸F] Fluorodeoxyglucose–Positron-Emission Tomography and MR Imaging Coregistration for Presurgical Evaluation of Medically Refractory Epilepsy

Lee¹,

Salamon²

2009

AJNR Am J Neuroradiol

View full text Add to dashboard Cite

SUMMARY:Epilepsy is a chronic disorder affecting approximately 1% of the population of the world. Approximately one third of patients with epilepsy remain refractory to medical therapy. For these patients, surgery is a curative option. In order for surgery to be considered, precise localization of the structural abnormality is needed. When MR imaging findings are normal, more sensitive techniques such as positron-emission tomography (PET) can help find the abnormality. Combining MR imaging and PET information increases the sensitivity of the presurgical evaluation. In this review, we discuss the clinical applications of coregistration of [18 F] fluorodeoxyglucose (FDG)-PET with MR imaging for medically refractory epilepsy. Because FDG-PET/MR imaging coregistration has been a routine component of the presurgical evaluation for patients with epilepsy at our institution since 2004, we also included cases from our data base that exemplify the utility of this technology to obtain better postsurgical outcomes.

show abstract

“…Virtually all subtypes of seizures (simple partial, complex partial, and generalized tonic-clonic) have been reported. 2,3 Hippocampal abnormalities are also recognized as highly epileptogenic precursor lesions in the general population, and they mainly manifest as MTS, which is the most common cause of partial complex seizures. It has been reported in 40%-60% of adults 4 and less frequently in children 5 undergoing neurosurgical treatment of epilepsy.…”

mentioning

confidence: 99%

Hippocampal Abnormalities in an MR Imaging Series of Patients with Tuberous Sclerosis

Gama¹,

Rocha²,

Valério³

et al. 2010

AJNR Am J Neuroradiol

View full text Add to dashboard Cite

BACKGROUND AND PURPOSE:Hippocampal abnormalities are known as highly epileptogenic precursor lesions in the general population, primarily manifesting as MTS. The purpose of this study was to evaluate the occurrence of hippocampal abnormalities on MR imaging in patients with TS to explore the possible underlying mechanisms of the abnormalities and to identify the relationship between an abnormal HF and epilepsy.

show abstract

Topical Review: Intractable Seizures in Tuberous Sclerosis Complex: From Molecular Pathogenesis to the Rationale for Treatment

Cited by 80 publications

References 33 publications

Tuberous sclerosis: A primary pathology of astrocytes?

Tuberous sclerosis: A primary pathology of astrocytes?

[¹⁸F] Fluorodeoxyglucose–Positron-Emission Tomography and MR Imaging Coregistration for Presurgical Evaluation of Medically Refractory Epilepsy

Hippocampal Abnormalities in an MR Imaging Series of Patients with Tuberous Sclerosis

Contact Info

Product

Resources

About

Topical Review: Intractable Seizures in Tuberous Sclerosis Complex: From Molecular Pathogenesis to the Rationale for Treatment

Cited by 80 publications

References 33 publications

Tuberous sclerosis: A primary pathology of astrocytes?

Tuberous sclerosis: A primary pathology of astrocytes?

[18F] Fluorodeoxyglucose–Positron-Emission Tomography and MR Imaging Coregistration for Presurgical Evaluation of Medically Refractory Epilepsy

Hippocampal Abnormalities in an MR Imaging Series of Patients with Tuberous Sclerosis

Contact Info

Product

Resources

About

[¹⁸F] Fluorodeoxyglucose–Positron-Emission Tomography and MR Imaging Coregistration for Presurgical Evaluation of Medically Refractory Epilepsy