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Cyst-like tubers are associated with TSC2 and epilepsy in tuberous sclerosis complex

From the Department of Neurology (C.J.C.-S., M.M., E.T.), Massachusetts General Hospital, Boston; and Service de Neurologie (P.M.), CHU Sainte-Justine, Montreal, QC, Canada.

Address correspondence and reprint requests to Dr. Elizabeth A. Thiele, Carol and James Herscot Center for Tuberous Sclerosis Complex, 175 Cambridge Street, Suite 340, Boston, MA 02114 ethiele{at}partners.org

Background: Tuberous sclerosis complex (TSC) is a genetic condition characterized by the presence of hamartomatous lesions in multiple organs, including tubers in the brain. The majority of patients with TSC have epilepsy. Some cortical tubers are epileptic foci, while others appear to be physiologically quiescent. It is unknown whether variations in tuber morphology may account for this difference. The objectives of this study were to determine the frequency of cyst-like tubers in patients with TSC, whether cyst-like tubers correlate with TSC genotype, and whether cyst-like cortical tubers are associated with a history of infantile spasms, epilepsy, or refractory epilepsy.

Methods: A retrospective chart review was performed of 173 patients with TSC. MRI images were evaluated for the presence of at least one cyst-like cortical tuber. Patient charts were then reviewed for genetic mutation, a history of infantile spasms, epilepsy, and epilepsy refractory to more than three medications.

Results: A total of 46% of patients had at least one cyst-like cortical tuber present on neuroimaging. Patients with a TSC2 mutation were more likely to have a cyst-like tuber than patients with TSC1 mutation (p = 0.002) or patients with no mutation identified (p = 0.039). Patients with at least one cyst-like cortical tuber were more likely to have a history of infantile spasms (p = 0.00005), epilepsy (p = 0.0038), and refractory epilepsy (p = 0.0007) than patients without a cyst-like cortical tuber.

Conclusion: Cyst-like cortical tubers are strongly associated with TSC2 gene mutation and a more aggressive seizure phenotype in patients with tuberous sclerosis complex.

Abbreviations: CaMD = calmodulin binding domain; CCD = coiled-coil domain; CI = confidence interval; ERM = Ezrin–radixin–moesin; FLAIR = fluid-attenuated inversion recovery; FSE = fast spin-echo; GAP = GTPase activating protein; LZD = leucine zipper domain; NEX = number of excitations; NMI = no disease-associated mutation identified; TAD = transcription activating domain; TE = echo time; TMD = transmembrane domain; TR = repetition time; TSC = tuberous sclerosis complex.

Disclosure: The authors report no disclosures.

Received September 25, 2008. Accepted in final form December 22, 2008.