Abstracts

Rationale: Tuberous Sclerosis Complex (TSC) is an autosomal dominantly inherited genetic disorder causing multi-organ system disease with phenotypic variability. It is caused by mutations in the genes encoding the proteins hamartin (tsc 1) or tuberin (tsc2). These proteins act together as a heterodimer to downregulate the mammalian target of rapamycin (mTOR) pathway. Loss of function mutations of hamartin or tuberin cause hyperactivation of the mTOR pathway and dysregulated cell proliferation. TSC is associated with a high degree of neurologic phenotypic variance. Common neurologic manifestations include epilepsy, intellectual impairment, and autism. The reported prevalence of epilepsy in TSC is 72.5-93.2%. Previous reports have also shown that a majority of TSC patients with epilepsy are medically refractory, with rates between 62.5-72.5%. We sought to evaluate the characteristics of epilepsy in adults with TSC, specifically to determine the frequency of specific seizure types and the rate of seizure freedom. Methods: Adult patients with TSC were identified by query of an ongoing database of epilepsy patients seen at the University of Virginia Epilepsy Clinic. A total of 23 patients with TSC were identified by database search. This was cross-referenced to the hospital EMR and to ensure data was as up to date as possible. Of the 23 patients identified, 7 were found to have less than 3 visits or were not seen in clinic in more than 10 years and therefore were excluded. The seizure frequency, duration and medication management of the 16 patients were analyzed. Results: The average age of the patient population at last follow up was 34.75 years. 62.5% (10/16) were seizure free at time of last visit. 37.5% (6/16) were refractory despite medical management. The average follow-up time was long: 146.8 months for seizure free patients and 147.5 months for medically refractory patients. Those who were seizure free at last visit tended to remain seizure free for long periods of time, with an average of 109 months of seizure freedom per person (seizure free 74.25% of months followed). The average number of antiepileptic medications at last visit was 2.1 per person in the well-controlled group, with an average of 4.5 AEDs tried during the course of follow-up. Medically refractory patients tended to have very short periods without seizures and rarely went an extended period of time without seizures, with an average of 11.6 months without seizure over the course of follow-up (7.9% of months followed). The average number of AEDs for refractory patients at last visit was 3.8, and the average number of AEDs attempted was 11.7. The medically refractory group also tended to have frequent seizures each month, with an average of 25.5 per month inclusive of all seizure types. The most commonly seen seizures in this group were: complex partial seizures (CPS) with average of 9.7/month (6 patients), CPS with secondary generalization with average of 9.6/month (4 patients), generalized tonic-clonic with average of 2.9/month (2 patients), and generalized tonic seizures 25.6/month (2 patients). Conclusions: These findings demonstrate there is wide variability in the severity of epilepsy in the TSC population. A majority of the patients in this study population eventually obtained sustained seizure freedom and typically did so while on average of 2 medications. However, those who were refractory despite best medical management tended to have multiple seizures per week despite a large number of AED trials and continuation of multiple AEDs at last clinic visit. Funding: There was no funding supporting this abstract.