Abstracts

Rationale: Tuberous sclerosis complex (TSC) is a multisystem disorder predominantly involving the brain, skin, kidneys, heart and lungs due to mutations in TSC1 or TSC2genes of the mTOR signaling pathway. Main neurological manifestations of TSC are intractable epilepsy, neurocognitive/communicative delays, autism spectrum disorder (ASD).  Intractable seizures are potentially result of hyper-excitable networks emanating from active tubers and excitatory networks formed between hyper excitable tubers and cortex.  The gold standard for treatment has been resection of active tuber conglomerates with multi-staged invasive monitoring/resective surgery. Our recent use of multi-staged, magnetic, resonance-guided laser interstitial thermal therapy (MRgLITT) has become a viable alternative to conventional surgery with better outcomes and reduction of neurological deficits.  This study also provides evidence for differing response rates among patients on different medical treatments for TSC. Methods: This is a retrospective review of TSC patients with intractable epilepsy, neurocognitive/communicative delays, behavioral difficulties and ASD, who underwent MRgLITT of active epileptogenic tubers, initial ablation targeting the most active tubers, followed by re-evaluation every 2 months to identify active tubers to be subsequently ablated. Clinical information abstracted include seizure semiology, tuber location, age of initial and subsequent ablations, antiepileptic medications used, surgical outcome, and quality of life measures. The patients were maintained on multiple antiepileptic medications. However, particularly three patients were additionally treated with vigabatrin and everolimus as part of their regimen.  Results: Seven patients, none of whom underwent previous conventional surgery, were identified.  Age at time of surgery ranged between 2 and17 years. Six patients required repeat ablation. Three patients were treated with vigabatrin and the same 3 patients were treated with everolimus. Three patients at latest follow up are seizure free with Engle class I postoperative outcome. Two patients became free of disabling seizures with only rare seizures, reaching Engel class II outcomes.  The last 2 patients had significant improvement in seizure frequency and intensity reaching Engel class III outcomes.  All patients have improved cognitive/behavioral abilities and quality of life.  Further analysis of patient data revealed that, 3 patients, who reached Engel class I outcomes postoperatively, had been those who were treated with everolimus and vigabatrin as part of their antiepileptic regimen. Conclusions: (1) Staged ablation of active tubers using MRgLITT is a promising minimally invasive therapeutic method for intractable epilepsy in TSC with great outcomes leading to:

- seizure freedom or significant reduction in seizure burden - significant improvements in quality of life in all patients - significant reversal of epileptic encephalopathy(2) Combined therapy with MRgLITT, everolimus, and/or vigabatrin may result in better outcomes due to combined effects of removal of excitation and seizure foci (by MRgLITT), mTOR pathway inhibition (by everolimus), and modulation of GABAergic inhibitory interneuron system and inflammation (by vigabatrin) which are frequently part of the pathology in TSC. Prospective studies are under way in our institutions in a multidisciplinary fashion to address this hypothesis. Funding: No funding