Abstracts

Rationale: Vigabatrin is the treatment of choice for the treatment of infantile spasms in tuberous sclerosis (TS). However, there is little data demonstrating its role in the prevention of infantile spasms. Furthermore, everolimus has been approved for use in TS to reduce subependymal giant cell astrocytoma (SEGA) volume. It is not currently known if this translates to improved seizure control. Here we report an eight month old infant with tuberous sclerosis who developed infantile spasms during treatment with vigabatrin and everolimus. Methods: This is a case report of an infant with prenatal diagnosis of TS that presented to the Children's Hospital of Wisconsin for evaluation of seizures at 3 weeks of life. Video electroencephalography (EEG), MRI brain with and without contrast, and genetic testing were employed for characterization of the case. Results: MRI of the brain showed a left lateral ventricle SEGA (Fig. 1A) and multiple tubers (Fig. 1B). At presentation, The diagnosis of TS was further confirmed by genetic testing (frameshift mutation in TSC2 gene). Video EEG monitoring demonstrated clinical and electrographic right central focal epileptiform activity (Fig. 2A). Seizures were refractory to first line antiepileptic therapies, including Phenobarbital, phenytoin and topiramate. As a result, levetiracetam (LEV) and vigabatrin (VGB) were used with minimal success to decrease seizure frequency. Given the refractory nature of the patient's seizures, everolimus was initiated with the goal of reducing tuber volume and possibly decrease seizure frequency. Focal seizures evolved into flexor spasms on maximal doses of VGB, LEV and everolimus at 7 months of age. This coincided with addition of lacosamide, given persistent focal seizures. EEG confirmed hypsarrythmia (Fig. 2B). Lacosamide was discontinued, as was everolimus, 2 weeks prior to starting ACTH therapy to prevent excessive immunosuppression. Chest X-ray demonstrated asymptomatic pneumonitis. On ACTH, VGA, LVT and valproic acid, hypsarrythmia resolved (Fig. 2C). The infant has developmental delay with rare refractory seizures consistent with left upper extremity focal seizures. Conclusions: To the best of our knowledge, this is the first example of a patient with TS developing infantile spasms on both VGB and everolimus. Focal electrographic abnormality progressed to hypsarrythmia on VGB and everolimus demonstrating the failure of 2 first line drugs in the treatment of TS. It is also unclear if there was activation of seizures with lacosamide, although abrupt discontinuation of the drug did not result in improvement of EEG. We also believe he is the youngest patient at age 5 months to be treated with everolimus with development of asymptomatic pneumonitis posing a unique challenge of immunosuppresion in infants with TS.