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Título

EVEROLIMUS IN THE TREATMENT OF REFRACTORY EPILEPSY IN TUBEROUS SCLEROSIS COMPLEX: A CASE SERIES

Resumo

Case presentation: Patient 1: A female infant was diagnosed with tuberous sclerosis complex (TSC) at 7 months of age after initiating generalized seizures associated with developmental delay and stereotyped behaviors. EEG showed generalized and focal epileptiform potentials and ictal activity from epileptic spasms. Brain MRI identified cortical dysplasias and subependymal nodules. The echocardiogram showed 2 cardiac rhabdomyomas and the exome revealed a deletion of 18 base pairs in exon 41 of the TSC2 gene in heterozygosity (chr16: g.2088293_2088310del; depth: 133x). First-line treatment for epilepsy in TSC was started with vigabatrin, but after an initial improvement period, seizures intensified, and social interaction worsened. Treatment with everolimus was then started, and the patient evolved with a substantial reduction of seizures, improved social and visual interaction and began to walk. Today, almost two years after starting treatment, the patient is in use of everolimus and oxcarbazepine and has good seizure control, with age appropriate development and without severe everolimus side effects. Patient 2: A 3-month-old male infant presented with clonic seizures in both eyelids, left hemiface and left arm. Brain MRI showed subependymal nodules in both lateral ventricles and cortical tubers in the middle gyri of both frontal lobes. EEG revealed epileptiform potentials in the left occipital region. A heterozygous missense variant was identified in the TSC2 gene (TSC Complex Subunit 2, OMIM*191092). Treatment was started with vigabatrin. Due to inefficient seizure control, levetiracetam was associated, followed by the introduction of oxcarbamazepine. However, the patient continued presenting 2 seizures weekly. After 5 months without adequate symptom control, everolimus was introduced, and seizure remission was achieved. Currently, about ten months after everolimus introduction, the patient remains seizure free and has adequate development for his age. Discussion and conclusion: TSC is a multisystem genetic disease in which epilepsy is a frequent manifestation and is often difficult to control. Everolimus is an mTOR inhibitor drug, with evidence suggesting benefits of its use in treating epilepsy in TSC. Inadequate control of seizures appears to play a crucial role in the cognitive and behavioral decline in patients with TSC, reiterating the importance of early diagnosis and treatment to improve the neurocognitive prognosis in these patients.

Palavras Chave

Tuberous sclerosis; epilepsy; everolimus; mTOR