Risk Factors Associated with Refractory Epilepsy in Patients with Tuberous Sclerosis Complex: A Systematic Review

Abstract

Background: Epilepsy affects 70–90% of patients with tuberous sclerosis complex (TSC). In one-third of them, the seizures become refractory to treatment. Drug-resistant epilepsy (DRE) carries a significant educational, social, cognitive, and economic burden. Therefore, determining risk factors that increase the odds of refractory seizures is needed. We reviewed current data on risk factors associated with DRE in patients with tuberous sclerosis. Methods: The review was performed according to the PRISMA guidelines. Embase, Cochrane Library, MEDLINE, and ClinicalTrial.gov databases were searched. Only full-text journal articles on patients with TSC which defined risk factors related to DRE were included. Results: Twenty articles were identified, with a cohort size between 6 and 1546. Seven studies were prospective. Three factors appear to significantly increase DRE risk: TSC2 mutation, infantile spasms, and a high number of cortical tubers. Conclusions: A proper MRI and EEG monitoring, along with genetic testing, and close observation of individuals with early onset of seizures, allow identification of the patients at risk of DRE.

Diagnosis of tuberous sclerosis complex in adulthood: A case report

“…However, recent studies have shown that the use of mTOR inhibitors, such as rapamycin or everolimus, can provide promising results for more than one of the affected systems. 5 , 7 , 9 The patient's management was based on the symptoms during her hospital stay and treatment for seizure control was continued upon discharge.…”

“…Vigabatrin is considered as the first‐line treatment for epileptic spasms, while surgery or vagal stimulation can also be considered as treatment options. However, recent studies have shown that the use of mTOR inhibitors, such as rapamycin or everolimus, can provide promising results for more than one of the affected systems 5,7,9 . The patient's management was based on the symptoms during her hospital stay and treatment for seizure control was continued upon discharge.…”

“… 6 More than 60% of cases are caused by sporadic de novo mutations, 30% are transmitted in an autosomal dominant inheritance pattern, and up to 10% have no mutations in these genes. 6 , 7 TSC is diagnosed on the basis of a combination of clinical manifestations, radiological findings, and genetic tests. These follow the criteria established by the International Consensus Conference for the Diagnosis of TSC, and two major criteria or one major criterion and two minor criteria are required for a definitive diagnosis (Table 1 ).…”

“…Tuberous sclerosis complex is caused by mutations in the genes TSC1 and TSC2 , which encodes hamartin (chromosome 9q34.13) and tuberin (chromosome 16p13.3), respectively 6 . More than 60% of cases are caused by sporadic de novo mutations, 30% are transmitted in an autosomal dominant inheritance pattern, and up to 10% have no mutations in these genes 6,7 . TSC is diagnosed on the basis of a combination of clinical manifestations, radiological findings, and genetic tests.…”

Effect of mTOR Inhibitors in Epilepsy Treatment in Children with Tuberous Sclerosis Complex Under 2 Years of Age

“…One-third of epileptic seizures in children with TSC become refractory to treatment, and it correlates with the early age at the first clinical seizure, a mutation in the TSC2 gene, and the number of cortical tubers [26].…”