From the Guidelines
TSC in pediatrics refers to Tuberous Sclerosis Complex, a genetic disorder that causes benign tumors to grow in multiple organs, including the brain, leading to seizures due to structural abnormalities called cortical tubers, which act as seizure foci. TSC is caused by mutations in either the TSC1 or TSC2 genes, which regulate cell growth and division, as noted in the European Journal of Nuclear Medicine and Molecular Imaging 1. In children with TSC, seizures are often the first presenting symptom, with infantile spasms being particularly common. The management of TSC typically involves anticonvulsant medications, with vigabatrin being a first-line treatment for infantile spasms in TSC, typically at a dose of 50-150 mg/kg/day divided twice daily, or everolimus, an mTOR inhibitor that can reduce both seizures and tumor growth 1.
Some key points to consider in the management of TSC include:
- Early diagnosis and treatment are crucial as seizure control can significantly improve developmental outcomes.
- Surgical removal of seizure-causing tubers may be considered in medication-resistant cases.
- Beyond seizures, children with TSC require multidisciplinary care to monitor for other manifestations, including cardiac rhabdomyomas, renal angiomyolipomas, and neurodevelopmental disorders.
- The use of [18F]FDG PET can play a valuable role in non-invasively lateralizing and localizing the main epileptogenic tuber as an area of glucose hypometabolism, often more extended than observed with MRI, indicating dysplastic cortex 1.
Overall, the goal of treatment in TSC is to control seizures, manage other manifestations of the disorder, and improve quality of life, with early intervention and a multidisciplinary approach being key to achieving the best possible outcomes.
From the Research
Definition and Characteristics of TSC
- Tuberous sclerosis complex (TSC) is a rare genetic disorder caused by mutations in the TSC1 or TSC2 genes, which encode proteins that antagonise the mammalian isoform of the target of rapamycin complex 1 (mTORC1) 2.
- TSC is characterised by the development of benign tumours in multiple organs, together with neurological manifestations including epilepsy and TSC-associated neuropsychiatric disorders (TAND) 2.
- Epilepsy occurs frequently in TSC and is associated with significant morbidity and mortality, with 80% to 90% of individuals with TSC developing epilepsy 3.
Structural Abnormality in TSC
- TSC is associated with abnormal cell growth, proliferation, protein synthesis, and cell differentiation and migration, which can lead to the development of structural abnormalities in the brain 3.
- The disruption of the mTOR pathway in TSC is believed to influence neuronal excitability and promote epileptogenesis, leading to the development of epilepsy 3.
Treatment and Management of TSC-Associated Epilepsy
- Various treatments are available for TSC-associated epilepsy, including antiepileptic drugs (AEDs), vigabatrin, everolimus, cannabidiol, and the ketogenic diet (KD) 2, 4, 5.
- Preventive treatment with vigabatrin has been shown to reduce the risk and severity of epilepsy in infants with TSC, and may modify the natural history of seizures in TSC 6.
- Epilepsy surgery, vagus nerve stimulation, and other non-pharmacologic therapies may also be effective in managing TSC-associated epilepsy 4, 3.