The Evolving Landscape of Therapeutics for Epilepsy in Tuberous Sclerosis Complex
Giovanni Vitale,
Gaetano Terrone,
Samuel Vitale,
Francesca Vitulli,
Salvatore Aiello,
Carmela Bravaccio,
Simone Pisano,
Ilaria Bove,
Francesca Rizzo,
Panduranga Seetahal-Maraj,
Thomas Wiese
Affiliations
Giovanni Vitale
Neuroscience and Rare Diseases, Discovery and Translational Area, Roche Pharma Research and Early Development (pRED), F. Hoffmann–La Roche, 4070 Basel, Switzerland
Gaetano Terrone
Department of Translational Medical Sciences, Child and Adolescent Neuropsychiatry, University of Naples Federico II, 80138 Naples, Italy
Samuel Vitale
School of Medicine and Surgery, University of Naples Federico II, 80138 Naples, Italy
Francesca Vitulli
Department of Neurosciences and Reproductive and Dental Sciences, Division of Neurosurgery, University of Naples Federico II, 80138 Naples, Italy
Salvatore Aiello
Department of Translational Medical Sciences, Child and Adolescent Neuropsychiatry, University of Naples Federico II, 80138 Naples, Italy
Carmela Bravaccio
Department of Translational Medical Sciences, Child and Adolescent Neuropsychiatry, University of Naples Federico II, 80138 Naples, Italy
Simone Pisano
Department of Translational Medical Sciences, Child and Adolescent Neuropsychiatry, University of Naples Federico II, 80138 Naples, Italy
Ilaria Bove
Department of Neurosciences and Reproductive and Dental Sciences, Division of Neurosurgery, University of Naples Federico II, 80138 Naples, Italy
Francesca Rizzo
Department of Neuroscience “Rita Levi Montalcini”, University of Turin, 10126 Turin, Italy
Panduranga Seetahal-Maraj
Department of Neurosurgery, King’s College Hospital NHS Foundation Trust, London SE5 9RS, UK
Thomas Wiese
Neuroscience and Rare Diseases, Discovery and Translational Area, Roche Pharma Research and Early Development (pRED), F. Hoffmann–La Roche, 4070 Basel, Switzerland
Tuberous sclerosis complex (TSC) is a rare multisystem genetic disorder characterized by benign tumor growth in multiple organs, including the brain, kidneys, heart, eyes, lungs, and skin. Pathogenesis stems from mutations in either the TSC1 or TSC2 gene, which encode the proteins hamartin and tuberin, respectively. These proteins form a complex that inhibits the mTOR pathway, a critical regulator of cell growth and proliferation. Disruption of the tuberin–hamartin complex leads to overactivation of mTOR signaling and uncontrolled cell growth, resulting in hamartoma formation. Neurological manifestations are common in TSC, with epilepsy developing in up to 90% of patients. Seizures tend to be refractory to medical treatment with anti-seizure medications. Infantile spasms and focal seizures are the predominant seizure types, often arising in early childhood. Drug-resistant epilepsy contributes significantly to morbidity and mortality. This review provides a comprehensive overview of the current state of knowledge regarding the pathogenesis, clinical manifestations, and treatment approaches for epilepsy and other neurological features of TSC. While narrative reviews on TSC exist, this review uniquely synthesizes key advancements across the areas of TSC neuropathology, conventional and emerging pharmacological therapies, and targeted treatments. The review is narrative in nature, without any date restrictions, and summarizes the most relevant literature on the neurological aspects and management of TSC. By consolidating the current understanding of TSC neurobiology and evidence-based treatment strategies, this review provides an invaluable reference that highlights progress made while also emphasizing areas requiring further research to optimize care and outcomes for TSC patients.
