Exploring the Role of SCN1A in Temporal Lobe Epilepsy: A Systematic Review of Associations and Clinical Implications
Bassel Alrabadi1, Mahmoud Marouf1, Natalie Bandak1, Zaid Badran1, Sohail Batarseh3, Haitham Hazaimeh2
1Jordan University of Science and Technology, 2Faculty of medicine, Jordan University of Science and Technology, 3Jordan University Of science and Technology
Objective:
To evaluate the relationship between SCN1A mutations and Temporal Lobe Epilepsy (TLE).
Background:
TLE is the most common focal epilepsy. It often results from brain injuries, infections, strokes, or tumors. Genetic factors play a lesser role. Although, Mutations in the SCN1A gene are known to cause generalized epilepsies. However, their link to TLE is still unclear.
Design/Methods:
A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Cochrane Library from inception until September 2024. Multiple reviewers independently selected relevant studies and synthesized data using a standardized collection form. The study was registered on Prospero with ID CRD42024597297.
Results:
This review combines findings from 24 studies on SCN1A's role in TLE. The analysis shows that SCN1A mutations cause febrile seizures and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Specific mutations raised the risk of MTLE-HS in some groups, but did not affect the risk of febrile seizures. Cortical malformations like focal cortical dysplasia and periventricular nodular heterotopia are common co-diagnoses with SCN1A mutations. This complicates diagnosis and treatment of TLE. Altered splicing of SCN1A caused drug resistance. This shows the need for precision in targeting these mutations for treatment. Variants had diverse effects on treatment response and drug resistance. This was likely due to changes in NF-kB activity and sodium channel function. Carbamazepine significantly reduced seizures by lowering SCN1A expression in the hippocampus. Some mutations caused drug-resistant epilepsy in patients with hippocampal sclerosis. This highlights the need for personalized treatments.
Conclusions:
These findings highlight the genetic, clinical, and therapeutic implications of SCN1A in temporal lobe epilepsy (TLE). They provide valuable insights for developing targeted therapies tailored to both drug-resistant and drug-responsive patient populations.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.