Irradiation-induced Seizures in High-grade Gliomas: Potential Causative Factors and Means of Prevention
Neeva Shafiian1, Emma R. Handwerker2, Allison Winter1, Isabella Tincher1, Anna M. Bank3, A. Gabriella Wernicke4
1Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 2Deparment of Neurology, NewYork-Presbyterian/Columbia University Irving Medical Center, 3Department of Neurology, Lenox Hill Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 4Department of Radiation Medicine, Lenox Hill Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/ Northwell Health Cancer Institute
Objective:
To assess the average time of onset of irradiation-induced seizures in high-grade glioma treatment, examine the relationship between radiation techniques and doses with seizures, and evaluate prevention strategies.
Background:
Radiation toxicity is a well-known cause of iatrogenic seizures in high-grade gliomas (HGG). However, the prevalence of irradiation-induced seizures and factors influencing their development remain incompletely understood. Seizures complicate clinical outcomes and impair quality of life. Current seizure prophylaxis methods lack consensus. This study assesses seizure timing relative to radiotherapy, techniques like brachytherapy and stereotactic radiosurgery (SRS), and prevention strategies.
Design/Methods:
A PubMed literature review included publications from 1947 to 2024. Search terms include ("glioblastoma" OR "high-grade glioma" OR "GBM" OR “Anaplastic Astrocytoma”) AND ("radiation" OR "irradiation" OR "radiotherapy" OR "radiation therapy") AND ("seizure" OR "epilepsy" OR "post-treatment seizure" OR "late-onset seizure"); "radiation-induced seizures"; "radiation necrosis" AND "seizures"; "hospitalization" AND "glioblastoma" AND "radiation." 28 papers were included. Exclusion criteria eliminated pediatric patients, low-grade gliomas, and HGG patients with seizures from disease progression or other interventions.
Results:
392 patients with HGG experiencing irradiation-induced seizures were identified. Data on seizure onset was available for 381 patients. 29.1% (111/381) developed seizures during or within the first month of RT. 70.3% (268/381) developed seizures between 1 to 24 months (p = 0.00). There was no significant association between radiation dose and the onset of seizures (p = 0.25). In recurrent HGG, there was no significant difference in the percentage of patients who developed seizures following SRS compared to brachytherapy (p = 0.60). Valproic acid showed radiosensitizing and radioprotective effects.
Conclusions:
Irradiation-induced seizures in patients with HGG most commonly occur between 1 to 24 months post-treatment. No significant dose-related association with seizure onset was found. Valproic acid shows promise as both a radiosensitizer and seizure preventive measure. Further research is needed to assess seizure risk factors and refine prevention strategies.
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