Epileptogenesis in meningioma: Theories, putative biomarkers, and postoperative risk.

Cranial meningioma are the most common type of primary brain tumor, and focal onset, tumor-related seizures affect a significant proportion of patients. Seizures affect 30% of symptomatic preoperative patients and a further 12% of postoperative patients. Although most patients may be cured of their oncological disease by surgery, seizures confer disability, reduced quality-of-life, delayed return to driving and work, and increase the risk of sudden death. Tumor-associated seizures are also more likely to be resistant to antiseizure medications (ASMs). ASMs are limited to treating the symptoms of epilepsy-seizures-but have no disease-modifying effect on the mechanisms that cause or maintain seizure susceptibility. There is a need to be able to predict who is at risk of developing postoperative seizures for targeted prevention or closer monitoring of those at greater risk. Mechanisms underpinning brain tumor-related seizures are most likely multifactorial and related to morphological, biochemical, and metabolic causes. Brain tumors likely cause cortical hyperexcitability due to irritation caused by mass effect, brain invasion, and peritumoral brain edema. Inflammatory mediators are involved in epileptogenesis in animal models and human seizure syndromes and there are experimental data to support the development of inflammatory mediators as biomarkers for epileptogenesis. Meningioma-associated seizures are incompletely understood and consequently unpredictable with current knowledge. In this review, we discuss the proposed mechanisms of epileptogenesis in brain tumors and putative neuroinflammatory mechanisms for meningioma-associated seizures. Ultimately, we evaluate the potential of neuroinflammatory biomarkers of epileptogenesis in meningioma and the current challenges with extrapolating from current literature, which primarily consider epilepsy and intrinsic brain tumors. A prospective randomized controlled trial (STOP'EM: ISRCTN14381346) is open in the UK and will determine the role of two weeks of prophylactic levetiracetam in seizure-naïve patients undergoing meningioma surgery and provide an opportunity to obtain serial blood measurements from patients to assist with biomarker discovery.