Gliomas originate from the abnormal proliferation of glial cells in the brain (1, 2), and they are common primary central nervous system tumors (3), with a high mortality risk (4). The annual occurrence of gliomas is about 5–8 cases per 100,000 people, while the annual mortality rate is as high as 30,000, ranking third after pancreatic and lung cancers (5–7). In patients with gliomas, seizures are often the initial symptom and the reason for seeking medical attention. Glioma-related seizures are typical accompanying symptoms of gliomas, especially in low-grade gliomas (8, 9), where the main symptoms are sudden paroxysmal convulsions, foaming at the mouth, loss of consciousness, and convulsions of the limbs (10). The specific mechanisms underlying glioma-related seizures are not yet fully understood, and pathological changes and pathogenic mechanisms are diverse, likely resulting from the combined effects of multiple factors (11, 12). The abnormal expression of tumor-related genes is considered to be closely associated with the occurrence and development of seizures in brain tumors, especially gliomas (13). Although advances in surgery and chemoradiotherapy have improved the prognosis of glioma cases, the presence of seizures severely affects the quality of life for patients (14). Currently, the clinical efficacy of treating glioma-related seizures remains unsatisfactory because of an incomplete understanding of the pathophysiological, biochemical, molecular, and pharmacological mechanisms underlying its occurrence (15, 16). Giraldi et al. (17) found that there exist an obviously increased cumulative risk of new-onset seizures after craniotomy. Previous studies confirmed that seizures are a common complication of intracranial gliomas that can lead to disability or even death. Therefore, it is important to determine the relevant risk factors for early postoperative seizures in gliomas cases. However, the risk factors associated with gliomas remain controversial (18). Therefore, this study aimed to address these controversies through a meta-analysis investigating such risk factors. It is hoped that, by preventing and treating early postoperative seizures, the quality of life and outcomes of glioma patients can be improved.

This systematic review is conducted according to the preferred reporting items of the Protocol for Systematic Reviews and Meta-analyses (PRISMA-P) guidelines. The review will be conducted according to PRISMA criteria (19). The registration number is CRD42023415658.

The publication bias was assessed based on Egger's test for each risk factor. The p-values for each indicator, whether in univariate or multifactorial analysis, were >0.05, indicating no publication bias (see Supplementary Tables S3, S4).

Many recent reports have used the review and meta-analysis to report the prevalence of seizures in patients with glioma. However, Zhang et al. (33) focused their study on assessing the relationship between tumor location and preoperative seizures in patients with glioma, Shan et al. (34) studied the prognostic factors of postoperative glioma and Audrey et al. (35) focused on the incidence of seizures in different glioma types. To the best of our knowledge, this study is the first to explore the risk factors of gliomas complicated by early postoperative seizures using a meta-analysis, the inclusion criteria for the current study differed from those used in all of the previous studies. Through the analysis of single and multiple factors, this study found that a history of seizures is a key risk factor of glioma complicated by seizures, indicating that the risk of seizures in glioma cases with preoperative seizures increased significantly. This may be related to the instability of neuronal membrane potential, decrease in seizure threshold, and abnormal discharge in patients with seizures, which is caused by abnormal and excessive discharge of cortical neurons. Therefore, patients with preoperative seizures should actively use drugs to reduce its occurrence (36). The present study also found an obviously higher occurrence of seizures in patients with dyskinesia in cranial glioma. However, previous literature found that there was no strong correlation between early postoperative epilepsy and dyskinesia (37). This conclusion may be due to the limited number of preoperative dyskinesia cases included in the present research; however, this highlights the need for future studies to pay closer attention to this aspect. Patients with preoperative dyskinesia, which indicates that their neurological function has been damaged to some extent and that they are more prone to epilepsy due to their inability to perform movements, need to be given priority attention to prevent epilepsy. The occurrence of seizures is significantly higher in cases with peri-tumoral edema ≥2 cm. A possible reason for this is that peritumoral edema includes both vasogenic and cytotoxic brain edema. Vasogenic brain edema increases capillary permeability and broken blood–brain barrier, leading to an abnormal distribution of ions inside and outside the cells, which in turn stimulates nerves and triggers seizures (38). In addition, when astrocytes are involved in cytotoxic brain edema due to increased occupancy effects, their ability to take up glutamate is reduced, which in turn affects the stability of the nerve cell membrane, inducing neuroexcitability and ultimately leading to seizures (39). This study also found that intratumoral hemorrhage is an independent risk factor for gliomas complicated by seizures. Intratumoral hemorrhage can cause brain tissue hypoxia and energy metabolism disorders. Iron ions in the blood can catalyze the production of oxygen free radicals, form lipid peroxides, and cause neuronal necrosis, leading to seizures. Therefore, intratumoral hemorrhage is considered a cause of early seizures (40). It has been shown that the tumor pathological grade is usually negatively correlated with early postoperative seizure events, possibly because seizures are characterized by abnormal neuronal firing. As the pathological grade of the glioma increases, infiltrative growth tends to become more pronounced, and this infiltrative growth of tumor cells may destroy projection fibers and neurons, thereby inhibiting the spread of seizure firing (41). This is in line with the previous study, which indicated that a pathological grade of ≤ 2 is an independent risk factor for tumor-associated seizures. For cases with larger tumors, the tumor is more likely to compress adjacent normal brain tissues, causing ischemia and metabolic disorders in the brain. This compression can result in an imbalance of intra- and extra-cellular ion levels, increasing the risk of seizures, which further supports the findings of the present study, indicating that tumors ≥3 cm are an independent risk factor for tumor-associated seizures (42, 43). Telfeian et al. observed that the smaller the size of glioblastoma multiforme, the higher the risk of postoperative seizures. This could be because more brain tissue dissection may be required to reach smaller tumors, thus explaining the higher risk of seizures after surgery for smaller tumors (44). In patients with partially resected gliomas, the residual tumor may continue to invade brain tissues and stimulate the cerebral cortex, leading to abnormal cortical discharges and triggering seizures (45). Therefore, the patient's condition should be considered during clinical treatment, and the tumor should be removed as completely as possible. If complete removal of the tumor is not possible, early prevention and treatment of seizures should be actively pursued before and after surgery to decrease the risk of early postoperative seizures and improve prognosis.

The current study has the following limitations: First, the number of articles included in this review was small, and most of these articles were from China, which may be subject to selection bias. Second, the diagnostic criteria for glioma and seizures used in the included studies were not consistent, which may account for significant heterogeneity. Third, the analysis process of this study did not distinguish between odds ratio (OR), relative risk (RR), or hazard ratio (HR), and although the actual difference between the three is not significant, there is some difference in the risk assessments of the diseases they essentially measure, which may lead to some bias in the results.

Based on the available evidence, history of seizures, dyskinesia, frontal lobe tumors, pathological grade ≤ 2, tumor ≥3 cm, partial tumor resection, peritumor edema ≥2 cm, and glioma cavity hemorrhage are identified as risk factors for early postoperative seizures, and clinical practitioners can combine these indicators for early detection, diagnosis, and intervention in such kind of cases, thereby improving the quality of life of affected individuals.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.

BS: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. YS: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. ZW: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Software, Writing – original draft. CZ: Investigation, Methodology, Software, Writing – original draft. LY: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – review & editing.