A Study On Prophylactic Use Of Drugs And Inflammatory Mechanism Of Post-cranioplasty

Objective: To study the incidence of epilepsy, risk factors and the efficacy and safety of prophylactic antiepileptic drugs (AEDs) administration after cranioplasty, prospectively. To investigate the role of inflammatory mediators such as high mobility group box protein1(HMGB1) in the formation of epilepsy after cranioplasty, and find new targets for prevention.Methods: 317 cases undergoing cranioplasty were prospectively enrolled and randomly divided into LEV24 group (prophylactic LEV for 24 weeks,97 cases), LEV4 group(prophylactic LEV for 4 weeks,40 cases), phenytoin (PHT) group (prophylactic PHT for 4 weeks,40 cases), methylprednisolone (MPS) group (prophylactic MPS for 4 weeks,40 cases) and control group (no prophylactic AEDs, 100 cases). Electroencephalogram(EEG), 3d CT scan, MRI scan, and cognitive evaluation are assessed before the operation.The operation was performed under general anesthesia with the 3d pre-shaping titanium mesh. Postoperative 2, 4, 24, 48 weeks were recorded for epileptic seizures, and 48 weeks for cognitive changes and drug-related adverse reactions, patient satisfaction rate, etc. The serum and cerebrospinal fluid samples were collected 24 hours before and 2 weeks after operation. The levels of HMGB1, Interleukin (IL) -6, interleukin-1? (IL-1?), complement C3, tumor necrosis alpha (TNF-?) and intercell adhesion molecule-1(ICAM-1) were measured by enzyme-linked immunosorbent assay (ELISA). SPSS software was used to analyze the morbidity and influencing factors of epilepsy after cranoplasty, the influence of seizures on patients, and the relationship between inflammatory factors and seizures and prophylaxis.Results: . A total of 31 patients (9.78%) underwent postoperative seizures in patients with craniotomy, including 13 patients (4.1%) with early seizures, 18 patients (5.9%) with late epileptic seizures, and 69.2% of patients with early seizures develop late epileptic seizures,and 72,4% of the patients with postoperative seizures still appear at least once seizures after the application of antiepileptic drugs. In the control group, the rate of early seizures was 9%, and the late 8%, 17% in total. Early postoperative seizures of each groups have obvious difference (P = 0.0335), in which AEDs prevention group (LEV24 group, LEV4 group and PHTgroup) was significantly lower than the control group (P=0.004). Patients with preoperative or postoperative EEG abnormalities are more prone to epilepsy. There were significant differences in intelligence quotient, memory quotient, quality of life improvement, patient satisfaction and postoperative hospital stay in patients with seizure and those without after operation (P<0.01). The level of IL-6, HMGB1, IL-1? and ICAM-1 in the blood and the levels of IL-6 and ICAM-1 in the cerebrospinal fluid of the patients with postoperative seizures were higher than those without both before and after the operation. The levels of IL-6 and ICAM-1 in the blood and cerebrospinal fluid were significantly lower in the LEV group than in the control group. The levels of IL-6 in the blood and cerebrospinal fluid were significantly lower in the MPS group than in the control group.Conclusions: The incidence of epilepsy after cranioplasty was high, and its response to drug therapy is poor. Patients with preoperative or postoperative EEG abnormalities were prone to postoperative epilepsy. Prophylactic use of AEDs can reduce early seizures. LEV can reduce the duration of seizures during treatment with less side effects than PHT.Inflammatory response is associated with seizures after cranioplasty, and IL-6 and ICAM-1 can be targeted for epilepsy prevention after cranioplasty.