Do prophylactic anticonvulsant drugs alter the pattern of seizures after craniotomy? Prophylactic anticonvulsants for prevention of immediate and early postcraniotomy seizures. Enhancing antiepileptic drug adherence: a randomized controlled trial. Influence of surgery and antiepileptic drugs on seizures symptomatic of cerebral tumours. Psychomotor development and minor anomalies in children exposed to antiepileptic drugs in utero: a prospective population-based study. Randomized prospective study of early discontinuation of antiepileptic drugs in children with epilepsy. Comparative double blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: efficacy, tolerability, and cognitive effects. Effect of prophylactic ondansetron on postoperative nausea and vomiting after elective craniotomy. Randomized, double-blinded comparison of tropisetron and placebo for prevention of postoperative nausea and vomiting after supratentorial craniotomy.
A total of 276 patients with a high risk of developing postoperative seizures were randomised to treatment with carbamazepine or phenytoin for six or 24 months, or to no treatment. No significant differences were found (though the confidence limits were fairly wide) between the regimes in respect of the incidence of seizures or death. In a substantial proportion of the patients postoperative epilepsy remained a continuing disability. A high incidence of drug-related side effects was found in the treatment groups. Prophylactic anticonvulsants cannot therefore be recommended routinely following supratentorial craniotomy. Phenytoin (15 mg/kg) was administered intravenously to 189 patients shortly before their intracranial, supratentorial surgery was completed. Intravenous phenytoin of 5-6 mg/kg/day in three divided doses was administered daily for the first 3 postoperative days. Therapeutic serum levels (10-20 micrograms/mL) were achieved in 113 (59.8%) patients. An equally constituted, randomized control group of 185 patients received a placebo under identical conditions. The group receiving phenytoin had only one immediate and two early postoperative seizures. The 185 controls had four immediate and nine early postoperative seizures. None of the follow-up computed tomography scans of the patients with seizures showed postoperative hematoma. One patient had a significant tension pneumocranium, a possible cause of postoperative seizures. To avoid a decrease in the serum anticonvulsant level due to intraoperative blood loss, it is suggested that for patients who need an urgent or emergent craniotomy, prophylatic anticonvulsant medication should be given at least 20 minutes before completion of wound closure. Suboptimal adherence to antiepileptic drug (AED) treatment is commonplace, and increases the risk of status epilepticus and sudden unexplained death in epilepsy. This randomized controlled trial was designed to demonstrate whether an implementation intention intervention involving the completion of a simple self-administered questionnaire linking the intention of taking medication with a particular time, place, and other activity can improve AED treatment schedule adherence. Of the 81 patients with epilepsy who were randomized, 69 completed a 1-month monitoring period with an objective measure of tablet taking (electronic registration of pill bottle openings, Medication Event Monitoring System [MEMS]). Intervention participants showed improved adherence relative to controls on all three outcomes: doses taken in total (93.4% vs. 79.1%), days on which correct dose was taken (88.7% vs. 65.3%), and doses taken on schedule (78.8% vs. 55.3%) (P<0.01). The implementation intention intervention may be an easy-to-administer and effective means of promoting AED adherence. One hundred and twenty-eight adult patients presenting with and operated on for supratentorial neoplasms were studied. Sixty-five had preoperative seizures and were treated with antiepileptic drugs (AEDs). Among the 63 patients without preoperative epileptic fits, 41 were given AEDs (either phenobarbital or phenytoin) as prophylactic treatment and 22 were not treated. The preoperative epilepsy course was considered with respect to tumour site and histological type. Early and late postoperative seizure occurrence was considered in the different groups of patients. The results suggest the usefulness of a short term preventive treatment with AEDs after surgery in patients without preoperative seizures. In patients with preoperative epilepsy, AEDs should be continued after surgery. However long-term AEDs treatment should not be recommended in patients without preoperative epilepsy. In fact, no significant difference in late seizure occurrence was found between preventively treated and untreated patients. The aim of this study was to assess psychomotor development, using Griffiths' test, and the incidence of minor anomalies at birth in children who had been exposed to antiepileptic drugs (AEDs) in utero. The study sample comprised 100 children of mothers who were treated with AEDs during pregnancy and 100 matched control children. Women with epilepsy were recruited from a pregnant urban population (450 000 inhabitants). The lowest possible dose of the fewest AEDs to maintain seizure control was used. Drug levels were controlled on a monthly basis. The children were assessed at 9 months of age. The study children had a significant increase in the number of minor anomalies (31 compared with 18 control children; odds ratio 2.4, CI 1.15 to 5.02, P=0.02 McNemars test), and an increased number of facial anomalies after carbamazepine exposure (11 compared with six control children). Drug exposure did not influence the Griffiths' score at 9 months of age. Even a meticulous AED treatment strategy during pregnancy increases the number of minor anomalies. However, treatment with AEDs does not necessarily influence short-term psychomotor development. We studied recurrence rate, risk factors for recurrence, and outcome after recurrence in children after early withdrawal of antiepileptic drugs (AEDs). One hundred sixty-one children with newly diagnosed epilepsy who had become seizure free within 2 months after starting treatment and remained so for 6 months were randomly assigned to immediate withdrawal of AEDs (n = 78) or continuation of treatment for another 6 months followed by withdrawal (n = 83). The probability of remaining seizure free at 24 months after randomization was 51% (95% CI, 40 to 62) in Group A and 52% (41 to 63) in Group B. Significant predictive factors for relapse were partial epilepsy, seizure onset at 12 years or older, defined etiology, and epileptiform EEG before randomization. At the end of follow-up (median, 41.9 months), 129 children (80.6%) had a terminal remission of at least 1 year, 88 without AEDs and 41 with AEDs. No significant difference in outcome was found between Groups A and B. In children with epilepsy and an early response to therapy, AED withdrawal after 6 or 12 months of treatment leads to seizure recurrence in approximately half of all patients regardless of the duration of therapy. More than 60% of those with one or more recurrences reach a terminal remission of at least 1 year after long-term follow-up with or without AEDs. To determine the efficacy, tolerability, and impact on quality of life and cognitive functioning of anticonvulsant prophylaxis with phenytoin or sodium valproate in patients after craniotomy.
                A prospective, stratified, randomised, double blind single centre clinical trial was performed, comparing two groups of 50 patients each, who underwent craniotomy for different pathological conditions and who were treated for 1 year after surgery with either 300 mg phenytoin/day or 1500 mg sodium valproate/day. During the study period patients were seen in the outpatient clinic at 1.5, 3, 6, and 12 months, when medical history, adverse events, and drug plasma concentrations were evaluated. Neuropsychological functioning and quality of life were assessed on the last three visits. In cases of a seizure an EEG was performed, drug plasma concentration assessed, and medication subsequently increased.
                Of the 100 included patients 14 (seven in each group) experienced one or more postoperative seizures. Severity of the seizures was comparable in the two groups. In all patients, drug plasma concentrations were in the low or subtherapeutic ranges at the time of the first postoperative seizure. Five patients in the phenytoin group and two in the valproate group had to stop their treatment due to drug related adverse events. Sixty patients completed the 12 month period. Analysis of neuropsychological and quality of life data showed no significant differences.
                For efficacy, tolerability, impact on cognitive functioning, and quality of life, no major differences were found between phenytoin and valproate prophylaxis. Valproate is an alternative for anticonvulsant prophylaxis in patients after craniotomy. This prospective, randomized, placebo-controlled, double-blind study was designed to evaluate the efficacy of ondansetron, a 5-HT3 antagonist, in preventing postoperative nausea and vomiting (PONV) after elective craniotomy in adult patients. The authors also tried to discover certain predictors for postcraniotomy nausea and vomiting. We studied 170 ASA physical status I and II patients, aged 15 to 70 years, undergoing elective craniotomy for resecting various intracranial tumors and vascular lesions. A standardized anesthesia technique and postoperative analgesia were used for all patients. Patients were divided into two groups and received either saline placebo (Group 1) or ondansetron 4 mg (Group 2) intravenously at the time of dural closure. Patients were extubated at the end of surgery and episodes of nausea and vomiting were noted for 24 hours postoperatively in the neurosurgical intensive care unit. Demographic data, duration of surgery, and anesthesia and analgesic requirements were comparable in both groups. Overall, a 24-hour incidence of postoperative emesis was significantly reduced in patients who received ondansetron compared with those who received a saline placebo (39% in Group 1 and 11% in Group 2, P = .001). There was a significant reduction in the frequency of emetic episodes and rescue antiemetic requirement in patients treated with ondansetron; however, ondansetron did not significantly reduce the incidence of nausea alone (14% in Group 2 vs 5% in Group 1, P = .065). Prophylactic ondansetron had a favorable influence on PONV outcome measures such as patient satisfaction and number needed to prevent emesis (3.5). Side effects were similar in both groups. We conclude that ondansetron 4 mg given at the time of dural closure is safe and effective in preventing emetic episodes after elective craniotomy in adult patients. This prospective, randomized, placebo-controlled, double-blinded study was designed to evaluate the efficacy of tropisetron in preventing postoperative nausea and vomiting after elective supratentorial craniotomy in adult patients. We studied 65 ASA physical status I-III patients aged 18 to 76 years who were undergoing elective craniotomy for resection of various supratentorial tumors. Patients were divided into two groups and received either 2 mg of tropisetron (group T) or saline placebo (group P) intravenously at the time of dural closure. A standard general anesthetic technique was used. Episodes of nausea and vomiting and the need for rescue antiemetic medication were recorded during 24 hours postoperatively. Demographic data, duration of surgery and anesthesia, and sedation scores were comparable in both groups. Nausea occurred in 30% of group T patients and in 46.7% of group P patients (P >.05). The incidence of emetic episodes was 26.7% and 56.7% in the two groups (P <.05). Rescue antiemetic medication was needed in 26.7% and 60% of the patients (P <.05). Administration of a single dose of tropisetron (2 mg intravenously) given at the time of dural closure was effective in reducing postoperative nausea and vomiting after elective craniotomy for supratentorial tumor resection in adult patients.
There is little evidence to suggest that AED treatment administered prophylactically is effective or not effective in preventing post-craniotomy seizures. The current evidence base is limited due to the differing methodologies employed in the trials and inconsistencies in reporting of outcomes. Further evidence from good-quality, contemporary trials is required in order to assess the effectiveness of prophylactic AED treatment compared to control groups or other AEDs in preventing post-craniotomy seizures properly.