Effectiveness of antiepileptic prophylaxis used with supratentorial craniotomies: a meta-analysis

Thirty publications on the effectiveness of prophylactic antiepileptic drugs (AEDs) with supratentorial craniotomies were reviewed (1980–1995). After a first selection, six controlled studies remained (11 publications). These six were evaluated according to previously defined methodological criteria. The criteria were divided into three main categories: (1) internal validity, (2) proper and relevant outcome-measures and (3) analysis. In this way a maximum of 145 points could be obtained for each study. Three studies were considered to be of satisfactory methodological quality (≥55% of 145 points) and the odds ratios were calculated as a measure of association between treatment and occurrence of convulsions. The odds ratios of these three studies were statistically pooled using the Mantel-Haenszel Estimator. From this test it appeared that prophylactically used AEDs showed a tendency to prevent postoperative convulsions, but this effect was certainly not statistically significant (P = 0.1 one-tailed). Points of attention concerning possible future investigations are stressed

Intraoperative magnetic resonance imaging versus standard neuronavigation for the neurosurgical treatment of glioblastoma: A randomized controlled trial.

BACKGROUND: Although the added value of increasing extent of glioblastoma resection is still debated, multiple technologies can assist neurosurgeons in attempting to achieve this goal. Intraoperative magnetic resonance imaging (iMRI) might be helpful in this context, but to date only one randomized trial exists. METHODS: We included 14 adults with a supratentorial tumor suspect for glioblastoma and an indication for gross total resection in this randomized controlled trial of which the interim analysis is presented here. Participants were assigned to either ultra-low-field strength iMRI-guided surgery (0.15 Tesla) or to conventional neuronavigation-guided surgery (cNN). Primary endpoint was residual tumor volume (RTV) percentage. Secondary endpoints were clinical performance, health-related quality of life (HRQOL) and survival. RESULTS: Median RTV in the cNN group is 6.5% with an interquartile range of 2.5-14.75%. Median RTV in the iMRI group is 13% with an interquartile range of 3.75-27.75%. A Mann-Whitney test showed no statistically significant difference between these groups (P =0.28). Median survival in the cNN group is 472 days, with an interquartile range of 244-619 days. Median survival in the iMRI group is 396 days, with an interquartile range of 191-599 days (P =0.81). Clinical performance did not differ either. For HRQOL only descriptive statistics were applied due to a limited sample size. CONCLUSION: This interim analysis of a randomized trial on iMRI-guided glioblastoma resection compared with cNN-guided glioblastoma resection does not show an advantage with respect to extent of resection, clinical performance, and survival for the iMRI group. Ultra-low-field strength iMRI does not seem to be cost-effective compared with cNN, although the lack of a valid endpoint for neurosurgical studies evaluating extent of glioblastoma resection is a limitation of our study and previous volumetry-based studies on this topic.Peer reviewe

Occipital nerve stimulation in medically intractable, chronic cluster headache. The ICON study: Rationale and protocol of a randomised trial

Background:\ud About 10% of cluster headache patients have the chronic form. At least 10% of this chronic group is intractable to or cannot tolerate medical treatment. Open pilot studies suggest that occipital nerve stimulation (ONS) might offer effective prevention in these patients. Controlled neuromodulation studies in treatments inducing paraesthesias have a general problem in blinding. We have introduced a new design in pain neuromodulation by which we think we can overcome this problem. \ud \ud Methods/design:\ud We propose a prospective, randomised, double-blind, parallel-group international clinical study in medically intractable, chronic cluster headache patients of high- versus low-amplitude ONS. Primary outcome measure is the mean number of attacks over the last four weeks. After a study period of six months there is an open extension phase of six months. Alongside the randomised trial an economic evaluation study is performed. \ud \ud Discussion:\ud The ICON study will show if ONS is an effective preventive therapy for patients suffering medically intractable chronic cluster headache and if there is a difference between high- and low-amplitude stimulation. The innovative design of the study will, for the first time, assess efficacy of ONS in a blinded way

Safety and efficacy of occipital nerve stimulation for attack prevention in medically intractable chronic cluster headache (ICON): a randomised, double-blind, multicentre, phase 3, electrical dose-controlled trial

Background Occipital nerve stimulation (ONS) has shown promising results in small uncontrolled trials in patients with medically intractable chronic cluster headache (MICCH). We aimed to establish whether ONS could serve as an effective treatment for patients with MICCH.Methods The ONS in MICCH (ICON) study is an investigator-initiated, international, multicentre, randomised, double-blind, phase 3, electrical dose-controlled clinical trial. The study took place at four hospitals in the Netherlands, one hospital in Belgium, one in Germany, and one in Hungary. After 12 weeks' baseline observation, patients with MICCH, at least four attacks per week, and history of being non-responsive to at least three standard preventive drugs, were randomly allocated (at a 1:1 ratio using a computer-generated permuted block) to 24 weeks of occipital nerve stimulation at either 100% or 30% of the individually determined range between paraesthesia threshold and neardiscomfort (double-blind study phase). Because ONS causes paraesthesia, preventing masked comparison versus placebo, we compared high-intensity versus low-intensity ONS, which are hypothesised to cause similar paraesthesia, but with different efficacy. In weeks 25-48, participants received individually optimised open-label ONS. The primary outcome was the weekly mean attack frequency in weeks 21-24 compared with baseline across all patients and, if a decrease was shown, to show a group-wise difference. The trial is closed to recruitment (ClinicalTrials.gov NCT01151631).Findings Patients were enrolled between Oct 12, 2010, and Dec 3, 2017. We enrolled 150 patients and randomly assigned 131 (87%) to treatment; 65 (50%) patients to 100% ONS and 66 (50%) to 30% ONS. One of the 66 patients assigned to 30% ONS was not implanted and was therefore excluded from the intention-to-treat analysis. Because the weekly mean attack frequencies at baseline were skewed (median 15.75; IQR 9.44 to 24.75) we used log transformation to analyse the data and medians to present the results. Median weekly mean attack frequencies in the total population decreased from baseline to 7.38 (2.50 to 18.50; p<0.0001) in weeks 21-24, a median change of -5.21 (-11.18 to -0.19; p<0.0001) attacks per week. In the 100% ONS stimulation group, mean attack frequency decreased from 17.58 (9.83 to 29.33) at baseline to 9.50 (3.00 to 21.25) at 21-24 weeks (median change from baseline -4.08, -11.92 to -0.25), and for the 30% ONS stimulation group, mean attack frequency decreased from 15.00 (9.25 to 22.33) to 6.75 (1.50 to 16.50; -6.50, -10.83 to -0.08). The difference in median weekly mean attack frequency between groups at the end of the masked phase in weeks 21-24 was -2.42 (95% CI -5.17 to 3.33). In the masked study phase, 129 adverse events occurred with 100% ONS and 95 occurred with 30% ONS. None of the adverse events was unexpected but 17 with 100% ONS and eight with 30% ONS were labelled as serious, given they required brief hospital admission for minor hardware-related issues. The most common adverse events were local pain, impaired wound healing, neck stiffness, and hardware damage.Interpretation In patients with MICCH, both 100% ONS intensity and 30% ONS intensity substantially reduced attack frequency and were safe and well tolerated. Future research should focus on optimising stimulation protocols and disentangling the underlying mechanism of action. Copyright (C) 2021 Elsevier Ltd. All rights reserved.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care