Neuroprotective effect of dapsone in patients with aneurysmal subarachnoid hemorrhage: a prospective, randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: In this study, the authors sought to define the differences in the incidence of delayed cerebral ischemia (DCI) between patients treated with dapsone and those treated with placebo. Secondary objectives were to define the clinical outcome at discharge and 3 months and the incidence of brain infarction. METHODS: A prospective, randomized, double-blind, placebo-controlled study was performed and included patients with aneurysmal subarachnoid hemorrhage (SAH) within 5 days from ictus who were candidates for aneurysm occlusion, and who had a Fisher grade of 3 or 4. Patients with sulfa or sulfone drug allergies, hemoglobin < 11 g/dl, known G6PD deficiency, and those refusing informed consent were excluded. A minimal relevant effect decrease of 35% in the incidence of DCI was established. Patients were randomly assigned to receive a regimen of dapsone 2.5 ml (100 mg) daily or a placebo (aluminum hydroxide suspension, 2.5 ml daily). Both groups received validated treatment for aneurysmal SAH. The appearance of DCI on CT was assessed in every patient at discharge and 3 months later. We used the chi-square test to compare the DCI incidence between both groups, and the Student t-test or nonparametric tests to compare quantitative variables. RESULTS: Overall, 48 patients (70.8% women and 29.2% men) were included. The mean age was 50 years (SD 14.28 years, range 18-72 years). Prerandomization and postrandomization characteristics were balanced, except for the necessity of intra-arterial nimodipine administration in patients treated with placebo (15.4% vs 45.5%, p = 0.029. The incidence of DCI, the primary endpoint, for the whole cohort was 43.8% and was significantly lower in the dapsone group (26.9% vs 63.6%, p = 0.011). In addition, the irreversible DCI incidence was lower in the dapsone group (11.5% vs 54.5%, p = 0.12). A favorable modified Rankin Scale score was more frequent in the dapsone group at discharge and at 3 months (76.9% vs 36.4%, p = 0.005 and 80% vs 38.9%, p = 0.019, respectively). Also, the brain infarction incidence was lower in the dapsone group (19.2% vs 63.6%, p = 0.001). There was no difference between groups regarding adverse events. CONCLUSIONS: Dapsone seems to play a role as a prophylactic agent in patients at high risk of developing DCI after aneurysmal SAH. A multicenter investigation is necessary to increase the study population and confirm the consistency of the results observed in this study.

Trigeminal neuralgia secondary to arteriovenous malformations of the posterior fossa.

BACKGROUND: Trigeminal neuralgia secondary to a posterior fossa AVM has been seldom reported in the literature. Most of the cases have been published on a case report basis, and there is not a general agreement about the best way of treatment. METHODS: In this work, we analyze our experience with 5 cases of TN secondary to a posterior fossa AVM, treated at the Division of Neurosurgery from the National Institute of Neurology and Neurosurgery, "Manuel Velasco Suarez," Mexico City, Mexico, from January 1985 to December 2004. RESULTS: Trigeminal neuralgia associated with an AVM occurred in 1.3% of 375 brain AVMs and 9.8% of 37 posterior fossa AVMs. All had received drug therapy unsuccessfully, and 2 of them underwent a percutaneous thermocoagulation without solving the neuralgia. In 4 patients, a microvascular decompression was completed with excellent results. CONCLUSIONS: Even when different ways of treatment have been reported, it seems that percutaneous procedures (glycerol injection, thermocoagulation, or microcompression of the gasserian ganglia) give variable clinical results. The reported experience and our own results support the microvascular decompression of the trigeminal nerve as the best treatment whenever the total excision of the AVM cannot be accomplished.