Current Update on the Randomized Controlled Trials of Intracranial Aneurysms

Endovascular coiling has become the primary treatment modality for the treatment of intracranial ruptured aneurysms in many centers. A multicenter randomized controlled trial (RCT), ISAT study, has demonstrated that endovascular coiling of ruptured intracranial aneurysms has benefits over surgical clipping in those patients suitable for either treatment. Because RCT comparing conservative management with surgical clipping and with endovascular coiling have not been performed to date for unruptured intracranial aneurysms, the best management for unruptured aneurysm remains unclear. A RCT is ongoing to answer the question whether active treatment can improve the outcome of patients with unruptured intracranial aneurysms as compared with observation

Effects of intraoperative hypothermia on neuropsychological outcomes after intracranial aneurysm surgery

Objective Subarachnoid hemorrhage and surgical obliteration of ruptured intracranial aneurysms are frequently associated with neurological and neuropsychological abnormalities. We reported that intraoperative cooling did not improve neurological outcome in good-grade surgical subarachnoid hemorrhage patients, as assessed by the Glasgow Outcome Scale score or other neurological and functional measures (National Institutes of Health Stroke Scale, Rankin Disability Scale, Barthel Activities of Daily Living). We now report the results of neuropsychological testing in these patients. Methods A total of 1,001 patients who bled ≤14 days before surgery were randomly assigned to intraoperative hypothermia (t = 33°C) or normothermia (37°C). Outcome was assessed approximately 3 months after surgery. Patients underwent the Benton Visual Retention, Controlled Oral Word Association, Rey–Osterrieth Complex Figure, Grooved Pegboard, and the Trail Making tests. T -scores for each test were calculated from normative data. T -scores were averaged to calculate a Composite Score. A test result (or the Composite Score) was considered “impaired” if the T -score was two or more standard deviations below the norm. A Mini-Mental State Examination was also performed. Results Neurological outcome data were available in 1,000 patients. Sixty-one patients died. Of the 939 survivors, 873 completed 3 or more tests (exclusive of the Mini-Mental State Examination). Patients with poor neurological outcomes were less likely to complete testing; only 3.9% of Good Outcome (Glasgow Outcome Scale score = 1) patients were untested, compared with 38.6% of patients with Glasgow Outcome Scale scores of 3 and 4. There were no prerandomization demographic differences between the two treatment groups. For hypothermic patients, 16.8% were impaired from their Composite Score versus 20.0% of patients in the normothermic group ( p = 0.317). For patients in the hypothermic group, 54.5% were impaired on at least one test, compared with 55.5% of patients in the normothermic group ( p = 0.865). Similar results were seen in patients with baseline WFNS scores = I. Mini-Mental State Examination scores in the hypothermic and normothermic groups were 27.4 ± 3.8 and 26.8 ± 4.5, respectively. Interpretation This is the largest prospective evaluation of neuropsychological function after subarachnoid hemorrhage to date. Testing was completed in a high fraction of patients, demonstrating the feasibility of such testing in a large trial. However, the frequent inability to complete testing in poor-outcome patients suggests that testing may be best used to refine outcome assessments in good-grade patients. Many patients showed impairment on at least one test, with global impairment present in 17 to 20% of patients (18–21% of survivors). This was true even among the patients with the best preoperative condition (WFNS = 1). There was no difference in the incidence of impairment between hypothermic and normothermic groups. Ann Neurol 2006;60:518–527Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55889/1/21018_ftp.pd

Endothelial Nitric Oxide Gene T-786C Polymorphism and Subarachnoid Hemorrhage in Korean Population

We aimed to elucidate whether the eNOS T-786C mutant allele is implicated in subarachnoid hemorrhage (SAH) susceptibility or vasospasm after SAH, and whether the mutant allele is differentially expressed in those with small and large ruptured aneurysms in Korean population. 136 consecutive patients diagnosed with aneurismal SAH and 113 controls were recruited. Polymerase chain reaction and direct sequencing of both strands were performed to determine genotypes with respect to the eNOS T-786C mutation. No significant difference was found between cases and controls with respect to the distributions of the two eNOS T-786C single nucleotide polymorphism (SNP) genotypes. No significant differences in the distributions of the eNOS T-786C SNP genotypes were found with regard to the sizes of ruptured aneurysms or the occurrence of vasospasm after SAH. Multiple logistic regression analysis after controlling for age and sex showed the eNOS T-786C SNP T/C genotype was independently associated with an unfavorable outcome (GOS grade 3-5) of SAH (Exp (β)=4.27, 95% CI 1.131-16.108, p=0.032). In conclusion, the eNOS T-786C mutation was not found to be associated with either a susceptibility to SAH or vasospasm after SAH, or with aneurysm size in Korean population. The eNOS T-786C SNP T/C genotype could be used as a prognostic marker in individuals with SAH

Microsurgical Strategies Following Failed Endovascular Treatment with the Pipeline Embolization Device: Case of a Giant Posterior Cerebral Artery Aneurysm

Treatment of giant posterior circulation aneurysms, via endovascular or microsurgical approaches, carries a high risk of morbidity and mortality. While flow-diverting stents (FDSs) represent a potent therapy for endovascular reconstruction of complex aneurysms, they are also associated with novel complications for which effective salvage techniques are lacking. We present a unique complication from failed treatment with a FDS. A 51 year-old male presented with increasing headaches secondary to a giant, fusiform aneurysm of the left posterior cerebral artery, which was largely thrombosed. Due to progressive enlargement of the aneurysm corresponding to worsening clinical symptoms, the lesion was treated with two Pipeline embolization devices (ev3, Plymouth, MN, United States). Three months after Pipeline embolization device treatment, complete posterior cerebral artery occlusion was observed at the origin of the proximal stent. Despite the lack of arterial inflow, the aneurysm dome continued to grow, resulting in obstructive hydrocephalus. Therefore microsurgical intervention was undertaken to trap and excise the aneurysm. The patient's postoperative course was complicated by multiple venous infarcts, ultimately resulting in death. Successful microsurgical obliteration of aneurysms previously treated with FDSs is extremely difficult. A combination of judicious preoperative planning and meticulous intraoperative surgical technique are requisite for effective management of these complicated cases

Unruptured intracranial aneurysms--risk of rupture and risks of surgical intervention

Background The management of unruptured intracranial aneurysms requires knowledge of the natural history of these lesions and the risks of repairing them. Methods A total of 2621 patients at 53 participating centers in the United States, Canada, and Europe were enrolled in the study, which had retrospective and prospective components. In the retrospective component, we assessed the natural history of unruptured intracranial aneurysms in 1449 patients with 1937 such aneurysms; 727 of the patients had no history of subarachnoid hemorrhage from a different aneurysm (group 1), and 722 had a history of subarachnoid hemorrhage from a different aneurysm that had been repaired successfully (group 2). In the prospective component, we assessed treatment-related morbidity and mortality in 1172 patients with newly diagnosed unruptured intracranial aneurysms. Results In group 1, the cumulative rate of rupture of aneurysms that were less than 10 mm in diameter at diagnosis was less than 0.05 percent per year, and in group 2, the rate was approximately 11 times as high (0.5 percent per year). The rupture rate of aneurysms that were 10 mm or more in diameter was less than 1 percent per year in both groups, but in group 1, the rate was 6 percent the first year for giant aneurysms (≥25 mm in diameter). The size and location of the aneurysm were independent predictors of rupture. The overall rate of surgery-related morbidity and mortality was 17.5 percent in group 1 and 13.6 percent in group 2 at 30 days and was 15.7 percent and 13.1 percent, respectively, at 1 year. Age independently predicted surgical outcome. Conclusions The likelihood of rupture of unruptured intracranial aneurysms that were less than 10 mm in diameter was exceedingly low among patients in group 1 and was substantially higher among those in group 2. The risk of morbidity and mortality related to surgery greatly exceeded the 7.5-year risk of rupture among patients in group 1 with unruptured intracranial aneurysms smaller than 10 mm in diameter