Saccular intracranial aneurysms (IAs) are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with ∼832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with IA in the combined data set, including intervals near RBBP8 on 18q11.2 (OR=1.22, P=1.1×10-12), STARD13/KL on 13q13.1 (OR=1.20, P=2.5×10-9) and a gene-rich region on 10q24.32 (OR=1.29, P=1.2×10-9). We also confirmed prior associations near SOX17 (8q11.23-q12.1; OR=1.28, P=1.3×10-12) and CDKN2A/B (9p21.3; OR=1.31, P=1.5×10-22). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting proliferation and senescence of progenitor cell populations that are responsible for vascular formation and repair.

Key PointsQuestionDoes the use of adjunct intra-arterial thrombolysis following an angiographically successful thrombectomy improve functional outcomes in patients with large vessel occlusion acute ischemic stroke?FindingsIn this randomized clinical trial that included 121 adults, treatment with intra-arterial alteplase compared with placebo resulted in a modified Rankin Scale score of 0 or 1 in 59.0% vs 40.4% of patients at 90 days. This difference was statistically significant.MeaningAmong patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days; however, the findings should be considered preliminary until replicated.

T he management of patients with unruptured cerebral aneurysms (UA) remains controversial because of their uncertain natural history. Although estimates of the prevalence of intracranial aneurysms range from 0.5% to 6% on radiological and autopsy studies, the incidence of aneurismal subarachnoid hemorrhage (SAH) is 10/100.000 per year in the United States, leading to the conclusion that the majority of UAs do not rupture.1,2 The average risk of rupture of a UA is estimated to be between 1% and 2% per year. 3,4 The International Study of Unruptured Intracranial Aneurysms (ISUIA) reported on a retrospective and prospective multicenter study in 1998 and 2003. 5,6 In the latter, they observed that aneurysm location, size, and previous SAH were risk factors for rupture, with posterior circulation (PC) aneuryms collectively (including posterior communicating artery [PcoA] aneurysms) and aneurysms >7 mm located in the anterior circulation (AC) rupturing with at rates high enough to justify intervention. This observation seems to contradict the clinical perception that patients Background and Purpose-According to the International Study of Unruptured Intracranial Aneurysms (ISUIA), anterior circulation (AC) aneurysms of <7 mm in diameter have a minimal risk of rupture. It is general experience, however, that anterior communicating artery (AcoA) aneurysms are frequent and mostly rupture at <7 mm. The aim of the study was to assess whether AcoA aneurysms behave differently from other AC aneurysms. Methods-Information about 932 patients newly diagnosed with intracranial aneurysms between November 1, 2006, and March 31, 2012, including aneurysm status at diagnosis, its location, size, and risk factors, was collected during the multicenter @neurIST project. For each location or location and size subgroup, the odds ratio (OR) of aneurysms being ruptured at diagnosis was calculated. Results-The OR for aneurysms to be discovered ruptured was significantly higher for AcoA (OR, 3.5 [95% confidence interval, 2.6-4.5]) and posterior circulation (OR, 2.6 [95% confidence interval, 2.1-3.3]) than for AC excluding AcoA (OR, 0.5 [95% confidence interval, 0.4-0.6]). Although a threshold of 7 mm has been suggested by ISUIA as a threshold for aggressive treatment, AcoA aneurysms <7 mm were more frequently found ruptured (OR, 2.0 [95% confidence interval, 1.3-3.0]) than AC aneurysms of 7 to 12 mm diameter as defined in ISUIA. Conclusions-We found that AC aneurysms are not a homogenous group. Aneurysms between 4 and 7 mm located in AcoA or distal anterior cerebral artery present similar rupture odds to posterior circulation aneurysms. Bijlenga et al Risk of Aneurysm Rupture by Location and Size 3019commonly present with ruptured small aneurysms. Moreover, aneurysm locations were segregated only as being either AC or PC for risk assessment, raising concerns that the effects of pathophysiological mechanisms specific to individual arteries were combined reducing sensitivity to location as a risk factor. Work has since been published dem...

Neurotoxicity from contrast media used in angiography is a rare complication from these procedures. The infrequency with which it is encountered makes it a diagnostic challenge. We present the case of a 51-year-old male who, 30 min after successful angiography for treatment of a right carotid-ophthalmic fusiform aneurysm with a stent, developed psychomotor agitation, disorientation, and progressive left faciobrachial hemiparesis (4/5). An emergency nonenhanced CT showed marked cortical enhancement and edema in the right cerebral hemisphere. Cortical enhancement is thought to be secondary to contrast extravasation due to disruption of the blood-brain barrier. Angiography was performed immediately, without any pathologic findings. After this procedure there was an increase in the left faciobrachial hemiparesis (3/5), right gaze deviation, Gerstmann syndrome, and left anosognosia and left homonymous hemianopsia. Endovenous dexamethasone and mannitol were initiated. Twenty-four hours later an MRI showed no signs of acute infarct, just gyriform signal increase in the right cerebral hemisphere on FLAIR and a decrease in the edema observed before. The patient had progressive improvement of his neurological deficit. A control MRI done 5 days later was normal. The patient recovered completely and was discharged. This rare entity should be kept in mind but diagnosed only when all other causes have been ruled out, because more important and frequent causes, such as acute infarct, must be excluded promptly.

These data suggest that flow abnormalities may interfere with language lateralization assessment with functional MR imaging.