Molecular Sequence of Events and Signaling Pathways in Cerebral Metastases

Brain metastases are the leading cause of morbidity and mortality among cancer patients, and are reported to occur in about 40% of cancer patients with metastatic disease in the United States of America. Primary tumor cells appear to detach from the parent tumor site, migrate, survive and pass through the blood brain barrier in order to establish cerebral metastases. This complex process involves distinct molecular and genetic mechanisms that mediate metastasis from these primary organs to the brain. Furthermore, an interaction between the invading cells and cerebral milieu is shown to promote this process as well. Here, we review the mechanisms by which primary cancer cells metastasize to the brain via a mechanism called epithelial-to-mesenchymal transition, as well as the involvement of certain microRNA and genetic aberrations implicated in cerebral metastases from the lung, breast, skin, kidney and colon. While the mechanisms governing the development of brain metastases remain a major hindrance in treatment, understanding and identification of the aforementioned molecular pathways may allow for improved management and discovery of novel therapeutic targets

Isolated Intraventricular Hemorrhage Associated with Cerebral Vasospasm and Delayed Cerebral Ischemia following Arteriovenous Malformation Rupture

Background: Although it is well characterized in aneurysmal subarachnoid hemorrhage, vasospasm is exceedingly rare following cerebral arteriovenous malformation (AVM) rupture. Subsequently, this complication is poorly characterized with regard to delayed cerebral ischemia (DCI). We review cases of ruptured AVM to assess the frequency and severity of vasospasm on cerebral angiography, and DCI. Summary: We reviewed our institutional database of acute intracranial hemorrhages between 2005 and 2014. We identified patients with cerebral AVM rupture and evidence of vasospasm, which was confirmed with digital subtraction angiography (DSA). Cerebral angiograms were evaluated by 2 blinded neurointerventionalists for vasospasm. Statistical analyses were conducted on the angiographic results and variables of interest to determine predictors and associations of vasospasm and DCI. Thirty-six patients with acute intracranial hemorrhage due to ruptured cerebral AVM subsequently underwent cerebral angiography. The interrater reliability for vasospasm was 0.81. The incidence of vasospasm was 13.9% and the incidence of subsequent DCI was 11.1%. A significant relationship existed between isolated intraventricular hemorrhage and vasospasm (p = 0.001) and subsequent DCI (p = 0.006). Radiographic vasospasm was associated with DCI in 80% of the patients (p\u3c0.0001). No statistical significance existed between subarachnoid hemorrhage and the development of vasospasm or DCI (p = 1.000 and p = 0.626, respectively). All differences were significant at a 99% level of significance. Key Message: In cases of ruptured AVM, isolated intraventricular hemorrhage appears to be an independent risk factor for vasospasm and DCI. Vasospasm must be considered during late neurological deterioration following AVM hemorrhage, especially in the setting of isolated intraventricular hemorrhage

Trial of Endovascular Thrombectomy for Large Ischemic Strokes

BACKGROUND: Trials of the efficacy and safety of endovascular thrombectomy in patients with large ischemic strokes have been carried out in limited populations. METHODS: We performed a prospective, randomized, open-label, adaptive, international trial involving patients with stroke due to occlusion of the internal carotid artery or the first segment of the middle cerebral artery to assess endovascular thrombectomy within 24 hours after onset. Patients had a large ischemic-core volume, defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower scores indicating larger infarction) or a core volume of at least 50 ml on computed tomography perfusion or diffusion-weighted magnetic resonance imaging. Patients were assigned in a 1:1 ratio to endovascular thrombectomy plus medical care or to medical care alone. The primary outcome was the modified Rankin scale score at 90 days (range, 0 to 6, with higher scores indicating greater disability). Functional independence was a secondary outcome. RESULTS: The trial was stopped early for efficacy; 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group. The generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (95% confidence interval [CI], 1.20 to 1.89; P CONCLUSIONS: Among patients with large ischemic strokes, endovascular thrombectomy resulted in better functional outcomes than medical care but was associated with vascular complications. Cerebral hemorrhages were infrequent in both groups. (Funded by Stryker Neurovascular; SELECT2 ClinicalTrials.gov number, NCT03876457.)