Brain arteriovenous malformations (bAVMs) are anomalies forming vascular tangles connecting the arteries and veins, which cause hemorrhagic stroke in young adults. Current surgical approaches are highly invasive, and alternative therapeutic methods are warranted. Recent genetic studies identified KRAS mutations in endothelial cells of bAVMs; however, the underlying process leading to malformation in the postnatal stage remains unknown. Here we established a mouse model of bAVM developing during the early postnatal stage. Among 4 methods tested, mutant KRAS specifically introduced in brain endothelial cells by brain endothelial cell–directed adeno-associated virus (AAV) and endothelial cell–specific Cdh5 - CreERT2 mice successfully induced bAVMs in the postnatal period. Mutant KRAS led to the development of multiple vascular tangles and hemorrhage in the brain with increased MAPK/ERK signaling and growth in endothelial cells. Three-dimensional analyses in cleared tissue revealed dilated vascular networks connecting arteries and veins, similar to human bAVMs. Single-cell RNA-Seq revealed dysregulated gene expressions in endothelial cells and multiple cell types involved in the pathological process. Finally, we employed CRISPR/CasRx to knock down mutant KRAS expression, which efficiently suppressed bAVM development. The present model reveals pathological processes that lead to postnatal bAVMs and demonstrates the efficacy of therapeutic strategies with CRISPR/CasRx.

Intraprocedural rupture (IPR) during coil embolization (CE) of an intracranial aneurysm is a significant clinical concern that necessitates a comprehensive understanding of its clinical and hemodynamic predictors. Between January 2012 and December 2023, 435 saccular cerebral aneurysms were treated with CE at our institution. The inclusion criterion was extravasation or coil protrusion during CE. Postoperative data were used to confirm rupture points, and computational fluid dynamics (CFD) analysis was performed to assess hemodynamic characteristics, focusing on maximum pressure (Pmax) and wall shear stress (WSS). IPR occurred in six aneurysms (1.3%; three ruptured and three unruptured), with a dome size of 4.7 ± 1.8 mm and a D/N ratio of 1.5 ± 0.5. There were four aneurysms in the internal carotid artery (ICA), one in the anterior cerebral artery, and one in the middle cerebral artery. ICA aneurysms were treated using adjunctive techniques (three balloon-assisted, one stent-assisted). Two aneurysms (M1M2 and A1) were treated simply, yet had relatively small and misaligned domes. CFD analysis identified the rupture point as a flow impingement zone with Pmax in five aneurysms (83.3%). Time-averaged WSS was locally reduced around this area (1.3 ± 0.7 [Pa]), significantly lower than the aneurysmal dome (p < 0.01). Hemodynamically unstable areas have fragile, thin walls with rupture risk. A microcatheter was inserted along the inflow zone, directed towards the caution area. These findings underscore the importance of identifying hemodynamically unstable areas during CE. Adjunctive techniques should be applied with caution, especially in small aneurysms with axial misalignment, to minimize the rupture risk.

Intraprocedural rupture (IPR) is a severe complication of coil embolization (CE) for intracranial aneurysms, yet the clinical and hemodynamic features of rupture risk areas remain unclear. From January 2013 to December 2023, 435 saccular cerebral aneurysms (316 unruptured, 119 ruptured) underwent CE at our institution. Included were cases where extravasation or coil protrusion occurred during CE. The rupture point was determined from postoperative data, and computational fluid dynamics (CFD) analysis was conducted to assess hemodynamic features. IPR occurred in six aneurysms (1.3%; three ruptured, three unruptured; dome size: 4.7±1.8 mm, D/N: 1.5±0.5, locations: four internal carotid artery [ICA], one anterior cerebral artery, one middle cerebral artery). ICA aneurysms were treated using adjunctive techniques (three balloon-assisted, one stent-assisted). Two aneurysms (M1M2 and A1) were treated simply, yet had relatively small and misaligned domes. CFD analysis identified the rupture point as a flow impingement zone with maximum pressure (Pmax) in five aneurysms (83.3%). Time-averaged wall shear stress (WSS) was locally reduced around this area (1.3±0.7 [Pa]). Hemodynamically unstable areas indicated fragile, thin walls with rupture risk. Microcatheter insertion along the inflow zone, directed towards the caution area, was practiced. The presence of a flow impingement zone with Pmax and low WSS suggests potential aneurysm rupture in CE, particularly with adjunctive techniques. Small aneurysms, especially those with axial misalignment, warrant careful consideration due to the risk of excessive flow impact stress on the aneurysm wall.

Background: Perianeurysmal edema (PAE) has been suggested as an indicator of potential aneurysm rupture; however, the hemodynamic features of these aneurysms are still unknown. A computational fluid dynamic (CFD) analysis was performed to evaluate the hemodynamic features of a very rare case of a ruptured middle cerebral artery (MCA) aneurysm with PAE. Case Description: A 65-year-old woman presented with disturbed consciousness. A subarachnoid hemorrhage due to an azygos anterior cerebral artery (ACA) aneurysm rupture was suspected. An unruptured MCA aneurysm with PAE was identified in the left temporal lobe. Although the ACA aneurysm was clipped to prevent re-bleeding, the MCA aneurysm subsequently ruptured 6 days later. Clipping of the MCA aneurysm was performed, and hemosiderin deposits suggestive of sentinel bleeding were found on the surface of the aneurysm dome. CFD analysis revealed unstable hemodynamic stress at the expanded bleb area after rupture, localized to the rupture site. Moreover, this analysis revealed flow impingement with pressure elevation and low wall shear stress, which indicated increased inflammation and aneurysm wall thinning that likely led to rupture. Conclusion: Hemosiderin deposits at the aneurysm wall and PAE indicates leakage from a cerebral aneurysm. Hemodynamic stress at the aneurysm may promote an inflammatory response and lead to wall weakening accompanied by PAE. Based on our findings, we recommend that surgical intervention should be considered as the first line of treatment for such aneurysms to prevent rupture.

Background: Contrast-induced encephalopathy (CIE) is a rare complication arising from neurotoxicity caused by iodinated contrast agents. Its clinical presentation closely resembles that of acute stroke, which can occur following endovascular procedures. Distinguishing these two conditions is essential for proper patient management but is challenging based on clinical symptoms alone. While characteristic computed tomography findings for CIE and magnetic resonance imaging (MRI) findings for acute stroke are well established, early MRI findings of CIE – particularly in magnetic resonance angiography (MRA) and perfusion imaging (MRP) – remain underrecognized. In addition, delayed cortical hypointensities on T2*-weighted imaging (T2*WI) in chronic-stage cases have not been previously reported. Case Description: A 78-year-old woman developed CIE immediately following endovascular coil embolization for an unruptured cerebral aneurysm. Small artery vasospasms and hypoperfusion were identified on MRA and MRP, respectively, in the affected hemisphere 6 h postprocedure and resolved a day before symptom improvement. Ten months later, asymptomatic, punctate, and short linear cortical hypointensities appeared on T2*WI, suggesting microhemorrhages. Conclusion: Early transient small artery vasospasms and hypoperfusion on neuroimaging are indicative of CIE and likely contribute to the neurological symptoms of this condition. Persistent blood–brain barrier dysfunction may underlie the delayed development of cortical hypointensities on T2*WI, seen in chronic-stage CIE cases.

The etiology of a non-sinus-type dural arteriovenous fistulas (DAVFs) with shunt points located on the sinus wall, previously described as on-the-wall-type DAVFs, is unknown.