A Transcriptomic Comparative Study of Cranial Vasculature.

In genetic studies of cerebrovascular diseases, the optimal vessels to use as controls remain unclear. Our goal is to compare the transcriptomic profiles among 3 different types of control vessels: superficial temporal artery (STA), middle cerebral arteries (MCA), and arteries from the circle of Willis obtained from autopsies (AU). We examined the transcriptomic profiles of STA, MCA, and AU using RNAseq. We also investigated the effects of using these control groups on the results of the comparisons between aneurysms and the control arteries. Our study showed that when comparing pathological cerebral arteries to control groups, all control groups presented similar responses in the activation of immunological processes, the regulation of intracellular signaling pathways, and extracellular matrix productions, despite their intrinsic biological differences. When compared to STA, AU exhibited upregulation of stress and apoptosis genes, whereas MCA showed upregulation of genes associated with tRNA/rRNA processing. Moreover, our results suggest that the matched case-control study design, which involves control STA samples collected from the same subjects of matched aneurysm samples in our study, can improve the identification of non-inherited disease-associated genes. Given the challenges associated with obtaining fresh intracranial arteries from healthy individuals, our study suggests that using MCA, AU, or paired STA samples as controls are feasible strategies for future large-scale studies investigating cerebral vasculopathies. However, the intrinsic differences of each type of control should be taken into consideration when interpreting the results. With the limitations of each control type, it may be most optimal to use multiple tissues as controls.

Ruptured Fisher grade 3 blister aneurysms have a higher incidence of delayed cerebral ischemia than ruptured Fisher grade 3 saccular aneurysms.

BACKGROUND: Blister aneurysms are a rare subclass of aneurysms, which remain challenging to treat both with open cerebrovascular and endovascular techniques, and clinicians continue to see poor outcomes in some cases despite improvements in technology. Based on our clinical observations, we hypothesized that patients with a Fisher grade 3 subarachnoid hemorrhage (SAH) from a ruptured anterior circulation blister aneurysm are significantly more likely to develop poor outcome due to delayed cerebral ischemia than patients with a Fisher grade 3 SAH from a ruptured anterior circulation saccular aneurysm. METHODS: In this consecutive case series, we reviewed management, outcomes, and rates of delayed cerebral ischemia for all ruptured anterior circulation blister aneurysms from 2012 to 2018 at our institution and compared them to a concurrent cohort of ruptured saccular anterior circulation aneurysms. A blister aneurysm was defined as an aneurysm that arises from a nonbranching point and demonstrates hemispherical anatomy on diagnostic angiography. RESULTS: We identified 14 consecutive ruptured anterior circulation blister aneurysms. Thirteen aneurysms were treated operatively- 5 with clip remodeling and 8 with flow diversion embolization. While clip remodeling had a high intraoperative rupture rate (80%), there was only one (12.5%) intraoperative rupture with flow diversion embolization. Outcomes were worsened by delayed cerebral ischemia from vasospasm in patients with Fisher 3 hemorrhages from blister aneurysms (86%). The rate of delayed cerebral ischemia from vasospasm was significantly higher for ruptured blister aneurysms than for a concurrent cohort of ruptured saccular aneurysms (8.6%, P = 0.0001). CONCLUSION: Ruptured Fisher grade 3 anterior circulation blister aneurysms have a significantly higher incidence of delayed cerebral ischemia from vasospasm compared to saccular aneurysms, regardless of the treatment modality.

Mechanical injury and blood are drivers of spatial memory deficits after rapid intraventricular hemorrhage.

Aneurysmal intraventricular hemorrhage (IVH) survivors may recover with significant deficits in learning and memory. The goal of this study was to investigate the mechanism of memory decline after intraventricular aneurysm rupture. We developed an aneurysmal IVH rat model by injecting autologous, arterial blood over the period of two minutes into the right lateral ventricle. We also evaluated the effects of a volume-matched artificial cerebrospinal fluid (CSF) control, thrombin and the mode of delivery (pulsed hand injection versus continuous pump infusion). We performed magnetic resonance brain imaging after 1 and 5 weeks to evaluate for hydrocephalus and histological analysis of the dentate gyrus after 6 weeks. Only animals which underwent a whole blood pulsed hand injection had a spatial memory acquisition and retention deficit 5 weeks later. These animals had larger ventricles at 1 and 5 weeks than animals which underwent a continuous pump infusion of whole blood. We did not find a decline in dentate gyrus granule cell neurons or an impairment in dentate gyrus neurogenesis or differentiation 6 weeks after IVH. Rapid injections of blood or volume resulted in microglial activation in the dentate gyrus. In conclusion, our results point to mechanical injury as the predominant mechanism of memory decline after intraventricular aneurysmal rupture. However, volume-matched pulsed injections of artificial CSF did not create a spatial memory deficit at 5 weeks. Therefore, whole blood itself must play a role in the mechanism. Further research is required to evaluate whether the viscosity of blood causes additional mechanical disruption and hydrocephalus through a primary injury mechanism or whether the toxicity of blood causes a secondary injury mechanism that leads to the observed spatial memory deficit after 5 weeks.

Comparison of 3D TOF MR angiographic accuracy in predicting Raymond grade of flow-diverted versus coiled intracranial aneurysms.

The accuracy of 3D time of Flight Magnetic Resonance Angiography (TOF MRA) has been studied extensively for following coiled intracranial aneurysms. It is used by many clinicians for non-invasive follow-up because of its adequate sensitivity in predicting aneurysmal recanalization compared to diagnostic cerebral angiography. The data on the accuracy of 3D TOF MRA for the Pipeline™ Embolization Device (PED) are sparse. In a retrospective chart review, we compared the accuracy of 3D TOF MRA of PED to coil embolization at our institution. 3D TOF MRA had a lower sensitivity and positive predictive value in detecting aneurysmal filling in PED-treated versus coiled aneurysms (57% versus 87% and 80% versus 100%, respectively). Analysis of discrepancies between conventional diagnostic angiography and 3D TOF MRA revealed that 3D TOF MRA was inaccurate in the setting of small residual necks and slow residual filling of the dome with fluid-fluid layers. Therefore, contrasted studies such as contrast-enhanced MRA may be preferred for non-invasively following PED-treated aneurysms to increase accuracy.

Resolution of third nerve palsy despite persistent aneurysmal mass effect after flow diversion embolization of posterior communicating artery aneurysms.

Posterior communicating artery (PCOM) aneurysms may cause third nerve palsies. The optimal treatment with clipping versus coiling remains controversial. Here we report on two cases of resolution of third nerve palsy after flow diversion embolization of large and giant PCOM aneurysms without adjuvant coil placement. The resolution of third nerve palsy was not preceded by significant shrinkage of the aneurysmal sac on MRI. However, one patient showed resolution of T2-weighted signal abnormalities in the midbrain and mesial temporal lobe despite a similar size of the aneurysm. Therefore, flow diversion embolization of a PCOM aneurysm may resolve oculomotor nerve palsies through decreasing arterial pulsations against the nerve or midbrain.