The biophysical role of hemodynamics in the pathogenesis of cerebral aneurysm formation and rupture.

The pathogenesis of intracranial aneurysms remains complex and multifactorial. While vascular, genetic, and epidemiological factors play a role, nascent aneurysm formation is believed to be induced by hemodynamic forces. Hemodynamic stresses and vascular insults lead to additional aneurysm and vessel remodeling. Advanced imaging techniques allow us to better define the roles of aneurysm and vessel morphology and hemodynamic parameters, such as wall shear stress, oscillatory shear index, and patterns of flow on aneurysm formation, growth, and rupture. While a complete understanding of the interplay between these hemodynamic variables remains elusive, the authors review the efforts that have been made over the past several decades in an attempt to elucidate the physical and biological interactions that govern aneurysm pathophysiology. Furthermore, the current clinical utility of hemodynamics in predicting aneurysm rupture is discussed.

Transcranial Doppler ultrasonography in neurological surgery and neurocritical care.

Transcranial Doppler (TCD) ultrasonography is an inexpensive, noninvasive means of measuring blood flow within the arteries of the brain. In this review, the authors outline the technology underlying TCD ultrasonography and describe its uses in patients with neurosurgical diseases. One of the most common uses of TCD ultrasonography is monitoring for vasospasm following subarachnoid hemorrhage. In this setting, elevated blood flow velocities serve as a proxy for vasospasm and can herald the onset of ischemia. TCD ultrasonography is also useful in the evaluation and management of occlusive cerebrovascular disease. Monitoring for microembolic signals enables stratification of stroke risk due to carotid stenosis and can also be used to clarify stroke etiology. TCD ultrasonography can identify patients with exhausted cerebrovascular reserve, and after extracranial-intracranial bypass procedures it can be used to assess adequacy of flow through the graft. Finally, assessment of cerebral autoregulation can be performed using TCD ultrasonography, providing data important to the management of patients with severe traumatic brain injury. As the clinical applications of TCD ultrasonography have expanded over time, so has their importance in the management of neurosurgical patients. Familiarity with this diagnostic tool is crucial for the modern neurological surgeon.

Analysis of cerebrovascular aneurysm treatment cost: retrospective cohort comparison of clipping, coiling, and flow diversion.

OBJECTIVE With the continuous rise of health care costs, hospitals and health care providers must find ways to reduce costs while maintaining high-quality care. Comparing surgical and endovascular treatment of intracranial aneurysms may offer direction in reducing health care costs. The Value-Driven Outcomes (VDO) database at the University of Utah identifies cost drivers and tracks changes over time. In this study, the authors evaluate specific cost drivers for surgical clipping and endovascular management (i.e., coil embolization and flow diversion) of both ruptured and unruptured intracranial aneurysms using the VDO system. METHODS The authors retrospectively reviewed surgical and endovascular treatment of ruptured and unruptured intracranial aneurysms from July 2011 to January 2017. Total cost (as a percentage of each patient's cost to the system), subcategory costs, and potential cost drivers were evaluated and analyzed. RESULTS A total of 514 aneurysms in 469 patients were treated; 273 aneurysms were surgically clipped, 102 were repaired with coiling, and 139 were addressed with flow diverter placements. Middle cerebral artery aneurysms accounted for the largest portion of cases in the clipping group (29.7%), whereas anterior communicating artery aneurysms were most frequently involved in the coiling group (30.4%) and internal carotid artery aneurysms were the majority in the flow diverter group (63.3%). Coiling (mean total cost 0.25% ± 0.20%) had a higher cost than flow diversion (mean 0.20% ± 0.16%) and clipping (mean 0.17 ± 0.14%; p = 0.0001, 1-way ANOVA). Coiling cases cost 1.5 times as much as clipping and flow diversion costs 1.2 times as much as clipping. Facility costs were the most significant contributor to intracranial clipping costs (60.2%), followed by supplies (18.3%). Supplies were the greatest cost contributor to coiling costs (43.2%), followed by facility (40.0%); similarly, supplies were the greatest portion of costs in flow diversion (57.5%), followed by facility (28.5%). Cost differences for aneurysm location, rupture status, American Society of Anesthesiologists (ASA) grade, and discharge disposition could be identified, with variability depending on surgical procedure. A multivariate analysis showed that rupture status, surgical procedure type, ASA status, discharge disposition, and year of surgery all significantly affected cost (p < 0.0001). CONCLUSIONS Facility utilization and supplies constitute the majority of total costs in aneurysm treatment strategies, but significant variation exists depending on surgical approach, rupture status, and patient discharge disposition. Developing and implementing approaches and protocols to improve resource utilization are important in reducing costs while maintaining high-quality patient care.

Complications associated with the use of flow-diverting devices for cerebral aneurysms: a systematic review and meta-analysis.

OBJECTIVE The objective of this study was to review the literature on the use of flow-diverting devices (FDDs) to treat intracranial aneurysms (IAs) and to investigate the safety and complications related to FDD treatment for IAs by performing a meta-analysis of published studies. METHODS A systematic electronic database search was conducted using the Springer, EBSCO, PubMed, Medline, and Cochrane databases on all accessible articles published up to January 2016, with no restriction on the publication year. Abstracts, full-text manuscripts, and the reference lists of retrieved articles were analyzed. Random-effects meta-analysis was used to pool the complication rates across studies. RESULTS Sixty studies were included, which involved retrospectively collected data on 3125 patients. The use of FDDs was associated with an overall complication rate of 17.0% (95% confidence interval [CI] 13.6%-20.5%) and a low mortality rate of 2.8% (95% CI 1.2%-4.4%). The neurological morbidity rate was 4.5% (95% CI 3.2%-5.8%). No significant difference in the complication or mortality rate was observed between 2 commonly used devices (the Pipeline embolization device and the Silk flow-diverter device). A significantly higher overall complication rate was found in the case of ruptured IAs than in unruptured IA (odds ratio 2.3, 95% CI 1.2-4.3). CONCLUSIONS The use of FDDs in the treatment of IAs yielded satisfactory results with regard to complications and the mortality rate. The risk of complications should be considered when deciding on treatment with FDDs. Further studies on the mechanism underlying the occurrence of adverse events are required.

Endovascular treatment of an aneurysm arising from the minor limb of an upper basilar artery fenestration: illustrative case.

BACKGROUND: An aneurysm arising in an upper basilar artery (BA) fenestration is extremely rare. The authors reported a case involving successful endovascular treatment of an aneurysm arising from the minor limb of an upper BA fenestration. OBSERVATIONS: A 65-year-old woman presented with an incidentally detected upper BA aneurysm arising from the minor limb of an upper BA fenestration. The irregularly shaped aneurysm was 6.0 × 2.7 mm in diameter, and the minor limb had several perforators. The aneurysm was nearly completely occluded with a catheter-assisted technique. The authors preserved both limbs of the BA fenestration. The postoperative course was uneventful, and the patient had an excellent clinical course with no neurological deficits or aneurysmal recanalization. LESSONS: The case is the first report of an unruptured aneurysm arising at the minor limb of an upper BA fenestration. In this case, the authors preserved the minor limb with endovascular treatment. The authors believe catheter-assisted coil embolization to be a feasible endovascular technique in such cases.

Computational hemodynamic analysis of the offending vertebral artery at the site of neurovascular contact in a case of hemifacial spasm associated with subclavian steal syndrome: illustrative case.

BACKGROUND: Hemifacial spasm (HFS) is caused by neurovascular contact along the facial nerve's root exit zone (REZ). The authors report a rare HFS case that was associated with ipsilateral subclavian steal syndrome (SSS). OBSERVATIONS: A 42-year-old man with right-sided aortic arch presented with progressing left HFS, which was associated with ipsilateral SSS due to severe stenosis of the left brachiocephalic trunk. Magnetic resonance imaging showed contact between the left REZ and vertebral artery (VA), which had shifted to the left. The authors speculated that the severe stenosis at the left brachiocephalic trunk resulted in the left VA's deviation, which was the underlying cause of the HFS. The authors performed percutaneous angioplasty (PTA) to dilate the left brachiocephalic trunk. Ischemic symptoms of the left arm improved after PTA, but the HFS remained unchanged. A computational fluid dynamics study showed that the high wall shear stress (WSS) around the site of neurovascular contact decreased after PTA. In contrast, pressure at the point of neurovascular contact increased after PTA. LESSONS: SSS is rarely associated with HFS. Endovascular treatment for SSS reduced WSS of the neurovascular contact but increased theoretical pressure of the neurovascular contact. Physical release of the neurovascular contact is the best treatment option for HFS.

Endovascular treatment of a ruptured aneurysm arising from the proximal end of a partial vertebrobasilar duplication with a contralateral prominent persistent primitive hypoglossal artery: illustrative case.

BACKGROUND: Ruptured aneurysms associated with a partial vertebrobasilar duplication or a persistent primitive hypoglossal artery (PPHA) have been reported. Only rarely has endovascular treatment of ruptured aneurysms in association with both vascular variations been reported. OBSERVATIONS: A 66-year-old woman experienced the sudden onset of a severe headache caused by a subarachnoid hemorrhage. Cerebral angiograms demonstrated a prominent PPHA originating from the left internal carotid artery at the C2 vertebral level and a partial vertebrobasilar duplication between the hypoplastic right vertebral artery and proximal basilar artery with a small aneurysm at the proximal end of the duplication from where the anterior spinal artery originated. The left vertebral artery was aplastic. A microcatheter was introduced into the aneurysm via the PPHA under the control of high blood flow, using a balloon-assisted technique. The aneurysm was completely obliterated with a coil. Although small cerebellar and cerebral infarcts developed during the procedure, the patient was discharged without neurological symptoms. LESSONS: To avoid serious neurological complications, precise analysis of the complex vascular anatomy, including the anterior spinal artery and hemodynamics, is clinically important for endovascular therapy of cerebral aneurysms in patients with an association between a partial vertebrobasilar duplication and a PPHA.

Impact of perioperative aneurysm rebleeding after subarachnoid hemorrhage.

OBJECTIVE: Aneurysm rebleeding is a major cause of death and morbidity in patients with aneurysmal subarachnoid hemorrhage (SAH). Recognizing the predictors of rebleeding might help to identify patients who will benefit from acute management. This study was performed to investigate the predictors of aneurysm rebleeding and their impact on clinical outcomes in the preoperative, intraoperative, and postoperative periods. METHODS: The incidence of rebleeding, demographic data, and clinical data from 4933 patients with aneurysmal SAH beginning in the year 2000 were retrospectively analyzed in the Nagasaki SAH Registry Study. The authors performed multiple logistic regression analyses to identify the risk factors contributing to rebleeding and outcome after SAH. RESULTS: Preoperative rebleeding occurred in 7.2% of patients. Patient age (p = 0.01), multiple aneurysms (p < 0.01), aneurysm size (p < 0.0001), and heart disease (p = 0.03) were significantly associated with preoperative rebleeding. Conversely, intraoperative rebleeding occurred in 11.2% of patients. Aneurysm location (anterior communicating artery [ACoA]), family history (p = 0.02), preoperative rebleeding (p < 0.01), and clipping/coiling (p < 0.0001) were significantly associated with intraoperative rebleeding. Interaction analysis showed that clipping significantly affected intraoperative rebleeding at the ACoA (OR 4.00; 95% CI 1.82-8.80; p < 0.001). Postoperative rebleeding occurred in 2.4% of patients. Coiling/clipping (p < 0.0001) and intraoperative rebleeding (p < 0.01) were significantly associated with postoperative rebleeding. Rebleeding in all time periods examined significantly contributed to the clinical outcome after SAH. CONCLUSIONS: Aneurysm rebleeding after SAH has specific characteristics in the preoperative, intraoperative, and postoperative periods, and all of these characteristics contribute to the clinical outcome. The ACoA has a higher risk of intraoperative rebleeding, and endovascular coiling could be a good candidate in terms of techniques for preventing intraoperative rebleeding, although complete aneurysm obliteration should be accomplished.

Optical coherence tomography imaging after endovascular thrombectomy for basilar artery occlusion: report of 3 cases.

Studies evaluating individuals for endothelial injury after endovascular thrombectomy (EVT) have been done by means of retrieved human thrombus, MR vessel-wall imaging, and animal histopathological studies. These techniques have limitations, because MR imaging has insufficient spatial resolution to directly visualize endothelium, and histopathological examinations are performed ex vivo and are unable to provide real-time patterns of injury. The purpose of the current study was to obtain in vivo intraluminal imaging after EVT by using optical coherence tomography (OCT), examining for evidence of endothelial injury in real time.Three consecutive patients with acute basilar artery occlusion underwent OCT imaging immediately after EVT. There were no complications and adequate images were obtained for all patients. Anatomical features of the vessel wall were discernible, including intima, media, adventitia, and internal/external elastic lamina. Basilar artery thick concentric plaque fibrosis was present, causing outward remodeling and loss of the internal/external lamina in certain regions. Evidence of significant residual thrombus was also visible, with mostly red thrombus present despite complete angiographic revascularization. The residual thrombus was not visible on CT, MR, or cerebral angiography and could certainly cause ongoing function-limiting strokes with occlusion of adjacent vital basilar perforators after EVT.

Rupture risk of small unruptured cerebral aneurysms.

OBJECTIVEThe annual rupture rate of small (3-4 mm) unruptured cerebral aneurysms (UCAs) is 0.36% per year, however, the proportion of small ruptured aneurysms < 5 mm is 35%. This discrepancy is explained by the hypothesis that most acute subarachnoid hemorrhage (SAH) is from recently formed, unscreened aneurysms, but this hypothesis is without definitive proof. The authors aimed to clarify the actual number of screened, ruptured small aneurysms and risk factors for rupture.METHODSThe Unruptured Cerebral Aneurysm Study Japan, a project of the Japan Neurosurgical Society, was designed to clarify the natural course of UCAs. From January 2001 through March 2004, 6697 UCAs among 5720 patients were prospectively registered. At registration, 2839 patients (49.6%) had 3132 (46.8%) small UCAs of 3-4 mm. The registered, treated, and rupture numbers of these small aneurysms and the annual rupture rate were investigated. The rate was assessed per aneurysm. The characteristics of patients and aneurysms were compared to those of larger unruptured aneurysms (≥ 5 mm). Cumulative rates of SAH were estimated per aneurysm. Risk factors underwent univariate and multivariate analysis.RESULTSTreatment and rupture numbers of small UCAs were 1132 (37.1% of all treated aneurysms) and 23 (20.7% of all ruptured aneurysms), respectively. The registered, treated, rupture number, and annual rupture rates were 1658 (24.8%), 495 (16.2%), 11 (9.9%), and 0.30%, respectively, among 3-mm aneurysms, and 1474 (22.0%), 637 (20.9%), 12 (10.8%), and 0.45%, respectively, among 4-mm aneurysms. Multivariate risk-factor analysis revealed that a screening brain checkup (hazard ratio [HR] 4.1, 95% confidence interval [CI] 1.2-14.4), history of SAH (HR 10.8, 95% CI 2.3-51.1), uncontrolled hypertension (HR 5.2, 95% CI 1.8-15.3), and location on the anterior communicating artery (ACoA; HR 5.0, 95% CI 1.6-15.5) were independent predictors of rupture.CONCLUSIONSAlthough the annual rupture rate of small aneurysms was low, the actual number of ruptures was not low. Small aneurysms that ruptured during follow-up could be detected, screened, and managed based on each risk factor. Possible selection criteria for treating small UCAs include a history of SAH, uncontrolled hypertension, location on the ACoA, and young patients. Further large prospective and longitudinal trials are needed.Clinical trial registration no.: C000000418 (https://www.umin.ac.jp/ctr).

Vasa vasorum formation is associated with rupture of intracranial aneurysms.

OBJECTIVE: Subarachnoid hemorrhage (SAH) has a poor outcome despite modern advancements in medical care. The development of a novel therapeutic strategy to prevent rupture of intracranial aneurysms (IAs) or a novel diagnostic marker to predict rupture-prone lesions is thus mandatory. Therefore, in the present study, the authors established a rat model in which IAs spontaneously rupture and examined this model to clarify histopathological features associated with rupture of lesions. METHODS: Female Sprague Dawley rats were subjected to bilateral ovariectomy; the ligation of the left common carotid, the right external carotid, and the right pterygopalatine arteries; induced systemic hypertension; and the administration of a lysyl oxidase inhibitor. RESULTS: Aneurysmal SAH occurred in one-third of manipulated animals and the locations of ruptured IAs were exclusively at a posterior or anterior communicating artery (PCoA/ACoA). Histopathological examination using ruptured IAs, rupture-prone IAs induced at a PCoA or ACoA, and IAs induced at an anterior cerebral artery-olfactory artery bifurcation that never ruptured revealed the formation of vasa vasorum as an event associated with rupture of IAs. CONCLUSIONS: The authors propose the contribution of a structural change in an adventitia, i.e., vasa vasorum formation, to the rupture of IAs. Findings from this study provide important insights about the pathogenesis of IAs.

FRED Italian Registry: a multicenter experience with the flow re-direction endoluminal device for intracranial aneurysms.

OBJECTIVE: The introduction of flow-diverter devices (FDDs) has revolutionized the endovascular treatment of intracranial aneurysms. Here the authors present their Italian multicenter experience using the flow re-direction endoluminal device (FRED) in the treatment of cerebral aneurysms, evaluating both short- and long-term safety and efficacy of this device. METHODS: Between February 2013 and December 2014, 169 consecutive aneurysms treated using FRED in 166 patients were entered into this study across 30 Italian centers. Data collected included patient demographics, aneurysm location and characteristics, baseline angiography, adverse event and serious adverse event information, morbidity and mortality rates, and pre- and posttreatment modified Rankin Scale scores, as well as angiographic and cross-sectional CT/MRI follow-up at 3-6 months and/or 12-24 months per institutional standard of care. All images were reviewed and adjudicated by an independent core lab. RESULTS: Of the 169 lesions initially entered into the study, 4 were later determined to be extracranial or nonaneurysmal by the core lab and were excluded, leaving 165 aneurysms in 162 patients treated in 163 procedures. Ninety-one (56.2%) patients were asymptomatic with aneurysms found incidentally. Of the 165 aneurysms, 150 (90.9%) were unruptured. One hundred thirty-four (81.2%) were saccular, 27 (16.4%) were fusiform/dissecting, and the remaining 4 (2.4%) were blister-like. One hundred thirty-seven (83.0%) arose from the anterior circulation.FRED deployment was impossible in 2/163 (1.2%) cases, and in an additional 4 cases (2.5%) the device was misdeployed. Overall mortality and morbidity rates were 4.3% and 7.3%, respectively, with rates of mortality and morbidity potentially related to FRED of up to 2.4% and 6.2%, respectively. Neuroimaging follow-up at 3-6 months showed complete or nearly complete occlusion of the aneurysm in 94% of cases, increasing to 96% at 12-24 months' follow-up. Aneurysmal sac shrinkage was observed in 78% of assessable aneurysms. CONCLUSIONS: This preliminary experience using FRED for endovascular treatment of complex unruptured and ruptured aneurysms showed a high safety and efficacy profile that is comparable to those of other FDDs currently in use.

Aspirin associated with decreased rate of intracranial aneurysm growth.

OBJECTIVE: Aspirin has emerged as a potential agent in the prevention of rupture of intracranial aneurysms (IAs). In this study, the authors' goal was to test if aspirin is protective against aneurysm growth in patients harboring multiple IAs ≤ 5 mm. METHODS: The authors performed a retrospective review of a prospectively maintained database covering the period July 2009 through January 2019. Patients' data were included if the following criteria were met: 1) the patient harbored multiple IAs; 2) designated primary aneurysms were treated by surgical/endovascular means; 3) the remaining aneurysms were observed for growth; and 4) a follow-up period of at least 5 years after the initial treatment was available. Demographics, earlier medical history, the rupture status of designated primary aneurysms, aneurysms' angiographic features, and treatment modalities were gathered. RESULTS: The authors identified 146 patients harboring a total of 375 IAs. At the initial encounter, 146 aneurysms were treated and the remaining 229 aneurysms (2-5 mm) were observed. During the follow-up period, 24 (10.48%) of 229 aneurysms grew. All aneurysms observed to grow later underwent treatment. None of the observed aneurysms ruptured. Multivariate analysis showed that aspirin was significantly associated with a decreased rate of growth (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.05-0.63). Variables associated with an increased rate of growth included hypertension (OR 14.38, 95% CI 3.83-53.94), drug abuse (OR 11.26, 95% CI 1.21-104.65), history of polycystic kidney disease (OR 9.48, 95% CI 1.51-59.35), and subarachnoid hemorrhage at presentation (OR 5.91, 95% CI 1.83-19.09). CONCLUSIONS: In patients with multiple IAs, aspirin significantly decreased the rate of aneurysm growth over time. Additional prospective interventional studies are needed to validate these findings.

De novo giant posterior cerebral artery aneurysm developing 25 years after basilar bifurcation aneurysm treatment using a Drake tourniquet: case report and implications for aneurysm follow-up.

The objective of this paper was to report a rare complication of basilar artery (BA) tourniquet treatment of a giant basilar tip aneurysm, and to discuss possible causes for the formation of a de novo giant posterior cerebral artery (PCA) aneurysm. A 34-year-old woman underwent satisfactory treatment of a ruptured giant basilar bifurcation aneurysm by BA ligation (Drake tourniquet) in 1985. She presented 25 years later with a new aneurysm in the left PCA, successfully treated by coil embolization. To the authors' knowledge, this is the first case of de novo aneurysm formation on a PCA, and the first de novo aneurysm reported as a complication of BA ligation therapy by Drake tourniquet. Long-term follow-up is necessary in patients with treated cerebral aneurysms, particularly those occurring in young patients, those with multiple aneurysms, those with complex posterior circulation aneurysms, and those undergoing flow diversion or flow-altering therapies.

Accuracy of detecting enlargement of aneurysms using different MRI modalities and measurement protocols.

OBJECTIVE: Aneurysm growth is considered predictive of future rupture of intracranial aneurysms. However, how accurately neuroradiologists can reliably detect incremental aneurysm growth using clinical MRI is still unknown. The purpose of this study was to assess the agreement rate of detecting aneurysm enlargement employing generally used MRI modalities. METHODS: Three silicone flow phantom models, each with 8 aneurysms of various sizes at different sites, were used in this study. The aneurysm models were identical except for an incremental increase in the sizes of the 8 aneurysms, which ranged from 0.4 mm to 2 mm. The phantoms were imaged on 1.5-T and 3-T MRI units with both time-of-flight (TOF) and contrast-enhanced MR angiography. Three independent expert neuroradiologists measured the aneurysms in a blinded manner using different measurement approaches. The individual and agreement detection rates of aneurysm enlargement among the 3 experts were calculated. RESULTS: The mean detection rate of any increase in any aneurysmal dimension was 95.7%. The detection rates of the 3 observers (observers A, B, and C) were 98.0%, 96.6%, and 92.7%, respectively (p = 0.22). The detection rates of each MRI modality were 91.3% using 1.5-T TOF, 97.2% using 1.5-T with Gd, 95.8% using 3.0-T TOF, and 97.2% using 3.0-T with Gd (p = 0.31). On the other hand, the mean detection rate for aneurysm enlargement was 54.8%. Specifically, the detection rates of observers A, B, and C were 49.0%, 46.1%, and 66.7%, respectively (p = 0.009). As the incremental enlargement value increased, the detection rate for aneurysm enlargement increased. The use of 1.5-T Gd improved the detection rate for small incremental enlargement (e.g., 0.4­1 mm) of the aneurysm (p = 0.04). The location of the aneurysm also affected the detection rate for aneurysm enlargement (p < 0.0001). CONCLUSIONS: The detection rate and interobserver agreement were very high for aneurysm enlargement of 0.4­2 mm. The detection rate for at least 1 increase in any aneurysm dimension did not depend on the choice of MRI modality or measurement protocol. Use of Gd improved the accuracy of measurement. Aneurysm location may influence the accuracy of detecting enlargement.

Induction of aneurysmogenic high positive wall shear stress gradient by wide angle at cerebral bifurcations, independent of flow rate.

OBJECTIVE: Endothelium adapts to wall shear stress (WSS) and is functionally sensitive to positive (aneurysmogenic) and negative (protective) spatial WSS gradients (WSSG) in regions of accelerating and decelerating flow, respectively. Positive WSSG causes endothelial migration, apoptosis, and aneurysmal extracellular remodeling. Given the association of wide branching angles with aneurysm presence, the authors evaluated the effect of bifurcation geometry on local apical hemodynamics. METHODS: Computational fluid dynamics simulations were performed on parametric bifurcation models with increasing angles having: 1) symmetrical geometry (bifurcation angle 60°-180°), 2) asymmetrical geometry (daughter angles 30°/60° and 30°/90°), and 3) curved parent vessel (bifurcation angles 60°-120°), all at baseline and double flow rate. Time-dependent and time-averaged apical WSS and WSSG were analyzed. Results were validated on patient-derived models. RESULTS: Narrow symmetrical bifurcations are characterized by protective negative apical WSSG, with a switch to aneurysmogenic WSSG occurring at angles ≥ 85°. Asymmetrical bifurcations develop positive WSSG on the more obtuse daughter branch. A curved parent vessel leads to positive apical WSSG on the side corresponding to the outer curve. All simulations revealed wider apical area coverage by higher WSS and positive WSSG magnitudes, with increased bifurcation angle and higher flow rate. Flow rate did not affect the angle threshold of 85°, past which positive WSSG occurs. In curved models, high flow displaced the impingement area away from the apex, in a dynamic fashion and in an angle-dependent manner. CONCLUSIONS: Apical shear forces and spatial gradients are highly dependent on bifurcation and inflow vessel geometry. The development of aneurysmogenic positive WSSG as a function of angular geometry provides a mechanotransductive link for the association of wide bifurcations and aneurysm development. These results suggest therapeutic strategies aimed at altering underlying unfavorable geometry and deciphering the molecular endothelial response to shear gradients in a bid to disrupt the associated aneurysmal degeneration.

Pure arterial malformations.

OBJECTIVE Over the last half century, there have been isolated case reports of purely arterial malformations. In this study, the authors report a consecutive series of patients with pure arterial malformations, emphasizing the clinical and radiological features of these lesions. METHODS Pure arterial malformations were defined as dilated, overlapping, and tortuous arteries with a coil-like appearance and/or a mass of arterial loops without any associated venous component. Demographic characteristics of the patients, cardiovascular risk factors, presentation, radiological characteristics, and follow-up data were collected. Primary outcomes were new neurological symptoms including disability, stroke, and hemorrhage. RESULTS Twelve patients meeting the criteria were identified. Ten patients were female (83.3%) and 2 were male (16.6%). Their mean age at diagnosis was 26.2 ± 11.6 years. The most common imaging indication was headache (7 patients [58.3%]). In 3 cases the pure arterial malformation involved the anterior cerebral arteries (25.0%); in 4 cases the posterior communicating artery/posterior cerebral artery (33.3%); in 2 cases the middle cerebral artery (16.6%); and in 1 case each, the superior cerebellar artery, basilar artery/anterior inferior cerebellar artery, and posterior inferior cerebellar artery. The mean maximum diameter of the malformations was 7.2 ± 5.0 mm (range 3-16 mm). Four lesions had focal aneurysms associated with the pure arterial malformation, and 5 were partially calcified. In no cases was there associated intracranial hemorrhage or infarction. One patient underwent treatment for the pure arterial malformation. All 12 patients had follow-up (mean 29 months, median 19 months), and there were no cases of disability, stroke, or hemorrhage. CONCLUSIONS Pure arterial malformations are rare lesions that are often detected incidentally and probably have a benign natural history. These lesions can affect any of the intracranial arteries and are likely best managed conservatively.

Flow diversion of a recurrent, iatrogenic basilar tip aneurysm in a pediatric patient: case report.

Endoscopic third ventriculostomy (ETV) is a common treatment for noncommunicating hydrocephalus. Although rare, vascular injury and traumatic pseudoaneurysm development during ETV have been reported. The authors present the case of a 13-year-old boy who underwent repeat ETV (rETV) for shunt and ETV failure, and who suffered an intraoperative subarachnoid hemorrhage due to iatrogenic injury to the basilar tip, with subsequent development of a pseudoaneurysm. Despite initial primary coil embolization, the aneurysm recurred and was definitively treated with flow diversion. In this report, the authors review complication rates associated with ETV and rETV as well as the emerging use of flow diversion and its applications in vessel reconstruction within the pediatric population.

Intravenous infusion of mesenchymal stem cells for protection against brainstem infarction in a persistent basilar artery occlusion model in the adult rat.

OBJECTIVE: Morbidity and mortality in patients with posterior circulation stroke remains an issue despite advances in acute stroke therapies. The intravenous infusion of mesenchymal stem cells (MSCs) elicits therapeutic efficacy in experimental supratentorial stroke models. However, since there are few reliable animal models of ischemia in the posterior circulation, the therapeutic approach with intravenous MSC infusion has not been tested. The objective of this study was to test the hypothesis that intravenously infused MSCs provide functional recovery in a newly developed model of brainstem infarction in rats. METHODS: Basilar artery (BA) occlusion (BAO) was established in rats by selectively ligating 4 points of the proximal BA with 10-0 nylon monofilament suture. The intravenous infusion of MSCs was performed 1 day after BAO induction. MRI and histological examinations were performed to assess ischemic lesion volume, while multiple behavioral tests were performed to evaluate functional recovery. RESULTS: The MSC-treated group exhibited a greater reduction in ischemic lesion volume, while behavioral testing indicated that the MSC-infused group had greater improvement than the vehicle group 28 days after the MSC infusion. Accumulated infused MSCs were observed in the ischemic brainstem lesion. CONCLUSIONS: Infused MSCs may provide neuroprotection to facilitate functional outcomes and reduce ischemic lesion volume as evaluated in a newly developed rat model of persistent BAO.

Serum glucose/potassium ratio as a clinical risk factor for aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (SAH) can result in poor outcomes, and biomarkers for predicting poor prognosis have not yet been established. The aim of this study was to clarify the significance of the serum glucose/potassium ratio for predicting the prognosis of aneurysmal SAH. METHODS: The authors retrospectively reviewed the records of 565 patients with aneurysmal SAH between 2006 and 2016. The patient group comprised 208 men and 357 women (mean age 61.5 years, range 10-95 years). A statistical analysis was conducted of the clinical and laboratory risk factors of poor outcome, including the serum glucose/potassium ratio. RESULTS: On estimation of the initial assessment using Hunt and Kosnik (H-K) grading, 233 patients (41.2%) were classified as the severe SAH group (H-K Grade IV or V). There were significant correlations between the severe SAH group and serum glucose/potassium ratio (p < 0.0001). Serum glucose/potassium ratio was elevated in an H-K grade-dependent manner (Spearman's r = 0.5374, p < 0.0001). With the estimation of the Glasgow Outcome Scale (GOS) score at discharge, 355 patients (62.8%) were classified as poor outcome (GOS score 1-3). The serum glucose/potassium ratio was elevated in a GOS score at discharge-dependent manner (Spearman's r = 0.4006, p < 0.0001), and was significantly elevated in the poor outcome group compared with the good outcome group (GOS score 4 or 5; p = 0.0245). There were significant correlations between poor outcome and serum glucose/potassium ratio (p < 0.0001), age (p < 0.0001), brain natriuretic peptide levels (p = 0.011), cerebral infarction due to vasospasm (p < 0.0001), and H-K grade (p < 0.0001). Multivariate logistic regression analyses showed significant correlations between poor outcome and serum glucose/potassium ratio (p = 0.009). CONCLUSIONS: In this study, the serum glucose/potassium ratio of patients with aneurysmal SAH at admission was significantly correlated with H-K grade and GOS score at discharge. Therefore, this ratio was useful for predicting prognosis of aneurysmal SAH, especially in severe cases.