Cerebral venous ischemia can result in severe brain edema. Inhibition of vascular endothelial growth factor (VEGF) activity by a neutralizing antibody can completely block the hypoxia-induced increase in vascular permeability. VEGF, which induces angiogenesis, also acts as a vascular permeability (VP) factor. We previously showed that inhibition of VEGF attenuates VP and reduces cerebral venous infarction (CVI) in the acute stage. The present study investigated the therapeutic time window during which inhibition of VEGF can reduce CVI in a rat two-vein occlusion (2-VO) model. A 2-VO model was created by photochemically occluding two adjacent cortical veins. Male Wistar rats (n = 42) were assigned to one of four groups: Group 1 was treated with a VEGF antagonist at 24 hours after 2-VO (n = 11); Group 2 was treated with phosphate-buffered solution (PBS) at 24 hours after 2-VO (n = 11); Group 3 was treated with a VEGF antagonist at 48 hours after 2-VO (n = 10); and Group 4 was treated with PBS at 48 hours after 2-VO (n = 10). The developing ischemic infarct was evaluated histologically at 7 days after 2-VO. CVI areas were significantly smaller in Group 1 than in Groups 2, 3, and 4 (p <0.05) but were similar when comparing Groups 3 and 4. Anti-VEGF therapy was effective in reducing CVI in rats if started within 24 hours after 2-VO.
Impairment of executive functions (EFs) was investigated in patients with cerebral hypoperfusion after cerebral angiostenosis/occlusion. Several EFs were measured in patients with cerebral angiostenosis/occlusion and healthy subjects. The vascular conditions, regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), mean transit time (MTT), time to peak (TTP), and delay time were assessed. The scores of the vascular stenosis/occlusion group were significantly lower than those of the control group. rCBV and rCBF were negatively correlated with the error response times in the Stroop test, and the persistent error responses in the Wisconsin Card Sorting Test (WCST) were positively correlated with the Montreal Cognitive Assessment (MoCA) scores. TTP was positively correlated with the reaction and error reaction times, and the persistent error response in WCST was negatively correlated with the times of sorting in WCST and MoCA scores. MTT was positively correlated with the persistent error response in WCST. In the Stroop test, delay time was positively correlated with response time, and negatively correlated with error response times, and the persistent error response in WCST and MoCA scores. Patients with cerebral hypoperfusion after cerebral angiostenosis/occlusion had executive dysfunctions in working memory, sustained attention, response inhibition, cognitive flexibility, thought organization, planning, and implementation. Moreover, their executive dysfunctions were related with the decline in rCBF and rCBV. The prolonged TTP, MTT, and delay time suggested a slow blood flow and the poor compensation of collateral circulation, resulting in impairment of the EFs.
Five patients aged 55 to 73 years (mean 63 years) underwent one-stage clipping for unruptured aneurysms in the bilateral middle cerebral arteries (mean size 4.5 mm, range 2 to 7 mm) via the bilateral pterional keyhole approach in our institute. Important points are as follows: the head is affixed with no rotation; one side manipulation is started 5 minutes after the other side to avoid conflict of surgical instruments; a 5-cm curvilinear skin incision is made inside the hairline and pterional keyhole craniotomy is made bilaterally using 2 burr holes; the whole operating table is rotated 15 degrees to one side to facilitate the microsurgical trans-sylvian approach and aneurysm clipping; the operating table is rotated to the other side for the contralateral procedure; and particular care is taken to avoid bilateral brain injury. This approach provided minimum but sufficient working space required for trans-sylvian dissection. Aneurysm neck clipping was safely performed in a mean operation time of 5 hours 17 minutes. No complications occurred and satisfactory cosmetic results were obtained in all patients. Postoperative neuroimaging studies exhibited bilateral complete clipping with minimal intracranial air content and minimum consequences of brain retraction. One-stage clipping via the pterional keyhole approach is a safe and effective therapeutic option for small bilateral aneurysms.
Giant intracranial aneurysms on the anterior communicating artery (AComA) or anterior cerebral artery (ACA) are rare and treatment is very difficult. The outcome of direct surgical treatment of giant intracranial aneurysms on the AComA or ACA using vascular reconstruction techniques was assessed in five patients treated between 2006 and 2009. In all five patients, cerebral revascularization of ACA territory was performed to ensure blood flow in the distal ACA prior to treating the aneurysm. Trapping was performed in two patients, trapping and partial removal of the aneurysm in two patients, and total removal of the aneurysm with reanastomosis of ACA in one patient. Minor ischemic complication due to perforator ischemia was recognized in one patient and frontal lobe contusion in one patient. All patients were able to achieve functionally favorable outcome (modified Rankin scale 0 or 1). Insurance cerebral revascularization of the ACA territory enabled appropriate direct surgical strategies for giant AComA or ACA aneurysms tailored to each individual case, including trapping with or without removal of the aneurysm, and reanastomosis of the ACA with removal of the aneurysm.
Subarachnoid hemorrhage (SAH) is rare in young adults and little is known about aneurysms in this subgroup. The effect of clinical and prognostic factors on the outcome based on the Glasgow Outcome Scale (GOS) scores and the predictors of unfavorable outcomes were analyzed in young adults with aneurysmal SAH. A retrospective review of the clinical parameters, including age, sex, hypertension, smoking status, hyperlipidemia, location of the cerebral aneurysm, size of the aneurysm, multiplicity, perioperative complication such as hydrocephalus, vasospasm, and hematoma, and Hunt and Hess and Fisher grading on presentation, was conducted in 108 young adults (mean age 34.8 years) managed at our institute. The outcome was classified based on GOS grading into unfavorable (GOS scores 1-3) or favorable (GOS scores 4 or 5). The overall mortality rate was 3.7% (4/108 patients). Univariate regression analysis for the outcomes at discharge found that age at the time of presentation, male sex, size of aneurysm, multiple aneurysms, hyperlipidemia, and poor Hunt and Hess and Fischer grades were associated with unfavorable outcome. Multivariate regression analysis found independent effects of sex, multiple aneurysms, size of aneurysm, and Hunt and Hess grade on the outcome at discharge. Size of aneurysm, presence of multiple aneurysms, Hunt and Hess grade, and hypertension were the predictors of outcome at mean 2-year follow up based on multivariate exact regression analysis. The multimodal approach with aggressive medical management, early intervention, and surgical treatment might contribute to favorable long-term outcomes in patients with poor expected outcomes.
The clinical effects of two different types of antiplatelet drugs, cilostazol and thienopyridine drugs, were compared in patients treated by carotid artery stenting (CAS). Two hundred patients scheduled for CAS were randomized to either cilostazol or a thienopyridine drug (ticlopidine or clopidogrel). The study was conducted in open-label design. Aspirin was also given to all patients. All episodes of periprocedural hemodynamic instability (bradycardia, hypotension) were recorded together with all instances of stroke, cardiac morbidity, and death within 30 days of the procedure. Angiographic follow-up studies were conducted about 6 months after CAS. Finally, 197 patients were enrolled in this study; 97 were treated with cilostazol (cilostazol group) and 100 with a thienopyridine drug (thienopyridine group). In the 30-day follow-up period, the incidence of stroke, cardiac adverse effects, and death was not significantly different between the 2 groups (cilostazol group 7.2%, thienopyridine group 11.0%; p = 0.85). The incidence of intra- and postprocedural bradycardia was significantly lower in the cilostazol group (cilostazol group 18.6% and 2.1%, thienopyridine group 40.0% and 18.0%, respectively; p < 0.01). Although the incidence of intraprocedural hypotension did not significantly differ between the 2 groups, postprocedural hypotension was significantly lower in the cilostazol group (16.5% vs. 34.0%, p < 0.01). In-stent restenosis on follow-up angiograms was lower in the cilostazol group but not significantly (0% vs. 4.4%, p = 0.12). This small open-label study shows that cilostazol may reduce periprocedural bradycardia and hypotension compared with thienopyridine drugs in patients treated by CAS.
Stent-assisted coil embolization has enabled the endovascular treatment of wide-necked cerebral aneurysms. Moreover, recent reports demonstrated that stent-assisted coil embolization was associated with a significant decrease in angiographic recurrences of coiled cerebral aneurysms. One of the possible explanations for this adjunctive effect of stent-assisted coil embolization is changes in the local hemodynamics caused by placing intracranial stents. This study investigated the hemodynamic effect of intracranial stents using computational fluid dynamics (CFD) analysis. The geometry of the intracranial stent, EnterpriseTM VRD, was acquired by using micro computed tomography and virtually placed across the aneurysm orifice of a saccular aneurysm model (saccular model) and a blister-like aneurysm model (blister-like model) constructed from patient-specific three-dimensional (3D) rotational angiography data. Transient CFD analysis was performed with these models with and without stents. Stent placement induced no significant changes in the 3D streamline in the saccular model and slight changes in the blister-like model. Both saccular and blister-like models with stents had lower wall shear stress (WSS) and flow velocity, and higher oscillatory shear index, WSS gradient, and relative residence time than the equivalent models without stents, indicating the possibility that stent placement induced stagnant and disturbed blood flow. Cross-sectional vector velocity around the stent strut revealed complex blood flow patterns with variable direction and velocity. Although this study was a simulation under limited conditions, similar hemodynamic changes might be induced in the neck remnants treated with stent-assisted coil embolization.
Symptomatic common carotid artery (CCA) occlusion is relatively rare, and requires an elaborate vascular reconstruction procedure with which many neurosurgeons are unfamiliar. We describe a case of CCA occlusion managed by vertebral artery (VA)-internal carotid artery (ICA) saphenous vein interposition graft. An 80-year-old man presented with deterioration of consciousness, transient aphasia, and severe right hemiparesis. Angiography revealed proximal occlusion of the left CCA with concomitant patent ICA. Cerebral blood flow measurement using iodine-123 N-isopropyl-p-iodoamphetamine and single photon emission computed tomography showed corresponding hemodynamic insufficiency of the left hemisphere. The patient underwent a novel revascularization procedure, in which the saphenous vein was used as an interposition graft between the V3 segment of the VA and the left proximal ICA. Postoperative course was uneventful, and patency of the bypass graft was confirmed. VA-ICA bypass with interposition graft is an alternative treatment option for symptomatic proximal CCA occlusion.
Stent-assisted coil embolization has been recently accepted as a treatment option for wide-neck or complex cerebral aneurysms. Delayed in-stent occlusion is described due to stent-related changes in vascular geometry. A 66-year-old man underwent stent-assisted coil embolization for an unruptured aneurysm of the vertebral artery. The treatment was successfully performed using the Enterprise stent. Follow-up angiography at 6 months showed asymptomatic in-stent occlusion. Three-dimensional analysis of the vascular geometry revealed that the left vertebral artery was straightened by 40° due to the stent placement. Such straightening of the vessel presumably caused kinking and occlusion of the vessel. Stent-related changes in vascular geometry may cause kinking of a vessel and result in occlusion after the treatment of cerebral aneurysms. Pre-treatment strategy may avoid this risk.
A 33-year-old woman presented with a ruptured, partially thrombosed carotid bifurcation aneurysm after partial coiling, which was successfully treated by “tasuki” (a cloth sash crossing from one shoulder to the opposite hip, worn by relay marathon runners) clipping combined with radial artery and external carotid artery-to-middle cerebral artery bypass. “Tasuki” clipping can overcome the dilemma between achieving early complete thrombosis in the blind sac and maintaining anterograde flow of the parent artery to prevent inadvertent occlusion of the perforators and anterior choroidal artery.
A 48-year-old Japanese woman with Behçet's disease suffered successive rupture of thoracic aortic and cerebral aneurysms within one year. The patient underwent successful surgical treatment for both aneurysms. Histological examination of the aneurysm walls revealed lymphocyte infiltration into the adventitia with smooth muscle cell hyperplasia in the thickened intima. This is an extremely unusual presentation of Behçet's disease associated with both cerebral and aortic aneurysms.
A 37-year-old male with a 20-year history of systemic lupus erythematosus (SLE) was referred to our hospital for an unruptured right middle cerebral artery (MCA) aneurysm. Right cerebral angiography detected a saccular aneurysm (9.6 × 7.1 mm) arising from the bifurcation of the right MCA, and a dilatation of the inferior trunk M2 in which three small branches were involved. The MCA aneurysm was treated with neck clipping. The aneurysmal dilatation of the inferior trunk M2 was treated with proximal clipping, followed by double superficial temporal artery-MCA anastomosis. The patient was discharged from our hospital without complications. This is an extremely unusual case of surgical flow reduction treatment using bypass surgery for a complicated cerebral aneurysm in a patient with SLE.
A 76-year-old man presented with subarachnoid hemorrhage. Selective angiography revealed a dural arteriovenous fistula (DAVF) at the right anterior clinoid process, draining into the superficial middle cerebral vein in a retrograde fashion. Two internal carotid artery aneurysms were also demonstrated at the origin of the posterior communicating artery and the anterior choroidal artery on the same side. The patient underwent craniotomy, and all lesions were treated simultaneously. Rupture of the anterior choroidal artery aneurysm was confirmed. DAVF draining directly into the superficial middle cerebral vein is extremely rare. The precise location of the shunt, the anatomical features, and venous drainage must be evaluated to consider treatment.