Roles of Phytoestrogen in the Pathophysiology of Intracranial Aneurysm.

Background and Purpose: The incidences of intracranial aneurysm and aneurysmal subarachnoid hemorrhage are high in postmenopausal women. Although population-based studies suggest that hormone replacement therapy is beneficial for postmenopausal women with intracranial aneurysms, estrogen replacement may no longer be recommended for the prevention of chronic diseases given its association with adverse outcomes, such as cancer and ischemic stroke. The isoflavone daidzein and its intestinal metabolite equol are bioactive phytoestrogens and potent agonists of estrogen receptors. Given their estrogenic properties, we investigated whether the isoflavones daidzein and equol are protective against the formation and rupture of intracranial aneurysms in a mouse model of the postmenopausal state. Methods: We induced intracranial aneurysms in ovariectomized adult female mice using a combination of induced systemic hypertension and a single injection of elastase into the cerebrospinal fluid. We fed the mice with an isoflavone-free diet with/without daidzein supplementation, or in a combination of intraperitoneal equol, or oral vancomycin treatment. We also used estrogen receptor beta knockout mice. Results: Both dietary daidzein and supplementation with its metabolite, equol, were protective against aneurysm formation in ovariectomized mice. The protective effects of daidzein and equol required estrogen receptor-ß. The disruption of the intestinal microbial conversion of daidzein to equol abolished daidzein's protective effect against aneurysm formation. Mice treated with equol had lower inflammatory cytokines in the cerebral arteries, suggesting that phytoestrogens modulate inflammatory processes important to intracranial aneurysm pathogenesis. Conclusions: Our study establishes that both dietary daidzein and its metabolite, equol, protect against aneurysm formation in ovariectomized female mice through the activation of estrogen receptor-ß and subsequent suppression of inflammation. Dietary daidzein's protective effect required the intestinal conversion to equol. Our results indicate the potential therapeutic value of dietary daidzein and its metabolite, equol, for the prevention of the formation of intracranial aneurysms and related subarachnoid hemorrhage.

Neutrophil Extracellular Traps Promote the Development of Intracranial Aneurysm Rupture.

[Figure: see text].

Potential Influences of Gut Microbiota on the Formation of Intracranial Aneurysm.

Gut microbiota modulates metabolic and immunoregulatory axes and contributes to the pathophysiology of diseases with inflammatory components, such as atherosclerosis, diabetes mellitus, and ischemic stroke. Inflammation is emerging as a critical player in the pathophysiology of an intracranial aneurysm. Therefore, we hypothesized that the gut microbiota affects aneurysm formation by modulating inflammation. We induced intracranial aneurysms in mice by combining systemic hypertension and a single injection of elastase into the cerebrospinal fluid. Depletion of the gut microbiota was achieved via an oral antibiotic cocktail of vancomycin, metronidazole, ampicillin, and neomycin. Antibiotics were given 3 weeks before aneurysm induction and either continued until the end of the experiment or stopped 1 day before aneurysm induction. We also assessed the effects of the gut microbiota depletion on macrophage infiltration and mRNA levels of inflammatory cytokines. Gut microbiota depletion by antibiotics reduced the incidence when antibiotics were started 3 weeks before aneurysm induction and continued until the end of the experiment (83% versus 6%, P<0.001). Even when antibiotics were stopped 1 day before aneurysm induction, the gut microbiota depletion significantly reduced the incidence of aneurysms (86% versus 28%, P<0.05). Both macrophage infiltration and mRNA levels of inflammatory cytokines were reduced with gut microbiota depletion. These findings suggest that the gut microbiota contributes to the pathophysiology of aneurysms by modulating inflammation. Human studies are needed to determine the exact contribution of the gut microbiota to the pathophysiology of aneurysm formation and disease course in humans.

Roles of Nicotine in the Development of Intracranial Aneurysm Rupture.

Background and Purpose- Tobacco cigarette smoking is considered to be a strong risk factor for intracranial aneurysmal rupture. Nicotine is a major biologically active constituent of tobacco products. Nicotine's interactions with vascular cell nicotinic acetylcholine receptors containing α7 subunits (α7*-nAChR) are thought to promote local inflammation and sustained angiogenesis. In this study, using a mouse intracranial aneurysm model, we assessed potential contributions of nicotine exposure and activation of α7*-nAChR to the development of aneurysmal rupture. Methods- Intracranial aneurysms were induced by a combination of deoxycorticosterone-salt induced hypertension and a single-dose elastase injection into cerebrospinal fluid in mice. Results- Exposure to nicotine or an α7*-nAChR-selective agonist significantly increased aneurysm rupture rate. Coexposure to an α7*-nAChR antagonist abolished nicotine's deleterious effect. In addition, nicotine's promotion of aneurysm rupture was absent in smooth muscle cell-specific α7*-nAChR subunit knockout mice but not in mice lacking α7*-nAChR on endothelial cells or macrophages. Nicotine treatment increased the mRNA levels of vascular endothelial growth factor, platelet-derived growth factor-B, and inflammatory cytokines. α7*-nAChR antagonist reversed nicotine-induced upregulation of these growth factors and cytokines. Conclusions- Our findings indicate that nicotine exposure promotes aneurysmal rupture through actions on vascular smooth muscle cell α7*-nAChR.

Endoscopic hematoma evacuation for acute and subacute subdural hematoma in elderly patients.

OBJECT: Endoscopic surgery was performed for acute or subacute subdural hematoma (SDH), and its effectiveness and safety in elderly patients were evaluated. METHODS: Between September 2007 and November 2013, endoscopic surgery was performed in 11 elderly patients with acute SDH (8 patients) and subacute SDH (3 patients). The criteria for surgery were as follows: 1) the presence of clinical symptoms; 2) age older than 70 years; 3) no brain injury (intracerebral hematoma, brain contusion); 4) absence of an enlarging SDH; and 5) no high risk of bleeding. Hematoma evacuation was performed with a 4-mm rigid endoscope with a 0° lens and a malleable irrigation suction cannula. RESULTS: Endoscopic surgery was performed under local anesthesia. The mean age of the patients was 82.6 years (range 73-91 years). There were 5 female and 6 male patients. The mean preoperative Glasgow Coma Scale score was 12, and 5 patients had been receiving antithrombotic drug therapy. The mean operation time was 85 minutes. Only 1 patient had rebleeding, and reoperation with the same technique was performed uneventfully in this individual. A total of 7 patients had a good recovery (modified Rankin Scale Score 0-2) at discharge. CONCLUSIONS: Endoscopic hematoma evacuation of acute and subacute SDH is a safe and effective method of clot removal that minimizes operative complications. This technique may be a less invasive method for treating elderly patients with acute and subacute SDHs.

[A mixed germ cell tumor that underwent dramatic size changes].

This report describes a mixed germ cell tumor that underwent dramatic size changes. A 12-year-old boy presented to our hospital with a headache that had persisted for two months. Initial magnetic resonance imaging (MRI) revealed a pineal tumor and hydrocephalus. The patient required external ventricular drainage and underwent two endoscopic biopsies. His evaluation involved a total of nine computed tomography (CT) scans prior to the second biopsy;the tumor size had decreased before the second endoscopic biopsy. The tumor consisted of both a germinoma and a teratoma component. The patient was treated with three courses of carboplatin-etoposide (CBDCA-VP) chemotherapy and whole-ventricle radiotherapy (32.1 Gy). However, during the adjuvant therapy, the tumor size increased, necessitating total tumor resection. We speculate that the tumor's initial size reduction was caused by leakage of the cyst component and exposure to the brain CT irradiation. The tumor's subsequent increase in size was due to the recollection of the cystic components and intracranial growing teratoma syndrome (iGTS). Therefore, frequent brain CTs and angiography should be avoided before definitive pathological diagnosis is achieved. Further, the tumor size should be considered, with surgical resection being performed at the optimal time.

Chronic encapsulated intracerebral hematoma: Three case reports and a literature review.

BACKGROUND: Chronic encapsulated intracerebral hematoma (CEIH) is one type of intracerebral hematoma that sometimes grows progressively while forming a capsule and presenting with neurological deficits. Although many cases of CEIH have been reported, correct preoperative diagnosis is very difficult. Only around 20% of cases are diagnosed preoperatively. CASE DESCRIPTION: We encountered three cases of CEIH in which causes were unidentified and difficult to diagnose. All three cases were treated surgically. In the first case, a 59-year-old male was diagnosed preoperatively with metastatic brain tumor. In the second case, a 62-year-old female was diagnosed preoperatively with glioblastoma. The third case involved a 58-year-old female diagnosed preoperatively with CEIH. CONCLUSION: We should keep in mind that CEIH is a differential diagnosis for intracerebral space-occupying lesions. This report describes these three cases and discusses imaging findings and characteristics of CEIH.

Prediction of cerebral vasospasm using early stage transcranial Doppler.

Transcranial Doppler (TCD) is widely used to monitor vasospasm after subarachnoid hemorrhage (SAH), but its ability to predict the future occurrence of the symptomatic vasospasm (SVS) remains controversial. We investigated the utility of TCD for predicting the future occurrence of SVS after SAH in 45 patients with aneurysmal SAH. TCD was performed on days 1, 3, 5, 7, 10, and 14 after SAH. The mean flow velocity (MFV) of the horizontal portion of the middle cerebral artery (M1) was recorded. SVS occurred in 24.4% of patients (n = 11). MFV of M1 increased progressively in patients with SVS, but did not increase in patients without SVS. The mean MFV values were significantly higher in patients with SVS than in patients without SVS (p = 0.031). The mean MFV value on day 3 was already significantly higher in patients with SVS than in patients without SVS (88.5 cm/sec versus 62.7 cm/sec, respectively) (p = 0.018). The receiver operating characteristic curve of MFV on day 3 showed the threshold of 72.5 cm/sec for predictive value of SVS in the future (sensitivity 71.4%, specificity 68.1%, and accuracy 82.3%). Increased MFV of M1 during the early stage of SAH may predict the future occurrence of SVS. The threshold value of 72.5 cm/sec MFV of M1 on SAH day 3 was one of the best predictor of future SVS. To prevent delayed cerebral ischemia, aggressive treatment for vasospasm is needed for patients with increased MFV in the early stages of SAH.

Microbleeds as a prognostic factor for acute subdural hematoma.

This study investigated the frequency of poor outcome at discharge of acute subdural hematoma (SDH) patients with and without microbleeds. We retrospectively examined the records of 37 patients with acute SDH who were surgically treated with hematoma removal and received magnetic resonance (MR) imaging within 2 weeks of head injury onset. MR images were used to determine the presence or absence of microbleeds and contusional hemorrhage (CH). Patient outcome was categorized as good (moderate disability or good recovery) or poor (severely disability, vegetative state, or dead) according to the Glasgow Outcome Scale at discharge. Microbleeds were found in 23 patients (62%) and CH was found in 26 patients (70%). Fifteen patients (41%) had both microbleeds and CH. Poor outcome at discharge was more common in SDH patients with both microbleeds and CH than in SDH patients with neither microbleeds nor CH (14/15, 93% vs. 14/22, 64%; p = 0.04). Poor outcome at discharge was more common in SDH patients under 60 years of age with microbleeds (6/8, 75%) than patients under 60 years of age without microbleeds (0/4, 0%; p = 0.03). The location of the microbleed was not related to the outcome at discharge. These results suggest that the presence of microbleeds and CH on MR images may indicate poor prognosis in patients with acute SDH.

Ruptured distal accessory anterior cerebral artery aneurysm--case report.

A 48-year-old man presented with an extremely rare aneurysm arising from an accessory anterior cerebral artery (ACA) manifesting as sudden onset of headache lasting for 5 days. Neurological examination on admission revealed no abnormalities. Computed tomography showed subarachnoid hemorrhage of the interhemispheric fissure and intraparenchymal hematoma of the left cingulate gyrus. Magnetic resonance and cerebral angiography revealed a saccular aneurysm of the distal portion of the accessory ACA classified as the bihemispheric type. Neck clipping of the aneurysm was performed via an interhemispheric approach 17 days after symptom onset. The patient made a good postoperative recovery without neurological deficit. Distal accessory ACA aneurysms tend to arise from the first bifurcation and supply parietal branches. The aneurysms tend to occur on the bihemispheric type of distal accessory ACA. Hemodynamic stress may contribute to formation or development of these aneurysms.

Freehand technique for putaminal hemorrhage--technical note.

We designed a new endoscopic surgical procedure for putaminal hemorrhage (freehand technique) and evaluated its effectiveness and safety in patients with putaminal hemorrhage. Computed tomography (CT) data sets from 40 healthy patients were used. The CT data were transformed into three-dimensional images using AZE VirtualPlace(TM) Plus. The nasion and external auditory foramen were the intraoperative reference points. The median point from medial of the globus pallidus to the insula was the target point. The location of the burr hole point was 80-125 mm above and 27.5 mm lateral to the nasion, and the direction was parallel to the midline and a line drawn from the burr hole to the ipsilateral external auditory foramen. This point was used for 15 patients with putaminal hemorrhage. In all cases, only one puncture was required, and there were no complications. The median surgical time was 91.7 minutes, and the median hematoma removal rate was 95.9%. No recurrent bleeding or operative complications occurred. The freehand technique is a simple and safe technique for patients with putaminal hemorrhage. We believe that this technique of endoscopic hematoma evacuation may provide a less-invasive method for treating patients with putaminal hemorrhage.

Extraneural metastasis of high grade glioma without simultaneous central nervous system recurrence: case report.

A 21-year-old man presented with extraneural metastases to the peritoneum, pleura, bone marrow, lymph nodes, and other organs from a pulvinar high grade glioma. He had undergone a shunt operation and three tumor removals during a 6-year period. He also received radiotherapy and adjuvant chemotherapy with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride and interferon-beta. Two and a half years after the last surgery, extraneural metastasis to the peritoneal cavity was discovered. He died 13 months after the occurrence of extraneural metastases and 10 years after the initial diagnosis. Autopsy revealed tumor masses in the peritoneum, pleura, bone marrow, lymph nodes, and other organs, but no recurrent tumor of the primary lesion or metastases to other areas in the central nervous system. Systemic metastases from primary intracranial tumors are rare, but are likely to become more frequent as the prognosis of patients with brain tumors improves and the duration of survival lengthens.

[A case of subdural hematoma associated with dural metastasis of lung cancer].

A 62-year-old male developed headache, restlessness and left hemiparesis three months after being diagnosed with advanced lung cancer. Computed tomography on admission revealed a crescent-shaped, mixed intensity area in the right fronto-parietal subdural region and multiple tumors in the brain parenchyma. Under a diagnosis of chronic subdural hematoma and multiple brain metastases due to lung carcinoma, burr hole irrigation was performed. Adenocarcinoma cells were found in the dura matter and hematoma. Nontraumatic chronic subdural hematoma secondary to dural metastasis is a very rare condition. Only 52 cases of such spontaneous subdural hematoma have been reported. We describe the clinical features and discuss the mechanism referring to the pertinent literature.

Resection of arteriovenous malformation in the middle cerebellar peduncle by a posterior transpetrosal approach: illustration of a case and correlative microsurgical anatomy.

BACKGROUND: Lesions located in the posterolateral brain stem, particularly the middle cerebellar peduncle, have presented surgeons with a challenge associated with significant morbidity. METHODS: We present a case of a 20-year-old woman who had a hematoma in the right middle cerebellar peduncle with a ventricular rupture. Angiography revealed an arteriovenous malformation (AVM) located in the same portion, extending from the lateral surface near the entry zone of the trigeminal nerve to the paraventricular area of the fourth ventricle, which was completely resected through a posterior transpetrosal approach. We also describe the microsurgical anatomy of this region in a cadaveric specimen, presenting the anatomic landscape at the target when approaching through this route. RESULTS: The patient's postoperative course was uneventful and her neurologic deficits progressively but gradually improved. When a lesion exists at or close to the surface of the middle cerebellar peduncle, the best approach, in our estimation, is a transpetrosal approach because the lesion can be approached perpendicularly with a short working distance, various angles for dissection are available, and minimal retraction of the temporal lobe and cerebellum is required. CONCLUSION: An AVM embedded in the middle cerebellar peduncle can be successfully resected using a posterior transpetrosal approach, though we concede this approach is slightly labor-intensive and time-consuming.

[Autopsy findings of meningitis associated with multiple brain infarctions in two adult patients].

Cerebrovascular complications of meningitis have been extensively documented in the literature. It is little known, however, that paroxysmal, devastating, and potentially fatal complications can occur when the early signs of infection are subtle and missed. We describe the clinical course and neuropathological findings of the occurrence of brain infarctions during two atypical clinical courses of meningitis. In one patient, it was due to Serratia marcescens detected only by an autopsy specimen, and in the other, it was due to Aspergillus detected by a surgical biopsy. Death followed multiple, extensive, and progressively multiplicative infarctions in the basal ganglia, brainstem, and cerebral cortices. Autopsies revealed that the infarctions were caused by severe inflammatory change in the vascular walls, mainly of the arteries of the skull base, including the basilar and carotid arteries. Thrombus formation was also recognized in the lumen of several arteries. A number of characteristic Aspergillus hyphae were recognized in the arterial wall of one patient. Meningitis, which may be associated with severe vasculitis and lead to cerebral infarction, should be considered in the differential diagnosis of these conditions. Early diagnosis and initiation of vigorous therapy should be stressed for therapeutic success.