Alterations of gut microbiota contribute to the progression of unruptured intracranial aneurysms.

Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Whether changes in gut microbial composition participate in the development of UIAs remains largely unknown. We perform a case-control metagenome-wide association study in two cohorts of Chinese UIA patients and control individuals and mice that receive fecal transplants from human donors. After fecal transplantation, the UIA microbiota is sufficient to induce UIAs in mice. We identify UIA-associated gut microbial species link to changes in circulating taurine. Specifically, the abundance of Hungatella hathewayi is markedly decreased and positively correlated with the circulating taurine concentration in both humans and mice. Consistently, gavage with H. hathewayi normalizes the taurine levels in serum and protects mice against the formation and rupture of intracranial aneurysms. Taurine supplementation also reverses the progression of intracranial aneurysms. Our findings provide insights into a potential role of H. hathewayi-associated taurine depletion as a key factor in the pathogenesis of UIAs.

Transcallosal, transchoroidal clipping of a hypothalamic collateral vessel aneurysm in Moyamoya disease.

Peripheral collateral vessel aneurysms in Moyamoya disease (MMD) remain difficult to treat due to their deep location, small size, and vascular fragility. We report the case of an aneurysm localized in the hypothalamus, which was rapidly increasing in size with repeated hemorrhage despite revascularization surgery. Aneurysm clipping was performed to prevent further progress and rerupture with favorable outcome. To our best knowledge, this is the first description of a hypothalamic aneurysm in MMD being clipped via a transcallosal, transchoroidal approach through the third ventricle.

Paradoxical undressing associated with subarachnoid hemorrhage in a non-hypothermia case?

Paradoxical undressing is a phenomenon characterizing some fatal hypothermia cases. The victims, despite low environmental temperatures, paradoxically remove their clothes due to a sudden feeling of warmth. In this report, we describe a case of suspected paradoxical undressing in a non-hypothermia case. The victim, a 51-year-old Caucasian man, was found dead wearing only sneakers and socks. All other clothing was found in his car. Postmortem investigations allowed the hypothesis of hypothermia to be ruled out and revealed the presence of a ruptured cerebral aneurysm that caused a subarachnoid hemorrhage, the latter responsible for the death. The absence of any elements suggesting a voluntary undressing or any third party's DNA profile or involvement along with the possibility that the subarachnoid hemorrhage might have determined a hypothalamic injury, somehow rendered conceivable the hypothesis of an inappropriate feeling of warmth due to hemorrhage-induced dysregulation of the hypothalamic temperature-regulating centers.

Healing of saccular aneurysms following platinum coil embolization: lack of improved efficacy with vitamin C supplementation.

BACKGROUND AND PURPOSE: To test the hypothesis that systemic administration of vitamin C, through its action of stimulating collagen synthesis and crosslinking, would decrease the recurrence and improve the occlusion of experimental aneurysms treated with platinum coils. METHODS: Experimental aneurysms were created in female rabbits and were embolized with platinum coils (>30% packing density). The animals were divided into three groups: group 1 (n=6) rabbits served as controls, group 2 (n=5) rabbits were fed with a vitamin C supplemented feed and group 3 (n=8) rabbits were medicated with vitamin C pills. Digital subtraction angiography was used to evaluate stability after embolization. Subjects were euthanized at 12 weeks after coil implantation, and serum vitamin C levels were then measured. Histological samples were examined with a grading system (range 0-12) based on the neck and dome features. Masson Trichrome staining was used to evaluate collagen deposition. Parametric data were analyzed with one way analysis of variance and non-parametric data were examined using a Kruskal-Wallis test. RESULTS: There were no significant differences between groups in mean aneurysm size. Mean serum vitamin C concentration was significantly higher in group 3 and group 2 compared with group 1, while vitamin C levels between group 2 and group 3 were statistically comparable. Coil compaction was noted in one of six subjects in group 1 and in three of eight subjects in group 3. All of the remaining aneurysms in the test and control groups showed stable occlusion. There were no significant differences in histological scores or collagen deposition among groups. CONCLUSIONS: Vitamin C supplementation following platinum coil embolization does not demonstrate improvement of long term occlusion rates of aneurysms.

Magnetic microparticles for endovascular aneurysm treatment: in vitro and in vivo experimental results.

OBJECTIVE: Endovascular treatment of intracranial aneurysms employing endosaccular coiling can be associated with aneurysm perforation, coil herniation or incomplete obliteration fueling the interest to investigate novel endovascular techniques. We aimed to test a novel embolization material in experimental aneurysms in vitro and in vivo whereby intra-arterially administered magnetic microparticles (MMPs) are navigated into the lumen of vascular aneurysms with assistance from an external magnetic field. METHODS: MMPs are core-shell particles suspended in saline that have a shell made of a polymeric material and a core made of magnetite (Fe3O4). They have a diameter of 1.4 µm. During MMP administration via a microcatheter, a magnetic field was applied externally to direct the particles with the use of a solid-state neodymium magnet. Experiments were performed in a perfused silicone vessel and aneurysm model to evaluate application techniques and fluid dynamics and in the elastase aneurysm model in rabbits to evaluate in vivo compatibility, including multiorgan histological examinations and long-term stability of aneurysm embolization. RESULTS: It was possible to steer and hold the MMPs within the aneurismal cavity where they occluded the lumen progressively. After removal of the external magnetic field, the results remained stable in vivo for the remainder of the observational period (30 minutes); after a 12-week observational period, recanalization of the aneurysm occurred. CONCLUSION: MMPs can be magnetically directed into aneurysms, allowing short-term obliteration. Although the method has yet to show reliable long-term stability, these experiments provide proof of concept, encouraging further investigation of intravascular magnetic compounds.

Bilateral paramedian thalamic and mesencephalic infarcts after basilar tip aneurysm coiling: role of the artery of Percheron.

Aneurysm embolization using Guglielmi detachable coils (GDC) is gaining acceptance as a viable alternative for surgery in the treatment of aneurysms. Recent reports describe a significant rate of thromboembolic complications. Thalamic and midbrain blood supply can arise from complex anatomical variations. The rare variation: "artery of Percheron", is a solitary arterial trunk arising from one of the proximal segments of a posterior cerebral artery and supplies the paramedian thalami and rostral midbrain bilaterally. We describe a patient that underwent elective endovascular treatment for a basilar tip aneurysm using GDC and stents in each PCA; 12 hours later patient was comatose and not following commands. Sequential magnetic resonance imaging (MRI) of brain showed bilateral paramedian thalamic and mesencephalic infarcts presumably secondary to artery of Percheron occlusion. Thromboembolic event related to the use of the GDC embolization and stents is a rare clinical sequelae, but catastrophic. The use of antiplatelets agents should be reinforced in the scenario. When bilateral medial thalamic and midbrain infarcts are found, occlusion of the artery of Percheron should be considered. Angiography may not b helpful and lack of visualization of the artery does not exclude its presence. In this case the MRI findings confirmed the presence of the infarction based on the anatomical distribution.

Y-stent-assisted coil embolization for the management of unruptured cerebral aneurysms: report of six cases.

BACKGROUND: The advent of stent-assisted coil embolization has revolutionized the endovascular management of complex intracranial aneurysms. Although performed routinely in most cerebrovascular centers, there are not many case series reported about the Y-stent technique for coil placement in cerebral aneurysms. The authors present the second largest series available within the neurosurgical literature. METHODS: The authors have retrospectively reviewed the medical records and angiographic data of six patients who were diagnosed as having unruptured cerebral aneurysms and subsequently treated using "Y" stent-assisted coil embolization. Five out of six cerebral aneurysms in this study were located at the basilar tip while the remaining one was at the left MCA trifurcation. Aneurysms ranged in size from 8-22 mm. All patients were female with ages ranging from 37-70 years. One patient presented with recurrence of an aneurysm previously managed with a balloon-assisted coil embolization. Another patient presented after a failed trial of a balloon-assisted procedure. One patient had originally been diagnosed with multiple aneurysms of varying size and location. RESULTS: A "Y" configuration was successfully established in all six patients. Five patients have had a symptom-free recovery period at average follow-up period of 36.7 months. The remaining patient is notable for recurrence that was discovered on angiogram 32 months postoperatively. CONCLUSIONS: The proposed Y-stent technique is a safe and effective option that can be employed in the endovascular reconstruction of unruptured intracranial aneurysms of complex location and orientation. These methods serve as an acceptable alternative in the management of aneurysms traditionally managed with microsurgery. Hemodynamic assessment has shown Y-stenting to be an advantageous therapy option, yet further studies are required to assess these parameters in alternative therapies.

Nifedipine inhibits the progression of an experimentally induced cerebral aneurysm in rats with associated down-regulation of NF-kappa B transcriptional activity.

Cerebral aneurysm (CA) causes a life-threatening subarachnoid hemorrhage. However, no effective medical treatment to prevent the growth of CA is available. Nifedipine, a widely used calcium antagonist, was shown to improve endothelial function in various cardiovascular diseases. We examined whether nifedipine has a protective effect on CA progression. CAs were experimentally induced in Sprague-Dawley rats followed by intraperitoneal injection of either 10mg/kg of nifedipine per day or vehicle. The size and media thickness of CAs were measured one month after aneurysm induction. NF-kappa B (NF-kappaB) activity in aneurysmal walls was assessed by immunohistochemistry for activated NF-kappaB p65 subunit and electrophoretic mobility shift assay (EMSA). Expression of monocyte chomoattractant protein-1 (MCP-1) and matrix metalloproteinase (MMP) -2 in aneurysmal walls was examined by RT-PCR and immunohistochemistry. To examine whether nifedipine has a suppressive effect on preexisting CAs, nifedipine administration started at one month after aneurysm induction and pathological changes were assessed at two months after aneurysm induction. Aneurysm size was smaller and the media was thicker in the nifedipine-treated group even though blood pressure was not different between groups. Nifedipine inhibited DNA binding of NF-kappaB in aneurysmal walls. As regards MCP-1 expression and macrophage, which is the main inflammatory cell in the aneurysmal walls, infiltration into aneurysmal walls was decreased by nifedipine. Immunohistochemistry and gelatin zymography showed that the expression and activity of MMP-2 was also reduced by nifedipine. Furthermore, nifedipine significantly prevented the enlargement and degeneration of aneurysmal walls of preexisting CAs. Nifedipine may be useful as a medical drug for patients with CAs.

Dissection of the posterior inferior cerebellar artery in a young adult with cerebellar infarct.

The posterior inferior cerebellar artery (PICA) is frequently involved in dissection of the vertebral artery (VA); however, isolated PICA dissection has rarely been reported. A 37-year-old man experienced acute and progressive drowsiness, vertigo, occipital headache, vomiting, and ataxia. There was no precedent trauma or chiropractic manipulation. Neurologically, he had dysmetria of the left extremities. His NIHSS score was 3. Brain magnetic resonance imaging showed an acute cerebellar infarct in the left PICA territory. Magnetic resonance angiography showed a faint signal adjacent to the junction of the left VA and PICA, suggesting a vascular shadow. Catheter angiography showed focal stenosis with a post-stenotic fusiform aneurysmal dilatation of the left proximal PICA that was highly suggestive of dissection with pseudoaneurysm formation. He was treated with clopidogrel and was free of neurological symptoms 3 months after the stroke event. Isolated PICA dissection may be considered in patients with PICA territory infarct or subarachnoid hemorrhage. Treatment depends on the manifestations; ruptured dissecting aneurysms are often treated with surgery or embolization, and infarcts are usually treated with antithrombotic agents.

Growth factor receptor expression and remodeling of saccular cerebral artery aneurysm walls: implications for biological therapy preventing rupture.

OBJECTIVE: Remodeling of the saccular cerebral artery aneurysm (SCAA) wall, known to be associated with rupture, might be modified with bioactive endovascular implants or systemic drug therapy targeted at growth factor receptors to prevent rupture. The receptors regulating SCAA wall remodeling are, however, unknown. MATERIALS AND METHODS: Immunostaining for 12 growth factor receptors, and markers for matrix synthesis, proliferation, and inflammatory cell infiltration, were analyzed in 21 unruptured and 35 ruptured aneurysm fundi resected after microsurgical clipping of the aneurysm neck. The results were compared with clinical and radiological data. RESULTS: Eleven of the 12 receptors studied were expressed at varying intensities in the 56 SCAA walls. Only transforming growth factor (TGF)beta-R2 and vascular endothelial growth factor (VEGF)-R1 were associated with rupture and basic fibroblast growth factor-R1 with minor leaks (P = 0.018). TGFbeta-R3 and VEGF-R1 was associated with wall remodeling (P = 0.043 and 0.027), and VEGF-R1 was associated with T-cell and macrophage infiltration as well as organization of luminal thrombosis (P = 0.019). VEGF-R2 was associated with myointimal hyperplasia (P = 0.017) and proliferation (P < 0.001). CONCLUSION: VEGF, TGFbeta, and basic fibroblast growth factor receptors were associated with SCAA wall remodeling, making them potential targets for bioactive endovascular implants or drug therapy aiming to reinforce the SCAA wall.

Does gender play a role in functional asymmetry of ventromedial prefrontal cortex?

We found previously in a lesion study that the right-sided sector of the ventromedial prefrontal cortices (VMPCs) was critical for social/emotional functioning and decision-making, whereas the left side appeared to be less important. It so happened that all but one of the subjects in that study were men, and the one woman did not fit the pattern very well. This prompted a follow-up investigation, in which we explored the following question: Does gender play a role in the development of defects in social conduct, emotional functioning and decision-making, following unilateral VMPC damage? We culled from our Patient Registry same-sex pairs of men or women patients who had comparable unilateral VMPC damage in either the left or right hemisphere. Two male pairs and one female pair were formed, and we included two additional women with unilateral right VMPC damage (8 patients in all). The domains of measurement covered social conduct, emotional processing and personality, and decision-making. We found a systematic effect of gender on the pattern of left-right asymmetry in VMPC. In men, there were severe defects following unilateral right VMPC damage, but not following left-sided damage. In women, there were defects following unilateral left VMPC damage; following right-sided damage, however, defects were mild or absent. The findings suggest that men and women may use different strategies to solve similar problems--e.g. men may use a more holistic, gestalt-type strategy, and women may use a more analytic, verbally-mediated strategy. Such differences could reflect asymmetric, gender-related differences in the neurobiology of left and right VMPC sectors.

Arm chorea secondary to an unruptured giant aneurysm.

We describe the case of a 20-year-old male who developed right-arm choreic movements secondary to a giant unruptured aneurysm impinging upon the left thalamus, putamen, globus pallidus, cerebral peduncle, midbrain, and subthalamic nucleus. The aneurysm was treated successfully with coils and a supraclinoid balloon. Abnormal movements initially failed to ameliorate, but within a few months, it was possible to discontinue symptomatic haloperidol therapy, with only mild residual abnormal movements.

Dissection of the internal carotid artery after chiropractic manipulation of the neck.

A 29-year-old woman died from a right hemispheric infarction caused by dissection and subsequent thrombosis of the internal carotid artery after chiropractic manipulations of the neck. Pathologic study of several arteries of muscular and elastic type revealed a mediolytic arteriopathy with widespread mucoid degeneration and cystic transformation of the vessel wall caused by segmental degeneration of smooth muscle cells of the tunica media. We hypothesize that mediolytic arteriopathy was a predisposing factor for the dissection of the internal carotid artery after chiropractic manipulations in our patient.

Consideraciones clínico-quirúrgicas de los aneurismas arteriovenosos cerebrales en el Hospital Regional Honorio Delgado de Arequipa en los años de 1961 a 1994

El presente trabajo se trata de un estudio retrolectivo en pacientes con el diagnóstico de Aneurisma Arteriovenoso Cerebral, también denominados Malformaciones arteriovenosas congénitas cerebrales hospitalizados en el Servicio de Neurocirugía del Hospital Regional Honorio Delgado de Arequipa en los años de 1961 a 1994; se registraron 20 casos, que guarda relación con otros estudios. También en este estudio se realizó con respecto al tema. Se utilizó el método estadístico descriptivo. La edad de aparición de la sintomatología varió desde los 30 años. No se encontró diferencia por sexo. En cuanto a la forma clínica de presentación preponderante se tiene a la cefálea en un 70 por ciento de casos, luego se presentó la hemorragía en un 65 por ciento de casos. En relación al procedimiento diagnóstico de mayor uso se tiene a la arteriografía cerebral, y por medio de ello se evidenció que el vaso arterial de mayor compromiso fue la cerebral anterior y luego la cerebral media, que en conjunto abarcan el 70 por ciento del total de los casos. El tratamiento quirúrgico más empleado lo constituyó la excéresis total, se realizó en seis pacientes, de ellos todos tuvieron una buena evolución, tal es así que al momento del alta mostraron una recuperación total

Delayed cerebral ischaemia: the pathological substrate.

Ischaemic complications both at the level of the cortex and the hypothalamus are well recognised after an aneurysmal subarachnoid haemorrhage. We have studied histological changes in the cortex (53 patients) and hypothalamus (48 patients) in patients who died after an aneurysmal subarachnoid haemorrhage. Cortical ischaemic lesions were demonstrated in 41 of the 53 patients studied. These changes were more common in patients who had impaired control of systemic blood pressure (p = 0.0004) and in patients who died gradually (p = 0.0003). Hypothalamic lesions were found in 24 of 48 patients studied; 23 of these patients had widespread associated changes in the cerebral cortex. Patients with moderate/severe cortical changes tended to have hypothalamic lesions and it was uncommon for patients with no cortical lesions to have changes in the hypothalamus (p = 0.0007). We believe that these histological changes are due to diffuse microangiopathy which develops slowly after a subarachnoid haemorrhage and affects the cortex and hypothalamus. Because the cortical lesions are widespread we postulate that they may be implicated in the aetiology of the well described psychosocial or cognitive problems in patients who survive a subarachnoid haemorrhage.

Branches of the anterior communicating artery. Microsurgical anatomy.

The anterior communicating artery (ACoA) and its branches were examined in 22 human brains after injecting Indian ink or methylmethacrylate. The ACoA branches were divided into the small and the large. Small branches were from 1 to 5 in number (mean 2), and from 70 to 270 microns in diameter (mean 151 microns). Seventy-six percent of the branches originated directly from the ACoA. They tended to arise closer to the left than to the right anterior cerebral artery. Fourteen percent of them arose from the junctional site of the ACoA with the anterior cerebral arteries, and 10% from the site of origin of the subcallosal artery. Large branches were identified as the median artery of the corpus callosum, and the subcallosal artery, respectively. The former vessel was present in 9% of the patients, and the latter in 91%. The subcallosal artery was from 320 to 640 microns in size (mean 486 microns). It tended to arise from the middle of the ACoA. In spite of the very frequent anastomoses involving the ACoA branches, care must be taken to avoid injury to these important vessels during operations of the ACoA aneurysms.

[A case of unruptured A1 aneurysm causing ischemic compression to the medial proximal striate artery].

A 58-year-old female was admitted to our hospital because of weakness of the right lower extremity and dysesthesia of the right upper extremity. From her clinical symptoms the patient was tentatively diagnosed as having a sort of cerebral infarction and treated with administration of urokinase and antiplatelet agents. However, angiographical examination revealed a unruptured aneurysm of the A1 portion of the left anterior cerebral artery. Preoperative angiogram showed that the dome of the aneurysm compressed one of the neighboring perforating artery which arose from adjacent to the neck of the aneurysm. The patient underwent neck clipping of aneurysm successfully. During the operation, the perforator was hardly adhered to the dome of the aneurysm. So, careful dissection was made only around the neck and the perforator was spared. Her symptoms were disappeared immediately after surgery. The perforator was demonstrated with better filling in the postoperative angiogram than that in the preoperative angiogram. The pathomechanisms of cerebral ischemia caused by unruptured aneurysm were reviewed on the literature. Most of the cases were caused by release of fragmental thrombi from a large aneurysm. There was a very exceptional case whose symptoms had seemed to be related to the direct compression of the neighboring perforator by the aneurysm. The compressed perforator in this case was seemed to be corresponded with the medial proximal striate artery stated by Yasargil.