Oral bacterial genic expression detection in aneurysm wall of a French population sample - preliminary monocentric study.

INTRODUCTION: The etiology of brain aneurysms remains poorly understood. Finnish research suggests that oral bacteria might contribute to the development and rupture of brain aneurysms. Previous studies by our team have not confirmed these findings, likely due to methodological differences. We aimed to replicate the Finnish study with a French population, using the same primers and comparing the results to internal controls. METHODS: We used RT-qPCR to retrospectively analyze the expression of oral bacterial genes in eight patients. During surgical procedures, four tissue types were consistently sampled from each patient: the aneurysmal wall, the superficial temporal artery (STA), the middle meningeal artery (MMA), and the dura mater (DM). Results were expressed as fold differences employing the 2-∆∆Ct method, and statistical analyses were performed accordingly. RESULTS: Our cohort included eight patients, evenly split into ruptured and unruptured groups. The sex distribution was balanced (4 females, 4 males). We observed DNA expression from oral bacteria in all sampled tissues; however, there were no significant differences between the ruptured and unruptured groups. CONCLUSION: We detected oral bacterial gene expression in the aneurysmal wall, STA, MMA, and DM in a sample of French patients. Although limited by the small sample size, our results suggest a potential role for bacterial involvement in vascular invasiveness related to bacteremia. These findings do not definitively link oral bacteria to the pathogenesis of aneurysm development and rupture.

Dysbiosis of Gut Microbiome Is Associated With Rupture of Cerebral Aneurysms.

BACKGROUND AND PURPOSE: Environmental factors are important with respect to the rupture of cerebral aneurysms. However, the relationship between the gut microbiome, an environmental factor, and aneurysm rupture is unclear. Therefore, we compared the gut microbiome in patients with unruptured intracranial aneurysms (UIAs) and ruptured aneurysms (RAs) to identify the specific bacteria causing the rupture of cerebral aneurysms. METHODS: A multicenter, prospective case-control study was conducted over one year from 2019 to 2020. The fecal samples of patients with stable UIAs and RAs immediately after onset were collected. Their gut microbiomes were analyzed using 16S rRNA sequencing. Subsequently, a phylogenetic tree was constructed, and polymerase chain reaction was performed to identify the specific species. RESULTS: A total of 28 RAs and 33 UIAs were included in this study. There was no difference in patient characteristics between RAs and UIAs: age, sex, hypertension, dyslipidemia, diabetes status, body mass index, and smoking. No difference was observed in alpha diversity; however, beta diversity was significantly different in the unweighted UniFrac distances. At the phylum level, the relative abundance of Campylobacter in the RA group was larger than that in the UIA group. Furthermore, the gut microbiome in the RA and UIA groups exhibited significantly different taxonomies. However, Campylobacter was focused on because it is widely known as pathogenic among these bacteria. Then, a phylogenetic tree of operational taxonomic units related to Campylobacter was constructed and 4 species were identified. Polymerase chain reaction for these species identified that the abundance of the genus Campylobacter and Campylobacter ureolyticus was significantly higher in the RA group. CONCLUSIONS: The gut microbiome profile of patients with stable UIAs and RAs were significantly different. The genus Campylobacter and Campylobacter ureolyticus may be associated with the rupture of cerebral aneurysms.

Utility of Susceptibility-Weighted Angiography Sequence in the Diagnosis of Ruptured Infectious Aneurysms.

In a patient with infective endocarditis (IE), susceptibility-weighted angiography (SWAN) sequence revealed 2 intracranial infectious aneurysms (IIAs) as bright signal lesion, related to the high-velocity arterial flow within the IIAs. In addition, SWAN revealed a convexal subarachnoid hemorrhage-related to distal IIA rupture-as a dark signal. The risk of IIA rupture emphasizes the need for serial imaging follow-up in patients with IE receiving antibiotic therapy after endovascular treatment and after valve surgery. Considering its specific risks, particularly in patients with IE who may be on anticoagulation, digital subtraction angiography is not used routinely in this context. Therefore, SWAN might be an alternative method for selecting patients with IE who need conventional angiography and might be useful for serial follow-up and monitoring after treatment. Future studies should investigate the role of SWAN for the detection of IIAs.

Role of oral pathogens in the pathogenesis of intracranial aneurysm: review of existing evidence and potential mechanisms.

Degeneration of intracranial aneurysm wall is under active research and recent studies indicate an increased risk of rupture of intracranial aneurysm among patients with periodontal diseases. In addition, oral bacterial DNA has been identified from wall samples of ruptured and unruptured aneurysms. These novel findings led us to evaluate if oral diseases could predispose to pathological changes seen on intracranial aneurysm walls eventually leading to subarachnoid hemorrhage. The aim of this review is to consider mechanisms on the relationship between periodontitis and aneurysm rupture, focusing on recent evidence.

[Therapeutic and endovascular management of cerebral mycotic aneurysms]. / Traitement interventionnel des anévrismes mycotiques cérébraux.

Infective endocardites are associated with both ischemic and hemorrhagic neurological complications and also with cerebral abscesses and the development of "mycotic" aneurysms, which are detected in about 5 % of patients in the acute and sub-acute phase of the infection. Data about their natural history and their hemorrhagic risk are scarce and fragmented. The therapeutic management is represented by the medical treatment of the infection with interventional abstention, the surgical treatment and the endovascular approach by selective embolization of the aneurysm. No evidence is provided concerning the superiority of a specific approach. Mycotic aneurysms remain a diagnostic and therapeutic challenge and their management is necessarily based on a multidiscplinary approach.

An unusual ischaemic presentation of thrombosed intracranial mycotic aneurysm with subsequent subarachnoid haemorrhage.

We present an unusual case of acute ischaemic stroke secondary to thrombosed mycotic aneurysm with subsequent early aneurysmal rupture and subarachnoid haemorrhage, successfully treated with endovascular coil embolisation of the thrombosed segment. Imaging correlates are presented demonstrating successful endovascular management despite vessel occlusion precluding angiographic visualisation of the aneurysmal segment. Imaging and clinical follow-up is provided demonstrating durable occlusion and excellent clinical outcome with full functional recovery.

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.

The "connecting vessel" sign: an imaging biomarker to differentiate ruptured infected (mycotic) intracranial aneurysm mimicking the CTA spot sign.

PURPOSE: Infected (mycotic) intracranial aneurysms (IIA) are a prevalent source of morbidity in patients with systemic infection. Unlike saccular aneurysms, ruptured IIA frequently presents with intracerebral hemorrhage (ICH), and the appearance of ruptured IIA on CTA overlaps with the CTA "Spot Sign" (SS), an imaging finding in non-infectious, spontaneous ICH. The purpose of this study was to investigate the imaging and clinical features which may differentiate these two entities on CTA for which treatment strategies differ substantially. METHODS: In an IRB-approved, retrospective case series, we compared 14 patients with confirmed IIA and 14 patients with positive SS due to other non-infectious etiology (SS(+) ICH). Clinical history, laboratory studies, and CTA reports and images were reviewed to define imaging characteristics of IIA and SS(+) ICH, including the diagnostic criteria for SS used in clinical trials. RESULTS: A total of 7/14 patients (50.0%) diagnosed with IIA had ICH at presentation. Of these, 3/7 patients (42.9%) with ruptured IIA and ICH met diagnostic imaging criteria of SS. The remaining 4/7 patients did not meet criteria due to presence of a connecting vessel. Compared with SS(+) ICH of non-infectious etiology, patients with ruptured IIA were younger (40.7 vs. 66.4 years) and had higher rates of IVDU and bacteremia (p < 0.01) and lower rates of hypertension (p < 0.01). Hematoma volume was similar in both groups, but lobar location was more frequent in ruptured IIA (p = 0.06). Mortality at 1 year from diagnosis was equally high in both groups (42.9%). CONCLUSION: This study characterizes ruptured IIA as an imaging mimic of SS and provides a framework for differentiating these lesions, allowing prompt diagnosis and appropriate treatment.

Flow-Diverter Stenting of Intracavernous Internal Carotid Artery Mycotic Aneurysm.

This is the first reported case in which a mycotic aneurysm refractory to the first medical treatment was treated with a Pipeline embolization device (PED), and the first case of a mycotic aneurysm from Brucella treated by endovascular therapy. A 35-year-old man presented with left eye pain and ptosis, and fever for 2 weeks. Before symptom onset, he visited Vietnam where he developed a flu-like illness; however, antibiotics were ineffective. We suspected Brucella as the most likely infectious etiology for the patient's intracavernous aneurysm. Since the aneurysm did not reduce in size following 2 weeks of antibiotic therapy, we placed a PED in the left internal carotid artery. Follow-up angiogram 4 months later showed no residual aneurysm, and cranial nerve palsies had completely resolved. From the results of this case, it appears that flow diverter stenting may be a safe and effective treatment of mycotic aneurysms of the cavernous segment of ICA.

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.

Mycotic intracranial aneurysms rupture presenting as pure acute subdural hematoma in infectious endocarditis. Report of 2 cases and review of the literature.

Acute subdural hematoma (ASDH) revealing mycotic aneurysm (MA) is an exceptional occurrence. We report 2 cases of MA-related pure ASDH in the course of infective endocarditis (IE) without history of head trauma, hypertension or coagulopathy. Case 1: A 54-year-old man presented with a 10-day history of headache, fever. At admission neurologic examination and Brain-CT were normal. Blood cultures showed Streptococcus bovis. MRI 5 days later revealed ischemic spots and minime ASDH over the right convexity. Cerebral angiography, revealed a 3 mm saccular aneurysm at the bifurcation of a distal branch of the right posterior cerebral artery (PCA). Case 2: A 42-year-old man presented with a 8-day history of fever, and worsening headache. Mitral regurgitation was evidenced. A methicillin-sensitive staphylococcus aureus left-sided IE was diagnosed. Pre- and post-contrast Brain-CT were normal. He presented 15 days later a secondarily generalized status epilepticus. Brain CT showed an ASDH over the convexity with falco-tentorial extension, midline shift and temporal herniation. It was removed in emergency. Cerebral angiography revealed a MA of a peripheral branch of the left PCA. The 2 patients were successfully treated by endovascular glue embolization and recovered without complications. Even rare, ruptured MA should be considered as a cause of pure ASDH of unknown origin. As MA can be missed on CT- and MR-Angiography because of mass effect, cerebral angiography may be mandatory.

Cerebral mycotic aneurysms secondary to Streptococcus Agalactiae induced infective endocarditis.

Subarachnoid and intraparenchymal haemorrhages due to cerebral mycotic aneurysms are rare and associated with high mortality. Streptococcus agalactiae, is a rare cause of endocarditis and there are no reported cases of cerebral mycotic aneurysms secondary to this organism. We report a rare case of streptococcus agalctiae induced intracranial mycotic aneurysm.

Vessel wall MRI revealing inflammation on brain aneurysm associated to chronic mucocutaneous candidiasis.

Some authors have reported the association between CMC and brain aneurysms. In this paper it is reported a fusiform brain aneurysm associated to CMC and the vessel wall MRI findings.

Intracranial vessel occlusion preceding the development of mycotic aneurysms in patients with endocarditis.

Mycotic aneurysms (MA) are an uncommon complication of infectious endocarditis. Septic emboli are thought to be the precipitating event in their development, but the evidence for this is sparse. We present three cases in which septic embolic occlusion preceded MA development at the occlusion site, suggesting that documented angiographic emboli in patients with infectious endocarditis and bacteremia constitute a risk factor for MA formation. Two adult patients with a history of intravenous drug use and one child with congenital heart disease are described. They were all diagnosed with infectious endocarditis and developed neurological symptoms during their hospital course. Initial catheter-based cerebral angiograms demonstrated vascular occlusions, which were followed by the development of MA at the same sites within 1 month. Septic emboli, documented on cerebral angiogram, in patients with infectious endocarditis may precede the appearance of MA. Patients with angiographic occlusions in the setting of endocarditis warrant close follow-up.

Systematic Review of Endovascular, Surgical, and Conservative Options for Infectious Intracranial Aneurysms and Cardiac Considerations.

INTRODUCTION: With rising rates of intravenous drug use, Infectious Intracranial aneurysms (IIAs) are a relevant topic for investigation. We performed a systematic review to better understand current practice patterns and limits of current published literature. METHOD: 131 publications with a total of 499 patients (665 aneurysms) were included. Of the 499 patients, 83 were single case reports, and 20.5% of the total had multiple aneurysms. 35.8% of all aneurysms were ruptured. Of those reporting treatment, options included conservative antibiotic therapy (30.0%), open surgical intervention (31.1%), and endovascular occlusion (31.8%). Chronologically, publication of IIAs has increased. Usage of endovascular therapies has grown, while conservative and surgical management have declined in the literature. Overall, 56.2% of aneurysms for which conservative therapy was initiated eventually either underwent intervention or death of patient occurred. RESULTS: The issue of cardiac valve surgery in relationship to aneurysm therapy was discussed in 20.8% (80 patients) of all 384 infectious endocarditis patients; of which 15.0% (12) underwent valve surgery before aneurysm treatment and 85.0 patients (68)% underwent valve surgery after aneurysm treatment. For 51 of the patients where valve surgery followed aneurysm management, the corresponding aneurysm treatment modality could be determined; 58.8% (30) of whom were managed endovascularly. 32.7% (26) of all cases reporting cardiac surgery details underwent cardiac surgery during their admission with the IIA. CONCLUSIONS: Overall, increasing trend of endovascular management of IIAs is evident, and a strong temporal preference exhibited by providers to perform cardiac surgery subsequently to IIA management.

Ruptured Intracranial Mycotic Aneurysm in Infective Endocarditis With Left Ventricular Assist Device and Implantable Cardiac Defibrillator Device: A Clinical Course.

We report the first case of a ruptured intracranial aneurysm-related Staphylococcus epidermidis bacteremia in a patient supported by a continuous flow left ventricular assist device (LVAD). Mycotic aneurysms (MAs) are aneurysmal degeneration of the arterial wall as a result of infection. Current recommendations for management of intracranial mycotic aneurysms are based on a few retrospective case studies. There are only a few cases of intracranial MA reported in patients with LVAD infections caused by Pseudomonas aeruginosa and Klebsiella rhinos. Here, we describe the first case of a ruptured intracranial aneurysm caused by a less virulent organism (Staphylococcus epidermidis) and conclude that screening for asymptomatic MA should be strongly considered in patients with persistent LVAD- and implantable cardiac defibrillator pacemaker-associated infections.