Microbial Heterogeneity Identification of Cerebral Thrombi Via Metagenomic Next-Generation Sequencing-Based Strategy.

BACKGROUND: Diagnosis of the cause of cerebral thrombi is vital for recurrence prevention but also challenging. The presence of the microbiome has recently been confirmed in thrombus, suggesting a novel approach to distinguish cerebral thrombi of different origins. However, little is known about whether there is heterogeneity in microbiological colonization of cerebral thrombi of different sources. METHODS AND RESULTS: Forty patients experiencing acute ischemic stroke were included and clinical data were collected. Metagenomic next-generation sequencing was adopted to detect bacterial and genomic signatures of human cerebral thrombi samples. We found similar species diversity between the large-artery atherosclerosis thrombi and cardioembolic thrombi but different species composition and distribution of cerebral thrombus microbiota. Compared with the group with cardioembolism, the group with large-artery atherosclerosis showed a significantly higher relative abundance of Ralstonia insidiosa among the top 10 bacterial species in cerebral thrombi. Twenty operational taxonomy units were correlated with 11 clinical indicators of ischemic stroke. The Gene Ontology enrichment analysis revealed 9 different enriched biological processes (translation and carbohydrate metabolic process, etc). The enriched Kyoto Encyclopedia of Genes and Genomes pathways included ribosome, butanoate metabolism, and sulfur metabolism. CONCLUSIONS: This study, based on the approach of metagenomic next-generation sequencing, provides a diagnostic microbiological method to discriminate individuals with cardioembolic thrombi from those with large-artery atherosclerosis thrombi with human cerebral thrombi samples. Our findings provide a fresh perspective on microbial heterogeneity of cerebral thrombi and demonstrate biological processes and pathway features of cerebral thrombi.

Anticoagulant Treatment for Pediatric Infection-Related Cerebral Venous Thrombosis.

BACKGROUND: We aimed to describe the clinical presentation, risk of bleeding and recurrent thrombosis, and perioperative anticoagulant management of children with cerebral venous thrombosis (CVT) and an associated head or neck infection. METHODS: In this subgroup analysis of the EINSTEIN-Jr study, we included children with CVT and an associated head or neck infection who received therapeutic anticoagulants with either low-molecular-weight heparin (with or without subsequent vitamin K antagonists) or rivaroxaban for a period of 3 months. Analyses are descriptive. RESULTS: Of 74 included children, 59 (80%) had otomastoiditis, 21 (28%) a central nervous system infection, 18 (24%) sinusitis, and 9 (12%) another upper respiratory tract infection; 29 (39%) had infection of multiple regions of the head or neck. All 74 children received antibiotics and therapeutic anticoagulants; 41 (55%) underwent surgery, of whom 34 were diagnosed with CVT preoperatively. Anticoagulation was started before surgery in 12 children and interrupted 0-1 days prior to surgery. Anticoagulation was (re)started in all 34 children at a median of 1 day (interquartile range: 0-1) postoperatively, in therapeutic doses in 94%. Overall, one child (1%, 95% confidence interval: 0-7) had recurrent thrombosis, and one (1%, 95% confidence interval: 0-7) had major bleeding; neither was associated with surgery. At 3 months, no children had died, 3 (4%) had persistent focal neurologic deficits, and 2 (3%) had impaired vision. CONCLUSIONS: Children with CVT and an associated head or neck infection administered therapeutic anticoagulants generally had low risks of bleeding and thrombotic complications, including those who had surgical interventions with delay or interruption of anticoagulation.

Sphenoid sinusitis complicated by extensive septic thrombosis after coiling of a ruptured intracranial aneurism.

We report here the case of a 40-year-old man who presented with sphenoid sinusitis complicated by jugular and cerebral venous thrombosis and intracranial infection 6 weeks after coiling of an anterior choroidal artery aneurysm. The pathogeny of this unusual and severe complication is discussed.

Child with tuberculous meningitis and COVID-19 coinfection complicated by extensive cerebral sinus venous thrombosis.

We herein report a case of a child with tuberculous meningitis and COVID-19 coinfection complicated by hydrocephalus, arterial ischaemic stroke and extensive cerebral sinus venous thrombosis. Both conditions induce a proinflammatory cytokine drive resulting, among others, in a prothrombotic state. The disruption of the coagulation system in this case was supported by elevated D-dimers, fibrinogen and ferritin levels, consistent with thrombotic complications reported in some adult patients infected with COVID-19. The child also exhibited prolonged viral shedding that suggests severe disease.

Oral Bacterial Signatures in Cerebral Thrombi of Patients With Acute Ischemic Stroke Treated With Thrombectomy.

Background Chronic infections have been reported to be risk factors for both coronary heart disease and ischemic stroke. DNA of oral bacteria, mainly from the viridans streptococci group, has been detected in coronary thrombus aspirates of myocardial infarction and cerebral aneurysms. Viridans streptococci are known to cause infective endocarditis and possess thrombogenic properties. We studied the presence of oral bacterial DNA in thrombus aspirates of patients with acute ischemic stroke treated with mechanical thrombectomy. Methods and Results Thrombus aspirates and arterial blood were taken from 75 patients (69% men; mean age, 67 years) with acute ischemic stroke. The presence of Streptococcus species, mainly the Streptococcus mitis group, belonging to viridans streptococci as well as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans in samples were determined using a quantitative polymerase chain reaction with specific primers and probes. The relative amount of bacterial DNA in a sample was determined with the comparative threshold cycle method. Bacterial DNA was detected in 84% (n=63) of aspired thrombi, and 16% (n=12) of samples were considered bacterial DNA negative. DNA of Streptococcus species, mainly the S mitis group, was found in 79% (n=59) of samples. The median relative amount of Streptococcus species DNA was 5.10-fold higher compared with the control blood samples from the same patients. All thrombi were negative for both P gingivalis and A actinomycetemcomitans. Conclusions This is the first study showing the common presence of bacterial DNA from viridans streptococci in aspired thrombi of patients with acute ischemic stroke. Streptococcal bacteria, mostly of oral origin, may contribute to the progression and thrombotic events of cerebrovascular diseases.

Cerebral venous thrombosis: comparing characteristics of infective and non-infective aetiologies: a 12-year retrospective study.

BACKGROUND: Most cases of cerebral venous thrombosis (CVT) have non-infective causes. Infective CVT, though less common, often results in a catastrophic outcome. The distinctive clinical characteristics of infection-associated CVT (IACVT) and non-infection-associated CVT (NIACVT) would facilitate early detection and proper management. OBJECTIVE: To compare the characteristics of IACVT and NIACVT. METHODS: All patients with CVT admitted to Songklanagarind Hospital between January 2002 and December 2013 with the ICD10 codes I636, I676, O225 and G08 were identified and recruited. We compared the clinical presentations, neuroimaging results and hospital outcomes for patients with IACVT and those with NIACVT. We analysed the differences using descriptive statistics. Additionally, for patients with IACVT, we described the primary sites of infection, associated CVT, host immune status and microbiological results. RESULTS: Twenty of the 83 patients with CVT (24.1%) had IACVT. Male gender (70.0% vs 34.9%) and pre-existing diabetes mellitus (35.0% vs 4.8%) were significantly more prevalent in the IACVT than the NIACVT group. Additionally, cavernous sinus thrombosis predominated in IACVT (80.0% vs 11.1%), whereas focal neurological syndrome was more common among patients with NIACVT (50.8% vs 15.0%). Paracranial infections, mostly sinusitis and orbital cellulitis, were common primary infections (80.0%) among patients with IACVT. Lastly, fungus was a devastating causative pathogen in IACVT-five of six patients with fungal infection had intracranial complications. CONCLUSIONS: Cavernous sinus thrombosis is a distinctive clinical presentation of IACVT, whereas focal neurological syndrome is a hallmark feature of NIACVT. Paracranial fungal infections are highly virulent and frequently associated with intracranial complications.

Intracranial and internal jugular vein thrombosis secondary to ENT infections: a report of 3 cases.

We report 3 cases of rare, life-threatening intracranial and internal jugular vein (IJV) thrombosis that were caused by common ENT infections. These infections included otitis media in a 6-year-old girl, tonsillitis in a 21-year-old woman, and odontogenic sepsis in a 56-year-old woman. All 3 patients were treated with culture-directed systemic antibiotics; 2 of them also required surgical drainage (the child and the older adult). The 2 adults also received therapeutic anticoagulation, which was continued until venous recanalization was documented; the duration of combined antibiotic and anticoagulation treatment was 6 weeks. All 3 patients made uneventful recoveries. Significant morbidities associated with intracranial and IJV thrombosis were avoided as a result of prompt diagnosis and judicious treatment.

Role of imaging in the diagnosis of acute bacterial meningitis and its complications.

Acute bacterial meningitis is a common neurological emergency and a leading cause of death and neurological disability worldwide. Diagnosis is based on clinical and microbiological findings with neuroimaging in the form of CT reserved for those with specific adverse clinical features or when an underlying cause such as mastoiditis is suspected. MRI is extremely useful for detecting and monitoring the complications of meningitis. These can be remembered by the mnemonic HACTIVE (hydrocephalus, abscess, cerebritis/cranial nerve lesion, thrombosis, infarct, ventriculitis/vasculopathy and extra-axial collection). Diffusion weighted imaging (DWI) and magnetic resonance spectroscopy (MRS) are useful to distinguish abscess from other ring enhancing lesions.

Fungal infections of the nervous system: current perspective and controversies in management.

In the last two decades, more elaborative use of intensive care units for serious medical disorders, advancements in transplant procedures and concomitant use of immunosuppressive therapies as well as the pandemic spread of HIV, etc. have increased the incidence of systemic fungal infections, especially life threatening central nervous system (CNS) infections. The CNS fungal infections present with various clinical syndromes: meningitis; encephalitis; hydrocephalus/raised intracranial pressure (raised ICP); space occupying lesions; orbito-rhino-cerebral syndromes; acute cerebro-vascular events and spinal infections. However, the common presentations among these ones are basal meningitis, hydrocephalus, space occupying lesions (cerebral abscesses and granulomas) and stroke syndromes. Clinical picture may mimic tubercular meningitis and therefore, needs careful evaluation. The CNS mycoses carry higher risks of morbidities and mortality as compared to other infective processes and therefore promptly require precise diagnosis and appropriate medical and/or surgical management strategies to optimize the outcome. Among the antifungal drugs, the Amphotericin B had remained first line of therapy for many decades in invasive fungal infections but is not effective in many forms of mycoses. Fortunately, many useful antifungal drugs were introduced during the last two decades. Initially, the lipid based formulations of the Amphotericin B, then the new triazoles and most recently, echinocandins. These medications are used more frequently in combinations. Now evidence based data are gathering together in favor of their usefulness in the management of invasive fungal infections. But still, many questions are unanswered and controversies persist relating to their selection and use.

Delayed cerebral thrombosis after initial good recovery from pneumococcal meningitis.

OBJECTIVE: To report an unusual clinical course in 6 patients with community-acquired acute bacterial meningitis and to compare clinical features with cases reported in the literature. METHODS: Case series from Dutch hospitals from 2003 to 2008. RESULTS: Five out of six patients were male, age ranged from 30 to 73 years (mean age, 47 years). All patients had pneumococcal meningitis, received adjunctive dexamethasone treatment on admission, and made a good or excellent initial recovery. After 7 to 19 days, patients suddenly deteriorated, developing headache, fever, a decreased level of consciousness, brainstem signs, or hemiparesis. Imaging studies showed infarctions involving the thalamus or brainstem in all patients. Repeated lumbar puncture showed a pleocytosis, but CSF cultures were sterile. Five patients were treated with high-dose steroids on deterioration. Outcome was poor: 4 patients died and 2 remained disabled. Autopsies, performed in 2 patients, showed infarctions predominantly involving the posterior circulation territory, thrombosis in penetrating arteries, but no evidence of vasculitis. We identified 5 meningitis cases with delayed vasculopathy in the literature, but these patients did not exactly resemble the clinical course of our patients. CONCLUSIONS: Delayed cerebral thrombosis may occur in patients with excellent recovery from pneumococcal meningitis. All patients were treated initially with adjunctive dexamethasone therapy, suggesting a dexamethasone-associated effect. Pathology suggests an immunologic reaction targeting cerebral blood vessels.

Two cases of fatal meningitis due to Fusobacterium necrophorum.

It is extremely important to consider Fusobacterium necrophorum as a cause of meningitis in children after otitis or other upper respiratory tract infections, because of its increasing incidence. A high index of suspicion and prompt microbiological identification are mandatory; as this organism is often penicillin-resistant, prolonged antibiotic therapy is required and invasive infection carries a high risk of fatal cerebral vessel thrombosis. This report presents two fatal cases who presented to our pediatric intensive care unit in December 2004.

Infection related cerebral venous thrombosis.

The incidence of cerebral venous thrombosis (CVT) has dropped dramatically in recent years. In the past, before the introduction of antibiotics, infection was the main cause of CVT. But this is no longer true. Recently, the occurance of septic CVT is rare, which leads to an increased chance of misdiagnosis and treatment delay. Early suspicion and recognition is very crucial to improve mortality and morbidity rates of this potentially fatal disease. Intravenous, wide spectrum, antibiotics and early surgical drainage of the primary site of infection whenever possible are essential. Anticoagulation with intravenous heparin infusion and corticosteroids use are of uncertain benefit, although some reports have shown some favorable response.

Tuberculosis: an uncommon cause of cerebral venous thrombosis?

Several infectious etiologies are related to cerebral venous thrombosis (CVT), but a review of literature showed only few cases related to tuberculosis (TB), and only one with neurological manifestations. We report an unusual case of CVT related to TB and mutation in prothrombin gene. A 38-man black presented abrupt right hemiparestesis, and hemiparesis. Investigations revealed CVT. Cerebral spinal fluid (CSF) examination evidenced an infection by Mycobacterium. He was heterozygous for G20210A prothrombin mutation. Probably, hypercoagulability mechanisms of TB, added to mutation of prothrombin gene increase the risk of CVT.

[Imaging of rhinocerebral mucormycosis]. / L'imagerie dans la mucormycose rhinocérébrale.

PURPOSE: Rhinocerebal mucormycosis is a rare life threatening fungal infection observed in immunocompromised patients. We report six cases of patients with rhinocerebral mucormycosis confirmed histologically. Our study confirms the necessity of early diagnosis when clinical and CT findings are suggestive. MATERIALS AND METHODS: This is a retrospective study including 6 diabetic patients (3 women and 3 men) aged from 28 and 63 years. Five patients had ethmoiditis evolving for a few days (3 to 5 days), and one patient was in an ketoacidotic coma and had a severe infectious syndrome with purulent rhinorrhea evolving for 4 days. All of our patients underwent computed tomography (CT) scan of the paranasal sinuses. MRI was performed in two patients with neurological findings. RESULTS: Unilateral ethmoido-maxillary sinusitis was noted in 5 cases. Only one case of pansinusitis was found. All patients presented orbital involvement. Cerebral involvement was noted in 4 cases (cerebral venous thrombosis: 2 cases; abscess: 2 cases; cerebral ischemia: 2 cases). The diagnosis of mucormycosis was based on endonasal biopsy. When available, MRI allowed a more precise evaluation of the orbital and cerebral extension. CONCLUSION: Mucormycosis is an opportunist mycosis due to mucoralis fungus. It is very invasive with a highly aggressive potential in diabetic or immunocompromised patients. Imaging study particularly CT scan, plays an important role in diagnosis especially to evaluate cerebral extension.

Tuberculosis: an uncommon cause of cerebral venous thrombosis?

Several infectious etiologies are related to cerebral venous thrombosis (CVT), but a review of literature showed only few cases related to tuberculosis (TB), and only one with neurological manifestations.We report an unusual case of CVT related to TB and mutation in prothrombin gene. A 38-man black presented abrupt right hemiparestesis, and hemiparesis. Investigations revealed CVT. Cerebral spinal fluid (CSF) examination evidenced an infection by Mycobacterium. He was heterozygous for G20210A prothrombin mutation. Probably, hypercoagulability mechanisms of TB, added to mutation of prothrombin gene increase the risk of CVT.

As mais variadas etiologias infecciosas estão relacionadas a trombose venosa cerebral (TVC), mas revisando-se a literatura há apenas poucos relatos de casos que se devem à tuberculose (TB), sendo que em apenas um deles havia manifestações no sistema nervoso central.Relatamos um caso de TVC associado a TB e a mutação do gene da protrombina. Homem 38 anos, negro, apresentou hemiparestesia de instalação súbita à direita, evoluindo com hemiparesia homolateral. Durante a internação, foi coletado líquor que evidenciou infecção por micobactéria. A pesquisa de trombofilias mostrou positividade somente para mutação do gene da protrombina(G20210A). Provavelmente os mecanismos de hipercoagulabilidade intrínsecos à tuberculose somados à mutação do gene da protrombina, potencializam o risco de TVC.

Cerebral venous thrombosis and Escherichia coli infection in neonates.

AIM: To present a possible association between cerebral venous thrombosis (CVT) and infection with Escherichia coli. METHODS: Four neonates with deep CVT occurring during an E. coli infection are presented. RESULTS: In these patients the thrombotic disease was found by Doppler ultrasonography. The thrombosis involved at least the sagittal sinus and the transverse sinus according to subsequent MRI scans. The E. coli strains did not produce verotoxin or haemolysin. Disseminated intravascular coagulation was not demonstrated. Three patients presented with seizures. At discharge, all of the patients had signs of neurological damage, but two of them have improved significantly since then. None of the patients has had recurrent (venous) thrombosis. CONCLUSION: E. coli infections in neonates may predispose to CVT, a finding that has clinical implications.

Pathology of listerial encephalitis in chickens in Japan.

Neural signs (torticollis, drowsiness) and mortality were observed in five chickens of a native chicken flock (reared for meat) that included 450 male birds on a farm that had 2300 native chickens and 1120 layers. Histologic lesions were observed in the medulla oblongata, optic lobe, cerebellum, and spinal cord of the affected birds. The lesions, which were most severe in the medulla oblongata, were massive abscesses with rarefaction (demyelination and malacia) of the parenchyma with gram-positive bacteria. The degenerative and necrotic areas were characterized by fibrin thrombosis, hemorrhages, and congestion in the blood vessels. Immunohistochemically, the bacteria positive for L. monocytogenes antigen were observed in the medulla oblongata, cerebellum, and spinal cord. Ultrastructurally, the small rod-shaped and thin-cell-walled bacteria were observed in the parenchyma of the medulla oblongata. Listeria monocytogenes (serotype 4b) was isolated from the medulla oblongata and spinal cord. The pathogenesis of listerial encephalitis in chickens was discussed.