The Gut Ecosystem: A Critical Player in Stroke.

The intestinal microbiome is emerging as a critical factor in health and disease. The microbes, although spatially restricted to the gut, are communicating and modulating the function of distant organs such as the brain. Stroke and other neurological disorders are associated with a disrupted microbiota. In turn, stroke-induced dysbiosis has a major impact on the disease outcome by modulating the immune response. In this review, we present current knowledge on the role of the gut microbiome in stroke, one of the most devastating brain disorders worldwide with very limited therapeutic options, and we discuss novel insights into the gut-immune-brain axis after an ischemic insult. Understanding the nature of the gut bacteria-brain crosstalk may lead to microbiome-based therapeutic approaches that can improve patient recovery.

Management of Large Vessel Occlusion Stroke Related to Infective Endocarditis: Is Mechanical Thrombectomy a Safe Option?

INTRODUCTION: Acute ischemic stroke is the most common neurological complication of infective endocarditis. Intravenous thrombolysis is contraindicated in these patients due to a higher risk of hemorrhagic complications. Whether mechanical thrombectomy has some benefit in these patients remains unanswered although some favorable results can be found in literature. METHODS: We report twelve cases of acute ischemic stroke due to septic emboli treated with mechanical thrombectomy in two comprehensive stroke centers. RESULTS: Median age was 63 years (IQR 58.8-77.5 years). Diagnosis of infective endocarditis was previous to the diagnosis of stroke in three of the patients. There were five cases of prosthetic-valve endocarditis and eight cases of native-valve endocarditis. Two patients were treated with intravenous thrombolysis with an extensive subarachnoid hemorrhage in 24 h follow-up CT in one of them. Another patient suffered an arterial perforation during the endovascular procedure without successful recanalization. 6 of the patients (50%) developed some type of hemorrhagic complications with three cases of symptomatic intracerebral hemorrhage. Early neurological recovery was achieved in 3 (25%) patients. Functional independence at 3 months in patients with successful revascularization was reached in 50% of the cases. CONCLUSIONS: In patients with large vessel acute ischemic stroke related to infective endocarditis, mechanical thrombectomy might be considered with some potential benefit reported. There may be a high risk of hemorrhagic complications, as known for intravenous thrombolysis in this condition, suggesting that this procedure should be carefully evaluated in these patients.

Serum IgG titers to periodontal pathogens predict 3-month outcome in ischemic stroke patients.

Several cohort studies have shown that periodontal disease is associated with an increased risk for stroke. However, it remains unclear whether serum antibody titers for a specific periodontal pathogen are associated with outcome after ischemic stroke, and which kinds of pathogens are associated with ischemic stroke. We examined the relationship between serum IgG titers to periodontal pathogens and outcome in ischemic stroke patients. A total of 445 patients with acute ischemic stroke (194 female [44.0%], mean age 71.9±12.3 years) were registered in this study. Serum IgG titers to 9 periodontal pathogens (Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Prevotella nigrescens, Fusobacterium nucleatum, Treponema denticola, Tannerella forsythensis, Campylobacter rectus, Eikenella corrodens) were evaluated using the enzyme-linked immunosorbent assay (ELISA) method. An unfavorable outcome was defined as a 3 or higher on the modified Rankin Scale. The proportion of patients with unfavorable outcome was 25.4% (113 patients). Based on multivariate logistic regression analysis, numbers of IgG antibodies positive for periodontal pathogens (odds ratio 1.20, 95% CI 1.02-1.41, p = 0.03) were independent predictors of unfavorable outcome in ischemic stroke patients.

Distinct Commensal Bacterial Signature in the Gut Is Associated With Acute and Long-Term Protection From Ischemic Stroke.

Background and Purpose- Commensal gut bacteria have a profound impact on stroke pathophysiology. Here, we investigated whether modification of the microbiota influences acute and long-term outcome in mice subjected to stroke. Methods- C57BL/6 male mice received a cocktail of antibiotics or single antibiotic. After 4 weeks, fecal bacterial density of the 16S rRNA gene was quantitated by qPCR, and phylogenetic classification was obtained by 16S rRNA gene sequencing. Infarct volume and hemispheric volume loss were measured 3 days and 5 weeks after middle cerebral artery occlusion, respectively. Neurological deficits were tested by the Tape Test and the open field test. Results- Mice treated with a cocktail of antibiotics displayed a significant reduction of the infarct volume in the acute phase of stroke. The neuroprotective effect was abolished in mice recolonized with a wild-type microbiota. Single antibiotic treatment with either ampicillin or vancomycin, but not neomycin, was sufficient to reduce the infarct volume and improved motorsensory function 3 days after stroke. This neuroprotective effect was correlated with a specific microbial population rather than the total bacterial density. In particular, random forest analysis trained for the severity of the brain damage revealed that Bacteroidetes S24.7 and the enzymatic pathway for aromatic metabolism discriminate between large versus small infarct size. Additionally, the microbiota signature in the ampicillin-treated mice was associated with a reduced gut inflammation, long-term favorable outcome shown by an amelioration of the stereotypic behavior, and a reduction of brain tissue loss in comparison to control and was predictive of a regulation of short-chain fatty acids and tryptophan pathways. Conclusions- The findings highlight the importance of the intestinal microbiota in short- and long-term outcomes of ischemic stroke and raises the possibility that targeted modification of the microbiome associated with specific microbial enzymatic pathways may provide a preventive strategy in patients at high risk for stroke. Visual Overview- An online visual overview is available for this article.

Central Nervous System Fungal Infection-Related Stroke: A Descriptive Study of Mold and Yeast-Associated Ischemic Stroke.

OBJECTIVE: Central nervous system (CNS) ischemic events caused by fungal infections are rare, and clinical characteristics of these ischemic events are largely unknown. The objective of this manuscript is to highlight characteristics of fungal-related strokes and describe possible mechanistic differences between CNS mold and yeast infection-related strokes. METHODS: We report a single-center retrospective case series of all adult patients who presented with concurrent CNS fungal infection and stroke between 2010 and 2018. Patients believed to have a stroke etiology due to cardioembolic, atheroembolic, or strokes nontemporally associated with a CNS fungal infection and those with incomplete stroke workups were excluded from analysis. RESULTS: Fourteen patients were identified with ischemic stroke and concurrent CNS fungal infection without other known ischemic stroke etiology. Eight patients had a CNS yeast infection, and 6 had a CNS mold infection. All patients presented with recurrent or progressive stroke symptoms. Six patients were immune-compromised. Four patients admitted to intravenous drug use. All yeast infections were identified by cerebrospinal fluid culture or immunologic studies while all but one of the mold infections required identification by tissue biopsy. Leptomeningeal enhancement was only associated with CNS yeast infections, while basal ganglia stroke was only associated with CNS mold infections. CONCLUSION: Ischemic stroke secondary to CNS fungal infections should be considered in patients with recurrent or progressive cryptogenic stroke, regardless of immune status and cerebrospinal fluid profile. CNS yeast and mold infections have slightly different stroke and laboratory characteristics and should have a distinct diagnostic method. Depending on clinical suspicion, a thorough diagnostic approach including spinal fluid analysis and biopsy should be considered.

Protective Effect of Tong-Qiao-Huo-Xue Decoction on Inflammatory Injury Caused by Intestinal Microbial Disorders in Stroke Rats.

Tong-Qiao-Huo-Xue Decoction (TQHXD) is a classic traditional Chinese medicine prescription for treating cerebral ischemia. The purpose of this study was to investigate the effect of TQHXD on intervening inflammatory response of ischemic stroke by regulating intestinal flora and repairing the intestinal barrier. A rat model of cerebral ischemia was established using middle cerebral artery occlusion (MCAO) and behavioral scores were performed. Additionally, the high throughput 16S ribosomal DNA (rDNA) sequence of intestinal bacteria in fecal samples of rat was also carried out. Our results showed that TQHXD could change the main components of intestinal flora in stroke rats, and reduced the excessive increase of Bacteroidetes, and also regulated the abnormal changes of abundance of some flora as well. In addition, the intestinal epithelial barrier was damaged after stroke, allowing bacterial metabolites to enter the blood, while TQHXD had an improved effect on this phenomenon. Meanwhile, pathological changes in the brain tissue and infarct volume were also alleviated by TQHXD. Due to the disorder of the intestinal flora and the destruction of the barrier, the peripheral immune imbalance caused an inflammatory reaction. TQHXD improved the imbalance of T cells, and inhibited the inflammatory response. Finally, the therapeutic transplantation of fecal microbiota also improved the outcome of stroke in rats. Our presented results suggest that TQHXD may improve the gut microbiota disorder and its induced inflammatory response after stroke, which could be a new target and mechanism for the treatment of stroke.

Reproductive Senescence and Ischemic Stroke Remodel the Gut Microbiome and Modulate the Effects of Estrogen Treatment in Female Rats.

Our previous work has shown that reproductively senescent (or middle-aged; 10-12-month-old) Sprague-Dawley female rats, that are naturally estrogen-deficient, have worse stroke outcomes as compared to normally estrous-cycling adult (5-6-month-old) females. Paradoxically, estrogen replacement to this middle-aged group exacerbates stroke outcomes, while it is neuroprotective in adult females. Recent studies reveal an important role for the gut microbiome and gut metabolites in cardiovascular health, including stroke outcomes. To determine whether gut dysbiosis underlies stroke severity in reproductive senescent females, and underlies the anomalous effects of estrogen on stroke, we compared the gut microbiota and gut metabolites pre and post stroke in (a) gonadally intact adult and middle-aged females, (b) in ovariectomized and estrogen-treated (OVX+E) adult and OVX+E middle-aged females, and (c) in middle-aged OVX+E females after fecal microbiome transfer. Our data show significant gut dysbiosis in reproductive senescent females at baseline and after stroke as indicated by an elevated ratio of the major phyla, Firmicutes/Bacteroidetes (F:B), reduced alpha diversity, and significant shifts in beta diversity as compared with adult females. Specific bacterial families were also altered as a result of reproductive aging, as well as gut metabolites, including elevated serum endotoxin levels and decreased short-chain fatty acids (SCFAs), with a concomitant increase in IL-17A, indicating that reproductive senescence significantly affects gut communities under pathologic conditions. Despite the differences in gonadally intact adult and middle-aged females, estrogen-treated ovariectomized (OVX+E) females of either age group displayed no differences in the major phyla, but there was increased abundance in specific bacterial taxa, including Prevotella and Lactobacillus. The SCFA butyrate was significantly reduced at baseline in the middle-aged OVX+E females, while circulating endotoxin LPS were elevated in this group after stroke, suggesting that gut metabolites were differently affected by estrogen treatment in the two age groups. A fecal transfer from adult OVX+E females to middle-aged OVX+E females significantly reduced infarct volume, improved behavioral recovery and transiently reduced IL-17A expression. These data provide the first evidence that microbial gut communities and metabolites are altered by reproductive senescence in female rats at baseline and after stroke, and suggest that estrogen may impact stroke recovery differently in adult and reproductive senescent females due to an age-specific effect on gut microbiota and metabolites.

Ischemic stroke alters immune cell niche and chemokine profile in mice independent of spontaneous bacterial infection.

INTRODUCTION: Stroke-associated pneumonia (SAP) is a major cause of mortality in patients who have suffered from severe ischemic stroke. Although multifactorial in nature, stroke-induced immunosuppression plays a key role in the development of SAP. Previous studies using a murine model of transient middle cerebral artery occlusion (tMCAO) have shown that focal ischemic stroke induction results in functional defects of lymphocytes in the spleen, thymus, and peripheral blood, leading to spontaneous bacterial infection in the lungs without inoculation. However, how ischemic stroke alters immune cell niche and the expression of cytokines and chemokines in the lungs has not been fully characterized. METHODS: Ischemic stroke was induced in mice by tMCAO. Immune cell profiles in the brain and the lungs at 24- and 72-hour time points were compared by flow cytometric analysis. Cytokine and chemokine expression in the lungs were determined by multiplex bead arrays. Tissue damage and bacterial burden in the lungs following tMCAO were evaluated. RESULTS: Ischemic stroke increases the percentage of alveolar macrophages, neutrophils, and CD11b+ dendritic cells, but reduces the percentage of CD4+ T cells, CD8+ T cells, B cells, natural killer cells, and eosinophils in the lungs. The alteration of immune cell niche in the lungs coincides with a significant reduction in the levels of multiple chemokines in the lungs, including CCL3, CCL4, CCL5, CCL17, CCL20, CCL22, CXCL5, CXCL9, and CXCL10. Spontaneous bacterial infection and tissue damage following tMCAO, however, were not observed. CONCLUSION: This is the first report to demonstrate a significant reduction of lymphocytes and multiple proinflammatory chemokines in the lungs following ischemic stroke in mice. These findings suggest that ischemic stroke directly impacts pulmonary immunity.

Transplantation of fecal microbiota rich in short chain fatty acids and butyric acid treat cerebral ischemic stroke by regulating gut microbiota.

The gut microbiota and its short chain fatty acid (SCFA) metabolites have been established to play an important protective role against neurodegenerative diseases. Our previous study demonstrated that cerebral ischemic stroke triggers dysfunctional gut microbiota and increased intestinal permeability. In this study, we aimed to clarify the mechanism by which gut microbiota and SCFAs can treat cerebral ischemic stroke in rat middle cerebral artery occlusion models and use the information to develop new therapies. Our results show that oral administration of non-absorbable antibiotics reduced neurological impairment and the cerebral infarct volume, relieved cerebral edemas, and decreased blood lipid levels by altering the gut microbiota. We also found that ischemic stroke decreased intestinal levels of SCFAs. And that transplanting fecal microbiota rich in these metabolites was an effective means of treating the condition. Compared with other SCFAs, butyric acid showed the highest negative correlation with ischemic stroke. Supplementation with butyric acid treated models of ischemic stroke effectively by remodeling the gut microbiota, enriching the beneficial Lactobacillus, and repairing the leaky gut. In conclusion, interfering with the gut microbiota by transplanting fecal bacteria rich in SCFAs and supplementing with butyric acid were found to be effective treatments for cerebral ischemic stroke.

Change of intestinal microbiota in cerebral ischemic stroke patients.

BACKGROUND: Gut microbiota has been suggested to play a role in stroke patients. Nevertheless, little is known about gut microbiota and the clinical indexes in stroke patients. METHODS: Total of 30 cerebral ischemic stroke (CI) patients and 30 healthy control were enrolled in this study and the fecal gut microbiota was profiled via Illumina sequencing of the 16S rRNA V1-V2. The National Institutes of Health Stroke Scale (NIHSS) were used to quantify stroke severity and modified Rankin scale (mRS) to assess outcome for CI patients. The correlations between the clinical indexes and microbiota were evaluated. RESULTS: Though the microbial α-diversity and structure is similar between CI patients and healthy controls, the gut microbiota of CI patients had more short chain fatty acids producer including Odoribacter, Akkermansia, Ruminococcaceae_UCG_005 and Victivallis. We also found that the special microbes were correlation with serum index, such as norank_O_ _Mollicutes_RF9, Enterobacter, Ruminococcaceae_UCG-002 were negative correlation with LDL (r = - 0.401, P < 0.01), HDL (r = - 0.425, P < 0.01) and blood glucose (r = - 0.439, P < 0.001), while the HDL was significantly positive correlation with the genus Ruminococcus_1 (r = 0.443, P < 0.001). The Christensenellaceae_R-7_group and norank_f_Ruminococcaceae was significantly positive correlation with NIHSS1M (r = 0.514, P < 0.05; r = 0.449, P < 0.05) and mRS (r = 0.471, P < 0.05, r = 0.503, P < 0.01), respectively. On the other hand, the genus Enterobacter was significantly negative correlation with NIHSS1M (r = 0.449, P < 0.05) and mRS (r = 0.503, P < 0.01). CONCLUSIONS: This study suggests that CI patients showed significant dysbiosis of the gut microbiota with enriched short chain fatty acids producer, including Odoribacter, Akkermansia. This dysbiosis was correlation with the outcomes and deserves further study.

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.

Clots retrieved by mechanical thrombectomy from acute ischemic stroke patients show no evidence of bacteria.

BACKGROUND: Bacteria and bacterial components have been associated with the activation of coagulation factors and initiating the blood clot formation. The aim of this study was to investigate whether bacterial populations are present in clots retrieved from patients that have suffered a large vessel occlusion acute ischemic stroke (AIS). MATERIALS AND METHODS: Clot samples were collected from 20 AIS patients who underwent clot retrieval with mechanical thrombectomy. Patient clinical demographic details were noted. Expression of bacterial 16S rDNA was analyzed by standard and real-time polymerase chain reaction (PCR). Gram staining was performed to identify Gram-positive and Gram-negative bacteria. RESULTS: Both the real-time and standard PCR demonstrated no expression of 16S rDNA in any of the 20 clots samples from AIS patients. Gram staining results showed no expression of Gram-positive or Gram-negative bacteria present in the clot samples. CONCLUSION: Our current study found no bacteria populations in the clots of AIS patients.

Puerariae Lobatae Radix with chuanxiong Rhizoma for treatment of cerebral ischemic stroke by remodeling gut microbiota to regulate the brain-gut barriers.

The combination of Puerariae Lobatae Radix (PLR) and Chuanxiong Rhizoma (CXR) is commonly used to treat cerebrovascular diseases. This work aimed to clarify the mechanisms of their action in treating cerebral ischemic stroke from the perspective of gut microecology. The PLR and CXR combination effectively improved the neurological function, reduced the cerebral infarction and relieved the complications of cerebral ischemic stroke, including dyslipidemia, increased blood viscosity and thrombotic risk. Cerebral ischemic stroke triggered gut microbial disturbances by enriching pathogens and opportunistic microorganisms, including Bacteroides, Escherichia_Shigella, Haemophilus, Eubacterium_nodatum_group, Collinsella, Enterococcus, Proteus, Alistipes, Klebsiella, Shuttleworthia and Faecalibacterium. Cerebral ischemic stroke also increased the intestinal permeability, disrupted the gut barrier and caused intestinal microbial translocation. Occludin, claudin-5 and ZO-1 levels in the brain-gut barriers showed a high positive correlation. However, the combination remodeled the gut microecology by modulating endogenous bacteria whose effects may mitigate cerebral damage, such as Alloprevotella, Ruminococcaceae, Oscillospira, Lachnospiraceae_NK4B4_group, Akkermansia and Megasphaera, protected the brain-gut barriers by increasing claudin-5 and ZO-1 levels; and weakened the gut microbiota translocation by decreasing diamine oxidase, lipopolysaccharide and d-lactate. Although nimodipine effectively reduced the cerebral infarction, it did not relieve the gut microbiota dysbiosis and instead aggravated the gut barrier disruption and microbiota translocation. In conclusion, cerebral ischemic stroke caused gut microbiota dysbiosis, increased intestinal permeability, disrupted the gut barrier and triggered gut microbiota translocation. The PLR and CXR combination was an effective treatment for cerebral ischemic stroke that relieved the gut microbiota dysbiosis and brain-gut barriers disruption.

Validación externa de las escalas A2DS2 e ISAN para predecir la infección respiratoria asociada al ictus isquémico / External validation of the A2SD2 and ISAN scales for predicting infectious respiratory complications of ischaemic stroke

Antecedentes y objetivo: La neumonía asociada al ictus es una complicación relacionada con mal pronóstico. Las escalas A2DS2 e ISAN se han desarrollado recientemente por un grupo alemán e inglés, respectivamente, para predecir la neumonía intrahospitalaria tras un ictus agudo. Realizamos una validación externa de estas escalas en una serie consecutiva de pacientes ingresados por ictus isquémico en nuestro centro. Método: El modelo pronóstico se realiza sobre una muestra de 340 sujetos consecutivos ingresados por ictus en 2015. La discriminación se evaluó mediante el cálculo del área bajo la curva de eficacia diagnóstica (curva ROC). La calibración se evaluó mediante la realización del test de bondad de ajuste de Hosmer-Lemeshow y la representación gráfica de la curva. Se realiza un análisis de regresión logística para determinar los predictores independientes de infección respiratoria después del ictus. Resultados: La muestra final evaluada fue de 285 sujetos, entre los cuales 45 pacientes (15,8%) tuvieron infección respiratoria tras el ictus según unos criterios preestablecidos. La edad media de los pacientes fue de 71,01 (DE 12,62) años. De ellos, 177 (62,1%) fueron varones. Setenta y dos pacientes (25,3%) tenían síntomas o signos de disfagia, 42 (14,7%) tenían fibrilación auricular, 14 (4,9%) tenían situación de dependencia previa al ictus y la mediana de la puntuación NIHSS fue de 4 puntos. La puntuación media de la escala A2DS2 fue 3,25 (DE 2,54) y la de ISAN fue 6,49 (DE 3,64). El análisis muestra que por cada punto en la escala A2DS2 se incrementa el riesgo de infección respiratoria (OR = 1,576; IC 95%: 1,363-1,821), al igual que en la escala ISAN (OR = 1,350; IC 95%: 1,214-1,501). Conclusión: La puntuación alta en las escalas A2DS2 e ISAN son un fuerte predictor de infección respiratoria asociada al ictus agudo en una cohorte consecutiva de pacientes con ictus. Estas escalas son simples de usar y realizar, siendo herramientas prometedoras para la predicción de esta complicación en la práctica habitual

Background and purpose: Pneumonia as a complication of stroke is associated with poor outcomes. The A2DS2 and ISAN scales were developed by German and English researchers, respectively, to predict in-hospital stroke-associated pneumonia. We conducted an external validation study of these scales in a series of consecutive patients admitted to our hospital due to ischaemic stroke. Method: These predictive models were applied to a sample of 340 consecutive patients admitted to hospital in 2015 due to stroke. Discrimination was assessed by calculating the area under the ROC curve for diagnostic efficacy. Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test and graphing the corresponding curve. Logistic regression analysis was performed to determine the independent predictors of respiratory infection secondary to stroke. Results: We included 285 patients, of whom 45 (15.8%) had respiratory infection after stroke according to the study criteria. Mean age was 71.01 ± 12.62 years; men accounted for 177 of the patients (62.1%). Seventy-two patients (25.3%) had signs or symptoms of dysphagia, 42 (14.7%) had atrial fibrillation, and 14 (4.9%) were functionally dependent before stroke; the median NIHSS score was 4 points. Mean scores on A2DS2 and ISAN were 3.25±2.54 and 6.49 ± 3.64, respectively. Our analysis showed that higher A2DS2 scores were associated with an increased risk of infection (OR = 1.576; 95% CI: 1.363-1.821); the same was true for ISAN scores (OR = 1.350; 95% CI: 1.214-1.501). Conclusion: High scores on A2DS2 and ISAN were found to be a strong predictor of respiratory infection associated with acute stroke in a cohort of consecutive patients with stroke. These easy-to-use scales are promising tools for predicting this complication in routine clinical practice

A Puzzling Case of Cryptogenic Stroke.

BACKGROUND: Stroke is a common neurological complication of infective endocarditis (IE) and it is associated with increased morbidity and mortality but infective endocarditis in acute stroke setting is hard to discover. MATERIAL AND METHODS: A 75-year-old man referred to hospital for the onset of left hemiparesis and dysarthria. His past medical history included hypertension. He had 3 months history of fatigue, fever, and weight loss. Neurological examination revealed left hemiparesis and dysarthria. FINDINGS: Brain CT and CT angiography revealed a right M1 segment occlusion. Thrombolysis was delivered followed by mechanical thrombectomy by clot aspiration and recanalization was achieved. Anatomopathological analysis of the clot showed necrotic material and bacterial colonies consistent with septic emboli. The day after he developed fever and brain CT revealed a right parieto-occipital intraparenchymal and subarachnoid hemorrhage. Blood cultures demonstrated growth of Enterococcus faecalis. Treatment with vancomycin and ampicillin was started. CONCLUSION: Management of acute ischemic stroke related to IE is difficult. The great clinical challenge for the physician is recognizing the signs suggestive of IE in the acute stroke setting. Anatomo-pathological and bacteriological analysis of the clot in patients eligible to mechanical thrombectomy can provide the remarkable advantage to analyse directly the extracted material, allowing an early diagnosis and appropriate antibiotic therapies and treatments.

External validation of the A2SD2 and ISAN scales for predicting infectious respiratory complications of ischaemic stroke. / Validación externa de las escalas A2DS2 e ISAN para predecir la infección respiratoria asociada al ictus isquémico.

BACKGROUND AND PURPOSE: Pneumonia as a complication of stroke is associated with poor outcomes. The A2DS2 and ISAN scales were developed by German and English researchers, respectively, to predict in-hospital stroke-associated pneumonia. We conducted an external validation study of these scales in a series of consecutive patients admitted to our hospital due to ischaemic stroke. METHOD: These predictive models were applied to a sample of 340 consecutive patients admitted to hospital in 2015 due to stroke. Discrimination was assessed by calculating the area under the ROC curve for diagnostic efficacy. Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test and graphing the corresponding curve. Logistic regression analysis was performed to determine the independent predictors of respiratory infection secondary to stroke. RESULTS: We included 285 patients, of whom 45 (15.8%) had respiratory infection after stroke according to the study criteria. Mean age was 71.01±12.62 years; men accounted for 177 of the patients (62.1%). Seventy-two patients (25.3%) had signs or symptoms of dysphagia, 42 (14.7%) had atrial fibrillation, and 14 (4.9%) were functionally dependent before stroke; the median NIHSS score was 4 points. Mean scores on A2DS2 and ISAN were 3.25±2.54 and 6.49±3.64, respectively. Our analysis showed that higher A2DS2 scores were associated with an increased risk of infection (OR=1.576; 95% CI: 1.363-1.821); the same was true for ISAN scores (OR=1.350; 95% CI: 1.214-1.501). CONCLUSION: High scores on A2DS2 and ISAN were found to be a strong predictor of respiratory infection associated with acute stroke in a cohort of consecutive patients with stroke. These easy-to-use scales are promising tools for predicting this complication in routine clinical practice.

Risk of Myocardial Infarction and Ischemic Stroke after Dental Treatments.

The association between invasive dental treatments (IDTs) and a short-term risk of myocardial infarction (MI) and ischemic stroke (IS) remains controversial. Bacterial dissemination from the oral cavity and systemic inflammation linked to IDT can induce a state of acute vascular dysfunction. The aim of study is to investigate the relation of IDTs to MI and IS by using case-only study designs to analyze data from a large Taiwanese cohort. A nationwide population-based study was undertaken by using the case-crossover and self-controlled case series design to analyze the Taiwanese National Health Care Claim database. Conditional logistic regression model and conditional Poisson regression model were used to estimate the risks of MI/IS. In addition, we used burn patients as negative controls to explore the potential effect of residual confounding. In total, 123,819 MI patients and 327,179 IS patients in the case-crossover design and 117,655 MI patients and 298,757 IS patients were included in the self-controlled case series design. Results from both study designs showed that the risk of MI within the first 24 wk after IDT was not significantly different from or close to unity except for a modest risk during the first week for patients without other comorbidities (odds ratios [95% confidence intervals] of 1.31 [1.08-1.58] and 1.15 [1.01-1.31] for 3 d and 7 d, respectively). We also observed no association between IDTs and IS, or the risk ratio was close to unity. IDTs did not appear to be associated with a transient risk of MI and IS in the Taiwanese population, with consistent findings from both case-only study designs. However, we cannot exclude that dental infections and diseases may yield a long-term risk of MI and IS.

Bidirectional gut-brain-microbiota axis as a potential link between inflammatory bowel disease and ischemic stroke.

Emerging evidence suggests that gut-brain-microbiota axis (GBMAx) may play a pivotal role linking gastrointestinal and neuronal disease. In this review, we summarize the latest advances in studies of GBMAx in inflammatory bowel disease (IBD) and ischemic stroke. A more thorough understanding of the GBMAx could advance our knowledge about the pathophysiology of IBD and ischemic stroke and help to identify novel therapeutic targets via modulation of the GBMAx.