Astragaloside IV reversed the autophagy and oxidative stress induced by the intestinal microbiota of AIS in mice.

Acute ischaemic stroke (AIS) seriously affects patient quality of life. We explored the role of the intestinal microbiota on oxidative stress and autophagy in stroke, and Astragaloside IV (AS-IV) reversed the changes induced by intestinal microbiota. We determined the characteristics of the intestinal microbiota of AIS and transient ischaemic attack (TIA) patients by 16S sequencing and found that the structure and diversity of the intestinal microbiota in patients with AIS and TIA were significantly different from those in healthy subjects. Specifically, the abundance of genus Bifidobacterium, Megamonas, Blautia, Holdemanella, and Clostridium, content of homocysteine and triglyceride was increased significantly, thus it may be as a potential mechanism of AIS and TIA. Furthermore, germ-free mice were infused intracolonically with fecal supernatants of TIA and AIS with/without feed AS-IV for 12 weeks, and we found that the feces of AIS up-regulated the autophagy markers Beclin-1, light chain 3 (LC3)-II and autophagy-related gene (Atg)12, and the expression of reactive oxygen species (ROS) and NADPH oxidase 2/4 (NOX2/4), malondialdehyde (MDA), however, the expression of total antioxidant capacity (T-AOC) and activity of superoxide dismutase (SOD) and glutathione (GSH) was down-regulated in brain tissue, the content of homocysteine and free fatty acids (FFA) in serum of the mice. Meanwhile, AS-IV could reverse the above phenomenon, however, it does not affect the motor function of mice. AS-IV reversed these changes and it may be a potential drug for AIS therapeutics.

Dysbiosis of Gut Microbiota With Reduced Trimethylamine-N-Oxide Level in Patients With Large-Artery Atherosclerotic Stroke or Transient Ischemic Attack.

BACKGROUND: Gut microbiota has been suggested to play a role in almost all major diseases including cardio- and cerebrovascular diseases. A possible mechanism is the transformation of dietary choline and l-carnitine into trimethylamine by gut bacteria. This metabolite is further oxidized into trimethylamine-N-oxide (TMAO) in liver and promotes atherogenesis. Nevertheless, little is known about gut microbial diversity and blood TMAO levels in stroke patients. METHODS AND RESULTS: We performed a case-control study of patients with large-artery atherosclerotic ischemic stroke and transient ischemic attack. TMAO was determined with liquid chromatography tandem mass spectrometry. Gut microbiome was profiled using Illumina sequencing of the 16S rRNA V4 tag. Within the asymptomatic control group, participants with and without carotid atherosclerotic plaques showed similar levels of TMAO without a significant difference in gut microbiota; however, the gut microbiome of stroke and transient ischemic attack patients was clearly different from that of the asymptomatic group. Stroke and transient ischemic attack patients had more opportunistic pathogens, such as Enterobacter, Megasphaera, Oscillibacter, and Desulfovibrio, and fewer commensal or beneficial genera including Bacteroides, Prevotella, and Faecalibacterium. This dysbiosis was correlated with the severity of the disease. The TMAO level in the stroke and transient ischemic attack patients was significantly lower, rather than higher, than that of the asymptomatic group. CONCLUSIONS: Participants with asymptomatic atherosclerosis did not exhibit an obvious change in gut microbiota and blood TMAO levels; however, stroke and transient ischemic attack patients showed significant dysbiosis of the gut microbiota, and their blood TMAO levels were decreased.

Infections with the tick-borne bacterium "Candidatus Neoehrlichia mikurensis" mimic noninfectious conditions in patients with B cell malignancies or autoimmune diseases.

BACKGROUND: Candidatus Neoehrlichia mikurensis is a newly discovered noncultivatable bacterium spread among ticks and rodents in Europe and Asia that can infect humans, particularly immunocompromised patients. METHODS: We compiled clinical and laboratory data from 11 patients with hematological malignances or autoimmune diseases who were diagnosed with Candidatus N. mikurensis infection in Europe 2010-2013. Both published (6) and unpublished cases (5) were included. RESULTS: The patients had a median age of 67, were mostly male (8/11), and resided in Sweden, Switzerland, Germany, and the Czech Republic. All but one had ongoing or recent immune suppressive treatment and a majority were splenectomized (8/11). Less than half of them recalled tick exposure. The most frequent symptoms were fever (11/11), localized pain afflicting muscles and/or joints (8/11), vascular and thromboembolic events (6/11), that is, deep vein thrombosis (4), transitory ischemic attacks (2), pulmonary embolism (1), and arterial aneurysm (1). Typical laboratory findings were elevated C-reactive protein, leukocytosis with neutrophilia, and anemia. Median time from onset of symptoms to correct diagnosis was 2 months. In at least 4 cases, the condition was interpreted to be due to the underlying disease, and immunosuppressive therapy was scheduled. All patients recovered completely when doxycycline was administered. CONCLUSIONS: Candidatus N. mikurensis is an emerging tick-borne pathogen that may give rise to a systemic inflammatory syndrome in persons with hematologic or autoimmune diseases that could be mistaken for recurrence of the underlying disease and/or unrelated arteriosclerotic vascular events. Awareness of this new pathogen is warranted among rheumatologists, hematologists, oncologists, and infectious disease specialists.

Prevalence of positive syphilis serology and meningovascular neurosyphilis in patients admitted with stroke and TIA from a culturally diverse population (2005-09).

The study aims were to determine the prevalence of positive syphilis serology and meningovascular neurosyphilis (NS) in patients admitted with transient ischaemic attack (TIA) and stroke to a tertiary hospital serving a culturally diverse community. A retrospective cohort analysis was conducted using routinely collected administrative data and medical records to identify patients admitted with TIA, stroke and other conditions, with positive syphilis serology, between 2005 and 2009. Direct medical record review confirmed diagnoses of meningovascular NS. Syphilis serology was requested in 27% (893/3270) of all patients with TIA and stroke (2005-09) of whom 4% (38/893) were positive. Thirty-seven patients with positive serology had clinical characteristics consistent with meningovascular NS. Their mean age was 72±13 years; 65% were male and 68% had a recorded place of birth in South-East Asia or the Pacific Islands. One of 12 patients with suspected meningovascular NS with cerebrospinal fluid (CSF) analysis had a positive CSF Venereal Disease Research Laboratory (VDRL) test. Three patients (8%) met diagnostic criteria for "definite or probable" meningovascular NS. All three patients with a "definite or probable" meningovascular NS and 15 (44%) of the remainder who had positive serology without confirmation of NS were treated with intravenous or intramuscular penicillin. Lumbar puncture (LP) and penicillin were underutilised in patients with TIA and stroke with positive serology. In conclusion, syphilis testing should be considered part of the diagnostic work-up of TIA and stroke, particularly in ethnically diverse populations. In patients with TIA and stroke with positive syphilis serology, it would seem appropriate to further pursue diagnosis and treatment and in patients unable to undergo LP, empiric treatment for NS should be considered.

Chlamydia pneumoniae and stroke: is there a direct relationship?

OBJECTIVE: To investigate the possible relationship between atherothrombotic stroke and Chlamydia pneumoniae. METHOD: 150 patients with carotid atherothrombosis were enrolled. The casuistic was divided in three groups: ischemic stroke (IS): 65 patients; transient ischemic attack (TIA): 26 patients; and control: 59. The IS or TIA onset was up to 30 days from the beginning of the study. Carotid atheromatoses was diagnosed by Doppler-ultrasonography. Patients with cardioembolic risk or non-atherothrombotic origin were excluded. Comparisons were done between the three groups, and within each group according to the different age sub-groups, to the main arteries affected, and to the atherogenic risk factors. Bacteria detection was done using polimerase chain reaction. RESULTS: Only one patient tested positive for C. pneumoniae belonging to the control group. CONCLUSION: These results do not suggest that C. pneumoniae participated in the onset of IS or TIA or that it has a role in carotid plaque destabilization.

Chlamydia pneumoniae and stroke: is there a direct relationship? / Chlamydia pneumoniae e acidente vascular cerebral aterotrombótico: existe relação direta?

OBJECTIVE: To investigate the possible relationship between atherothrombotic stroke and Chlamydia pneumoniae. METHOD: 150 patients with carotid atherothrombosis were enrolled. The casuistic was divided in three groups: ischemic stroke (IS): 65 patients; transient ischemic attack (TIA): 26 patients; and control: 59. The IS or TIA onset was up to 30 days from the beginning of the study. Carotid atheromatoses was diagnosed by Doppler-ultrasonography. Patients with cardioembolic risk or non-atherothrombotic origin were excluded. Comparisons were done between the three groups, and within each group according to the different age sub-groups, to the main arteries affected, and to the atherogenic risk factors. Bacteria detection was done using polimerase chain reaction. RESULTS: Only one patient tested positive for C. pneumoniae belonging to the control group. CONCLUSION: These results do not suggest that C. pneumoniae participated in the onset of IS or TIA or that it has a role in carotid plaque destabilization.

OBJETIVO: Investigar a possível relação entre Chlamydia pneumoniae e acidente vascular cerebral aterotrombótico (AVC). MÉTODO: 150 pacientes com aterotrombose carotídea foram estudados. A casuística foi dividida em 3 grupos: AVC: 65 pacientes; ataque isquêmico transitório (AIT): 26 pacientes e controles: 59. O início do AVC ou AIT era até 30 dias da inclusão no estudo. A ateromatose carotídea foi diagnosticada por ultrassonografia com Doppler. Os pacientes com risco cárdio-embólico ou sem evidência de aterotrombose foram excluídos. Foram estabelecidas comparações entre os 3 grupos e dentro de cada grupo, formado sub-grupos de acordo com diferentes idades, território arterial comprometido e fatores de risco. A detecção da bactéria foi feita por reação de polimerização em cadeia. RESULTADOS: Somente um paciente, pertencente ao grupo controle, teve resultado positivo. CONCLUSÃO: Estes achados não sugerem que a C. pneumoniae participe no desencadeamento do AVC ou AIT ou que tenha papel na desestabilização da placa.

Helicobacter pylori gastritis and risk of ischaemic stroke.

OBJECTIVE: To identify the association between H. Pylori gastritis and stroke. METHOD: Patients with biopsy proven H. Pylori gastritis and non H. Pylori gastritis were enrolled. Patients were followed for a period of two years. RESULTS: A total of 326 patients were included in the study. 162 patients were with H. Pylori gastritis. There was no significance difference in age, sex and duration of symptoms in the two groups. Three patients in H. Pylori group had stroke or TIA as compared to one in non H. Pylori group. Patients with H. Pylori gastritis were more likely to die or have cardiac and or neurological event as compared to Non H. pylori gastritis (OR 1.23, 95% CI 0.89-1.67). This relationship was not significant after adjusting for cardiovascular risk factors (AOR 0.85, 95% CI 0.45-1.31). CONCLUSION: H. Pylori gastritis is not independently associated with increased risk for stroke. Larger, randomized studies are needed to confirm our findings.

Neurobrucellosis as an exceptional cause of transient ischemic attacks.

We report a series of four cases presented with transient ischemic attacks (TIA) or ischemic stroke as the predominant manifestation of neurobrucellosis (NB). Three of the patients were 20-28 years of age, and one patient was 53 years old. They all used to consume unpasteurized milk or its products. Two patients had systemic brucellosis in the past and received antibiotic treatment. Other causes of TIA including cardiac embolism, hypercoagulability, vascular malformations, systemic vasculitis, and infective endocarditis were excluded. NB was diagnosed with serological tests or cultures for Brucella in the cerebrospinal fluid. None of the patients had any further TIA after the initiation of specific treatment. NB should always be sought in young patients with TIA or ischemic stroke, especially if they have no risk factors for stroke and live in an endemic area for brucellosis, even if they do not have other systemic signs of brucellosis.

Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila in elderly patients with stroke (C-PEPS, M-PEPS, L-PEPS): a case-control study on the infectious burden of atypical respiratory pathogens in elderly patients with acute cerebrovascular disease.

BACKGROUND AND PURPOSE: Multiple studies have suggested an association between Chlamydia pneumoniae and Mycoplasma pneumoniae infection and cardiovascular disease. We investigated whether the risk of cerebrovascular disease is associated with Legionella pneumophila infection and the aggregate number/infectious burden of these atypical respiratory pathogens. METHODS: One hundred patients aged >65 years admitted with acute stroke or transient ischemic attack (TIA) and 87 control patients admitted concurrently with acute noncardiopulmonary, noninfective conditions were recruited prospectively. Using enzyme-linked immunosorbent assay (ELISA) kits, we previously reported the seroprevalences of C pneumoniae and M pneumoniae in these patients. We have now determined the seroprevalences of L pneumophila IgG and IgM in this cohort of patients using ELISA. RESULTS: The seroprevalences of L pneumophila IgG and IgM were 29% (n=91) and 12% (n=81) in the stroke/TIA group and 22% (n=86) and 10% (n=72) in the controls, respectively. Using logistic regression to adjust for age, sex, hypertension, smoking, diabetes, ischemic heart disease, and ischemic ECG, the odds ratios for stroke/TIA in relation to L pneumophila IgG and IgM were 1.52 (95% CI, 0.70 to 3.28; P=0.29) and 1.49 (95% CI, 0.45 to 4.90; P=0.51), respectively. The odds ratios in relation to IgG seropositivity for 1, 2, or 3 atypical respiratory pathogens after adjustment were 3.89 (95% CI, 1.13 to 13.33), 2.00 (95% CI, 0.64 to 6.21), and 6.67 (95% CI, 1.22 to 37.04), respectively (P=0.06). CONCLUSIONS: L pneumophila seropositivity is not significantly associated with stroke/TIA. However, the risk of stroke/TIA appears to be associated with the aggregate number of chronic infectious burden of atypical respiratory pathogens such as C pneumoniae, M pneumoniae, and L pneumophila.

Chlamydia pneumoniae in elderly patients with stroke (C-PEPS): a case-control study on the seroprevalence of Chlamydia pneumoniae in elderly patients with acute cerebrovascular disease.

BACKGROUND AND PURPOSE: Multiple studies have suggested an association between Chlamydia pneumoniae infection and atherosclerotic vascular disease. We investigated whether serological markers of C. pneumoniae infection were associated with acute stroke or transient ischaemic attack (TIA), exclusively in elderly patients. METHODS: One-hundred white patients aged over 65 years admitted with acute stroke or TIA, and 87 control patients admitted with acute non-cardiopulmonary, non-infective disorders were recruited prospectively. Using an enzyme-linked immunosorbent assay kit, the presence of C. pneumoniae immunoglobulins IgA, IgG, IgM in patients' sera was determined. RESULTS: The seroprevalence of C. pneumoniae-specific IgA, IgG, IgM were 63, 71, and 14% in the stroke/TIA group (median age = 80), and 62, 65, and 17% in the control group (median age = 80), respectively. Using a logistic regression statistical model, adjusting for age and sex, history of hypertension, smoking, diabetes, ischaemic heart disease (IHD), ischaemic electrocardiogram (ECG), the odds ratios (ORs) of having a stroke/TIA in relation to C. pneumoniae-specific IgA, IgG, IgM were 1.04, 1.24, 0.79 (p = NS). Further analysis identified 43 acute stroke/TIA cases and 44 controls without history of IHD or ischaemic ECG or both. After adjusting for history of hypertension, smoking, diabetes, age and sex, the ORs in this subgroup were 1.40 for IgA [95% confidence interval (CI) 0.53-3.65; p = 0.49], 2.41 for IgG (95% CI 0.90-6.46; p = 0.08) and 1.55 for IgM (95% CI 0.45-5.40; p = 0.49). CONCLUSIONS: Although a high seroprevalence of C. pneumoniae in elderly patients was confirmed, no significant association between serological markers of C. pneumoniae infection and acute cerebrovascular events was found. There was, however, a weak trend towards increased ORs for acute cerebrovascular disease in a subgroup of C. pneumoniae seropositive elderly patients without any history of IHD or ischaemic ECG.

Group A beta-haemolytic streptococcal infection and Henoch-Schonlein purpura with cardiac, renal and neurological complications.

A 6-year-old girl had a group A beta-haemolytic streptococcal (GABS) throat infection and Henoch-Schonlein purpura (HSP). The clinical course was complicated by nephrotic syndrome due to crescentic glomerulonephritis, transient neurological symptoms due to focal ischaemia of the brain, and congestive cardiac failure due to myocarditis. The clinical presentation highlights the diversity of systemic involvement in HSP, the transient nature of apparently serious central nervous system involvement, and a possible role of GABS in its aetiology.