Receptor for advanced glycation end products up-regulation in cerebral endothelial cells mediates cerebrovascular-related amyloid ß accumulation after Porphyromonas gingivalis infection.

Cerebrovascular-related amyloidogenesis is found in over 80% of Alzheimer's disease (AD) cases, and amyloid ß (Aß) generation is increased in the peripheral macrophages during infection of Porphyromonas gingivalis (P. gingivalis), a causal bacterium for periodontitis. In this study, we focused on receptor for advanced glycation end products (RAGE), the key molecule involves in Aß influx after P. gingivalis infection to test our hypothesis that Aß transportation from periphery into the brain, known as "Aß influx," is enhanced by P. gingivalis infection. Using cultured hCMEC/D3 cell line, in comparison to uninfected cells, directly infection with P. gingivalis (multiplicity of infection, MOI = 5) significantly increased a time-dependent RAGE expression resulting in a dramatic increase in Aß influx in the hCMEC/D3 cells; the P. gingivalis-up-regulated RAGE expression was significantly decreased by NF-κB and Cathepsin B (CatB)-specific inhibitors, and the P.gingivalis-increased IκBα degradation was significantly decreased by CatB-specific inhibitor. Furthermore, the P. gingivalis-increased Aß influx was significantly reduced by RAGE-specific inhibitor. Using 15-month-old mice (C57BL/6JJmsSlc, female), in comparison to non-infection mice, systemic P. gingivalis infection for three consecutive weeks (1 × 108  CFU/mouse, every 3 days, intraperitoneally) significantly increased the RAGE expression in the CD31-positive endothelial cells and the Aß loads around the CD31-positive cells in the mice's brains. The RAGE expression in the CD31-positive cells was positively correlated with the Aß loads. These observations demonstrate that the up-regulated RAGE expression in cerebral endothelial cells mediates the Aß influx after P. gingivalis infection, and CatB plays a critical role in regulating the NF-κB/RAGE expression. Cover Image for this issue: https://doi.org/10.1111/jnc.15073.

Pathogenic characteristics of nosocomial infections in patients with cerebrovascular diseases and characteristics and treatment of pathogenic bacteria in different seasons.

OBJECTIVE: The objective of this study is to explore the bacterial distribution characteristics of air and bed environment in patients with cerebrovascular diseases and to analyze the relationship between bacterial distribution and nosocomial infection in patients with cerebrovascular diseases. METHODS: In this study, the inpatients with cerebrovascular diseases who suffer from nosocomial infection are taken as the research objects. The pathogenic characteristics of the air environment in the ward and the environment in the bed unit are monitored, and the samples of cerebrovascular patients are collected for identification and drug sensitivity detection. The changes of the number of pathogens in different seasons are statistically compared, and the drug sensitivity test results of various pathogens are analyzed. RESULTS: In large wards, the number of pathogens in the air environment in winter is significantly higher than that in spring. In summer, the number of pathogens in pillow environment is significantly more than that in small wards. Gram-negative bacilli are the main pathogens in the four seasons, followed by Gram-positive cocci and less fungal infections. Among them, Staphylococcus aureus is the main Gram-positive coccus, which is sensitive to vancomycin and other therapeutic drugs, and resistant to erythromycin and other therapeutic drugs. Gram-negative bacteria are mainly Klebsiella pneumoniae and Pseudomonas aeruginosa. K. pneumoniae is sensitive to imipenem, tekacillin, meropenem and ceftitam, and resistant to ampicillin. P. aeruginosa is sensitive to cefuroxime ester, cefazolin and cefuroxime sodium. It is resistant to ampicillin, ceftitam, compound sinomine and ampicillin plus sulbactam. Candida albicans is the main fungus, which is sensitive to ketoconazole, fluconazole, amphotericin and nystatin. CONCLUSION: The number of pathogenic bacteria in the ward environment of patients with cerebrovascular disease is affected by the size of the room and season. The main pathogenic bacteria are Gram-negative bacilli, followed by Gram-positive cocci and less fungal infections.

Variation in coagulation and fibrinolysis genes evaluated for their contribution to cerebrovascular complications in adults with bacterial meningitis in the Netherlands.

OBJECTIVE: To study whether genetic variation in coagulation and fibrinolysis genes contributes to cerebrovascular complications in bacterial meningitis. METHODS: We performed a nationwide prospective genetic association study in adult community-acquired bacterial meningitis patients. The exons and flanking regions of 16 candidate genes involved in coagulation and fibrinolysis pathways were sequenced. We analyzed whether genetic variation in these genes resulted in a higher risk of cerebrovascular complications, unfavorable outcome and differences in thrombocyte count on admission. RESULTS: From 2006 to 2011, a total of 1101 bacterial meningitis patients were identified of whom 622 supplied DNA for genotyping and passed genetic quality control steps. In 139 patients (22%) the episode of bacterial meningitis was complicated by cerebral infarction, and 188 (30%) had an unfavorable outcome. We identified the functional variant rs494860 in the protein Z (PROZ) gene as our strongest association with occurrence of cerebral infarction (odds ratio (OR) 0.49 (95% confidence interval 0.33-0.73), p = 5.2 × 10-4). After Bonferroni correction for multiple testing no genetic variant was significantly associated (p-value threshold 2.7 × 10-4). CONCLUSION: Our study suggests a functional genetic variation in the PROZ gene, rs494860, may be of importance in bacterial meningitis pathogenesis and cerebral infarction risk. Replication of this finding in other cohort studies populations is needed.

Gut-Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet.

BACKGROUND: Gut microbiota is emerging as a novel risk factor for atherothrombosis, but the predictive role of gut-derived lipopolysaccharide (LPS) is unknown. We analyzed (1) the association between LPS and major adverse cardiovascular events (MACE) in atrial fibrillation (AF) and (2) its relationship with adherence to a Mediterranean diet (Med-diet). METHODS AND RESULTS: This was a prospective single-center study including 912 AF patients treated with vitamin K antagonists (3716 patient-years). The primary end point was a composite of MACE. Baseline serum LPS, adherence to Med-diet (n=704), and urinary excretion of 11-dehydro-thromboxane B2 (TxB2, n=852) were investigated. Mean age was 73.5 years; 42.9% were women. A total of 187 MACE (5.0% per year) occurred: 54, 59, and 74 in the first, second, and third tertile of LPS, respectively (log-rank test P=0.004). Log-LPS (hazard ratio 1.194, P=0.009), age (hazard ratio 1.083, P<0.001), and previous cerebrovascular (hazard ratio 1.634, P=0.004) and cardiac events (hazard ratio 1.822, P<0.001) were predictors of MACE. In the whole cohort, AF (versus sinus rhythm) (ß 0.087, P=0.014) and low-density lipoprotein cholesterol (ß 0.069, P=0.049) were associated with circulating LPS. Furthermore, Med-diet score (ß -0.137, P<0.001) was predictive of log-LPS, with fruits (ß -0.083, P=0.030) and legumes (ß -0.120, P=0.002) negatively associated with log-LPS levels. Log-LPS and log-TxB2 were highly correlated (r=0.598, P<0.001). Log-LPS (ß 0.574, P<0.001) and Med-diet score (ß -0.218, P<0.001) were significantly associated with baseline urinary excretion of TxB2. CONCLUSIONS: In this cohort of AF patients, LPS levels were predictive of MACE and negatively affected by high adherence to Med-diet. LPS may contribute to MACE incidence in AF by increasing platelet activation.

Late-onset group B streptococcal meningitis has cerebrovascular complications.

OBJECTIVE: To describe cerebrovascular diseases related to late-onset group B Streptococcus (GBS) meningitis. STUDY DESIGN: Retrospective case series. Patients treated for cerebrovascular complication of late-onset GBS meningitis over 5 years were identified through neuroradiology and microbiology databases. Patient charts were reviewed with regard to clinical presentation, laboratory findings, including GBS subtype, treatment, clinical course, and outcome. Cerebral magnetic resonance imaging was reviewed with special emphasis on stroke pattern and cerebrovascular findings. RESULTS: Fourteen patients were identified. In 6 out of 9 patients serotype III was causative and positive for surface protein hvgA in 5. Ten had arterial ischemic stroke accompanied by a cerebral sinovenous thrombosis in 2 patients. Evidence of cerebral vasculopathy was found in 4 cases. The stroke pattern was variable with cortical, multifocal ischemia, basal ganglia involvement, or had a clear territorial arterial infarction. Ten patients were treated with anticoagulation. No significant bleeding complications, and no recurrent strokes occurred. Twelve patients had clinical and/or subclinical seizures. Developmental outcome was good in 8 cases. Six patients had moderate to severe developmental delay. Central nervous system complications included subdural empyema, hydrocephalus, epilepsy, microcephaly, and hemiplegia. CONCLUSIONS: Late-onset GBS meningitis can be complicated by severe cerebrovascular disease, including arterial ischemic stroke and cerebral sinovenous thrombosis. These complications may be underestimated. We recommend a low threshold for cerebral imaging in these cases. Future studies on the exact incidence, the role of GBS subtypes, and on safety and efficiency of preventive anticoagulation therapy are warranted.

Characteristics and prognosis of pulmonary infection in patients with neurologic disease and hypoproteinemia.

OBJECTIVE: To examine the characteristics and the prognostic influence of pulmonary infections in neurologic disease patients with mild-to-severe hypoproteinemia. METHODS: We used a retrospective survey method to analyze the characteristics and prognoses of 220 patients with hypoproteinemia complicated with pulmonary infection in the Internal Medicine-Neurology Intensive Care Unit at the First Affiliated Hospital of Chongqing Medical University from January 2010 to December 2013. The patients were divided into mild, moderate and severe hypoproteinemia groups according to their serum albumin levels. The analysis included patient age, sex, acute physiology and chronic health evaluation (APACHE II score), and characteristics of the pulmonary infection, nutritional support and prognosis, among others. RESULTS: Differences in the general information of the 220 cases of hypoalbuminemia patients complicated with varying degrees of pulmonary infection (APACHE II score, age, disease distribution) were statistically significant. The pulmonary infection onset time and pathogen susceptibility in the patients with mild-to-severe hypoalbuminemia were not significantly different. Pulmonary infection onset was more frequently observed within the first 3-11 days following admission in all groups. The nutritional support method did not significantly influence serum albumin protein levels. However, the neurological intensive care unit stay length, total hospitalization cost and disease distribution were significantly different among the patient groups. CONCLUSIONS: Patients with cerebrovascular disease, intracranial infections and epilepsy complicated with pulmonary infection represent the high-risk groups for hypoalbuminemia. The Acinetobacter baumannii complex represents the main group of pathogenic bacteria causing lung infections, and the high-risk period for lung infections is 3-11 days after the occurrence of hypoalbuminemia. Patients with severe hypoalbuminemia complicated with pulmonary infection have the worst prognoses.

Outcome of MRSA carriers in neurological early rehabilitation.

BACKGROUND: Colonization with MRSA is believed to have deteriorating effects on neurological rehabilitation patients because MRSA carriers need to be isolated. METHODS: Medical records of neurological early rehabilitation patients (most of them after stroke) admitted to a large rehabilitation facility in Northern Germany in 2010 have been carefully reviewed with respect to MRSA status, outcome variables (functional independence), morbidity, and length of stay (LOS). RESULTS: 74/569 (13.0%) patients were MRSA positive on admission. MRSA carriers had a significantly longer LOS in early neurological rehabilitation (63.7 (37.1) vs. 25.8 (24.5) days, p < 0.001), worse functional status on admission (Barthel index (BI) 13.6 (9.9) vs. 25.6 (24.1), p < 0.001), worse Glasgow Coma Scale (9.5 (3.2) vs. 12.0 (3.3), p < 0.001), more co-diagnoses (20.5 (5.1) vs. 13.3 (5.5), p < 0.001), and higher Patient Clinical Complexity Levels (PCCL). The outcome was significantly worse among MRSA positive patients (BI 25.5 (21.2) vs. 47.4 (31.0), p < 0.001; Early Rehabilitation Index -47.3 (51.4) vs. -26.0 (35.4), p < 0.001). Isolated patients had slightly less therapy per day (131.6 (16.6) vs. 140.2 (18.7) min/day, p < 0.001), but the overall sum of therapy was significantly larger in the MRSA positive group due to longer LOS. CONCLUSIONS: Functional recovery of MRSA carriers in early neurological rehabilitation is worse than in MRSA negative patients. Poorer outcome is not resulting from isolation (less therapy) but from functional status and higher morbidity on admission.

Management of infective endocarditis with cerebral complications.

PURPOSE: Management of patients with infective endocarditis complicated by neurological deficits is challenging. No clear management guidelines have been defined, and the timing of surgery remains controversial. The purpose of this study was to evaluate our management algorithm. METHODS: Thirty-eight adult patients with left-sided infective endocarditis undergoing valve surgery were analyzed. Before the operation, enhanced brain computed tomography (CT) was performed to rule out a cerebral complication. Pre and postoperative data were retrospectively reviewed to clarify whether our algorithm was effective. Sixteen patients having neurological complication (CVC group) were compared with 22 patients without neurological complication. RESULTS: Age, sex, New York Heart Association (NYHA) functional class, affected valve and pathogens were not different between two groups. Mean interval from the onset of neurological dysfunction to cardiac operation was 27.8 ± 27.8 days (median 23 days). Of the 16 CVC group patients, 12 experienced cerebral infarction. Mass effects were seen in 3 patients, with 1 of these 3 patients died following aneurysm rupture. Mycotic aneurysm was detected in 4 patients, with 3 undergoing successful staged operations. Mortality and postoperative neurological exacerbation in CVC group was 6.3% (1 patient). Most patients who fulfilled the algorithm showed good outcomes. CONCLUSIONS: Our suggested management algorithm for infective endocarditis appears effective.

Chlamydia pneumoniae infection and cerebrovascular disease: a systematic review and meta-analysis.

BACKGROUND: A wealth of published studies have been published on association between Chlamydia pneumoniae (C.pneumoniae) infection and cerebrovascular (CV) disease, but the results were inconsistent. This meta-analysis provides a systematic review of the available evidence from all serological and pathological studies of CV disease and C.pneumoniae. METHODS: A comprehensive research was conducted of MEDLINE, EMBASE, CNKI, WanFang technological periodical database and reference lists of articles to identify eligible case-control and cohort studies. Odds radio (OR) was calculated for each study outcome. Random effect model was used as pooling method and publication bias was estimated for the results. RESULTS: Fifty-two published studies that met criteria were selected. In case control studies, an association between C.pneumoniae infection and CV disease was revealed by serum specific IgG (OR, 1.61; 95% CI: 1.34 to 1.94), serum IgA (OR, 2.33; 95% CI: 1.76 to 3.08) and PCR technique of C.pneumoniae in peripheral blood cells (OR, 1.90; 95% CI: 1.17 to 3.07). No significant association was found in serum anti-C.pneumonae IgM seropositivity or in-situ-detection of C.pneumoniae in arterial biopsies with CV disease. Subgroup analysis by available studies suggested that C.pneumoniae may paly a role in atherosclerotic stroke, but be less significant in stroke of cardioembolism or other etiologies. CONCLUSION: Association between C.pneumoniae infection and CV disease depends on the analytical method adopted, which seems stronger with stroke due to large artery atherosclerosis. Establishing a causal relationship between C.peumoniae infection and CV disease will require more prospective studies with combination of techniques and stratified by etiological subtypes.

The impact of pulmonary Acinetobacter baumannii infection on the prognosis of inpatients in a neurological intensive care unit.

OBJECTIVE: To investigate the impact of pulmonary Acinetobacter baumannii infection on the prognosis of patients in a Chinese neurological intensive care unit (NICU). METHODS: Patients with pulmonary infection and positive sputum culture findings were retrospectively enrolled. Logistic regression analysis was used to determine the factors influencing prognosis. Neurological disease improvement/nonimprovement and mortality rates were assessed. RESULTS: The study included 374 NICU patients with pulmonary infection (110 [29.4%] with A. baumannii, 264 [70.6%] with other micro-organisms). A. baumannii infection (OR = 2.987) and invasive mechanical ventilation (OR = 16.898) were independent factors in disease prognosis. A. baumannii infection was associated with longer NICU stay, fewer improved patients and increased mortality rate compared with other pulmonary infections. CONCLUSIONS: A. baumannii infection prolongs the duration of the NICU stay and negatively impacts on prognosis. Prognosis of NICU patients could be improved by controlling A. baumannii infection.

Scrub typhus and cerebrovascular injury: a phenomenon of delayed treatment?

Abstract. Three patients diagnosed with scrub typhus through serology and polymerase chain reaction tests, experienced delayed administration of effective antibiotics after the appearance of symptoms, presented with subdural hemorrhage, intracerebral hemorrhage, or cerebral infarction in the late acute phase. Orientia tsutsugamushi should be considered as a causal or provoking factor for cerebrovascular accidents in regions where scrub typhus is endemic, especially in those who receive delayed treatment.

Multiple cerebral arterial occlusions related to Mycoplasma pneumoniae infection.

We report the case of a 33-year-old man with a brainstem infarction due to concomitant occlusions in the left internal carotid, both vertebral, and basilar arteries. The patient had experienced a severe Mycoplasma pneumoniae infection about 10 months prior to symptom onset, and his Mycoplasma antibody titre was positive when the stroke occurred. Despite performing meticulous neurological, vascular, and medical evaluations, we were unable to detect other possible causes of the stroke. Therefore, the multiple occlusions in the major cerebral arteries of our patient were concluded to be related to M. pneumoniae infection.

Proteus Takayasu's arteritis with unusual intracranial granulomatosis as initial manifestation.

Takayasu's arteritis (TA) is an inflammatory vasculitis of aorta and its branches, its low incidence limited our recognition to this entity. We sometimes can confuse this disease with polyarteritis nodosa and other vasculitis when no conventional "big artery" involved in TA cases. Here we report a 26-year-old man with Takayasu's arteritis who presented with a provisional intracranial granulomatosis first and then saccular aneurysms between celiac trunk and arteria hepatica communis and many other proteus manifestations, which is seldom described before.

Mycoplasmal cerebral vasculopathy in a lymphoma patient: presumptive evidence of Mycoplasma pneumoniae microvascular endothelial cell invasion in a brain biopsy.

A 73-year-old man had episodic encephalopathy, ataxia and neuropathy. Symptoms largely resolved but adenopathy later lead to the diagnosis of a low-grade follicular lymphoma. The neurological symptoms soon recurred with new pontine calcifications identified by computed tomography. Brain biopsy revealed microvascular endothelial cell nuclear changes. Electron microscopy identified small polymorphic bacteria without a cell wall and with terminal and attachment organelles within endothelial cells and clustered in some microvascular lumina. Immunostaining was positive for Mycoplasma pneumoniae and convalescent serum enzyme immunoassay was positive for M. pneumoniae IgG. The patient again recovered and he was neurologically stable 33 months after the initial episode. The ultrastructural findings of the bacterial cells are distinctive of some mycoplasmal species when compared to other small bacteria. Mycoplasma-like organisms are reported in four autopsied patients who had chronic encephalopathy, movement disorders, and some of the same light- and electron-microscopic findings in the brain as our patient. Direct neuroinvasion by Mycoplasma species has been suggested, while anatomic observations in our patient and in the four autopsy cases show microvascular invasion but not parenchymal invasion. Most mycoplasmal encephalitis may be immune-mediated. The frequency of neurovascular invasion is not known. It may be rare and it may persist.

[Meningovascular neurosyphilis as the cause of ischemic cerebrovascular disease in a young man]. / Meningovascularis neurosyphilis miatti fiatalkori ischaemiás cerebrovascularis betegség.

Authors report a case of a 35-year-old male with right-sided mild paresis, incontinence, dysexecutive syndrome, short-term memory loss and behavioral changes. Bilateral cerebral infarcts in the region of the caudate nuclei and the adjacent white matter were proved by brain MRI and multiple stenoses of the branches of Willis-circle were confirmed by MR angiography. Elevated protein level and pleocytosis were found in the cerebrospinal fluid with intrathecal IgG synthesis. Serum rapid plasma reagin, Treponema pallidum Particle Agglutination test, Treponema pallidum ELISA, liquor Venereal Disease Research Laboratory tests were positive. Meningovascular neurosyphilis was diagnosed. 24M U/day intravenous penicillin-G treatment was given for 14 days. The patient has vascular dementia due to the bilateral strategic infarcts disconnecting the prefrontal circuits; his symptoms are similar to general paresis. Laboratory and radiologic improvement was observed. Still, the patient have severe residual cognitive decline.

[Vaccinoprophylaxis of chronic somatic diseases exacerbations in groups of risk].

Modem version of I. Mechnikov's hypothesis on association of somatic diseases with infectious agents is presented. List of bacteria and viruses associated with various types of cardiomyopathies, atherosclerosis, gastritis, gastric and duodenal ulcerative disease, type 1 diabetes mellitus. Literature data showing that influenza vaccination reduces number of fatal myocardial infarctions and strokes during winter seasons as well as number of hospitalizations due to exacerbations of chronic cardiovascular and cerebrovascular diseases are summarized. Data on probability of coincidence of influenza vaccination and sudden death in elderly persons are reviewed.

The association of carotid plaque inflammation and Chlamydia pneumoniae infection with cerebrovascular symptomatology.

OBJECTIVE: Inflammation and infection have been implicated in the pathogenesis of carotid artery atherosclerosis, but their role in cerebrovascular disease symptomatology is not so well defined. We hypothesized that carotid disease symptomatology was associated with specific serologic markers of inflammation and Chlamydia pneumoniae infection and the presence of the pathogen and concentration of tumor necrosis factor-alpha (TNF-alpha) on the atheroma. METHODS: In 2004, 78 patients underwent carotid endarterectomy in our department, 46 of whom were symptomatic (group A) and 32 were asymptomatic (group B). A detailed medical history, the presence of atherosclerosis risk factors, ankle-brachial index and boxy mass index were recorded. We measured preoperatively the levels of C-reactive protein, fibrinogen, TNF-alpha, and the titers of immunoglobulin (Ig) A and IgG antibodies against C pneumoniae in the serum. Finally, the atherosclerotic plaques of all patients were immunohistochemically examined for the presence of C pneumoniae and their TNF-alpha concentration was determined. RESULTS: Isolation of the pathogen on the atheromatous lesion was statistically correlated with several risk factors and some of the variables that were tested. After testing independence of association, using the multiple regression analysis, only male gender (P = .024), hypertension (P = .008), hypercholesterolemia (P = .001), and TNF-alpha plaque values (P = .008) remained significantly associated. Hypertension, serum levels of fibrinogen and anti-C pneumoniae immunoglobulin A, detection of C. pneumoniae on the plaque, and plaque TNF-alpha values were significantly correlated with carotid disease symptomatology. After multiple analyses, only the presence of the pathogen on the lesion (P = .008) and atheroma TNF-alpha levels (P = .025) remained significantly associated with cerebrovascular events. CONCLUSIONS: It seems that hypertensive hypercholesterolemic men are more likely to have C. pneumoniae infected carotid plaques and that these plaques have higher TNF-alpha concentrations. Cerebrovascular disease symptomatology is strongly correlated with both C. pneumoniae infection and TNF-alpha concentration of the atheroma.

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.