The Association between Cerebral Small Vessel Disease and the Gut Microbiome: A Cross-Sectional Analysis.

BACKGROUND: Recent studies have demonstrated an association between the gut microbiome and cognitive function. However, the associations between the gut microbiome and brain parenchyma damage, and their underlying mechanisms, remain unclear. MATERIALS AND METHODS: We performed a cross-sectional sub-analysis using data from our prospective cohort study to determine the association between the gut microbiome and cerebral small vessel disease (SVD). We assessed patient demographics, risk factors, cognitive function, brain imaging, voxel-based specific regional analysis system for Alzheimer's Disease (VSRAD, indicating brain atrophy), and the gut microbiome as indicated by enterotypes and faecal microbiome metabolites. We then analysed the associations between total SVD scores, cognitive function, and the gut microbiome. RESULTS: We analysed data from 87 patients without dementia or a history of stroke, 64 of whom exhibited mild cognitive impairment. Higher total SVD scores were associated with cognitive decline and behavioural and psychological symptoms. Compared with all other patients, patients with enterotype I (Bacteroides >30%) were more likely to have cognitive decline (median scores: Mini-Mental State Examination, 25 vs. 27, P = 0.047; Clinical Dementia Rating-Sum of Boxes, 1.5 vs. 0.5, P = 0.002) and present with cerebral SVD and high VSRAD scores (1.01 vs. 0.57, P = 0.012). Furthermore, faecal metabolites were significantly higher in patients with higher total SVD scores compared with those with lower scores. Multivariable logistic regression analyses indicated that certain gut microbiomes may double the risk of white matter hyperintensity. CONCLUSIONS: The gut microbiome is associated with cerebral SVD.

Association between infectious burden and cerebral microbleeds: a pilot cross-sectional study.

OBJECTIVE: Cerebral microbleeds (CMBs) is a subtype of cerebral small vessel disease. Their underlying pathogenesis remains unclear. The aim of this study was to investigate the association between infectious burden (IB) and CMBs. METHODS: Seven hundred and seventy-three consecutive patients who were hospitalized in the Department of Neurology in General Hospital of Western Theater Command without severe neurological symptoms were recruited and selected in this pilot cross-sectional study. CMBs were assessed using the susceptibility-weighted imaging sequence of magnetic resonance imaging. Immunoglobulin G antibodies against common pathogens, including herpes simplex virus (HSV)-1, HSV-2, cytomegalovirus (CMV), Chlamydia pneumoniae (C. pneumoniae), Mycoplasma pneumoniae (M. pneumoniae), Epstein-Barr virus (EBV), Helicobacter pylori (HP), and Borrelia burgdorferi (B. burgdorferi), were measured by commercial ELISA assays. IB was defined as a composite serologic measure of exposure to these common pathogens. RESULTS: Patients with and without CMBs were defined as the CMBs group (n = 76) and the non-CMBs group (n = 81), respectively. IB was significantly different between the CMBs and non-CMBs groups. After adjusted for other risk factors, the increased IB was independently associated with the presence of CMBs (P = 0.031, OR = 3.00, 95% CI [1.11-8.15]). IB was significantly positively associated with the number of CMBs (Spearman ρ = 0.653, P < 0.001). The levels of serum inflammatory markers were significantly different between the CMBs and non-CMBs groups and among the categories of IB. INTERPRETATION: IB consisting of HSV-1, HSV-2, CMV, C. pneumoniae, M. pneumoniae, EBV, HP, and B. burgdorferi was associated with CMBs. All the findings suggested that pathogen infection could be involved in the pathogenesis of CMBs.

Neurologic Complications of Infective Endocarditis: A Joint Model for a Septic Thromboembolism and Inflammatory Small Vessel Disease.

OBJECTIVES: Embolic events from vegetations are commonly accepted as the main mechanism involved in neurologic complications of infective endocarditis. The pathophysiology may imply other phenomena, including vasculitis. We aimed to define the cerebral lesion spectrum in an infective endocarditis rat model. DESIGN: Experimental model of Staphylococcus aureus or Enterococcus faecalis infective endocarditis. Neurologic lesions observed in the infective endocarditis model were compared with three other conditions, namely bacteremia, nonbacterial thrombotic endocarditis, and healthy controls. SETTING: Research laboratory of a university hospital. SUBJECTS: Male Wistar rats. INTERVENTIONS: Brain MRI, neuropathology, immunohistochemistry for astrocyte and microglia, and bacterial studies on brain tissue were used to characterize neurologic lesions. MEASUREMENTS AND MAIN RESULTS: In the infective endocarditis group, MRI revealed at least one cerebral lesion in 12 of 23 rats (52%), including brain infarctions (n = 9/23, 39%) and cerebral microbleeds (n = 8/23, 35%). In the infective endocarditis group, neuropathology revealed brain infarctions (n = 12/23, 52%), microhemorrhages (n = 10/23, 44%), and inflammatory processes (i.e., cell infiltrates including abscesses, vasculitis, meningoencephalitis, and/or ependymitis; n = 11/23, 48%). In the bacteremia group, MRI studies were normal and neuropathology revealed only hemorrhages (n = 2/11, 18%). Neuropathologic patterns observed in the nonbacterial thrombotic endocarditis group were similar to those observed in the infective endocarditis group. Immunochemistry revealed higher microglial activation in the infective endocarditis group (n = 11/23, 48%), when compared with the bacteremia (n = 1/11, 9%; p = 0.03) and nonbacterial thrombotic endocarditis groups (n = 0/7, 0%; p = 0.02). CONCLUSIONS: This original model of infective endocarditis recapitulates the neurologic lesion spectrum observed in humans and suggests synergistic mechanisms involved, including thromboembolism and cerebral vasculitis, promoted by a systemic bacteremia-mediated inflammation.

Intramural Vascular Edema in the Brain of Goats With Clostridium perfringens Type D Enterotoxemia.

Enterotoxemia caused by Clostridium perfringens type D is an important disease of sheep and goats with a worldwide distribution. Cerebral microangiopathy is considered pathognomonic for ovine enterotoxemia and is seen in most cases of the disorder in sheep. However, these lesions are poorly described in goats. In this article, we describe the vasculocentric brain lesions in 44 cases of caprine spontaneous C. perfringens type D enterotoxemia. Only 1 goat had gross changes in the brain, which consisted of mild cerebellar coning. However, 8 of 44 (18%) cases showed microscopic brain lesions, characterized by intramural vascular proteinaceous edema, a novel and diagnostically significant finding. The precise location of the edema was better observed with periodic acid-Schiff, Gomori's, and albumin stains. Glial fibrillary acidic protein and aquaporin 4 immunostaining revealed strong immunolabeling of astrocyte foot processes surrounding microvessels. The areas of the brain most frequently affected were the cerebral cortex, corpus striatum (basal ganglia), and cerebellar peduncles, and both arterioles and venules were involved. Most of the goats of this study showed lesions in the intestine (enteritis, colitis, and typhlitis), although pulmonary congestion and edema, hydrothorax, hydropericardium, and ascites were also described. Although the intramural edema described, for the first time, in these caprine cases is useful for the diagnosis of enterotoxemia when observed, its absence cannot exclude the disease.

Outcome of Chlamydia pneumoniae associated acute ischemic stroke in elderly patients: a case-control study.

BACKGROUND: Limited data exists about the role of Chlamydia pneumoniae elderly patients with acute ischemic stroke. OBJECTIVE: To study the role of C. pneumoniae in elderly patients (age more than 65 years) with acute ischemic stroke and its impact on stroke out come. METHODS: We recruited 100 elderly patients with acute ischemic stroke and 100 age and sex matched controls over a period of 2 years. IgG and IgA anti C. pneumoniae antibodies were measured by microimmunofluorescence technique in patients and controls. Good outcome was defined as a Modified Rankin score (mRS) of ≤2. RESULTS: We found C. pneumoniae antibodies in 35% stroke patients and in 18% control subjects (p=0.01). Good out come at 90 days follow up was found in 20/35(57.1%) seropositive stroke patients compared to 37/65(56.9%) seronegative stroke patients (p=0.9). CONCLUSIONS: C. pneumoniae antibody positivity was independently associated with ischemic stroke in elderly patients and its presence does not alter the stroke outcome.