Circulating bacterial lipopolysaccharide-induced inflammation reduces flow in brain-irrigating arteries independently from cerebrovascular prostaglandin production.

Brain dysfunction is a frequent complication of the systemic inflammatory response to bacterial infection or sepsis. In the present work, the effects of intravenous bacterial lipopolysaccharide (LPS) administration on cerebral arterial blood flow were assessed with time-of-flight (TOF)-based magnetic resonance angiography (MRA) in mice. Cerebral expression of the transcription factors nuclear factor-kappaB (NF-κB) and c-Fos and that of enzymes synthesizing vasoactive mediators, such as prostaglandins and nitric oxide, known to be increased under inflammatory conditions, were studied in the same animals. Time-resolved TOF MRA revealed no differences in blood flow in the internal carotids upstream of the circle of Willis, but indicated lower flow in its lateral parts as well as in the middle and anterior cerebral arteries after intravenous LPS injection as compared to saline administration. Although LPS did not increase c-Fos expression in ventral forebrain structures of these animals, it did induce NF-κB in meningeal blood vessels. LPS also increased cerebral expression of cyclooxygenase-2 and prostaglandin E synthase mRNAs, but de novo expression occurred in veins rather than in arteries. In conclusion, our work indicates that LPS-induced systemic inflammation does not necessarily affect filling of the circle of the Willis from the periphery, but that circulating LPS alters outflow from the circle of Willis to the middle and anterior cerebral arteries. These modifications in arterial flow were not related to increased cerebral synthesis of prostaglandins, but may instead be the consequence of the action of circulating prostaglandins and other vasoactive mediators on brain-irrigating arteries during systemic inflammation.

Subcortical intracerebral hemorrhage caused by mucormycosis in a patient with a history of bone-marrow transplantation.

We report on a rare case of a patient with rhinocerebral mucormycosis that presented as intracerebral hemorrhage (ICH). A 54-year-old man who was immunosuppressed had ophthalmoplegia. Four days later, ICH developed in his left frontal lobe. The ICH was surgically removed totally. Pathology specimen surgically obtained from brain surface adjacent to hematoma cavity showed blood vessels filled with Mucor mycelium. Combined with surgical findings, venous occlusion by Mucor mycelium might be the cause of ICH in the patient.

Differential regulation of blood-brain barrier permeability in brain trauma and pneumococcal meningitis-role of Src kinases.

Increased vascular permeability causing vasogenic brain edema is characteristic for many acute neurological diseases such as stroke, brain trauma, and meningitis. Src family kinases, especially c-Src, play an important role in regulating blood-brain barrier permeability in response to VEGF, but also mediate leukocyte function and cytokine signalling. Here we demonstrate that pharmacological inhibition of Src or c-Src deficiency does not influence cerebrospinal fluid (CSF) pleocytosis, brain edema formation, and bacterial outgrowth during experimental pneumococcal meningitis despite the increased cerebral expression of inflammatory chemokines, such as IL-6, CCL-9, CXCL-1, CXCL-2 and G-CSF as determined by protein array analysis. In contrast, inhibition of Src significantly reduced brain edema formation, lesion volume, and clinical worsening in cold-induced brain injury without decreasing cytokine/chemokine expression. While brain trauma was associated with increased cerebral VEGF formation, VEGF levels significantly declined during pneumococcal meningitis. Therefore, we conclude that in brain trauma blood-brain barrier tightness is regulated by the VEGF/Src pathway whereas c-Src does not influence brain edema formation and leukocyte function during bacterial meningitis.

Different modalities of treatment of intracranial mycotic aneurysms: Report of 4 cases.

BACKGROUND: Intracranial mycotic aneurysms, although rare neurovascular pathology, represented a neurosurgical challenge that required careful stepwise decision making. Different approaches for their management were used. We present our experience with 4 patients treated in terms of indications and efficacy of different treatment modalities. METHODS: Four patients with infective endocarditis and 5 intracranial mycotic aneurysms were treated during the last 5 years. All of the patients were men; their ages ranged between 29 and 62 years (mean, 47.3 years). Distal MCA was the commonest site (3 patients) of aneurysm, 1 was located at the distal PCA, whereas the remaining aneurysm was at the distal ACA. Angiographic studies were done in 2 patients because of neurologic signs and for screening in 2 patients with documented endocarditis. RESULTS: One patient was treated conservatively because of his moribund general condition; 1 patient was treated with direct surgical clipping; 1 patient was treated with surgical trapping and resection of the aneurysm without revascularization; and the remaining patient, harboring 2 distal mycotic aneurysms, was treated with selective embolization for his PCA aneurysm and endovascular trapping for the distal ACA aneurysm. Follow-up angiographic results showed stable occlusion of the aneurysms. No periprocedural technical complications were reported, and none of the patients, including the patient with medical treatment only, has ever experienced new neurologic events after definitive treatment. CONCLUSIONS: Prolonged courses of antibiotics are recommended for all patients with mycotic aneurysms. Selective endovascular embolization or trapping with soft and ultrasoft electrolytically detachable coils seems to be an effective technique that should be considered for treatment of dynamic unruptured mycotic aneurysms, with conventional surgical repair restricted for ruptured aneurysms with associated hematoma and high intracranial pressure.

Identification of Chlamydia pneumoniae in intracranial and extracranial arteries in patients with stroke and in controls: combined immunohistochemical and polymerase chain reaction analyses.

An association of the obligatory intracellular gram-negative pathogen Chlamydia pneumoniae with coronary artery disease, myocardial infarction, and atherosclerosis was suggested. The presence of C pneumoniae was determined in different arteries (n = 165) from 23 control cases and 10 patients with stroke including coronary arteries, carotid arteries, basilar artery, and middle cerebral arteries of normal controls and patients with stroke using nested polymerase chain reaction (PCR) and immunohistochemistry (IHC). Atherosclerosis was detected in 51.5% of all investigated arteries. No significant differences were detected between controls (59.1% by IHC, 45.5% by nested PCR) and patients with stroke (40% by IHC, 40% by nested PCR). This is the first investigation demonstrating C pneumoniae by IHC and nested PCR in different intracerebral arteries in control persons and patients with stroke. No significant correlation between the presence of chlamydial DNA or antigens in arteries and stroke could be demonstrated. The presence of the C pneumoniae is indicative of a correlation between infection and atherosclerosis, but not of a specific vascular neuropathology such as stroke.

[Cerebral hematoma caused by mucormycosis]. / Hematoma cerebral causado por mucormicosis.

INTRODUCTION: Invasion of the central nervous system by mucormycosis is rare. It is mainly seen in diabetic ketoacidosis, immunosensitive or severely debilitated patients and in cases of hematological neoplasias. We describe a case of cerebral hemorrhage with documented evidence of invasion of the cerebral vessels by mucormycosis, in a patient with a gastric adenocarcinoma. CLINICAL CASE: A 38 year old woman complained of the sudden onset of headache and disorder of vision which progressed rapidly to coma. Computerized tomography showed the presence of a parieto occipital hematoma. The patient died six hours later. She had had an operation for gastric carcinoma eight months previously. Anatomopathological study of the brain showed invasion of the arterial wall by mucormycosis. CONCLUSION: Solid tumors may lead to cerebral hemorrhage caused by mucormycosis.

Acute isolated cerebral mucormycosis in a patient with high grade non-Hodgkins lymphoma.

A 57-year-old female in complete remission of grade IV non-Hodgkin lymphoma whilst on intensive chemotherapy, suddenly developed unilateral hemispheric stroke with a fatal outcome in 3 days. She was apyrexial and had received antifungal prophylaxis during her treatment. Post-mortem examination showed complete thrombosis of the internal carotid artery leading to infarction in the territory of the middle and anterior cerebral arteries. Microscopic examination of the brain showed involvement of intra-cranial vessel walls and brain parenchyma by mucormyces, with no evidence of systemic mucormycosis. Isolated cerebral mucormycosis is a rare occurrence, more commonly found in intravenous drug abusers, but can occur in patients with haematological malignancy.

Cerebral vasculitis in chronic mucocutaneous candidiasis: autopsy case report.

An autopsy case of chronic mucocutaneous candidiasis (CMCC) is reported here, in which cerebral vasculitis developed in the final stage. A 32-year-old man who had suffered from superficial candidial infection since his childhood was diagnosed as having CMCC. During the past 7 years the patient had developed various associated disorders including insulin-dependent diabetes mellitus (IDDM), common variable immunodeficiency (CVID), candidial esophagitis, multiple digestive tract ulcers and pyothorax. In 1998, at the age of 32, he developed convulsions that were accompanied by impairment of consciousness, and which were temporarily treated with steroid pulsed-medication. Epileptic status associated with widespread cerebral infarctions occurred subsequently, however, and the patient died of sepsis 2 months later. At autopsy, multiple cerebral infarctions and arterial thrombosis were evident. These were histologically proven to be primary vasculitis which was confined solely to the brain, and this was verified by general pathological examination. Thus, some as yet unknown cerebrovascular factors might be involved in the onset of an autoimmune-related vasculitis in patients with a longstanding immunodeficiency state such as CMCC.

Varicella-zoster virus DNA in CSF and arteries in delayed contralateral hemiplegia: evidence for viral invasion of cerebral arteries.

A 78-year-old woman presented with a right basal ganglia infarct 6 weeks after a left herpes zoster ophthalmicus. MR angiography showed focal segmental stenosis of the proximal segments of the anterior, middle, and posterior cerebral arteries. Varicella DNA was detected in the CSF by polymerase chain reaction (PCR). Treated with dexamethasone and acyclovir without improvement, she died 1 month later. There was focal endarteritis in the left anterior, middle, and posterior cerebral arteries at autopsy. Varicella DNA was detected by PCR of extracts from these vessels but not from the arteries on the right side. This study provides further evidence that the vasculopathy after herpes zoster ophthalmicus results from direct viral invasion of the vessel wall.

Neurotropic herpesviruses, neural mechanisms and arteritis.

Cumulative evidence suggests that varicella-zoster virus (VZV) can infect walls of CNS arteries, causing stroke in man. We review observations relating infection with this neurotropic virus to the development of arteritis in the CNS and note evidence supporting the hypothesis that VZV spreads from ganglionic reactivation sites to the arterial wall by neural pathways. Problems relating to the pathogenesis of arteritis and experimental approaches to their solution are suggested.

Delayed contralateral hemiplegia following herpes zoster ophthalmicus: should antiviral therapy be used?

We review clinical virological studies in the syndrome of delayed contralateral hemiplegia following herpes zoster ophthalmicus. Virus could not be isolated from the cerebrospinal fluid (CSF) of the present case, nor was antiviral antibody found in the CSF. There appear to have been no reports of successful virus isolation from the CSF although there are reports of antibody in the spinal fluid. Thus the evidence for ongoing viral replication in the central nervous system is marginal. It is suggested that the sensitive antibody assay against membrane antigens (FAMA) be used in the future as a guide to antiviral therapy.

Acute subdural hematoma and intracerebral hemorrhage. Rare complications of rhinocerebral mucormycosis.

Rhinocerebral mucormycosis is a short-term and often rapidly lethal fungal disease. It is generally seen in uncontrolled cases of diabetes with ketoacidosis. This case exhibits many of the features of a typical fulminating rhinocerebral mucormycosis. However, the fatal complications of acute subdural hematoma and massive intracerebral hemorrhage due to rupture of aneurysm, as demonstrated by angiography, are unique clinical manifestations of patients with rhinocerebral mucormycosis.

Multiple major cerebral artery thromboses with profound thrombocytopenia in acute leukaemia.

A child with acute lymphoblastic leukaemia complicated by prolonged gastrointestinal and skin haemorrhages due to profound thrombocytopenia finally died of thrombotic occlusions of major cerebral arteries due to mucormycosis. Biopsy of any suspect lesion is needed urgently before prolonged therapy with amphotericin B is started. So far there have been no cures in childhood.