Brain infection with Staphylococcus aureus leads to high extracellular levels of glutamate, aspartate, γ-aminobutyric acid, and zinc.

Staphylococcal brain infections may cause mental deterioration and epileptic seizures, suggesting interference with normal neurotransmission in the brain. We injected Staphylococcus aureus into rat striatum and found an initial 76% reduction in the extracellular level of glutamate as detected by microdialysis at 2 hr after staphylococcal infection. At 8 hr after staphylococcal infection, however, the extracellular level of glutamate had increased 12-fold, and at 20 hr it had increased >30-fold. The extracellular level of aspartate and γ-aminobutyric acid (GABA) also increased greatly. Extracellular Zn(2+) , which was estimated at ∼2.6 µmol/liter in the control situation, was increased by 330% 1-2.5 hr after staphylococcal infection and by 100% at 8 and 20 hr. The increase in extracellular glutamate, aspartate, and GABA appeared to reflect the degree of tissue damage. The area of tissue damage greatly exceeded the area of staphylococcal infiltration, pointing to soluble factors being responsible for cell death. However, the N-methyl-D-aspartate receptor antagonist MK-801 ameliorated neither tissue damage nor the increase in extracellular neuroactive amino acids, suggesting the presence of neurotoxic factors other than glutamate and aspartate. In vitro staphylococci incubated with glutamine and glucose formed glutamate, so bacteria could be an additional source of infection-related glutamate. We conclude that the dramatic increase in the extracellular concentration of neuroactive amino acids and zinc could interfere with neurotransmission in the surrounding brain tissue, contributing to mental deterioration and a predisposition to epileptic seizures, which are often seen in brain abscess patients.

Hyperoxic resuscitation after hypoxia-ischemia induces cerebral inflammation that is attenuated by tempol in a reporter mouse model with very young mice.

BACKGROUND: Oxygen supplementation is still part of international resuscitation protocols for premature children. Mechanisms for tissue damage by hypoxia/ischemia in the extreme premature involve inflammation. AIM AND METHOD: To study cerebral inflammation after hypoxia/ischemia and oxygen treatment in the premature, we measured NF-κB activity in 5-day-old transgenic reporter mice in response to experimental hypoxia/ischemia. results were correlated to cerebral histological evaluation and plasma cytokine levels. A treatment strategy with the antioxidant tempol was tested. RESULTS: One day after hypoxia/ischemia NF-κB activation was increased compared to controls [mean difference: 10.6±4.6% (P=0.03)]. Exposure to 100% oxygen after hypoxia/ischemia further increased NF-κB activation compared to hypoxia/ischemia alone [mean difference: 15.0±5.5% (P=0.01)]. Histological changes in the brain were positively correlated with NF-κB activity (P<0.001), but we found no significant difference in tissue damage between resuscitation with air and resuscitation with pure oxygen. Administration of tempol reduced NF-κB activation [mean difference: 14.6±5.0% (P=0.01)] and the plasma level of cytokines; however, the histological damage score was not affected. CONCLUSION: Cerebral inflammatory response after hypoxia/ischemia in a mouse model with immature brain development corresponding to human prematurity prior to 32 weeks' gestation was influenced by administration of oxygen. Tempol treatment attenuated inflammation but did not reduce the extent of histological cerebral damage.

Vaccine Induced Immune Thrombotic Thrombocytopenia Causing a Severe Form of Cerebral Venous Thrombosis With High Fatality Rate: A Case Series.

During a 2-week period, we have encountered five cases presenting with the combination of cerebral venous thrombosis (CVT), intracerebral hemorrhage and thrombocytopenia. A clinical hallmark was the rapid and severe progression of disease in spite of maximum treatment efforts, resulting in fatal outcome in for 4 out of 5 patients. All cases had received ChAdOx1 nCov-19 vaccine 1-2 weeks earlier and developed a characteristic syndrome thereafter. The rapid progressive clinical course and high fatality rate of CVT in combination with thrombocytopenia in such a cluster and in otherwise healthy adults is a recent phenomenon. Cerebral autopsy findings were those of venous hemorrhagic infarctions and thrombi in dural venous sinuses, including thrombus material apparently rich in thrombocytes, leukocytes and fibrin. Vessel walls were free of inflammation. Extra-cerebral manifestations included leech-like thrombi in large veins, fibrin clots in small venules and scattered hemorrhages on skin and membranes. CVT with thrombocytopenia after adenovirus vectored COVID-19 vaccination is a new clinical syndrome that needs to be recognized by clinicians, is challenging to treat and seems associated with a high mortality rate.

A Middle-Aged Man Presenting With Progressive Heart Failure, Myopathy, and Monoclonal Gammopathy of Uncertain Significance.

A 48-year-old man presented with rapidly progressive heart failure and monoclonal gammopathy of uncertain significance. No specific cause was detected on endomyocardial biopsy. As the heart failure worsened, he also developed progressive skeletal myopathy. This provided the clue to the diagnosis, and cardiac function recovered rapidly with cause-directed therapy. (Level of Difficulty: Intermediate.).

Benign Sphenoid Wing Meningioma Presenting with an Acute Intracerebral Hemorrhage - A Case Report.

BACKGROUND AND STUDY OBJECT: We report an unusual case of a benign lateral sphenoid wing meningioma that presented with, and was masked by, an acute intracerebral hemorrhage. CASE REPORT: A 68-year-old woman was admitted after sudden onset of coma. Computed tomography (CT) revealed an intracerebral hemorrhage, without any underlying vascular pathology on CT angiography. During the surgery, we found a lateral sphenoid wing meningioma with intratumoral bleeding that extended into the surrounding brain parenchyma. RESULTS: We removed the hematoma and resected the tumor completely in the same session. The histopathological classification of the tumor was a WHO grade I meningothelial meningioma. The patient recovered very well after surgery, without significant neurological sequelae. CONCLUSIONS: Having reviewed the relevant references from the medical literature, we consider this event as an extremely rare presentation of a benign sphenoid wing meningioma in a patient without any predisposing medical factors. The possible mechanisms of bleeding from this tumor type are discussed.

Fatal primary amoebic meningoencephalitis in a Norwegian tourist returning from Thailand.

INTRODUCTION: Primary amoebic meningoencephalitis (PAM) is a rare disease caused by the free-living amoeba Naegleria fowleri. Infection occurs by insufflation of water containing amoebae into the nasal cavity, and is usually associated with bathing in freshwater. Nasal irrigation is a more rarely reported route of infection. CASE PRESENTATION: A fatal case of PAM in a previously healthy Norwegian woman, acquired during a holiday trip to Thailand, is described. Clinical findings were consistent with rapidly progressing meningoencephalitis. The cause of infection was discovered by chance, owing to the unexpected detection of N. fowleri DNA by a PCR assay targeting fungi. A conclusive diagnosis was established based on sequencing of N. fowleri DNA from brain biopsies, supported by histopathological findings. Nasal irrigation using contaminated tap water is suspected as the source of infection. CONCLUSION: The clinical presentation of PAM is very similar to severe bacterial meningitis. This case is a reminder that when standard investigations fail to identify a cause of infection in severe meningoencephalitis, it is of crucial importance to continue a broad search for a conclusive diagnosis. PAM should be considered as a diagnosis in patients with symptoms of severe meningoencephalitis returning from endemic areas.

Neuropathological findings in 9 cases of listeria monocytogenes brain stem encephalitis.

Brain stem encephalitis is a particular manifestation of infection with the bacterium Listeria monocytogenes. Here, we present the neuropathological findings in 9 such cases. In the brain stem, the inflammatory infiltrates were located predominantly within nuclei and tracts of cranial nerves innervating the oropharynx. These findings support the hypothesis that the food-borne bacterium Listeria monocytogenes invades the brain stem along cranial nerves.

Staphylococcal α-hemolysin is neurotoxic and causes lysis of brain cells in vivo and in vitro.

Formation of a bacterial brain abscess entails loss of brain cells and formation of pus. The mechanisms behind the cell loss are not fully understood. Staphylococcus aureus, a common cause of brain abscesses, produces various exotoxins, including α-hemolysin, which is an important factor in brain abscess formation. α-Hemolysin may cause cytolysis by forming pores in the plasma membrane of various eukaryotic cells. However, whether α-hemolysin causes lysis of brain cells is not known. Nor is it known whether α-hemolysin in the brain causes cell death through pore formation or by acting as a chemoattractant, recruiting leukocytes and causing inflammation. Here we show that α-hemolysin injected into rat brain causes cell damage and edema formation within 30 min. Cell damage was accompanied by an increase in extracellular concentrations of zinc, GABA, glutamate, and other amino acids, indicating plasma membrane damage, but leukocytic infiltration was not seen 0.5-12h after α-hemolysin injection. This was in contrast to injection of S. aureus, which triggered extensive infiltration with neutrophils within 8h. In vitro, α-hemolysin caused concentration-dependent lysis of isolated nerve endings and cultured astrocytes. We conclude that α-hemolysin contributes to the cell death inherent in staphylococcal brain abscess formation as a pore-forming neurotoxin.

Listeriosis in Norway 1977-2003.

In Europe, the incidence of invasive listeriosis has increased substantially during the last decades. We here present data from 289 listeriosis cases reported in Norway during the period 1977-2003, of which 12 cases were associated with 2 outbreaks and 39 cases were pregnancy-related. Medical records were obtained from 209 cases with listeriosis reported in 1977-2000. While the incidence of pregnancy-related listeriosis has remained stable at an average rate of 34 per million pregnant women per y during the period, the incidence of sporadic, non-pregnancy-related cases has increased from 1.1 to 3.7 per million per y. The present Norwegian incidence of reported cases is lower than in Denmark, but the case fatality rate is higher, indicating a possible under-reporting of mild listeriosis cases in Norway. We discuss how preventive measures, case identification and surveillance may have influenced listeriosis incidence in Norway.

Brain stem encephalitis in listeriosis.

Serious infection with the bacterium L. monocytogenes mainly manifests as sepsis and/or meningitis. A particular entity is Listeria brain stem encephalitis, which is characterized by progressive brain stem deficits. The condition is fatal unless early treated. The purpose of the present study was to assess the incidence of brain stem encephalitis in a population-based listeriosis material. Medical records from 212 of the 240 patients with serious listeriosis reported in Norway from 1977 to 2000, as well as autopsy material from 8 of these patients, were available. This material was searched for clinical and neuropathological evidence of brain stem infection. Findings indicating brain stem encephalitis were present in 19 of the 172 patients with adult listeriosis (11%) but none of the 40 pregnancy-related listeriosis cases. None of the 19 patients had been diagnosed with Listeria brain stem infection originally. We conclude that brain stem encephalitis is relatively common in this Norwegian listeriosis material.