Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased permeability of the blood-brain barrier (BBB) is important in neurological disorders. Neuroinflammation is associated with increased BBB breakdown and brain injury. Tumor necrosis factor (TNF)-alpha is involved in BBB injury and edema formation through a mechanism involving matrix metalloproteinase (MMP) up-regulation. There is emerging evidence indicating that cyclooxygenase (COX) inhibition limits BBB disruption following ischemic stroke and bacterial meningitis, but the mechanisms involved are not known. We used intracerebral injection of TNF-alpha to study the effect of COX inhibition on TNF-alpha-induced BBB breakdown, MMP expression/activity, and oxidative stress. BBB disruption was evaluated by the uptake of (14)C-sucrose into the brain and by magnetic resonance imaging utilizing gadolinium-diethylenetriaminepentaacetic acid as a paramagnetic contrast agent. Using selective inhibitors of each COX isoform, we found that COX-1 activity is more important than COX-2 in BBB opening. TNF-alpha induced a significant up-regulation of gelatinase B (MMP-9), stromelysin-1 (MMP-3), and COX-2. In addition, TNF-alpha significantly depleted glutathione as compared with saline. Indomethacin (10 mg/kg i.p.), an inhibitor of COX-1 and COX-2, reduced BBB damage at 24 h. Indomethacin significantly attenuated MMP-9 and MMP-3 expression and activation and prevented the loss of endogenous radical scavenging capacity following intracerebral injection of TNF-alpha. Our results show for the first time that BBB disruption during neuroinflammation can be significantly reduced by administration of COX inhibitors. Modulation of COX in brain injury by COX inhibitors or agents modulating prostaglandin E(2) formation/signaling may be useful in clinical settings associated with BBB disruption.
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PMID:Cyclooxygenase inhibition limits blood-brain barrier disruption following intracerebral injection of tumor necrosis factor-alpha in the rat. 1770 56

The central nervous system (CNS) has long been regarded as an immune privileged organ implying that the immune system avoids the CNS not to disturb its homeostasis, which is critical for proper function of neurons. Meanwhile, it is accepted that immune cells do in fact gain access to the CNS and that immune responses are mounted within this tissue. However, the unique CNS microenvironment strictly controls these immune reactions starting with tightly regulating immune cell entry into the tissue. The endothelial blood-brain barrier (BBB) and the epithelial blood-cerebrospinal fluid (CSF) barrier control immune cell entry into the CNS, which is rare under physiological conditions. During a variety of pathological conditions of the CNS such as viral or bacterial infections, or during inflammatory diseases such as multiple sclerosis (MS), immunocompetent cells readily traverse the BBB and subsequently enter the CNS parenchyma. Most of our current knowledge on the molecular mechanisms involved in immune cell entry into the CNS has been derived from studies performed in experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Thus, a large part of our current knowledge on immune cell entry across the BBBs is based on the results obtained in this animal model. Similarly, knowledge on the benefits and potential risks associated with therapeutic targeting of immune cell recruitment across the BBB in human diseases are mostly derived from such treatment regimen in MS. Other mechanisms of immune cell entry into the CNS might therefore apply under different pathological conditions such as bacterial meningitis or stroke and need to be considered.
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PMID:Therapeutic targeting of leukocyte trafficking across the blood-brain barrier. 1822 Sep 56

Bacterial meningitis and viral encephalitis are life-threatening infections with high mortality rates. Patients who survive these infections often remain permanently disabled. Potential neurologic complications requiring careful attention include impaired consciousness, elevated intracranial pressure (ICP), hydrocephalus, stroke, and seizures. Systemic complications are also common and are frequently the immediate cause of death. The importance of emergent administration of appropriate antimicrobial therapy cannot be overstated, but critical care of these patients should focus not only on treatment of the underlying infection and its immediate complications but also on minimizing secondary brain injury. Given the increasing complexity of the diagnostic and therapeutic modalities available to manage central nervous system (CNS) infections, the involvement of neurocritical care units and neurointensivists may be particularly helpful in improving outcomes. It is our opinion that ICP measurement should be strongly considered in selected patients with CNS infections, particularly those who are comatose. Treatments for intracranial hypertension, specifically in the setting of CNS infection, are described in this paper. For bacterial meningitis, intravenous dexamethasone should be administered, beginning concomitantly with the initial dose of antibiotics, at least until Streptococcus pneumoniae can be excluded as a pathogen. Clinicians should maintain a high index of suspicion for nonconvulsive seizures. Deterioration in neurologic status should also prompt early use of CT or magnetic resonance angiography and venography to exclude cerebrovascular complications.
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PMID:Neurocritical care of patients with central nervous system infections. 1857 24

Infections of the central nervous system are a frequent cause for admission to the intensive care unit (ICU). These infections can be the reason for presentation to a hospital or a complication of an injury or surgical procedure. Diagnosing these infections can be very challenging, given the relative paucity of tests with high sensitivity and specificity. Regardless, identifying and treating the underlying cause remains the primary objective in each of these cases, but management of complications is the most common reason for ICU admission. Frequent complications include increased intracranial pressure, stroke, coma, and status epilepticus. Although the underlying infection often causes harm, the immune response to the agent and ensuing complications are often responsible for greater damage to the host. Even if the underlying infectious agent does not have a specific therapy, identifying it is important for limiting unnecessary testing. When certain infections are suspected, such as bacterial meningitis or viral encephalitis, empiric therapy should be initiated immediately. Outcomes for these conditions are linked to how quickly appropriate therapies are initiated.
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PMID:Central nervous system infections in the intensive care unit. 1911 74

There is paucity of data evaluating intracranial pressure (ICP) rise and its management in acute viral encephalitis (AVE). Noteworthy is the current prevalence of unselective and broad utilization of ICP lowering therapies in clinical practice. Trends in current management of ICP in AVE emanate from data extrapolated from results of studies done on cerebral malaria, bacterial meningitis, stroke, and brain trauma patients. In this article we review (1) clinical correlates of raised ICP, (2) pathology, (3) imaging data, (4) monitoring, and, (5) treatment, of raised ICP in AVE. ICP monitoring is a useful adjunct to management of raised ICP in adults, becoming especially important in Herpes encephalitis and encephalitis with status epilepticus. In children it substantially influences clinical management and continuous monitoring of mean blood pressure (MBP) and ICP can aid in early diagnosis and treatment when cerebral perfusion pressure (CPP) falls below critical levels. Current evidence suggests that the pathomechanisms that contribute to the development of raised intracranial pressure vary in viral encephalitides of different etiology, and different forms of cerebral edema result at different times in the course of the illness, thus creating a need for studies to investigate the usefulness of various edema-specific ICP lowering modalities in AVE.
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PMID:Raised intracranial pressure in acute viral encephalitis. 1937 1

Bacterial meningitis remains a major cause of death and neurological and hearing sequels. In adults, the death rate ranges from 16 to 37% in meningitis due to Pneumococcus pneumoniae and neurological sequels occur in 30 to 52% of survivors. In childhood, the prognosis is better, with a death rate ranging from 2 to 15%, higher for Pneumococcus pneumoniae. Seventy-five percent of children survive without any sequel, 15% with hearing disorders (up to 30% with Pneumococcus), and rarely (3-4%) present with mental retardation, motor deficit, or epilepsy. In addition to the type of germ, the risk of sequels is six times higher in case of Pneumococcus, several factors of poor prognosis are described on admission: degree of coma, neurological deficit, cranial nerve palsy, high protein level, high erythrocytes count and low leukocytes count in CSF (less than 600 or 1000 leukocytes per microliter). Any neurological complication such as epilepsy, stroke, brain edema, hydrocephalus, or hemodynamic failure will be correlated to a poor outcome. Hearing must be tested within 15 days, followed by audiologic consultation and MRI focused on labyrinths to detect early onset cochlear ossification. One year after meningitis, behavior and cognitive skills must be assessed, including IQ, memory, attention and executive functions, adaptive abilities, to set up specific educative and teaching strategies.
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PMID:[Long-term follow-up of bacterial meningitis - sequels in children and adults: incidence, type, and assessment issues]. 1939 75

In a wide variety of acute and chronic central nervous system (CNS) disorders, inflammatory processes contribute to the damage of brain cells and progression of the disease. Along with other regulatory cytokines, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is involved in the pathology of multiple sclerosis (MS) and murine experimental autoimmune encephalomyelitis (EAE), bacterial meningitis (BM), HIV encephalitis (HIVE), stroke and Alzheimer's disease (AD). In these conditions, TRAIL is released within the brain mainly by activated microglia and leukocytes infiltrating from the blood stream. TRAIL promotes apoptosis of parenchymal cells in MS/EAE, HIVE, AD and stroke through interaction with TRAIL death receptors expressed on these cells. Frequently, cells in the diseased brain display increased susceptibility to apoptosis induction by TRAIL due to upregulation of death receptors and downregulation of decoy receptors. On the other hand, TRAIL inhibits the proliferation of encephalitogenic T cells in EAE, and it is involved in the clearance of infected brain macrophages in HIVE and of activated neutrophils in BM by interaction with their death receptors. Especially in BM, the ability of TRAIL to limit an acute granulocyte-driven inflammation carries significant neuroprotective potential. Given the diversity of beneficial and harmful effects in the immune and nervous system, TRAIL is a double-edged sword in diseases involving CNS inflammation.
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PMID:Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in central nervous system inflammation. 1944 43

The clinical features, investigations, treatment and outcome were studied in 104 patients with definite or probable tuberculous meningitis. The diagnosis of definite tuberculous meningitis required the growth of Mycobacterium tuberculosis from cultures, or a positive polymerase chain reaction (PCR) assay for M. tuberculosis. In probable tuberculous meningitis, cultures and the PCR assay were negative, but other causes of meningitis were excluded and there was a response to anti-tuberculosis treatment. Of the 104 patients, 36% had a poor outcome (severe disability, persistent vegetative state or death), 12% moderate disability and 52% good recovery. A diagnosis of definite tuberculous meningitis, the severity of the symptoms at presentation and the occurrence of a stroke were significant predictors of a poor outcome. The most common reasons for a delayed diagnosis were presentation with mild symptoms wrongly attributed to a systemic infection, incorrectly attributing CSF abnormalities to non-tuberculous bacterial meningitis and failure to diagnose extraneural tuberculosis associated with meningitis. Recognition of the difficulties in making a diagnosis of tuberculous meningitis may facilitate earlier diagnosis in the future.
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PMID:A review of tuberculous meningitis at Auckland City Hospital, New Zealand. 2060 61

Neonatal group B streptococcus meningitis causes neurologic morbidity and mortality. Cerebrovascular involvement is a common, poorly studied, and potentially modifiable pathologic process. We hypothesized that imaging patterns of focal brain infarction are recognizable in neonatal group B streptococcal meningitis. A consecutive case series included term neonates with the following: (1) bacterial meningitis, (2) acute group B streptococcal infection (positive cerebrospinal fluid/blood culture), (3) brain magnetic resonance imaging within 14 days, and (4) acute intraparenchymal focal infarctions (restricted diffusion). Lesions within known arterial territories were classified as arterial ischemic stroke. Clinical presentations, investigations, and neurologic outcomes were recorded. Eight newborns (50% female) with focal infarction were identified. Five presented early (<1 week), and all manifested clinical shock and elevated acute-phase reactants. Less than 50% had prenatal group B streptococcal screening, while 2 of 3 screened were negative. Two distinct patterns of focal infarction were identified: (1) deep perforator arterial stroke to basal ganglia, thalamus, and periventricular white matter (7/8, 88%), and (2) superficial injury with patchy, focal infarctions of the cortical surface (6/8, 75%). Outcomes (mean 23.8 months) were poor, with severe disability or death in 6/8 (75%). Recognizable stroke patterns contribute to severe neurologic outcomes and represent a potentially modifiable pathophysiologic process in neonatal group B streptococcal meningitis.
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PMID:Stroke patterns in neonatal group B streptococcal meningitis. 2139 70

We describe unusual delayed recurrent episodes of ischemic stroke in a patient with initial good recovery from pneumococcal meningitis due to progressive arterial stenosis for over 3 months. We postulate that any of the following may have been responsible for his condition: widespread cerebral vasculopathy due to the effects of purulent material bathing the base of the brain, an immune-mediated para-infectious condition, or a rebound effect of the primary inflammatory reaction that was initially suppressed by dexamethasone. This case demonstrates that progressive arterial stenosis can evolve months after bacterial meningitis and should be recognized as a potential vascular complication.
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PMID:Delayed recurrent ischemic stroke after initial good recovery from pneumococcal meningitis. 2244 77


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