PATHOGENESIS OF BACTERIAL MENINGITIS

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Bacterial meningitis is the most common serious infection of the central nervous system. Infection of the subarachnoid space leads to cerebrospinal fluid (CSF) inflammation, meningeal irritation, and the clinical triad of headache, fever, and meningismus. Approximately 10,000 cases of bacterial meningitis occur each year in the United States, whereas other parts of the world have substantially higher incidences.72 Even when treated with highly effective antibiotics, the disease is fatal in 5% to 40% of the patients and causes neurologic sequelae in up to 30% of the survivors.5, 28

Neurologic sequelae from bacterial meningitis can be grouped into three categories: (1) hearing impairment, which is most commonly the result of direct invasion of the inner ear by the subarachnoid space inflammation; (2) obstructive hydrocephalus; and (3) damage to the brain parenchyma, leading to neurologic sequelae such as focal sensory-motor deficits, mental retardation, and seizure disorders.5, 28

Over the last 3 decades, it has become clear that the multiplication of bacteria within the central nervous system (CNS) compartment triggers a host response with an overshooting progression of inflammation. Some of the inflammatory and neurotoxic mediators involved in the processes leading to neuronal injury during meningitis have been identified in recent years.81, 84 As a result, the therapeutic approach to bacterial meningitis has widened from eradicating the bacterial pathogen with antibiotics to attenuation of the detrimental effects of host defenses. Corticosteroids represent an example of the therapeutic strategies aimed at modulating and decreasing inflammation in bacterial meningitis.46 This article reviews current concepts of the pathophysiology of the disease with an emphasis on possible therapeutic strategies to prevent brain damage.

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PATHOGENESIS OF BACTERIAL MENINGITIS

The development of bacterial meningitis progresses through four interconnected phases: (1) bacterial invasion of the host with subsequent infection of the CNS; (2) bacterial multiplication and induction of inflammation in the subarachnoid and ventricular space; (3) progression of inflammation with associated pathophysiologic alterations; and (4) development of neuronal damage (Fig. 1). The structure of this review follows this conceptual framework.

References (98)

  • J. Mertsola

    Cytokines in the pathogenesis of bacterial meningitis

    Trans R Soc Trop Med Hyg

    (1991)
  • G.A. Rosenberg et al.

    Tumor necrosis factor-alpha-induced gelatinase B causes delayed opening of the blood-brain barrier: An expanded therapeutic window

    Brain Res

    (1995)
  • H. Sprenger et al.

    Chemokines in the cerebrospinal fluid of patients with meningitis

    Clin Immunol Immunopathol

    (1996)
  • J.F. Stover et al.

    Cerebrospinal fluid hypoxanthine, xanthine and uric acid levels may reflect glutamate-mediated excitotoxicity in different neurological diseases

    Neurosci Lett

    (1997)
  • K. Sugiyama et al.

    Glial uptake of excitatory amino acids influences neuronal survival in cultures of mouse hippocampus

    Neuroscience

    (1989)
  • M. Unhanand et al.

    Gram-negative enteric bacillary meningitis: A twenty-one-year experience

    J Pediatr

    (1993)
  • M. Virji

    Meningococcal disease: Epidemiology and pathogenesis

    Trends Microbiol

    (1996)
  • J.R. Weber et al.

    Histamine (H1) receptor antagonist inhibits leukocyte rolling in pial vessels in the early phase of bacterial meningitis in rats

    Neurosci Lett

    (1997)
  • P.B. Andersson et al.

    Intracerebral injection of proinflammatory cytokines or leukocyte chemotaxins induces minimal myelomonocytic cell recruitment to the parenchyma of the central nervous system

    J Exp Med

    (1992)
  • M. Arditi et al.

    Lipopolysaccharide stimulates the tyrosine phosphorylation of mitogen-activated protein kinases p44, p42, and p41 in vascular endothelial cells in a soluble CD14-dependent manner. Role of protein tyrosine phosphorylation in lipopolysaccharide-induced stimulation of endothelial cells

    J Immunol

    (1995)
  • L.J. Baraff et al.

    Outcomes of bacterial meningitis in children: A meta-analysis

    Pediatr Infect Dis J

    (1993)
  • J.S. Beckman et al.

    Nitric oxide, superoxide, and peroxynitrite: The good, the bad, and ugly

    Am J Physiol

    (1996)
  • R.A. Black et al.

    A metalloproteinase disintegrin that releases tumor-necrosis factor-alpha from cells

    Nature

    (1997)
  • A.L. Blank et al.

    Acute Streptococcus pneumoniae meningogenic labyrinthitis. An experimental guinea pig model and literature review

    Arch Otolaryngol Head Neck Surg

    (1994)
  • I. Bogdan et al.

    Tumor necrosis factor-alpha contributes to apoptosis in hippocampal neurons during experimental group B streptococcal meningitis

    J Infect Dis

    (1997)
  • A.J. Bruce et al.

    Beta-amyloid toxicity in organotypic hippocampal cultures: Protection by Euk-8, a synthetic catalytic free radical scavenger

    Proc Natl Acad Sci U S A

    (1996)
  • M. Burroughs et al.

    Bacterial components and the pathophysiology of injury to the blood-brain barrier: Does cell wall add to the effects of endotoxin in gram-negative meningitis

    J Infect Dis

    (1992)
  • B.L. Buster et al.

    Potential role of nitric oxide in the pathophysiology of experimental bacterial meningitis in rats

    Infect Immun

    (1995)
  • H. Cairns et al.

    Cerebral arteritis and phlebitis in pneumococcal meningitis

    J Pathol

    (1946)
  • J.M. Carney et al.

    Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone

    Proc Natl Acad Sci U S A

    (1991)
  • K.J. Carroll et al.

    A prospective investigation of the long-term auditory-neurological sequelae associated with bacterial meningitis: A study from Vanuatu

    J Tropical Medicine and Hygiene

    (1994)
  • P.H. Chan et al.

    Pathogenesis of vasogenic edema in focal cerebral ischemia. Role of superoxide radicals

    Adv Neurol

    (1990)
  • J.A. Clemens et al.

    Global ischemia activates nuclear factor-kappa B in forebrain neurons of rats

    Stroke

    (1997)
  • M.C. Cohen et al.

    Cytokine function, a study in biologic diversity

    Am J Clin Pathol

    (1996)
  • de VriesF.P. et al.

    Invasion of primary nasopharyngeal epithelial cells by Neisseria meningitidis is controlled by phase variation of multiple surface antigens

    Infect Immun

    (1996)
  • S.L. Free et al.

    Bilateral hippocampal volume loss in patients with a history of encephalitis or meningitis

    Epilepsia

    (1996)
  • A.J. Gearing et al.

    Processing of tumor necrosis factor-alpha precursor by metalloproteinases

    Nature

    (1994)
  • K. Gijbels et al.

    Reversal of experimental autoimmune encephalomyelitis with a hydroxamate inhibitor of matrix metalloproteases

    J Clin Invest

    (1994)
  • A. Glabinski et al.

    Tumor necrosis factor-alpha induced pathology in the rat brain: Characterization of stereotaxic injection model

    Folia Neuropathol

    (1998)
  • P.E. Gottschall et al.

    Regulation of matrix metalloproteinase expressions in astrocytes, microglia and neurons

    Neuroimmunomodulation

    (1996)
  • B.M. Greenwood

    The epidemiology of acute bacterial meningitis in tropical Africa

  • K. Grimwood et al.

    Adverse outcomes of bacterial meningitis in school-age survivors

    Pediatrics

    (1995)
  • L. Guerra-Romero et al.

    Amino acids in cerebrospinal and brain interstitial fluid in experimental pneumococcal meningitis

    Pediatr Res

    (1993)
  • K.S. Kim et al.

    The K1 capsule is the critical determinant in the development of Escherichia coli meningitis in the rat

    J Clin Invest

    (1992)
  • U. Koedel et al.

    Experimental pneumococcal meningitis: Cerebrovascular alterations, brain edema, and meningeal inflammation are linked to the production of nitric oxide

    Ann Neurol

    (1995)
  • U. Koedel et al.

    Increased endothelin levels in cerebrospinal fluid samples from adults with bacterial meningitis

    Clin Infect Dis

    (1997)
  • Pfister LA, Leib SL, Weinmann O, et al: The endothelin receptor antagonist bosentan is neuroprotective in experimental...
  • S.L. Leib et al.

    Inducible nitric oxide synthase and the effect of aminoguanidine in experimental neonatal meningitis

    J Infect Dis

    (1998)
  • S.L. Leib et al.

    Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci

    J Clin Invest

    (1996)

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    Address reprint requests to Stephen L. Leib, MD, Institute for Medical Microbiology, University of Bern, Friedbühlstrasse 51, 3010 Bern, Switzerland, e-mail: [email protected]

    This work was supported by Grants from the National Institutes of Health (NS34028 and NS35902) and from the Swiss National Science Foundation (NFPNR 38: 4038-52841)

    *

    Institute for Medical Microbiology, University of Bern, Bern, Switzerland

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