title: Pathogenesis and pathophysiology of pneumococcal meningitis.
abstract: Until the introduction of antibiotics in the 1930s and 1940s, acute bacterial meningitis was fatal in most cases. Since then it has become curable with a variable mortality and morbidity rate for individual pathogens and patients. Neuropathological and clinical studies have shown that a fatal outcome of the disease is often due to central nervous system (CNS) complications including cerebrovascular involvement, brain oedema formation, and hydrocephalus resulting in increased intracranial pressure and seizure activity. During recent years, experimental studies with animal models have substantially increased our knowledge of the interactions of bacterial pathogens with mammalian cells and their entry into the CNS, and the complex pathophysiological mechanisms of brain dysfunction during acute bacterial meningitis. There is now a substantial body of evidence that cytokines, chemokines, proteolytic enzymes, and oxidants are involved in the inflammatory cascade that leads to tissue destruction in bacterial meningitis. Genetic targeting and/or pharmacological blockade of these pathways was beneficial in experimental bacterial meningitis. Apart from dexamethasone, these treatment strategies hold major promise for the adjunctive therapy of acute bacterial meningitis in clinical practice.
authors.affiliation: UK and H-WP are at the Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany
authors.forename: Uwe
authors.initials: U
authors.lastname: Koedel
authors.forename: William Michael
authors.initials: WM
authors.lastname: Scheld
authors.forename: Hans-Walter
authors.initials: HW
authors.lastname: Pfister
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D004198:Disease Susceptibility; D006801:Humans; D008586:Meningitis, Pneumococcal / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology*; D011379:Prognosis; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology
chemical_list: D016207:Cytokines