Anne T Kloek1, Mercedes Valls Seron1, Ben Schmand2,3, Michael W T Tanck4, Arie van der Ende5,6, Matthijs C Brouwer1, Diederik van de Beek7,8. 1. Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. 2. Department of Medical Psychology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. 3. Department of Psychology, Brain and Cognition, University of Amsterdam, Nieuwe Achtergracht 129 B, 1001 NK, Amsterdam, The Netherlands. 4. Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. 5. Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam Infection and Immunity, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. 6. Department of Medical Microbiology and Infection Prevention, The Netherlands Reference Laboratory for Bacterial Meningitis, Amsterdam Infection and Immunity, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. 7. Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. d.vandebeek@amsterdamumc.nl. 8. Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, PO Box 22660, 1100DD, Amsterdam, The Netherlands. d.vandebeek@amsterdamumc.nl.
Abstract
BACKGROUND: Patients with pneumococcal meningitis are at risk for death and neurological sequelae including cognitive impairment. Functional genetic polymorphisms of macrophage migration inhibitory factor (MIF) alleles have shown to predict mortality of pneumococcal meningitis. METHODS: We investigated whether MIF concentrations during the acute phase of disease were predictive for death in a nationwide prospective cohort study. Subsequently, we studied whether individual ex vivo MIF response years after meningitis was associated with the development of cognitive impairment. RESULTS: We found that in the acute illness of pneumococcal meningitis, higher plasma MIF concentrations were predictive for mortality (p = 0.009). Cognitive impairment, examined 1-5 years after meningitis, was present in 11 of 79 patients after pneumococcal meningitis (14%), as compared to 1 of 63 (2%) in controls, and was consistently associated with individual variability in MIF production by peripheral blood mononuclear cells after ex vivo stimulation with various infectious stimuli. CONCLUSIONS: Our study confirms the role of MIF in poor disease outcome of pneumococcal meningitis. Inter-individual differences in MIF production were associated with long-term cognitive impairment years after pneumococcal meningitis. The present study provides evidence that MIF mediates long-term cognitive impairment in bacterial meningitis survivors and suggests a potential role for MIF as a target of immune-modulating adjunctive therapy.
BACKGROUND:Patients with pneumococcal meningitis are at risk for death and neurological sequelae including cognitive impairment. Functional genetic polymorphisms of macrophage migration inhibitory factor (MIF) alleles have shown to predict mortality of pneumococcal meningitis. METHODS: We investigated whether MIF concentrations during the acute phase of disease were predictive for death in a nationwide prospective cohort study. Subsequently, we studied whether individual ex vivo MIF response years after meningitis was associated with the development of cognitive impairment. RESULTS: We found that in the acute illness of pneumococcal meningitis, higher plasma MIF concentrations were predictive for mortality (p = 0.009). Cognitive impairment, examined 1-5 years after meningitis, was present in 11 of 79 patients after pneumococcal meningitis (14%), as compared to 1 of 63 (2%) in controls, and was consistently associated with individual variability in MIF production by peripheral blood mononuclear cells after ex vivo stimulation with various infectious stimuli. CONCLUSIONS: Our study confirms the role of MIF in poor disease outcome of pneumococcal meningitis. Inter-individual differences in MIF production were associated with long-term cognitive impairment years after pneumococcal meningitis. The present study provides evidence that MIF mediates long-term cognitive impairment in bacterial meningitis survivors and suggests a potential role for MIF as a target of immune-modulating adjunctive therapy.
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