Vol 53, No 4 (2019)
Invited Review Article
Published online: 2019-08-21

open access

Page views 5077
Article views/downloads 4326
Get Citation

Connect on Social Media

Connect on Social Media

Acute bacterial meningitis and stroke

Jason L. Siegel1
Pubmed: 31441497
Neurol Neurochir Pol 2019;53(4):242-250.

Abstract

Introduction. Acute bacterial meningitis remains a common disease, especially in developing countries. Although advances over the last century have improved mortality and morbidity, the neurological adverse effects remain high. Specifically, acute ischaemic stroke is a serious comorbidity that represents both disease severity and poor prognosis. This review presents the clinical connection between meningitis and stroke, and discusses the neuroinflammatory components that have direct ties between these diseases. State of the art. Ischaemic stroke is the direct result of the inflammatory response produced to eradicate infectious pathogens. Bacterial virulence factors and pathogen-associated molecular patterns cause direct damage to the blood-brain barrier and trigger leukocytes to react to the infection. Cytokines are released that cause further destruction of the blood-brain barrier, lead to neuronal death, and recruit the prothrombotic effects of the coagulation cascade through the complement system. Unfortunately, this inflammatory response causes vasculopathy and hypercoagulation of the cerebral blood vessels, leading to cerebral ischaemia. Clinical implications. Pharmacological attempts to mitigate this inflammatory response have produced both positive and negative results. On the one hand, corticosteroids have been shown to improve mortality if given early in patients with bacterial meningitis, particularly pneumococcal meningitis. On the other hand, corticosteroids have been linked to delayed cerebral infarction and other adverse effects. Future directions. New targets for specific inflammatory markers have shown success in rodent models, but have not yet been proven beneficial in humans. Genetic markers are on the horizon, and may serve as individualised targets for diagnosis and therapy.

Article available in PDF format

View PDF Download PDF file

References

  1. Brouwer MC, van de Beek D. Epidemiology of community-acquired bacterial meningitis. Curr Opin Infect Dis. 2018; 31(1): 78–84.
  2. Adriani KS, Brouwer MC, van de Beek D. Risk factors for community-acquired bacterial meningitis in adults. Neth J Med. 2015; 73(2): 53–60.
  3. Palmgren H. Meningococcal disease and climate. Glob Health Action. 2009; 2.
  4. Schwentker FF, Gelman S, Long PH. Landmark article April 24, 1937. The treatment of meningococcic meningitis with sulfanilamide. Preliminary report. By Francis F. Schwentker, Sidney Gelman, and Perrin H. Long. JAMA. 1984; 251(6): 788–790.
  5. Pfister HW, Feiden W, Einhäupl KM. Spectrum of complications during bacterial meningitis in adults. Results of a prospective clinical study. Arch Neurol. 1993; 50(6): 575–581.
  6. Kastenbauer S, Pfister HW. Pneumococcal meningitis in adults: spectrum of complications and prognostic factors in a series of 87 cases. Brain. 2003; 126(Pt 5): 1015–1025.
  7. van de Beek D, de Gans J, Spanjaard L, et al. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med. 2004; 351(18): 1849–1859.
  8. Buchholz G, Koedel U, Pfister HW, et al. Dramatic reduction of mortality in pneumococcal meningitis. Crit Care. 2016; 20(1): 312.
  9. Brouwer MC, McIntyre P, Prasad K, et al. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2015(9): CD004405.
  10. Brouwer MC, Heckenberg SGB, de Gans J, et al. Nationwide implementation of adjunctive dexamethasone therapy for pneumococcal meningitis. Neurology. 2010; 75(17): 1533–1539.
  11. Vergouwen MDI, Schut ES, Troost D, et al. Diffuse cerebral intravascular coagulation and cerebral infarction in pneumococcal meningitis. Neurocrit Care. 2010; 13(2): 217–227.
  12. Schut ES, Lucas MJ, Brouwer MC, et al. Cerebral infarction in adults with bacterial meningitis. Neurocrit Care. 2012; 16(3): 421–427.
  13. Pfister HW, Borasio GD, Dirnagl U, et al. Cerebrovascular complications of bacterial meningitis in adults. Neurology. 1992; 42(8): 1497–1504.
  14. Katchanov J, Heuschmann PU, Endres M, et al. Cerebral infarction in bacterial meningitis: predictive factors and outcome. J Neurol. 2010; 257(5): 716–720.
  15. Klein M, Koedel U, Pfefferkorn T, et al. Arterial cerebrovascular complications in 94 adults with acute bacterial meningitis. Crit Care. 2011; 15(6): R281.
  16. Weisfelt M, Determann RM, de Gans J, et al. Procoagulant and fibrinolytic activity in cerebrospinal fluid from adults with bacterial meningitis. J Infect. 2007; 54(6): 545–550.
  17. Lucas MJ, Brouwer MC, van de Beek D. Delayed cerebral thrombosis in bacterial meningitis: a prospective cohort study. Intensive Care Med. 2013; 39(5): 866–871.
  18. Morris NA, Matiello M, Lyons JL, et al. Neurologic complications in infective endocarditis: identification, management, and impact on cardiac surgery. Neurohospitalist. 2014; 4(4): 213–222.
  19. Dickerman SA, Abrutyn E, Barsic B, et al. ICE Investigators. The relationship between the initiation of antimicrobial therapy and the incidence of stroke in infective endocarditis: an analysis from the ICE Prospective Cohort Study (ICE-PCS). Am Heart J. 2007; 154(6): 1086–1094.
  20. Cunha BA, Jimada I, Chawla K. Intracranial complications of acute bacterial endocarditis. Surg Neurol Int. 2018; 9: 107.
  21. Tureen JH, Dworkin RJ, Kennedy SL, et al. Loss of cerebrovascular autoregulation in experimental meningitis in rabbits. J Clin Invest. 1990; 85(2): 577–581.
  22. Schut ES, Brouwer MC, de Gans J, et al. Delayed cerebral thrombosis after initial good recovery from pneumococcal meningitis. Neurology. 2009; 73(23): 1988–1995.
  23. Gallegos C, Tobolowsky F, Nigo M, et al. Delayed Cerebral Injury in Adults With Bacterial Meningitis: A Novel Complication of Adjunctive Steroids? Crit Care Med. 2018; 46(8): e811–e814.
  24. Engelen-Lee JY, Brouwer MC, Aronica E, et al. Delayed cerebral thrombosis complicating pneumococcal meningitis: an autopsy study. Ann Intensive Care. 2018; 8(1): 20.
  25. Klein M, Koedel U, Kastenbauer S, et al. Delayed cerebral thrombosis after initial good recovery from pneumococcal meningitis: past as prologue: delayed stroke as a parainfectious process of bacterial meningitis? Neurology. 2010; 75(2): 193; author reply 193–4.
  26. Hoffman O, Weber RJ. Pathophysiology and treatment of bacterial meningitis. Ther Adv Neurol Disord. 2009; 2(6): 1–7.
  27. Johanson CE, Stopa EG, McMillan PN. The blood-cerebrospinal fluid barrier: structure and functional significance. Methods Mol Biol. 2011; 686: 101–131.
  28. Laterra J. Blood—Brain—Cerebrospinal Fluid Barriers. In: Siegel GJ, Bernard WA, Alberts RW, et al. ed. Basic Neurochemistry. Vol 6. Lippincott-Raven, Philadelphia 1999.
  29. Nau R, Eiffert H. Modulation of release of proinflammatory bacterial compounds by antibacterials: potential impact on course of inflammation and outcome in sepsis and meningitis. Clin Microbiol Rev. 2002; 15(1): 95–110.
  30. Levi M, van der Poll T, Büller HR. Bidirectional relation between inflammation and coagulation. Circulation. 2004; 109(22): 2698–2704.
  31. Rittirsch D, Flierl MA, Ward PA. Harmful molecular mechanisms in sepsis. Nat Rev Immunol. 2008; 8(10): 776–787.
  32. Wall EC, Gordon SB, Hussain S, et al. Persistence of pneumolysin in the cerebrospinal fluid of patients with pneumococcal meningitis is associated with mortality. Clin Infect Dis. 2012; 54(5): 701–705.
  33. Srinivasan L, Kilpatrick L, Shah SS, et al. Cerebrospinal fluid cytokines in the diagnosis of bacterial meningitis in infants. Pediatr Res. 2016; 80(4): 566–572.
  34. Coutinho LG, Grandgirard D, Leib SL, et al. Cerebrospinal-fluid cytokine and chemokine profile in patients with pneumococcal and meningococcal meningitis. BMC Infect Dis. 2013; 13: 326.
  35. Low PS, Lee BW, Yap HK, et al. Inflammatory response in bacterial meningitis: cytokine levels in the cerebrospinal fluid. Ann Trop Paediatr. 1995; 15(1): 55–59.
  36. Perdomo-Celis F, Torres MA, Ostos H, et al. Patterns of Local and Systemic Cytokines in Bacterial Meningitis and its Relation with Severity and Long-Term Sequelae. Biomark Insights. 2015; 10: 125–131.
  37. Woehrl B, Brouwer MC, Murr C, et al. Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis. J Clin Invest. 2011; 121(10): 3943–3953.
  38. de Gans J, van de Beek D. European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002; 347(20): 1549–1556.
  39. Korshin A, Køster-Rasmussen R, Meyer CN, et al. Danish Bacterial Meningitis Group. Adjunctive steroid treatment: local guidelines and patient outcome in adult bacterial meningitis. Scand J Infect Dis. 2007; 39(11-12): 963–968.
  40. van de Beek D, Farrar JJ, de Gans J, et al. Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data. Lancet Neurol. 2010; 9(3): 254–263.
  41. Zwijnenburg PJG, van der Poll T, Florquin S, et al. C1 inhibitor treatment improves host defense in pneumococcal meningitis in rats and mice. J Infect Dis. 2007; 196(1): 115–123.
  42. Hoffmann O, Priller J, Prozorovski T, et al. TRAIL limits excessive host immune responses in bacterial meningitis. J Clin Invest. 2007; 117(7): 2004–2013.
  43. Grandgirard D, Schürch C, Cottagnoud P, et al. Prevention of brain injury by the nonbacteriolytic antibiotic daptomycin in experimental pneumococcal meningitis. Antimicrob Agents Chemother. 2007; 51(6): 2173–2178.
  44. Jun JS, Lee ST, Kim R, et al. Tocilizumab treatment for new onset refractory status epilepticus. Ann Neurol. 2018; 84(6): 940–945.
  45. Brouwer M, Read R, Beek Dv. Host genetics and outcome in meningococcal disease: a systematic review and meta-analysis. The Lancet Infectious Diseases. 2010; 10(4): 262–274.