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Chronic Meningitis: Simplifying a Diagnostic Challenge

  • Infection (J Halperin, Section Editor)
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Abstract

Chronic meningitis can be a diagnostic dilemma for even the most experienced clinician. Many times, the differential diagnosis is broad and encompasses autoimmune, neoplastic, and infectious etiologies. This review will focus on a general approach to chronic meningitis to simplify the diagnostic challenges many clinicians face. The article will also review the most common etiologies of chronic meningitis in some detail including clinical presentation, diagnostic testing, treatment, and outcomes. By using a case-based approach, we will focus on the key elements of clinical presentation and laboratory analysis that will yield the most rapid and accurate diagnosis in these complicated cases.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Ellner JJ, Bennett JE. Chronic meningitis. Medicine (Baltimore). 1976;55:341–69.

    Article  CAS  Google Scholar 

  2. Bisbe J et al. Disseminated candidiasis in addicts who use brown heroin: report of 83 cases and review. Clin Infect Dis Off Publ Infect Dis Soc Am. 1992;15:910–23.

    Article  CAS  Google Scholar 

  3. Martínez-Vázquez C et al. Candida albicans endophthalmitis in brown heroin addicts: response to early vitrectomy preceded and followed by antifungal therapy. Clin Infect Dis Off Publ Infect Dis Soc Am. 1998;27:1130–3.

    Article  Google Scholar 

  4. Treatment of tuberculosis: guidelines. World Health Organization 4th edition. Geneva; 2010.

  5. Thwaites GE, Chau TTH, Farrar JJ. Improving the bacteriological diagnosis of tuberculous meningitis. J Clin Microbiol. 2004;42:378–9.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Stewart SM. The bacteriological diagnosis of tuberculous meningitis. J Clin Pathol. 1953;6:241–2.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Zunt JRM, Baldwin KJ. Chronic and subacute meningitis. [Review]. Contin Lifelong Learn Neurol. 2012;18:1290–318.

    Article  Google Scholar 

  8. U.S. Preventive Services Task Force. Screening for syphilis infection: recommendation statement. Ann Fam Med. 2004;2:362–5.

    Article  PubMed Central  Google Scholar 

  9. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Tickborne diseases of the United States: a reference manual for health care providers, Third edition, 2015; 2015. at <http://stacks.cdc.gov/view/cdc/30740>.

  10. Halperin JJ. Nervous system Lyme disease. Infect Dis Clin North Am. 2015;29(2):241–53.

    Article  PubMed  Google Scholar 

  11. Wormser GP et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089–134.

    Article  PubMed  Google Scholar 

  12. Mitchell TG, Perfect JR. Cryptococcosis in the era of AIDS—100 years after the discovery of Cryptococcus neoformans. Clin Microbiol Rev. 1995;8:515–48.

    PubMed Central  CAS  PubMed  Google Scholar 

  13. Perfect JR et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2010;50:291–322.

    Article  PubMed  Google Scholar 

  14. Kabanda T, Siedner MJ, Klausner JD, Muzoora C, Boulware DR. Point-of-care diagnosis and prognostication of cryptococcal meningitis with the cryptococcal antigen lateral flow assay on cerebrospinal fluid. Clin Infect Dis. 2014;58:113–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Day JN. Cryptococcal meningitis. Pract Neurol. 2004;4:274–85.

    Article  Google Scholar 

  16. Charlier C et al. Cryptococcal neuroradiological lesions correlate with severity during cryptococcal meningoencephalitis in HIV-positive patients in the HAART era. PLoS ONE. 2008;3, e1950.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Graybill JR et al. Diagnosis and management of increased intracranial pressure in patients with AIDS and cryptococcal meningitis. The NIAID Mycoses Study Group and AIDS Cooperative Treatment Groups. Clin Infect Dis Off Publ Infect Dis Soc Am. 2000;30:47–54.

    Article  CAS  Google Scholar 

  18. Wilson MR et al. Actionable diagnosis of neuroleptospirosis by next-generation sequencing. N Engl J Med. 2014;370:2408–17. Depicts rapid diagnosis with NGS in a child with worsening idiopathic chronic meningitis. Treatment was instituted after detection leading to resolution.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Naccache SN et al. Diagnosis of neuroinvasive astrovirus infection in an immunocompromised adult with encephalitis by unbiased next-generation sequencing. Clin Infect Dis. 2015;60:919–23. Demonstrates a case with discovered diagnosis of rare virus that would never had been previously tested in meningitis cases using NGS.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Quan PL et al. Astrovirus encephalitis in boy with X-linked agammaglobulinemia. Emerg Infect Dis. 2010;16:918–25.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Segal BH, Walsh TJ. Current approaches to diagnosis and treatment of invasive aspergillosis. Am J Respir Crit Care Med. 2006;173:707–17.

    Article  CAS  PubMed  Google Scholar 

  22. Kleinschmidt-DeMasters BK. Central nervous system aspergillosis: a 20-year retrospective series. Hum Pathol. 2002;33:116–24.

    Article  CAS  PubMed  Google Scholar 

  23. Herbrecht R et al. Aspergillus galactomannan detection in the diagnosis of invasive aspergillosis in cancer patients. J Clin Oncol Off J Am Soc Clin Oncol. 2002;20:1898–906.

    Article  Google Scholar 

  24. Herbrecht R et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347:408–15.

    Article  CAS  PubMed  Google Scholar 

  25. Walsh TJ et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:327–60.

    Article  CAS  PubMed  Google Scholar 

  26. Bradsher RW. Histoplasmosis and blastomycosis. Clin Infect Dis Off Publ Infect Dis Soc Am. 1996;22 Suppl 2:S102–111.

    Article  Google Scholar 

  27. Wheat LJ et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis Off Publ Infect Dis Soc Am. 2007;45:807–25.

    Article  Google Scholar 

  28. Bariola JR et al. Blastomycosis of the central nervous system: a multicenter review of diagnosis and treatment in the modern era. Clin Infect Dis. 2010;50:797–804.

    Article  PubMed  Google Scholar 

  29. Chapman, SW. in Principles and practice of infectious diseases (eds. Mandell, G. L., Douglas, R. G. & Bennett, J. E.) 3026–3040 Churchill Livingstone; 1990.

  30. Chapman SW et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:1801–12.

    Article  CAS  PubMed  Google Scholar 

  31. Johnson RH, Einstein HE. Coccidioidal meningitis. Clin Infect Dis Off Publ Infect Dis Soc Am. 2006;42:103–7.

    Article  Google Scholar 

  32. Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007;357:2153–65.

    Article  CAS  PubMed  Google Scholar 

  33. Carlson ML et al. Cranial base manifestations of neurosarcoidosis: a review of 305 patients. Soc Eur Acad Otol Neurotol. 2015;36:156–66.

    Article  Google Scholar 

  34. Zajicek JP et al. Central nervous system sarcoidosis—diagnosis and management. QJM Mon J Assoc Physicians. 1999;92:103–17.

    Article  CAS  Google Scholar 

  35. Ginsberg L, Kidd D. Chronic and recurrent meningitis. Pract Neurol. 2008;8:348–61.

    Article  CAS  PubMed  Google Scholar 

  36. Williams PL et al. Levels of matrix metalloproteinase-9 within cerebrospinal fluid in a rabbit model of coccidioidal meningitis and vasculitis. J Infect Dis. 2002;186:1692–5.

    Article  CAS  PubMed  Google Scholar 

  37. Bañuelos AF et al. Central nervous system abscesses due to Coccidioides species. Clin Infect Dis Off Publ Infect Dis Soc Am. 1996;22:240–50.

    Article  Google Scholar 

  38. Galgiani JN et al. Coccidioidomycosis. Clin Infect Dis Off Publ Infect Dis Soc Am. 2005;41:1217–23.

    Article  Google Scholar 

  39. Lynch JP. Neurosarcoidosis: how good are the diagnostic tests? J Neuro-Ophthalmol Off J North Am Neuro-Ophthalmol Soc. 2003;23:187–9.

    Article  Google Scholar 

  40. Gleissner B, Chamberlain MC. Neoplastic meningitis. Lancet Neurol. 2006;5:443–52.

    Article  PubMed  Google Scholar 

  41. Chowdhary S, Chamberlain M. Leptomeningeal metastases: current concepts and management guidelines. J Natl Compr Cancer Netw JNCCN. 2005;3:693–703.

    PubMed  Google Scholar 

  42. Chamberlain MC. Neoplastic meningitis. Oncologist. 2008;13:967–77.

    Article  PubMed  Google Scholar 

  43. Kaplan JG et al. Leptomeningeal metastases: comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias. J Neurooncol. 1990;9:225–9.

    Article  CAS  PubMed  Google Scholar 

  44. Garg RK, Sinha MK. Tuberculous meningitis in patients infected with human immunodeficiency virus. J Neurol. 2011;258:3–13.

    Article  PubMed  Google Scholar 

  45. Thwaites GE et al. Comparison of conventional bacteriology with nucleic acid amplification (amplified mycobacterium direct test) for diagnosis of tuberculous meningitis before and after inception of antituberculosis chemotherapy. J Clin Microbiol. 2004;42:996–1002.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Prasad, K. & Singh, M. B. Corticosteroids for managing tuberculous meningitis. Cochrane Database Syst. Rev. CD002244. 2008. doi:10.1002/14651858.CD002244.pub3.

  47. Baldwin KJ, Zunt JR. Evaluation and treatment of chronic meningitis. Neurohospitalist. 2014;4:185–95. Clinical approach to chronic meningitis.

    Article  PubMed Central  PubMed  Google Scholar 

  48. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines. MMWR Recomm Rep. 2015;64(RR-03):1–137.

    PubMed  Google Scholar 

  49. Marra CM et al. The rapid plasma reagin test cannot replace the venereal disease research laboratory test for neurosyphilis diagnosis. Sex Transm Dis. 2012;39:453–7.

    Article  PubMed Central  PubMed  Google Scholar 

  50. García P et al. Laboratory diagnosis of Treponema pallidum infection in patients with early syphilis and neurosyphilis through a PCR-based test. Rev Chil Infectol Órgano Soc. 2011;28:31–315.

    Google Scholar 

  51. Halperin JJ. Lyme disease: a multisystem infection that affects the nervous system. Contin Minneap Minn. 2012;18:1338–50.

    Google Scholar 

  52. Halperin JJ, Logigian EL, Finkel MF, Pearl RA. Practice parameters for the diagnosis of patients with nervous system Lyme borreliosis (Lyme disease). Neurology. 1996;46:619–27.

    Article  Google Scholar 

  53. Steere AC, Berardi VP, Weeks KE, Logigian EL, Ackermann R. Evaluation of the intrathecal antibody response to Borrelia burgdorferi as a diagnostic test for Lyme neuroborreliosis. J Infect Dis. 1990;161:1203–9.

    Article  CAS  PubMed  Google Scholar 

  54. Nocton JJ et al. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in cerebrospinal fluid in Lyme neuroborreliosis. J Infect Dis. 1996;174:623–7.

    Article  CAS  PubMed  Google Scholar 

  55. Halperin JJ, Volkman DJ, Wu P. Central nervous system abnormalities in Lyme neuroborreliosis. Neurology. 1991;41:1571–82.

    Article  CAS  PubMed  Google Scholar 

  56. Day JN et al. Combination antifungal therapy for cryptococcal meningitis. N Engl J Med. 2013;368:1291–302.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Gwak HS et al. Recent advancements of treatment for leptomeningeal carcinomatosis. J Korean Neurosurg Soc. 2015;58(1):1–8.

    Article  PubMed Central  PubMed  Google Scholar 

  58. Glass JP, Melamed M, Chernik NL, Posner JB. Malignant cells in cerebrospinal fluid (CSF): the meaning of a positive CSF cytology. Neurology. 1979;29:1369–75.

    Article  CAS  PubMed  Google Scholar 

  59. Wasserstrom WR, Glass JP, Posner JB. Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer. 1982;49:759–72.

    Article  CAS  PubMed  Google Scholar 

  60. Taylor JW et al. Primary leptomeningeal lymphoma. Neurology. 2013;81(19):1690–6.

    Article  PubMed Central  PubMed  Google Scholar 

  61. Smith JE, Aksamit AJ. Outcome of chronic idiopathic meningitis. Mayo Clin Proc. 1994;69:548–56.

    Article  CAS  PubMed  Google Scholar 

  62. Naccache SN et al. A cloud-compatible bioinformatics pipeline for ultrarapid pathogen identification from next-generation sequencing of clinical samples. Genome Res. 2014;24:1180–92. Rapid diagnosis with a new informatics pipeline that compares DNA results to database of living organisms.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Schubert RD, Wilson MR. A tale of two approaches: how metagenomics and proteomics are shaping the future of encephalitis diagnostics. Curr Opin Neurol. 2015;28:283–7.

    Article  CAS  PubMed  Google Scholar 

  64. Calistri A, Palù G. Editorial commentary: unbiased next-generation sequencing and new pathogen discovery: undeniable advantages and still-existing drawbacks. Clin Infect Dis Off Publ Infect Dis Soc Am. 2015;60:889–91.

    Article  Google Scholar 

  65. Siva A et al. Behçet’s disease: diagnostic and prognostic aspects of neurological involvement. J Neurol. 2001;248:95–103.

    Article  CAS  PubMed  Google Scholar 

  66. Kidd D, Steuer A, Denman AM, Rudge P. Neurological complications in Behçet’s syndrome. Brain J Neurol. 1999;122(Pt 11):2183–94.

    Article  Google Scholar 

  67. Criteria for diagnosis of Behçet’s disease. International Study Group for Behçet’s Disease. Lancet Lond. Engl. 1990;335:1078–80.

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Correspondence to Kelly Baldwin.

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Baldwin, K., Whiting, C. Chronic Meningitis: Simplifying a Diagnostic Challenge. Curr Neurol Neurosci Rep 16, 30 (2016). https://doi.org/10.1007/s11910-016-0630-0

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