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August 2018

What’s Next (Generation) for the Diagnosis of Chronic Meningitis?

Author Affiliations
  • 1Department of Neurology, University of Colorado School of Medicine, Aurora
  • 2Department of Medicine, University of Colorado School of Medicine, Aurora
  • 3Department of Immunology-Microbiology, University of Colorado School of Medicine, Aurora
  • 4Neuroinfectious Diseases Section, University of Colorado School of Medicine, Aurora
  • 5Editorial Board, JAMA Neurology
JAMA Neurol. 2018;75(8):915-917. doi:10.1001/jamaneurol.2018.0473

Chronic meningitis is a syndrome defined by the presence of clinical signs and symptoms of meningitis or meningoencephalitis with a persisting cerebral spinal fluid (CSF) pleocytosis that are present for at least 4 weeks.1 The differential diagnosis is broad, with categories including neoplastic, paraneoplastic, autoimmune, and noninfectious inflammatory disorders and central nervous system (CNS) infections.1-3 The exact frequency of the different etiologies often varies tremendously across reports;4 however, among most institutions, common infectious causes of chronic meningitis include Mycobacterium tuberculosis and fungal meningitis (eg, Cryptococcus, Coccidioides, and Histoplasma species) and noninfectious causes include neoplastic meningitis, sarcoidosis, and primary and systemic vasculitis. However, these causes just scratch the surface of the many possible and reported etiologies, and the diagnostic potentials are multiplied enormously among individuals with HIV infection or other immunocompromising conditions. The diagnostic process typically begins with a substantial and expensive battery of tests on serum and spinal fluid and comprehensive imaging of the neuraxis and often of other organs.1-3 Not surprisingly, there are many opportunities for errors of omission (eg, failure to test for a cause that should have been considered) or commission (unnecessary testing). Even when conventional diagnostic algorithms are pursued, an answer may not be apparent, and patients then typically undergo a second level of testing that often includes invasive procedures, such as arteriography and meningeal or brain biopsy. Brain biopsy may be particularly informative among the approximately 50% of patients with meningeal enhancement, among whom diagnostic yields can approach 80%, as compared with those lacking meningeal enhancement, among whom the yield is 9%.5 Biopsy commonly facilitates diagnosis of tuberculosis, neoplasia, and noninfectious granulomatous diseases, such as sarcoidosis and vasculitis.6 Despite comprehensive diagnostic efforts, up to a third of cases remain enigmatic, and those patients often receive empirical therapy, typically in the form of antituberculous, antifungal, or immunomodulatory drugs or even drug combinations.4 Specific diagnoses are rewarding because they often lead to specific and effective therapies, but the process is frustratingly expensive and often extraordinarily time-consuming.