What is the role of cerebrospinal fluid (CSF) studies in the diagnosis of aseptic meningitis?

Updated: Jul 17, 2018
  • Author: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS; Chief Editor: Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM  more...
  • Print

The following CSF studies may be considered:

  • Gram stain, bacterial culture and sensitivity

  • Acid-fast bacillus, India ink

  • Cryptococcal antigen

  • Cell count

  • Protein, glucose, and gamma globulin

  • Latex agglutination test for Haemophilus influenzae type b


  • PCR for HSV (varicella-zoster virus also in immunocompromised patients), M tuberculosis

  • IgM antibodies to B burgdorferi and Brucella, Histoplasma, and Coccidioides species

  • Angiotensin-converting enzyme (ACE) level

  • Tuberculostearic acid

  • Cytology

Nucleic acid CSF tests are more sensitive than cultures in diagnosing enteroviral infections. There can be substantial cost savings and avoidance of unnecessary treatment of aseptic meningitis with antibiotics when the turnaround time for these tests is less than 24 hours.

A CSF protein level of 0.5 g/L or higher suggests bacterial rather than aseptic meningitis in children 28 days to 16 years old. However, this finding has relatively low sensitivity and specificity. [1, 13]

TNF alpha, which is a potent mediator of inflammation, has been demonstrated to have potential as a predictor of clinical outcome in children with acute bacterial meningitis. In one study, CSF levels of TNF alpha were markedly higher in children with acute bacterial meningitis than in controls. All patients with TNF alpha levels greater than 1500 pg/mL died.

Bishara et al found elevated levels of soluble triggering receptor expressed on myeloid cells (sTREM-1) in the CSF in 7 of 9 (78%) patients with culture-positive specimens and in 0 of 12 pati.e.nts with culture-negative specimens (sensitivity, 78%; specificity, 100%). This suggests that sTREM-1 is upregulated in the CSF of patients with bacterial meningitis with high specificity and that its presence can potentially assist in the diagnosis of bacterial meningitis. [14]

Mollaret cells (large endothelial cells) are considered by many to be the hallmark of Mollaret meningitis, although their presence in CSF is not pathognomonic. They may comprise 60-70% of cells in the CSF; however, they are usually present for only the first 24 hours and can be missed easily.

After the first 24 hours, the CSF shows a lymphocytic predominance with cell counts usually less than 3000/µL. Hypoglycorrhachia (i.e., low CSF glucose concentration) is reported in one third of the patients. CSF protein usually is elevated mildly.

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!