Aseptic Meningitis Workup

Updated: Mar 01, 2021
  • Author: Nitin Butala, MBBS, MS; Chief Editor: Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM  more...
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Blood Studies

The selection of blood tests is guided by the etiologic clues gleaned from the clinical evaluation. Tests that may be useful include the following:

  • CBC with differential

  • Sedimentation rate, antinuclear antibody, rheumatoid factor

  • Sjögren syndrome antigens A and B

  • Serum protein electrophoresis

  • Lyme titer (enzyme-linked immunosorbent assay [ELISA])

  • VDRL, fluorescent treponemal antibody absorption test (FTA-ABS)

  • Acute and convalescent sera for virus-specific IgG or IgM to enteroviruses, arboviruses, adenoviruses, LCMV, Epstein-Barr virus, and HSV-2

Dubos et al found that measurement of blood procalcitonin (PCT) levels, in combination with other clinical and laboratory parameters, can help distinguish aseptic meningitis from bacterial meningitis. In a study of 198 consecutive children with acute meningitis (aged 29 days to 18 years), a PCT level ≥ 0.5-ng/mL indicated bacterial rather than aseptic meningitis with 99% sensitivity and 83% specificity. [12]


Cerebrospinal Fluid Studies

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.


Other Tests

Stool studies

Detection of enterovirus in stool specimens is an important adjunct study for diagnosing enteroviral infections in children.

Imaging studies

The following imaging studies should be performed:

  • Chest radiography, posteroanterior and lateral

  • MRI of brain/spine

Tuberculosis testing

In the appropriate epidemiologic settings, consider an intradermal tuberculin test (purified protein derivative [PPD]) or other tests for tuberculosis.