subacute meningitis

Meningeal inflammation that lasts > 2 wk (subacute meningitis) or > 1 mo (chronic meningitis) may have infectious or noninfectious causes (eg, cancer). Diagnosis requires CSF analysis, usually after CT or MRI. Treatment is directed at the cause.


Subacute or chronic meningitis may have infectious or noninfectious causes and may be an aseptic meningitis (see Table 4: Meningitis: Other Causes of CSF Inflammatory Response*). Infectious causes include fungal infections (most commonly with Cryptococcus neoformans), TB, Lyme disease, AIDS, Actinomyces infections, and syphilis; noninfectious causes include sarcoidosis, vasculitis, Behçet’s syndrome, and cancers such as lymphomas, leukemia, melanomas, certain carcinomas, and gliomas (particularly glioblastoma, ependymoma, and medulloblastoma). Other causes include chemical reactions to certain intrathecal injections.

Use of immunosuppressants and the AIDS epidemic have increased the incidence of fungal meningitis. Cryptococcus sp (see Fungi: Cryptococcosis) is the most common cause in patients with AIDS, Hodgkin lymphoma, or lymphosarcoma and in those taking high-dose, long-term corticosteroids. Coccidioides, Candida, Actinomyces, Histoplasma, and Aspergillus spp are less common causes (see Fungi).

Symptoms and Signs

Most manifestations are similar to those of acute meningitis but evolve over weeks. Fever may be minimal. Headache, backache, and cranial nerve or spinal nerve root deficits are common. Communicating hydrocephalus may develop and cause dementia. Intracranial pressure may remain elevated and cause headache, vomiting, and decreased alertness for days or weeks. Without treatment, death can occur within a few weeks or months (eg, with TB or tumor), or symptoms can continue for years (eg, with Lyme disease).



CSF analysis

The diagnosis is suspected if meningeal symptoms or signs develop over > 2 wk, with or without symptoms of cerebral dysfunction, particularly if a potential cause of meningitis (eg, active TB, cancer) exists.

The diagnosis requires CSF analysis. CT or MRI is done to exclude mass lesions that cause slowly evolving cerebral dysfunction (eg, tumors, abscesses, subdural effusions) and to determine whether lumbar puncture can be done safely. CSF pressure is often elevated but may be normal. CSF cell count is elevated with a lymphocytic predominance; glucose is slightly or moderately reduced but may be significantly decreased in TB or fungal meningitis. CSF protein is high (see Table 1: Meningitis: Cerebrospinal Fluid Abnormalities in Various Infections).

Other CSF tests (eg, special stains, fungal and acid-fast bacillus culture) are determined by the patient’s risk factors. For example, TB is suspected in patients who are alcoholic, HIV-positive, or from areas where TB is endemic (see Mycobacteria: Tuberculosis (TB)). Identification of TB by microscopy has a notoriously low yield and requires acid-fast staining or immunofluorescence and an exhaustive microscopic search of CSF sediment, ideally from a large volume of CSF (30 to 50 mL), which may require 2 or 3 lumbar punctures (typically 20 to 30 mL can be withdrawn at a time). Positive cultures are the gold standard for diagnosis but also require 30 to 50 mL of CSF, and results take 2 to 6 wk. Although results differ among laboratories, PCR has a yield of about 50% in TB meningitis and can provide a specific diagnosis within days. Measurement of CSF tubulostearic acid by gas-liquid chromatography is specific but technically complex and not widely used.

Fungi may be detected microscopically in wet mounts or, for Cryptococcus sp, in India ink preparations (see also Fungi: Diagnosis). CSF cultures grow Cryptococcus and Candida spp in a few days and less common fungi in weeks. CSF cryptococcal antigen is highly specific and sensitive.

Neurosyphilis is diagnosed using the CSF Venereal Disease Research Laboratories (VDRL) test (see Sexually Transmitted Diseases (STDs): Diagnostic tests for syphilis). In Lyme disease (see Spirochetes: Diagnosis), diagnosis can be made by testing for serum antibodies against Borrelia burgdorferi. If serology is negative but clinical signs of meningitis are found, testing for intrathecal antibodies can be useful for diagnosis.

Diagnosis of neoplastic meningitis requires detecting cancer cells in CSF; detection depends on adequate CSF volume, frequency of collection (malignant cells may shed periodically; multiple samples increase the yield), sampling site (cisternal CSF is more often positive), and prompt fixation to preserve cell morphology. For 95% sensitivity, 30 to 50 mL of CSF (typically requiring several lumbar punctures) is collected and delivered to the laboratory promptly. For suspected neurosarcoidosis, ACE in CSF is measured; it is elevated in up to 24 to 50% of patients. For certain tumors, CSF tumor markers (eg, IL-10 for lymphoma; soluble CD27 for lymphoid cancers, such as acute lymphoblastic leukemia and non-Hodgkin lymphoma) can help with diagnosis or monitoring disease activity.

Some causes of subacute or chronic meningitis (eg, Behçet’s syndrome) cannot be diagnosed by CSF analysis and must be diagnosed clinically.


Treatment depends on the cause (see elsewhere in the manual).

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