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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.
Etiology
Subacute or chronic meningitis may have infectious or noninfectious causes and may be an aseptic meningitis (see Table 4: Meningitis: Causes of Aseptic Meningitis* ). Infectious causes include fungi (most commonly Cryptococcus neoformans), TB, Lyme disease, AIDS, actinomyces, 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.
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 produce dementia. Intracranial pressure may remain elevated and produce 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).
Diagnosis
and Treatment
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 produce 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 reduced, and 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: Epidemiology). Identification of TB by microscopy requires acid-fast staining or immunofluorescence and an exhaustive microscopic search of at least 30 to 50 mL of CSF, which requires 3 to 5 lumbar punctures. Positive cultures are the gold standard for diagnosis but also require 30 to 50 mL of CSF, and results take 2 to 6 wk. Measurement of CSF tubulostearic acid by gas-liquid chromatography is specific but technically complex and not widely used. PCR is the most promising method for rapid TB diagnosis but may be false-positive or false-negative, partly because standards between different laboratories vary.
Fungi are 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 or, with less common fungal infections, 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 (STD): Diagnostic tests for syphilis). In Lyme disease (see Spirochetes: Lyme Disease), definitive diagnosis requires intrathecal antibodies against Borrelia burgdorferi.
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 (requiring 5 lumbar punctures) is collected and delivered to the laboratory promptly. For suspected neurosarcoidosis, ACE in CSF is measured; it is elevated in up to 50% of patients. For certain tumors, CSF tumor markers (eg, 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).
Last full review/revision November 2005
Content last modified November 2005
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