Subacute and chronic meningitis: causes, symptoms, diagnosis, treatment

Inflammation of the meninges lasting more than 2 weeks (subacute meningitis) or more than 1 month (chronic meningitis) of infectious or non-infectious origin (for example, with cancer).

Diagnosis is based on CSF examination, usually after preliminary CT or MRI. Treatment is directed at the underlying cause.

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What causes subacute and chronic meningitis?

Subacute or chronic meningitis may be infectious or noninfectious in origin and may be aseptic meningitis. The most likely infectious causes are fungal infections (primarily Cryptococcus neoformans), tuberculosis, Lyme disease, AIDS, actinomycetosis, and syphilis; noninfectious causes of subacute or chronic meningitis include many diseases, including sarcoidosis, vasculitis, Behcet's disease, malignancies such as lymphomas, leukemias, melanomas, some types of carcinomas, and gliomas (particularly glioblastoma, ependymoma, and medulloblastoma). Chemical reactions to endolumbar administration of certain drugs are also considered noninfectious causes.

The widespread use of immunosuppressants and the AIDS epidemic have led to an increase in the incidence of fungal meningitis. The most likely pathogen in patients with AIDS, Hodgkin's lymphoma or lymphosarcoma, as well as in individuals receiving high doses of glucocorticoids for a long time, will be representatives of Cryptococcus spp., while representatives of the genera Coccidioides, Candida, Actinomyces, Histoplasma and Aspergillus are detected much less frequently.

Symptoms of subacute and chronic meningitis

In most cases, the clinical manifestations are the same as in acute meningitis, but the course of the disease is slower with gradual development of symptoms over several weeks. Fever may be minimal, while headache, back pain, symptoms of cranial nerve damage and peripheral nerves are almost always present. Complications in the form of communicating hydrocephalus are fraught with the development of dementia. Increased intracranial pressure induces persistent headache, vomiting and reduces work capacity over a period of several days to several weeks. Without treatment, either a fatal outcome is possible in several weeks or months (for example, with tuberculosis or a tumor), or chronic symptoms for many years (for example, with Lyme disease).

Diagnosis and treatment of subacute and chronic meningitis

Acute or chronic meningitis should be suspected in patients with prolonged (>2 weeks) symptoms, including meningeal symptoms and focal neurologic symptoms (optional), especially if the patient has other medical conditions that could potentially cause meningitis (eg, active tuberculosis, cancer). CSF is examined to confirm the diagnosis. CT or MRI is needed to exclude a mass lesion responsible for focal neurologic symptoms (ie, tumor, abscess, subdural effusion) and to confirm the safety of lumbar puncture. CSF pressure is often elevated but may be normal, lymphocyte-predominant pleocytosis is characteristic, glucose concentration is slightly decreased, and protein level is high.

The need for additional examination of the cerebrospinal fluid (specific staining, seeding on selective nutrient media for fungal cultures and acid-fast bacilli) is determined based on clinical and anamnestic data and existing risk factors. In particular, in individuals who abuse alcohol, are HIV-infected or from regions endemic for tuberculosis, there is reason to suspect tuberculosis. Bacteriological identification of the pathogen requires special staining for acid resistance or the use of immunofluorescent dyes, as well as a more labor-intensive and thorough bacterioscopy of 30-50 ml of cerebrospinal fluid, which requires 3-5 lumbar punctures. The gold standard for diagnosis is obtaining a culture with subsequent identification, which requires an additional 30-50 ml of cerebrospinal fluid, as well as 2 to 6 weeks of time. One of the specific methods for diagnosing tuberculosis infection is the detection of tubulostearic acid in cerebrospinal fluid by gas-liquid chromatography, but due to technical complexity this method has limited application. PCR is the most promising method for rapid diagnosis of tuberculosis, but it can give a false-positive or false-negative result, partly due to differences in the standards in force in laboratories.

Bacterioscopic diagnostics of Cryptococcus fungi is performed in a wet preparation or after staining with India ink. In CSF cultures, Cryptococcus and Candida grow within a few days, while cultures of other, less common fungal pathogens grow within a few weeks. A highly sensitive and specific method for diagnosing cryptococcal infection is the determination of cryptococcal antigen in CSF. To detect neurosyphilis, a nontreponemal reaction is performed with CSF (VDRL test - venereal disease research laboratories). Detection of antibodies to Borrelia burgdorferi in the cerebrospinal fluid confirms the diagnosis of Lyme disease.

To verify neoplastic meningitis, tumor cells must be detected in the CSF. The probability of detection depends on the amount of CSF available, the frequency of CSF collection (malignant cells may enter the CSF circulation episodically, so repeated punctures increase the probability of their detection), the site of CSF collection (the probability of detection is higher in CSF from cisterns), and immediate fixation of the sample to preserve cell morphology. 95% sensitivity of the analysis is ensured by collecting CSF in an amount of 30 to 50 ml (which requires 5 lumbar punctures) with immediate delivery to the laboratory. If neurosarcoidosis is suspected, the level of ACE in the CSF is determined; it is usually elevated in half of the subjects. Tumor markers (e.g. soluble CD27 in lymphoid tumors - acute lymphoblastic leukemia and non-Hodgkin's lymphoma) are used to diagnose and monitor the activity of some types of tumors. However, the diagnosis of Behcet's disease is made only on the basis of clinical symptoms and is not confirmed by specific changes in the cerebrospinal fluid.

Treatment is aimed at the underlying disease that caused subacute or chronic meningitis.

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