MM 331-337; 586-588, ID 1132-1140
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NAMES OF DISEASE:         Fungal meningitis
                                              Tubercular meningitis
                                              Amoebic meningitis
                                              Syphilitic meningitis

ETIOLOGICAL AGENTS:     Cryptococcus neoformans (Serotypes A,B,C,D)
                                                Treponema pallidum                                             ) All slow
                                                Mycobacterium tuberculosis                                 ) growers in
                                                Naegleria fowleri                                                  ) the CNS
                                                Human immunodeficiency virus                               )
                                                Coccidioides immitis                                            )


    This is a fungal disease which begins with a lung infection due to inhalation of the organism. This organism is commonly present in avian feces, especially pigeon feces. Almost every person in this country has been exposed to the organism yet there are only 200-300 cases per year of fungal meningitis. It is thought that the host must be compromised in some respect in order to develop fungal meningitis, although the fungal pneumonia is fairly common. Predisposing factors include:

    1.     Glucosteroid therapy

    2.     Malignancy (particularly of the lymphoreticular system)

    3.     Collagen - vascular disease (particularly disseminated lupus erythematosus - an acute or
            subacute, remitting febrile disease principally of young women, with widespread collagen
            damage in many organs and systems)

    4.     Sarcoidosis - a disorder involving many organs where there is formation of epithelioid cell

    5.     Diabetes mellitus

    6.     Pregnancy

    7.     Alcoholism

    8.     Genetic impairment of host defense mechanisms - 50%. T-cell diseases (Di George
            Syndrome, Nezelof's syndrome)

    9.     AIDS

    When aerosols containing C. neoformans are inhaled, the cells are engulfed by pulmonary alveolar macrophages. In people with a normal immune system, the fungus either fails to survive intracellularly or is quickly contained so that either no disease, or mild, subclinical illness occurs. If the infecting dose is so large that normal cellular defenses are overwhelmed or if the host is compromised, a chronic pneumonia ensues. The growing cryptococci do not elaborate toxins or engender hypersensitivity. They cause disease by compression of surrounding structures as an infected focus enlarges. Because the lungs are readily compressible, there is little or no clinical manifestation of the lung infection. However, the lesions are evident on chest x-rays. If C. neoformans cells are not successfully restrained in the pulmonary parenchyma they will pass to the hilar lymph nodes. Again there is little or no clinical response. From here they may become blood borne and lodge in any organ or tissue where they may give rise to lesions. However, they show a predilection for the CNS.


    In the CNS, deep space-occupying lesions are most likely to occur in the grey matter around the ventricles and aqueduct, in the basal ganglia, cerebral white matter and cerebellar dentate nucleus. Infection of the meninges leads to seeding of the CSF and spread throughout the subarachnoid space. A grayish, mucinous exudate accumulates at the base of the brain and over the cerebellum; leptomeningitis is most pronounced in the same areas. In most patients there are lesions in the brain and the meninges-a meningoencephalitis. Each lesion will be the site of granuloma and abscess formation.

    If the cells lodge in the skin or mucous membranes they grow and form nodules which may

    If the fungi grow in bone, there is destruction of the bone.


    The course of cryptococcoses is typically indolent and protracted with symptoms waxing and waning for weeks or months before the diagnosis is made. The patient may feel unwell, lose some weight and have no other symptoms. There may be no fever or low fever (102°F, 39°C). In the normal host the symptoms are mild. In the compromised host, the course may be acute or chronic. In almost all patients there is a mingling of the manifestations of encephalitis and meningitis. Patients present with:

    1.     Headache - frontal, temporal or retro-orbital. Most common feature and it becomes
            progressively more frequent and severe.

    2.     Mental aberrations (from simple irritability to psychosis)

    3.     Motor abnormalities (altered reflexes to paralyses)

    4.     Cranial nerve dysfunctions (aphasia, visual disturbances, hearing loss)

    5.     Cerebellar signs (dyssynergia, dysmetria, dysrhythmia, intentional tremor, slurring of speech)

    6.     Evidence of increased intracranial pressure

    7.     Fever in about 1/3 of patients

    As the manifestations of cryptococcoses are nonspecific, the diagnosis is often arrived at by eliminating neoplastic disease, TB and other fungal diseases. Exposure to pigeon or other avian feces is a good clue. All blood and urine analyses are normal. REMEMBER: you cannot test for antibodies to C. neoformans because (1) the immune system is generally defective and (2) fungi do not elicit a strong antibody response in normal people. Best evidence is from CSF.

    1.     Increased CSF pressure

    2.     Protein is elevated

    3.     Leukocytosis (40-400/mm3 - mostly mononuclear cells)

    4.     Glucose is decreased (45% of blood glucose)

    5.     C. neoformans present in India ink preparations

    6.     Serological tests for cryptococcal antigen


    Almost always fatal if it goes untreated (90% of patients die within one year).


    1.     Amphotericin B injected I.V. and into the subarachnoid space. NOTE: This is poorly
            absorbed into CSF. Treat for 6 weeks. Toxic.

    2.     Flucytosine (5-fluorocytosine)-penetrates into all body fluids, including CSF. Less toxic but
            higher doses required.

    3.     Miconazole-an imidazole derivative     )
    4.     Amphotericin B methyl ester               ) Experimental

    Whatever regimen of antifungal drug therapy is used, surveillance is an essential part of treatment. Examine CSF weekly for all parameters.

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