Meningitis in children - I.V. Bogadelnikov 2005

Aseptic meningitis in children. General data
Aseptic meningitis of fungal etiology
Cryptococcal meningitis

Fungal (mycotic) meningitis is a relatively rare disease, especially in temperate regions. However, its incidence has recently been rising, which is attributed to both improved Diagnostics and an increase in immunodeficiency states in both adults and children. Immunodeficiencies are the primary factor contributing to the hematogenous dissemination of the fungal pathogen from its primary site, leading in most cases to the involvement of the Meninges. The most common pathogens of mycotic meningitis are Cryptococcus (Cryptococcus neoformans) and Coccidioides (Coccidioides immitis). Other Fungi, such as Histoplasma, Blastomyces, Candida, and Aspergillus, are rarely detected in serous meningitis (K.F. Kanareikin et al., 1984; M.N. Sorokina et al., 2000).

Cryptococcal meningitis is a serous Meningitis caused by pathogenic fungi of the genus Cryptococcus, characterized by a subacute or chronic course, a meningeal symptom complex, and mental and visual disturbances.

Etiology. The CAUSATIVE AGENT OF cryptococcal meningitis is Cryptococcus neoformans. It is a Yeast-like fungus of the genus Cryptococcus, which is a unicellular spherical or ovoid microorganism with a diameter of 4 to 6 µm. It reproduces by budding or binary fission. The fungal Cell has a Nucleus surrounded by a nuclear envelope and a bilayer cytoplasmic membrane. Based on The Structure of capsular Polysaccharides, four serotypes of Cryptococcus neoformans are distinguished (A, B, C, D); among them, serotypes A and D dominate globally, while serotypes B and C cause sporadic cases in the tropics and subtropics.

Cryptococcus neoformans grows well on standard mycological media at a Temperature of 25⁰C, forming typical shiny, mucoid colonies due to the presence of a polysaccharide capsule. This capsule is a key pathogenicity factor of Cryptococcus, as it protects the pathogen from the action of phagocytes and humoral defense factors, non-specifically activates the T-suppressor subpopulation, and induces the Cleavage of Complement components and serum opsonins.

The pathogen does not produce toxins. The enzyme phenoloxidase, secreted by the fungus, is considered a potential pathogenicity factor of Cryptococcus.

Cryptococcus neoformans fungi are resistant to chemical and physical factors; their optimal temperature range for in vitro growth is from 25° to 37°C. Direct sunlight inhibits fungal growth in cultures; they are minimally sensitive to ultraviolet and X-ray radiation, and the latter, in low doses, even stimulates fungal growth.

Epidemiology. Cryptococcus neoformans is ubiquitous. In the majority of the population (especially urban dwellers), Antibodies to fungal Antigens can be detected in the complete absence of corresponding symptoms. Currently, Cryptococcus is considered a classic opportunistic pathogen.

It is commonly isolated from bird droppings and nests, particularly pigeon nests, and is present in soil contaminated with bird droppings. Birds themselves do not contract cryptococcosis. Human infection occurs via the aerosol route by inhaling airborne dust containing the pathogen. The incidence is sporadic, more frequently reported in males, as well as in patients with immunodeficiencies. As a rule, there is no age dependence.

Pathogenesis. The Lungs serve as the portal of entry for the infection, where a primary inflammatory focus forms, potentially involving regional Lymph Nodes. In most cases, the process resolves spontaneously; however, dissemination of the pathogen from the primary focus is possible. The corresponding inflammatory response varies depending on the patient's immune status and, primarily, on the functional state of the elements mediating cellular immune responses. The risk group for Cryptococcus neoformans dissemination consists of individuals with T-lymphocyte deficiency or dysfunction. The main conditions predisposing to The Development of cryptococcal meningitis include AIDS, leukemia, Hodgkin's disease, Metabolic Disorders, post-organ transplantation status, prolonged use of cytostatics or glucocorticoids, and diabetes.

In the presence of factors promoting pathogen dissemination, the infection breaks through from the primary endogenous focus (most commonly the lungs or Kidneys) into the bloodstream, followed by dissemination to various Organs, including the meninges, leading to the development of cryptococcal meningitis. Another route of Cryptococcus entry into the Brain and its membranes is also possible from affected areas of the Middle ear or Paranasal Sinuses lymphogenously through the perivascular spaces.

Cytotoxic reactions play the primary role in the elimination of the pathogen, while the humoral response of the body plays a minor role.

Pathological anatomy. Changes in the brain parenchyma and its meninges vary widely and depend on the severity of the course and the CHARACTERISTICS OF THE lesion. The following forms of CNS involvement are distinguished: 1) diffuse meningitis with cellular infiltrates of the leptomeninges containing fungi; 2) granulomatous lesions of the meninges and the brain parenchyma itself; 3) cysts and emboli in the Gray matter of the brain; 4) torulomas in the form of elastic gray tumors or gelatinous formations (P.N. Kashkin, N.D. Shcheklakov, 1978).

Clinical presentation. Meningitis is the primary clinical form of cryptococcosis. Up to 80% of cryptococcal meningitis cases are observed in AIDS patients. Clinical manifestations of meningitis vary depending on the extent of meningeal involvement and differ from those of bacterial meningitis.

Cryptococcal meningitis is more typically characterized by a slow onset (subacute or chronic) and the absence of specific signs in the initial stage, although an acute onset is also possible. Typical signs of meningitis are noted, including high body temperature, nuchal rigidity, Kernig's and Brudzinski's signs, and increased intracranial pressure. A characteristic feature of the disease is a headache that gradually increases in intensity and is localized in the frontal region. Such a headache can be the sole symptom of meningitis for a long time. Frequent dizziness, nausea, and vomiting are common. Subsequently, irritability, weight loss, and mental and visual disturbances develop, such as amblyopia, diplopia, strabismus, nystagmus, and photophobia. Against the Background of meningeal manifestations, symptoms characteristic of both meningoencephalitis and tumors are observed. Limb paresis, aphasia, epileptic seizures, and cranial nerve palsies may occur, and fundoscopy reveals papilledema. The Early Development of symmetric papilledema and the appearance of retinal exudates are characteristic of cryptococcal meningitis (M. Dokic et al., 1987).

In 10% of patients, concurrent involvement of the Skin, Skeletal System, lymphadenitis, and other visceral fungal lesions is observed alongside meningitis. Children with congenital cryptococcosis may present with clonic-tonic seizures, jaundice, hepatosplenomegaly, chorioretinitis, skin rash, and cerebral calcifications (M.B. Titov, B.D. Lutsyk, 1990).

More than 50% of patients who have recovered from cryptococcal meningitis exhibit residual neurological deficits. The duration of the disease varies from a few days to several years. Progressive deterioration of the patients' condition develops over a period of several weeks to several months.

Cryptococcal meningitis is characterized by a high recurrence rate and chronicity of the process, and the prognosis is always serious.

Upon lumbar puncture, CSF flows under pressure, is clear or slightly opalescent, with pleocytosis ranging from 50 to 500 Cells per 1 µl with a predominance of lymphocytes; the protein content is usually elevated, and the glucose level is 20-40% of its Blood level, presenting a picture similar to that of Tuberculous meningitis.

Key diagnostic criteria for cryptococcal meningitis:

1. Epidemiological history: contact with birds (most commonly pigeons) or soil contaminated with bird droppings, or a history of visceral disease involving the skin, lungs, or kidneys.

2. Predisposing factors: the presence of immunodeficiency or another disease accompanied by it, or prolonged use of cytostatics or glucocorticoids.

3. The onset of cryptococcal meningitis is usually gradual, beginning with a headache that increases in intensity, followed by the onset of meningeal symptoms, vomiting, and dizziness.

4. Subsequently, against the background of meningeal symptoms, focal neurological signs of CNS involvement, epileptic seizures, and visual and cognitive disturbances appear.

5. Early development of symmetric papilledema and the appearance of retinal exudates are characteristic.

6. A high percentage (up to 50%) of residual neurological deficits remains after recovery from meningitis.

7. The disease is typically characterized by a prolonged course (up to several months), with a tendency to relapse and progress to chronicity.

8. CSF is under increased pressure, clear or slightly opalescent, with pleocytosis ranging from 50 to 500 cells per 1 µl with mononuclear predominance; protein levels are usually elevated, and the glucose level is 20-40% of the Blood Glucose Level.

Laboratory Diagnosis. Complete blood count. Leukocytosis, neutrophilia, potential eosinophilia, and an elevated ESR are observed in the peripheral blood of patients.

Microscopic examination of CSF allows detection of the pathogen in 50-70% of patients. India ink wet mounts of CSF reveal encapsulated fungal cells, which confirms the diagnosis of cryptococcal meningitis and provides grounds for initiating specific Chemotherapy.

Isolation and identification of the pathogen. The pathogen is relatively easy to isolate on appropriate (mycological) media to determine its chemical and physical properties. Colonies grow within 1-5 days. In addition to CSF, other biological fluids (blood, urine) can be used to isolate the pathogen. However, the isolation of Cryptococcus requires specific conditions and highly skilled laboratory personnel.

Serological testing. This is performed in case of negative culture results or to confirm the diagnosis. In 90-94% of patients with cryptococcal meningitis, the capsular antigen can be detected in the CSF or blood serum by latex agglutination.

However, it should be kept in mind that the presence of rheumatoid factor in a blood sample can cause a false-positive result in the cryptococcal antigen assay.