Cryptococcal meningitis is an inflammatory lesion of the meninges with cryptococcus. Clinically manifested by symptoms of meningitis, hydrocephalus. When the process spreads to the cerebral tissue, focal disorders are added. Diagnosis is carried out according to the results of lumbar puncture, cerebral CT, MRI, microbiological and serological analyses, immunograms. Therapy is carried out with antimycotic pharmaceuticals, symptomatic means. It is necessary to treat the underlying disease and detoxification therapy, with hydrocephalus — to ensure adequate outflow of cerebrospinal fluid.
ICD 10
B45.1 Cerebral cryptococcosis
General information
Cryptococcal meningitis is one of the etiological variants of inflammation of the membranes of the central nervous system. It is common among individuals with significantly reduced cell-mediated immunity. 80-95% of cases are patients suffering from AIDS. Cryptococcal meningitis is the main cause of deaths in this group. In Africa, the number of deaths reaches 500-600 thousand per year. The last 30 years have been characterized by a tendency to a significant increase in morbidity, which is explained by the global increase in the prevalence of HIV.
Causes
The main pathogens initiating cryptococcal meningitis are Cryptococcus neoformans and Cryptococcus gattii. In encapsulated form, they are transmitted by airborne droplets with dust particles. The ecological reservoir of both subtypes is bird droppings, decomposing organic matter, and soil.
Cryptococci belong to saprophytic fungi and do not cause diseases with the normal functioning of the immune system. Opportunistic infection develops with immunodeficiency, accompanied by a decrease in the number of T-helper cells (CD4) less than 100 in 1 ml (norm 600-1200). The risk factors for meningitis are immunodeficiency conditions with a violation of T-cell immunity:
- AIDS. The human immunodeficiency virus has a cytolytic effect on T-helpers, significantly reducing their number.
- Immunodeficiency. Primary immunodeficiency conditions with cellular link damage manifest in early childhood. They include Digiorgi syndrome, combined immune deficiency.
- Iatrogenic decrease in immunocompetence. Artificial immunosuppression is necessary for organ transplantation. Treatment with cytostatic drugs, carried out in oncopathology, autoimmune diseases, leads to a decrease in immunity.
Pathogenesis
In immunocompetent individuals, the penetration of cryptococcal infection does not cause pathological changes, since the spread of fungi through the body is suppressed by a normally functioning immune system. In immunosuppression with damage to the cellular component, T-lymphocytes do not recognize the pathogen, do not prevent its penetration into the blood.
With the blood flow, cryptococci penetrate the central nervous system, pass the blood-brain barrier and enter the meninges. By persisting and multiplying in the cerebral membranes, cryptococci cause their damage with the development of an inflammatory reaction, a violation of the circulation of cerebrospinal fluid.
Morphologically, inflammation leads to thickening of the membranes. Macroscopically, their turbidity, petechial hemorrhages are noted. The surface becomes bumpy. When inflammatory changes spread to the cerebral substance, concomitant encephalitis develops.
Symptoms
The manifestation of the disease is nonspecific. Patients report constant headache of an intense nature, nausea, decreased appetite. Repeated vomiting is possible, which does not bring relief. Subfebrility is typical, in some patients the body temperature reaches 38-39 degrees. There is weakness, fatigue, drowsiness, some inhibition of reactions. Patients do not tolerate bright lighting well. In some cases, there is a disorder of consciousness, convulsive syndrome, anxiety.
With the development of meningoencephalitis, focal symptoms in the form of paresis, paralysis, sensory disorders are added to the clinical picture of meningitis. Increasing hydrocephalus is characterized by increased cephalgia, increased vomiting, signs of visual and auditory dysfunction. Possible discoordination when walking.
Complications
Violation of the outflow and accumulation of cerebrospinal fluid in the cerebrospinal fluid spaces of the brain leads to compression of the optic nerve. Progressive vision loss develops, which, in the absence of adequate treatment, quickly leads to complete loss of visual function. Similar complications are possible on the part of the hearing organ. Thickening of the cerebral membranes and overflow of the arachnoid spaces in them with cerebrospinal fluid cause compression of the underlying cerebral cortex, which leads to cognitive disorders. Complications are observed in 48-50% of cases of cryptococcal meningitis.
Diagnostics
The neurological status shows signs of increased intracranial pressure. Rigidity of the occipital muscles and other meningeal symptoms are detected only in 20% of patients. The presence of immunodeficiency pathology in the patient’s anamnesis allows the neurologist to suspect the cryptococcal etiology of the disease. Confirmation of the clinical diagnosis is possible after the following studies:
- Cerebrospinal puncture. The expiration of the cerebrospinal fluid under increased pressure indicates hydrocephalus. Microscopic examination of the cerebrospinal fluid reveals lymphocytic pleocetosis and signs of inflammation. In 10-15% of patients, no changes are detected.
- Microbiological examination of the cerebrospinal fluid. Identification of the pathogen is traditionally carried out using light microscopy after ink staining, but this method is not always sensitive. Sowing liquor on a Saburo medium allows you to isolate creptococci, determine their sensitivity to pharmaceuticals.
- Serological studies. Detection of the cryptococcal antigen is carried out using a latex agglutination test or immunoassay. The sensitivity of the studies is 85-90%.
- Immunogram. A drop in the number of T-helpers to 100 cells per ml (norm 600-1200) indicates in favor of the cryptococcal etiology of meningitis.
- Neuroimaging. It is carried out to exclude other intracranial pathology. It is typical for fungal meningitis. CT scan of the brain reveals strengthening of cerebral membranes, aggregates of cryptococci, hydrocephalus. Cerebral MRI is more informative in terms of detecting cryptococcus localized in the membranes, medulla, basal ganglia. AIDS patients are characterized by atrophic signs of the cerebral cortex.
Differential diagnosis
Cryptococcal meningitis has no specific clinical manifestations. It should be differentiated from meningitis of other genesis: bacterial, viral, oncogenic. Bacterial meningitis is characterized by febrile temperature, intoxication, pronounced meningeal signs. Neoplasms of the membranes and the underlying medulla are well visualized on tomograms. The differential diagnosis should include chronic or subacute meningoencephalitis.
Cryptococcal meningitis treatment
Drug therapy
Basic therapy is carried out with antifungal drugs. Recent clinical studies in the field of neurology have shown an increase in the effectiveness of treatment when using a combination of two drugs. An indicator of the success of the therapy is the rate of elimination of fungi from the cerebrospinal fluid. In parallel, symptomatic therapy, antiretroviral treatment, detoxification measures are carried out. In the complex pharmacotherapy of cryptococcal meningitis are used:
- Antifungal agents. The treatment is carried out in 3 phases. Induction is carried out by intravenous administration of a combination of two antimycotics for 2 weeks. Oral use of the second drug is possible. The consolidation phase lasts 8 weeks, is carried out orally. Then supportive therapy is applied. The doses of drugs in all phases are calculated by the doctor individually according to the severity of the process. In order to reduce the nephrotoxic effect, liposomal forms of antifungal agents are recommended.
- Detoxification. It is aimed at leveling the toxic side effect of antimycotics. It is carried out by intravenous drip infusions of electrolyte solutions.
- Antiretroviral therapy. It is necessary for patients with AIDS. It is carried out by modern inhibitors of protease, reverse transcriptase, integrase.
Drug treatment of hydrocephalus in patients with cryptococcal meningitis is ineffective. Reduction of intracranial pressure is carried out by regular therapeutic spinal punctures. It is possible to install a temporary catheter for drainage or perform ventricular-peritoneal bypass surgery.
Experimental treatment
Currently, options for immunotherapy of cryptococcal infection are being studied. Therapy with monoclonal antibodies to cryptococcal capsule polysaccharides is considered the most promising. These drugs have demonstrated efficacy in animal models. The first stage of clinical studies of the action of antiriptococcal antibodies in patients recovering from HIV-associated meningitis was carried out.
Prognosis and prevention
The outcome of the disease is determined by the severity of the lesion, the timeliness and adequacy of the antimycotic therapy. The combined method in the induction phase allowed to reduce mortality to 9.4%. In countries with a low social level, mortality reaches 40%, which is associated with late initiation of therapy, monotherapy.
Mortality from HIV-associated cryptococcal meningitis remains high (10-30%) even in developed countries. Patients who survive for the first 6 months have a subsequent 5-year survival rate of 88%. Supportive therapy helps prevent the recurrence of meningitis. Prevention consists in avoiding places with chicken droppings. Preventive antifungal therapy is recommended for AIDS patients.
