Brain aspergillosis is a fungal lesion of brain tissues caused by aspergillus. It occurs mainly in patients with immunosuppressive conditions against the background of blood diseases, malignant tumors, organ transplantation, prolonged glucocorticoid treatment. It is manifested by weakness, nausea, fever, headache, focal neurological symptoms. Aspergillosis is diagnosed according to the results of neurological examination, MRI / CT of the brain, analysis of cerebrospinal fluid, ELISA, PCR studies. Treatment is based on long-term use of systemic antimycotics.
B44.8 Other types of aspergillosis
Brain aspergillosis has previously been extremely rare. In economically developed countries, the annual incidence was 34 cases per 1 million population. The main forms were lesions of the lungs and paranasal sinuses. Aspergillosis of other organs, including the brain, accounted for 5%. People with immunodeficiency conditions are susceptible to the disease. Recently, there has been an increase in the number of cases of aspergillosis in general and brain aspergillosis in particular, due to the increased number of patients with immune suppression. Every 5th immunocompromised patient suffers from fungal diseases. Aspergillosis accounts for up to 70% of such cases. There are no age and gender differences in morbidity.
The causative agent of the disease is mold fungi of the genus Aspergillus. They are widespread everywhere: in soil, grain, dust, ventilation systems, indoor plants, food. They are found in the dust of medical institutions. Cases of infection of medical instruments for inhalation therapy, air conditioners of hospital wards, which provoked the occurrence of nosocomial infection, are described. The fungus enters the human body mainly by airborne droplets during inhalation of air with mycelium-containing dust particles. There are cases of infection through damaged skin and with food. A sick person is not a source of infection. Factors contributing to the development of cerebral aspergillosis include:
- Hemoblastoses accompanied by severe neutropenia and agranulocytosis (acute leukemia, aplastic anemia). A drop in the number of immune blood cells leads to the development of secondary immunodeficiency.
- HIV infection. Viral damage to the immune system is accompanied by a sharp decrease in the body’s resistance.
- Long-term corticosteroid therapy. The use of glucocorticoids for more than 3 weeks has a negative effect on the immune system.
- Cytostatic treatment. It is prescribed to cancer patients, patients undergoing bone marrow or organ transplantation. Leads to neutropenia and immunodeficiency.
- Chronic diseases, the long course of which is complicated by immune suppression. The group includes: tuberculosis, COPD, sarcoidosis, bronchiectatic disease, diabetes mellitus.
- Injuries, burns, surgical interventions – contribute to infection of the wound surface against the background of reduced immunity due to injury.
- Installation of venous catheters. Infection is possible if the skin at the catheter site is contaminated with aspergillus spores.
The greatest risk is a combination of several factors. For example, surgical operations in HIV patients, bone marrow transplantation in leukemia.
Normally, due to the adequate work of the immune system, when fungal spores enter the human body, aspergillosis does not develop. In the absence of a proper immune response, the spores settle in the lungs and sinuses, and are carried into the cerebral tissues with the blood flow. Infection with GM without prior damage to the lungs or other organs is extremely rare. Fungi form colonies in brain tissues, cause inflammatory changes with the formation of abscesses. Aspergillus obturation of the lumen of intracranial vessels with the development of zones of ischemia and hemorrhagic impregnation, intracerebral hemorrhages is characteristic. Damage to the membranes of the brain with the occurrence of meningitis is noted in rare cases.
Clinical symptoms have no specific manifestations. Usually cerebral aspergillosis begins with headache, nausea, weakness, dizziness. Often there is an increase in temperature. Fever may occur at the very onset of cerebral lesion and a few days after the onset of clinical manifestations. Acute manifestation with symptoms of cerebral circulatory disorders (ischemic, hemorrhagic stroke) is possible.
Focal neurological deficit develops in the first days of the disease, sometimes acutely, with rapid progression, impaired consciousness. The symptoms depend on the location of aspergillosis foci. There is weakness in half of the body (hemiparesis), facial numbness, unilateral smoothness of the nasolabial fold, dysarthria. The occurrence of these manifestations is characteristic in patients with diagnosed aspergillosis of a different localization, against the background of cytostatic chemotherapy, hemoblastosis.
A formidable complication of cerebral aspergillosis is compression of the brain, accompanied by a violation of the vital functions of the central nervous system. Compression is caused by intracerebral abscesses growing in volume, blood pouring into the medulla with massive intracranial bleeding. The compression is also caused by the impregnation of brain tissues with blood in constant diapedetic hemorrhages caused by aspergillus damage to cerebral vessels.
Brain aspergillosis is a complex diagnostic task. The rare occurrence in practical neurology, the nonspecific nature of symptoms, the difficulty of detecting the pathogen in the blood and liquor complicate the diagnosis. The algorithm for diagnosing the disease includes:
- Collecting anamnesis. Allows to establish the presence of HIV, blood diseases, previously identified lung aspergillosis; to obtain data on the treatment with cytostatics / glucocorticosteroids.
- Neurologist’s examination. By the nature of changes in the neurological status, it is possible to judge the presence of organic damage to brain structures, localization of the pathological process.
- Neuroimaging. CT or brain MRI is used, sometimes a combination of them. Tomograms indicate the presence of abscesses, ischemic areas with hemorrhages, intracerebral hemorrhages.
- Lumbar puncture. It is made for the intake of liquor. Aspergilli are rarely detected when examining the resulting cerebrospinal fluid. The analysis helps to exclude other cerebral diseases, diagnose the fact of intracranial hemorrhage.
- Laboratory diagnostics. ELISA of blood, cerebrospinal fluid, urine is used to detect aspergillosis antigen. PCR diagnostics is performed. The reliability of the latter is 67%, the specificity is 95%.
- Examination of the respiratory organs. It is necessary for the diagnosis / exclusion of lesions of the respiratory system. Chest X-ray, lung CT, bronchoscopy with sputum sampling and its subsequent examination are performed.
Cerebral aspergillosis is differentiated from tuberculosis, cysticercosis, toxoplasmosis, bacterial abscess of GM, lymphomas of cerebral localization, intracerebral tumors. The leading role in the differential diagnosis is played by the results of laboratory tests, the detection of respiratory lesions.
Therapy is carried out with systemic antimycotic drugs. The complexity of the treatment of GM lesions is associated with poor penetration of most antifungal agents through the blood-brain barrier (BBB). In addition, the occlusion of cerebral vessels by aspergilli prevents the entry of drugs into brain tissues. Currently, the drugs of choice in the treatment of cerebral aspergillosis are:
- Amphotericin B is a highly effective drug, but it is difficult to pass the BBB. It is used in combination therapy with voriconazole.
- Intraconazole can be prescribed as monotherapy. It accumulates well by brain tissues. The concentration in the cerebrospinal fluid is low.
- Voriconazole – gives a good concentration in the cerebrospinal fluid, accumulates the substance of the brain. It is used independently, with the ineffectiveness of monotherapy – together with amphotericin.
Antifungal therapy is carried out for from six months to several years. The criterion of effectiveness is the stable stabilization of neurological symptoms, the absence of an increase in the number and size of cerebral foci according to magnetic resonance imaging.
Prognosis and prevention
Aspergillosis of cerebral localization always has a serious prognosis, which is also associated with the main disease that caused immune suppression (hemoblastosis, malignant neoplasms, AIDS). Timely initiated and adequately selected antimycotic therapy allows to achieve remission, prolong the life of patients. The exclusion of agricultural work, contact with soil, communication with animals, and being in dusty places helps to prevent aspergillosis in patients with immunodeficiency. In the room where the patient is located (at home, in a medical institution), it is not recommended to keep indoor plants. In hospitals, for the prevention of infection, immunocompromised patients are placed in individual wards with special airlocks and air filters.