Fungal meningitis is the defeat of the soft and dura mater by a fungal infection with the development of inflammatory changes. The clinical picture is characterized by a subacute / chronic course with fever, headache, drowsiness, mild severity of shell symptoms. The diagnosis of fungal meningitis allows neurological examination, lumbar puncture, analysis of cerebrospinal fluid, detection of the pathogen in the blood and liquor. The basis of treatment is antifungal pharmaceuticals used as monotherapy, combined and anti-relapse treatment.
G02 B37.5 B38.4
Fungal (mycotic) meningitis is a rare form of infectious damage to the cerebral membranes. Pathology is found everywhere, the incidence rate is the same for both sexes. Fungal meningitis mainly affects immunocompromised patients and people in endemic zones of pathogens. Among AIDS patients, fungal cryptococcal meningitis is diagnosed in 6-13% of cases. In endemic areas, a large number of infected with the fungus are detected, but only 1% have dissemination of the pathogen, which in 35% of cases is accompanied by damage to the meninges.
The causative agents of the disease are various pathogenic and conditionally pathogenic fungi. Penetration into the body is carried out by airborne droplets (when inhaling fungal spores), alimentary (when eating spore-seeded food, water) ways. A sick person is not a source of infection for others. The most common pathogens of meningitis of fungal etiology are:
- Cryptococci. The most common pathogen is C. Neoformans. It is released into the environment with bird droppings, is present on vegetables, fruits, in the soil. Infection occurs with food, by inhaling dust particles with spores. The overwhelming number of cases of the disease are AIDS patients.
- Candida. They belong to the natural flora of the human body. They cause the development of infectious diseases only against the background of immunodeficiency. Meningitis caused by these fungi accounts for 15% of all candidiasis lesions of the central nervous system.
- Coccidia. Among the causative agents of coccidiosis, C. Immitis is the most common. Mycosis is observed in endemic regions of the USA, South and Central America. Damage to the membranes of the brain occurs against the background of disseminated infection more often in the elderly, pregnant women, patients with immune suppression.
The risk group for the development of mycotic meningitis of any etiology includes persons with immunodeficiency conditions: newborns, patients with HIV infection who have undergone cytostatic therapy for organ transplantation, cancer, patients with CRF, diabetes mellitus, alcoholism, blood diseases, persons over 60 years old.
Once in the body, the pathogen encounters a reaction of protective immunological factors that prevent the development of infection. Against the background of a reduced immune response, fungal spores are not destroyed, the blood current spreads to various organs and tissues where the pathogen develops. The introduction of spores into the brain membranes becomes possible due to the increased permeability of the blood-brain barrier, which normally protects brain tissues from the penetration of large molecules circulating in the blood, including various infectious agents.
Fungal meningitis is accompanied by a serous inflammatory process. There is a thickening, clouding of the shell tissues, their surface acquires a fine-grained character. Petechial hemorrhages are noted. The inflammatory process can pass to the cerebral substance with the development of encephalitis, to the membranes of the spinal cord.
In practical neurology, the separation of mycotic lesions of the membranes is used, depending on its specified etiology, features of the clinical course. According to the type of pathogen, cryptococcal, candidiasis, coccidiosis, histoplasma, aspergillosis meningitis are distinguished. According to the course of the disease , fungal meningitis is classified into:
- Acute — characterized by sudden appearance, rapid development of symptoms. It is rare, mainly with candidiasis etiology.
- Subacute — characterized by a delayed onset with a gradually progressive increase in symptoms. The most common option. Subsequently, it can turn into a chronic form.
- Chronic — symptoms are observed for more than 4 weeks. The severity of clinical manifestations is moderate.
The onset of the disease is usually subacute (less often acute), the subsequent course is chronic. The main symptoms are intense headache (cephalgia), vomiting, fever, anorexia, drowsiness. In a number of patients, cephalgia occurs with repeated, non-relieving vomiting. The body temperature is kept at 37.2-37.9 degrees, sometimes reaches febrile values. There is a loss of appetite, possibly aversion to food. The patient is sluggish, sleeps a lot, gets tired quickly, looks inhibited. There is an increased sensitivity to light. Convulsive paroxysms, anxiety, disorders of consciousness, focal symptoms are possible.
A distinctive feature is the low severity of meningeal syndrome, sometimes its complete absence. The meningeal symptom complex is a typical sign of a lesion of the membranes, includes tension (rigidity) of the muscles of the occiput, a specific pose of the patient, general hyperesthesia, tonic phenomena detected during the examination. With subacute and chronic course, fungal meningitis may not be accompanied by meningeal symptoms, which significantly complicates diagnosis.
In 40% of cases, fungal meningitis occurs with intracranial hypertension, exacerbating cephalgia and causing nausea, vomiting. When the infectious process spreads to the spinal membranes, a radicular syndrome occurs, signs of spinal cord damage: peripheral and central paresis, sensitivity disorders. The transition of the infectious and inflammatory process to the cerebral tissues is accompanied by the development of focal symptoms, severe disorders of consciousness. Fungal encephalitis is dangerous by the occurrence of cerebral edema, coma, and the fatal outcome of the disease.
Diagnostic difficulties are caused by erased symptoms, the absence of pronounced meningeal syndrome, the presence of immunosuppression, which complicates the immunological diagnosis of the disease. Diagnosis is made using the following studies:
- Neurological examination. The neurologist pays attention to the presence and severity of meningeal symptoms, assesses the level of consciousness, identifies focal neurological deficit, signs of spinal cord injury (if any).
- Lumbar puncture. Allows you to determine the liquor pressure, evaluate the color, the degree of transparency of the liquor. Subsequent examination of the cerebrospinal fluid confirms lymphocytic pleocytosis, the level of which depends on the type of pathogen, the stage of the disease. Microscopy of smears reveals the presence of filaments of the fungus in 50% of cases.
- MRI of the brain. It is necessary to exclude concomitant cerebral lesions: tuberculosis, toxoplasmosis. Mixed fungal-bacterial, protozoal-fungal infection occurs in immunocompromised patients.
- Laboratory tests. They are aimed at verifying the pathogen, determining its sensitivity to antimycotic drugs. Blood culture for sterility, microbiological examination of the liquor can exclude bacterial etiology, detect the growth of fungal colonies. The enzyme immunoassay of the liquor for the presence of antimycotic antibodies is close to 100% in its specificity, however, in immunodeficiency conditions it can give false negative results.
Differential diagnosis is carried out with bacterial meningitis, tuberculous meningitis, viral lesion of the membranes. In some cases, differentiation with meningioma, brain abscess, cerebral tumor is required.
The basis of therapy is the use of antimycotic pharmaceuticals. Until the results of sensitivity determination are obtained, treatment is carried out empirically, then — taking into account the data obtained. The following therapy options are used:
- Monotherapy. It is carried out by slow intravenous drip. With cryptococcal etiology, life-threatening candidiasis meningitis, amphotericin B is indicated before receiving data on the sensitivity of coccidia. In other cases, fluconazole has proven itself well. If indicated, intrathecal administration of the drug by lumbar or ventricular puncture is possible. Pharmacotherapy is carried out for a long time (1.5-2.5 months). until the complete rehabilitation of the liquor.
- Combined treatment. It is carried out with amphotericin in combination with fluconazole, flucytosine. This type of therapy is considered effective in patients with cryptococcal infection without a concomitant HIV clinic. The optimal combination of drugs has not yet been found.
- Anti-relapse therapy. It is necessary for the prevention of relapse of the disease, even in the case of complete sanitation of the cerebrospinal fluid from the pathogen. The drug of choice is fluconazole.
In parallel, symptomatic therapy is carried out. The relief of vomiting is achieved by the use of antiemetics, intracranial pressure is reduced by diuretics, the treatment of convulsive syndrome is carried out by anticonvulsants.
Prognosis and prevention
Before the introduction of amphotericin into medical practice, fungal meningitis was fatal in 100% of cases. Now timely initiated, properly selected therapy allows you to save the patient’s life, to achieve his recovery. The prognosis of the disease depends on age, the state of the immune system, the timeliness of therapy, the rate of rehabilitation of the cerebrospinal fluid in response to the treatment. Recurrent fungal meningitis is observed in 40% of cases. In case of recovery, residual phenomena in the form of a persistent increase in intracranial pressure, epilepsy, cognitive disorders are possible.
50% of surviving newborns have hydrocephalus, 56% have mental retardation, which is due to the disease itself and the toxic side effect of antimycotics. Primary preventive measures consist in the implementation of measures to strengthen immunity, prevent the spread of HIV. Secondary prevention is reduced to monitoring the rehabilitation of cerebrospinal fluid, adequate anti-relapse treatment.