Cryptococcal meningitis

Introduction to new cryptococcal meningitis The new type of cryptococcus neoformer meningitis (cryptococcus neoformsmeningitis) is caused by the infection of meninges and/or brain parenchyma by Cryptococcus neoformans. Due to the atypical symptoms and irregular treatment, the misdiagnosis rate and mortality rate are still high. In recent years, with the broad-spectrum antibiotics, the widespread or inappropriate application of hormones, immunosuppressive drugs, and the increase in immunodeficiency diseases and organ transplant patients, the prevalence of the disease is also increasing. basic knowledge The proportion of illness: 0.003% Susceptible people: no special people Mode of infection: respiratory transmission Complications: disturbance of consciousness

The cause of new cryptococcal meningitis

Causes:

Reduced immunity (30%):

Cryptococcus is a soil fungus that is parasitic on birds, especially pigeons. Cryptococcus is a conditional pathogen that invades the human body from the respiratory tract, causing mild inflammation of the lungs. When the body's immunity declines, such as systemic chronic wasting disease, severe trauma, long-term high-dose use of antibiotics, corticosteroids or immunosuppressive agents, The blood is spread into the skull and has a philophilic effect on the central nervous system.

Virus infection (45%):

The central nervous system infection of cryptococcus is mainly caused by meningeal inflammatory lesions, extensive thickening of the meninges, edema of brain tissue, and flattening of the brain. Small granuloma, small cysts or small abscesses can be seen along the sulci or cerebral cistern. Large granulomas or cysts are sometimes seen in deep tissues of the brain. Under the microscopic examination, the meninges were infiltrated with lymphocytes and monocytes. Granuloma consists of fibroblasts, macrophages, and necrotic tissue. The cyst contains a large denier gelatinous substance. Cryptococcus can be found in these diseased tissues.

Pathogenesis:

1. Pathogenesis: Domestic Chen Yuchong reported in 2000 that polysaccharide capsule is the most important component of capsular toxicity. It mainly mediates the inhibition of phagocytic cells and reduces the specific T lymphocyte reaction. It is positively correlated with its anti-phagocytic ability and is mainly related to the high molecular weight fragment of capsular polysaccharide. In addition, the polysaccharide capsule inhibits the immune response of the body by inhibiting the release of cytokines IL-6 and IL-1 by phagocytic cells. The bacteria escape from the removal of the host defense system and cause disease.

Melanin is another important pathogenic factor of Cryptococcus, which is related to the membrane-bound phenol oxidase of the cell wall. The abundant catecholamines in the brain can be used as an important substrate for its action. It is speculated that Cryptococcus may have a high degree of central nervous system. One of the reasons for affinity is that the toxicity of melanin is mainly anti-free radicals. Foreign studies have found that a melanin produced by a cryptococcal cell is sufficient to remove a large amount of cellular oxidant produced by activated macrophages, in vivo, it is cleared by Superoxides and other oxides protect yeast cells from oxides produced by host cells. In addition, melanin also has anti-fungal effects against UV rays, reducing the sensitivity of amphotericin B, etc., which may result in Cryptococcus continues to spread in the body and is one of the reasons for its difficulty in curing.

Long-term use of broad-spectrum antibiotics, immunosuppressive drugs, anticancer drugs, organ transplantation and leukemia, AIDS, lymphosarcoma, systemic lupus erythematosus, tuberculosis, diabetes and other patients become the main susceptible population of the disease, when the body's immune function is low At the time, Cryptococcus reproduces in the brain and produces a large number of virulence factors that resist the host defense response, causing cryptococcal meningitis or meningoencephalitis.

2. Pathological changes: gross neovascularization of the meninges, widening of the cerebral gyrus, shallow sulcus, opacity of the pia mater, especially the bottom of the brain, bridge pool, chiasm, cisterna magna, lateral sulcus, brain bottom And in the dilated subarachnoid space, yellow viscous jelly-like exudates can be seen, and small granular nodules or vesicles can be seen in the sulci, cerebral cistern or brain main substance, and there is a gel-like exudate.

A large number of cryptococcal bacteria can be seen in the colloidal mucus, and some are engulfed by multinucleated giant cells. There are a large number of inflammatory cells infiltrated by lymphocytes, monocytes and multinucleated giant cells in the brain, meninges and subarachnoid space. Slow onset can be seen by a large number of fibroblasts and capillaries granuloma and small abscesses, domestic Zheng Jianzhong and other reports in 1999 reported a group of cryptococcal meningitis autopsy cases, found that there are inflammatory cell infiltration around the small artery, and there is a brain Intraplasma hemorrhage and multiple softening necrosis.

Novel cryptococcal meningitis prevention

1. Pigeons may be the main source of infection, pay attention to prevent infection through this route.

2. The new type of cryptococcus is inhaled by the respiratory tract; pay attention to enhance physical fitness and prevent upper respiratory tract infection.

3. Avoid long-term application of broad-spectrum antibiotics and immunosuppressive drugs.

4. Prevention of tuberculosis, diabetes, etc. may cause cryptococcal meningitis or meningoencephalitis.

5. Early comprehensive treatment to reduce complications and reduce mortality.

New cryptococcal meningitis complications Complications

1. There may be varying degrees of disturbance of consciousness, mental disorders, and restlessness.

2. Skull base arachnoiditis, the most common optic nerve damage, followed by VIII, III, VII, VI cranial nerve damage.

3. Some patients may have symptoms of focal brain tissue damage such as hemiplegia, convulsions and aphasia.

New cryptococcal meningitis symptoms common symptoms intermittent headache meningeal irritation meningitis convulsion hypothermia nausea edema consciousness disorder

1. More subacute or chronic onset, a small number of acute onset, can occur in all ages, 20 to 40 years old young adults are the most common.

2. The first symptoms are often intermittent headache, nausea and vomiting, with low fever, general discomfort, lack of energy and other non-specific symptoms. As the disease progresses, the headache gradually increases to persistent, mental abnormalities, restlessness, and severe cases. Disorder of consciousness.

3. About half of the patients with cranial nerve damage, the most common optic nerve, followed by the VIII, III, VII, VI cranial nerve, partial hemiplegia, convulsions, aphasia and other focal brain tissue damage symptoms.

4. Meningeal irritation is the most common positive sign in the early stage, and fundus edema and pyramidal tract sign can occur in the advanced stage.

Examination of new cryptococcal meningitis

1. Cerebrospinal fluid: the pressure is increased, the appearance is slightly mixed or light yellow, the protein content is light to moderately elevated, the number of cells is increased, mostly at 100×106/L, mainly lymphocytes, chloride and glucose are reduced, cerebrospinal fluid Smear ink staining can directly find Cryptococcus, the cells are round, non-nuclear, the capsule is lightly dyed, and it is a double-layered reflective circle. The size of the cells is different, and the granular material is visible. The budding cells are gourd-shaped or dumbbells. shape.

Early cerebrospinal fluid examination, regardless of routine, biochemical, cytology, has more than 95% abnormalities, mainly manifested as inflammatory changes, although similar changes with tuberculous meningitis, 99% can detect cryptococcus from the first lumbar cerebrospinal fluid , or Cryptococcus neoformans reverse latex agglutination test is positive, strong positive reaction, therefore, cerebrospinal fluid examination is an important basis for the diagnosis of occult brain.

2. Immunological examination: Latex agglutination (LA) test: It can detect the cryptococcal polysaccharide capsule antigen component in early serum or cerebrospinal fluid. This method has higher specificity and sensitivity than ink staining, and the positive rate of cerebrospinal fluid detection can be as high. 99%, if the antigen positive titer> 1:8, can be diagnosed as active cryptococcal meningitis, and its titer is proportional to the degree of infection. Some people think that Cryptococcus neoformans antigen-linked immunoassay is faster than LA. More superior.

Imaging examination: CT CT lacks specificity, 40% to 50% shows normal, and its positive rate is related to different stages of the disease course. The longer the course of disease, the higher the positive rate, the enlargement of ventricle, hydrocephalus, meninges and brain Irregular large-scale, patchy or miliary low-density shadows, a small number of small infarcts or hemorrhagic lesions, brain MRI can show a low signal in the brain parenchyma, T2 high signal circular or round The mass, the perivascular space is enlarged, and some of them have multiple miliary nodular changes.

Diagnosis and identification of new cryptococcal meningitis

diagnosis

Long-term use of antibiotics, immunosuppressive drugs and immunosuppressive diseases such as AIDS, lymphoma, leukemia, organ transplantation, subacute or chronic progression of headache, jet vomiting, cranial nerve damage and meningeal irritation, cerebrospinal fluid protein Quantitative increase, chloride and glucose reduction, should consider this disease.

Clinical diagnosis requires the discovery of Cryptococcus neoformans in the cerebrospinal fluid. Because the detection rate is affected by the location of the lesion and the stage of development of the disease, it is necessary to repeatedly stain the cerebrospinal fluid for meningitis with suspicious or long-term recurrence, culture or animal inoculation. Pathogens, usually the positive rate of ink staining is low, so it is necessary to use early detection of cryptococcal antigen by cerebrospinal fluid latex agglutination (LA) or antigen-enzyme immunoassay to improve the early diagnosis rate.

Differential diagnosis

The clinical manifestations, cerebrospinal fluid routine, imaging features and the like are very similar to tuberculous meningitis. The identification of the two depends on pathogenic evidence. In addition, it should be associated with viral encephalitis, brain abscess, intracranial tumor, and cysticercosis. Disease (cysticercosis) and other phase identification.

Other brain mycosis, aspergillosis and mucormycosis, should also be identified.

1. Aspergillosis: a group of chronic fungal diseases caused by Aspergillus. As a conditional pathogen, Aspergillus is widely found in the surface of natural and human skin mucosa. The disease is chronic or subacute. A small number of patients with severely impaired immune function can be acutely onset, mainly manifested as symptoms of intracranial space-occupying lesions caused by brain abscess, often with fever, headache, nausea, vomiting, seizures, and, in addition, depending on the route of infection and the formation of abscesses At the site, there are different focal symptoms, such as hemiplegia, aphasia, ataxia, mental disorders, visual field defects, etc., severe cases may die due to cerebral palsy.

Cranial CT or MRI often shows single or multiple brain abscesses, cerebral infarction, hemorrhagic infarction, etc., direct infection or secretion of primary infection sites such as sputum, nasal discharge, pus, etc., can find hyphae and Spores, but can not be used as a basis for diagnosis, because these parts can be normal Aspergillus parasitic, serum or cerebrospinal fluid PCR detection of Aspergillus DNA, is of great significance for early diagnosis, pathological examination found that the pathological tissue hyphae and spores have the most diagnostic significance.

2. Mucormycosis: a rare lethal fungal disease caused by Mucor fungi, mainly invading the nose, brain, lungs, gastrointestinal tract and skin. In severe cases, it can be spread to the whole body by blood. Among them, brain hair fungus disease is the most common, diabetes acidosis is the main predisposing factor, followed by immunodeficiency disease, a large number of antibiotics, immunosuppressive drugs, organ transplantation and other patients, infection often originates in the turbinate, paranasal sinus or pharynx Causes cellulitis, further invades the eyelids to the brain, meninges; can also invade local blood vessels, through the internal carotid artery to the brain.

Once invaded into the brain, the bacteria quickly cause encephalitis, meningitis, mostly acute onset, a small number of subacute or chronic, early manifestations of nasal congestion, headache and other symptoms of sinusitis, followed by fever, swelling of one side, pain Dark red secretions in the nasal cavity flow out, invading the eye causing eyelid edema, eyeballs protruding and limited activity, dilated pupils, decreased vision and even blindness, brains are often affected, with the most common neurological damage in V, VII Peripheral facial paralysis, facial numbness, corneal reflex disappeared, arterial thrombosis can cause hemiplegia, aphasia, etc., some meningeal irritation, headache, vomiting, disturbance of consciousness, and late cerebral palsy due to increased intracranial pressure.

Brain CT or MRI showed brain abscess, cerebral infarction, sinus turbidity, bone destruction, a small number of changes in cerebral hemorrhage, and direct secretion smear or culture of secretions such as pus and blood stasis at the site of infection. Mucor, histopathology can be found. Finding the most common cause of the disease.

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