Tubercolous meningitis is the most important type of pediatric tuberculosis and usually develops within 3 months to 1 year after the primary tuberculosis infection, mostly in children aged 1 to 3 years. The duration of tuberculous meningitis from onset to death is about 3 to 6 weeks, and it is the most important cause of death from pediatric tuberculosis. Before the introduction of anti-tuberculosis drugs, the mortality rate was almost 100%. Since BCG vaccination and tuberculosis prevention and control have been widely promoted in China, the incidence of this disease has decreased significantly compared with the past, and the prognosis has improved greatly, and most cases can be cured if diagnosed early and treated reasonably early. However, if the diagnosis is not timely and the treatment is not appropriate, the mortality rate and the incidence of sequelae are still high. Therefore, early diagnosis and reasonable treatment are the keys to improve the prognosis of this disease.
Clinical manifestations of tuberculous meningitis.
Tuberculous meningitis often has a slow onset, but there are also sudden onset cases.
A. The clinical manifestations of typical tuberculosis brain can be divided into three phases.
1, the prodromal phase (early).
About 1 to 2 weeks, generally slow onset, on the basis of the original tuberculosis, there are temperament changes, such as irritability, irritability, crying, or mental lethargy, dullness, drowsiness or sleepy eyes, staring, loss of appetite, wasting, and low fever, constipation or unexplained recurrent vomiting. Older children may complain of headache, which may be intermittent at first and then persistent. Infants show frowning, hitting head with hands, crying, etc.
2. Meningeal irritation (middle stage).
About 1 to 2 weeks Mainly for meningeal and intracranial pressure increase performance. Low fever, increasing headache may be persistent. Vomiting is frequent, often in the form of jets, there may be sensory hypersensitivity, drowsiness and impaired consciousness. Typical meningeal irritation is usually seen in older children, while infants mainly show full or bulging fontanelle, loss of abdominal wall reflexes and hyperactive tendon reflexes. If the disease continues to progress, the infant will enter a coma and may have convulsive episodes. The most common symptoms of cranial nerve involvement are facial nerve, ophthalmic nerve and abducens nerve paresis, mostly unilateral, manifested as nasolabial fold disappearance, eyelid drooping, eye exotropia, diplopia and pupil dilatation, fundus examination shows optic neuritis, optic papillary edema, choroid may occasionally see nodules.
3. Late stage (coma stage).
About 1 to 2 weeks: repeated convulsions with aggravation of intentional error disorder, and the state of semi-coma and coma with dilated pupils, loss of light reflex, irregular respiratory rhythm and even tidal breathing or apnea. There is often metabolic acidosis, cerebral sodium iron loss syndrome, hypokalemia and other disorders of water and electrolyte metabolism. Finally, the body temperature may rise to more than 40℃, and eventually death is caused by respiratory and circulatory failure.
Second, atypical tuberculous meningitis.
1, when larger children suffer from tuberculosis brain, mostly due to sudden rupture of hidden lesions in the brain parenchyma. A large number of tuberculosis bacilli invade the cerebrospinal tract causing an acute reaction of the meninges. The onset of the disease is rapid, with sudden fever, convulsions, and obvious signs of meningeal irritation, while the lungs and other parts of the body may not have obvious tuberculosis lesions; the peripheral blood picture has an increased total leukocyte count and neutrophil percentage; the cerebrospinal tract is mildly cloudy, and the leukocyte count may be ≥1×109/L (1000/mm3) with neutrophils in the majority, which is easily misdiagnosed as septic meningitis.
2. Sometimes, the patient shows signs of persistent increase in intracranial pressure, low fever, progressive headache, and gradually increasing jet vomiting. The cerebrospinal fluid pressure is increased, white blood cells are mildly increased, protein is increased, sugar is decreased, chloride is normal, brain ultrasonography suggests ventricular dilatation or midline displacement, and brain scan shows radiotracer-intense areas, which can be easily misdiagnosed as brain abscess or brain tumor.
3. If the disease is caused by the spread of middle ear or mastoid nodules, it often starts with fever, earache and vomiting, and is easily misdiagnosed as acute otitis media, and is easily misdiagnosed as otitis media combined with cerebral chemistry when meningeal irritation signs appear, and is easily misdiagnosed as brain abscess when limited neurological localization signs appear.
In infants under six months of age with systemic hematogenous disseminated tuberculosis, tuberculosis may occur secondary to or concurrent with cerebral nodules, fever, enlarged liver and spleen lymph nodes, and may be accompanied by a rash, but chest radiographs may reveal corniform tuberculosis.
Diagnosis and differential diagnosis of tuberculous meningitis.
Early diagnosis of pediatric tuberculous meningitis is a prerequisite for early and reasonable treatment. According to a recent report in China, there was no death in any of the early cases of this disease, 4.8-24% of those treated in the middle ridge died, and 40.6-72.4% of those treated in the late stage died.
I. Diagnosis based on.
1, medical history and clinical manifestations.
Early diagnosis mainly relies on detailed medical history, thorough clinical observation, and a high degree of vigilance for the disease. The possibility of the disease should be considered in children with primary pulmonary tuberculosis or corn type tuberculosis who develop symptoms of obscure causes, especially fever and vomiting after measles or whooping cough. In other cases, if the child has vomiting with no obvious cause, change in temperament, headache, neck resistance, and persistent fever that is not effective by general anti-infection, the child should be asked if there is a history of tuberculosis contact and previous history of tuberculosis, and if tuberculous meningitis is suspected, cerebrospinal fluid examination should be performed.
2.X-ray examination.
Tuberculosis lesions in the lungs of children with tuberculosis brain is about 42-92%, of which about 44% belong to the corn type tuberculosis. Therefore, where the disease is suspected, chest X-ray should be carried out, such as the detection of tuberculosis in the lungs, especially when the corn type pulmonary tuberculosis, to help the diagnosis; but the chest X-ray is normal, can not be denied nodular brain.
3.Cerebrospinal fluid examination.
(1) routine examination: In tuberculous meningitis, the cerebrospinal fluid pressure is increased, the appearance is clear or hairy glass-like or slightly cloudy, the cell count is generally 0.05 to 0.5 × 109/L, (50 to 500/mm3), the acute progressive stage or tuberculoma rupture can be significantly higher, or even more than 1 × 109/L, the early stage of the disease cell count may be below 0.05 × 109/L or even normal The cell count in early stage of the disease may be below 0.05×109/L or even normal. The cell classification is dominated by monocytes, which may account for 70-80%, and neutrophils may exceed 50% in a few cases in the early stage. The globulin test is positive, and the protein quantification increases, mostly above 0.4g/L, usually 1-3g/L. If it exceeds 3g/L, it should be considered that the pearl retina is adherent, or even the vertebral canal is obstructed. Sugar quantification can be normal in the early stage, and then gradually decrease, often below 1.65mmol/L (30mm/dl). Cerebrospinal fluid sugar content is 60-70% of blood glucose, and blood glucose should be measured at the same time as cerebrospinal fluid sugar is measured for comparison. The chloride level is often below 102.6 mmol/L (600 mg/dl) or even <85.5 mmol/L (500 mg/dl). The simultaneous decrease in glucose and chloride is typical of tuberculous meningitis. After 12 to 24 hours in a small upright test tube, a gauze curtain-like film may be formed, and tuberculosis bacilli may be found in this film or in the cerebrospinal fluid precipitate by antacid staining or by direct fluorescent antibody methods. Culture of cerebrospinal fluid for Mycobacterium tuberculosis or guinea pig inoculation can help to confirm the final diagnosis, but it takes a long time and is not significant for early diagnosis. For positive cultures, drug tests should be performed for reference when adjusting chemotherapy.
(2) Lymphocyte transformation test: 3H-TdR participation method is used to determine the cerebrospinal fluid lymphocyte transformation. In tuberculous meningitis, the cerebrospinal fluid lymphocyte transformation rate increases significantly under the stimulation of PPD, which has early assertion value.
(3) Immunoglobulin determination: Cerebrospinal fluid immunoglobulin determination has some significance for the differential diagnosis of meningitis. IgG is mainly increased in cerebrospinal fluid in nodal brain, IgG and IgM are increased in chemical brain, IgG is mildly increased in viral brain, and IgM is not increased.
(4) Lactate and lactate dehydrogenase measurement: lysozyme index measurement and cerebrospinal fluid anti-tuberculosis antibody test. Cerebrospinal fluid PCR method to detect tuberculosis antigen, etc.. All of them can help to distinguish the assertion.
4.Other tests.
(1) Positive tuberculin test is helpful for diagnosis, but negative results cannot exclude the disease.
(2) Fundus examination reveals tuberculosis nodules in the choroid. If there are changes in the cerebrospinal fluid, the diagnosis can be made with certainty.
(3) The peripheral blood picture shows an elevated total white blood cell count and neutrophil ratio. Mild anemia. Blood pressure is increased, but there are also normal cases.
(2) Differential assertion.
Tuberculous meningitis must be distinguished from the following diseases.
1, septic meningitis.
Older children can be caused by the breakdown of tuberculous lesions under the brain parenchyma. A large number of tuberculosis bacteria suddenly enter the subarachnoid space and acute onset, or acute hematogenous dissemination of infants and young children secondary to nodular brain, can appear significantly higher cerebrospinal fluid cells, increased percentage of neutrophils, easily misdiagnosed as septic meningitis. However, septic meningitis has a more acute onset, lesions are mainly at the top of the skull, so cranial nerve damage is rare, and cerebrospinal fluid lactate levels return to normal soon after treatment. However, the cerebrospinal fluid changes in untreated septic meningitis are not easily distinguished from those in the nodal brain, and should be analyzed in conjunction with the medical history.
2. Viral meningoencephalitis.
Cerebrospinal fluid cells are mildly to moderately elevated, predominantly mononuclear cells, elevated protein, etc. must be distinguished from nodular encephalitis. However, viral meningoencephalitis has an acute onset, early onset of meningeal irritation signs, and can be combined with respiratory and gastrointestinal symptoms. Cerebrospinal fluid sugar and chloride are mostly normal, and lactate content is less than 300 mg/L.
3. Novel cryptococcal meningitis.
Both clinical manifestations and cerebrospinal fluid routine biochemical changes are very similar, but the new cryptococcal meningitis starts more slowly, with significant increase in brain pressure, severe headache, and may have visual impairment, while the cranial nerves are generally not infringed, and symptoms can be temporarily relieved. The diagnosis can be confirmed by finding cryptococcal spores on cerebrospinal fluid smears with ink staining or by growing Cryptococcus novelis in Stachybotrys culture.