Tuberculous meningitis is a cerebrovascular disease caused by Mycobacterium tuberculosis. The incidence of tuberculous meningitis has been gradually increasing in recent years, and its causes are not very clear, and it is estimated that it may be related to environmental pollution. Typical cases are relatively easy to diagnose, but there are many atypical cases, which cause serious sequelae and even affect the patient’s life if treatment is delayed.
Brief introduction
Tuberculous 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.
Pathogenesis
According to domestic data, among 1180 cases of tuberculous meningitis, 44.2% of them were diagnosed with corniform tuberculosis. 143 cases (94%) of 152 cases of tuberculous meningitis were found to have tuberculosis of other organs of the body, and 142 cases (93.4%) were combined with pulmonary tuberculosis, of which corniform tuberculosis was the first. Among them, the first one was the cornified tuberculosis.
When the primary tuberculosis lesion becomes established, the tubercle bacilli in the lesion can stay in the meninges, brain parenchyma and spinal cord through blood flow, forming hidden tuberculosis lesions, including tuberculosis nodules and tuberculoma. When the above lesions once break down. The tuberculosis bacilli directly enter the subarachnoid space, causing tuberculous inflammation. In addition, tuberculous lesions in tissues near the brain such as the middle ear, mastoid process, cervical spine, and skull can also spread directly and invade the meninges, but this is less common.
The occurrence of tuberculous meningitis is associated with a high degree of hypersensitivity of the body patch at the time of the primary tuberculosis. From the pathogenesis point of view, tuberculous meningitis is secondary to tuberculosis, therefore, attention should be paid to finding the primary lesion. However, there are a few cases where the primary lesion has healed or cannot be found, and in such cases, vigilance should be increased to avoid misdiagnosis. Pathological typing
1.Plasma type
2.Low cerebral meningoencephalitis type
3.Meningoencephalitis type
4.Tuberculous spinal cord soft and hard meningitis type
Clinical manifestations
The onset of tuberculous meningitis is often slow, but there are also sudden onset cases.
(a) The clinical manifestations of typical tuberculous meningitis can be divided into three stages
1, the prodromal period (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 sleeplessness, two 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 and young children show frowning, hitting head with hands, crying, etc.
2.The meningeal irritation period (middle period) is about 1~2 weeks mainly for meningeal and intracranial pressure increase. Low fever, increased headache can be continuous. Vomiting is frequent, often in the form of jets, there may be sensory hypersensitivity, drowsiness and impaired consciousness. The typical meningeal stimulation signs are mostly seen in older children, while infants mainly show a 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.
At this stage, cranial nerve involvement is often seen, the most common being paralysis of the facial nerve, the motoneurotic nerve and the abducens nerve, mostly unilateral, manifested by the disappearance of the nasolabial fold, drooping eyelids, exotropia, diplopia and dilated pupils, optic neuritis, optic papillary edema, and occasional nodules in the choroid.
3. In the late stage (coma stage), about 1 to 2 weeks, consciousness impairment is aggravated by repeated convulsions, and the consciousness enters semi-consciousness or coma, with dilated pupils, loss of light reflex, irregular respiratory rhythm or 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.
(B) Atypical tuberculous meningitis
1. When larger children suffer from tuberculosis, the brain parenchyma is often suddenly broken due to hidden lesions. 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 manifested as signs of persistent increase in intracranial pressure, hypothermia, progressive headache, 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 tuberculosis, nodular brain may develop secondary to or concurrent with nodular brain, fever, enlarged liver and spleen lymph nodes, and may be accompanied by rash, but chest radiographs may reveal corniform tuberculosis.
Diagnosis and differential diagnosis
Early diagnosis of pediatric tuberculous meningitis is a prerequisite for early and reasonable treatment. According to recent reports in China, there was no death in early diagnosis and treatment of this disease, 4.8-24% of those treated in the middle stage and 40.6-72.4% of those treated in the late stage.
(A) Diagnosis basis
1, 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 cornual 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 with general anti-infection, the child should be asked if there is any 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 cerebral nodules are about 42-92%, of which about 44% belong to the cornified tuberculosis. Therefore, any suspicion of this disease, should be chest X-ray, such as the detection of tuberculosis in the lungs, especially the corn type of tuberculosis, will 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 increased, and it can be significantly increased in the acute progressive stage or when the tuberculoma breaks down. However, the cell count may be normal early in the disease. Protein quantification increases, mostly above 0.4g/L, generally 1 to 3g/L. If it is more than 3g/L, it should be considered as pearl retinal adhesions or even spinal canal obstruction. Sugar quantification may be normal in the early stage and gradually decrease later.
Cerebrospinal fluid sugar content is reduced. The chloride content is often reduced. A decrease in both 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 mycobacterium tuberculosis may be found by antacid staining or direct fluorescent antibody method using this film or cerebrospinal fluid precipitation.
(2) Lymphocyte transformation test 3H-TdR participation method can be 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 measurement Cerebrospinal fluid immunoglobulin measurement, for the differential diagnosis of meningitis has some significance. IgG is predominantly increased in cerebrospinal fluid in nodular brain, IgG and IgM are increased in chemobrain, and IgG is mildly increased in viral brain.IgM is not increased.
(4) Lactate and lactate dehydrogenase assay. Lysozyme index determination and cerebrospinal fluid anti-tuberculosis antibody test. Cerebrospinal fluid PCR method to detect tuberculosis antigen, etc.
4.Other tests
(1) Positive tuberculin test is helpful for diagnosis, but negative results cannot exclude the disease.
(2) Fundus examination reveals tuberculosis nodules on the choroid. Cerebrospinal fluid changes can be definitely concluded.
(3) Peripheral blood picture shows elevated total leukocyte count and neutrophil ratio. Mild anemia. Blood pressure is increased, but there are also normal cases.
(B) Differential diagnosis
Tuberculous meningitis must be differentiated from the following diseases.
1.Septic meningitis
2.Viral meningoencephalitis
3.New cryptococcal meningitis
Treatment
(A) General treatment
Early cases should be hospitalized, bed rest, supply nutritious food with high vitamin (A, D, C) and high protein, nasal feeding for coma, if you can swallow, you can try to feed by. The room should be regularly ventilated and disinfected, and the air in the room should be fresh and well-lit. Pay attention to eye, nose and mouth care, turning, and prevent the occurrence of hemorrhoids and pulmonary stasis.
(B) Anti-tuberculosis treatment
Anti-tuberculosis drugs should be selected as bactericidal agents with strong penetration and high cerebrospinal fluid concentration, and toxic side effects should be observed during treatment to avoid the combination of drugs with the same toxic side effects as far as possible. Currently, the commonly used therapeutic drugs are isoniazid, streptomycin and ethambutol, para-aminosalicylic acid, rifampin, pyrazinamide, etc.
(C) Application of adrenocorticosteroids
Adrenocorticotropic hormone can inhibit the inflammatory reaction and has the effect of anti-fibrous tissue formation; it can reduce endarteritis, thus rapidly reducing the symptoms of poisoning and meningeal irritation signs; it can lower the brain pressure, reduce cerebral edema and prevent the obstruction of the spinal canal. It is an effective adjunctive therapy to anti-tuberculosis drugs. Generally early application is more effective. Prednisone can be used 1~2mg/kg per day orally for 6~12 weeks, and the drug can be gradually reduced and stopped 4~6 weeks after the condition improves. Or use dexamethasone 0.25-1mg/kg per day in tranquilization. In the acute stage, hydrocodisone can be used 5-10mg/kg per day for 3-5 days and then changed to prednisone orally.
(D) Symptomatic treatment
1. Increased cerebral pressure
(1) 20% mannitol 5-10ml/kg rapid intravenous injection, if necessary once every 4-6 hours, 50% glucose 2-4ml/kg sedation, alternating with mannitol.
(2) Acetazolamide 20-40mg/kg/day in 2-3 doses for 3 days and stop for 4 days.
(3) If necessary, ventricular puncture and drainage, not more than 200ml per day for 2-3 weeks.
2, hyperthermia, convulsions According to the post-treatment.
3, due to vomiting, insufficient intake, cerebral hyponatremia should be replenished with the required water and sodium.
(E) Intrathecal medication
In advanced severe cases, high cerebral pressure, severe hydrocephalus, obstruction in the spinal canal and persistent decrease in cerebrospinal fluid sugar or persistent increase in protein, intrathecal injection can be considered.
(F) Precautions
1, improper timing
Tuberculous meningitis must be treated early, as long as tuberculous meningitis cannot be ruled out, it should not be misdiagnosed due to atypical clinical manifestations and atypical cerebrospinal fluid, thus losing the best time for cure. According to statistics: the first week to start anti-tuberculosis treatment, 70% remission; the second week to start anti-tuberculosis treatment, 50% remission; more than 3 weeks before anti-tuberculosis treatment, the efficacy is extremely poor, and the mortality rate is extremely high.
2, no combination of drugs, insufficient course of treatment
The principle of combined medication: the first choice of bactericidal drugs, with antibacterial drugs, WHO recommends the selection of at least three kinds of drugs
Combination therapy, commonly used isoniazid, rifampin and pyrazinamide. At present, the main first-line anti-tuberculosis drugs are recommended.
3.Whether to apply hormone reasonably
For severe tuberculous meningitis, a certain amount of hormone is applied in a short course in the early stage, which can reduce exudation and cerebral edema, and can be injected intrathecally if necessary to prevent complications. According to statistics, the survival rate: 45% with hormones, 25% without hormones, and a course of 6-8 weeks is appropriate.
4, whether to deal with complications in a timely manner
There are many complications of tuberculous meningitis, such as hydrocephalus, cerebrospinal arachnoiditis, tuberculoma and so on. If not treated in a timely manner, it will definitely affect the efficacy of treatment.
5.Whether there is mixed infection
If TB meningitis is accompanied by bacterial and viral infections, failure to detect and treat them in a timely manner can make treatment difficult, so clinicians must be highly aware of them.
6. The presence or absence of tuberculosis foci in other parts of the body may make treatment difficult.
7. Presence of underlying diseases
The presence of autoimmune disorders, HIV infection, tumors, etc. can also make treatment difficult.
8.Individual differences
Due to individual differences, the sensitivity to anti-tuberculosis drugs is different, which inevitably affects the efficacy.
Prognosis of tuberculous meningitis
In recent years, the prognosis of tuberculous meningitis has greatly improved due to the improvement of diagnostic methods and the development and continuous improvement of chemotherapy regimens. Early and rational treatment can lead to complete cure.
The criteria for its cure are.
① Clinical symptoms and signs completely disappear without sequelae.
② Normal cerebrospinal fluid examination.
③No recurrence after two years of follow-up observation after the course of treatment. If the diagnosis is not timely, the treatment is not reasonable, or the child is too young or the lesion is too serious, there is still a high mortality rate (15-36%). In the course of treatment follow-up, recurrence cases are found, and reasonable treatment can still improve the prognosis.