Tuberculous meningitis

Introduction to tuberculous meningitis Tuberculous meningitis (tuberculous meningitis) is the most serious type of extrapulmonary tuberculosis in tuberculosis, and is also the leading cause of death from tuberculosis in children. It usually occurs within 1 year of primary dyeing of tuberculosis, especially in the first 3 to 6 months of primary dyeing. Due to the extensive vaccination of BCG and the prevention and treatment of tuberculosis, its incidence has been significantly reduced. However, due to the insufficient balance of prevention and treatment work, the disease is still more common in some areas, and the patients found are still more advanced. Therefore, mastering the law of its occurrence and development, early diagnosis and reasonable treatment are of great significance in reducing the mortality rate and reducing the sequelae. basic knowledge The proportion of illness: 0.0028% Susceptible people: no specific population Mode of infection: non-infectious Complications: epilepsy, disturbance of consciousness, somatosensory disturbance

Causes of tuberculous meningitis

Bacterial infection (65%):

Mycobacterium tuberculosis invades the lymphatic system and enters the local lymph nodes. The bacteremia is spread through the bloodstream into the meninges and brain parenchyma, including the subependymal and other parts, and is replicated here. When the host immune function is reduced or due to age, the tuberculosis within the lesion The bacteria activate and break into the subarachnoid space and spread with the cerebrospinal fluid, which can cause tuberculous meningitis for several days to several weeks.

Disease factors (35%):

Tuberculous meningitis is mostly part of systemic miliary tuberculosis. It spreads through blood. In 1180 cases of brains seen in Beijing Children's Hospital from 1964 to 1977, 44.2% of miliary tuberculosis were diagnosed. In these 14 years, From the pathological anatomy of 152 cases of brain, it was found that there were 143 cases (94%) of other organs and tuberculosis in the whole body; 142 cases (93.4%) with tuberculosis (including miliary tuberculosis in the first place); 62%, 41% of renal miliary tuberculosis, and 24% of intestinal and mesenteric lymphatic tuberculosis.

Pathogenesis

Tuberculosis affects the meninges mainly through the blood-cerebrospinal fluid pathway. The occurrence of brain formation is related to the high degree of hypersensitivity of the body. In addition, the brain can also be caused by the destruction of brain parenchyma or meninges, occasionally the spine, skull or middle ear The mastoid tuberculosis directly spreads to invade the meninges.

1. Pathogenesis Mycobacterium tuberculosis is an aerobic bacteria. The bacteria wall is rich in a variety of lipids. Tuberculosis enters the lungs through the respiratory tract and forms a small area of infection. It does not cause immunity because it does not secrete enzymes or toxins. Or inflammatory reaction, the host also has no symptoms. After several weeks, the bacillus invades the lymphatic system and enters the local lymph node. The bacteremia is spread by blood to the meninges and the brain parenchyma including the subependymal and other parts, and is replicated here.

When the host immune response is caused, the T lymphocytes are sensitized, the macrophages are activated and moved to the infected foci, and the macrophages can engulf the bacilli and fuse together to form multinucleated giant cells (Langer hans giant cells), at which time most of the bacilli are This immune response is killed, a small amount can still be left in macrophages, this granulomatous lesion is surrounded by incomplete cyst wall tissue, its small size can exist in the meninges or brain parenchyma for many years or life. .

When the host immune function is reduced or due to old age, the tuberculosis in the lesion activates and breaks into the subarachnoid space, which spreads with the cerebrospinal fluid, which can cause tuberculous meningitis for several days to several weeks, and the inflammatory reaction can increase rapidly. However, the degree is related to the hypersensitivity reaction caused by the antigenic material of the bacterial wall. A large amount of exudate produced by the inflammatory process is deposited in the brain pool, which may cause arachnoiditis with the progress of time. Into the exudate, the meninges gradually proliferate and thicken, when the absorption of the meninges on the cerebrospinal fluid can cause traffic hydrocephalus, if the blockage of the fourth ventricle median and lateral holes can cause obstructive hydrocephalus.

2. Pathological changes of the brain swelling, pia mater diffuse turbidity, gray-yellow serum fibrinous exudate throughout it, to the bottom of the brain pool, the most prominent chiasm and frontal lobe, inflammatory exudate invaded the brain The nerve sheath can surround and squeeze the nerve fibers. Under the microscope, the diffuse inflammatory cells of the pia mater can be seen. The mononuclear and lymphocytes are mainly composed, and there are a few macrophages and plasma cells. The pia mater can be seen in the miliary granules. Tuberculosis nodules, consisting of several multinucleated giant cells, a large number of mononuclear cells and fibroblasts, and a small number of plasma cells, the latter more common in the late stage, in addition, there are often caseous necrotic substances in the nodules, brain parenchyma edema Tuberculoma is sometimes seen, but its cause is not clear. The ependymal membrane and choroid plexus can show inflammatory reaction or tuberculous nodules. The cerebral arteries and the small arteries in the brain parenchyma often have vascular inflammatory changes. The inflammatory process consists of The outer membrane begins, destroys the elastic fibers and causes endovascular inflammation, further causing vascular occlusion, cerebral infarction or bleeding.

Domestic Hu Changheng et al reported in 1986 an autopsy case of tuberculous meningitis with large intracerebral hemorrhage. In cases of irregular treatment or chronic process, meningeal fibrous connective tissue hyperplasia thickened and adhesion to the brain can cause hydrocephalus. Most of the nerve cells were acutely swollen, the gap around the cells was widened and the glial cells in the brain parenchyma increased. Domestic Ma Huaizhen, Li Wei reported a group of 65 cases of autopsy data in 1988, of which 62 cases had extracerebral tuberculosis, more common in the lungs. Bone and lymph nodes, etc., it is considered that tuberculous meningitis is a manifestation of systemic tuberculosis.

Tuberculous meningitis prevention

The main principles are to enhance physical fitness, pay attention to prevent respiratory infections; strengthen management and treatment of TB patients; newborns and children actively implement planned immunization as required; early comprehensive treatment to reduce complications and sequelae.

The most basic way to prevent brain infection is to prevent children from being infected with tuberculosis. The effective measures are as follows:

1. BCG primary and multiple cropping work experience must be done. Effective BCG vaccination can prevent or reduce the occurrence of nodulation. According to clinical observation, children with nodules are mostly unvaccinated with BCG, and a small number of children are vaccinated at birth. However, it has not been re-planted regularly, so the newborn vaccination with BCG and the subsequent re-planting work cannot be ignored.

2. Early detection and active treatment of infectious sources Early detection of adult tuberculosis patients, especially in close contact with children such as parents, nursery nurses and teachers in kindergartens and primary schools, to prevent flooding and strengthen the management of adult tuberculosis And treatment.

3. Improve the correct feeding of children's body resistance, a reasonable living system and adhere to planned immunization to improve the body's resistance and reduce acute infectious diseases.

4. Early detection and thorough treatment of primary pulmonary tuberculosis in children and complete cure of primary tuberculosis in children can greatly reduce the occurrence of brain formation. The use of INH for chemoprevention has practical significance in preventing brain formation.

Tuberculous meningitis complications Complications, epilepsy, consciousness, somatosensory

1. Systemic tuberculosis.

2. Whole brain or focal signs caused by brain lesions: limb movement, sensory disturbance; secondary epilepsy; disturbance of consciousness; various syndromes of brain stem.

Tuberculous meningitis symptoms Common symptoms Before convulsions, coma, fullness, high fever, blood pressure, irritability, loss of appetite, pulse, fine speed, neck, toughness, weight loss

Main performance

(1) more subacute, a small number of acute or chronic onset, but in the infant can be seen more acute onset and convulsions as the first symptom, and was misdiagnosed as hand and foot spasm.

(2) Early low fever, general weakness, headache and jet vomiting.

(3) In turn, high fever, increased headache, irritability, and mental confusion.

(4) The neck is strong and the Klinefelter's sign () appears earlier, advanced cranial nerve disorder, hemiplegic palsy, convulsions and optic disc edema.

According to clinical symptoms can be divided into:

1 meningitis type;

2 meningoencephalitis type;

3 spinal cord type;

4 mixed type.

2. Tuberculous meningeal inflammation in children

(1) General symptoms: mainly symptoms of tuberculosis, including fever, loss of appetite, weight loss, restless sleep, temperament and mental state changes.

(2) Neurological symptoms include 5 aspects:

1 Meningeal symptoms are caused by pathological changes directly stimulating the pia mater.

2 symptoms of cranial nerve damage.

3 brain parenchymal or destructive symptoms.

4 symptoms of increased intracranial pressure.

5 symptoms of spinal cord disorders.

3. Course of disease

The course of the disease is generally 3 to 4 weeks. The mortality rate is 100% before the treatment without specific treatment. After the anti-tuberculosis drugs appear, if they can be diagnosed early and treated correctly, they can be completely cured.

According to clinical manifestations, the course of disease can be divided into three phases:

(1) prodromal period (early stage): about 1 to 2 weeks, prodromal symptoms include changes in mental state, such as irritability, crying, or mental retardation, do not like games, in addition to low fever, loss of appetite, restless sleep, see thin , constipation or vomiting without cause, older children can complain of headache, early or mild or non-sustainable, infants and young children can be onset, acute, prodromal period is short or no, a symptom of meningeal irritation.

(2) meningeal stimulation period (intermediate): about 1 to 2 weeks, headache persists and aggravates, vomiting is aggravated and can become sprayed, vomiting is the most common symptom in all age groups, gradually appearing sleepiness, or lethargy and irritability Alternate, the child may have hypersensitivity, shouting because of pain when touching him or checking, constipation plus the boat-like abdomen that often appears at the same time, which is one of the typical symptoms of pediatric brain, may have seizures, but after the attack Still awake.

Signs of this period may have full or bulging anterior iliac crest, hyperbaric, Kernig's sign, Krupp's sign, Brudzinski's sign and pathological reflex ( Babinski's sign, Pap's sign is positive, shallow reflexes generally weaken or disappear, sputum reflexes are hyperthyroidism, and there are muscle tremors and red skin scratches.

Common symptoms of cranial nerve disorders, such as oculomotor nerve paralysis can be seen drooping eyelids, ocular oblique, diplopia, dilated pupils, nerves and facial paralysis.

Many children in this period have obvious symptoms and signs of high intracranial pressure and hydrocephalus, such as high fever, abnormal breathing, cranial suture with broken pot sound, scalp vein anger, scalp and eyelid edema, pupils ranging from Large, optic disc edema, etc., in the end can occur angulation, partial hemiplegia or limb rigidity.

(3) coma (late): about 1 to 3 weeks, the above symptoms gradually worsened, the consciousness from the consciousness, half coma and into complete coma, more than convulsions into a coma, frequent clonic or tonic seizures.

Increased intracranial pressure and hydrocephalus are more obvious. Finally, the muscles of the limbs are slack, sputum, urinary retention, all reflexes disappear, or the brain is strong; when the crisis is at risk, the body temperature can suddenly increase, the blood pressure drops, the pulse speeds, and Chen appears. Shi's breathing eventually died of paralysis caused by respiratory and cardiovascular movements.

Tuberculous meningitis check

1. The peripheral blood leukocyte count is normal or slightly elevated.

2. The pressure of cerebrospinal fluid is increased, the appearance can be frosted glass, and white fiber film can be formed after being placed for several hours. The direct smear of acid-fast staining of the membrane is easy to find Mycobacterium tuberculosis, and the number of white blood cells is dozens to hundreds, and most of them are mixed type. About 85% of the dominant ones are mononuclear cells, the protein content is light, moderately elevated, and sodium chloride and glucose are reduced.

3. Basis for pathogens

(1) The detection rate of CSF bacterial smear and bacterial culture is low.

(2) Skin tuberculin test.

(3) Early diagnosis: Polymerase chain reaction (PCR) is used to detect the DNA of tuberculosis in CSF.

In addition, enzyme-linked immunosorbent assay (ELISA) can be used to detect tuberculosis antibodies in CSF. The simultaneous application of the above two tests can improve the reliability of diagnosis, but attention should be paid to the possibility of false positives and false negatives.

4. X-ray examination of chest X-ray is particularly important, and tuberculosis lesions can be found.

5. CT , MRI examination, about half of the brain CT showed abnormality, inflammatory exudate filled the basal pool and lateral cerebral fissure, some patients showed tubercosis in the brain parenchyma, diameter 0.5 ~ 5cm, single or multiple, more in the amount, The sputum and parietal lobe, enhanced scanning showed annular enhancement or increased density.

Brain MR is enhanced by Gd-DTPA, which shows that the basal pool and other parts are strengthened, and tuberculoma and small infarcts in the brain parenchyma are easier to find.

Diagnosis and diagnosis of tuberculous meningitis

Diagnostic criteria

The main diagnostic basis is as follows:

1. Patients with tuberculosis history and early history of tuberculosis exposure rely on detailed medical history including close contact history and BCG vaccination history, careful clinical observation and high vigilance against the disease; Beijing Children's Hospital 1180 cases of brain, 63% have In the history of tuberculosis exposure, 92% were not vaccinated with BCG and about 1/3 occurred in spring.

It is helpful for the diagnosis of tuberculin test in children with suspected disease as early as possible, but the reaction of tuberculosis test is sometimes weak, so when OT 0.1mg or PPD 5U does not cause reaction, OT 1 ~ 2mg or PPD 250U dose retest, Beijing Children's Hospital has analyzed 345 children with brain disease, about 7% of children until OT 1mg only positive, and 4.4% of children are false negative, so It is not easy to deny the diagnosis of the brain due to the negative tuberculin test. Recently, a specific antigen such as PPD has been used in vitro to perform lymphocyte transformation test to assist in the diagnosis of brain-stasis, and children with negative skin test can be positive for this test.

2. Early fever, headache, neck stiffness and the discovery of subacute development of skin malignant rash are decisive for diagnosis. Fundus examination is also helpful for diagnosis. Miliary nodules are found on the choroid and on the lung X-ray. Tuberculosis has equal value, and it has been reported that 14% of patients with choroidal malignant nodules have choroidal miliary nodules.

3. Lumbar puncture examination of cerebrospinal fluid shows more typical tuberculous meningitis changes. Those who are clinically suspected of this disease should promptly check cerebrospinal fluid. When the diagnosis is not decided, antipyretic, sedative and adrenal cortex hormones should not be used to cover up the symptoms. Delay early diagnosis and timely treatment.

4. The exact diagnosis of this disease should have the basis of etiology. Due to the low detection rate of CSF bacterial smear and bacterial culture, the skin tuberculin test is not very reliable, so the current early diagnosis mostly uses polymerase chain reaction ( PCR) The DNA of tuberculosis in CSF was detected, and the positive rate was 88.8% in the course of 6 to 15 days.

Enzyme-linked immunosorbent assay (ELISA) was used to detect tuberculosis antibodies in CSF. The positive rate of more than one month was more than 90%. The application of the above two tests can improve the reliability of diagnosis.

5. Chest X-ray photography is helpful for diagnosis According to X-ray examination of 1180 children with cerebral palsy, it shows that 86.9% of patients with active tuberculosis, including 454 cases of miliary tuberculosis, accounting for 44.2% of active tuberculosis, but need Note that 8.6% of the children have normal lungs. These are older children.

6. Brain CT examination Beijing Children's Hospital from 1986 to 1992 for 50 cases of children with brain brain CT scan found that the most common abnormalities are hydrocephalus (66%), followed by cerebral infarction (34%), brain atrophy (16 %), cerebral edema (12%), tuberculoma (10%), calcification (8%) and subdural effusion (4%), only 10% of children had no abnormalities.

7. EEG examination of most patients with acute EEG abnormalities, manifested as diffuse delta wave (3 weeks / s) and wave (4 ~ 7 weeks / s) slow activity, asymmetry, visible no Symmetrical sporadic spike-like spikes; visible asymmetry in severe anomalies, multiple sharp, spines, sharp-slow, spine-slow and other pathological waves, visible or focal changes in patients with tuberculosis or local cerebral infarction: It is characterized by local delta wave, but the change of EEG is not specific. It can only be used as a clinical auxiliary diagnosis, but it has little significance in the differential diagnosis of pathogens. It is helpful for the follow-up treatment effect, prognosis and sequelae.

8. The exact diagnosis of this disease should have the basis of etiology. The most reliable diagnosis is to check the tubercle bacillus from the cerebrospinal fluid. Try to try to check carefully before the treatment, and the protein membrane formed after the cerebrospinal fluid is still fixed. Acid staining on glass tablets, can be found tuberculosis, has been counted 50 cases of cerebrospinal fluid film examination tuberculosis positive rate of up to 54%, in addition to direct smear examination, cerebrospinal fluid precipitation can be used for pathological biopsy, cerebrospinal fluid culture or guinea pig Vaccination.

Due to the low detection rate of CSF bacterial smear and bacterial culture, the skin tuberculin test is not very reliable. Therefore, the early diagnosis uses PCR to detect the DNA of tuberculosis in CSF. The course of disease is 6 to 15 days. The positive rate was 88.8%.

Enzyme-linked immunosorbent assay (ELISA) was used to detect tuberculosis antibodies in CSF. The positive rate of more than one month was more than 90%. The application of the above two tests can improve the reliability of diagnosis.

The typical diagnosis of the brain is easier, but some are atypical, the diagnosis is difficult, and the atypical brain is about the following:

1 Infants and young children have an acute onset, and they are progressing rapidly. Sometimes they can be convulsed as the first symptom.

2 early symptoms of brain parenchymal damage, manifested as chorea or mental disorders,

3 early cerebrovascular damage, manifested as limb paralysis,

4 when combined with brain tuberculoma, it can be like intracranial tumor performance,

5 other parts of the tuberculosis lesions are extremely serious, can mask the symptoms and signs of meningitis and are not easy to identify,

6 When meningitis occurs during anti-tuberculosis treatment, it often appears to be frustrated. For the above atypical cases, the diagnosis needs to be particularly careful to prevent misdiagnosis.

Differential diagnosis

It should be differentiated from acute suppurative meningitis, viral encephalitis, fungal meningitis and meningococcal cerebral cysticercosis. Different changes in cerebrospinal fluid and pathogenic examination are the main differential diagnosis.

Before the appearance of obvious meningeal irritation, it should be differentiated from general non-neurological diseases, including upper respiratory tract infection, pneumonia, dyspepsia, ascariasis, typhoid fever, hand and foot sputum, etc. At this time, the cerebrospinal fluid can be diagnosed by lumbar puncture. In the presence of meningeal irritation symptoms and signs, even after cerebrospinal fluid examination still need to be differentiated from a series of central nervous system diseases, according to 180 cases of misdiagnosed brain analysis in Beijing Children's Hospital, the most easily misdiagnosed as viral encephalitis, suppurative Meningitis and brain tumors.

1. Suppurative meningitis Infants with sudden onset of brain disease are easily misdiagnosed as suppurative meningitis; conversely, suppurative meningitis is treated with irregular antibiotics and the number of cerebrospinal fluid cells is not very high, and it is easily misdiagnosed as the brain. About 15% of children under 2 years old are misdiagnosed as purulent meningitis before hospitalization. The most confusing person is Haemophilus influenzae meningitis. Because it is more common in children under 2 years old, the number of cerebrospinal fluid cells is sometimes not very high; Followed by meningococcal meningitis and pneumococcal meningitis.

Identification of the history of tuberculosis exposure, lignin reaction and pulmonary X-ray examination can help diagnosis, the important thing is cerebrospinal fluid examination, the number of cells is higher than 1000×106/L (1000/mm3), and the classification is neutral polymorphism When neutrophils are predominant, suppurative meningitis should be considered; but more importantly, bacteriological examination, the first cerebrospinal fluid smear and culture is essential.

2. Viral central nervous system infections are mainly viral encephalitis. Viral meningoencephalitis and viral myelitis can be confused with the brain, and the viral encephalitis that is emitted needs to be identified more than the epidemic.

(1) Epidemic encephalitis B: epidemic in summer and autumn, severe and frequent onset is extremely dangerous, early symptoms of encephalitis, fever, headache, lethargy, 3 to 4 days later into the extreme period, high fever, convulsions, coma and Respiratory circulatory failure, at this time, it is difficult to identify with the brain, and the mild cases are easy to be confused with the early brain. The symptoms of brain parenchymal damage in the early stage of the brain are easily misdiagnosed as encephalitis, but the history of JE has an epidemic, protein in cerebrospinal fluid. Only mild increase, sugar or chloride normal or increased are helpful to identify.

(2) Mumps meningoencephalitis: can be popular in winter and spring, can also be distributed, especially when encephalitis occurs before mumps or no mumps at all, it is easy to be confused with the brain, according to the history of mumps exposure, tuberculosis The bacteriocin test was negative, the lungs were free of tuberculosis and the onset was more acute, and the content of sugar and chloride in the cerebrospinal fluid was not reduced and the protein increase was not significant.

(3) polio: popular in summer and autumn, the onset is more urgent, there is a typical bimodal fever type, more unconscious disorder, affected limb paralysis reflex disappears, flaccid paralysis occurs faster, compared with limb paralysis Late and different for tonic paralysis.

(4) Enterovirus: such as Coxsackie virus, encephalitis caused by encephalitis or meningitis is more common in summer and autumn, the onset is more urgent, meningeal irritation is obvious, there may be rash and muscle pain, and the course of disease is shorter.

(5) lymphocytic choroidal plexus meningitis: more often occur in the winter and spring, common symptoms of cold, meningitis symptoms after fever and systemic symptoms, characterized by more acute onset, shorter duration, generally in 7 It can be recovered in ~10 days, and the prognosis is good. The characteristics of cerebrospinal fluid are the majority of lymphocytes, which can reach more than 95%, the sugar is normal, and the protein is slightly increased.

The diagnostic points of various viral meningitis are:

1 There are often specific seasons.

2 each has its own special systemic manifestations, such as enteroviruses may be associated with diarrhea, rash or myocarditis.

3 cerebrospinal fluid changes in addition to cell number and classification and brain is not easy to identify, biochemical changes are not the same, viral meningoencephalitis cerebrospinal fluid sugar and chloride normal or slightly higher, protein is not obvious, more than 1g / L (100mg / Dl).

4 various viral encephalitis or meningitis have their own specific laboratory diagnostic methods, such as serological examination and virus isolation.

3. The clinical manifestations of the new cryptococcal meningoencephalitis, chronic disease course and cerebrospinal fluid changes can be similar to the brain, but the course of disease is longer, can be accompanied by spontaneous relief, chronic progressive high intracranial pressure symptoms are more prominent, and other manifestations of meningitis are not parallel, The disease is rare in children, so it is easy to be misdiagnosed as the brain, the diagnosis is based on the smear of the cerebrospinal fluid, stained with black ink to reflect the round, cryptococcal spores with thick capsule refraction, sand preservation medium may have Cryptococcus neoformans growth, in addition, the detection of cryptococcal polysaccharide antigen in blood and cerebrospinal fluid by latex agglutination or complement binding test can aid diagnosis.

4. Brain abscess Brain abscess children have a history of otitis media or head trauma, sometimes secondary to sepsis, often accompanied by congenital heart disease, children with brain abscess in addition to meningitis and high intracranial pressure symptoms, often have focal Sexual brain sign, cerebrospinal fluid changes in the absence of secondary purulent meningitis, the number of cells can be from normal to hundreds, most of them are lymphocytes, sugar and chloride are normal, protein is normal or increased, differential diagnosis can be done with ultrasound , EEG, brain CT and cerebral angiography.

5. Brain tumors Brain tumors can be misdiagnosed as brains.

(1) Common causes of misdiagnosis:

1 pediatric brain tumor is about 70% under the curtain, especially in the fourth ventricle and cerebellum. Because of the small cranial cavity under the cerebellum, it is easy to have high intracranial pressure, but in small infants, the cranial suture is easy to split, making the symptoms of high intracranial pressure It is not obvious that symptoms will not appear until the late high intracranial pressure is high. The course of the disease seems to be very short, which is different from the long history of the older children.

2 pediatric brain tumors are mostly located in the midline, often lacking localization symptoms;

3 common cerebral vascular tumors in children may have meningeal irritation;

4 common medulloblastoma in infants and young children can be transmitted through the subarachnoid space, prone to brain signs, cranial nerve disorders and cerebrospinal fluid changes, almost like the brain.

(2) Brain tumor and knot brain identification points:

1 less fever.

2 convulsions are less common, even if there is convulsions, most of them are conscious after pumping, and children with advanced cerebral palsy are in a coma after convulsions.

3 coma is less common.

4 high intracranial pressure symptoms and brain signs are not parallel.

5 Cerebrospinal fluid changes are little or slight.

6 tuberculin test was negative and the lungs were normal.

7 for the diagnosis of brain tumors should be timely brain CT scan to assist in diagnosis.

(3) The brain must be differentiated from various encephalitis, cerebral cysticercosis and cerebral vascular malformation.

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