What Is Tuberculous Meningitis?

According to the classification method of the British Medical Research Council, Jie Nao can be divided into the following 3 phases:

Su Yingying	(Chief physician)	Department of Neurology, Xuanwu Hospital, Capital Medical University
Zhang Yunzhou	(Deputy Chief Physician)	Department of Neurology, Xuanwu Hospital, Capital Medical University

Tuberculous meningitis (TBM) is a non-purulent inflammatory disease of the meninges and meninges caused by Mycobacterium tuberculosis. About 5% to 15% of patients with extrapulmonary tuberculosis involve the nervous system, and tuberculous meningitis is the most common, accounting for about 70% of tuberculosis of the nervous system. In recent years, the incidence and mortality of tuberculosis at home and abroad have gradually increased due to genetic mutations in tuberculosis, relatively late development of anti-tuberculosis drugs, and an increase in patients with AIDS.

Western Medicine Name

Tuberculous meningitis

English name

tuberculous meningitis. TBM

Disease site

brain

Main cause

Mycobacterium tuberculosis infection

Classification of tuberculous meningitis diseases

According to the classification method of the British Medical Research Council, Jie Nao can be divided into the following 3 phases:

Phase 1: no specific symptoms and signs, unconscious ambiguity, no impaired nervous system function;

Phase 2: Meningeal irritation, mild impaired nervous system function (such as cerebral palsy), and abnormal motor function;

Stage 3: Convulsions or convulsions, lethargy or coma, severe impaired nervous system function (such as paralysis or general paralysis).

Etiology of tuberculous meningitis

The pathogen of tuberculosis is Mycobacterium tuberculosis. Mycobacterium tuberculosis belongs to the genus Actinomycetes, Mycobacterium, and Mycobacterium in classification. Including human, cattle, African and mouse types. More than 90% of the pathogens of humans infected with tuberculosis are human-type Mycobacterium tuberculosis, and a few are bovine-type and African-type Mycobacterium. Mycobacterium tuberculosis has biological characteristics such as polymorphism, acid resistance, slow growth, strong resistance, and complex bacterial structure.

Pathogenesis and pathophysiology of tuberculous meningitis

In the early stage of the disease, due to the inflammatory response of the meninges, choroid plexus, and ependyme, the production of cerebrospinal fluid increased, the absorption of arachnoid particles decreased, and traffic hydrocephalus was formed. The intracranial pressure was mild and moderately increased. Late arachnoid and choroid plexus adhesions, showing complete or incomplete obstructive hydrocephalus, cause marked increase in intracranial pressure.

The tuberculous exudate around the ruptured tubercle nodules at the base of the brain spread in the subarachnoid space to the basal cistern and lateral fissure. Light microscopy exudates consist of polymorphonuclear leukocytes, macrophages, lymphocytes and red blood cells with different numbers of bacteria in the fibrin network. As the disease progresses, lymphocytes and connective tissue dominate. The arterioles and middle arteries through which the exudate passes, as well as some other blood vessels (capillaries and veins), can become infected, forming tuberculous vasculitis, leading to blockage of blood vessels and cerebral infarction. In chronic infection, tuberculous exudate can block the basal pool and the fourth ventricle outflow pathway, causing hydrocephalus.

Clinical manifestations of tuberculous meningitis

Multiple episodes are concealed, the chronic course can also be acute or subacute, and the history of tuberculosis exposure is lacking. Symptoms are often of different severity. The natural course of the disease is generally expressed as:

Tuberculous meningitis tuberculosis symptoms

Low fever, night sweats, loss of appetite, general malaise, and malaise.

Tuberculous meningitis meningeal irritation and increased intracranial pressure

Early manifestations are fever, headache, vomiting, and meningeal irritation. Increased intracranial pressure is caused by inflammatory reactions of the meninges, choroid plexus, and ventricles in the early stage, resulting in increased production of cerebrospinal fluid, decreased absorption of arachnoid particles, and formation of traffic hydrocephalus. Intracranial pressure is mostly mild and moderately elevated, usually lasting 1 to 2 weeks. Late arachnoid and choroid plexus adhesions, showing complete or incomplete obstructive hydrocephalus, increased intracranial pressure, and manifested headache, vomiting, and papillary edema. In severe cases, a denervation or decortical state occurs.

Tuberculous meningitis brain parenchymal damage

If early treatment is not timely, symptoms of brain parenchymal damage often occur 4 to 8 weeks after the onset, such as dementia, indifference, delirium or delusion, partial or systemic seizures or persistent state of epilepsy, lethargy or confusion; limb paralysis such as cause It is caused by tuberculous arteritis, which may be stroke-like, with hemiplegia, cross paralysis, etc .; if it is caused by tuberculoma or cerebrospinal arachnoiditis, it appears as a chronic paralysis similar to a tumor.

Tuberculous meningitis cerebral nerve damage

Stimulation, adhesion, and compression of inflammatory exudates at the base of the skull can cause brain nerve damage. Eye movement, abduction, facial and optic nerves are the most susceptible, showing visual loss, diplopia, and facial nerve paralysis.

TBM Characteristics of TBM in the elderly with tuberculous meningitis

Headache and vomiting are mild, and the symptoms of increased intracranial pressure are not obvious. About half of the patients' cerebrospinal fluid changes are not typical, but tuberculous endarteritis occurs on the basis of arteriosclerosis and causes more cerebral infarction. ^[1]

Diagnosis and differential diagnosis of tuberculous meningitis

Diagnosis of tuberculous meningitis

1) The patient has a history of tuberculosis in other parts, such as a history of tuberculosis.

2) Most acute or subacute onset.

3) Mainly manifested as fever, headache, vomiting, general weakness, loss of appetite, poor spirit, and positive meningeal irritation sign. In the later stage of the disease, there may be manifestations of cerebral nerve and brain parenchyma, such as diplopia, limb paralysis, coma, seizures, brain Hernia, etc.

4) Peripheral blood white blood cell count increased, erythrocyte sedimentation rate increased, skin tuberculin test positive or chest X-ray showed active or old tuberculosis infection evidence.

5) CSF pressure can be increased to 400mmH2O or above, the appearance is colorless and transparent or slightly yellow, and a film can be formed after standing; lymphocytes increase significantly, often 50 to 500 × 106 / L; protein increases, usually 1 2g / L, sugar and chloride decreased, acid-fast staining of cerebrospinal fluid smear showed tuberculosis bacteria.

6) Skull CT or MRI mainly manifests as meningeal enhancement. Obstructive hydrocephalus, cerebral infarction, tuberculosis, etc. can also be found. ^[2]

Differential diagnosis of tuberculous meningitis

1) Cryptococcal meningitis: Subacute or chronic meningitis, similar to the course of TBM and changes in CSF. When early clinical manifestations of TBM are not typical, it is not easy to identify them with cryptococcal meningitis. Try to find tuberculosis and new cryptococcal infections. Laboratory evidence.

2) Purulent meningitis: The clinical manifestations of severe TBM are similar to those of purulent meningitis. The number of CSF cells> 1000 × 106 / L and the classification of neutrophils are more difficult to identify, and two-way treatment can be performed if necessary.

3) Viral meningitis: Mild or early TBM cerebrospinal fluid changes are similar to viral meningitis, and can be antituberculosis and antiviral treatment at the same time. Observation and search for diagnostic evidence. Viral infections are usually self-limiting, with a marked improvement or healing around 4 weeks, and the course of TBM is prolonged and cannot be cured in a short time.

4) Sarcoid meningitis: Sarcoidosis is a chronic granulomatous disease involving multiple organs. It is common in the lungs and lymph nodes. It often involves the meninges and peripheral nerves. Autopsy finds that meningeal involvement accounts for 100%, but clinically only 64% Patients had symptoms and signs of meningeal involvement. Intracranial pressure was normal or increased, 70% of patients had increased CSF cells, increased protein (up to 20 g / l), and decreased sugar (0.8-2.2 mmol / l).

5) Meningeal cancer: Meningeal cancer is caused by the transfer of malignant tumors from other organs of the body to the meninges, and extracranial cancerous lesions can be found through a comprehensive examination. Very few patients have cerebral tuberculoma, showing progressively increasing headaches for several weeks or months, accompanied by seizures and acute focal brain injury. Enhanced CT shows single lesions in the cerebral hemisphere and other parts. CSF tests are usually normal. ^[3]

Treatment of tuberculous meningitis disease

The principle of treatment of this disease is early administration, rational drug selection, combined use and systemic treatment. As long as the patient's clinical symptoms, signs and laboratory tests are highly suggestive of the disease, antituberculosis treatment should be started immediately even if the acid-fast staining is negative.

Antituberculous treatment for tuberculous meningitis

Isoniazidyl (hydrazide (INH), rifampicin (RFP), pyrazinamide (PZA) or ethambutol (EMB), streptomycin (SM) are the best treatments for TBM An effective combination regimen is not recommended for children due to the neurotoxic effects of ethambutol and pregnant women due to the effects of streptomycin on the auditory nerve.

a) Isoniazid: Isoniazid can inhibit the DNA synthesis of Mycobacterium tuberculosis, destroy the enzyme activity in the bacteria, and have a killing effect on Mycobacterium tuberculosis inside and outside the cell. Regardless of meningeal inflammation, it can quickly penetrate into the cerebrospinal fluid. Application alone is prone to drug resistance. The main adverse reactions were peripheral neuritis and liver damage.

b) Rifampicin: Rifampicin combines with bacterial RNA polymerase, interferes with mRNA synthesis, inhibits bacterial growth and reproduction, and causes bacterial death. It has a killing effect on tubercle bacilli inside and outside the cell. Rifampicin cannot pass through the normal meninges, but only partially through the inflammatory meninges. It is a commonly used drug for treating nodule. Application alone is also prone to drug resistance. The main adverse reactions are liver toxicity and allergic reactions.

c) Pyrazinamide: strong bactericidal effect in acidic environment, the strongest bactericidal effect at pH 5.5, can kill Mycobacterium tuberculosis in slow-growing phagocytic cells in acidic environment, and against Mycobacterium tuberculosis in neutral and alkaline Almost no effect. Pyrazinamide penetrates into phagocytic cells and enters the body of Mycobacterium tuberculosis. Amidase in the bacteria deaminates the amido group, converts it into pyrazinate and exerts bactericidal effect. Pyrazinamide can pass freely through normal and inflammatory meninges, and is an important anti-tuberculosis drug for the treatment of tuberculous meningitis. The main adverse reactions were liver damage, joint pain, swelling, rigidity, limited mobility, and increased blood uric acid.

d) Streptomycin: It is an aminoglycoside antibiotic, which only kills tuberculosis bacteria that phagocytose outside the cell. It is a semi-effective bactericide. Mainly by interfering with aminoacyl-tRNA and binding to the ribosomal 30S subunit, it inhibits the formation of 70S complexes, inhibits peptide chain extension, protein synthesis, and causes bacterial death. Streptomycin can penetrate part of the inflammatory blood-brain barrier and is one of the important drugs for early treatment of tuberculous meningitis. The main adverse reactions were ototoxicity and renal toxicity.

e) Ethambutol: complexes with divalent zinc ions, interferes with the functions of polyamines and metal ions, affects pentose metabolism and the synthesis of DNA and nucleotides, and inhibits the growth of tubercle bacilli. It has an effect on the growth and reproduction of Mycobacterium tuberculosis, and has almost no effect on the bacteria in the stationary state. The main adverse reactions were optic nerve damage, peripheral neuritis, and allergic reactions.

The WHO recommends that at least three drugs should be selected for combination therapy. Isoniazid, rifampicin, and pyrazinamide are commonly used. Pyrazinamide can be discontinued after 3 months of treatment in mild patients, and isoniazid and rifampicin can be continued. 7 Months. Drug-resistant strains can be added with a fourth drug such as streptomycin or ethambutol. Rifampicin-resistant strains are sufficient for 9 months; rifampicin-resistant strains need to be treated continuously for 18 to 24 months. Due to the rapid isoniazid type in Chinese, the daily dose for adult patients can be increased to 900-1200mg, but hepatoprotective treatment should be taken to prevent liver damage and take vitamin B6 at the same time to prevent peripheral neuropathy caused by the drug.

Corticosteroids for tuberculous meningitis

It can be used in severe patients with increased intracranial pressure caused by cerebral edema, with focal neurological signs and obstruction of the subarachnoid space. It can reduce symptoms of poisoning, suppress inflammation and reduce cerebral edema. Adults often take prednisone 60mg orally, which is gradually reduced after 3 to 4 weeks and discontinued within 2 to 3 weeks.

Intrathecal injection of tuberculous meningitis drug

Cerebrospinal fluid protein was significantly increased, early spinal obstruction, liver function abnormalities caused some anti-tuberculosis drugs to be discontinued, chronic, relapsed or drug resistant. Intrathecal injection can be supplemented with systemic drug treatment, isoniazid 0.1 g. Dexamethasone 5-10mg, -chymotrypsin 4000U, hyaluronidase 1500U, once every 2 to 3 days, the injection should be slow; twice a week after the symptoms disappear, and 1 to 2 weeks after the signs disappear 1 time until CSF examination is normal. Use this method with caution in patients with high cerebrospinal fluid pressure.

Tuberculous meningitis reduces intracranial pressure

Those with increased intracranial pressure can choose osmotic diuretics, such as 20% mannitol, glycerol fructose, or glycerol saline, etc., and need to replenish the lost fluids and electrolytes in time.

Prognosis of tuberculous meningitis disease

The prognosis is related to the patient's age, condition, and timely treatment. Coma is an important indicator of poor prognosis at the time of onset; clinical symptoms and signs have completely disappeared, and the CSF cells, protein, sugar, and chloride return to normal, indicating a good prognosis. The case fatality rate was related to advanced age, delayed diagnosis and treatment, and irrational medication, and was positively correlated with patient's disturbance of consciousness, neurological signs, and increased cerebrospinal fluid protein (> 3g / L). The clinical manifestations of elderly patients with TBM are atypical, with poor general conditions, more comorbidities, and a higher mortality rate. The mortality rate of TBM with HIV infection is higher. TBM deaths are caused by conventional multiple organ failure, cerebral hernia, etc. Survivors may have sequelae such as mental retardation in children, seizures, visual disturbances and paralysis of extraocular muscles.

Tuberculous meningitis disease prevention

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

Nursing for tuberculous meningitis disease

Tuberculous meningitis general care

Patients with nodule should be absolutely bed rested, keep the ward clean, tidy, quiet, and dim, pay attention to ventilation, and focus on nursing operations as much as possible to avoid moving the patient's neck multiple times or changing positions suddenly. Keep your stools open, and constipation give laxatives to prevent cerebral hernias caused by intracranial pressure fluctuations caused by increased abdominal pressure.

Tuberculous meningitis psychological care

Patients with nodular brain have a long illness and high mental stress. They often have fear, even pessimism and disappointment, have a sense of dying, and are nervous and lose confidence in treatment. Therefore, the nurse should explain the etiology, pathogenesis, diagnosis and treatment process and prognosis of the patient in detail, and introduce the role, adverse reactions and preventive measures of the drug to the patient before using the drug, so that they have a full understanding and preparation for the disease. Relieve ideological anxieties, build confidence in defeating the disease, and actively cooperate with treatment with the best psychological state.

Observation of tuberculous meningitis

Closely observe the changes in the patient's vital signs, such as body temperature, breathing, pulse, blood pressure, close observation of pupil size, reflection of light, and found that headache and vomiting increase, progressive increase in disturbance of consciousness, bilateral pupil size unequal, irregular breathing, pulse change Slow and elevated blood pressure, etc., suggest that increased intracranial pressure and the formation of cerebral hernia should be reported to the doctor in a timely manner for rescue work.

Nursing for tuberculous meningitis

a) Application and care of dehydrating agents: The dehydrating agents commonly used in the nodule are hypertonic dehydrating agents and diuretics. Therefore, firstly, it is necessary to keep the venous channel unobstructed and accurately record the 24h intake and output. At present, the commonly used dehydrating agent is 20% mannitol, which is very irritating to blood vessels. The nurse should protect the patient's blood vessels. If there is leakage or leakage, immediately apply a 50% magnesium sulfate solution to reduce the irritation of the skin and mucous membranes. .

b) Hormone application and care: Inaccurate metering of hormones, excessive dosage or improper reductions may cause rebound phenomena, so it is necessary to strictly follow the doctor's order to administer, and instruct patients not to add or reduce drugs at will.

c) Application and care of anti-tuberculosis drugs: Adverse drug reactions such as gastrointestinal reactions, liver damage, renal damage, hearing impairment, allergic reactions, etc. should be closely observed when applying tuberculosis drugs. .

d) Diet and nursing: Frequent vomiting due to high intracranial pressure in patients with nodular brain, appetite decreased due to anti-tuberculosis drugs irritating the gastrointestinal tract, persistent fever and the application of a large number of dehydrating agents caused disorders in water, electrolyte and acid-base balance. Therefore, patients should be encouraged to drink more water, eat small meals, and give high-calorie, high-protein, high-vitamin, and high-calcium diets after consciousness. Patients with coma should use a nasal feeding fluid diet. Patients with gastrointestinal bleeding and severe illness should increase parenteral nutrition. ^[4]