Tuberculous meningitis
Release time : 01/18/2025 18:13:27
Tuberculous meningitis is the most important type of tuberculosis in children. It is an inflammatory disease of the meninges and spinal cord caused by Mycobacterium tuberculosis.
In recent years, the incidence and mortality of tuberculosis have increased due to genetic mutations of Mycobacterium tuberculosis, relatively delayed development of anti-tuberculosis drugs, and the increase in AIDS patients.
However, if diagnosed in the early stages and treated appropriately, the majority can recover.
What is Tuberculous meningitis? Tuberculous meningitis (TBM) is a non-suppurative inflammatory disease of the meninges and spinal membranes caused by Mycobacterium tuberculosis, and is one of the most important types of childhood tuberculosis. It generally occurs within 3 months to 1 year after the initial tuberculosis infection, and is more common in children aged 1-3 years.
The disease progresses over 3-6 weeks, from onset to death in tuberculous meningitis, and is the most important cause of death among children with tuberculosis.
Before the advent of antituberculosis drugs, mortality from tuberculosis approached 100%.
The incidence of this disease has been significantly reduced and the prognosis has greatly improved since widespread vaccination of BCG vaccine and vigorous prevention and treatment of tuberculosis. If early diagnosis and early reasonable treatment, most cases can be cured.
In recent years, due to the genetic mutations of Mycobacterium tuberculosis, the lag in drug development for tuberculosis, and an increase in AIDS patients, the incidence and mortality rates of tuberculosis have been rising domestically and internationally.
However, once promptly identified and treated, patients can recover completely. However, if the diagnosis is delayed or treatment is improper, the mortality rate and incidence of sequelae remain high.
Therefore, early diagnosis and rational treatment are key to improving the prognosis of this disease.
Additionally, many mothers are curious about whether tuberculous meningitis can be transmitted. In fact, tuberculous meningitis is not contagious; mothers need not worry.
The etiology of tuberculous meningitis is not clear. It accounts for 6% of all cases of tuberculosis. Tuberculous bacilli spread through the blood and colonize beneath the pia mater, forming tuberculomas. When these tumors rupture, a large number of tubercle bacilli enter the subarachnoid space.
Tuberculous bacilli invade the lymphatic system and enter localized lymph nodes. Due to hematogenous dissemination, they spread throughout the meninges and brain parenchyma, including subventricular regions, and replicate there.
When the host's immune function is reduced or due to aging, the TB bacilli within the lesion activate and break into the subarachnoid space, spreading along with the cerebrospinal fluid, which can cause tuberculous meningitis over a period of days to weeks.
Tuberculous meningitis is often a part of the generalized miliary tuberculosis and spreads through hematogenous dissemination.
Among 1,180 cases of meningococcal sepsis seen in Peking Children's Hospital from 1964 to 1977, 44.2% were found to have miliary tuberculosis.
Among the 14 cases of encephalitis, 94% had other TB in other organs.
There were 142 cases of tuberculosis (93.4%) (among whom miliary type was the most frequent).
Consolidated sputum tuberculosis of the liver and spleen accounts for about 62%, renal sputum tuberculosis 41%, and intestinal and mesenteric lymphadenitis accounts for about 24%.
During the formation of primary tuberculosis lesions, Mycobacterium tuberculosis can be spread via blood circulation to settle in the meninges, brain parenchyma, and spinal cord, forming concealed tuberculosis foci. These include tuberculous nodules and tuberculomas.
Once the aforementioned lesions are breached,
Tuberculous bacilli directly penetrate the subarachnoid space, causing tuberculous inflammation.
Additionally, lesions in adjacent tissues such as the middle ear, mastoid, cervical spine, and skull can directly spread and invade the meninges, although this is somewhat less common.
The occurrence of tuberculous meningitis is associated with a heightened hypersensitivity to the causative organism at the time of primary tuberculosis infection.
From the viewpoint of pathogenesis, tuberculous meningitis is a secondary infection and therefore should be emphasized in search for the primary focus.
However, there are also a few cases where the primary lesion has been cured or cannot be found. In such cases, it is even more important to remain vigilant to avoid misdiagnosis.
What are the symptoms of tuberculous meningitis? The severity of symptoms varies for tuberculous meningitis; generally, there are 10 to 20 days of prodromal symptoms before the onset of the disease. These include mental restlessness, general weakness, loss of appetite, emotional instability, irritability, low-grade fever, nausea, vomiting, constipation, etc.
Subsequently, patients with tuberculous meningitis gradually exhibit symptoms of somnolence, intensified headache, and expulsive vomiting accompanied by neck stiffness, all of which indicate elevated intracranial pressure due to cerebral encephalitis.
Even more so, there may be confusion or even a loss of consciousness, gradually leading to coma.
At this time, all reflections disappear, incontinence occurs, pupils fixate, the pulse rate increases, respiration becomes irregular, and ultimately leads to death.
Tuberculous meningitis often presents with a hidden onset and a chronic course, but may also manifest acutely or subacutely, lacking a history of tuberculosis contact. The symptoms of tubercular meningitis are generally: 1. Tuberculous toxemia symptoms such as low fever, night sweats, loss of appetite, general malaise, fatigue, and lethargy.
2. The early manifestations of meningeal irritation and increased intracranial pressure include fever, headache, vomiting, and signs of meningeal irritation.
In the early stages, intracranial hypertension is caused by inflammatory responses in the meninges, cisterns, and ventricles due to increased production of cerebrospinal fluid, decreased absorption by arachnoid granulation cells, resulting in communicating hydrocephalus.
Intracranial hypertension is typically mild to moderate and lasts for 1 to 2 weeks.
Advanced cerebrospinal fluid (CSF) and arachnoid bands are adherent, presenting either complete or incomplete obstructive hydrocephalus.
The intracranial pressure is significantly elevated, presenting symptoms such as headache, vomiting, and papillary edema of the optic nerve.
In severe cases, it can also present with tonic seizures or delirium.
3. In cases of cerebral lesion where the early treatment is not timely, symptoms of cerebral lesion may appear 4-8 weeks after onset. These symptoms include lethargy, apathy, delirium or delusions, partial or generalized seizures or status epilepticus, and stupor or confusion.
Paraplegia caused by tuberculous arteritis may present as a stroke-like episode, resulting in hemiplegia and crossed hemiplegia.
In cases caused by tuberculous nodules or cerebellar-spinal meningitis, the manifestation is similar to a tumoric chronic paralysis.
4. Brain nerve damage due to inflammation in the cranial base and exudates can stimulate, adhere, and compress nerves, leading to brain nerve damage. The oculomotor, abducens, facial, and visual nerves are most susceptible to injury, manifesting as diminished vision, diplopia, and facial paralysis, respectively.
5. Characteristics of tuberculous meningitis in the elderly: If the elderly develop tuberculous meningitis, they may have mild headache and vomiting symptoms, and the symptoms of increased intracranial pressure may not be prominent. Approximately half of the patients may exhibit atypical changes in their cerebrospinal fluid. However, there is a higher incidence of cerebral infarction caused by tuberculous arteritis on the basis of atherosclerosis.
Tuberculous meningitis examination and diagnosis: How is tuberculous meningitis diagnosed? Tuberculous meningitis patients' blood routine tests are mostly normal, but some may have elevated erythrocyte sedimentation rates. Patients with antidiuretic hormone syndrome may present with hyponatremia and hypochloremia.
Approximately half of the patients exhibit positive skin tuberculin test results or evidence of active or old tuberculosis infection in chest X-rays.
The CSF pressure may reach 400 mmH2O or more, and its appearance is clear or slightly yellowish. After standing, a film may form.
Lymphocytes are significantly increased, often at (50-500) x 106/L.
Protein elevation, typically between 1 to 2 g/L, along with a decrease in glucose and chloride, are characteristic findings that strongly suggest the diagnosis.
CSF anti-acid staining may be positive in only a few cases, while CSF culture for Mycobacterium tuberculosis can confirm the diagnosis but requires large amounts of cerebrospinal fluid and several weeks.
CT can display the basal cisterns and cortical meninges, enhancement, and hydrocephalus.
Based on a history of tuberculosis or exposure, symptoms such as headache and vomiting, meningeal irritation signs, and characteristic changes including increased lymphocytes in the cerebrospinal fluid and decreased sugar content. Diagnosis can be made by CSF acid-fast smear, tuberculosis culture, and PCR tests.
The early diagnosis of tuberculous meningitis is crucial.
However, if the doctor lacks experience, it will lead to a delay in making a diagnosis.
Patients with afternoon fever, headache, vomiting and urinary retention should seek medical attention as early as possible. Especially when the doctor suggests a lumbar puncture to obtain cerebrospinal fluid (CSF), one should not refuse it because this examination is the only reliable method for diagnosing the disease. Its significance sometimes exceeds that of CT and MRI scans.
The principle of treatment and prevention of tuberculous meningitis is early drug administration, rational drug selection, combined drug use, and systematic treatment. Patients who present with high clinical symptoms and signs and laboratory examinations suggestive of this disease should start anti-tubercular treatment even if acid-fast staining is negative.
1. The most effective combined medication regimen for the treatment of tuberculous meningitis includes isoniazid, rifampin, pyrazinamide, or ethambutol and streptomycin.
Children are advised to avoid the use of Ethambutol due to its ocular toxicity and pregnant women should refrain from using Streptomycin for its effect on auditory nerves.
Isoniazid.
Isoniazid can inhibit the DNA synthesis of Mycobacterium tuberculosis, and destroy the enzyme activity in the bacterium. It can kill both the intracellular and extracellular Mycobacterium tuberculosis.
Regardless of whether there is inflammation in the meninges, it can quickly penetrate into the cerebrospinal fluid.
Individual use can easily lead to the emergence of drug resistance.
The primary adverse reactions include peripheral neuropathy and hepatic damage.
(2) Rifapentine.
Rifampin binds to the RNA polymerase of bacteria and interferes with the synthesis of mRNA, inhibiting the growth and reproduction of bacteria and leading to their death.
It possesses bactericidal activity against both intracellular and extracellular Mycobacterium tuberculosis.
Rifampin is not able to penetrate through the normal meninges but only partially through the inflammatory meninges, making it a commonly used medication for treating meningitis.
Isolated application can also easily lead to drug resistance.
The main adverse reactions include hepatotoxicity and allergic reactions.
Pyrazinamide.
It has a better antibacterial effect in acid environment, and its activity is the highest at pH 5.5, which can kill Mycobacterium tuberculosis slowly growing in phagocytic cells in acidic environment, but it has almost no effect on Mycobacterium tuberculosis in neutral and alkaline environment.
Pyrazinamide can freely cross the normal and inflamed meninges, and is an important anti-tuberculous drug for treating tuberculous meningitis.
The primary adverse reactions include liver damage, joint pain, swelling, stiffness, limited mobility, and increased uric acid levels.
Streptomycin.
This is an aminoglycoside antibiotic, which only has killing effect on Mycobacterium tuberculosis outside phagocytic cells and is a semi-lethal bactericide.
Streptomycin can penetrate the partial inflammatory meningeal barrier and is one of the important drugs in early treatment of tuberculous meningitis.
The main adverse reactions include ototoxicity and nephrotoxicity.
(5) Ethambutol.
Ethambutol forms a complex with divalent zinc ions, interfering with the functions of polyamines and metal ions, affecting pentose metabolism and the synthesis of deoxyribonucleic acid and nucleotides, thereby inhibiting the growth of Mycobacterium tuberculosis.
It is effective against actively growing and reproducing tuberculosis bacteria, but has little to no effect on bacteria in a dormant or stationary state.
The main adverse reactions include optic nerve damage, peripheral neuritis, allergic reactions, etc.
Corticosteroids are a type of medication used for patients with severe conditions such as increased intracranial pressure caused by cerebral edema, accompanied by focal neurological signs and subarachnoid space obstruction. They can alleviate toxic symptoms, suppress inflammatory responses, and reduce cerebral edema.
In cases where intrathecal drug administration leads to a significant increase in cerebrospinal fluid (CSF) protein levels, early spinal canal obstruction, abnormal liver function resulting in the discontinuation of some anti-tuberculosis drugs, and in chronic, recurrent, or drug-resistant situations, intrathecal injection can be used as an adjunct to systemic drug therapy until CSF examination results return to normal.
However, this method must be used with caution in patients with elevated cerebrospinal fluid pressure.
For patients with increased intracranial pressure, osmotic diuretics such as 20% mannitol, glycerol fructose, or glycerol saline can be used to reduce intracranial pressure. It is also essential to promptly replenish lost fluids and electrolytes.
Tuberculous meningitis is a treatable condition and is not as frightening as it may seem.
Antituberculosis drugs such as isoniazid and pyrazinamide can effectively "cross the blood-brain barrier." When used in combination with streptomycin and ethambutol, they generally yield satisfactory results. However, the dosage required is higher than that for treating pulmonary tuberculosis, and the treatment duration is longer, typically lasting about two years. Premature discontinuation of the medication can easily lead to relapse.
Patients must adhere strictly to the doctor's instructions, cooperate closely with medication administration, and complete treatment.
Finally, how can we prevent tuberculous meningitis? 1. Strengthen physical exercise to enhance physical fitness, maintain optimism, balance work and rest, and ensure vigorous vital energy, thereby reducing the incidence of disease.
2. Positively treat the primary tuberculosis, thoroughly eliminate the lesions of tuberculosis and prevent secondary infection.
The administration of the Bacillus Calmette-Guérin (BCG) vaccine not only prevents the occurrence of tuberculosis but also significantly reduces the incidence rate of tuberculous meningitis in newborns when administered at this stage.
The medical information provided in this text is for reference only.
Should you experience discomfort, it is recommended to seek medical attention immediately, with the diagnosis and treatment provided by a face-to-face clinician.