bubble_chart Overview

Subcutaneous node meningitis (tuberculous meningitis), abbreviated as tuberculous meningitis, is one of the severe subcutaneous node diseases, with a fatality rate as high as 100% if left untreated. It is more common in infants and young children, often occurring within 6 months to 1 year after the primary infection. If diagnosis and treatment are delayed or inappropriate, it can still lead to death and leave sequelae.

bubble_chart Clinical Manifestations

1. The onset is generally slow, with changes in temperament, irritability, easy agitation, headache, unexplained vomiting, and constipation. In infants and young children, the onset may be more acute, and seizures may occur first.
2. General subcutaneous node poisoning symptoms, as mentioned earlier.
3. Neurological changes and signs. (1) Meningeal irritation signs: neck stiffness, positive Kernig's sign. (2) Cranial nerve disorders: damage to the facial nerve (VII), oculomotor nerve (III), trochlear nerve (IV), optic nerve (II), etc. (3) Brain parenchyma damage: hemiplegia or crossed hemiplegia, aphasia, hyperactivity, chorea, etc. (4) Spinal cord symptoms: spinal nerve root symptoms, spinal cord compression symptoms, which may manifest as paraplegia, urinary retention, etc. (5) Hydrocephalus symptoms: headache, vomiting, high fever, seizures; decerebrate rigidity, sunset eyes, bulging anterior fontanelle, cranial suture separation, cranial "cracked pot" sound, irregular breathing, and in severe cases, brain herniation.

The above symptoms vary at different stages. 1 and 2 are early-stage symptoms, lasting about 1–2 weeks. 3(1) represents intermediate stage [second stage] manifestations, lasting about 1–2 weeks, while 3(2)–(5) are all advanced-stage manifestations, lasting about 1–3 weeks.

bubble_chart Auxiliary Examination

1. Cerebrospinal fluid examination:
   1. The typical appearance is ground-glass-like, with a total cell count of 100–300/mm³, predominantly lymphocytes, elevated protein, and decreased glucose and chloride.
   2. Detection of acid-fast bacilli in the cerebrospinal fluid membrane via acid-fast staining has specific diagnostic significance.
   3. Measurement of immunoglobulins in the cerebrospinal fluid: In affected children, IgG and IgA are primarily elevated, with IgM also increased; viral meningoencephalitis shows only grade I IgG elevation, with no increase in IgA or IgM; purulent meningitis exhibits elevated IgG and IgM. This aids in differential diagnosis. Using ELISA to measure anti-tuberculous antibodies in the cerebrospinal fluid or PCR to detect Mycobacterium tuberculosis DNA in the cerebrospinal fluid provides more specific diagnostic significance.
   4. Measurement of cerebrospinal fluid fluorescein sodium: The concentration of fluorescein sodium in the cerebrospinal fluid of affected children is ≥6×10⁻⁷, while other conditions such as viral encephalitis, cryptococcal meningitis, and brain tumors are below this value.
   5. Measurement of cerebrospinal fluid lactate: In untreated cases or those treated for less than two weeks, the lactate value is above 1.68 mmol/L (30 mg/dl); viral encephalitis is below this value.
   6. Blood and cerebrospinal fluid Mycobacterium tuberculosis nucleic acid tests are positive.
   7. Erythrocyte sedimentation rate (ESR) is increased, though it may not rise in the days before death in fulminant cases.
   8. OT or PPD test shows positive or strongly positive reactions. However, false negatives may occur in the following situations:
      1. Malnutrition, post-pandemic illness, and severely affected children;
      2. Approximately 1/6 show negative reactions about one week before death;
      3. Immunosuppressive therapy for three days can affect immune responses, resulting in negative results.
2. X-ray examination: About 80–90% of children with tuberculous meningoencephalitis have active pulmonary tuberculosis. This may present as miliary tuberculosis, which has greater diagnostic significance. A minority show old pulmonary tuberculosis. Normal lung findings do not exclude the diagnosis of tuberculous meningoencephalitis.

bubble_chart Treatment Measures

(1) General Treatment Strict bed rest is required, and a nutritious, easily digestible diet should be provided. For patients with unconsciousness, nasogastric feeding is necessary. Turn the patient and pat their back regularly to prevent hypostatic pneumonia and bedsore. Pay attention to the cleanliness of the eyes, mouth, nose, and skin. For those whose eyes cannot fully close, apply oil gauze to prevent corneal ulcers.

(2) Anti-subcutaneous node drugs should be selected based on the disease stage and drug characteristics. Combination therapy can prevent the emergence of drug-resistant strains. The treatment course should be sufficiently long and is divided into two phases.

1. **Intensive Treatment Phase**
   1. For severe cases: Use a combination of three anti-subcutaneous node drugs. Options include:
      1. - **INH + SM + RFP (or RFD)**: - INH: Half of the daily dose + 10% glucose, administered intravenously at 5 mg/h, with the remaining dose taken orally. - SM: Dosage same as for foxtail millet-type subcutaneous node, for 3 months. - RFP: Dosage as before. After 1–2 weeks of treatment, switch to oral administration if the condition improves. Concurrently administer vitamin B6.
      2. - **INH + RFP + EBM**: Dosage and usage as before, for 3 months.
      3. - **INH + ETH + EBM**: Dosage and usage as before, for 3 months.
      4. - **INH + PZA + EBM**: - INH: Dosage as before. - PZA (Pyrazinamide): 20–25 mg/(kg·d), maximum 1.5 g/d, for 3 months. Contraindicated in children under 3 years old. - EBM: Dosage as before.
   2. For mild or early-stage cases, use: - **INH + SM + EBM**: - INH: Dosage as before. - SM: Dosage as before, for 3–6 months. - EBM: Dosage as before.
2. **Consolidation Treatment Phase**: Similar to foxtail millet-type subcutaneous node, but the total course of isoniazid (INH) should be 1.5–2 years, or even 2.5 years in some cases.
3. **Intrathecal or Lateral Ventricle Injection**: Intrathecal injection is generally not recommended nowadays. However, for advanced-stage tuberculous meningitis, unsatisfactory treatment outcomes, or abnormal liver function requiring reduction or discontinuation of INH, intrathecal INH may be used. For children at risk of or already experiencing spinal cord obstruction, lateral ventricle puncture and drug injection can be performed. Each dose consists of: - INH: 25–50 mg - Dexamethasone: 0.5–1 mg or hydrocortisone acetate: 25 mg Diluted with normal saline to 5 ml, slowly injected after withdrawing an equal volume of cerebrospinal fluid. Start with a small dose and gradually increase. Initially administer once daily for 4 weeks. If clinical symptoms and cerebrospinal fluid improve, reduce to 3 times per week, then twice weekly, and finally once weekly. Continue for 3–4 months to consolidate efficacy.

(3) **Use of Adrenal Cortical Hormones** While administering sufficient anti-subcutaneous node drugs, appropriate use of hormones can rapidly alleviate toxic symptoms, reduce cerebral edema, lower intracranial pressure, and prevent skull base adhesions. Typically, prednisone is given at 1–2 mg/(kg·d), with gradual tapering and discontinuation as the condition improves. The course should not exceed 2–3 months, and long-term use is not recommended.

(4) **Treatment for Increased Intracranial Pressure**

1. In addition to hormones, diuretics and dehydrating agents may be used.
   1. - **Mannitol**: 1–2 g/kg per dose, administered via rapid IV drip or push, alternating with 50% glucose every 6 hours.
   2. - **Acetazolamide**: 20–40 mg/(kg·d), divided into 2–3 intermittent oral doses, taken for 4 days and stopped for 3 days.
   3. - **Hydrochlorothiazide**: Oral administration is less effective.
   4. - **Furosemide**: 2 mg/kg per dose, diluted in 50 ml of normal saline and administered IV, 2–3 times daily.
2. **Indications for Lateral Ventricle Drainage and Decompression**:
   1. - Initial treatment cases with impending brain herniation due to hydrocephalus. - Suspected brain herniation in children.
   3. Acute exacerbation of chronic hydrocephalus. Continuous closed drainage can be maintained, with a daily drainage volume generally ranging from 30 to 150ml, not exceeding 200ml/d. Pay attention to local disinfection to avoid secondary infection. The drainage duration is approximately 1 to 2 weeks. After drainage, the child's breathing may change from apnea and slowing to regular, high fever may subside, convulsions may stop, and consciousness may recover. This can buy time to receive anti-subcutaneous node treatment.
3. The goal of neurosurgical treatment is to thoroughly resolve the issue of increased intracranial pressure. The indications are:
   1. Obstructive hydrocephalus, ineffective after lateral ventricular drainage for decompression. If cerebrospinal fluid has returned to normal, a lateral ventricle-cisterna magna shunt can be performed.
   2. Chronic communicating hydrocephalus, ineffective with conservative treatment. After cerebrospinal fluid normalizes, a ventriculoperitoneal shunt can be performed.

(5) Symptomatic Treatment

1. For convulsions, phenobarbital sodium can be administered intramuscularly, or diazepam can be given intravenously or intramuscularly.
2. For peripheral neuritis or limb tremor and excessive mental excitement, administer diazepam and oral vitamins.
3. Correction of water and electrolyte imbalances: Unconscious children may experience varying degrees of water and electrolyte imbalances due to vomiting or insufficient intake. These should be corrected as needed, especially for cerebral hyponatremia, where rehydration should primarily use hypotonic solutions.

(6) Treatment of Sequelae

1. For epilepsy: Administer antiepileptic drugs such as phenobarbital, diazepam, phenytoin sodium, or carbamazepine.
2. For limb paralysis: Use acupuncture, physical therapy, and tuina to aid recovery.

bubble_chart Differentiation

1. Purulent meningitis: The key distinguishing feature is the cerebrospinal fluid (CSF) examination results, particularly the identification of purulent pathogens through smear or culture.
2. Viral encephalitis: The onset is relatively acute, with colorless and transparent CSF, normal chloride and sugar levels, and no membrane formation upon standing. It typically resolves spontaneously within 2–3 weeks. CSF immunoglobulin measurement and virus isolation aid in diagnosis.
3. Cryptococcal meningitis: It has a slower onset compared to tuberculous meningitis, with severe headache and disproportionately elevated intracranial pressure relative to other symptoms. Symptoms may occasionally resolve spontaneously. Multiple CSF smear examinations should be performed, and the diagnosis is confirmed by identifying thick-capsule round, shiny fungal bodies with India ink staining or by culturing Cryptococcus on Sabouraud's medium.