Tuberculosis - I.T. Pyatnochka 2005

Extrapulmonary tuberculosis
Tuberculosis of the nervous system and meninges

Tuberculous meningitis is an inflammation of the Meninges of the Brain and/or Spinal Cord caused by Mycobacterium tuberculosis. Specific involvement of the meninges and brain parenchyma is known as tuberculous meningoencephalitis.

In Ukraine, throughout the 1990s, the incidence of tuberculous meningitis remained stably low at 0.08–0.13 per 100,000 population, while mortality was relatively high (0.053–0.086 per 100,000 population). In recent years, these figures have worsened.

Pathogenesis. Tuberculous meningitis can be primary (in 20% of cases) or secondary (in 80%), occurring as a complication of Primary tuberculosis in children and adolescents, and predominantly Disseminated Pulmonary Tuberculosis in adults. Mycobacteria penetrate the subarachnoid space of the brain and/or spinal cord via hematogenous, lymphogenous, and rarely, perineural routes.

Pathological anatomy. The specific process localizes predominantly in the pia mater of the Base of the brain, affecting the Cranial Nerves located in this area. The disease may manifest as meningoencephalitis (64–70%), involving inflammation of both the meninges and the brain parenchyma; as Basal meningitis (20–30%), involving the cerebral meninges; or as spinal meningitis (4–6%), involving the spinal meninges.

In tuberculous meningitis, exudate, tuberculous tubercles, and delicate fibrin strands appear on the pia mater. Pathological changes are also observed in the choroid plexus of the brain ventricles.

Clinical presentation. Tuberculous meningitis typically has a gradual onset, preceded by a prodromal period lasting from 1 to 4 weeks. Patients experience generalized weakness, irritability, Sleep disturbances, emotional lability, mild intermittent headaches, often low-grade fever, and a tendency toward constipation. Subsequently, overt clinical signs of leptomeningeal inflammation emerge, including a rise in Temperature to a febrile range, severe throbbing headaches accompanied by vomiting, and the gradual development of meningeal signs: nuchal rigidity, and Kernig's and Brudzinski's signs. Inflammation of the pia mater at the base of the brain leads to involvement of the oculomotor and abducens cranial nerves. Brain edema causes central-type paresis of the VII, IX, X, and XII pairs of cranial nerves. Involvement of the diencephalic region results in neurocirculatory disturbances manifested by vasomotor reactions, persistent red dermographism, Trousseau's spots, relative bradycardia, and sleep and appetite disorders. The disease may progress as meningoencephalitis, in which case focal neurological signs of brain damage are observed, such as hemiparesis and hemiplegia. When the spinal meninges and roots become involved, pain appears in the thoracic and lumbar spine, accompanied by peripheral paresis and paralysis. As the meningitis progresses, lower paraparesis and pelvic organ dysfunction develop, presenting with urinary hesitancy, constipation, and urinary and fecal incontinence.

In the third, terminal stage of tuberculous meningitis (the stage of paresis and paralysis), patients exhibit profound adynamia, complete apathy toward their surroundings, clouded consciousness, and progression into a stupor or coma. All of this may be accompanied by a characteristic lateral decubitus posture with the HEAD hyperextended and the legs drawn up toward the abdomen.

Overall, the clinical picture of tuberculous meningitis comprises five key components (syndromes):

I. Intoxication syndrome;

II. meningeal syndrome: headache, vomiting, hyperesthesia.

Meningeal signs: nuchal rigidity, positive Kernig's, Brudzinski's, Guillain's, and Lesage's signs; scaphoid abdomen, "gundog" (fetal) posture.

III. symptoms of cranial nerve damage (III, VI, VII, XII) and spinal nerve roots. Depressed tendon and periosteal Reflexes, as well as asymmetric abdominal reflexes.

IV. CEREBROSPINAL FLUID (CSF) alterations: the fluid is typically clear or opalescent, emerging under increased pressure (normal is up to 60 drops per minute); elevated Cell count (100–300 Cells per 1 mL, normal is up to 10), increased protein content (0.6–1.0 g/L or more, normal is 0.2–0.4 g/L), decreased glucose concentration (1.5 mmol/L or less, normal is 2.22–3.88 mmol/L), decreased chloride concentration (110 mmol/L or less, normal is 120–130 mmol/L), positive Pandy and Nonne-Apelt reactions, and The formation of a delicate web-like fibrin pellicle in the CSF within 24 hours, in which Mycobacterium tuberculosis is detected in 10–20% of cases.

Notably, During the first days of the disease, neutrophil leukocytes predominate in the CSF, but pleocytosis rapidly shifts to a lymphocytic profile.

V. Symptoms of neurological deficit and irritation due to brain tissue involvement: central-type paresis and paralysis, speech disorders (aphasia, alalia), and mental status changes (clouded consciousness, stupor, and coma).

Depending on the primary site of meningeal involvement, three forms of tuberculous meningitis are distinguished: basal, spinal, and meningoencephalitis. Basal meningitis is characterized by meningeal signs and frequently by evidence of cranial nerve involvement, predominantly the oculomotor, abducens, facial, and hypoglossal nerves. In the spinal form of tuberculous meningitis, the initial manifestations are symptoms of spinal meningeal and ROOT irritation—specifically, pain in the lumbar and thoracic spine, pelvic organ dysfunction, paresthesias, and lower limb paresis—which are subsequently followed by the picture of classic meningitis. Meningoencephalitis is characterized by a meningeal symptom complex, cranial nerve deficits, focal brain lesions, and central hemiparesis and paralysis.

Diagnosis. The single most important diagnostic method for tuberculous meningitis is CSF analysis. Normalization of the cerebrospinal fluid during Treatment takes no less than 2–4 months. If normalization occurs within a month, the tuberculous Etiology of the meningitis becomes doubtful—in other words, it is not tuberculous meningitis. In cases of diagnostic uncertainty regarding the etiology of meningitis and at the slightest suspicion of a tuberculous origin, the decision is always made in favor of tuberculosis, and treatment with 3–4 antitubercular drugs is initiated, with rifampicin and streptomycin being mandatory components.

Cytology/practical/136.html">Differential diagnosis OF tuberculous meningitis is most frequently conducted with meningococcal, viral, and secondary Purulent meningitis, as well as "meningism" developing in conditions characterized by severe systemic intoxication.

Meningococcal meningitis has an acute onset and rapid course, accompanied by pronounced intoxication, high fever, altered consciousness, occasionally herpetic rashes, and severe peripheral leukocytosis. Cranial nerve involvement is rare. The cerebrospinal fluid is turbid, with a pleocytosis of 1,000 or more per 1 mL (predominantly neutrophilic), forming a coarse clot upon standing; protein content is elevated, and glucose levels are reduced. The diagnosis is confirmed by Bacteriological examination OF the CSF, which reveals the causative agent, Neisseria meningitidis. Intensive antibiotic therapy leads to rapid CSF sterilization and Clinical Recovery.

Secondary purulent meningitis is frequently caused by the metastasis of purulent foci, most commonly from the ears (otitis), Paranasal Sinuses (sinusitis, frontal sinusitis), or The Development of septicemia (Pneumonia, abscess, Osteomyelitis, carbuncle, etc.). The etiology of secondary purulent meningitis is typically staphylococcal or pneumococcal. Patient history and a comprehensive physical examination are of critical differential-diagnostic importance. The absence of a primary purulent focus does not exclude the Diagnosis of Secondary purulent meningitis. The onset is acute, with focal Central Nervous system deficits appearing on the 1st–2nd day. Loss of consciousness, generalized clonic-tonic seizures, cranial nerve palsies, and hemi- or paraparesis are frequently observed. The diagnosis is confirmed by bacteriological examination of the CSF.

In leptospirosic meningitis, the meningeal syndrome typically develops on the 3rd–6th day of illness against the Background of characteristic clinical symptoms (pain in the lumbar region, sacrum, and calf Muscles, hepatosplenomegaly, persistent high fever for 5–7 days, and peripheral leukocytosis). This is accompanied by a secondary temperature spike, worsening headache, vomiting, generalized hyperesthesia, and icterus of the Skin and sclerae. Timely recognition of leptospirosic meningitis is facilitated by the patient history (animal contact, swimming in rivers or stagnant Water bodies, fishing, etc.). Leptospirosic meningitis may present with either purulent or serous inflammation of the meninges. The CSF is most often opalescent, with a pleocytosis ranging from 800 to 4,000 cells per 1 mm³, which is neutrophilic or mixed. The etiology is confirmed in the first days of illness by identifying leptospires in the Blood, urine, and cerebrospinal fluid.

Certain challenges arise in the differential diagnosis between tuberculous meningoencephalitis and serous meningoencephalitides. Among primary serous meningoencephalitides, lymphocytic choriomeningitis is the most common, while meningitis of other viral etiologies is less frequent. Acute serous lymphocytic choriomeningitis is characterized by an acute onset without prodromal symptoms. Headaches and occasional vomiting appear abruptly, accompanied by chills, sometimes pain in the extremities, lower back, and spine, and temperatures reaching up to 40 °C in the first days. Meningeal signs are sharply pronounced. The duration of fever ranges from 5–7 to 10–12 days. The cerebrospinal fluid shows moderately severe inflammatory changes, occasionally forming a fibrin pellicle and exhibiting decreased glucose levels, with a lymphocytic pleocytosis ranging from 50 to 1,000 cells per 1 mL. The clinical course is favorable, with meningeal signs resolving within a few days and the cerebrospinal fluid normalizing within 15–30 days.

Secondary serous meningitis and meningoencephalitis occur in association with various infections, such as Influenza, mumps, poliomyelitis, infectious hepatitis, chickenpox, herpes zoster, and typhoid fever. In clinical practice, influenza-associated meningitis or meningoencephalitis and Mumps Meningitis are observed most frequently. The clinical picture exhibits Features of the underlying infection compounded by a superimposed meningeal syndrome and CSF abnormalities similar to those seen in primary serous meningitis.

In isolated cases, meningism may occur As a result of toxic meningeal irritation triggered by drug intoxication, renal disease, helminthic infestations, or various intercurrent infections. In cases of meningism, lumbar puncture may exacerbate meningeal irritation signs, whereas in tuberculous meningoencephalitis, it provides clinical relief to the patient. The CSF emerges under elevated pressure, while its protein-cellular composition remains normal or shows only minimal alterations. The manifestations of meningism resolve rapidly once the toxic agent is removed.

Treatment is carried out in a specialized inpatient facility until clinical symptoms resolve and the cerebrospinal fluid normalizes, but for a period of no less than 6 months. Four antimycobacterial drugs (isoniazid, rifampicin, streptomycin, pyrazinamide) are prescribed at optimal maximum daily doses. If swallowing is impaired, medications are administered parenterally or intrarectally. In severe cases of tuberculous meningitis, endoluminal administration of the streptomycin-calcium chloride complex (0.1–0.2 g daily for 10–14 days) is employed, alongside glucocorticosteroids (25–30 mg daily for 1.5–2 months). To reduce cerebral edema and Hydrocephalus, patients are prescribed dehydration therapy (lasix, hypothiazide, 10% mannitol solution, albumin). For seizures, chloral hydrate retention enemas, a 25% magnesium sulfate solution intramuscularly, depakine (0.5–1.0 g daily), and diazepam (2 mL of a 0.5% solution intramuscularly or intravenously) are used, along with Vitamins B₁, B₆, and C. Following the subsidence of the acute phase of meningitis, in cases of paresis or paralysis, dibazol is administered (1–3 mL of a 1% solution subcutaneously or 0.02 g 2–3 times daily), as well as neostigmine (1 mL of a 0.05% solution subcutaneously 1–2 times daily, or orally at 0.015 g 2–3 times daily). It should be noted that nervous system and meningeal tuberculosis is currently treated under clinical categories 1, 2, and 4 of dispensary registration, depending on the type of tuberculous process. The duration of the main course of Chemotherapy ranges from 8 to 12 months. Medications must be administered in the intensive phase strictly within an inpatient Setting (or in an intensive care unit for severe cases); subsequently, therapy may be continued in a hospital setting—including day hospitals—outpatient clinics, or sanatoriums.

After inpatient treatment, patients are referred to a anti-tuberculosis sanatorium to continue chemotherapy with two antimycobacterial drugs, alongside rehabilitation measures for at least 4 months. Subsequently, patients are monitored at anti-tuberculosis dispensaries and prescribed preventive courses of isoniazid combined with pyrazinamide or ethambutol for 2–3 years.

The most severe complication of tuberculous meningitis is hydrocephalus. Paresis, paralysis, visual and Hearing impairments, as well as cognitive decline, are also frequently observed.