Meningitis in children - I. V. Bogadelnikov 2005

Aseptic meningitis in children. General data
Aseptic meningitis of bacterial etiology
Tuberculous meningitis

Tuberculous meningitis is a severe complication of Primary tuberculosis, which most frequently occurs in the presence of active Pulmonary Tuberculosis or its extrapulmonary forms, and less commonly in isolation. It is characterized by an insidious onset with involvement of the Meninges, cranial nerve palsies, and damage to the Brain AND SPINAL cord parenchyma.

Tuberculous meningitis was recognized as a distinct clinical entity in 1893, 11 years after the Discovery of the CAUSATIVE AGENT OF tuberculosis.

Etiology. The causative agent of tuberculosis was discovered by Robert Koch in 1882 and was initially referred to as "Koch's bacillus", later named Mycobacterium tuberculosis (MBT).

Mycobacterium tuberculosis are typical Representatives of the Mycobacteriaceae family. They appear as slightly curved, homogeneous, or granular rods, 0.8 to 3-5 µm in length and 0.3-0.5 µm in width. Within the bacterial Cell, a cell membrane, Cytoplasm with individual Organelles, and nuclear material can be differentiated. Acid-fast pathogenic mycobacteria, like other microorganisms, adapt to changing environmental conditions through interaction with their surroundings. Mycobacterial pleomorphism is manifested by their ability to form various shapes: filamentous, actinomycotic, granular, coccoid, as well as non-acid-fast variants that are pathogenic to experimental animals. In addition, there are filterable forms and various Cell wall-deficient mycobacterial variants that lead to deeper functional and morphological Changes in the microorganism, promoting The formation of unstable or stable L-forms of Bacteria.

Chemically, mycobacteria consist of: Proteins (tuberculoproteins) at 56%, CARBOHYDRATES (tuberculopolysaccharides) at 15.3%, tuberculophospholipids at 22.7%, and minerals at 6%. Tuberculoproteins are the primary carriers of the mycobacteria's antigenic properties. The polysaccharide fraction of the microbes is non-toxic, as it possesses neither antigenic nor sensitizing properties. Among the lipid fractions, the phosphatide fraction is the most active, inducing a specific reaction in the body characterized by the formation of epithelioid and Pirogov-Langhans giant Cells. The lipid fraction is associated with the acid-fastness of mycobacteria. It is also referred to as the cord factor, which causes mycobacteria to adhere and grow in serpentine cords, and serves as a key determinant of mycobacterial virulence.

The primary feature determining the species of mycobacteria is their differing pathogenicity for animals and humans. Among pathogenic mycobacteria, four species are distinguished: M. tuberculosis - the causative agent of human tuberculosis, M. bovis - the causative agent of bovine tuberculosis, M. avium - the causative agent of avian tuberculosis, and M. microti/OVS or Oxford vole strain - the causative agent of vole tuberculosis. Transitional forms also exist between individual species of mycobacteria. The main species-specific characteristic of Mycobacterium tuberculosis is its pathogenicity, i.e., The ability to live and multiply in the Tissues of a living Organism and trigger specific host responses that lead to tuberculosis. Guinea pigs are the most susceptible to tuberculosis and are used as models for bioassays in tuberculosis Diagnosis. Different strains of Mycobacterium tuberculosis also vary in their degree of virulence. Virulence is an individual trait of a specific microbial strain and is characterized by The rate of multiplication of the microorganism in tissues (O.I. Kagramanov, 1968).

Epidemiology. Apart from its social aspects, tuberculosis is primarily an infectious disease. Human infection with Mycobacterium tuberculosis occurs mainly via droplet or airborne transmission, meaning the pathogen is transmitted from an infected individual to a susceptible person during coughing, sneezing, speaking, or via dried sputum in street dust, etc. Alimentary transmission is also possible through the consumption of raw milk, butter, cheese, and other products obtained from tuberculosis-infected cattle.

According to modern concepts, Mycobacterium tuberculosis entering The Human Body does not cause disease in most cases, as humans are relatively resistant to tuberculosis infection. When Mycobacterium tuberculosis penetrates the body, The Immune System is activated, specifically the T-cell-mediated Immunity. The disease occurs only when the body's resistance is lowered under METABOLISM/18.html">The Influence of unfavorable environmental and internal factors. These include acute infections (measles, pertussis, mumps, etc.), seasonal factors (winter and spring periods), hypothermia, HEAD trauma, hyperinsolation, etc. Undoubtedly, the inoculum size (massiveness) and virulence of the tuberculous infection play a major role in transmission.

Among animals, goats and dogs are the most resistant to tuberculosis infection, while guinea pigs, as mentioned above, are the most susceptible. Infants are also as susceptible to tuberculosis infection as guinea pigs. This is because cell-mediated immunity, which is responsible for resistance to tuberculosis infection, is not fully developed at this age. Therefore, to protect the child from tuberculosis, BCG Vaccination is administered as early as the 3-5th day of life. However, even with proper administration of preventive vaccinations, BCG vaccination does not always prevent The Development of tuberculous meningitis in children, especially During the first year of life.

Pathogenesis. Secondary tuberculous meningitis occurs in 60-80% of cases (O.M. Ivanyuka et al., 1987) and can develop during any clinical form and phase of pulmonary tuberculosis (disseminated or miliary, Primary tuberculous complex, intrathoracic Lymph node tuberculosis). Less frequently, tuberculous meningitis develops in extrapulmonary forms of tuberculosis. However, in 20-40% of patients, tuberculous meningoencephalitis occurs as a primary isolated lesion of the meninges and Central Nervous system, meaning that no pathogenetic link between tuberculous meningitis and tuberculosis of other Organs can be identified.

In the pathogenesis of tuberculous meningoencephalitis, the hematogenous-liquorogenous mechanism of Mycobacterium tuberculosis dissemination is paramount. The First stage—hematogenous—is manifested by bacteremia, which under certain conditions leads to the pathogen breaching the Blood-brain barrier, followed by infection and specific lesions of the choroid plexuses of the brain ventricles. The Second Stage is liquorogenous, where MBT from the affected choroid plexus penetrate the CSF and settle at the Base of the brain, causing inflammation of the meninges and later, if Treatment is delayed, of the brain parenchyma. Therefore, tuberculous meningitis is initially always basilar. Lymphogenous and contact mechanisms of tuberculous meningitis development are secondary.

Pathological anatomy. As previously noted, the site where MBT breach the vascular bed into the CNS is at the level of the choroid plexus of the brain ventricles. From there, the infection enters the subarachnoid space and circulates in the CSF. Therefore, in the early stage of the disease, inflammation is predominantly localized in the choroid plexus and ventricular ependyma, as well as in the intima and adventitia of the vessels at the base of the brain and Brainstem. The changes are of an exudative-proliferative and productive nature.

Concurrently, endarteritis, panarteritis, and panphlebitis may occur, leading to single or multiple foci of cerebral softening. If the inflammatory process spreads to the brain parenchyma, meningoencephalitis develops. In basilar meningoencephalitis, tuberculous tubercles appear at the base of the brain, consisting of clusters of epithelioid, lymphoid, and plasma cells, accompanied by a serous exudate that later becomes serofibrinous. The process then spreads to the optic chiasm, Pons, and Medulla Oblongata. In severe forms of tuberculous meningoencephalitis, tubercles are also found in the Midbrain and Diencephalon. The inflammatory process in the ventricles of the brain leads to impaired CSF outflow and the development of Hydrocephalus. Further progression of the disease leads to paresis, limb paralysis, and cranial nerve palsies.

Serous tuberculous meningitis is the mildest form, characterized by the fact that the inflammatory process usually does not extend beyond the choroid plexus of the brain ventricles. Under the influence of specific treatment, complete recovery occurs rapidly.

Clinical Features. Tuberculous meningitis rarely starts abruptly in a state of full health. As a rule, such an onset is observed in infants (Yu.P. Chagaev, 1989). Most often, the full clinical picture is preceded by a prodromal period, manifested by general malaise lasting 1-1.5 weeks. The child becomes lethargic, inactive, refuses to play or eat, and exhibits stubbornness, irritability, and tearfulness. At this stage of the disease, brief periods of improvement (for 1-2 days) are possible, which are then replaced by even more pronounced behavioral and mental disturbances.

However, in the modern course of tuberculous meningitis, the prodromal period may be absent in nearly 50% of cases (L.V. Lebedev, M.E. Syroechkovskaya, 1977).

The initial signs of tuberculous meningitis are headache, vomiting, and a persistent rise in body Temperature to high levels.

Vomiting, according to K.P. Berkos and T.I. Tsareva, is observed in 88.6% of cases. Vomiting is often projectile and usually unrelated to food intake. Headache is observed in 94-96% of cases and is persistent. Body temperature rises to 38°-39°C. In the past, the fever persisted for 2-4 months; currently, it lasts 1-2 weeks with successful and early treatment.

The most common symptom of tuberculous meningitis is headache, which is observed in 94-96% of cases. It is persistent and localized in the frontal and occipital regions.

At the same time, meningeal syndrome develops.

Three signs most characteristic of tuberculous meningitis are distinguished: nuchal rigidity, back Muscle rigidity, and Kernig's sign. All of these symptoms are associated with irritation of the meninges. Nuchal rigidity varies at different ages; in young children, it is rarely detected, especially in the Cytology/cytology/16.html">Early stages of the disease. Thus, out of 48 children under 2 years of age during the initial examination for tuberculous meningitis, nuchal rigidity was detected in less than half (F.I.W. Miller, R. McDougale, 1954). Nevertheless, this is a highly valuable diagnostic sign, the detection of which requires training, technical mastery, and experience on the part of the physician.

Rigidity of the back Muscles is, in fact, analogous to neck stiffness, but detecting this sign requires the active cooperation of the sick child. Therefore, in children aged 4-5 years, this sign can be quite difficult to detect.

In the first days of the illness, the child usually retains interest in their surroundings and the doctor, Answers questions, and follows simple commands. In the following days, young children typically lie curled on their side, while older children move cautiously and wince; if they need to turn their head or perform any action, a grimace of pain appears on their face. As the meningitis progresses, consciousness becomes increasingly impaired. The child, initially agitated and demanding attention, becomes withdrawn, and stupor develops. Even at this stage of the disease, focal neurological symptoms may appear, such as hemiparesis or seizures.

Seizures, which are not characteristic of the early stages of meningitis, increase as the disease progresses. The onset of seizures indicates the development of vascular complications such as thrombosis and cerebral infarction. Seizures, often unilateral, are followed by hemiplegia on the corresponding side.

With further progression of the disease, Cranial Nerves are often affected, primarily the Optic nerve, as the process develops around the chiasm. Specific miliary tubercles and exudative inflammatory changes appear in it, leading to the development of optic neuritis and chorioretinitis. The Oculomotor nerve is frequently affected, initially manifesting as mild strabismus, which worsens as hydrocephalus increases; ptosis often ensues. Pupillary dilation, anisocoria, and "pupillary play" are observed.

The Abducens nerve is affected in the early stages of tuberculous meningitis. In such cases, unilateral or bilateral convergent strabismus is observed.

The Trigeminal nerve is rarely affected, occurring only in advanced cases of meningitis. Conversely, the Facial Nerve is frequently involved. Facial Asymmetry, which becomes apparent when showing the Teeth, is observed early on.

The auditory nerve is involved in the late stage of the disease. It is important to remember that The Use of streptomycin, especially long-term, can cause auditory nerve damage associated with antibiotic therapy.

Bulbar nerves (glossopharyngeal, vagus, and hypoglossal) are always affected late. In contrast, extrabulbar autonomic structures are involved early, causing changes in blood pressure, Heart rate, and Respiration.

Motor disorders are observed in the late stage of the disease; paresis and paralysis develop strictly as central (upper motor neuron) types. On average, hyperkinesias develop on days 12-14 of the illness.

Speech impairment can be observed both in the absence and presence of paralysis.

In tuberculous meningitis, persistent red dermographism and Trousseau's spots appear early, serving as important differential signs. The presence of white dermographism argues against tuberculous meningitis.

Hemodynamic disturbances also play a role in the diagnosis of the disease. At the end of the prodromal period and the beginning of the acute phase, bradycardia is noted, which subsequently transitions into tachycardia. BP may rise, and a persistent elevation in blood pressure is an unfavorable prognostic sign.

In the terminal stage of meningitis, consciousness is lost, and the child lies supine in a state of decerebrate rigidity: the arms and legs are extended and tense. Recovery at this stage of the disease is highly unlikely.

Key diagnostic criteria for tuberculous meningitis:

1. Epidemiological history: contact with a tuberculosis patient; the primary route of infection is airborne droplets; children of any age can be affected, but infants and young children are at higher risk.

2. Tuberculous meningitis most commonly develops as a severe complication of primary active pulmonary tuberculosis or extrapulmonary forms, and less frequently as an isolated form.

3. The disease usually begins gradually with symptoms of general systemic intoxication, progressing over 1-1,5 weeks, followed by the onset of meningeal syndrome, cranial nerve involvement, and damage to the brain parenchyma.

4. An acute onset of tuberculous meningitis is observed in infants, with a rapid loss of consciousness being a characteristic feature of its course.

5. Autonomic disorders are characteristic, manifesting as sweating, persistent red dermographism, Trousseau's spots, and bradycardia.

6. A decrease in glucose and chloride levels in the CSF is of diagnostic significance.

7. Absolute confirmation of the tuberculous etiology of meningitis is the formation of a fibrin web when the CSF is allowed to stand for 12-24 hours, and the detection of MBT in the CEREBROSPINAL FLUID.

Laboratory Diagnostics. Complete blood count is characterized by leukocytosis, lymphopenia, and an elevated ESR.

Chest X-ray reveals evidence of recent or old primary infection, or active tuberculosis.

Tuberculin Skin tests are not decisive because they can be negative due to anergy. It is important to know if they were positive prior to the onset of the disease.

Ophthalmoscopy. Fundus examination reveals the presence of choroidal tubercles (most commonly in Miliary tuberculosis) and papilledema.

CSF analysis. The cerebrospinal fluid is clear, colorless, or xanthochromic; pressure is elevated; lymphocytic or mixed pleocytosis of 100 to 1000 cells/μL is detected; protein content is increased to 2-3 g/l; the glucose level is below 2 mmol/l. A characteristic feature is the formation of a fibrin web (formerly called the "thread of death") in the form of a delicate, funnel-shaped cobweb that settles to the bottom of the tube after standing for 12-24 hours (in 71-84% of cases). The most reliable diagnostic sign is the detection of Mycobacterium tuberculosis in the CSF. According to reports by individual authors, the detection rate ranges from 4-5% (V.S. Ivankova, V. A. Pavlov, 1991) to 12,6-14,6% (O.M. Tonkovyd, 1991). According to our data, this figure is 11,5%.

Oxidative index. CSF oxidizability is The amount of oxygen required to oxidize organic substances in 1 ml of cerebrospinal fluid. In tuberculosis, this parameter is high — 0,35 mg ПРО₂/ml of CSF; in the serous form, it is 0,12-0,16 mg ПРО₂; in Brain Tumors, it is 0,22 mg ПРО₂. In Purulent meningitis, this index is also high, but it normalizes quite rapidly, within 1 week, whereas in tuberculosis, it takes 1-1,5 months.