Meningitis in Children - I.V. Bogadelnikov 2005

Aseptic Meningitis in Children. General Overview
Aseptic Meningitis of Bacterial Etiology
Syphilitic Meningitis

Syphilitic meningitis is an infectious disease caused by Treponema pallidum, with either congenital or acquired transmission, characterized by an asymptomatic or acute course.

Etiology. The CAUSATIVE AGENT OF Syphilis is Treponema pallidum, a corkscrew-shaped spiral that tapers slightly toward the ends. It has 5 to 24 uniform coils, averaging 8–14. The length of each coil is about 1 μm, and the total length of the treponeme depends on the number of coils. The width of the treponeme ranges from 0.2 to 0.25 μm. Of great practical importance is the set of features that distinguish Treponema pallidum from other spirochetes that are Saprophytes or opportunistic flora of the mucous membranes, such as Sp. refringens, which is often found on the genitals, and Sp. buccalis and Sp. dentium in the Oral Cavity. Morphological differences between T. pallidum and other spirochetes can often be so minor that the latter group is referred to as pallidum-like. The only clear distinction between them lies in their patterns of movement. Therefore, diagnostic testing for Treponema pallidum is always performed on unfixed specimens. Treponema pallidum is highly motile. It exhibits four MAIN TYPES OF movement: translational (periodic, at varying speeds from 3 to 20 μm/h); rotational (spinning around its longitudinal axis); bending

(pendulum-like), and contractile (wave-like, spasmodic). Typically, all these movements are combined.

Treponema pallidum reproduces by transverse binary fission and can exist in three forms: spiral, cystic, and L-form, which accounts for various clinical courses of the infection. The most common ("classic") course of syphilis is due to the spiral form of the pathogen; other forms likely sustain a prolonged latent course. Treponema pallidum survives and reproduces poorly on artificial culture media. It is typically grown under anaerobic conditions. Cultured Treponema pallidum is non-pathogenic, meaning it does not cause disease upon inoculation. The optimal environment for Treponema pallidum is Lymph fluid, i.e., a Temperature of about 37⁰ C with low oxygen levels. It is a facultative anaerobe, making the conditions in arterial and venous Blood unfavorable. It usually appears in the blood during periods of the most florid clinical manifestations of syphilis, which most commonly occurs during the secondary stage of the disease. The high sensitivity of Treponema pallidum to oxygen determines its spread in the body primarily via lymphatic pathways and its constant presence in the Lymph Nodes. Treponema pallidum is thermolabile. Its optimal temperature is human body temperature. High temperatures are destructive to Treponema pallidum: it dies at 41 °C within 3–6 hours, at 60 °C within 5–20 minutes, and at 100 °C instantly. Thus, pasteurization of food products, rinsing dishes or instruments with boiling Water after use by patients, and boiling linens completely disinfect the material. Treponema pallidum tolerates low temperatures incomparably better. It retains its pathogenic properties in cadaveric Tissues stored at temperatures around 0 °C and below for 1–2 days. Thus, the corpses of syphilis patients remain infectious for a long time, even when stored in a refrigerator. The microbe persists for a long time in a moist environment (for example, it remains motile in wet handkerchiefs even for several days) but dies rapidly upon drying. Instant death of Treponema pallidum is observed in the following solutions: 0.05% chlorhexidine (hibitane), 1:1000 mercuric chloride solution, 1–2% phenol, and 70% or higher alcohol (in 40% alcohol, Treponema pallidum remains motile for 10–20 minutes). Potassium permanganate solution (even at a 1:1000 concentration) does not significantly affect the treponeme. The optimal pH is 7.4. Acidic and alkaline environments are destructive to it: in laundry soap lather and in weak (0.5%) solutions of alkalis or acids, treponemes instantly lose motility and soon dissolve.

Epidemiology. The only route of fetal infection is transplacental transmission from an infected mother. It is known that infection is not detected before 18 weeks of gestation, as the fetus prior to 16 weeks is not mature enough to respond to the antigen by producing Antibodies.

Treponema pallidum penetrates the fetal body through a syphilis-damaged Placenta at the end of the 4th or beginning of the 5th month of Pregnancy (the time when placental Circulation develops). Transplacental transmission of syphilis can occur in two ways: most commonly through the umbilical vein, where Treponema pallidum is carried into the fetal body as emboli; less frequently, Treponema pallidum enters the fetal Lymphatic system through the lymphatic clefts of the umbilical cord. A healthy placenta acts as an effective filter against Treponema pallidum.

Transmission of syphilis to offspring (in the absence of Treatment) occurs primarily During the first 3 years after maternal infection; subsequently, this capability gradually weakens but does not disappear entirely (Kassowitz's law).

Pathogenesis. The pathogenesis of congenital syphilis depends largely on the fetal Immune Response and, to a lesser extent, on the cytodestructive effect of Treponema pallidum.

Damage to The Nervous system in syphilis is associated with the penetration of Treponema pallidum into the vessels, Meninges, and parenchyma of the nervous system via hematogenous and lymphogenous routes. The latter is likely the primary pathway. Treponema pallidum can be detected in the spinal subarachnoid space immediately after infection. It enters this space through the perineural spaces of the spinal nerve roots from regional lymph nodes. Via the hematogenous route, Treponema pallidum enters the CSF when the blood-Brain barrier is compromised.

Reaching the leptomeninges via the lymphogenous pathway, Treponema pallidum induces hyperergic inflammation, as the meninges have already been sensitized by the hematogenously generalized infection. Initially, the inflammation is characterized by exudative manifestations. Later, with Changes in the reactivity of the meningeal reticuloendothelial tissue, proliferative and scarring processes begin to dominate the inflammatory picture. Along with the meninges, the Vessels of the nervous system, the perineurium, and the endoneurium of the nerve roots and peripheral nerves—essentially the entire mesenchymal apparatus of the nervous system—are involved in the inflammatory process. Over time, local mesenchymal Immunity develops, and the mesenchyme loses its ability to retain Treponema pallidum, which then penetrates the parenchyma of the CNS, causing degenerative changes. This leads to diseases involving the parenchyma of the BRAIN AND SPINAL cord, in contrast to early forms, which are characterized by damage only to the meninges and vessels of the nervous system (M.S. Margulis, 1949).

Pathological Anatomy. Postmortem examination of the brain in patients who died of syphilitic meningitis reveals edema of the brain parenchyma and meninges, and Circulatory Disorders such as Thrombosis of the deep cerebral vessels. In the acute form of syphilitic meningitis, meningeal involvement is diffuse: macroscopically, they are slightly edematous and hyperemic. The inflammatory process often extends to the meninges covering the cranial nerve roots, as well as to the choroid plexuses of the ventricles. Histologically, vasodilation and diffuse infiltration of leukocytes and plasma Cells are observed (K.K. Borysenko et al., 1999). Syphilitic meningoencephalitis, along with the thickening and clouding of the meninges and the presence of lymphocytic and plasmacytic infiltration characteristic of syphilitic meningitis, is distinguished by the extension of the inflammatory process to the brain parenchyma, where it spreads along the Blood Vessels and causes softening of the brain tissue.

Clinical presentation. Syphilitic meningitis can present asymptomatically or as an acute involvement of the leptomeninges.

Asymptomatic meningitis is not accompanied by clinical manifestations of nervous system involvement. The Diagnosis is made solely on The basis of inflammatory and/or serological changes in the CSF. Syphilitic meningitis, both asymptomatic and manifest, is an inevitable stage of all Other forms of neurosyphilis. R. Adams believes that from a clinical perspective, asymptomatic meningitis is the most important form of neurosyphilis. Meningitis can develop acutely, although acute syphilitic meningitis was rare even in the pre-penicillin era. It presents like viral meningitis, often with cranial nerve involvement (most commonly the auditory, optic, and facial nerves). In most cases, spontaneous regression of symptoms occurs.

Asymptomatic meningitis can also run its course without pronounced clinical symptoms but with changes in the CSF. Objectively, this form shows no signs of focal nervous system damage; only mild autonomic dysfunction may be detected. Some patients exhibit a mild meningeal syndrome. Cranial nerve involvement (auditory, oculomotor, abducens, facial) is occasionally observed. CSF changes are characterized by elevated pressure, sometimes mild xanthochromia, increased protein levels up to 6–12 g/L, pleocytosis within 100–200 cells/μL with a predominance of lymphocytes, positive serological and globulin reactions, and an altered Lange colloidal gold curve. Asymptomatic meningitis has a favorable course and resolves spontaneously or under METABOLISM/18.html">The Influence of specific therapy in most patients. In only 5–10% of cases does it progress to late meningovascular syphilis, tabes dorsalis, or general paresis.

Acute form of syphilitic meningitis. One of the earliest clinical signs of meningeal irritation in children with congenital syphilis is the so-called "unprovoked crying" of the child, which occurs both day and night and is unrelated to feeding. This crying is an expression of meningeal irritation caused by a specific toxin (Heine). In the first months of life, and sometimes even in the first weeks, children with congenital syphilis experience transient seizures, which in most cases leave no visible sequelae and are often observed concurrently with other specific manifestations.

The disease begins with an elevated body temperature. A characteristic syndrome of meningeal irritation is present, the primary signs of which, In addition to crying, are vomiting, hyperesthesia to sound and light, nuchal rigidity, Kernig's sign, Brudzinski's signs, and Lesage's "hanging" sign.

A characteristic meningeal posture and Flatau's sign are observed. In some patients, fundoscopy reveals hyperemia or edema of the optic discs. When the inflammatory process is localized on the Inferior surface of the brain, cranial nerve Functions are impaired, particularly the oculomotor nerves, resulting in diplopia, restricted Eyeball mobility, strabismus, ptosis, and anisocoria (L.O. Badalyan, 1984).

In the CSF, which flows under elevated pressure, pleocytosis increases to 100–200 cells/μL or more; the fluid is clear or slightly turbid, the protein content is increased to 6.0–12.0 g/L, and globulin reactions, as well as the Wassermann and Lange reactions, are positive.

Under the influence of specific treatment, the symptoms of the disease disappear rapidly, while CSF changes persist longer. However, at the height of the disease, deafness may occur, and vascular disorders, strokes with epileptic seizures, and cranial nerve palsies (facial, oculomotor, abducens) may develop.

Syphilitic meningoencephalitis. Syphilitic meningoencephalitis in children usually develops acutely. Symptoms of brain parenchyma involvement are added to headache, crying, seizures, loss of consciousness, vomiting, and meningeal signs. Monoparesis and hemiparesis, speech disorders, alternating syndromes, cranial nerve nuclei lesions, sensory disturbances, and impaired coordination of movements may occur. The CSF shows the same changes as in syphilitic meningitis.

Key diagnostic criteria for syphilitic meningitis:

1. Syphilitic meningitis, as a form of CNS involvement, occurs only in early congenital syphilis and can manifest before the age of 2 years.

2. Intrauterine fetal infection with syphilis occurs transplacentally, starting from the 4th–5th month of pregnancy.

3. The disease can present in two forms: asymptomatic and acute.

4. Asymptomatic meningitis is not accompanied by Clinical symptoms of CNS involvement and is diagnosed solely on the basis of inflammatory changes in the CSF; it typically has a favorable course.

5. The Development of acute syphilitic meningitis is preceded by unprovoked crying in the child, and transient seizures may occur.

6. Acute syphilitic meningitis begins with fever and symptoms of meningeal irritation; Oculomotor nerve disorders may also occur.

7. Specific therapy leads to rapid positive dynamics of clinical symptoms and a slower normalization of the CSF.

8. Occasionally, at the height of the disease, deafness may develop, accompanied by epileptic seizures and cerebral vascular disorders.

Laboratory Diagnostics. CSF analysis. To identify specific syphilitic changes in the CSF, the following tests are recommended: determination of total protein content, Cell count, globulin tests, the Wassermann reaction with three CSF dilutions, the colloidal gold test (Lange's test), TPI, FTA-10, and FTA-u (immunofluorescence assay with whole undiluted CSF).

Determination of total protein. In the pathologically altered CSF of a syphilis patient, the protein level increases. This is determined using serial dilutions of CSF with isotonic sodium chloride solution from 1:5 to 1:80.

Quantitative cell count. Normal CSF typically contains lymphocytes. An increase in The Cell count and the appearance of plasma cells and monocytes alongside lymphocytes in pleocytosis indicate pathological changes in the CSF.

Globulin tests. The Determination of the heavy protein fraction—globulins—in the CSF is of great importance in diagnosing CSF pathology. Globulin tests include the Nonne-Apelt and Pandy tests, which are based on the ability of certain salts at specific concentrations to selectively precipitate globulins from the CSF.

Lange's test (colloidal gold test). THE PRINCIPLE OF the test is based on the fact that colloidal gold solutions, which remain unchanged when mixed with serial dilutions of normal CSF, undergo changes in their degree of dispersion under the same conditions in pathologically altered CSF in the presence of electrolytes (sodium chloride solution), depending on the dilution of the fluid. This process is manifested by A change in the color of the colloidal solution as a precipitate forms. Lange's colloidal gold test has both diagnostic and differential diagnostic value in the early detection of syphilitic lesions of the nervous system.

Wassermann reaction with CSF. In syphilis, the CSF may contain reagins and anti-treponemal Complement-fixing antibodies, which are detected using appropriate Antigens. Since complement is absent in the CSF, the Wassermann reaction is performed using un-inactivated fluid. The CSF is tested in the Wassermann reaction both undiluted in a volume of 0.5 mL and diluted with isotonic sodium chloride solution at 1:1 and 1:4.

It has been established that strongly positive and positive Wassermann reactions with CSF prove the presence of syphilitic infection in the patient; however, it should be noted that negative Wassermann reaction results do not rule out syphilis. In such cases, other tests must be performed.

FTA and TPI with CSF. Currently, these CSF tests are considered absolutely specific for syphilis. The Procedures for performing and interpreting the FTA and TPI tests in the CSF are the same as those used for blood testing.