Meningitis in Children - I.V. Bohadelnykov 2005

Serous meningitis in children. General information
Viral serous meningitis
Acute lymphocytic choriomeningitis (LCM)

Acute lymphocytic choriomeningitis is a zoonotic infectious disease caused by the lymphocytic choriomeningitis virus. It is characterized by an acute onset, symptoms of general intoxication, and predominant involvement of The Nervous system and Internal Organs.

Etiology. The lymphocytic choriomeningitis virus was discovered by Armstrong and Lilly in 1934. However, its significance in human pathology was proven a year later by Rivers and Scott. The virus belongs to the family Arenaviridae. The most characteristic morphological feature of this family is the presence within Viral Particles of electron-dense granular granules (ribosomal aggregates) 20-30 nm in diameter, which gave the family its name (Latin arenaceus – sandy). Virions range in size from 50 to 300 nm. The LCM virus genome is formed by a single-stranded segmented RNA molecule. The virion contains several types of both viral and host-derived ribonucleoproteins that function as Ribosomes and contain all host RNA types. LCM virus Replication is analogous to that of other RNA Viruses. In a desiccated state, the virus can remain viable for over a year. It is sensitive to various detergents and temperatures exceeding 56⁰ C. The LCM virus is cultivated in most Cell cultures, chicken and mouse embryos, and mouse macrophage cultures. Currently, the possibility of a teratogenic effect of the virus is not ruled out, based on the established fact of congenital LCM infection in some children with Hydrocephalus. The virus is widespread in Eurasia and America, whereas it is significantly less common in the European region.

Epidemiology. The primary sources of human infection are various rodents, most commonly domestic mice and hamsters. By shedding the virus in urine, feces, and nasal mucus, rodents contaminate food supplies and surrounding objects. Carrier states have also been established in healthy guinea pigs, monkeys, and dogs.

Human infection occurs when the pathogen enters the mucous membranes of the respiratory tract and digestive tract via airborne droplets and dust. Entry of the virus into The Human Body is also possible through rodent bites, scratches, and other Skin lesions.

There is no distinct seasonality, but the highest incidence occurs during the winter-spring period. Pronounced endemicity is characteristic. Epidemic outbreaks of LCM are limited in nature and are more frequently observed in rural areas. Sporadic cases of the disease are possible. Men and women are affected with equal frequency. Children, especially those in their first year of life, rarely fall ill.

Pathogenesis. The portal of entry for the infection is the mucous membranes of the respiratory tract or gastrointestinal tract. After entering the body, LCM viruses settle in regional Lymph Nodes, multiply within them, and 36–72 hours later enter the bloodstream and disseminate throughout the Organism. Depending on the body's resistance and immune defenses, the disease may proceed in a mild, abortive, or inapparent form, or acquire a generalized character with pronounced symptoms of intoxication and damage to internal organs such as the Lungs, Heart, Salivary Glands, and the Central Nervous System.

The viremia period lasts for several days, during which the virus crosses the Blood-Brain barrier to the central nervous system, where it induces an inflammatory process primarily in the Meninges, and in some cases, in the parenchyma of the BRAIN AND SPINAL cord. During this time, the virus can be detected in the CEREBROSPINAL FLUID, urine, and nasal secretions.

Pathological anatomy. The most significant changes in LCM occur in the pia mater and brain tissue. Perivascular, and occasionally diffuse, infiltration of the pia mater and brain tissue by lymphocytes is observed. The choroid plexuses and the ependyma of the third and fourth ventricles are also involved in the pathological process, manifesting as edema, hyperemia, and diffuse lymphoid infiltration. An accumulation of a significant amount of serous fluid is found in the subarachnoid space and ventricular cavities of the brain. In protracted and chronic courses of LCM, Connective Tissue proliferation and obliteration of the subarachnoid space are observed, along with pronounced lymphocytic infiltration of perivascular spaces and gliosis in the Cerebral Cortex. Changes in the form of local and diffuse demyelination may be detected in the White matter OF the brain.

Clinical Features. The incubation period for LCM, established through experimental data and laboratory animal infection, lasts 36 to 72 hours. Depending on the route of infection, the disease manifests in various clinical forms.

Acute lymphocytic choriomeningitis. It begins acutely and suddenly with a sharp rise in body Temperature to 38–39 ⁰C and higher, severe headache, weakness, malaise, and nausea. Patients complain of intense headache, repeated vomiting, eye pain, and a sensation of pressure and fullness in the ears. Describing the headache, patients often say: "my HEAD is splitting with pain," "the headache is unbearable" (M.B. Zuker, 1975). After 2 weeks, the intensity of the headache decreases, but it persists for a fairly long time (3–5 weeks). Subsequently, the headache becomes paroxysmal, and its duration and severity diminish over time. The attacks are accompanied by vomiting, but the vomiting ceases earlier than the headache. Meningeal syndrome develops early, is clearly pronounced, and persists for a long time. Patients exhibit marked nuchal rigidity, upper and lower Brudzinski's signs, and bilateral Kernig's sign. Typically, the meningeal syndrome lasts 10–14 days, but in some cases, its resolution is delayed up to 4–6 weeks.

In some patients, focal symptoms appear from the very first days of the illness, manifested as hand tremors, pathological Babinski and Oppenheim Reflexes, ataxia, coordination disorders, transient cranial nerve palsies, and less commonly, hemiparesis. In young children, against the Background of pronounced lethargy, adynamia, and drowsiness, short-term convulsions may occur, while older children may experience delirium, hallucinations, and agitation.

Congestive or neuritic changes in the fundus oculi are considered a characteristic feature of LCM. Mild edema of the optic disc and venous dilation are detected. All pathological and focal symptoms disappear as the process subsides.

Depending on the severity of the meningitis, clouding of consciousness up to complete loss of consciousness, delirium, and functional disorders of The Cardiovascular system may develop: the pulse is usually accelerated, blood pressure is slightly lowered, and heart sounds are muffled. The Tongue is coated and dry, and the mucous membranes of the oropharynx are mildly hyperemic.

The acute period of LCM rarely lasts longer than 3–5 days. Starting from the 8th–14th day, body temperature drops to normal and rarely remains elevated longer. Headaches disappear, although they may return in the form of attacks during the early convalescence period. The severity of general cerebral symptoms decreases, but they may persist for up to 2–3 weeks or more. Normalization of cerebrospinal fluid parameters and a decrease in intracranial pressure occur later (by the 14th–20th day from the onset of the disease).

Main diagnostic criteria for LCM:

1. Epidemiological history: contact with mice or small rodents, consumption of contaminated food, winter-spring season.

2. Acute onset of the disease with high body temperature, pronounced headache, and repeated vomiting.

3. Presence of a clearly defined meningeal syndrome from the first days of the illness.

4. Frequent development of general cerebral and focal symptoms (tremor, tongue deviation, hand tremors, agitation, hallucinations, impaired consciousness, etc.).

5. Characteristic neurological and congestive phenomena in the fundus oculi.

6. Inflammatory changes in the cerebrospinal fluid: sharply elevated pressure, increased protein, pleocytosis with a predominance of lymphocytes, and cell-protein dissociation detected from the first days of illness.

7. Etiological Diagnosis is based on isolating the lymphocytic choriomeningitis virus from cerebrospinal fluid, blood, or nasopharyngeal secretions, and detecting Complement-fixing and virus-neutralizing Antibodies in the blood with a subsequent fourfold increase in their titer in paired sera.

Laboratory Diagnostics. Complete blood count. Peripheral blood shows normocytosis or leukopenia, significant lymphocytosis, and a slightly elevated ESR.

Virological examination. The material used for isolating the LCM pathogen is most often blood, cerebrospinal fluid, or throat washings. Inoculation into cell culture or infection of young mice and hamsters is performed. Other specimens (pleural fluid, urine, autopsy material) may also be used.

Examination of cerebrospinal fluid reveals sharply elevated pressure (up to 300–400 mm Water Column); the fluid is clear, less commonly opalescent or turbid. Pleocytosis is characteristic, ranging from 100 to 1300 per 1 µL, with a predominance of lymphocytes (70–90%) from the first day of illness. Protein content is slightly increased (0.6–1.2 g/L) or normal, and globulin reactions are strongly positive. Chloride content is within normal limits, and glucose levels are unchanged or slightly elevated.

Serological testing. Paired sera are examined to detect specific antibodies. The Complement Fixation Test (CFT) and the Indirect Immunofluorescence Assay (IFA) are the most accessible Methods.