Meningitis in Children - I.V. Bohadelnikov 2005

Serous Meningitis in Children. General Information
Serous Meningitis of Viral Etiology
Mumps Meningitis

Mumps virus exhibits a strong tropism for glandular tissue and The Nervous system. Therefore, it would be more accurate to refer to the disease as mumps infection. However, According to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, the traditional name has been retained. When glandular manifestations occur, the parotid, submandibular, sublingual, Pancreas, and Gonads are most frequently affected. Nervous system involvement typically includes serous meningitis, and less commonly, meningoencephalitis.

Mumps serous meningitis is a form of nervous system involvement in mumps characterized by a moderately severe to severe clinical course, marked by pronounced infectious-toxic syndrome and mild meningeal signs.

Etiology. The disease is caused by an RNA-containing virus belonging to the family Paramyxoviridae. The first viral strain was isolated by Johnson and Goodpasture in 1934. A key feature of the mumps virus is the absence of antigenic variants, which ensures the stability of its antigenic Structure. The single-stranded viral RNA is enclosed in an envelope containing surface HN and F Glycoproteins. The mumps virus also demonstrates hemadsorbing, neuraminidase, and syncytium-forming activities.

The virus is relatively stable in the environment and is inactivated by heat, ultraviolet irradiation, and desiccation; however, it can survive for several days at temperatures of 18°-20^о C, and for up to 6–8 months at lower temperatures. It is rapidly destroyed by chemical agents (1% lysol and bleaching powder solutions, 2% formalin solution) and upon contact with lipid-solvent solutions. Currently available Antibiotics AND CHEMOTHERAPEUTIC drugs are ineffective against it.

Epidemiology. Mumps is a classic anthroponosis. The only reservoir of infection is an infected human. However, confirmed cases of transmission to dogs from their owners have been reported. Furthermore, experimental infection of monkeys with the mumps virus is possible. Viral shedding begins during the last days of the incubation period and continues for up to 10 days after the onset of the disease. Infectivity peaks During the first 3–5 days of illness. From an epidemiological standpoint, patients with mild and asymptomatic forms pose the greatest risk.

The infection is transmitted via airborne droplets, spreading through saliva droplets during conversation and coughing. Proximity, duration, and intensity of contact with the infected individual (sharing a household, sitting at the same school desk, sharing a bedroom) play a critical role in transmission.

Contact-droplet transmission via fomites is also possible, but it holds no significant epidemiological importance.

The susceptibility index for mumps ranges from 50% to 85%. The highest incidence is observed in children aged 5 to 10 years and young adults aged 16 to 25. Infants under one year of age are exceptionally rarely affected, owing to maternal transplacental Antibodies. Boys are affected more frequently than girls.

By the end of the first week of illness, IgM antibodies appear in the Blood and circulate for 60 to 120 days. IgG antibodies appear after 3–4 weeks and persist for life, providing robust, lifelong Immunity.

Mumps is characterized by an autumn-winter seasonality. The disease occurs sporadically and in epidemic outbreaks. The latter most frequently arise in closed or semi-closed children's groups (nurseries, kindergartens, boarding schools) and are typically caused by breaches of Sanitary and epidemiological regulations (overcrowding, inadequate ventilation) or delayed Implementation of anti-epidemic measures (isolation, prophylactic vaccination, etc.).

A characteristic feature of mumps is the periodicity of incidence surges every 2–3 years, which is driven by fluctuations in herd immunity.

Pathogenesis. The portal of entry for the infection is the mucous membranes of the Upper Respiratory Tract. Initial viral Replication occurs in the nasopharyngeal epithelium, from which the virus enters the bloodstream. Mumps viremia persists for the first 5 days of the disease. Carried by the bloodstream, the virus disseminates throughout the body and invades various Organs: the parotid glands, Testes, Ovaries, pancreas, Thyroid Gland, Brain, and others. Notably, the Salivary Glands are primarily targeted. The possibility of hematogenous spread is evidenced by the involvement of widely separated organs and systems that lack direct lymphatic connections. At the same time, primary viral replication is also possible in the epithelium of the parotid glands, where the virus penetrates via Stensen's duct and is subsequently disseminated hematogenously to other organs. During the viremic phase, the mumps virus can cross the blood-brain barrier and accumulate in the subarachnoid space. This process lasts up to 4 weeks, representing the maximum timeframe for the onset of meningitis symptoms following the initial manifestation of mumps. Hydrocephalic-hypertensive syndrome develops both As a result of CEREBROSPINAL FLUID hyperproduction and due to the influx of serous inflammatory exudate into the subarachnoid space.

Nervous system involvement may manifest as meningoencephalitis or polyradiculoneuritis and presumably has a neuroallergic pathogenesis. This is supported by the fact that these forms of CNS involvement in mumps predominantly occur in children with an allergic predisposition.

Pathology. Autopsy findings in mumps meningitis reveal edema and hyperemia of the arachnoid and pia mater, the choroid plexuses of the ventricles, and the brain tissue. Diffuse infiltration is observed, predominantly mediated by lymphocytic and plasma Cells.

In the choroid plexuses and the subependymal region of the brain ventricles, autopsies reveal stasis and petechial hemorrhages; the brain ventricles are dilated and contain excessive amounts of cerebrospinal fluid and serous inflammatory exudate.

In mumps meningoencephalitis, the aforementioned changes are also found within the brain parenchyma, alongside foci of demyelination located in the Brainstem.

Clinical Features. The incubation period for mumps is 14–21 days. Serous meningitis typically develops on days 3–6 of the illness; less commonly, it may occur simultaneously with salivary gland involvement on days 1–2, or, in exceptional cases, precede it or appear later (up to 30 days into the illness). Occasionally, it runs its course entirely without clinically apparent symptoms of salivary gland inflammation. There are no significant differences in the clinical course of mumps meningitis regardless of the timing of its onset.

Meningitis has an acute onset, accompanied by a rise in body Temperature to 38–39 ∘С. The child complains of severe headache and pain in the eyeballs. Vomiting appears around the same time, typically recurrent and providing no relief. Photophobia and hyperesthesia are pronounced. Meningeal syndrome appears on the first day of illness and is generally of moderate severity. The dissociation of the meningeal syndrome is evident through pronounced nuchal rigidity and a positive upper Brudzinski's sign, whereas Kernig's sign and the middle Brudzinski's sign may be absent or weakly expressed.

During the acute period, autonomic dysfunctions typical of mumps are observed, manifesting as red macules on the face and torso, excessive sweating, enhanced red dermographism, pulse lability, and sometimes a tendency toward bradycardia.

The severity of general cerebral symptoms in the early days of meningitis largely depends on the patient's age. For instance, in young children, hyperthermia may be accompanied by generalized seizures, varying degrees of impaired consciousness up to coma, adynamia, or agitation.

In older children, delirious syndrome may develop, accompanied by delusions, hallucinations, and psychomotor agitation. This syndrome is particularly common in children with a pre-existing compromised neurological history, an unfavorable premorbid Background, an allergic predisposition, or altered reactivity.

The acute phase of mumps meningitis lasts for 5–7 days. The temperature drops by lysis on days 3–5; from days 2–3, vomiting occurs less frequently, and meningeal signs resolve by days 7–10 of the illness. Residual phenomena are rare and manifest as autonomic disturbances: increased fatigue, moderate headache, and Sleep disorders.

During lumbar puncture, CSF pressure rises to 250–500 mm H2O. The magnitude of intracranial pressure elevation directly correlates with the severity of meningitis and largely determines its clinical course. Lumbar puncture with the slow release of 5–8 ml of CSF rapidly leads to an improvement in the patient's general well-being, a reduction in headache intensity, and the cessation of vomiting. The protein content in the CSF is normal or moderately elevated (up to 0.3–0.6 g/L), and globulin tests are positive in approximately half of the patients. Pleocytosis ranges from 50 to 500 cells per µL, though it can be higher (up to 2000 cells per µL), and is predominantly lymphocytic. However, some patients may exhibit a transient admixture of neutrophil leukocytes, which subsequently disappear, confirming the serous Nature of the inflammation. CSF glucose levels remain normal.

Normalization of CSF parameters lags slightly behind the resolution of Clinical symptoms of serous meningitis. Complete Clinical Recovery occurs on average by day 14 of the illness. A mild pleocytosis observed during this period—within 100 cells per µL, consisting of small and medium lymphocytes—should not be interpreted as an indicator of ongoing inflammatory activity.

Meningoencephalitis clinically manifests on days 3–7 of mumps. While meningeal signs tend to recede during this period, cerebral symptoms, conversely, become more pronounced. This is evidenced by smoothing of the nasolabial fold, deviation of the Tongue to one side, hyperactive deep tendon Reflexes, the appearance of pathological reflexes (ankle clonus, Babinski sign), severe tremor, nystagmus, hyperkinesia, and other symptoms. The younger the child, the more sharply pronounced the focal manifestations are, particularly cerebellar disturbances presenting as ataxia: children stop walking or exhibit a "drunken" gait, and tip over to the side when attempting to sit. Young children are also characterized by autonomic disorders such as sweating, Skin flushing, and tachycardia. In older children, the Pyramidal Tracts and subcortical ganglia are more frequently affected, manifesting clinically as mild hemiparesis and choreoathetoid hyperkinesia. Starting from days 7–10, focal neurological symptoms gradually diminish and completely resolve within 2–6 weeks.

Isolated cranial nerve palsies may occur independently of serous meningitis or salivary gland Swelling. The Cranial Nerves most frequently affected are the VI, VII, VIII, and XII pairs. A characteristic feature of cranial nerve involvement in mumps is the slow recovery of impaired Functions over a period of 1-2 months.

Polyradiculoneuritis. As a rule, polyradiculoneuritis develops against the background of typical salivary gland involvement; however, it may occasionally occur without accompanying meningitis or meningoencephalitis. Starting from the 5th day of mumps, coinciding with a declining or normal body temperature, symmetrical peripheral-type pareses and paralysis (predominantly distal), sensory loss, and pain along the nerve trunks emerge. Polyradiculoneuritis is characterized by a protracted course (ranging from 1 to 6 months) and a favorable recovery of impaired functions.

Main diagnostic criteria for mumps-induced serous meningitis:

1. Epidemiological history: a reported contact with a mumps patient or the presence of another form of mumps preceding The Development of meningitis; predominantly affects preschool and early school-age children; autumn-winter seasonality; sporadic or epidemic occurrence of the disease.

2. The onset of meningitis is acute, accompanied by high fever, recurrent vomiting, severe headache, and less frequently, other symptoms of general cerebral involvement (impaired consciousness, seizures).

3. Meningeal signs appear from the 1st day of CNS involvement, are moderately pronounced, may exhibit dissociation, and disappear by the 7th–10th day of the illness.

4. Clinical recovery consistently precedes the normalization of CSF parameters.

Other Clinical forms of CNS involvement in mumps are significantly less common and resolve with recovery.

Laboratory Diagnostics. A complete blood count is characterized by moderate leukopenia and lymphocytosis (though a mild leukocytosis may occur in the first days of the illness), with a normal or elevated ESR of up to 18-20 mm/h. A shift to the left in the leukogram reflects the severity of toxemia.

Virological examination. Definitive proof of the mumps etiology in serous meningitis is the Isolation of the virus from the cerebrospinal fluid and its cultivation in chicken embryos and chick fibroblast Cell cultures. However, this is a complex and labor-intensive Procedure that is not routinely used in clinical practice.

Serological testing. The Complement fixation test (CFT) and indirect hemagglutination assay (IHA) are most commonly employed. A fourfold or greater increase in the titer of specific complement-fixing or hemagglutination-inhibiting antibodies in paired sera obtained at a 10-15 day interval confirms the mumps etiology of meningitis. Enzyme-linked immunosorbent assay (ELISA) is currently widely utilized. The detection of specific IgM antibodies in the blood indicates an active infectious process. Specific IgG antibodies appear later but persist for many years.

Cerebrospinal fluid analysis. CSF examination reveals moderate lymphocytic pleocytosis ranging from 50 to 500 cells per 1 µL, accompanied by a slight increase in protein levels (up to 0.3–0.6 g/L), indicative of cellular-protein dissociation. Microscopic examination of CSF smears yields limited diagnostic information.