Viral meningitis in children: clinical guidelines

List of Abbreviations

ABR – auditory brainstem responses

aPTT – activated partial thromboplastin time

WI – weighted image

VM — viral meningitis

EP — evoked potentials

ICH – intracranial hypertension

DNA — deoxyribonucleic acid

DTI-MRI — diffusion tensor magnetic resonance imaging

units

VEP — visual evoked potentials

IMV – invasive mechanical ventilation

ADC — apparent diffusion coefficient

PI — pulse sequence

EIA – enzyme immunoassay

ABDS – acid-base balance status

ABR — acid-base solution

PT – physical therapy

IU – international unit

ICD-X — International Classification of Diseases (10th Revision)

INR – international normalized ratio

MRI – magnetic resonance imaging

NSAIDs — nonsteroidal anti-inflammatory drugs and antirheumatic drugs

NSG – neurosonography

CE – cerebral edema

ARVI — acute respiratory viral infection

ICU — intensive care unit

PT – prothrombin index

PCR – polymerase chain reaction

NT – neutralization test

RNA – ribonucleic acid

CFT – complement fixation test

CVP – central venous pressure

CNS – central nervous system

CSF – cerebrospinal fluid

ECG — electrocardiography, registration of electrocardiogram, decoding, description and interpretation of electrocardiographic data, electrocardiographic data monitoring

ENMG – electroneuromyography

EchoCG – echocardiography

EEG – electroencephalography

DTI – diffuse tract imaging – diffusion tractography

DWI – diffusion-weighted imaging

FLAIR – fluid-attenuated inversion recovery MRI sequence

IgG – immunoglobulin G

IgM — immunoglobulin M

SWI – susceptibility-weighted imaging

IV – intravenous

i.m. – intramuscularly

Terms and Definitions

Alimentarily transmitted infection – a transmission mechanism in which the pathogen enters a susceptible organism through the mouth, mainly by swallowing food (alimentary route).

Disease – a condition arising from exposure to pathogenic factors, characterized by impaired activity of the organism, working capacity, and ability to adapt to changing environmental conditions of the internal and external milieu, accompanied by simultaneous alterations in the protective-compensatory and protective-adaptive reactions and mechanisms of the body.

Zooanthroponoses are infectious diseases that develop in humans as a result of interaction with an animal population in which the pathogen circulates.

Instrumental diagnostics – diagnostics using various devices, apparatus, and instruments to examine a patient.

Disease outcomes – medical and biological consequences of a disease.

Quality of medical care – a set of characteristics reflecting the timeliness of medical care, the correctness of the choice of prevention, diagnosis, treatment, and rehabilitation methods in providing medical care, and the degree of achievement of the planned result.

Laboratory diagnostics is a set of methods aimed at analyzing test material using various specialized equipment.

Meningitis – a group of diseases characterized by inflammation of the membranes of the brain and spinal cord (mainly the pia mater and arachnoid mater).

Nosological form – a set of clinical, laboratory, and instrumental diagnostic signs that allow a disease (poisoning, trauma, physiological state) to be identified and classified into a group of conditions with common etiology, pathogenesis, clinical manifestations, and general approaches to treatment and condition correction.

Disease complication – the addition to the disease of a physiological process impairment syndrome; disruption of the integrity of an organ or its wall; hemorrhage; developed acute or chronic failure of an organ or organ system function.

Paraneoplastic syndrome – clinical and laboratory manifestations of a malignant tumor caused by nonspecific reactions from various organs and systems or the ectopic production of biologically active substances by the tumor, rather than by its local or metastatic growth.

Patient – an individual who receives medical care or who applies for medical care regardless of the presence of a disease and their condition.

Symptom – any sign of a disease that can be determined regardless of the method used for this purpose.

Syndrome – a condition developing as a consequence of a disease and defined by a set of clinical, laboratory, and instrumental diagnostic signs that allow it to be identified and classified into a group of conditions with different etiologies but common pathogenesis, clinical manifestations, and general approaches to treatment, which nevertheless also depend on the diseases underlying the syndrome.

Concomitant disease – a disease that has no causal relationship with the primary disease, is secondary to it in terms of the need for medical care, impact on working capacity, and danger to life and health, and is not the cause of death.

Vector-borne transmission mechanism – a mechanism of infection transmission in which the pathogen is present in the circulatory system and lymph, and is transmitted through vector bites: the bite of a blood-sucking arthropod (insect or tick). In this route of transmission, the vector transfers the pathogen directly from the source of infection to a susceptible organism.

Severity of a disease or condition – a criterion determining the extent of damage to human organs and/or body systems or the impairment of their functions caused by the disease, condition, or their complications.

Level of certainty of evidence – reflects the degree of confidence that the found effect of a medical intervention is true.

Cerebrospinal fluid (synonyms: spinal fluid, liquor) – a biological fluid that constantly circulates in the cerebral ventricles, cerebrospinal fluid pathways, and the subarachnoid space of the brain and spinal cord.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Viral meningitis (VM) – a multi-etiology viral disease characterized by serous inflammation of the meninges with a predominance of hypertension-hydrocephalus syndrome [1].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Viral meningitis in children can develop in any viral infectious disease accompanied by involvement of the nervous system in the pathological process, and is a result of damage to the meninges due to impaired blood-brain barrier permeability. The most frequent etiological causes of VM are infectious diseases caused by enteroviruses, herpesviruses, and less frequently, adenovirus, measles virus, mumps virus, and influenza viruses. Vaccination helps reduce the likelihood of neurological complications against the background of an infectious process; however, in the presence of aggravating factors, viral dissemination with involvement of the meninges is possible [1, 2].

The volume, level of damage, and clinical presentation also depend on the characteristics of the virus.

Enterovirus-induced VM is most commonly caused by such serotypes as: Coxsackie A (types 2, 3, 4, 6, 7, 9, 10), Coxsackie B (types 1–6), ECHO (excluding serotypes 12, 24, 26, 29, 33, 34), and enteroviruses of serotypes 70 and 71. Enteroviruses are RNA-containing agents with a high tropism for the grey matter of the anterior horns of the spinal cord [1, 2, 3, 4, 5].

Adenovirus is one of the DNA-containing viral agents causing VM in 0.1% of children [1, 6]. This infectious agent is characterized by tropism for the epithelium of the respiratory tract, intestines, and conjunctiva, as well as the ability to affect lymphoid tissue. Involvement of the meninges is usually secondary and occurs during the generalization of the infectious process [1, 6].

The causative agent of acute lymphocytic choriomeningitis (synonyms: Armstrong's acute serous meningitis, acute benign lymphocytic meningitis) belongs to the family Arenaviridae, has a spherical shape, and contains a single-stranded RNA consisting of two components. The virus exhibits a cytopathogenic effect, is resistant to antibiotics and low temperatures, is rapidly inactivated by boiling, and is sensitive to ultraviolet and direct sunlight, ether, and an ambient pH below 6.0. The pathogenesis is based on the tropism of the arenavirus for the pia mater and the choroid plexuses of the brain ventricles.

Tick-borne encephalitis virus rarely causes VM; it is an RNA-containing virus belonging to the family Flaviviridae, genus Flavivirus, which is part of the togavirus family of the arbovirus ecological group. Currently, three main subtypes of the pathogen are distinguished—Far Eastern, European, and Siberian—along with two recently discovered subtypes: Baikal and Himalayan. Tick-borne encephalitis virus exhibits a marked tropism for the motor neurons of the medulla oblongata and spinal cord, which in most cases determines the nature of the clinical manifestations of the disease.

Mumps-induced VM is relatively rare, occurring in approximately 10% of mumps cases. The causative agent is an RNA-containing virus from the family Paramyxoviridae and is characterized by hemagglutinating, hemolyzing, neuraminidase, and symplast-forming properties, as well as tropism for the meninges. Cultivation of the mumps virus is possible in chicken embryos and cell cultures (primary trypsinized cell cultures, continuous cell lines), which forms the basis for the laboratory diagnosis of the disease etiology. Wild-type mumps virus has no antigenic variants. The mumps pathogen is detected in saliva 3–4 days before the onset of the disease and continues to be excreted into the environment with saliva and urine for 8–10 days or more.

Herpesviruses are among the most frequent etiological agents causing nervous system damage in the form of encephalitis and meningoencephalitis; however, isolated VM without involvement of the brain parenchyma is rare. The most frequent herpesviruses causing VM are DNA-containing herpes simplex viruses types 1, 2, and 3. Despite their fragility in the environment, they exhibit a remarkable ability to replicate in the human body and show tropism for the skin and mucous membranes, and to a lesser extent for neural tissue. Varicella-zoster virus, which causes chickenpox during primary infection and shingles upon reinfection, has the ability to persist long-term, mainly in the dorsal root ganglia. Herpes simplex viruses types 1 and 2 most frequently persist in the trigeminal and sacral ganglia, while varicella-zoster viruses persist in the ganglia innervating the skin areas most affected during the primary infection (chickenpox). The clinical presentation of VM can develop both in cases of mono-infection and in the presence of combined herpesvirus infection (cytomegalovirus, Epstein-Barr virus, human herpesvirus type 6).

The development of measles meningitis is an extremely rare situation and is possible in unvaccinated children and immunocompromised individuals. The measles virus contains RNA and is capable of affecting both the meninges and the parenchyma of the brain and spinal cord, as well as peripheral nerves. A characteristic feature of this infectious agent when affecting the nervous system is the potential for long-term viral persistence—up to 1 year or more [1, 7].

VM can also develop in acute respiratory viral infections of various etiologies, but they predominantly manifest as meningoencephalitis [1–5].

The absence of vaccination against vaccine-preventable infections significantly increases the risk of complications, including those involving the nervous system.

Pathogenesis. Infectious involvement of the central nervous system (CNS), whether in the form of meningitis or meningoencephalitis in any viral infection, occurs either through direct hematogenous spread of viruses or via axonal transport from peripheral nerves into the brain parenchyma, which is more commonly characterized by the clinical picture of encephalitis or meningoencephalitis. Viruses can also spread via extracellular clefts between cells and CNS processes (dendrites, axons, glia), along axonal and dendritic processes, or be carried by mobile leukocytes during inflammation. All of these viral dissemination pathways can be involved simultaneously, but to varying degrees in different infections. Following the penetration of the virus into the CNS, inflammation of the brain tissue develops, which depends more on the patient's age than on the pathogen itself. As a result of viral dissemination within the CNS, endothelial cells induce pro-inflammatory cytokines as early as 24 hours after the onset of the disease [1, 7–10].

Following the development of inflammation in the central nervous system and due to the increased permeability of the blood-brain barrier, serum proteins, including immunoglobulins, enter intrathecally. Intrathecal synthesis of immunoglobulins also occurs, as evidenced by an increased proportion of specific immunoglobulins in the cerebrospinal fluid compared to blood. The production of oligoclonal IgG antibodies in the CNS has been proven in meningitis caused by mumps virus, varicella-zoster virus, which may remain elevated for a year, particularly in mumps meningitis, indicating the possibility of intrathecal viral persistence and ongoing antigenic stimulation. It is possible that the cellular immune response is more important in protecting against CNS viral infection than the humoral response. Damage to CNS tissues may result from direct viral replication and cell destruction or occur indirectly through immune-mediated mechanisms [2,11].

To date, the mechanisms of cell death remain unclear. Both direct suppression of cellular macromolecular synthesis by the virus or the toxic effect of viral polypeptides, and virus-induced apoptosis may occur. In the neuropathogenesis of virulent enteroviruses, the presence of special proteins on their capsid surface is significant, as they interact with CNS receptors, attracting the virus and facilitating its intracellular digestion. Mutations in viral capsid proteins can alter virion thermostability and affect interaction with the cellular receptor. In immunocompromised individuals (X-linked agammaglobulinemia), enterovirus persistence and the development of chronic meningoencephalitis are possible. Viruses can also persist in a "healthy" organism by reducing the expression of their genome below the "visibility threshold" for T effectors or by infecting immunologically privileged tissues that are difficult for T lymphocytes to access. For example, herpes simplex and varicella-zoster viruses "freeze" most of their genes in the neurons of regional sensory nerve ganglia, cytomegalovirus persists in macrophages and salivary glands, hiding behind the blood-saliva barrier, the measles virus hides in brain neurons, etc. The trigger for the activation of persistent viruses can be exposure to physical and chemical factors, oxidative stress, or superinfection [2].

1.3 Epidemiology of the Disease or Condition

In children, viral meningitis occurs 5-8 times more often than in adults, and more frequently in boys. The incidence of serous meningitis in children can range from tens to hundreds depending on the epidemiological situation. Viral meningitis exhibits etiological polymorphism and can develop either as an independent disease (primary) or as a complication of any infectious disease (secondary) [2,12].

The portal of entry for infection in primary viral meningitis is the mucous membrane of the nasopharynx, bronchi, and gastrointestinal tract. Secondary viral meningitis is immune-complex and allergic in nature [2].

Epidemiological history plays a key diagnostic role in viral meningitis caused by: enteroviruses, tick-borne encephalitis virus, varicella-zoster, adenovirus, and arenavirus, for which seasonality of the infectious disease is more characteristic [2,12,14].

Enteroviruses predominate in the etiological structure of viral meningitis, accounting for up to 58%. Since enteroviral infection is more common in children aged 3 to 10 years (children under 3 months get sick extremely rarely due to transplacental immunity), the probability of developing viral meningitis is higher specifically in this patient group. The incidence is characterized by epidemic surges in the spring-summer-autumn months, peaking in June-October. Coxsackie and ECHO infections are highly contagious, so when introduced into a children's group, epidemic outbreaks easily occur, affecting a large number of children (up to 80% of children fall ill). Outbreaks are characterized by a sharp initial rise and a wave-like course (2-3 weeks). Large epidemics covering vast territories and individual countries have been described. In the Russian Federation, particularly large epidemic outbreaks occurred in Primorsky Krai and the Far East [2,13,15].

Adenovirus meningitis is more frequently secondary and occurs in 2% of children suffering from adenoviral infection. Adenovirus-induced infection is somewhat more common in the autumn-winter-spring months [2].

The prevalence of lymphocytic choriomeningitis is about 5% in adults and 1.9% in children. Since the reservoir and source of the virus in nature are most often grey house mice, and less commonly other animals (dogs, rats, guinea pigs, etc.) that excrete it with nasal mucus, urine, and feces, the disease is more often encountered in the form of sporadic cases. The disease occurs somewhat more frequently in winter and early spring; however, no strict seasonality is observed [2,12,13].

Viral meningitis caused by tick-borne encephalitis virus can develop in children of any age, most commonly 7-14 years, who are unvaccinated against tick-borne encephalitis virus. The disease can be suspected due to the characteristic spring-summer-autumn seasonality of tick-borne infections, with a maximum peak in May-June driven by tick activity periods [2,4,5,14].

Viral meningitis caused by the mumps virus develops in approximately 32.8% of cases and can be either primary or secondary. The source of infection is exclusively human (patients with manifest and inapparent forms of mumps): a patient becomes contagious 1-2 days before the appearance of clinical symptoms and during the first 5 days of the disease. Preschool and early school-age children are high-risk groups, and boys are affected more often. Mumps is characterized by seasonality: in mid-summer, the number of cases drops sharply and rises again in late November. Information on contacts with sick individuals and vaccination helps narrow down the diagnostic search [1,2,16].

Among herpesviruses, viral meningitis caused by herpes simplex viruses (2.6%), varicella-zoster (1.9%), and Epstein-Barr virus (0.7%) predominate. Herpesvirus infection poses the greatest danger to the fetus, newborns, older children, and individuals with immunodeficiency states. In 70-80% of cases, infection occurs during childbirth. Viral meningitis caused by infection or reactivation of the varicella-zoster virus most commonly presents as meningoencephalitis and develops against the background of severe immunosuppression. Since chickenpox often manifests as outbreaks in organized groups, predominantly in the autumn-winter period, chickenpox-associated viral meningitis is also more likely to develop during this time [1,2,8].

Viral meningitis caused by the influenza virus occurs in 0.9% of cases, rubella in 1.2%, and measles in 0.3%, predominantly in unvaccinated individuals and those with a burdened medical history [2].

1.4 Features of Coding the Disease or Condition

In the ICD-10, viral meningitis is represented in categories A87 "Viral meningitis", G02 "Meningitis in infectious and parasitic diseases classified elsewhere" and includes the codes:

A87.0 – Enteroviral meningitis

A87.1 – Adenoviral meningitis

A87.2 – Lymphocytic choriomeningitis, lymphocytic meningoencephalitis

A87.8 – Other viral meningitis

A87.9 – Viral meningitis, unspecified

B00.3 – Herpesviral meningitis (G02.0)

B05.1 – Measles complicated by meningitis (G02.0)

B26.1 – Mumps meningitis (G02.0)

B01.0 – Varicella with meningitis (G02.0)

B02.1 – Zoster with meningitis (G02.0)

G02.0 – Meningitis in viral diseases classified elsewhere

G03.9 – Meningitis, unspecified

1.5 Classification of the disease or condition

Currently, there is a classification of viral meningitis based on various criteria [2,5,6].

I. According to the primary focus, primary and secondary meningitis are distinguished

• Primary: enteroviral, lymphocytic choriomeningitis, tick-borne encephalitis virus-induced.

• Secondary: caused by influenza virus, herpes, HIV, and other viral infections.

Primary meningitis develops without a preceding general infection or any disease, whereas secondary meningitis is a complication of other infectious diseases, inflammatory lesions of organs and systems. The portal of entry for infection in primary meningitis is the mucous membrane of the nasopharynx, bronchi, and gastrointestinal tract. Secondary meningitis is immune-complex and allergic in nature. Transmission of infection in utero via the placenta or intranatally is possible.

II. According to the clinical course:

• Acute – cerebrospinal fluid normalization occurs within 4 weeks.

• Protracted – from 4 to 12 weeks.

• Chronic – when the inflammatory process in the central nervous system lasts more than 3 months.

The acute course of meningitis includes cases where cerebrospinal fluid normalization occurs within 4 weeks, protracted – 4-12 weeks, and chronic – when the inflammatory process in the central nervous system lasts more than 3 months.

Factors contributing to chronrization include prior traumatic brain injury, various immunodeficiency states including hypo- or agammaglobulinemia, and inadequate etiotropic therapy.

III. According to etiology:

• Enteroviral.

• Lymphocytic choriomeningitis.

• Herpesviral (herpes simplex virus types 1 and 2, Epstein-Barr virus, varicella-zoster virus, etc.).

• Mumps.

• Influenza.

• Adenoviral.

• Caused by measles virus, rubella virus, tick-borne encephalitis virus, HIV, etc.

IV. By form:

• Initial.

• Pronounced.

Based on the severity of meningeal symptoms and changes in the cerebrospinal fluid, it is advisable to distinguish between initial meningitis (cytosis from 15 to 50×10⁶/L) and pronounced meningitis (with high pleocytosis).

V. By complications:

• Intracranial hypertension.

• Hydrocephalic syndrome.

• Diencephalic syndrome.

VI. By severity of the course.

• Moderately severe.

• Severe.

The diagnostic criteria for moderately severe meningitis are moderately pronounced general infectious, cerebral, and meningeal symptoms, pleocytosis up to 150 × 10⁶/L, protein up to 0.7 g/L, and absence of complications, whereas for severe meningitis, they include greater severity of clinical manifestations, convulsive syndrome, involvement of the brain parenchyma, changes in the cerebrospinal fluid, and complications.

VII. Complications:

• Intracranial hypertension.

• Hydrocephalic syndrome.

• Diencephalic syndrome.

VIII. By pathogenesis and mode of infection:

• Generalized (viremia).

• Transplacental (intrauterine infection).

IX. By morphological feature:

• Without involvement of the brain and spinal cord parenchyma.

• With involvement of the brain and spinal cord parenchyma.

X. By outcome:

• With complete recovery.

• Recovery with residual effects: cerebasthenic, hypertensive, epileptiform syndromes, diencephalic disorders, and others.

This classification is a working classification, but its use in practical work allows the physician at the patient's bedside to assess the severity of the disease, clinical features, and outcomes, streamline the formulation of the diagnosis, and determine adequate therapy both in the acute period, taking into account the viral etiology, and in the period of early and late reconvalescence, which leads to improved outcomes [2].

1.6 Clinical presentation of the disease or condition

The clinical picture of any viral meningitis is characterized by a combination of cerebral symptoms, meningeal syndrome, general infectious syndrome, and, in case of brain tissue damage, focal syndrome [1,2,6,12,16].

The tropism of enteroviruses to nervous tissue, muscles, and epithelial cells often determines the development of secondary meningitis. Exanthema, enanthema, myalgic, and other syndromes are observed in 25–90% of patients and in some cases may precede the development of meningitis. In the presence of symptoms of enterovirus infection, fever is biphasic with anapyrexia period of 2–5 days. In children, meningeal symptoms are absent in 15–20% of cases, but headache, vomiting, and photophobia are observed, indicating increased intracranial pressure. In enteroviral meningitis, the cerebrospinal fluid is transparent, flowing out under a pressure of 300–400 mm water column, with moderate lymphocytic pleocytosis from 30 to 800 cells per 1 µL (in the first days it may be mixed or neutrophilic, acquiring a lymphocytic character from the 2nd–3rd day), protein content is normal or decreased ("diluted" protein), less frequently increased to 1.5–2.0 g/L; sugar and chloride levels are unchanged. Sanitation of the cerebrospinal fluid is noted on days 14–20. Peripheral blood shows moderate leukocytosis, neutrophilia, left shift of the leukocyte formula, less frequently leukopenia, and moderately increased ESR. The duration of fever is 6–7 days, most commonly 2–4 days. Already on the 3rd–4th day, the intensity of the headache decreases, and vomiting stops. In the first days, 14–25% of children exhibit transient focal symptoms: anisoreflexia, intention tremor, which disappear within 1–5 days as intracranial pressure normalizes. The course of meningitis is generally benign, but relapses are possible. Meningeal symptoms in relapses of meningitis persist for one week or slightly longer, but CSF sanitation occurs more slowly – in 14–21 days or even later [2,6,13,15]. The clinical picture of enteroviral meningitis will largely depend on the age of the patients. Since newborns and young children (under 2–3 months) belong to a special risk group, viral meningitis proceeds like neonatal sepsis and is often accompanied by the progressive development of systemic manifestations of infection, such as liver necrosis, myocarditis, necrotizing enterocolitis, and DIC syndrome.

Viral meningitis caused by Coxsackie B viruses, less frequently Coxsackie A, ECHO, EV-71, is characterized by a more severe course with a fatality rate of up to 70%, especially in children under 5 years of age. A biphasic course of the disease is characteristic. The first phase is a disease with hand, foot, and mouth disease (HFMD) syndrome. Among the preceding syndromes, abdominal and neuromyalgic syndromes, diarrhea, and upper respiratory catarrhal phenomena of the rhinopharyngitis type are observed. The symptoms are accompanied by fever up to 38–40°C, which lasts from 2 to 5 days. The duration of the rash period ranges from 1–2, sometimes up to 8 days. The hand-foot-mouth syndrome is registered predominantly in children aged 6 months to 5 years. The second phase is the involvement of the nervous system developing on days 3–6 from the onset of the disease and includes three main syndromes: serous meningitis; acute flaccid paralysis of the limbs; and the most formidable complication, rhombencephalitis, a variant of encephalitis characterized by predominant involvement of the brainstem (midbrain, pons, and medulla oblongata) and cerebellum, and to a lesser extent other structures – the basal ganglia [1,2,6,13,15,16].

Herpetic serous meningitis practically does not differ from other serous viral meningitis and is characterized by a relatively mild course. Herpetic meningoencephalitis or encephalitis is most frequently registered, which can manifest either as a localized form of CNS damage only or be one of the manifestations of generalized herpetic infection, combined with lesions of the skin and internal organs — liver, pancreas, kidneys. In terms of the frequency of nervous system symptoms, horizontal nystagmus, moderate hyperreflexia of tendon reflexes, general hyperesthesia, and photophobia predominate. Meningeal symptoms are detected in the majority of patients and are moderately expressed. In adults, herpetic meningitis is usually associated with the presence of genital herpes. The appearance of herpetic rashes on the skin and mucous membranes in children, especially at an early age, is not typical. The appearance of seizures or focal neurological symptoms indicates the development of meningoencephalitis. The cerebrospinal fluid is usually colorless, flows out under increased pressure, with lymphocytic pleocytosis up to 200–800 cells per 1 µL, sometimes with a moderate increase in protein. Body temperature normalizes within a week, headaches and meningeal symptoms disappear. In extremely severe forms of meningitis and meningoencephalitis, a fatal outcome is possible [1,2,16].

Meningitis caused by the varicella-zoster virus in primary infection most often occurs acutely against the background of chickenpox rash, on days 5–7 from the onset of the rash, after a period of anapyrexia, and is accompanied by a short-term temperature rise lasting 3–5 days. Cerebral symptoms are moderately expressed and persist for 1–3 days. Focal neurological symptoms in the form of aniso-/hyperreflexia and ataxia develop in 1/3 of the patients and disappear in 2–4 days. Meningeal symptoms are moderately expressed, often dissociated. In the cerebrospinal fluid, lymphocytic pleocytosis up to 600 cells per 1 µL is noted, with normal or slightly increased protein content and normal glucose level. Complete recovery after chickenpox meningitis usually occurs in the 3rd–4th week of the disease. The duration of the meningeal symptom is no more than 2 weeks, and sanitation of the cerebrospinal fluid occurs on the 3rd–4th week of the disease [1,2,6,13].

Unlike chickenpox meningitis, meningitis in herpes zoster (resulting from reactivation of the varicella-zoster virus) is characterized by a significantly greater severity of the general infectious syndrome and the frequency of simultaneous involvement of the peripheral nervous system with the development of ganglionitis and ganglioneuritis. The onset of the disease is acute with high fever, headache, and very mild meningeal symptoms. The course is benign, with recovery within 3–5 weeks [2].

Lymphocytic choriomeningitis can present acutely (flu-like, meningeal, or generalized forms) or as a chronic and latent (asymptomatic) form of the disease. In young children, the onset may feature generalized seizures, altered consciousness, and the development of septic shock. An extremely severe condition may occur, marked by fever or agitation, hallucinations, followed by loss of consciousness. The cerebrospinal fluid is clear, slightly opalescent, and emerges under significantly increased pressure (up to 300–400 mm H₂O). Pleocytosis ranges from 100 to 1,500 cells per 1 µL with a predominance of lymphocytes (90–95%). Protein levels are normal or moderately elevated (up to 1 g/L) due to a relative increase in globulins; sugar and chloride levels remain unchanged. Peripheral blood tests show leukopenia or normocytosis, marked lymphocytosis, and a slightly elevated ESR. The acutely onset febrile period lasts 1–2 weeks, with temperature dropping by lysis to normal; however, 1/3 of patients experience prolonged low-grade evening fever, and less commonly, an undulating temperature curve. Excruciating headaches persist for two weeks, becoming paroxysmal over the next 3–5 weeks and subsiding as the acute process resolves. Vomiting ceases somewhat earlier than the headache. Meningeal signs typically persist for 10–14 days, occasionally lasting considerably longer (4–6 weeks). Clinical symptoms regress faster than cerebrospinal fluid normalization, which occurs between 2 weeks and 1 month (rarely later). The disease has a benign course. Characteristic findings in lymphocytic choriomeningitis include fundoscopic changes observed in 30–50% of patients: dilated and tortuous veins, mild optic disc edema, and blurred optic nerve margins [1,2,6,17].

Viral meningitis caused by tick-borne encephalitis virus develops in 30–70% of children. Neurological status reveals hyperreflexia, sometimes anisoreflexia without pathological plantar signs, fine-amplitude nystagmus in extreme lateral gaze on both sides, and static ataxia without clear lateralization. In the monophasic course of tick-borne encephalitis meningitis developing after a tick bite, body temperature rises to 39–40°C and lasts for 6–7 days. In the biphasic course in patients with a history of a tick bite, the onset of the first wave is always acute, with body temperature rising to 37.2–39.5°C, accompanied by malaise, headache, back and limb pain, upper respiratory catarrhal symptoms, and gastrointestinal disorders (loose stools, abdominal pain). Theapyretic period ranges from 2 days to 4 weeks. The onset of the second wave is characterized by a new rise in body temperature to 38–39°C, lasting 4–10 days and accompanied by general cerebral symptoms. The severity of meningeal signs varies from complete absence to pronounced manifestations, lasting 1–5 days.

In alimentary transmission resulting from the consumption of raw goat milk, the course of meningitis can be either monophasic or biphasic. Peripheral blood shows leukocytosis, a left shift in the leukocyte formula, monocytopenia, lymphocytopenia, and an elevated ESR of up to 20–38 mm/h. In approximately 13% of children with viral meningitis caused by tick-borne encephalitis virus, peripheral blood parameters are normal. The cerebrospinal fluid is clear and colorless, with a cell count of 33–536 cells per 1 µL (initially mixed or neutrophilic, but typically lymphocytic by the end of the first week of illness). Protein levels are normal or moderately elevated up to 0.7 g/L; sugar and chloride levels are normal. Cerebrospinal fluid normalization occurs during the 3rd–4th week, but may be delayed up to the 6th–8th week of illness. Following recovery, an asthenoneurotic syndrome (impaired memory, reduced working capacity) may be observed for some time. Severe headache, nausea, and repeated vomiting persist for 5–7 days. It should be noted that a benign course of the acute period does not rule out subsequent chronicity of the infection (3%) [1,2,3,4,5,6,8,14].

Mumps meningitis most commonly develops on the 3rd–6th day, and less frequently up to the 30th day, after the appearance of salivary gland swelling. In 20% of children, meningitis occurs simultaneously with salivary gland swelling; in 5% it precedes the swelling by 3–5 days; and in 4% of cases, meningitis occurs without clinical symptoms of salivary gland inflammation [2]. In young children, generalized seizures, loss of consciousness, adynamia, or agitation may occur during the first two days of meningitis. In older children, a delirious syndrome with delusions, hallucinations, and psychomotor agitation is more common. On the 3rd–5th day of illness, some patients may develop focal neurological signs: cranial nerve palsies, spastic hemiparesis, pathological plantar reflexes, cerebellar ataxia, and various psychosensory disorders, indicating the development of meningoencephalitis. From the 7th–10th day, focal signs begin to recede and completely disappear within 2–6 weeks. Neuritis of the vestibulocochlear nerve (VIII cranial nerve) is frequent, presenting with systemic vertigo, vomiting, and nystagmus. Eye and head movements exacerbate the vertigo, and children attempt to lie motionless. Vestibular disturbances persist for several days and gradually resolve. Polyradiculoneuropathy may be combined with serous meningitis. The presence of salivary gland inflammation on the 5th–11th day, combined with symmetrical, predominantly distal peripheral-type paresis and paralysis, radiculoneuritic pain syndrome, and sensory loss, helps establish the correct diagnosis. The cerebrospinal fluid is clear, pressure is elevated (up to 300–500 mm H₂O), pleocytosis ranges from 88 to 500 cells per 1 µL but can reach 2,000 cells, and is predominantly lymphocytic. There is a slight protein elevation up to 0.6–0.93 g/L, while glucose and chlorides are within normal limits. The acute period of mumps meningitis lasts 5–7 days. From the 2nd–3rd day of illness, vomiting becomes less frequent, headache intensity decreases, and CSF normalization occurs by the 18th–20th day, occasionally being delayed (up to 1.5–2 months). It should be noted that mumps meningitis can develop as a post-vaccination complication of the mumps vaccine [2,18].

Viral meningitis caused by the measles virus has no specific clinical features. Secondary acute measles meningoencephalitis develops somewhat more frequently. Neurological symptoms may appear at any stage of measles. Measles can simultaneously affect the brain, spinal cord, meninges, and peripheral nerves. The severity of neurological disorders also varies from severe, leading to permanent residual consequences and death, to mild subclinical manifestations. Cerebrospinal fluid analysis in measles meningoencephalitis reveals moderate pleocytosis ranging from 10 to 250 cells per 1 µL of a monocytic or mixed character, along with elevated protein levels [6,13].

Viral meningitis caused by adenovirus or influenza viruses has no significant clinical features, resulting in delayed initiation of targeted etiotropic therapy. In cases where secondary viral meningitis develops, the clinical manifestations of the acute infectious disease help narrow down the diagnostic search [1,2].

2. Diagnostics, medical indications and contraindications for diagnostic methods

General Approaches to Diagnosis

Diagnosis of viral meningitis is performed through history taking, detailed clarification of complaints, clinical examination, and additional (laboratory and instrumental) diagnostic methods. It aims to determine the extent of CNS structural involvement, severity, and clinical course of the disease, as well as to identify historical factors that preclude immediate treatment initiation or require treatment adjustment. Such factors may include:

- known intolerance to medications and materials used at the current stage of treatment;

- inadequate psychoemotional state of the patient prior to treatment;

- life-threatening acute condition/disease or exacerbation of a chronic condition requiring the involvement of a specialist in that field for treatment administration;

- refusal of treatment [1,2,6,13,19].

Criteria for establishing the diagnosis/condition:

The diagnosis of viral meningitis is established based on pathognomonic data:

1) physical examination (presence of one or more clinical symptoms arising after an incubation period of 2–30 days: general cerebral, and/or focal, and/or meningeal signs);

2) laboratory tests (presence of specific total IgM antibodies and a rising titer of IgG antibodies in blood and CSF against suspected viral infections—enteroviruses, adenovirus, measles virus, mumps virus, varicella-zoster virus, lymphocytic choriomeningitis virus, tick-borne encephalitis virus—and/or detection of viral nucleic acid [viral RNA or DNA] by PCR in blood and CSF) [1,2].

3) epidemiological history (data on contact with infectious patients, stay in endemic regions for measles, poliomyelitis, enterovirus infection, tick-borne infections, contact with rodents, history of tick bite, consumption of unpasteurized raw goat's milk or products made from it; positive PCR or ELISA test results of the removed tick for the presence of TBE virus);

Comparative differential diagnosis of meningitis in children at the pre-hospital stage is presented in Appendix A3.

2.1 Complaints and Anamnesis

Comments: staying in regions endemic for poliomyelitis, tick-borne infections, and contact with unvaccinated patients with acute viral infections are clarified. The seasonality of symptom onset, visits to forest or park zones within the last month before the illness, tick bite history, contact with a tick (removal from an animal or another person), and consumption of raw goat's milk or raw goat's milk products are taken into account. Information regarding the results of tick testing, the use of tick-borne immunoglobulin, the timing of its administration, as well as tick-borne encephalitis vaccination and its timing is clarified. Vaccination does not always prevent the development of the disease, but significantly alleviates its course. The fact of administration of tick-borne encephalitis immunoglobulin** must be taken into account for the correct interpretation of serological diagnostic data and incubation period duration (prolonged by the administration of tick-borne immunoglobulin).

Comments: clinical symptoms depend on the etiology and form of VM. A comparative differential diagnosis of VM is presented in Appendix A3.

2.2 Physical Examination

Comments: detection of signs of optic disc edema, which is one of the manifestations of intracranial hypertension, is a contraindication for performing a lumbar puncture.

Comments: it is necessary to evaluate the level of consciousness (using the Glasgow Coma Scale – Appendices G1, G2, where 15 points corresponds to clear consciousness, and 3 points or less corresponds to deep coma), and the presence/absence of meningeal and focal neurological signs.

2.3 Laboratory Diagnostics

Comments: red blood cell indices, leukocytes and leukocyte formula, platelets and platelet indices are evaluated.

Comments: lumbar puncture is performed within the first 24 hours from the establishment of a probable VM diagnosis, in the absence of contraindications. If inflammation of the meninges is present, pleocytosis is detected, typically lymphocytic-monocytic, along with proteinorrachia (in some cases, protein content remains within normal limits). Typically, VM is characterized by moderate pleocytosis (up to 1000 cells/µL) with mononuclear predominance and a slight increase in total CSF protein. In addition, a cerebrospinal fluid lymphocyte subpopulation composition with a B-cell content of less than 2.7% is characteristic of VM. The scope of differential CSF diagnostics is presented in Appendix A3.

Comments: lumbar puncture is possible only in the absence of contraindications; if present, the procedure is performed after patient stabilization and regression of cerebral edema manifestations.

Comment: nucleic acid amplification of viral meningitis pathogens is carried out by PCR (determining viral RNA or DNA in blood and CSF). Diagnostic search is based on epidemiological history data and the clinical picture of extracerebral manifestations of the infectious disease.

Comment: nucleic acid amplification of viral meningitis pathogens is carried out by PCR (determining viral RNA or DNA agents in blood and CSF). This method is the most reliable, but rather labor-intensive and sensitive to procedural errors. A negative PCR result upon initial testing does not rule out the disease. Repeat dynamic tests are required depending on the etiology of VM. Given the possibility of concurrent infection with multiple viruses and the similarity of the clinical picture of VM, simultaneous screening for other infections that may present with a similar clinical picture is necessary.

Comment: ELISA screening is recommended to be performed simultaneously with PCR testing for the rapid establishment of a definitive diagnosis due to the high frequency of negative results in PCR assays. Detection of class M antibodies and/or a 2–4-fold or greater increase in class G antibody titers in paired sera (during the acute period of infection and early convalescence) indicates an acute infection complicated by viral meningitis. A single detection of class G antibodies, regardless of their titer, does not allow interpreting the result as evidence of acute infection. In the presence of prior vaccination against measles, mumps, tick-borne encephalitis, or varicella, the detection of virus-specific IgG antibodies causing these diseases may reflect post-vaccination immunity levels. IgG avidity serves as an additional serological marker that can be used when IgM results are borderline or negative in the presence of clinical manifestations, or when both IgM and IgG are positive and it is necessary to exclude potential cross-reactivity due to polyclonal IgM activation. If determining the etiology via ELISA is not feasible, antibodies (classes M and G) to highly specific proteins of suspected viruses can be detected in the blood using immunoblotting with qualitative evaluation of results in the acute period and dynamically. The detection of class M antibodies and/or class G antibodies (in the acute period of infection and early convalescence—after 7–10 days from disease onset) against highly specific viral proteins with a changing protein profile indicates the presence of viral meningitis.

Comments: a follow-up lumbar puncture is performed on days 7–10.

Comment: it is advisable to determine the quantitative and qualitative levels of total IgM and IgG antibodies against suspected infectious agents capable of causing viral meningitis in the cerebrospinal fluid; these are usually detected a few days later than in the blood, but almost always by the 10th day of the disease.

2.4 Instrumental Diagnostics

Comments: this is used to assess the state of cerebral structures, the severity of brain edema (narrowing of CSF spaces), and signs of midline brain structure shift. It is most informative in children under 1 year of age with an open anterior fontanelle, whereas in older children and those with a closed anterior fontanelle, a temporal bone approach is used.

Comment: thickening of the optic nerve along with its sheaths is observed in intracranial hypertension; as it progresses, an increase in nerve thickness and blurring of its contours are visualized, which correlates with the ophthalmological signs of cerebral edema. Monitoring optic nerve thickness dynamically throughout the course of the disease allows for the evaluation of the efficacy of therapy aimed at normalizing intracranial pressure and managing cerebral edema.

Comment: EEG is recommended for patients with viral meningitis in the acute period of the disease to determine the scope of therapy. Assessing the severity of bioelectrical brain activity disorders allows for an indirect evaluation of brain edema; focal changes in bioelectrical activity indicate focal brain lesions, i.e., the development of encephalitis; the detection of epileptiform activity patterns makes it possible to prescribe or adjust anticonvulsant therapy. The detection on EEG of pronounced disorganization of the background rhythm, frequent paroxysms of slow-wave and epileptiform activity is characteristic of progressive intracranial hypertension and epilepsy in the case of meningoencephalitis development, and may serve as a prognostically unfavorable symptom.

2.5 Other Procedures

Comments: these tests are necessary as an exploratory assessment of the hemostasis system to determine the scope of pathogenetic therapy. Viral meningitis may feature structural and functional impairment of the hemostasis system in the form of generalized vasculitis associated with both endothelial damage and disruptions in its functional activity and vascular tone, which requires timely therapeutic correction; it is advisable to determine the levels of circulating (desquamated) endothelial cells, endothelin, and von Willebrand factor.

Comments:

Comments: an elevated level of C-reactive protein is a marker of bacterial infection and developing sepsis. The assay is used in clinical practice as an indicator of a septic state and to clarify the nature of inflammation in order to differentiate the viral or bacterial etiology of viral meningitis.

Comments: the blood procalcitonin level reflects the presence of septic complications in the patient. An increase in blood procalcitonin indicates the development of severe bacterial infections and purulent-inflammatory processes. Timely diagnosis of sepsis allows for the adjustment of therapy, which improves treatment outcomes.

Comments: the study of brainstem auditory evoked potentials (BAEPs) allows for the diagnosis of meningoencephalitis and intracranial hypertension syndrome, which manifests as conduction abnormalities at the medullo-ponto-mesencephalic level; this may indicate greater diffuseness of impairments in the acute period of viral meningitis and determines the scope of pathogenetic therapy.

Comments: functional disorders detected using VEPs may indicate subclinical brain damage, particularly due to cortical involvement. Additionally, patients with signs of intracranial hypertension may exhibit a decreased amplitude of the cortical response, which indirectly indicates functional suppression of visual pathways, including due to the possible development of partial optic nerve atrophy. Furthermore, the VEP registration method makes it possible to diagnose critical illness encephalopathy.

Comments: the volume and composition of infusion therapy are determined by the leading clinical syndrome, taking into account laboratory parameters (acid-base status, glucose level) and functional examination data (electrocardiogram recording, analysis, description, and interpretation of electrocardiographic data, electrocardiographic monitoring, echocardiography, central venous pressure measurement).

Differential diagnosis of viral meningitis.

Comments: a differential diagnosis is carried out with oncological pathology and other diseases characterized by meningeal and focal symptoms not accompanied by inflammatory changes in the brain and spinal cord. Along with the clinical symptoms of the disease, the absence of inflammatory changes in the cerebrospinal fluid during its general (clinical) examination is of great importance. Attention should be paid to the seasonality of the disease and a history of forest visits, tick bites, and attacks. Alongside the clinical symptoms, virological and serological studies of blood serum and cerebrospinal fluid are of great importance.

Comments: in some cases, using routine parameters as the sole tool for the differential diagnosis of bacterial and serous meningitis is uninformative. Additionally, it is possible to determine the levels of neurospecific proteins: assaying serum S-100 protein, blood neuron-specific enolase, and blood glial fibrillary acidic protein. Significant changes in neurospecific protein concentrations often occur before changes are detected on instrumental imaging. The differential diagnostic values for viral meningitis (versus bacterial meningitis) in the acute period of the disease are: neuron-specific enolase up to 3.0 ng/mL, glial fibrillary acidic protein up to 1.0 ng/mL, and S100 protein up to 200 ng/L.

Comment: computed tomography of the brain and spinal cord (depending on the topographic lesion) is performed to rule out a space-occupying brain lesion that may mimic typical viral meningitis, subarachnoid hemorrhage, empyema, or subdural effusion.

Comment: the study should be performed for the differential diagnosis of meningoencephalitis and complications, in particular, critical illness encephalopathy. FLAIR and DWI sequences show high MR signal from the meninges, while contrast administration (T1-WI+C) demonstrates intense contrast enhancement due to blood-brain barrier disruption. To better visualize inflammatory meningeal changes, it is recommended to use the post-contrast FLAIR sequence. Detecting contrast enhancement allows for a differential diagnosis with meningism, which is not characterized by blood-brain barrier permeability impairment.

In cases of complicated viral meningitis involving the adjacent brain parenchyma, meningoencephalitis develops. Manifestations of meningoencephalitis are characterized by areas of structural alterations on T2-WI, T1-WI, and FLAIR. In patients with viral meningoencephalitis, DWI and corresponding ADC maps are used to detect parenchymal edema, showing increased ADC in inflammatory foci during vasogenic edema and decreased ADC during cytotoxic edema. DTI-MRI reveals decreased fractional anisotropy, reflecting the integrity and connectivity of brain white matter tracts and the degree of their involvement in various pathological processes, as well as changes in axial and radial diffusivity, which provide more detailed information on parenchymal structural changes. To detect small hemorrhages, hemoglobin breakdown products, tissue calcium deposits in the brain, and vascular malformations, susceptibility-weighted imaging (SWI) is used. T2*-perfusion is used to assess the microvasculature, allowing the evaluation of such important parameters as blood flow velocity and volume. Proton magnetic resonance spectroscopy in inflammatory foci demonstrates a decreased N-acetylaspartate peak (a marker of neuronal density), an increased choline peak (a marker of cell membrane integrity), and the appearance of a lactate peak during hypoxia and activated anaerobic glycolysis.

In complicated viral meningitis, signs of subcortical and cortical cerebrovascular disorders, cortical atrophy with subarachnoid space widening, aneurysms, and subdural hygroma formation may be visualized.

The development of focal neurological symptoms that completely regress within 3–5 days from onset without residual neurological deficit, in the absence of inflammatory changes in the cerebrospinal fluid and a normal MRI picture, may be observed in encephalitic reaction.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

General approaches to the treatment of viral meningitis.

In suspected viral meningitis, emergency hospitalization to a hospital (a department with infectious disease beds) featuring an intensive care unit is recommended for all patients due to the possibility of sudden clinical deterioration.

To select the treatment strategy, it is necessary to determine factors influencing treatment efficacy: the clinical form of the disease, severity, course, patient age, presence and nature of complications, and the availability and feasibility of providing medical care in accordance with the required type of care [1,2,3,14,21,51,54,55].

The principles of treating patients with viral meningitis involve simultaneously addressing several objectives: preventing the further progression of the pathological process caused by the disease; preventing the development and arresting pathological processes and complications; and preventing a chronic course of the disease and the formation of residual effects.

Pharmacotherapy methods include:

- etiotropic therapy agents;

- pathogenetic therapy agents;

- symptomatic therapy agents.

3.1 Regimen and diet

The child's nutrition (diet) is determined by the characteristics of their somatic status and the presence of comorbid conditions.

3.2. Conservative treatment

Etiotropic treatment.

Etiotropic treatment includes the use of systemic antiviral drugs and immunostimulants. To achieve maximum effectiveness, their earliest possible administration is required [1,2,3,14,21,53,54,55].

Comments: to achieve a virus-eliminating effect, it is advisable to prescribe immunostimulants (interferon alfa-2b) in accordance with the instructions for use.

Comments: for patients with viral meningitis of herpesvirus etiology, it is advisable to prescribe the drug acyclovir** in accordance with the instructions.

The drug #ribavirin** is indicated for patients with viral meningitis suspected of having tick-borne encephalitis virus disease at a dose of 10 mg/kg/day in 2–3 doses for a duration of 14 days [5]. Cardiac arrhythmias are possible during therapy with #ribavirin**, which requires an ECG.

In children older than 7 years, #tilorone** may be used as an antiviral agent in accordance with the instructions, including for enteroviral meningitis: at the age of 7–12 years at a dose of 60 mg/day; older than 12 years — 125 mg/day once daily for 7 days, and then every other day for 5 days to reduce the duration of infectious toxicosis [90].

The effectiveness of antiviral therapy in patients with viral meningitis of unknown etiology is enhanced by the additional administration of interferon alfa-2b in accordance with the instructions for use.

Comments: the drug #meglumine acridoneacetate** potentiates the production of endogenous interferon, prevents infection of the body with viruses and bacteria, and contributes to the formation of a protective barrier [58]. The drug is prescribed to children older than 7 years in age-appropriate dosages of 10 mg/kg in tablets according to the specified schedule (once a day before meals on days 1, 2, 4, 6, 8, 11, 14, 17, 20).

Comments: after finishing the main course of therapy, technologically processed antibodies to human gamma-interferon are prescribed in accordance with the instructions.

Comments: the clinical efficacy of cefotaxime**, ceftriaxone**, cefoperazone + sulbactam** as initial antibacterial therapy has been proven in accordance with the instructions for use. Patients without foci of bacterial infection are not indicated for systemic antibacterial therapy.

Pathogenetic therapy

Comments: it is preferable to use dexamethasone** in accordance with the instructions for use.

Comment: it is advisable to use #aescin beta-escin / sodium aescinate at a dose of 0.15 mg/kg 2 times a day in 200 ml of 0.9% physiological saline solution intravenously by drip, slowly, as an angioprotector in children. The course of treatment generally lasts from 10 days [92]. The drug has endothelium-tropic, venotonic, anti-inflammatory, and analgesic effects simultaneously. The drug normalizes increased vascular-tissue permeability, increases venous tone, reduces venous blood stasis, improves arterial and venous blood flow in the microvasculature, and provides a membrane-stabilizing effect.

Comment: in the acute period of the disease, due to the development of cerebral hypoxia, it is advisable to use #inosine + nicotinamide + riboflavin + succinic acid**. The drug has antioxidant and antihypoxic effects, exerting a positive effect on energy production in the cell, reducing the production of free radicals, and restoring enzyme activity. It activates oxidation-reduction enzymes of the mitochondrial respiratory chain, the resynthesis of high-energy compounds, and promotes the utilization of glucose and fatty acids. The drug has an anti-ischemic effect, improves coronary and cerebral blood flow, limits the necrosis zone, and improves metabolic processes in the central nervous system, restoring consciousness, reflex disorders, and sensory disturbances. The drug is prescribed from the moment of admission to the hospital due to the development of cerebral hypoxia at a daily dose of 0.6 ml per kg of body weight (maximum 10 ml per day), intravenously, once a day, with a course of up to 10 days [67,68].

Comment: it is advisable to prescribe levocarnitine to children in the reconvalescence period to compensate for energy losses in accordance with the instructions. The drug improves metabolism and the energy supply of tissues, which is especially important in children who have been in the ICU.

Comments: normal human immunoglobulin** (for intravascular administration) is used in accordance with the instructions for use.

Symptomatic therapy

Comments: in pediatric practice, the use of ibuprofen** in children older than 3 months and paracetamol** in children older than 1 month is acceptable in accordance with the instructions for use.

Comments: drugs are prescribed from the acute period and subsequently on a regular course basis during the periods of early and late reconvalescence. Piracetam** is prescribed in accordance with the instructions for use.

Comments: drugs are prescribed from the acute period onwards on a regular course basis during the early and late convalescence periods. The following drugs have shown good efficacy: hopantenic acid, #deanole aceglumate 20% solution in 100 ml vials (1 teaspoon = 5 ml = 1 g), used starting from the 5th day of hospitalization at a dose of 2.5 ml (0.5 g) twice daily in children aged 10 to 12 years, and 5.0 ml (1 g) twice daily in children older than 12 years. The treatment duration is 1.5–2 months [88]. Hopantenic acid is prescribed in accordance with the instructions for use, depending on the severity of the patient's condition. #Deanole aceglumate, which exerts a cerebroprotective effect, is prescribed to children aged 10 to 12 years at 2.5 ml (0.5 g) twice daily, and to those older than 12 years at 5.0 ml (1 g) twice daily [88]. The drug helps restore mental activity, improves learning, and stimulates tissue metabolism processes. #Cerebral tissue polypeptides of bovine origin**, which exert neuroprotective, neuromodulating, antioxidant, and anti-inflammatory effects, are prescribed from the 2nd to 4th days of hospital stay at a single daily dose of 10 mg for 10 days [94].

Comment: multivitamins are approved in children over 1 year of age and are used in accordance with the instructions for use. It is preferable for the multivitamins to contain vitamins with a targeted neurotropic effect. These include vitamins B1, B6, and B12—thiamine, pyridoxine, and cyanocobalamin—contained within the multivitamin complex.

Comments: fatty acid derivatives (valproates) are the drugs of choice for the initial therapy of convulsive seizures. In viral meningitis, even a single convulsive seizure serves as an indication for the use of valproic acid**, especially if it has a focal component clinically or electroencephalographically. Valproic acid** is prescribed in accordance with the instructions, preferably as monotherapy. Simultaneous administration of valproic acid** and meropenem** is not recommended in accordance with the instructions. Systemic antibacterial drugs such as meropenem** decrease blood concentrations of valproic acid**, resulting in the ineffectiveness of anticonvulsant therapy. In severe forms, therapy must be initiated with parenteral drug administration.

3.3 Surgical Treatment

Surgical treatment is not performed.

3.4 Other treatment

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Comments: the following basic principles must be observed during rehabilitation:

- rehabilitation measures should begin as early as the period of early convalescence;

- it is necessary to maintain the consistency and continuity of the measures carried out, ensuring continuity at various stages of rehabilitation and follow-up (dispensary observation);

- the complex nature of restorative measures involving various specialists and utilizing diverse methods of pharmacological and non-pharmacological interventions;

- the adequacy of rehabilitation and restorative measures and interventions relative to the adaptive and reserve capabilities of the convalescent. In this regard, it is important to gradually increase metered physical and mental loads, as well as apply differentiated intervention methods; continuous monitoring of the effectiveness of ongoing measures. This takes into account the speed and degree of restoration of the functional state and professionally significant functions of the convalescents (using indirect and direct methods).

When developing rehabilitation programs for children convalescing from viral meningitis, it is advisable to include an assessment of the autonomic nervous system state in the examination plan using time and frequency domain analyses of heart rate variability (ECG, echocardiography).

To overcome age restrictions in setting rehabilitation goals within the "active participation" domains in children aged 5 years and older, it is possible to use the Russian-translated and validated "Children's Assessment of Participation and Enjoyment" (CAPE) questionnaire (Appendix A3) both for planning individual interventions and assessing their effectiveness.

5. Prevention and Dispensary Observation

General approaches to prevention.

Vaccination

Prevention of viral meningitis includes specific and non-specific protective measures. Specific measures include active immunization (vaccination). Depending on the timing relative to the moment of infection, a distinction is made between pre-exposure (before infection) and emergency (post-exposure—after infection) prophylaxis. Non-specific measures include compliance with personal hygiene rules, increasing the body's immune reactivity through non-pharmacological methods (hardening, etc.) and pharmacological methods (the use of various immunomodulators, vitamin therapy, and other types), as well as measures aimed at preventing tick attachments and ensuring their earliest possible detection and removal [1,2,6,76].

5.1. Specific prevention of vaccine-preventable infections

Vaccination is a form of specific prophylaxis against infectious diseases.

Comments: all vaccines have high immunogenicity. Vaccination is carried out according to the schedules and timelines specified in the drug instructions and taking into account the regional epidemiological situation. Emergency schedules are recommended when necessary to provide rapid protection during seasonal incidence peaks. However, routine vaccination schedules take priority, as emergency vaccination schedules induce a lower immune response after the second dose, and protective antibodies decline faster than with routine vaccination.

5.2 Non-specific prevention

Non-specific prophylaxis includes a number of measures aimed at preventing infection:

1) tracking contacts with infectious patients;

2) continuous compliance with personal hygiene rules and heat treatment of food products;

3) prevention of contact with vectors of infectious agents.

5.3 Clinical follow-up (dispensary observation)

Comments: the frequency and timing of clinical follow-up are determined by the attending physician. The duration of follow-up is determined by the form of the disease, the presence of clinical symptoms, and the data from laboratory and instrumental monitoring. The grounds for discharging a patient from clinical follow-up are full recovery of work capacity/functional status, satisfactory well-being, absence of clinical signs of the disease and focal neurological symptoms, and seroconversion.

6. Organization of Medical Care

In case of suspected viral meningitis, emergency hospitalization in a medical organization is indicated—regardless of the etiology, form, or severity of the disease.

Transportation/hospitalization of a patient with progressive intracranial hypertension/cerebral edema due to the potential development of life-threatening conditions must be carried out by an anesthesiology-resuscitation team, including pediatric or emergency consultative teams, provided that mechanical ventilation can be performed.

Treatment of patients is carried out in a hospital setting (infectious diseases department / infectious beds) upon referral by a neurologist, general pediatrician, general practitioner, infectious disease physician, emergency physician, or other medical workers who identified viral meningitis.

Medical care for patients with viral meningitis is provided in:

- a hospital setting with an ICU.

• The outcome of the disease depends on early diagnosis and the initiation of prompt treatment, including etiotropic therapy.

• Indications for discharging a patient from a medical organization:

  - normalization of the general condition;

  - absence of intoxication;

  - significant reduction or disappearance of neurological deficit.

• Laboratory criteria for recovery based on blood and cerebrospinal fluid test results:

  - absence of viral RNA, DNA, or antigen detection by PCR;

  - ELISA results showing absence of IgM no later than 3 months from disease onset, or their decrease following therapy;

  - absence of a rising IgG antibody titer 3 or more months after the acute period of the infection, normalization of cerebrospinal fluid composition.

7. Additional Information

Possible outcomes of viral meningitis and their characteristics (Table 1) [1,2,3,4,6,14].

Table 1. Possible outcomes and their characteristics

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

Zhdanov K.V. - Honored Scientist of the Russian Federation, Doctor of Medical Sciences, Professor, Corresponding Member of the Russian Academy of Sciences, Director of the Research and Clinical Center for Neuroinfections and Antibiotic Resistance of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology of the FMBA of Russia, Chief freelance specialist in infectious diseases of the Health Committee of St. Petersburg, Member of the Euro-Asian Society of Infectious Diseases, Member of the National Scientific Society of Infectionists, Member of the Association of Infectious Disease Physicians of St. Petersburg and Leningrad Region, Chief freelance specialist in infectious diseases of the Health Committee of St. Petersburg;

Lobzin Yu.V. - Honored Scientist of the Russian Federation, Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences, Chief freelance specialist in pediatric infectious diseases of the Russian Ministry of Health and FMBA of Russia, Honorary President of the Research and Clinical Center for Neuroinfections and Antibiotic Resistance of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology of the FMBA of Russia, Head of the Department of Infectious Diseases at the North-Western State Medical University named after I.I. Mechnikov, President of the Euro-Asian Society of Infectious Diseases, Deputy Chairman of the National Scientific Society of Infectionists, Chairman of the Board of the Association of Infectious Disease Physicians of St. Petersburg and Leningrad Region;

Skripchenko N.V. - Honored Scientist of the Russian Federation, Doctor of Medical Sciences, Professor, Head of the Department of Pediatric Infectious Diseases at the Faculty of Postgraduate and Additional Professional Education of the St. Petersburg State Pediatric Medical University, Member of the National Scientific Society of Infectious Diseases, Member of the Board of the All-Russian Association of Neurologists, Member of the Board of the St. Petersburg Branch of the Union of Pediatricians of Russia; Euro-Asian Society of Infectious Diseases; Association of Infectious Disease Physicians of St. Petersburg and Leningrad Region;

Skripchenko E.Yu. - Doctor of Medical Sciences, Professor, Head of the Research Department of Neuroinfections and Organic Pathology of the Nervous System at the Federal Research and Clinical Center of Children's Infections of the Federal Medical-Biological Agency (FSBSI FRCCCI FMBA), Professor at the Department of Neonatology with Courses in Neurology and Obstetrics and Gynecology of the Faculty of Postgraduate and Additional Professional Education at the St. Petersburg State Pediatric Medical University of the Ministry of Health of the Russian Federation;

Ivanova G.P. - Doctor of Medical Sciences, Leading Researcher at the Research Department of Neuroinfections and Organic Pathology of the Nervous System at the Federal State Budgetary Institution "Children's National Research and Clinical Center of Infectious Diseases of the Federal Medical-Biological Agency" (FSBSI FRCCCI FMBA);

Irikova M.A. - Functional Diagnostics Physician, Researcher at the Research Department of Functional and Radiation Diagnostics Methods at the FSBSI FRCCCI FMBA. Member of the Association of Clinical Neurophysiology Specialists (ASKLIN);

Vasilyeva Yu.P. - Candidate of Medical Sciences, Researcher at the Research Department of Neurophysiological and Radiation Diagnostics at the FSBSI FRCCCI FMBA. Member of the Russian Association of Ultrasound Diagnostics Specialists in Medicine, member of the Association of Neurologists of St. Petersburg, member of the Association of Pediatric Neurologists and Neurorehabilitologists, member of the All-Russian Society of Neurologists;

Vilnits A.A. - Doctor of Medical Sciences, Senior Researcher, Head of the Research Department of Intensive Care of Emergency Conditions at the FSBSI FRCCCI FMBA, Associate Professor at the Department of Infectious Diseases in Children at the Faculty of Postgraduate and Additional Professional Education of the St. Petersburg State Pediatric Medical University, member of the National Scientific Society of Infectious Diseases Specialists; Euro-Asian Society of Infectious Diseases; Association of Infectious Diseases Physicians of St. Petersburg and Leningrad Region;

Alekseeva L.A. - Doctor of Medical Sciences, Head of the Research Department of Clinical Laboratory Diagnostics at the FSBSI FRCCCI FMBA;

Goleva O.V. - Candidate of Medical Sciences, Senior Researcher at the Research Department of Experimental Medical Virology, Molecular Genetics and Biobanking at the FSBSI FRCCCI FMBA, member of the Federal Register of Experts of the Research Institute of the Republican Research Scientific-Consulting Center of Expertise (RINCZ) for the Evaluation of Scientific, Technical and Innovation Activities of the Russian Federation;

Markova K.V. - Candidate of Medical Sciences, Junior Researcher at the Research Department of Neuroinfections and Organic Pathology of the Nervous System at the FSBSI FRCCCI FMBA, member of the National Scientific Society of Infectious Diseases Specialists;

Astapova A.V. - Candidate of Medical Sciences, Researcher at the Research Department of Neuroinfections and Organic Pathology of the Nervous System at the Federal State Budgetary Institution "Children's National Research and Clinical Center of Infectious Diseases of the Federal Medical-Biological Agency" (FSBSI FRCCCI FMBA);

Tkhakushinova N.H. - Doctor of Medical Sciences, Associate Professor, Head of the Department of Pediatric Infectious Diseases at Kuban State Medical University of the Russian Ministry of Health, Chief Pediatric Infectious Disease Specialist of Krasnodar Krai and the Southern Federal District, Chief Physician of the Children's Infectious Clinical Hospital, Krasnodar;

Shaturina T.T. - Assistant at the Department of Pediatric Infectious Diseases, Kuban State Medical University of the Russian Ministry of Health, Head of Department at the Children's Infectious Clinical Hospital, Krasnodar;

Rychkova S.V. - Doctor of Medical Sciences, Professor, Head of the Medical Care Organization Department at the FSBSI FRCCCI FMBA;

Klimkin Andrey Vasilievich - Candidate of Medical Sciences, Senior Researcher at the Research Department of Neuroinfections and Organic Pathology of the Nervous System, Functional Diagnostics Physician at the FSBSI FRCCCI FMBA. Member of the Association of Clinical Neurophysiology Specialists (ASKLIN).

The authors of the clinical guidelines confirm the absence of financial support/conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Methodology

Methods used for collecting/selecting evidence: electronic database search.

Description of methods used for evidence collection/selection: the evidence base for the guidelines includes publications indexed in the Cochrane Library, EMBASE, MEDLINE, Clinicalkey ELSEVIER databases, and the electronic library (www.elibrary.ru).

Methods used to assess the quality and strength of evidence:

- expert consensus;

- assessment of significance in accordance with the levels of evidence reliability and levels of recommendation conviction.

Methods used for evidence analysis:

- reviews of published meta-analyses;

- systematic reviews with evidence tables.

Description of methods used for analyzing evidence

When selecting publications as potential sources of evidence, the methodology used in each study is examined to ensure its validity. The result of this examination affects the level of evidence assigned to the publication, which in turn affects the strength of the recommendations.

To minimize potential bias, each study was evaluated independently. Any discrepancies in evaluations were discussed by the full panel of authors. If a consensus could not be reached, an independent expert was involved.

Evidence tables: compiled by the authors of the clinical guidelines.

Methods used for formulating recommendations: expert consensus.

Good Practice Points (GPPs)

Recommended good clinical practice is based on the clinical experience of the authors of these guidelines.

Economic analysis

Cost analysis was not performed, and pharmacoeconomic publications were not analyzed.

Method of guideline validation.

External expert review.

Internal expert review.

Description of the guideline validation method.

The draft of these recommendations was reviewed by independent experts who were primarily asked to comment on how comprehensible the interpretation of the evidence underlying the recommendations is.

All comments received from the experts were thoroughly systematized and discussed by the members of the working group (authors of the recommendations). Each item was discussed individually.

Consultation and peer review

The draft recommendations were reviewed by independent experts who were primarily asked to comment on the clarity and accuracy of the interpretation of the evidence base underlying the recommendations.

Working Group

For the final revision and quality control, the recommendations were re-evaluated by the members of the working group, who concluded that all comments and feedback from the experts had been taken into account and the risk of bias in the development of the recommendations was minimized.

Target audience for these clinical guidelines:

1. anesthesiologist-intensivist;

2. disinfectologist;

3. health station physician;

4. infectious disease physician;

5. clinical laboratory diagnostics physician;

6. clinical pharmacologist;

7. neurologist;

8. general practitioner (family physician);

9. pediatrician;

10. municipal (district) pediatrician;

11. primary care pediatrician;

12. medical prevention physician;

13. medical rehabilitation physician;

14. admitting department physician;

15. epidemiologist.

Table 1.Scale for evaluating levels of evidence (LoE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing levels of evidence (LoE) for prevention, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for assessing grades of recommendation (GoR) for prevention, diagnostic, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

1. Federal Law No. 323-FZ dated November 21, 2011, "On the Fundamentals of Protecting the Health of Citizens in the Russian Federation".

2. Order of the Ministry of Health and Social Development of Russia dated May 5, 2012, No. 521n "On Approval of the Procedure for Providing Medical Care to Children with Infectious Diseases".

3. Order of the Russian Ministry of Health dated April 14, 2025, No. 203n "On Approval of Quality Criteria for Assessing Medical Care".

4. Federal Law of the Russian Federation No. 326-FZ dated November 29, 2010, "On Compulsory Medical Insurance in the Russian Federation".

5. Federal Law of the Russian Federation No. 52-FZ dated March 30, 1999, "On the Sanitary and Epidemiological Welfare of the Population".

6. Order of the Ministry of Health of the Russian Federation No. 804n dated October 13, 2017, "On Approval of the Nomenclature of Medical Services."

7. Order of the Ministry of Health and Social Development of Russia dated July 23, 2010, No. 541n "On Approval of the Unified Qualification Handbook of Positions of Managers, Specialists, and Employees", section "Qualification Characteristics of Employee Positions in Healthcare".

8. Order of the Russian Ministry of Health dated April 11, 2025, No. 192n "On Approval of the Procedure for Minors Undergoing Dispensary Observation, Including During Education and Upbringing in Educational Organizations".

9. International Statistical Classification of Diseases and Related Health Problems (10th Revision), https://nsi.rosminzdrav.ru/dictionaries/1.2.643.5.1.13.13.11.1005/passport/2.27

10. Resolution of the Chief State Sanitary Doctor of the Russian Federation dated January 28, 2021, No. 4 "On Approval of Sanitary Rules and Norms SanPiN 3.3686-21 'Sanitary and Epidemiological Requirements for the Prevention of Infectious Diseases'" (along with "SanPiN 3.3686-21. Sanitary Rules and Norms...").

11. Order of the Federal Medical-Biological Agency dated April 3, 2017, No. 59 "On Improving Measures for the Prevention of Tick-Borne Viral Encephalitis Among the Population and in Territories Served by the FMBA of Russia".

12. "MU 3.5.3011-12. 3.5. Disinfectology. 'Nonspecific prevention of tick-borne viral encephalitis and ixodid tick-borne borrelioses (approved by the Chief State Sanitary Doctor of the RF on April 4, 2012) along with 'Rules of conduct in areas infested with ticks of the genus Ixodes').

13. Order of the Russian Ministry of Health dated December 6, 2021, No. 1122n (as amended on December 12, 2023) "On Approval of the National Schedule of Preventive Vaccinations and the Schedule of Preventive Vaccinations by Epidemiological Indications and the Procedure for Performing Preventive Vaccinations".

14. State Register of Medicines (http://www.grls.rosminzdrav.ru/grls.aspx).

15. Therapeutic Nutrition Standards. Methodological Guide. 2017. Access: http://cr.rosminzdrav.ru/#!/manuals/adults//

16. <Letter> of Rospotrebnadzor dated January 30, 2025, No. 02/1616-2025-27 "On the List of Endemic Territories for Tick-Borne Viral Encephalitis in 2024".

Differential diagnosis of meningitis [1,2,6,12,13,16]

Differential diagnosis of serous meningitis in children [2]

Differential cerebrospinal fluid diagnosis of viral meningitis in children [2]

Contraindications for lumbar puncture [30]

1. impaired level of consciousness (GCS less than 9 points), or fluctuating consciousness;

2. relative bradycardia and hypertension;

3. focal neurological symptoms;

4. seizures;

5. unstable hemodynamics;

6. inadequate pupillary response to light;

7. "doll's eyes" sign;

8. septic shock;

9. progressing hemorrhagic rash;

10. hemostatic disorders;

11. platelet count less than 100 x10⁹/L;

12. ongoing anticoagulant therapy;

13. local skin and soft tissue infection at the LP site;

14. respiratory failure.

Transportation/hospitalization of a patient with progressive intracranial hypertension (ICH)/brain edema due to the potential development of life-threatening conditions must be carried out by an anesthesiology and resuscitation team, including a pediatric or emergency consultation team, provided that mechanical ventilation can be performed.

Child and Adolescent Scale of Participation (CASP) [80]

-Instructions-

1. This scale asks questions about your participation in activities at home, at school, and in the community. There are also a few questions about assistive devices that are used or have been made to help you participate.

2. There are no right or wrong answers. You will need to choose and, in some cases, write an answer that best describes your situation and what helps or hinders your participation. If you are unsure how to answer a question, write down your best guess. 

Your name ___________________________

Your age (in years) ________________

Date of survey completion______________

                         (Day / Month / Year)

We are interested in learning about the activities you participate in at home, at school, and in the community. You will be asked about your current level of participation in activities compared to other children your age. For each item, choose one of the following responses: 

Full participation, you participate in activities as often as or more often than your peers.

[With or without assistive devices or equipment] 

Somewhat limited, you participate in activities somewhat less often than your peers.

[You may also need help] 

Very limited, you participate in activities much less often than your peers.

[You may also need help] 

Unable, you are unable to participate in activities even though your peers do. 

Not applicable, your peers would not be expected to participate in the activities.

Please describe the barriers that hinder your participation in the above-mentioned activities [Please write clearly]:

Please describe the assistive items/helpers that assist you in participating in the above-mentioned activities [Please write clearly]:

Do you currently use any assistive devices or equipment to help you participate (e.g., adapted kitchen utensils, shower chair, school notebook, planner, computer)?

□ YES

□ NO

[If Yes], please specify which ones.

Have any changes been made to your home or school (or work) environment to help you participate (e.g., rearranging furniture and materials, adjusting lighting or noise levels, building a ramp or other physical structures)?

□ YES

□ NO

[If Yes], please describe.

Appendix B. Physician Action Algorithms

Viral serous meningitis

Appendix C. Patient Information

Viral serous meningitis is a neuroinfectious disease characterized by inflammation of the meninges. 

Which infections carry a risk of developing viral meningitis?

Viral serous meningitis is a manifestation of lymphocytic choriomeningitis and can also develop as a complication of any viral infection. Viral meningitis is most commonly associated with enterovirus infection, adenovirus infection, herpesvirus infection (caused by herpes simplex virus types 1 and 2, varicella-zoster virus), measles, mumps, shingles, and tick-borne encephalitis virus infection.

Is there a seasonality to the diseases?

Seasonality is characteristic of enterovirus infection—predominantly the spring-summer periods (though cases may occur year-round)—and of infections transmitted by ixodid ticks—the period from April to October (until the first frosts), when ticks are active.

What are the risks of developing viral serous meningitis?

VM can lead to complications that may result in neurological deficits, potentially requiring multiple courses of medical rehabilitation.

Prevention of viral infections. The most effective method is vaccination against all vaccine-preventable infections according to the schedule specified in the National Immunization Schedule, as well as for epidemiological indications. In addition, the likelihood of developing neurological complications can be reduced by vaccination against varicella, tick-borne encephalitis, measles, mumps, and other viral pathogens. Furthermore, personal hygiene rules must be strictly observed; when preparing for a trip to the forest, one should choose clothing that covers as much of the body as possible to prevent ticks from reaching exposed areas, use anti-tick repellents, and perform self- and peer-examinations after spending an extended time in the forest. Contact with individuals suffering from viral infections should be avoided (or the duration of contact minimized). Vegetables, fruits, and herbs must be thoroughly washed before consumption, and food products should undergo heat treatment whenever possible. 

What to do if a tick bites?

In the event of a tick bite, you should promptly contact a medical facility where the tick will be removed and emergency prophylaxis for tick-borne encephalitis with tick-borne encephalitis immunoglobulin will be administered.

If for some reason you are unable to seek help at a medical facility, you will have to remove the tick yourself using tools that prevent the tick from contacting the skin. The sooner you remove the attached parasite, the better. The removed tick should be placed in a small, tightly sealed container with a small piece of slightly damp cotton or a napkin, and taken within two days to a laboratory that tests ticks.

What to do if a child develops altered consciousness or a headache?

A doctor should be called to the home for an examination. If VM is suspected, or if seizures, altered consciousness, or symptoms of nervous system damage appear, hospitalization is necessary.

Prevention of VM is carried out in two directions: vaccination—specific prevention of viral infections, and precautionary measures—nonspecific prevention.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Clinical scale for assessing the level of consciousness in patients over 4 years of age

[21]

Original title. Glasgow Coma Scale (GCS) GlasgowComaScale

Source: https://www.glasgowcomascale.org/

Type: scale

Purpose: criterion for assessing the level of consciousness and coma, correlating with the severity of cerebral injury and prognosis.

Content: the scale consists of three tests evaluating eye-opening, verbal, and motor responses. A specific number of points is awarded for each test. The eye-opening test ranges from 1 to 4 points, the verbal response test from 1 to 5 points, and the motor response test from 1 to 6 points. The level of consciousness is expressed as the sum of points for each parameter.

Glasgow Coma Scale /GlasgowComaScale/

Interpretation of results:

15 points — clear consciousness;

14–13 points — moderate stupor;

12–11 points — deep stupor;

10–8 points — sopor;

7–6 points — moderate coma;

5–4 points — deep coma;

3 points — beyond coma, brain death.

Appendix G2. Modified Glasgow Coma Scale for Infants and Children

[19].

Original title. Glasgow Coma Scale (GCS) GlasgowComaScale

Source: https://www.glasgowcomascale.org/

Type: scale

Purpose: criterion for assessing the level of consciousness and coma, correlating with the severity of cerebral injury and prognosis in infants and children under 4 years of age.

Content: the scale consists of three tests evaluating eye-opening, verbal, and motor responses. A specific number of points is awarded for each test. The eye-opening test ranges from 1 to 4 points, the verbal response test from 1 to 5 points, and the motor response test from 1 to 6 points. The level of consciousness is expressed as the sum of points for each parameter.

Interpretation of results:

15 points – alert / clear consciousness;

10–14 points – moderate and deep obtundation;

9–10 points – stupor;

7–8 points – moderate coma (coma 1);

5–6 points – terminal coma (coma 2);

3–4 points – cortical death (coma 3).