Meningitis in Children - I.V. Bohadelnikov 2005

Primary purulent meningitis in children. General data
Meningococcal meningitis

Meningococcal meningitis is one of the generalized Clinical forms of meningococcal infection caused by Neisseria meningitidis, characterized by an acute onset, prominent general cerebral and meningeal symptoms, as well as manifestations of toxemia and bacteremia.

Etiology. The causative agent is a non-motile, Gram-negative meningococcus characterized by high Variability. It is extremely fragile in the external environment: sensitive to drying, sunlight, and cold, and rapidly perishes when the Temperature deviates from 37 ^oC. The pathogenicity factors include a capsule that protects the microbe from phagocytosis and other unfavorable factors. The toxic Properties of the meningococcus are mediated by an endotoxin, which is a lipopolysaccharide similar in chemical and biological properties to enterobacterial endotoxins, yet 5 to 10 times more potent. Based on antigenic properties, meningococci are divided into 11 serogroups (A, B, C, D, Z, X, Y, as well as non-agglutinating serogroups 29E, 135, W135, and Z'). Epidemiologically, type A is the most hazardous as it causes outbreaks, along with types B, C, and Y, which cause sporadic cases. Typically, in smears, the meningococcus appears as a non-motile diplococcus arranged in pairs both intracellularly and extracellularly, resembling coffee beans. These characteristics are used for preliminary Diagnosis. Meningococci grow on media enriched with Blood, serum, ascitic fluid, milk, or egg yolk. The microbe is an aerobe; the optimal temperature for its reproduction is 36°–37° C, with a slightly alkaline pH of 7.2–7.4.

Epidemiology. The reservoir and source of infection are individuals ill with meningococcal infection or healthy carriers. Healthy meningococcal carriers are particularly dangerous from an epidemiological standpoint, accounting for 1% to 2% of the total population during periods of sporadic incidence. According to various sources, The ratio of patients to carriers can range from 1:2000 to 1:50000. In 1–3% of meningococcal infection cases, the source of infection is generalized forms; in 10–30%, it is patients with meningococcal nasopharyngitis; and in 70–80%, it is meningococcal carriers. The duration of carriage averages 11 days. The primary mechanism of transmission is airborne droplet. The pathogen is released into the environment from the nasopharynx during speaking, coughing, and sneezing. Contact transmission is of virtually no practical significance due to the fragility of the pathogen. Most effective transmission occurs at a distance of up to 50 cm from the source. Susceptibility to meningococcus is low, at 0.5%. Crucial factors for infection include the concentration of the pathogen in the air, overcrowding of children, prolonged and close contact, and disruptions in indoor temperature and humidity. We observed a case where in winter, during a heavy admission of patients to an infectious diseases hospital when no isolation room was available in the admission ward, a young physician entered an ambulance, examined a patient with meningococcal infection, and filled out the medical history right there. In total, the doctor spent no more than 30 minutes in the vehicle. Five days later, this doctor contracted meningococcal infection and, despite initiated measures, died.

Cyclical increases in incidence occur every 10–12 years, lasting up to 4–6 years. The beginning of the upcoming epidemic is expected in 2010–2011, though, considering demographic processes in the CIS countries (migration and other factors), it may start even earlier. It is believed that the rise in incidence will be driven by serogroup A meningococcus, which will be superseded by the serogroup B pathogen (A. A. Demina, 1999).

Children are particularly susceptible to meningococcus, accounting for 50% of all cases in those under 5 years of age. A distinct winter-spring seasonality (February–March) is characteristic, which is explained both by weather conditions (temperature fluctuations, humidity) and the increased incidence of Influenza and other acute respiratory viral infections (ARVI).

Pathogenesis. The deposition of meningococci onto the mucous membranes of the nasopharynx and oropharynx does not necessarily mean The Development of the disease. Only in 10–15% of cases does The entry of meningococci onto the nasopharyngeal mucosa lead to nasopharyngitis. This is related to a whole range of defense factors, primarily the bactericidal properties of the mucosa itself, the antagonistic properties of resident microorganisms, the levels of secretory IgA, IgM, IgG, C3, and C5 Complement factors, and other cellular defense mechanisms. The biological properties of the pathogen, notably its virulence and the number of pili serving as adhesion factors to the nasopharyngeal mucosa and possibly to meningeal Tissues, are undeniably crucial. The primary pathogenicity factors of the meningococcus are the bacterial capsule, which protects microbes from phagocytosis, and endotoxins (lipopolysaccharides), which cause toxic manifestations. Furthermore, meningococci secrete IgA proteases that cleave IgA molecules, shielding them from antibody-mediated effects. If local Immunity is not compromised by prior viral illnesses, hypothermia, stress, or other adverse factors, the outcome of meningococci reaching the mucous membranes will be their destruction or healthy carriage. Such an outcome of meningococci landing on the upper respiratory mucosa of a healthy child is observed in the majority of cases. However, if local defense mechanisms fail, an inflammatory process with the clinical manifestations of meningococcal nasopharyngitis develops at the site of invasion. Apparently, in some instances, meningococci breach local defense barriers and enter the bloodstream, developing primary bacteremia manifested by isolated roseolopapular or hemorrhagic exanthems, herpetic eruptions on the Lips and nasal alae, peripheral blood Changes in the form of a left shift in the leukocyte formula, elevated ESR, and Isolation of the pathogen from the blood. Nevertheless, primary bacteremia is short-lived; metaphorically speaking, it lacks the «momentum to develop systemic bodily reactions and activate 'secondary pathogenetic mechanisms'». At the same time, the development of clinically overt meningococcal nasopharyngitis is far from mandatory. This is evidenced by the fact that in 70–80% of patients with generalized forms of meningococcal infection, such a primary focus does not exist at all (M. V. Korshunov, 1991). The establishment of this phenomenon provided grounds to believe that The Mechanism of generalization of the pathological process in meningococcal infection lies in the Formation of secondary infection foci located in the capillary endothelium. This precisely explains the massive seeding of the Organism with meningococci during the disease, manifested by abundant hemorrhagic rash, adrenal insufficiency, and, above all, the fulminant development of Clinical symptoms of toxicosis. Bacteremia and endocoxemia are accompanied by elevated blood levels of cytokines, Eicosanoids, other BIOLOGICALLY ACTIVE SUBSTANCES, impaired metabolic products, and organ-system disorders. These conditions facilitate the penetration of meningococci across the blood-Brain barrier (BBB) into the subarachnoid space, leading to inflammation of the pia mater, and less frequently, inflammation of the BRAIN AND SPINAL cord. This is largely facilitated by the Anatomical and physiological Features of the mesodiencephalic region (abundant vascularization, high permeability of diencephalic vessels, and proximity to CEREBROSPINAL FLUID pathways). Occasionally, the penetration of meningococci into the CNS is possible along nerve fiber sheaths and lymphatic pathways passing through the cribriform plate. Infection is also possible in cases of traumatic brain injury and cranial bone defects. A case of recurrent meningococcal meningitis in a child has been described, who was cured only after reconstructive surgery for a cribriform plate defect (V. F. Uchaikin, 1998). We observed a case of triple recurrence of meningococcal meningitis in a child who had an epithelial tract representing a developmental anomaly of the caudal end of the embryo posterior to the sacrum. Following its excision, the meningitis recurred no more.

The purulent inflammatory process may also spread along the basal Meninges to the Medulla Oblongata, Spinal Cord, Cranial Nerves, and Spinal Nerves.

Pathological Anatomy. Morphological changes in purulent meningococcal meningitis are found in the pia mater, brain parenchyma, ventricular ependyma, and subependymal region. In the initial phase of inflammation, the pia mater is primarily affected, and the process is serofurulent, later becoming purulent and purulent-fibrinous.

As the pathological process progresses, In addition to the pia mater, the brain parenchyma is also affected due to the damaging impact of both the meningococci themselves and their toxins on brain tissue. Involvement of the ventricular ependyma, presence of diffuse and focal hemorrhages, proliferation of granulation tissue, obstruction of the foramina of Magendie and Luschka, sclerotic changes in perivascular spaces, dystrophic changes in the arachnoid membrane, and obliteration of the subarachnoid spaces lead to impaired cerebrospinal fluid outflow and the development of internal Hydrocephalus.

The parenchyma and membranes of the spinal cord are systematically involved in the pathological process. Changes therein differ little from those observed in the cerebral meninges. However, the clinical symptomatology of these lesions is mild or absent. In severe cases, a picture of myelitis develops.

Clinical Manifestations. The incubation period for meningococcal infection averages 2 to 7 days.

The clinical picture of purulent meningococcal meningitis consists of 3 syndromes: infectious-toxic, meningeal, and hypertensive. The infectious-toxic syndrome is paramount because a patient can succumb to intoxication even before meningitis develops, and in children under 1 year of age, all other syndromes may be entirely absent or barely noticeable. Meningococcal meningitis most often begins acutely, abruptly, and suddenly (often a mother can specify the exact hour the illness started). Less frequently, meningitis develops secondary to nasopharyngitis or meningococcemia. Body temperature reaches 38°–40 ^oC, accompanied by chills, fever, rapidly worsening throbbing headache, dizziness, and eye pain. Appetite disappears, accompanied by nausea, recurrent projectile vomiting that brings no relief to the patient, and thirst. Marked, sharp hyperesthesia to all types of stimuli (tactile, bright light, loud sounds) is present. Characteristic features include tendon hyperreflexia, tremors, twitching, startle responses, and other signs of convulsive readiness; in some cases, tonic-clonic seizures occur. Seizures in infants During the first year of life are frequently the first and earliest symptoms of meningitis, whereas other symptoms, including nuchal rigidity, have not yet had time to develop. Convulsive twitching at the onset of the disease in older children indicates severity of the course and is considered a formidable symptom. In some patients, seizures may present as a major tonic-clonic generalized seizure. A portion of children exhibit early disturbances of consciousness: adynamia, lethargy, and sometimes complete loss of consciousness. For most older patients, motor agitation, hallucinations, and delirium are characteristic. From the very first hours of the illness (within 10–12 hours), signs of meningeal irritation appear: nuchal rigidity, Brudzinski's and Kernig's signs, and others. By the end of the first day, the characteristic «Setting-dog» posture is observed. General muscular hypotonia is frequently detected. Tendon Reflexes are exaggerated, and anisoreflexia may be present. In severe intoxication, tendon reflexes may be absent, while Skin reflexes (abdominal, cremasteric) are typically diminished. Concurrently, Babinski's pathological reflexes and ankle clonus are quite frequently observed. On days 3–4 of the illness, many children develop herpetic eruptions on the face, and less commonly on other skin areas or the oral mucosa.

In severe forms of meningitis, cranial nerve involvement is possible. Damage to the extraocular motor nerves (cranial nerves III, IV, VI) is manifested by strabismus, ptosis of the upper eyelid, and sometimes anisocoria; involvement of the Facial Nerve (cranial nerve VII) results in facial Asymmetry. Special attention is required for the detection of Hearing impairments, particularly in young children, which can arise from the very first days of the illness; moreover, damage to the Auditory Analyzer can occur at various levels and lead to partial or total deafness. Cranial nerves II, IX, and X are rarely affected. Severe manifestations of meningococcal meningitis include the appearance of signs of cerebral edema and Swelling, manifested by bouts of psychomotor agitation transitioning into a soporous state and subsequently into coma.

Of substantial importance in the clinical diagnosis of meningococcal meningitis is its frequent combination with a hemorrhagic-necrotic rash, which appears on the skin and mucous membranes in 70–90% of children during the first hours of infection generalization. The mechanism of its formation lies in the development of skin capillary thrombovasculitis followed by local necrosis. The rash appears 4–6 hours after the onset of the disease, and the earlier the rash appears, the more severe the clinical course. The typical rash varies in size—from small petechiae to larger ecchymoses—stellar, irregular in shape, with central necrosis, sometimes taking the form of extensive (5–15 cm in diameter) hemorrhages, dense to the Touch, and protruding above the skin surface. Subsequently, necrotic areas slough off, leaving defects that heal into scars upon recovery. In exceptional cases, Gangrene of the nail Phalanges, fingers, toes, or auricles may develop (V. F. Uchaikin, 1998). The hemorrhagic rash is typically localized on the buttocks, thighs, legs, and eyelids, and less frequently on the upper extremities. However, the rash may also be of a different character—roseolopapular, papular, erythematous, or herpetic along the course of the Trigeminal nerve (upper and lower lips, Nose).

In past years, meningococcemia was characterized by joint involvement, observed in nearly 50% of cases, and vascular tunic of the eye involvement, noted in 11% of cases. Currently, joints are rarely affected, and when they are, smaller joints—metacarpal and wrist—suffer more frequently, while larger joints are rarely involved. Children hold their fingers spread apart, cry upon touch, the joints themselves appear swollen, and the skin over them is hyperemic. Nevertheless, the prognosis of Arthritis is favorable, requiring no specific Treatment.

Involvement of the vascular tunic of the eye (the «rusty eye» syndrome) in the form of iridochoroiditis (uveitis) is currently also extremely rare (1.8%) (A. I. Bobrovitskaya et al., 1998).

Main diagnostic criteria for meningococcal meningitis:

1. Epidermal history — winter-spring seasonality, contact with a patient suffering from any form of meningococcal infection or a healthy meningococcal carrier, airborne droplet transmission route, predominantly affecting young children.

2. Acute, sudden onset with rapidly progressing and sharply pronounced general toxic syndrome.

3. Characteristic high fever with chills, throbbing headache, recurrent vomiting, and marked hyperesthesia.

4. Meningeal syndrome distinguished by the full expression of the entire symptom complex, frequently running a course with the development of cerebral edema and swelling and impaired consciousness.

5. In 70–90% of meningitis cases, the regular appearance of a hemorrhagic rash ranging in size from petechiae to larger ecchymoses, sometimes extensive (5–15 cm), irregular, stellar in shape with central necrosis, with preferential localization on the buttocks, lower extremities, trunk, arms, face, and eyelids.

6. Characterized by pronounced inflammatory changes in blood and CSF analyses.

7. Cell/15.html">Microscopy of CSF smears, thick blood drops, and nasopharyngeal mucus reveals Gram-negative diplococci located predominantly intracellularly, suggesting the meningococcal etiology of the disease.

8. Bacteriological examination OF nasopharyngeal mucus, blood, and CSF isolates the meningococcus, confirming the etiological diagnosis.

Laboratory Diagnostics. Complete blood count. Peripheral blood analysis reveals leukocytosis ranging within 15-25∙10⁹/L with neutrophilia, a shift to the left involving band forms, metamyelocytes, and myelocytes, elevated ESR, and aneosinophilia. Literature sources indicate that in relatively mild forms of meningococcal meningitis, the blood count may remain within normal limits. We find this unlikely, suggesting a repeated complete blood count and diagnostic clarification.

Cerebrospinal fluid examination. The CSF is turbid, whitish, and resembles diluted milk in cases of severe pleocytosis; it emerges under increased pressure. Neutrophilic pleocytosis reaches several hundred or thousand Cells per 1 µL, protein levels are elevated, and glucose levels are decreased. When a lumbar puncture is performed on the first day of the disease, the CSF may still be clear, with moderate mixed-type pleocytosis. In late diagnoses (later than 3-5 days from the onset of the disease) or in the hypotensive form of meningitis, the CSF may not flow out, instead remaining stagnant («standing») in the needle. Firstly, this is caused by increased viscosity and the Organization of pus accompanied by the precipitation of fibrin strands; secondly, it is due to the absence of CSF pressure. In such cases, it should be aspirated using a syringe.

Bacterioscopic examination. The Materials examined include nasopharyngeal secretions, CSF, skin scrapings taken from the border between necrotic and healthy areas, blood smears (thick drops), as well as punctates from rash elements in patients with meningococcal meningitis. All biological samples are screened for Gram-negative cocci or diplococci located both extra- and intracellularly. The bacterioscopic detection of diplococci does not serve as etiological confirmation of the diagnosis, but merely indirectly indicates the presence of a meningococcal infection.

Bacteriological examination is performed on CSF, blood, urine, nasopharyngeal mucus, and, in fatal cases, autopsy material. To isolate meningococcal cultures, the samples are inoculated onto solid and semi-solid nutrient media containing serum, blood, or ascetic fluid (20% Agar and chocolate agar; blood is inoculated into 0.1% agar).

Serological tests. Serological Methods are used to determine the presence of specific Antibodies in blood serum via the indirect hemagglutination assay (IHA) and to measure the minimum concentration of meningococcal toxin in the blood and urine of patients using the counter-Immunoelectrophoresis (CIE) test. Blood, urine, and CSF can be utilized for quantitative immunoelectrophoresis assays to detect capsular Antigens of both viable and non-viable meningococci.