Meningitis in Children - I.V. Bohadelnikov 2005

Primary Purulent Meningitis in Children. General Overview
Features of CNS involvement in other forms of meningococcal infection

When meningococcus penetrates the Central Nervous system, it affects not only the Meninges but various other Brain structures to a greater or lesser extent. Therefore, regardless of the localization of the pathological process, the clinical picture and various symptom complexes often present uniformly. At the same time, each specific localization of the pathological process may exhibit distinct clinical and physiological features, including The Emergence of specific focal symptoms. Notable features of Meningococcal meningitis include its combination with meningococcemia, The Development of serous meningitis, Purulent meningitis with CEREBROSPINAL FLUID hypotension, Waterhouse-Friderichsen syndrome, as well as complications such as infectious-toxic Shock, meningoencephalitis, and ependymitis.

Meningococcal meningitis combined with meningococcemia

The combination of meningococcal meningitis and meningococcemia is the most common form of the disease. This is due to the underlying generalized spread of the pathogen throughout the body, affecting multiple Organs and systems. This is supported by the fact that the rash appears several hours or even a full day before the onset of meningeal symptoms. Researchers studying mixed forms of meningococcal infection hold divergent views regarding the severity and clinical course compared to isolated forms. For instance, M.F. Korshunov (1991) observed a more severe course, whereas V.F. Uchaikin (1998) reported a milder one. M.A. Dadiomova et al. (1985) consider the absence of meningitis in patients with meningococcemia to be a prognostically unfavorable sign. Nonetheless, most researchers note that the clinical picture of mixed forms can be dominated by either meningitis or meningococcemia symptoms, both determining the overall severity of the condition. Consequently, attempts by some researchers to distinguish two separate disease variants have been unsuccessful, as such a division remains largely conditional. The disease typically runs a moderate to severe course and is characterized by typical manifestations such as infectious-toxic, meningeal, and hypertensive syndromes, accompanied by a characteristic hemorrhagic-necrotic rash. At the same time, the mixed form is more straightforward for a physician to diagnose, as the classic manifestations of meningococcal infection—such as a stellate hemorrhagic rash with central necrosis—simultaneously indicate the Etiology of purulent meningitis. This allows the clinician, without waiting for bacteriological test results, to promptly and confidently prescribe early administration of penicillin, cefotaxime, chloramphenicol, ceftriaxone, and Other Antibiotics. Evidently, this proactive and hesitation-free therapy explains the faster and more complete cerebrospinal fluid clearance observed in mixed forms of meningococcal infection compared to isolated meningitis and meningoencephalitis (V.F. Uchaikin, 1998).

Meningococcal serous meningitis

In clinical practice, physicians occasionally encounter cases where the clinical and laboratory signs of meningococcal meningitis—specifically, pronounced infectious-toxic and meningeal syndromes, a characteristic stellate hemorrhagic rash with central necrosis, and significant peripheral Blood changes (neutrophilic leukocytosis, a left shift in the leukocyte formula, elevated ESR, and an eosinophilia)—are combined with cerebrospinal fluid changes typical of serous meningitis. This includes a marked increase in pressure, mixed or lymphocyte-predominant pleocytosis, elevated protein levels, and reduced glucose. In such instances, despite the obvious bacterial purulent etiology, the cerebrospinal fluid findings (lymphocyte-predominant pleocytosis) compel the physician to diagnose serous meningitis while treating it as a purulent infection. It is important to emphasize a crucial detail: the overwhelming majority of such patients are hospitalized within the first 24 hours and receive appropriate antibacterial therapy, which is believed to prevent the full development of purulent inflammation (V.I. Pokrovsky et al., 1987).

It must be noted that to this day, it remains unclear why, under identical circumstances (the same causative agent), serous inflammation develops in some cases and purulent inflammation in others. Several considerations can be made in this regard. As is well known, inflammation develops in three stages: (1) alteration (Primary and secondary); (2) exudation; and (3) proliferation and repair. Primary alteration involves structural and metabolic damage induced by the etiologic factor, whereas secondary alteration refers to cellular and tissue damage driven by secondary pathogenetic mechanisms (released lysosomal Enzymes, excessive activation of Proteolytic Enzymes, BIOLOGICALLY ACTIVE SUBSTANCES, etc.). The exudation stage represents the escape of fluid, electrolytes, Proteins, and Blood Cells from vessels into Tissues. The primary cause of exudation is increased permeability of the capillary and venule walls. Exudate in primary alteration contains high protein levels, whereas in secondary alteration, cells actively migrate into the inflammatory focus. According to modern inflammation theory, neutrophilic granulocytes migrate first, followed by monocytes, and finally lymphocytes (N.N. Zaiko and Yu.V. Bits, 1996). The Biological Significance of this sequence is the accumulation of cells essential for inflammatory processes, primarily phagocytosis. As the inflammatory process subsides, neutrophilic granulocytes disappear first, while lymphocytes persist the longest. Additional factors (immunological, allergic, chronic) can alter this standard progression, causing cellular disruption patterns to deviate from the classic model. It is therefore plausible to suggest that serous inflammation represents the typical, classic physiological response of the body to an infectious insult. Consequently, it is likely that all Clinical forms of meningococcal meningitis pass through a stage of serous inflammation and lymphocytic pleocytosis. These are only diagnosed when patients are admitted to the hospital within the first hours of illness and undergo a lumbar puncture during this timeframe. Other patients admitted on the second day or later already present with a fully developed picture of purulent inflammation. During convalescence, a predominance of lymphocytes in the cerebrospinal fluid aligns well with MODERN CONCEPTS OF post-purulent inflammation recovery and indicates a favorable disease course.

The Clinical Features of serous meningococcal meningitis include a prodromal phase of acute nasopharyngitis, a rapid resolution of meningeal symptoms within 5–10 days, and cerebrospinal fluid normalization by days 7–10 of illness. However, in some patients, despite intensive antibiotic therapy, serous meningitis may transform into purulent meningitis, accompanied by a worsening clinical picture, altered peripheral blood parameters, and cerebrospinal fluid indicators characteristic of purulent inflammation.

Waterhouse-Friderichsen syndrome

The development of adrenal insufficiency, to a greater or lesser extent, is characteristic of any acute infectious process. However, specific and profound adrenal damage leading to a fatal outcome is uniquely typical of meningococcal infection. At the same time, Waterhouse-Friderichsen syndrome occurs extremely rarely in the context of meningococcal meningitis. Nevertheless, given its potential occurrence, severe clinical course, and the significant diagnostic and therapeutic challenges it presents, we consider it essential to discuss.

The development of this clinical variant of meningococcal infection is undeniably driven by bacteremia and severe endotoxemia, alongside a compromised predisposing Background: various perinatal pathology factors such as fetal asphyxia, premature and complicated labor, allergic diathesis, and immunodeficiency states. Various hypotheses have been proposed to explain the Pathogenesis of this syndrome, including the leading role of endotoxic shock with subsequent microcirculatory bed damage, capillarotoxicosis, diffuse vascular injury, non-specific sensitization primarily by Mycoplasma and viral infections, autosensitization, stress, and excessive activation of the Hypothalamus-pituitary-adrenal axis (S.L. Kipnis, 1968; P.S. Gurevich, 1983; V.F. Uchaikin, 1998). However, none of these theories fully explain why this syndrome develops in a specific patient and not in other children who also exhibit allergic manifestations or frequently suffer from bacterial infections. Moreover, it has been observed that Waterhouse-Friderichsen syndrome frequently occurs in children who are otherwise healthy, rarely ill, and develop normally.

In our view, the mechanisms underlying this pathological state are best understood through the framework of the Sanarelli-Shwartzman phenomenon. We believe the primary driver of this syndrome is prior specific (rather than non-specific, as most researchers suggest) sensitization of the child's Organism. Specific sensitization occurs during the phase of primary meningococcal dissemination (according to M.F. Korshunov, 1991), when the Bacteria accumulate on the mucous membrane of the Upper Respiratory Tract, causing inflammation and rapidly overcoming local biological and humoral defense factors to breach the bloodstream. Within the bloodstream, a portion of the meningococci is destroyed, causing intoxication symptoms, while another portion undergoes phagocytosis by capillary endothelium and accumulates there. During this phase, specific sensitization of the organism is induced by meningococcal lipopolysaccharides, which can subsequently trigger the Sanarelli-Shwartzman phenomenon at concentrations 5–10 times lower than those required for lipopolysaccharides from enteric Gram-negative bacteria. A secondary influx of meningococci into the bloodstream during secondary dissemination is accompanied by massive bacterial destruction and the release of lipopolysaccharides acting as a triggering factor. Here, the microcirculatory system serves as the site for the Antigen-Antibody Reaction, realizing The Mechanism of blood Cell aggregation or agglutination characteristic of the Sanarelli-Shwartzman phenomenon (A.M. Chernukh et al., 1975). The plausibility of this mechanism is further supported by the fact that the cutaneous rash in meningococcal infection is indistinguishable from that observed in the Sanarelli-Shwartzman phenomenon induced by Gram-negative bacterial endotoxins.

Of particular interest, in our opinion, is the interpretation of a well-known clinical phenomenon in meningococcemia, which is most pronounced in Waterhouse-Friderichsen syndrome: the hemorrhagic rash first appears on the lower half of the trunk, predominantly on the buttocks and lower extremities. Furthermore, when a child is lying down, the entire lower surface of the body in contact with the surface assumes a purplish-blue discoloration alongside the hemorrhagic rash. In cases with a particularly fulminant course, a distinct demarcation line can sometimes be observed running along the midline of the trunk, separating normal pale Skin from purplish-blue areas. The Essence of this phenomenon is as follows. Under physiological conditions or during arterial hyperemia, blood cells are located primarily in the center of vessels (the so-called "axial stream"), whereas plasma and a small number of leukocytes occupy the space near the vessel walls ("plasma stream"). Under METABOLISM/18.html">The Influence of toxins, microvessels undergo a gravitational redistribution of formed elements and resulting cell aggregates (random cell clusters). The innermost layer adjacent to the endothelium consists of stationary erythrocyte aggregates, the middle layer comprises predominantly leukocytes, and the uppermost layer consists of plasma. Under these conditions, concentrated blood composed primarily of erythrocyte aggregates enters vessels branching downward at an angle from the main horizontal vessel, leading to the occlusion of terminal arterioles and capillaries (A.M. Chernukh et al., 1975). This creates conditions conducive to The formation of

a hemorrhagic rash with necrosis in locations typical of meningococcal infection.

The onset of this clinical form is typical of meningococcal infection: sudden, with a precisely noted time of disease manifestation. Body Temperature rises to 38.5°–39.5°C, accompanied by signs of intoxication such as headache, nausea, lethargy, and skin hyperesthesia. The severity of these symptoms generally does not cause acute alarm among parents, local pediatricians, or emergency medical teams delivering the child to the hospital. The most critical and striking sign for medical personnel is the appearance of a stellate hemorrhagic rash, initially on the lower extremities and buttocks, and subsequently on the trunk. Occasionally, incipient foci of necrosis were observed within some rash elements (evidently due to the short time elapsed between disease onset and hospital admission, typically a matter of hours). We also note that despite clearly pronounced Intoxication syndrome, central nervous system function remained relatively unaffected: consciousness was intact, and children remained calm yet slightly sluggish, tense, and focused, occasionally asking, "Am I going to die?" They responded clearly and promptly for their condition, oriented themselves well in their surroundings, and stepped out of the ambulance themselves upon arrival at the hospital. When asked, "What is your name?" a child would promptly answer, "Vova"; "How old are you?"—"Six," and so forth. Meningeal signs were either moderately expressed or absent. However, within literally 1–2 hours, the clinical picture progressed rapidly. Alongside the appearance of a new hemorrhagic rash covering the entire body surface, characteristic purplish-blue patches developed, featuring necrotic centers, with certain skin changes resembling "cadaveric lividity." The entire skin acquired a bluish tint and felt cold to the Touch. The coalescence of patches in the lower trunk and the emergence of new ones in the upper trunk, especially in the neck region, as well as the appearance of a hemorrhagic rash on the oral mucosa and conjunctiva, indicated a grave prognosis. Conversely, when the hemorrhagic rash and patches were localized predominantly in the lower half of the trunk (buttocks, thighs, lower legs, feet), the prognosis was more favorable (M.F. Korshunov, 1991). Cardiovascular alterations manifested as a precipitous drop in blood pressure, marked tachycardia, and a thready pulse. Respiration became rapid and occasionally intermittent, while diuresis decreased or ceased entirely. Even more dramatic changes occurred within the central nervous system. To the same questions—"What is your name? How old are you?"—the child would respond: "Vv-o-vv-a, s-s-i-x." Children exhibited somnolence, executing simple commands slowly and fatiguing quickly, with verbal contact limited to single-word Answers. An hour later, responses to the same questions deteriorated to "Vv-v-a," "Ss." Such impairment of consciousness corresponded to a state of sopor (pre-coma), where the child emerged from stupor only following intensive shaking and loudly voiced questions, yet remained unable to answer them. Shortly thereafter, stage I coma set in, characterized by a complete absence of verbal contact and absent consciousness, though pupillary light Reflexes, deep extremity reflexes, and swallowing were preserved. Subsequently, stage II (deep) coma developed, marked by a complete absence of reflexes and dilated pupils unresponsive to light.

Central nervous system alterations were accompanied by further deterioration across various Organ Systems. Total cutaneous cyanosis, cold clammy sweat, and a further decline in systolic and diastolic blood pressure—frequently dropping to zero—were observed, along with a body temperature falling to 36.6 °C and below. Respiratory findings included dyspnea, a tympanic Percussion note with a box-like Resonance, and scattered moist rales of varying calibers bilaterally. Heart sounds were muffled, accompanied by significant tachycardia. Diuresis was absent. Lumbar puncture revealed clear fluid flowing under elevated pressure; neutrophilic pleocytosis was moderate or absent, and protein levels were elevated. Cerebrospinal fluid changes largely depended on the timing of the puncture. If only hours had elapsed since disease onset, the fluid composition matched the description above; if a day or longer had passed, changes corresponded to those seen in purulent meningitis. It is particularly important to emphasize that this clinical form of meningococcal infection is characterized by an extremely high mortality rate (80–100%).