Enteroviral meningitis in children: from mechanisms of neuroinvasion to modern methods for outcome prediction

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Abstract

Enteroviral meningitis accounts for 85%–90% of serous meningitis cases in children. In 40%–70% of cases, it is accompanied by delayed neurological sequale, necessitating the development of methods for early outcome prediction.

This review aimed to formally analyze current data on the mechanisms of neuroinvasion and neuroinflammation in enteroviral infections that underlie enterovirus neurovirulence. The article comprehensively evaluates existing and promising approaches to predicting adverse neurological outcomes of enteroviral meningitis in children, focusing on the search for biomarkers and the development of risk stratification algorithms.

We reviewed current scientific publications on the pathogenesis of enteroviral infections, which address their neurotropism, neuroinvasion routes, and intrathecal inflammation. We systematized data on prognostic methods, including instrumental and laboratory studies of cerebrospinal fluid and blood serum, as well as complex mathematical models. Particular attention was paid to assessing the potential of the chemiluminescence for evaluating neutrophil function and metabolic activity.

The analysis revealed complex, complementary mechanisms of enterovirus neuroinvasion that underlie neuroinflammation and determine the risk of long-term sequelae. Current prognostic approaches were found to be highly heterogeneous; however, the most accurate risk stratification was provided by comprehensive models that integrate clinical, anamnestic, instrumental, and laboratory data. Chemiluminescence was identified as a promising approach for evaluating the neutrophil function, especially in cerebrospinal fluid, given their key role in the Trojan horse mechanism of neuroinvasion and in the modulation of neuroinflammation in enteroviral meningitis. Respiratory burst parameters (activation rate, peak intensity, total volume of reactive oxygen species, and activation index) may potentially serve as early biomarkers of the intrathecal inflammation severity, phagocytic reserve depletion, and complication risk.

The development and validation of algorithms for predicting adverse outcomes of enteroviral meningitis in children remains a priority. Such algorithms should comprize a combination of the most informative parameters, including promising indicators of the neutrophil function and metabolic activity in cerebrospinal fluid assessed by chemiluminescence. Implementation of such algorithms will optimize clinical monitoring and rehabilitation strategies to minimize the severity of neurological deficits.

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About the authors

Danil V. Zlobin

Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University

Author for correspondence.
Email: d_zy@mail.ru
ORCID iD: 0009-0004-8873-6764
SPIN-code: 1581-9213
ResearcherId: MFJ-6252-2025
Russian Federation, Krasnoyarsk

Galina P. Martynova

Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University

Email: doc-martynova@yandex.ru
ORCID iD: 0000-0002-2014-0698
SPIN-code: 7683-4597

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Krasnoyarsk

Andrei A. Savchenko

Krasnoyarsk Science Centre of the Siberian Branch of Russian Academy of Science

Email: aasavchenko@yandex.ru
ORCID iD: 0000-0001-5829-672X
SPIN-code: 3132-8260

MD, Dr. Sci. (Medicine), Professor, Research Institute of Medical Problems of the North

Russian Federation, Krasnoyarsk

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