Dídac Casas-Alba1, Ana Valero-Rello2, Jordi Muchart3, Thaís Armangué4, Iolanda Jordan5, María Cabrerizo6, Marta Molero-Luís7, Rafael Artuch8, Claudia Fortuny9, Carmen Muñoz-Almagro10, Cristian Launes11. 1. Department of Pediatrics, Hospital Sant Joan de Deu (University of Barcelona), Barcelona, Spain; Pediatric Infectious Diseases Research Group, Institut de Recerca Sant Joan de Deu, Barcelona, Spain. 2. Pediatric Infectious Diseases Research Group, Institut de Recerca Sant Joan de Deu, Barcelona, Spain; Department of Molecular Microbiology, Hospital Sant Joan de Deu (University of Barcelona), Barcelona, Spain. 3. Department of Diagnostic Imaging, Hospital Sant Joan de Deu (University of Barcelona), Barcelona, Spain. 4. Pediatric Neuroimmunology Unit, Department of Pediatric Neurology, Hospital Sant Joan de Deu (University of Barcelona), Barcelona, Spain; Neuroimmunology Program, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS)-Hospital Clinic (University of Barcelona), Barcelona, Spain; CIBER en Enfermedades Raras (CIBERER), Madrid, Spain. 5. Pediatric Infectious Diseases Research Group, Institut de Recerca Sant Joan de Deu, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Pediatric Intensive Care Unit, Hospital Sant Joan de Deu (University of Barcelona), Barcelona, Spain. 6. Enterovirus Unit, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain. 7. CIBER en Enfermedades Raras (CIBERER), Madrid, Spain; Department of Clinical Biochemistry, Institut de Recerca Sant Joan de Deu, Barcelona, Spain. 8. Department of Clinical Biochemistry, Institut de Recerca Sant Joan de Deu, Barcelona, Spain. 9. Department of Pediatrics, Hospital Sant Joan de Deu (University of Barcelona), Barcelona, Spain; Pediatric Infectious Diseases Research Group, Institut de Recerca Sant Joan de Deu, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. 10. Pediatric Infectious Diseases Research Group, Institut de Recerca Sant Joan de Deu, Barcelona, Spain; Department of Molecular Microbiology, Hospital Sant Joan de Deu (University of Barcelona), Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; School of Medicine, Universitat Internacional de Catalunya, Barcelona, Spain. 11. Department of Pediatrics, Hospital Sant Joan de Deu (University of Barcelona), Barcelona, Spain; Pediatric Infectious Diseases Research Group, Institut de Recerca Sant Joan de Deu, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Electronic address: claunes@sjdhospitalbarcelona.org.
Abstract
BACKGROUND: Enterovirus-A71 causes outbreaks of brainstem encephalitis, ranging from self-limited disease to acute flaccid paralysis. The aim of this study was to assess the role of cerebrospinal fluid (CSF) neopterin as a biomarker of disease severity in children with enterovirus-related brainstem encephalitis. METHODS: A descriptive, prospective cohort study was conducted from April 2016 to March 2017 in a tertiary hospital. Pediatric patients with a diagnosis of brainstem encephalitis with or without myelitis due to enterovirus infection were enrolled. The final study group comprised a convenience sample including all patients with sufficient CSF volume for neopterin determination. The major variables considered in estimating the severity were the diagnosis of encephalomyelitis, the presence of lesions and extensive lesions on brain and spinal magnetic resonance imaging (MRI), hospital stay length greater than seven days, and sequelae at day 30. RESULTS: Of 60 patients, CSF neopterin could be measured in 36. Median age was 26 months (interquartile range: 19 to 32). Thirty-three were diagnosed with brainstem encephalitis and three with encephalomyelitis. Enterovirus-A71 was the only identified genotype (25 of 25). CSF neopterin levels were elevated (>61 nmol/L) in 33 of 36 (92%), with a median of 347 nmol/L (interquartile range: 204 to 525). CSF neopterin was useful to distinguish patients with lesions on MRI (area under the receiver operating characteristic curve = 0.76; P = 0.02) and extensive lesions (area under the receiver operating characteristic curve = 0.76; P = 0.04). CONCLUSIONS: This study suggests an association between CSF neopterin levels and the presence of inflammatory lesions on MRI.
BACKGROUND:Enterovirus-A71 causes outbreaks of brainstem encephalitis, ranging from self-limited disease to acute flaccid paralysis. The aim of this study was to assess the role of cerebrospinal fluid (CSF) neopterin as a biomarker of disease severity in children with enterovirus-related brainstem encephalitis. METHODS: A descriptive, prospective cohort study was conducted from April 2016 to March 2017 in a tertiary hospital. Pediatric patients with a diagnosis of brainstem encephalitis with or without myelitis due to enterovirus infection were enrolled. The final study group comprised a convenience sample including all patients with sufficient CSF volume for neopterin determination. The major variables considered in estimating the severity were the diagnosis of encephalomyelitis, the presence of lesions and extensive lesions on brain and spinal magnetic resonance imaging (MRI), hospital stay length greater than seven days, and sequelae at day 30. RESULTS: Of 60 patients, CSF neopterin could be measured in 36. Median age was 26 months (interquartile range: 19 to 32). Thirty-three were diagnosed with brainstem encephalitis and three with encephalomyelitis. Enterovirus-A71 was the only identified genotype (25 of 25). CSF neopterin levels were elevated (>61 nmol/L) in 33 of 36 (92%), with a median of 347 nmol/L (interquartile range: 204 to 525). CSF neopterin was useful to distinguish patients with lesions on MRI (area under the receiver operating characteristic curve = 0.76; P = 0.02) and extensive lesions (area under the receiver operating characteristic curve = 0.76; P = 0.04). CONCLUSIONS: This study suggests an association between CSF neopterin levels and the presence of inflammatory lesions on MRI.
Authors: Marta Molero-Luis; Didac Casas-Alba; Gabriela Orellana; Aida Ormazabal; Cristina Sierra; Clara Oliva; Anna Valls; Jesus Velasco; Cristian Launes; Daniel Cuadras; Belén Pérez-Dueñas; Iolanda Jordan; Francisco J Cambra; Juan D Ortigoza-Escobar; Carmen Muñoz-Almagro; Angels Garcia-Cazorla; Thais Armangué; Rafael Artuch Journal: Sci Rep Date: 2020-10-26 Impact factor: 4.379