Highlights
- •Chitinase 3-like 1 and neurofilament light chain are increased in pediatric acquired demyelinating syndromes (ADS).
- •Chitinase 3-like 1 and neurofilament light chain better distinguish between ADS and non-ADS than oligoclonal bands alone.
- •Chitinase 3-like 1 is increased in ADEM compared with MS.
Abstract
Background
Chitinase 3-like 1 (CHI3L1), neurofilament light chain (NFL) and oligoclonal bands
(OCB) in cerebrospinal fluid are associated with central nervous system demyelination
in adults. CHI3L1 and OCB are markers of central nervous system inflammation, whereas
NFL is a marker of white-matter axonal injury. The aim was to examine whether CHI3L1
and NFL in cerebrospinal fluid are associated with acquired demyelinating syndromes
at disease onset in a pediatric population.
Methods
Children (<18 years) referred to hospital for possible neuroinflammatory disease were
retrospectively included from 2010 to 2016. Case ascertainment was by review of medical
records. NFL and CHI3L1 were measured by enzyme-linked immunosorbent assays. Endpoints
were differences in concentrations of cerebrospinal fluid NFL and CHI3L1.
Results
We included 193 children who all underwent cerebrospinal fluid OCB examination as
part of their diagnostic work-up and classified these children into 5 groups: acquired
demyelinating syndromes (n = 33), normal diagnostic work-up (n = 36), inflammatory
neurological disease (n = 50), other neurological disease (n = 55), and systemic inflammatory
diseases (n = 19). NFL and CHI3L1 in cerebrospinal fluid differed significantly between
the five groups (p = 0.0001). CHI3L1 was significantly higher in acquired demyelinating syndromes than
in all other groups, and NFL was significantly higher in acquired demyelinating syndromes
than in the other groups except systemic inflammatory disease. Children with acute
disseminated encephalomyelitis had significantly higher concentrations of CHI3L1 than
did children with multiple sclerosis.
Conclusion
We provide class II evidence that CHI3L1 and NFL are associated with pediatric acquired
demyelinating syndromes. CHI3L1 may help distinguishing between acute disseminated
encephalomyelitis and multiple sclerosis, but this needs further confirmation.
Keywords
ABBREVIATIONS:
ADEM (Acute disseminated encephalomyelitis), ADS (Acquired demyelinating syndromes), AUC (Area under the curve), CHI3L1 (Chitinase 3-like 1), CIS (Clinically isolated syndrome), CNS (Central nervous system), CSF (Cerebrospinal fluid), ELISA (Enzyme-linked immunosorbent assay), IPMSSG (International Pediatric MS Study Group), MOG (Myelin oligodendrocyte glycoprotein), MRI (Magnetic resonance imagining), MS (Multiple sclerosis), NFL (Neurofilament light chain), NMOSD (Neuromyelitis optica spectrum disorder), OCB (oligoclonal bands), ON (Optic neuritis), SIMOA (Single molecule array), ROC (Receiver operating characteristic), TM (Transverse myelitis)To read this article in full you will need to make a payment
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References
- Multiple sclerosis and acute disseminated encephalomyelitis diagnosed in children after long-term follow-up: comparison of presenting features.Dev. Med. Child. Neurol. Jun. 2009; 51: 480-486
- Neurofilament light chain level is a weak risk factor for the development of MS.Neurology Sep 13. 2016; 87: 1076-1084
- Clinical and diagnostic aspects of multiple sclerosis and acute monophasic encephalomyelitis in pediatric patients: a single centre prospective study.Mult. Scler. Houndmills Basingstoke Engl. Mar. 2009; 15: 363-370
- Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study.Lancet Neurol. May. 2011; 10: 436-445
- Pediatric-onset multiple sclerosis and other acquired demyelinating syndromes of the central nervous system in Denmark during 1977-2015: A nationwide population-based incidence study.Mult. Scler. J. 2018; 24: 1077-1086
- Implications of the International Paediatric Multiple Sclerosis Study Group consensus criteria for paediatric acute disseminated encephalomyelitis: a nationwide validation study.Dev. Med. Child Neurol. 2018; https://doi.org/10.1111/dmcn.13798
- In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases.J. Neuroinflammation Jun 11. 2010; 7: 34
- Role of MRI in the differentiation of ADEM from MS in children.Neurology Mar 17. 2009; 72: 968-973
- Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes.Brain J. Neurol. Apr. 2015; 138: 918-931
- Younger children with MS have a distinct CSF inflammatory profile at disease onset.Neurology Feb 2. 2010; 74: 399-405
- Cerebrospinal fluid chitinase 3-like 1 levels are associated with conversion to multiple sclerosis.Brain J. Neurol. Apr. 2010; 133: 1082-1093
- Early relapse risk after a first CNS inflammatory demyelination episode: examining international consensus definitions.Dev. Med. Child Neurol. Dec. 2007; 49: 887-893
- Guidelines on routine cerebrospinal fluid analysis. Report from an EFNS task force.Eur. J. Neurol. Sep. 2006; 13: 913-922
- Evaluation of CHI3L-1 and CHIT-1 expression in differentiated and polarized macrophages.Inflammation Apr. 2013; 36: 482-492
- Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis.Arch. Neurol. Jan. 2009; 66: 54-59
- Oligoclonal bands predict multiple sclerosis in children with optic neuritis.Ann. Neurol. Jun. 2015; 77: 1076-1082
- Chitinase 3-like proteins as diagnostic and prognostic biomarkers of multiple sclerosis.Mult. Scler. Houndmills Basingstoke Engl. Sep. 2015; 21: 1251-1261
- Clinical presentation of pediatric multiple sclerosis before puberty.Eur. J. Neurol. Mar. 2014; 21: 441-446
- Intense inflammation and nerve damage in early multiple sclerosis subsides at older age: a reflection by cerebrospinal fluid biomarkers.PloS One. 2013; 8: e63172
- International pediatric multiple sclerosis study group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions.Mult. Scler. 2013; 19 Sep: 1261-1267
- Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa.Clin. Chem. Lab Med. Oct 1. 2016; 54: 1655-1661
- Role of chitin and chitinase/chitinase-like proteins in inflammation, tissue remodeling, and injury.Annu. Rev. Physiol. 2011; 73: 479-501
- Neuropediatric KIDSEP study group of the french neuropediatric society. acute disseminated encephalomyelitis cohort study: prognostic factors for relapse.Eur. J. Paediatr. Neurol. EJPN Off. J. Eur. Paediatr. Neurol. Soc. Mar. 2007; 11: 90-95
- Cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain predict multiple sclerosis development and disability after optic neuritis.Mult. Scler. Houndmills Basingstoke Engl. 2015; (Feb 19)
- Prognostic factors after a first attack of inflammatory CNS demyelination in children.Neurology. 2008; 71 Sep 23: 967-973
- YKL-40 is elevated in cerebrospinal fluid from patients with purulent meningitis.Clin. Diagn. Lab Immunol. May. 2002; 9: 598-604
- Neurochemical markers of brain damage in cerebrospinal fluid during induction treatment of acute lymphoblastic leukemia in children.Pediatr. Blood Cancer Apr. 2008; 50: 793-798
- CSF characteristics in early-onset multiple sclerosis.Neurology Nov 23. 2004; 63: 1966-1967
- Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria.Ann. Neurol. Feb 1. 2011; 69: 292-302
- CSF neurofilament light chain is elevated in OMS (decreasing with immunotherapy) and other pediatric neuroinflammatory disorders.J. Neuroimmunol. Jan 15. 2014; 266: 75-81
- Natural history of multiple sclerosis with childhood onset.N. Engl. J. Med. 2007; 356: 2603-2613
- 2010 McDonald criteria for diagnosing pediatric multiple sclerosis.Ann. Neurol. 2012; 72 (Aug): 211-223
- Cerebrospinal fluid brain injury biomarkers in children: a multicenter study.Pediatr. Neurol. Jule2. 2013; 49: 31-39
- Acute disseminated encephalomyelitis in children: focus on relapsing patients.Pediatr. Neurol. Jul. 2008; 39: 12-17
- Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients.Neurology Oct 22. 2002; 59: 1224-1231
- Magnetic resonance imaging characteristics of children and adults with paediatric-onset multiple sclerosis.Brain J. Neurol. Dec. 2009; 132: 3392-3400
Article info
Publication history
Published online: June 11, 2018
Accepted:
May 27,
2018
Received in revised form:
May 22,
2018
Received:
January 5,
2018
Identification
Copyright
© 2018 Elsevier B.V. All rights reserved.
