Cerebrospinal fluid neopterin in paediatric neurology: a marker of active central nervous system inflammation

Dale, Russell C.; Brilot, Fabienne; Fagan, Elizabeth; Earl, John

doi:10.1111/j.1469-8749.2008.03225.x

Cited by 90 publications

(101 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other biomarkers, including CSF neopterin and oligoclonal bands (OCBs), are less specific, but they are still useful markers of immune activation or inflammation in the CNS. 2 Before the discovery of the NMDAR antibody biomarker, OCBs were used to support the hypothesis that encephalitis lethargica and immunemediated chorea encephalopathy syndrome were autoimmune diseases; these syndromes have subsequently been shown to be NMDAR encephalitis. [3][4][5] OCBs have also been useful in the identification of unusual variants of known autoimmune encephalopathy.…”

Section: Resultsmentioning

confidence: 99%

“…1,2 However, non-specific biomarkers are likely continue to be of clinical utility as they can alert the clinician to atypical variants of autoimmune encephalopathy or to potential autoimmune diseases yet to be fully defined. 6 Additionally, specific autoantibody tests are less widely available than OCBs and may have a longer processing time; given that early diagnosis and treat- ment can improve outcomes, OCBs are likely to continue to play a useful role.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical association of intrathecal and mirrored oligoclonal bands in paediatric neurology

Sinclair

Wienholt

Tantsis

et al. 2012

Develop Med Child Neuro

Self Cite

View full text Add to dashboard Cite

ABBREVIATIONS ADEMAcute disseminated encephalomyelitis CSF Cerebrospinal fluid HSV Herpes simplex virus NMDAR N-methyl-D-aspartate receptor OCB Oligoclonal band VGKC Voltage-gated potassium channel AIM Biomarkers such as autoantibodies, neopterin, and oligoclonal bands (OCBs) are increasingly used for the diagnosis of treatable inflammatory central nervous system (CNS) disorders. We investigated the correlation between the results of OCB testing and clinical diagnoses in a large contemporary cohort of children with a broad range of neurological conditions.METHOD Cerebrospinal fluid (CSF) and serum from 200 children (94 females, 106 males; age range 2mo-15y 10mo, mean age 6y 9mo, SD ±4.9) who underwent CSF investigation for their neurological condition were tested for OCBs using isoelectric focusing. RESULTSThe patients were divided into those with inflammatory (n=58) and non-inflammatory There is increasing interest in biomarkers that diagnose potentially treatable inflammatory central nervous system (CNS) disorders. 1 Some serum and cerebrospinal fluid (CSF) autoantibodies are specific biomarkers associated with autoimmune syndromes such as N-methyl-D-aspartate receptor (NMDAR) encephalitis and voltage-gated potassium channel (VGKC) encephalopathy. Other biomarkers, including CSF neopterin and oligoclonal bands (OCBs), are less specific, but they are still useful markers of immune activation or inflammation in the CNS.2 Before the discovery of the NMDAR antibody biomarker, OCBs were used to support the hypothesis that encephalitis lethargica and immunemediated chorea encephalopathy syndrome were autoimmune diseases; these syndromes have subsequently been shown to be NMDAR encephalitis. [3][4][5] OCBs have also been useful in the identification of unusual variants of known autoimmune encephalopathy. 6OCBs are clones of immunoglobulin (typically IgG) that can be detected in the CSF and ⁄ or serum. The qualitative method of isoelectric focusing on agarose gels followed by immunoblotting is the accepted standard method for OCB detection. The IgG index (the ratio of CSF ⁄ serum IgG to CSF ⁄ serum albumin), a quantitative method of analysis, is a less sensitive test, and when elevated is suggestive of a CNS B-cell response. There are limited reports of use of the IgG index in paediatric studies, but in adult studies the IgG index has been found to be only rarely elevated in patients with multiple sclerosis who have negative OCBs. [7][8][9][10][11]7 in a paediatric cohort, found that the IgG index was less frequently elevated in those with acute disseminated encephalo- When OCBs are present in the CSF and absent from the serum, this is termed an 'intrathecal pattern' and is indicative of local antibody production and hence a humoral immune response within the CNS. When identical clones of IgG are present in the CSF and serum, this is termed a 'mirrored pattern' and suggests that IgG has entered the CNS from the systemic circulation, such as occurs in blood-brain barrier damage.A combination of mirrored and intrathecal...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clinical association of intrathecal and mirrored oligoclonal bands in paediatric neurology

Sinclair

Wienholt

Tantsis

et al. 2012

Develop Med Child Neuro

Self Cite

View full text Add to dashboard Cite

show abstract

“…CSF neopterin, which is produced secondary to a-or g-interferon stimulation, was included as an alternative to CSF pleocytosis because it has been shown to be a useful marker of central nervous system (CNS) inflammation. 9 Encephalopathy was defined as an altered or reduced level of consciousness and a change in personality or behavior or confusion lasting .24 hours. We did not use lethargy and irritability as sole features of encephalopathy because of the nonspecific nature of these features in sick children unless supported by EEG features of encephalopathy.…”

Section: Definitionsmentioning

confidence: 99%

Infectious and Autoantibody-Associated Encephalitis: Clinical Features and Long-term Outcome

et al. 2015

Self Cite

View full text Add to dashboard Cite

BACKGROUND AND OBJECTIVES: Pediatric encephalitis has a wide range of etiologies, clinical presentations, and outcomes. This study seeks to classify and characterize infectious, immunemediated/autoantibody-associated and unknown forms of encephalitis, including relative frequencies, clinical and radiologic phenotypes, and long-term outcome.METHODS: By using consensus definitions and a retrospective single-center cohort of 164 Australian children, we performed clinical and radiologic phenotyping blinded to etiology and outcomes, and we tested archived acute sera for autoantibodies to N-methyl-D-aspartate receptor, voltage-gated potassium channel complex, and other neuronal antigens. Through telephone interviews, we defined outcomes by using the Liverpool Outcome Score (for encephalitis).RESULTS: An infectious encephalitis occurred in 30%, infection-associated encephalopathy in 8%, immune-mediated/autoantibody-associated encephalitis in 34%, and unknown encephalitis in 28%. In descending order of frequency, the larger subgroups were acute disseminated encephalomyelitis (21%), enterovirus (12%), Mycoplasma pneumoniae (7%), N-methyl-D-aspartate receptor antibody (6%), herpes simplex virus (5%), and voltage-gated potassium channel complex antibody (4%). Movement disorders, psychiatric symptoms, agitation, speech dysfunction, cerebrospinal fluid oligoclonal bands, MRI limbic encephalitis, and clinical relapse were more common in patients with autoantibodies. An abnormal outcome occurred in 49% of patients after a median follow-up of 5.8 years. Herpes simplex virus and unknown forms had the worst outcomes. According to our multivariate analysis, an abnormal outcome was more common in patients with status epilepticus, magnetic resonance diffusion restriction, and ICU admission. CONCLUSIONS:We have defined clinical and radiologic phenotypes of infectious and immunemediated/autoantibody-associated encephalitis. In this resource-rich cohort, immune-mediated/ autoantibody-associated etiologies are common, and the recognition and treatment of these entities should be a clinical priority. WHAT'S KNOWN ON THIS SUBJECT:Encephalitis is a serious and disabling condition. There are infectious and immune-mediated causes of encephalitis, but many cases remain undiagnosed. WHAT THIS STUDY ADDS:This large single-center study on childhood encephalitis provides insight into the relative frequency and clinicoradiologic phenotypes of infectious, autoantibody-associated, and unknown encephalitis. Risk factors for an abnormal outcome are also defined. 4 and a prospective study of adults (n = 134) and children (n = 69) with encephalitis found that infectious encephalitis and immunemediated forms were identified in 42% and 21% of the cohort, respectively. 5 However, most of the previous larger studies of encephalitis in children were undertaken before the advent of neuronal autoantibody testing. [6][7][8] We studied clinical and radiologic features, serum autoantibodies in acute archived samples, and longterm outcomes in a large ret...

show abstract

“…2). Where avaiable, other biomarkers of CNS inflammation including CSF oligoclonal bands 37 and CSF neopterin 38 should or if unavailable CT with contrast EEG †Collect up to 10 mL, if able, in four tubes in adults and children, and up to 5 mL in a small child (<2 years old). ‡Formal cytological examination is required to reliably differentiate eosinophils from other leukocytes and identify malignant cells.…”

Section: First-line Investigation Of All Patients With Suspected/probmentioning

confidence: 99%

Consensus guidelines for the investigation and management of encephalitis in adults and children in Australia and New Zealand

Britton

Eastwood

Paterson

et al. 2015

Internal Medicine Journal

View full text Add to dashboard Cite

Encephalitis is a complex neurological syndrome caused by inflammation of the brain parenchyma. The management of encephalitis is challenging because: the differential diagnosis of encephalopathy is broad; there is often rapid disease progression; it often requires intensive supportive management; and there are many aetiologic agents for which there is no definitive treatment. Patients with possible meningoencephalitis are often encountered in the emergency care environment where clinicians must consider differential diagnoses, perform appropriate investigations and initiate empiric antimicrobials. For patients who require admission to hospital and in whom encephalitis is likely, a staged approach to investigation and management is preferred with the potential involvement of multiple medical specialties. Key considerations in the investigation and management of patients with encephalitis addressed in this guideline include: Which first-line investigations should be performed?; Which aetiologies should be considered possible based on clinical features, risk factors and radiological features?; What tests should be arranged in order to diagnose the common causes of encephalitis?; When to consider empiric antimicrobials and immune modulatory therapies?; and What is the role of brain biopsy?

show abstract

Cerebrospinal fluid neopterin in paediatric neurology: a marker of active central nervous system inflammation

Cited by 90 publications

References 30 publications

Clinical association of intrathecal and mirrored oligoclonal bands in paediatric neurology

Clinical association of intrathecal and mirrored oligoclonal bands in paediatric neurology

Infectious and Autoantibody-Associated Encephalitis: Clinical Features and Long-term Outcome

Consensus guidelines for the investigation and management of encephalitis in adults and children in Australia and New Zealand

Contact Info

Product

Resources

About