Clinical association of intrathecal and mirrored oligoclonal bands in paediatric neurology

Abstract

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...

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

“…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.…”

Acute encephalitis in children: Progress and priorities from an Australasian perspective

“…CSF pleocytosis akin to that in viral meningitis is common though can be absent. Other markers such as CSF neopterin or oligoclonal bands can demonstrate inflammation with additional sensitivity . MRI is the imaging modality of choice and, if possible, should be performed on all children with suspected encephalitis .…”

Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases

“…Common features of MS in both children and adults are the intrathecal humoral immune responses characterized by the presence of CSFrestricted IgG oligoclonal bands (OCBs) and local synthesis of a limited antibody repertoire including antibodies against measles, rubella, and varicellazoster virus-features that are not entirely specific to MS and may be absent early in the disease course, particularly in children under age 10. [17][18][19][20] IgG OCBs are more common in children with MS than in those with ADEM or other diseases mimicking MS. [17][18][19]21 Presence of IgG OCBs combined with an abnormal MRI was associated with a .26-fold hazard ratio for developing MS in children presenting with incident ON. 22 CSF IgM OCBs can also be found in a subset of patients with pediatric-and adult-onset MS.…”