Clinical association of intrathecal and mirrored oligoclonal bands in paediatric neurology

Abstract

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. Cerebrospinal fluid (CSF) and serum from 200 children (94 females, 106 males; age range 2 mo-15 y 10 mo, mean age 6 y 9 mo, SD ±4.9) who underwent CSF investigation for their neurological condition were tested for OCBs using isoelectric focusing. The patients were divided into those with inflammatory (n=58) and non-inflammatory (n=142) CNS disorders. Intrathecal OCBs (OCBs restricted to the CSF) were found in 11 out of 58 (19%) of those with inflammatory CNS disorders compared with none of the 142 patients with non-inflammatory CNS disorders (p<0.001). Diseases associated with intrathecal OCB were multiple sclerosis, Rasmussen encephalitis, N-methyl-d-aspartate receptor (NMDAR) encephalitis, voltage-gated potassium channel (VGKC) encephalopathy, herpes (HSV) encephalitis, 'other' encephalitides, acute cerebellar ataxia, and aseptic meningitis. Mirrored OCBs (identical OCBs in the serum and CSF) were less specific but were still found in 14 out of 58 (24%) children with inflammatory CNS disorders compared with only 6 out of 142 (4%) children with non-inflammatory CNS disorders (p<0.001). Diseases associated with mirrored OCBs included acute disseminated encephalomyelitis (ADEM), VGKC encephalopathy, West syndrome, NMDAR encephalitis, 'other' encephalitides, polio-like illness, Rasmussen encephalitis, cerebral vasculitis, metachromatic leukodystrophy, and bacterial meningitis. Intrathecal OCBs and mirrored OCBs had a positive predictive value for inflammatory CNS disease of 1 (95% confidence interval [CI] 0.68-1) and 0.7 (95% CI 0.46-0.87) respectively. Intrathecal OCBs were restricted to patients with inflammatory CNS disorders. They are a useful, but non-specific, biomarker of CNS inflammation of multiple causes. Mirrored OCBs are less specific, but still support a possible inflammatory CNS disorder. The presence of either intrathecal or mirrored OCBs should raise suspicion of an inflammatory CNS disorder.