Abstract
BackgroundThe presence of ≥3 oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) without corresponding bands in serum represents a definite pathological pattern, whereas the clinical significance of 1–2 CSF bands (borderline pattern) is poorly investigated.MethodsWe screened 1986 consecutive CSF and serum samples which were collected over a four-year time period and had results of isoelectric focusing (IEF) available. Of patients with borderline OCB we reviewed individual medical charts for assessment of clinical diagnoses. Where feasible, IEF was replicated and results of follow-up samples were obtained. IEF was performed using polyacrylamide gel followed by immunoblotting and IgG-specific antibody staining. Additionally, we performed a systematic literature review of the diagnostic specificity of OCB using different cut-offs for CSF-restricted bands.ResultsOut of 253 patients with borderline OCB, 21.7% had an inflammatory neurological disease (IND) of the central nervous system, comprising 4% multiple sclerosis patients, and 14.2% had a peripheral IND, whereas the remaining 64.1% of patients showed non-inflammatory diseases. Frequency of one or two CSF bands without corresponding serum bands did not differ between the disease groups. In a subgroup of 100 patients IEF was repeated. Of those, 73% were OCB negative, while no sample was positive. In 26 patients IEF results were available of a follow-up sample collected after a median of 27 months. Of those, 4 (15.4%) turned positive. Systematic literature review revealed a diagnostic specificity of OCB of 97% and 92% using a cut-off ≥3 and ≥2 CSF bands in patients with mainly non-inflammatory neurological diseases.ConclusionThe clinical significance of one or two CSF-restricted bands is moderate and, hence, indicates a possible but not reliable proof of intrathecal B-cell activity. Sample re-testing, introduction of an additional diagnostic category, e.g. “possible intrathecal IgG synthesis”, and follow-up lumbar puncture might be possible options to address this scenario.
Highlights
Detection of intrathecal IgG synthesis is part of the routine cerebrospinal fluid (CSF) work-up [1]
Frequency of one or two CSF bands without corresponding serum bands did not differ between the disease groups
Systematic literature review revealed a diagnostic specificity of oligoclonal bands (OCB) of 97% and 92% using a cut-off 3 and 2 CSF bands in patients with mainly noninflammatory neurological diseases
Summary
Detection of intrathecal IgG synthesis is part of the routine cerebrospinal fluid (CSF) work-up [1]. With regard to the cut-off defining OCB positivity, one might think that a consensus on 2 CSF bands has already been reached, as this threshold is recommended in the current MS diagnostic criteria [4] and suggested by recent review articles [5]. The presence of 3 oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) without corresponding bands in serum represents a definite pathological pattern, whereas the clinical significance of 1–2 CSF bands (borderline pattern) is poorly investigated
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