No correlation between symptom duration and intrathecal production of IgM and/or IgG antibodies in Lyme neuroborreliosis – a retrospective cohort study in Denmark

•No association between symptom delay and presence of CSF B.burgdorferi IgM and/or IgG.•Most of LNB patients do not convert from B.burgdorferi IgM to IgG antibodies in CSF.•Type of CSF antibodies associated with different LNB symptom presentations.•B.burgdorferi CSF antibody type cannot be used to interpret stage of disease in LNB. In Europe, a definite diagnosis of Lyme neuroborreliosis (LNB) requires intrathecally produced Borrelia-specific antibodies. We aimed to examine if the time from symptom debut to lumbar puncture (LP) correlated with findings of intrathecal production of Borrelia-specific IgM and/or IgG antibodies in LNB A retrospective study of 544 patients with a positive Borrelia burgdorferi antibody index (Bb-AI) analysed at the Department of Clinical Microbiology, Odense University Hospital, Denmark, between 01.01.1995 and 31.12.2020 The delay from symptom onset to LP for patients with positive Bb-AI IgM was 30 days (IQR 14–95 days), IgG 24 days (IQR 11–62), IgM+IgG 24 days (IQR 14–48), P = 0.098. Ninety-three patients had a second LP after median 125 days (IQR 28–432) and 25 had a third LP after median 282 days (IQR 64–539). Most patients (66.7%) did not convert from their initial intrathecal antibody finding. The prevalence of different clinical manifestations differed significantly between the three Bb-AI groups. Intrathecal Borrelia-specific antibody production did not follow the typical immune response of initial IgM production followed by IgG production. Diagnosis of LNB stage should not be based on the type of antibodies found in the cerebrospinal fluid.