Lyme neuroborreliosis in adults: A nationwide prospective cohort study

Abstract

The goal of this paper is to characterize the clinical presentation, serological results, current antibiotic treatment practice, including compliance with current European guidelines, and outcome in adults with Lyme neuroborreliosis (LNB) diagnosed at departments of infectious diseases in Denmark. Using a nationwide prospective cohort of patients with central nervous system infections, we identified all adults (≥ 18 years of age) treated for LNB at departments of infectious diseases in Denmark from 2015 through 2017. The database contains information on baseline demographics, history of tick bite, erythema migrans, clinical presentation, laboratory results of blood samples, and cerebrospinal (CSF) biochemistry (e.g. specific Borrelia burgdorferi sensu lato (s.l.) antibodies in serum, B. burgdorferi s.l. intrathecal antibody index) as well as antibiotic therapy. Outcome was assessed by the Glasgow Outcome Scale (GOS) and the presence of residual symptoms at follow-up one month after discharge. We included 194 LNB patients with a median age of 59 years (range 18-85 years, interquartile range [IQR] 47-69 years). The female-to-male ratio was 0.8. A total of 177 of 191 (93 %) of patients had early (second stage) LNB. A history of tick bite or erythema migrans was registered in 75 (39 %) and 49 (25 %) patients, respectively. The median duration of neurological symptoms before first hospital contact was 21 days (range 0-600 days, IQR 10-42 days). Predominant symptoms consisted of radicular pain in 135 of 194 (70 %), cranial nerve paresis in 88 of 194 (45 %), headache in 71 of 185 (38 %), and extremity paresis in 33 of 194 (17 %) patients. Serum-B. burgdorferi s.l. IgM and/or IgG antibodies were detectable in 166 of 181 (92 %) patients at the time of first CSF investigation. Median duration of antibiotic treatment was 14 days (range 10-35 days, IQR 14-21 days) and 59 (39 %) of the patients received intravenous ceftriaxone and/or benzylpenicillin G throughout treatment. At the 1-month follow-up, GOS was unfavorable (< 5) in 54 of 193 (28 %) patients. An unfavorable GOS score was more often registered in patients with ≥ 45 days of symptom duration (20 of 45 (44 %) vs. 34 of 145 (23 %); P = 0.006). In conclusion, a European cohort of adult patients with LNB diagnosed between 2015-2017 presented with classic symptoms and CSF findings. However, a substantial diagnostic delay was still observed. In disagreement with current guidelines, a substantial part of LNB patients were treated with antibiotics longer than 14 days and/or intravenously as route of administration.

Keywords: Adults; Antibiotic therapy; Borrelia antibodies; Borrelia intrathecal antibody production; CSF lactate; Lyme neuroborreliosis.