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Lyme neuroborreliosis—epidemiology, diagnosis and management

Key Points

  • Diagnosis of Lyme neuroborreliosis is made by history taking, clinical examination, cerebrospinal fluid (CSF) analysis, and Borrelia burgdorferi antibody testing

  • B. burgdorferi antibody testing should be performed only in patients presenting with clinical signs suggestive of infection

  • CSF levels of the chemokine CXCL13 might be useful as a complementary diagnostic tool for early Lyme neuroborreliosis

  • Patients with post-treatment Lyme disease syndrome do not have ongoing B. burgdorferi infection and, thus, do not benefit from additional (for example, long-term) antibiotic therapy

  • Alternative treatment options must be established for patients with post-treatment Lyme disease syndrome

  • Chronic Lyme disease is a poorly defined term, used by some practitioners for patients with a wide variety of subjective complaints that can often be attributed to other illnesses

Abstract

Lyme disease, caused by the Borrelia burgdorferi bacterium, is the most common vector-borne disease in the northern hemisphere. The clinical presentation varies with disease stage, and neurological manifestations (often referred to as Lyme neuroborreliosis) are reported in up to 12% of patients with Lyme disease. Most aspects of the epidemiology, clinical manifestation and treatment of Lyme neuroborreliosis are well known and accepted; only the management of so-called chronic Lyme disease is surrounded by considerable controversy. This term is used for disparate patient groups, including those who have untreated late-stage infection (for example, late neuroborreliosis), those with subjective symptoms that persist after treatment (termed 'post-treatment Lyme disease syndrome' [PTLDS]), and those with unexplained subjective complaints that may or may not be accompanied by positive test results for B. burgdorferi infection in serum (here called 'chronic Lyme disease'). The incidence of PTLDS is still a matter of debate, and its pathogenesis is unclear, but there is evidence that these patients do not have ongoing B. burgdorferi infection and, thus, do not benefit from additional antibiotic therapy. Chronic Lyme disease lacks an accepted clinical definition, and most patients who receive this diagnosis have other illnesses. Thus, a careful diagnostic work-up is needed to ensure proper treatment.

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Figure 1: Ticks and Borrelia under the microscope.
Figure 2: Proposed diagnostic work-up for adult patients with early Lyme neuroborreliosis.
Figure 3: Proposed diagnostic algorithm for adult patients with late Lyme neuroborreliosis.
Figure 4: Follow-up MRI and CSF findings in two patients with late Lyme neuroborreliosis.

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Acknowledgements

The authors are very grateful for the clinical cooperation of K. Seelos and M. Wick from the University of Munich. The authors would also like to thank G. Wanner from Ludwig-Maximilians University Munich for his support in generating the electron microscopic images of Borrelia afzelii. The authors' work has been funded by the German Research Foundation, the Else Kröner Fresenius Stiftung, and the University of Munich (FöFoLe programme). V.F. receives research funding from the Robert Koch Institute (ZV2-1369-338 and ZV2-1369-488), the Bavarian State Ministry of Public Health and Care (Z3 12-04 and Z3 13-28) and INSTAND (Z3 13-28).

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U.K. and V.F. researched data for the article, and U.K. and H.-W.P. wrote the article. All authors made substantial contributions to the discussion of content, and V.F. and H.-W.P. reviewed and edited the manuscript before submission.

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Correspondence to Hans-Walter Pfister.

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Competing interests

V.F. has acted as a consultant for the European Centre for Disease Control and for QCMD (Quality Control for Molecular Diagnostics), and he has received honoraria from DiaSorin, Mikrogen, Siemens and Virotech. The other authors declare no competing interests.

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Koedel, U., Fingerle, V. & Pfister, HW. Lyme neuroborreliosis—epidemiology, diagnosis and management. Nat Rev Neurol 11, 446–456 (2015). https://doi.org/10.1038/nrneurol.2015.121

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