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Neuroborreliosis: Pathogenesis, Symptoms, Diagnosis, and Treatment

  • Authors: Tobias A. Rupprecht, MD; Volker Fingerle, MD
  • CME Released: 3/7/2011
  • Valid for credit through: 3/7/2012
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Target Audience and Goal Statement

This activity is intended for primary care clinicians, infectious disease physicians, neurologists, and other health professionals caring for patients with Lyme disease.

The goal of this activity is to describe the pathogenesis, symptoms, diagnosis, and management of neuroborreliosis, based on a review.

Upon completion of this activity, participants will be able to:

  1. Describe the epidemiology and pathogenesis of Lyme neuroborelliosis (LNB)
  2. Describe the characteristic symptoms and diagnosis of LNB
  3. Describe the treatment and management of LNB


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  • Tobias A. Rupprecht, MD

    Abteilung für Neurologie, AmperKliniken AG Dachau, Dachau, Germany


    Disclosure: Tobias A. Rupprecht, MD, disclosed the following relevant financial relationships:
    Served as a consultant for: Genzyme Corporation; Mikrogen; Virotech

  • Volker Fingerle, MD

    National Reference Centre for Borrelia, LGL Oberschleißheim, Germany


    Disclosure: Volker Fingerle, MD, has disclosed no relevant financial relationships.


  • Elisa Manzotti

    Editorial Director, Future Science Group, London, United Kingdom


    Disclosure: Elisa Manzotti has disclosed no relevant financial relationships.

CME Author(s)

  • Laurie Barclay, MD

    Freelance writer and reviewer, Medscape, LLC


    Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

CME Reviewer(s)

  • Nafeez Zawahir, MD

    CME Clinical Director, Medscape, LLC


    Disclosure: Nafeez Zawahir, MD, has disclosed no relevant financial relationships.

  • Sarah Fleischman

    CME Program Manager, Medscape, LLC


    Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.

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    For Physicians

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    Medscape, LLC staff have disclosed that they have no relevant financial relationships.

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Neuroborreliosis: Pathogenesis, Symptoms, Diagnosis, and Treatment: Treatment



While the diagnosis of LNB might be challenging, the therapy is both easy and well defined. Several studies have documented a response to 10–28-day courses of intravenous ceftriaxone (2 or 4 g daily), intravenous penicillin (20 million units daily), intravenous cefotaxime (3 × 2 g or 2 × 3 g daily) and oral doxycycline (200 mg daily). An overview of the treatment trials is reported by Mygland et al.[139] Significant resistance of B. burgdorferi to one of these antibiotics is reported to be very rare. A recent Norwegian class I study of 102 LNB patients has shown that oral doxycycline (200 mg daily for 14 days) is noninferior to a 14-day course of intravenous ceftriaxon (2 g per day).[157] Therefore, as already suggested by a North American meta-analysis,[158] both ceftriaxone and doxycycline are equal alternatives and are recommended first-line therapies for acute LNB. Doxycycline has the advantage of an oral route of administration.

The duration of treatment should be 14 days, although there are studies that recommend either a shorter therapy course of only 10 days (with a 2-year treatment failure-free survival rate of 99%),[134] while others discuss the need for 28 days of antibiotic therapy (especially for late LNB). No well-designed study so far could clearly demonstrate the need for prolonged antibiotic treatment beyond 1 month of treatment, as discussed previously. Therefore, oral adjunct antibiotics are not justified in the treatment of patients with LNB, who initially received an adequate intravenous ceftriaxone therapy.[159]

The outcome after antibiotic treatment is generally good. The pain, typical for Bannwarth’s syndrome, rapidly decreases under antibiotic therapy, and patients might be free of complaints even after one antibiotic dose [Rupprecht TA, Personal Observation].[160] Objective findings after 1 year are mostly discrete and can be observed in approximately 16–28% of patients. A delayed treatment initiation in particular is considered a risk factor for these persistent findings.[122,132,137] Persisting, objective symptoms after an adequate course of antibiotics are either due to irreversible damage (e.g., a limb paresis due to axonal loss) or might reflect a misdiagnosis in the majority of cases. Subjective symptoms can be more frequent, and the relevance of this was discussed previously. In rare cases, the borrelial infection might have initiated an autoimmune reaction due to molecular mimicry.[119] To differentiate between both pathogenic mechanisms, the determination of CXCL13 as the most reliable activity and treatment marker can be useful. The serology is not helpful as a follow-up marker: in only approximately 50% of patients does the antibody titer markedly decrease after 12 months.[159]