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^• These guidelines are very helpful in the diagnostic approach to a patient with suspected Lyme neuroborreliosis.
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Ljostad U, Skarpaas T, Mygland A: Clinical usefulness of intrathecal antibody testing in acute Lyme neuroborreliosis. Eur. J. Neurol. 14, 873—876 (2007).
Blanc F, Jaulhac B, Fleury M et al.: Relevance of the antibody index to diagnose Lyme neuroborreliosis among seropositive patients. Neurology 69, 953—958 (2007).
Zore A, Ruzic-Sabljic E, Maraspin V et al.: Sensitivity of culture and polymerase chain reaction for the etiologic diagnosis of erythema migrans. Wien. Klin. Wochenschr. 114, 606—609 (2002).
Rupprecht TA, Pfister HW: What are the indications for lumbar puncture in patients with Lyme disease? Curr. Probl. Dermatol. 37, 200—206 (2009).
Tjernberg I, Henningsson AJ, Eliasson I, Forsberg P, Ernerudh J: Diagnostic performance of cerebrospinal fluid chemokine CXCL13 and antibodies to the C6-peptide in Lyme neuroborreliosis. J. Infect. 62(2), 149—158 (2011).
Senel M, Rupprecht TA, Tumani H, Pfister HW, Ludolph AC, Brettschneider J: The chemokine CXCL13 in acute neuroborreliosis. J. Neurol. Neurosurg. Psychiatry 81, 929—933 (2010).
Schmidt C, Plate A, Angele B et al.: ProCL—a prospective study on the role of CXCL13 in Lyme neuroborreliosis. Neurology (2011) (In press).
van Burgel ND, Kroes ACM, van Dam A: CXCL13 in CSF as a biomarker for diagnosing Lyme neuroborreliosis. Presented at: International Conference on Lyme Borreliosis (ICLB) 2010. Ljubljana, Slovenia, 26—29 September 2010.
Wutte N, Berghold A, Löffler S et al.: The chemokine CXCL13 in Lyme borreliosis. Presented at: International Conference on Lyme Borreliosis (ICLB) 2010. Ljubljana, Slovenia, 26—29 September 2010.
Nordberg M, Forsberg P, Johansson A et al.: Cytokines IL-10, IL-17 and CXCL13 in CSF during neuroborreliosis. Presented at: International Conference on Lyme Borreliosis (ICLB) 2010. Ljubljana, Slovenia, 26—29 September 2010.
Owlasiuk P, Zajkowska J, Pancewicz S et al.: Concentrations of five CXC chemokines and fractalkine in serum and cerebrospinal fluid of patients with Lyme neuroborreliosis. Presented at: International Conference on Lyme Borreliosis (ICLB) 2010. Ljubljana, Slovenia, 26—29 September 2010.
Fischer L, Korfel A, Pfeiffer S et al.: CXCL13 and CXCL12 in central nervous system lymphoma patients. Clin. Cancer Res. 15, 5968—5973 (2009).
von Baehr V, Liebenthal C, Gaida B, Schmidt F-P, von Baehr R, Volk H-D: Evaluation of the diagnostic significance of the lymphocyte proliferation test in patients with Lyme borreliosis. J. Lab. Med. 149—158 (2007).
Valentine-Thon E, Ilsemann K, Sandkamp M: A novel lymphocyte transformation test (LTT-MELISA) for Lyme borreliosis. Diagn. Microbiol. Infect. Dis. 57, 27—34 (2007).
Stricker RB, Winger EE: Decreased CD57 lymphocyte subset in patients with chronic Lyme disease. Immunol. Lett. 76, 43—48 (2001).
Marques A, Brown MR, Fleisher TA: Natural killer cell counts are not different between patients with post-Lyme disease syndrome and controls. Clin. Vaccine Immunol. 16, 1249—1250 (2009).
Ljostad U, Skogvoll E, Eikeland R et al.: Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blind, randomised trial. Lancet Neurol 7, 690—695 (2008).
•• Demonstrates the equal efficacy of oral doxycycline and intravenous ceftriaxone and therefore advocates treatment via the oral route for patients with Lyme neuroborreliosis.
Halperin JJ, Shapiro ED, Logigian E et al.: Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 69, 91—102 (2007).
Oksi J, Nikoskelainen J, Hiekkanen H et al.: Duration of antibiotic treatment in disseminated Lyme borreliosis: a double-blind, randomized, placebo-controlled, multicenter clinical study. Eur. J. Clin. Microbiol. Infect. Dis. 26, 571—581 (2007).
Pfister HW, Preac-Mursic V, Wilske B, Einhaupl KM: Cefotaxime vs penicillin G for acute neurologic manifestations in Lyme borreliosis. A prospective randomized study. Arch. Neurol. 46, 1190—1194 (1989).
Horstrup P, Ackermann R: Tick-borne meningopolyneuritis (Garin-Bujadoux, Bannwarth). Fortschr. Neurol. Psychiatr. Grenzgeb. 41, 583—606 (1973).
Burgdorfer W, Barbour AG, Hayes SF, Benach JL, Grunwaldt E, Davis JP: Lyme disease — a tick-borne spirochetosis? Science 216, 1317—1319 (1982).
•• First description of Borrelia burgdorferi and therefore probably the most important publication on this topic.

Papers of special note have been highlighted as:
• of interest
•• of considerable interest

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Author(s)

Tobias A. Rupprecht, MD

Abteilung für Neurologie, AmperKliniken AG Dachau, Dachau, Germany

Disclosures

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

Disclosures

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

Editor(s)

Elisa Manzotti

Editorial Director, Future Science Group, London, United Kingdom

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Disclosure: Elisa Manzotti has disclosed no relevant financial relationships.

CME Author(s)

Laurie Barclay, MD

Freelance writer and reviewer, Medscape, LLC

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

CME Reviewer(s)

Nafeez Zawahir, MD

CME Clinical Director, Medscape, LLC

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

Sarah Fleischman

CME Program Manager, Medscape, LLC

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Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.

CME

Neuroborreliosis: Pathogenesis, Symptoms, Diagnosis, and Treatment

Authors: Tobias A. Rupprecht, MD; Volker Fingerle, MD
CME Released: 3/7/2011
THIS ACTIVITY HAS EXPIRED FOR CREDIT
Valid for credit through: 3/7/2012

Start Activity

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:

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

Disclosures

Author(s)

Tobias A. Rupprecht, MD

Abteilung für Neurologie, AmperKliniken AG Dachau, Dachau, Germany

Disclosures

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

Disclosures

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

Editor(s)

Elisa Manzotti

Editorial Director, Future Science Group, London, United Kingdom

Disclosures

Disclosure: Elisa Manzotti has disclosed no relevant financial relationships.

CME Author(s)

Laurie Barclay, MD

Freelance writer and reviewer, Medscape, LLC

Disclosures

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

CME Reviewer(s)

Nafeez Zawahir, MD

CME Clinical Director, Medscape, LLC

Disclosures

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

Sarah Fleischman

CME Program Manager, Medscape, LLC

Disclosures

Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.

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For Physicians

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Medscape, LLC designates this Journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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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]

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Page 6 of 8

Conclusion & Future Perspective

CME Information

References

CME

Neuroborreliosis: Pathogenesis, Symptoms, Diagnosis, and Treatment

Target Audience and Goal Statement

Disclosures

Author(s)

Tobias A. Rupprecht, MD

Volker Fingerle, MD

Editor(s)

Elisa Manzotti

CME Author(s)

Laurie Barclay, MD

CME Reviewer(s)

Nafeez Zawahir, MD

Sarah Fleischman

Accreditation Statements

For Physicians

Instructions for Participation and Credit

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

Treatment

Table of Contents

References

Faculty and Disclosures

Author(s)

Tobias A. Rupprecht, MD

Volker Fingerle, MD

Editor(s)

Elisa Manzotti

CME Author(s)

Laurie Barclay, MD

CME Reviewer(s)

Nafeez Zawahir, MD

Sarah Fleischman

CME

Neuroborreliosis: Pathogenesis, Symptoms, Diagnosis, and Treatment

Target Audience and Goal Statement

Disclosures

Author(s)

Tobias A. Rupprecht, MD

Volker Fingerle, MD

Editor(s)

Elisa Manzotti

CME Author(s)

Laurie Barclay, MD

CME Reviewer(s)

Nafeez Zawahir, MD

Sarah Fleischman

Accreditation Statements

For Physicians

Instructions for Participation and Credit

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

Treatment

Table of Contents