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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

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.

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.

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

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Executive Summary

Epidemiology

The incidence of Lyme borreliosis varies between regions and was 111/100,000 per year in a population-based study from Germany.
The probability of infection after a tick bite depends mainly on the rate of infected ticks, the borrelial species and the duration of feeding.
The CNS is the most frequent destination of dissemination, but Lyme neuroborreliosis (LNB) accounts for only approximately 3–11% of Lyme borreliosis cases in Europe.

Pathogenesis

Borrelia burgdorferi possesses several mechanisms of immune evasion, especially antigenic variation, inactivation of the host immune system and hiding in protective niches of the host.
Invasion of the CNS appears to vary between the USA (mainly hematogenous spread) and Europe (along structures such as the peripheral nerves).
CXCL13 appears to play a key role in the B-cell-dominated immune response in the cerebrospinal fluid in LNB.
The neuronal dysfunction is either the result of a direct process (cytotoxicity of B. burgdorferi) or indirectly (e.g., through lipoproteins, inflammatory bystander reactions or autoimmune phenomena).

Symptoms

The clinical picture of acute LNB is well defined and encompasses meningoradiculitis, cranial neuritis, focal neurological deficits and/or meningitis in the majority of cases.
Chronic neuroborreliosis is a rare disease with both clinical and laboratory objective findings.
Post-Lyme disease is a poorly defined syndrome as yet, which applies to treated patients with persisting (mostly subjective) symptoms but without evidence of an ongoing infection.

Diagnosis

According to the existing guidelines, a typical clinical picture in combination with inflammatory cerebrospinal fluid changes and an intrathecal production of B. burgdorferi-specific antibodies is required for a definite diagnosis of LNB.
CXCL13 appears to be a promising marker for the diagnosis of early cases with negative antibody index, for activity of disease and as a therapy marker.
Owing to the lack of adequate studies, the lymphocyte transformation test and CD57⁺ cell counts cannot be recommended for the diagnosis of acute or chronic LNB.

Treatment

Oral doxycycline and intravenous β-lactam antibiotics appear to be equally effective.
There is no evidence that antibiotic treatment beyond 21–28 days is more effective, especially in the prevention of persisting symptoms.

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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: Executive Summary

Executive Summary

Epidemiology

Pathogenesis

Symptoms

Diagnosis

Treatment

Table of Contents

Reprint Address

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: Executive Summary

Executive Summary

Epidemiology

Pathogenesis

Symptoms

Diagnosis

Treatment

Table of Contents

Reprint Address