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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

Disclosures

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, 11:59 PM EST

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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Epidemiology

The incidence of Lyme borreliosis varies considerably from region to region (an overview is given by Hubalek^[7]). In Germany, Lyme borreliosis must legally be notified to local health services in the six eastern states only. Between 2002 and 2009, the reported incidence in these six territories varied between 17.8 and 37.5 per 100,000 inhabitants.^[8] In a prospective, population-based study covering the region of Würzburg, the incidence was 111/100,000 per year.^[9] The individual probability of becoming infected with B. burgdorferi by a tick bite depends on several factors:

The proportion of infected ticks – a European meta-analysis found 18.6% of the adult and 10.1% of the nymphal ticks to be infected, but the rate varied, depending on the region and the tick stage, from 1.5 to 75%.^[10] Of note, there was no differentiation between human-pathogenic and -nonpathogenic B. burgdorferi species.
The duration of the tick’s feeding – while the North American tick Ixodes scapularis needs at least 24–48 h of feeding until Borrelia are transmitted, experiments with gerbils and Ixodes ricinus (endemic to Europe) have shown that after only 16.7 h of feeding, 50% of the animals were infected with B. burgdorferi.^[11–13] The reason for this discrepancy can be found at the location of B. burgdorferi inside of the ticks: while Ixodes scapularis harbors the bacteria only in the mid-gut (where they have to detach and migrate to the salivary gland before being injected into the host), a part of the Borrelia in I. ricinus can already be found directly in the salivary glands.^[14]
The borrelial species – skin biopsies from patients with erythema migrans reveal mostly B. afzelii (in 70–90% of the cases) and significantly less B. garinii (10–20%), while both species can be equally found in the ticks.^[3,7,10,15] This suggests that borrelial species vary in their infectivity.

Considering the necessary duration of feeding and the proportion of infected ticks, spirochetal inoculation after a tick bite is the exception and not the rule. A study from south-west Germany has shown that only approximately 2.6% of all tick bites lead to a clinically apparent infection.^[16]

The most frequent manifestation of Lyme borreliosis – accounting for approximately 90% of cases – is erythema migrans, while the CNS is the most frequent destination of dissemination. According to population-based prospective studies performed both in Germany and Sweden, the incidence of Lyme neuroborreliosis (LNB) is approximately 3–11/100,000 per year.^[9,17]

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Page 2 of 8

Pathogenesis

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: Epidemiology

Epidemiology

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: Epidemiology

Epidemiology

Table of Contents