Current Treatment Options in Neurology

, Volume 15, Issue 4, pp 454–464 | Cite as

Nervous System Lyme Disease: Diagnosis and Treatment


Opinion statement

The tick-borne spirochete responsible for Lyme disease is highly antibiotic-sensitive. Treatment related misconceptions can be attributed to confusion in three principal realms: (1) the appropriate approach to diagnosis (who should be treated); (2) necessary and appropriate treatment; and (3) what actually constitutes nervous system infection and to what extent this mandates different treatment. Contrary to often-repeated assertions, laboratory-based diagnosis—in the appropriate setting—is as valid as it is in most other serologically diagnosed infections. Treatment is highly effective in the vast majority of patients, including those with nervous system disease. Nervous system infection, most typically meningitis, cranial neuritis, radiculoneuritis, and other forms of mononeuropathy multiplex, is highly antibiotic responsive. The encephalopathy that can be seen in some patients with active infection represents the same phenomenon that occurs in patients with many other inflammatory disorders, is not evidence of central nervous system (CNS) infection, and does not require any different, more prolonged, or more intensive treatment. In patients with infection not involving the CNS, oral treatment with amoxicillin, cefuroxime axetil, or doxycycline for 2–4 weeks is almost always curative. Despite historic preferences for parenteral treatment with ceftriaxone, cefotaxime, or meningeal dose penicillin, patients with the forms of nervous system involvement listed above are highly responsive to oral doxycycline. Parenteral regimens can be reserved for those very rare patients with parenchymal CNS involvement, other severe forms of infection, or the approximately 5 % of patients who fail to respond to oral regimens.


Lyme disease Neuroborreliosis Diagnosis Treatment Borrelia burgdorferi Bannwarth syndrome 


Conflict of Interest

John J. Halperin has served as an expert witness in cases defending physicians accused of failure to diagnose Lyme disease, has received grant support from the Centers for Disease Control and Prevention, has received lecturing honoraria from the American Academy of Neurology and American Academy of Neuromuscular & Electrodiagnostic Medicine, and has received royalties from UpToDate.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of outstanding importance

  1. 1.
    Steere AC, Malawista SE, Hardin JA, Ruddy S, Askenase W, Andiman WA. Erythema chronicum migrans and Lyme arthritis. The enlarging clinical spectrum. Ann Intern Med. 1977;86(6):685–98.PubMedCrossRefGoogle Scholar
  2. 2.
    Reik L, Steere AC, Bartenhagen NH, Shope RE, Malawista SE. Neurologic abnormalities of Lyme disease. Medicine. 1979;58(4):281–94.PubMedCrossRefGoogle Scholar
  3. 3.
    Garin C, Bujadoux A. Paralysie par les tiques. J Med Lyon. 1922;71:765–7.Google Scholar
  4. 4.
    Benach JL, Bosler EM, Hanrahan JP, et al. Spirochetes isolated from the blood of two patients with Lyme disease. N Engl J Med. 1983;308:740–2.PubMedCrossRefGoogle Scholar
  5. 5.
    Steere AC, Grodzicki RL, Kornblatt AN, et al. The spirochetal etiology of Lyme disease. N Engl J Med. 1983;308:733–40.PubMedCrossRefGoogle Scholar
  6. 6.
    Asbrink E, Hederstedt B, Hovmark A. The spirochetal etiology of acrodermatitis chronica atrophicans Herxheimer. Acta Derm Venereol. 1984;64:506–12.PubMedGoogle Scholar
  7. 7.
    Bacon RM, Kugeler KJ, Mead PS. Surveillance for Lyme disease - United States, 1992–2006. Morb Mortal Wkly Rep. 2008;57(SS10):1–9.Google Scholar
  8. 8.
    Nadelman RB, Nowakowski J, Fish D, et al. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. 2001;345(2):79–84.PubMedCrossRefGoogle Scholar
  9. 9.
    Gerber MA, Shapiro ED, Burke GS, Parcells VJ, Bell GL, Pediatric Lyme Disease Study Group. Lyme disease in children in southeastern Connecticut. N Engl J Med. 1996;335(17):1270–4.PubMedCrossRefGoogle Scholar
  10. 10.
    Steere AC, Pachner AR, Malawista SE. Neurologic abnormalities of Lyme disease: successful treatment with high-dose intravenous penicillin. Ann Intern Med. 1983;99:767–72.PubMedCrossRefGoogle Scholar
  11. 11.
    Halperin JJ, Luft BJ, Volkman DJ, Dattwyler RJ. Lyme neuroborreliosis - peripheral nervous system manifestations. Brain. 1990;113:1207–21.PubMedCrossRefGoogle Scholar
  12. 12.
    Halperin JJ, Krupp LB, Golightly MG, Volkman DJ. Lyme borreliosis-associated encephalopathy. Neurology. 1990;40:1340–3.PubMedCrossRefGoogle Scholar
  13. 13.
    Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med. 1990;323(21):1438–44.PubMedCrossRefGoogle Scholar
  14. 14.
    Krupp LB, Masur D, Schwartz J, et al. Cognitive functioning in late Lyme borreliosis. Arch Neurol. 1991;48:1125–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Halperin JJ, Heyes MP. Neuroactive kynurenines in Lyme borreliosis. Neurology. 1992;42(1):43–50.PubMedCrossRefGoogle Scholar
  16. 16.
    Strle K, Drouin EE, Shen S, et al. Borrelia burgdorferi stimulates macrophages to secrete higher levels of cytokines and chemokines than Borrelia afzelii or Borrelia garinii. J Infect Dis. 2009;200(12):1936–43.PubMedCrossRefGoogle Scholar
  17. 17.
    Dressler F, Whalen JA, Reinhardt BN, Steere AC. Western blotting in the serodiagnosis of Lyme disease. J Infect Dis. 1993;167(2):392–400.PubMedCrossRefGoogle Scholar
  18. 18.•
    Wormser GP, Schriefer M, Aguero-Rosenfeld ME, et al. Single-tier testing with the C6 peptide ELISA kit compared with two-tier testing for Lyme disease. Diagn Microbiol Infect Dis. 2013;75(1):9–15. Nicely summarizes issues about sensitivity and specificity of conventional and C6 serologic testing in Lyme disease.PubMedCrossRefGoogle Scholar
  19. 19.••
    Halperin JJ, Baker P, Wormser GP. Common misconceptions about Lyme disease. Am J Med. 2013;126(3):264. e1–7. Concise summary of most of the misunderstandings about the diagnosis and treatment of Lyme disease.PubMedCrossRefGoogle Scholar
  20. 20.
    Halperin JJ, Shapiro ED, Logigian EL, et al. Practice parameter: treatment of nervous system Lyme disease. Neurology. 2007;69(1):91–102.PubMedCrossRefGoogle Scholar
  21. 21.
    Halperin JJ, Luft BJ, Anand AK, et al. Lyme neuroborreliosis: central nervous system manifestations. Neurology. 1989;39(6):753–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089–134.PubMedCrossRefGoogle Scholar
  23. 23.••
    Mygland A, Ljostad U, Fingerle V, Rupprecht T, Schmutzhard E, Steiner I. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol. 2010;17(1):8–16. e1–4. Excellent summary of evidence regarding diagnosis and treatment of neuroborreliosis in European patients.Google Scholar
  24. 24.
    Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med. 2001;345(2):85–92.PubMedCrossRefGoogle Scholar
  25. 25.
    Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology. 2003;60(12):1923–30.PubMedCrossRefGoogle Scholar
  26. 26.
    Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008;70:992–1003.PubMedCrossRefGoogle Scholar
  27. 27.
    Bockenstedt LK, Gonzalez DG, Haberman AM, Belperron AA. Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy. J Clin Invest. 2012;122(7):2652–60.PubMedCrossRefGoogle Scholar
  28. 28.
    Embers M, Barthold S, Borda JT, et al. Persistence of Borrelia burgdorferi in Rhesus Macaques following antibiotic treatment of disseminated infection. PLoS One. 2012;7(1):1–12.CrossRefGoogle Scholar
  29. 29.•
    Wormser GP, Baker PJ, O'Connell S, Pachner AR, Schwartz I, Shapiro ED. Critical analysis of treatment trials of Rhesus Macaques infected with Borrelia Burgdorferi reveals important flaws in experimental design. Vector-Borne Zoon Dis. 2012:120523085321004. Critical analysis of evidence about persistent organisms after treatment.Google Scholar
  30. 30.
    Shadick NA, Phillips CB, Sangha O, et al. Musculoskeletal and neurologic outcomes in patients with previously treated Lyme disease. Ann Intern Med. 1999;131(12):919–26.PubMedCrossRefGoogle Scholar
  31. 31.
    Seltzer EG, Gerber MA, Cartter ML, Freudigman K, Shapiro ED. Long-term outcomes of persons with Lyme disease. JAMA. 2000;283(5):609–16.PubMedCrossRefGoogle Scholar
  32. 32.
    Luo N, Johnson J, Shaw J, Feeny D, Coons S. Self-reported health status of the general adult U.S. population as assessed by the EQ-5D and Health Utilities Index. Med Care. 2005;43(11):1078–86.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of NeurosciencesOverlook Medical CenterSummitUSA

Personalised recommendations