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Semin Neurol 2011; 31(3): 317-324
DOI: 10.1055/s-0031-1287652
© Thieme Medical Publishers

Nervous System Lyme Disease: Is There a Controversy?

John J. Halperin1 , 2
  • 1Department of Neurosciences, Overlook Hospital and Atlantic Neuroscience Institute, Summit, New Jersey
  • 2Mount Sinai School of Medicine, New York, New York
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Publication History

Publication Date:
30 September 2011 (online)

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ABSTRACT

Infection with the tick-borne spirochete, Borrelia burgdorferi, affects the nervous system in well-defined ways. Accurate diagnostic tools and effective therapeutic regimens are now well established. Persistent misconceptions about (1) the role and interpretation of laboratory tests, (2) what is and is not evidence of nervous system infection, and (3) what constitutes an expected response to treatment have fostered widespread perceptions that this disease is highly controversial. Infection causes the classically described triad of meningitis, radiculoneuritis, and cranial neuritis; however, virtually every known neurologic disorder has been blamed on this infection. For most (multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer disease, Parkinson disease), evidence is scant, nonexistent, or coincidental. For some (cerebral vasculitis with stroke, optic neuritis) a few case reports suggest a rare possible causal link.

KEYWORDS

Lyme disease - nervous system - neuroborreliosis - Garin-Bujadoux-Bannwarth syndrome - Borrelia burgdorferi

REFERENCES

  • 1 Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2007 Supplement, Syphilis Surveillance Report. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2009
    Google Scholar
  • 2 Scrimenti R J. Erythema chronicum migrans.  Arch Dermatol. 1970;  102 (1) 104-105
    CrossrefPubMedGoogle Scholar
  • 3 Afzelius A. Verhandlugen der dermatorischen Gesellshaft zu. Stockholm.  Arch Derm Syphiligr. 1910;  101 404
    PubMedGoogle Scholar
  • 4 Garin C H, Bujadoux C. Paralysie par les tiques.  J Med Lyon. 1922;  71 765-767
    PubMedGoogle Scholar
  • 5 Reik L, Steere A C, Bartenhagen N H, Shope R E, Malawista S E. Neurologic abnormalities of Lyme disease.  Medicine (Baltimore). 1979;  58 (4) 281-294
    CrossrefPubMedGoogle Scholar
  • 6 Keller T L, Halperin J J, Whitman M. PCR detection of Borrelia burgdorferi DNA in cerebrospinal fluid of Lyme neuroborreliosis patients.  Neurology. 1992;  42 (1) 32-42
    CrossrefPubMedGoogle Scholar
  • 7 Klempner M S, Schmid C H, Hu L et al.. Intralaboratory reliability of serologic and urine testing for Lyme disease.  Am J Med. 2001;  110 (3) 217-219
    CrossrefPubMedGoogle Scholar
  • 8 Nowakowski J, Schwartz I, Liveris D Lyme Disease Study Group et al. Laboratory diagnostic techniques for patients with early Lyme disease associated with erythema migrans: a comparison of different techniques.  Clin Infect Dis. 2001;  33 (12) 2023-2027
    CrossrefPubMedGoogle Scholar
  • 9 Centers for Disease Control and Prevention. . Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease.  MMWR Morb Mortal Wkly Rep. 1995;  44 (31) 590-591
    PubMedGoogle Scholar
  • 10 Aguero-Rosenfeld M E, Nowakowski J, Bittker S, Cooper D, Nadelman R B, Wormser G P. Evolution of the serologic response to Borrelia burgdorferi in treated patients with culture-confirmed erythema migrans.  J Clin Microbiol. 1996;  34 (1) 1-9
    PubMedGoogle Scholar
  • 11 Dattwyler R J, Volkman D J, Luft B J, Halperin J J, Thomas J, Golightly M G. Seronegative Lyme disease. Dissociation of specific T- and B-lymphocyte responses to Borrelia burgdorferi .  N Engl J Med. 1988;  319 (22) 1441-1446
    CrossrefPubMedGoogle Scholar
  • 12 Hollander D H, Turner T B, Nell E E. The effect of long continued subcurative doses of penicillin during the incubation period of experimental syphilis.  Bull Johns Hopkins Hosp. 1952;  90 (2) 105-120
    PubMedGoogle Scholar
  • 13 Bacon R M, Kugeler K J, Mead P S. Surveillance for Lyme Disease—United States, 1992–2006.  MMWR Morb Mortal Wkly Rep. 2008;  57 (SS10) 1-9
    PubMedGoogle Scholar
  • 14 Halperin J J. Facial nerve palsy associated with Lyme disease.  Muscle Nerve. 2003;  28 (4) 516-517
    CrossrefPubMedGoogle Scholar
  • 15 Halperin J J, Luft B J, Volkman D J, Dattwyler R J. Lyme neuroborreliosis. Peripheral nervous system manifestations.  Brain. 1990;  113 (Pt 4) 1207-1221
    CrossrefPubMedGoogle Scholar
  • 16 Roberts E D, Bohm Jr R P, Lowrie Jr R C et al.. Pathogenesis of Lyme neuroborreliosis in the rhesus monkey: the early disseminated and chronic phases of disease in the peripheral nervous system.  J Infect Dis. 1998;  178 (3) 722-732
    CrossrefPubMedGoogle Scholar
  • 17 Stiernstedt G, Gustafsson R, Karlsson M, Svenungsson B, Sköldenberg B. Clinical manifestations and diagnosis of neuroborreliosis.  Ann N Y Acad Sci. 1988;  539 46-55
    CrossrefPubMedGoogle Scholar
  • 18 Sibony P, Halperin J, Coyle P K, Patel K. Reactive Lyme serology in optic neuritis.  J Neuroophthalmol. 2005;  25 (2) 71-82
    CrossrefPubMedGoogle Scholar
  • 19 Blanc F, Ballonzoli L, Marcel C, De Martino S J, Jaulhac B, de Seze J. Lyme optic neuritis.  J Neurol Sci. 2010;  295 (1-2) 117-119
    CrossrefPubMedGoogle Scholar
  • 20 Ackermann R, Rehse-Küpper B, Gollmer E, Schmidt R. Chronic neurologic manifestations of erythema migrans borreliosis.  Ann N Y Acad Sci. 1988;  539 16-23
    CrossrefPubMedGoogle Scholar
  • 21 Halperin J J, Luft B J, Anand A K et al.. Lyme neuroborreliosis: central nervous system manifestations.  Neurology. 1989;  39 (6) 753-759
    CrossrefPubMedGoogle Scholar
  • 22 Logigian E L, Kaplan R F, Steere A C. Chronic neurologic manifestations of Lyme disease.  N Engl J Med. 1990;  323 (21) 1438-1444
    CrossrefPubMedGoogle Scholar
  • 23 Henriksson A, Link H, Cruz M, Stiernstedt G. Immunoglobulin abnormalities in cerebrospinal fluid and blood over the course of lymphocytic meningoradiculitis (Bannwarth's syndrome).  Ann Neurol. 1986;  20 (3) 337-345
    CrossrefPubMedGoogle Scholar
  • 24 Hansen K, Lebech A M. Lyme neuroborreliosis: a new sensitive diagnostic assay for intrathecal synthesis of Borrelia burgdorferi—specific immunoglobulin G, A, and M.  Ann Neurol. 1991;  30 (2) 197-205
    CrossrefPubMedGoogle Scholar
  • 25 Steere A C, Berardi V P, Weeks K E, Logigian E L, Ackermann R. Evaluation of the intrathecal antibody response to Borrelia burgdorferi as a diagnostic test for Lyme neuroborreliosis.  J Infect Dis. 1990;  161 (6) 1203-1209
    CrossrefPubMedGoogle Scholar
  • 26 Halperin J J, Logigian E L, Finkel M F, Pearl R A. Quality Standards Subcommittee of the American Academy of Neurology . Practice parameters for the diagnosis of patients with nervous system Lyme borreliosis (Lyme disease).  Neurology. 1996;  46 (3) 619-627
    CrossrefPubMedGoogle Scholar
  • 27 Hörstrup P, Ackermann R. [Tick born meningopolyneuritis (Garin-Bujadoux, Bannwarth) (author's transl)].  Fortschr Neurol Psychiatr Grenzgeb. 1973;  41 (11) 583-606
    PubMedGoogle Scholar
  • 28 Halperin J J. Stroke in patients with Lyme disease. In: Caplan L, ed. Uncommon Causes of Stroke. 2nd ed. Cambridge, UK: Cambridge University Press; 2008: 59-68
    Google Scholar
  • 29 Topakian R, Stieglbauer K, Nussbaumer K, Aichner F T. Cerebral vasculitis and stroke in Lyme neuroborreliosis. Two case reports and review of current knowledge.  Cerebrovasc Dis. 2008;  26 (5) 455-461
    CrossrefPubMedGoogle Scholar
  • 30 Hemmer B, Glocker F X, Kaiser R, Lücking C H, Deuschl G. Generalised motor neuron disease as an unusual manifestation of Borrelia burgdorferi infection.  J Neurol Neurosurg Psychiatry. 1997;  63 (2) 257-258
    CrossrefPubMedGoogle Scholar
  • 31 Halperin J J, Kaplan G P, Brazinsky S et al.. Immunologic reactivity against Borrelia burgdorferi in patients with motor neuron disease.  Arch Neurol. 1990;  47 (5) 586-594
    CrossrefPubMedGoogle Scholar
  • 32 Fredrikson S, Link H. CNS-borreliosis selectively affecting central motor neurons.  Acta Neurol Scand. 1988;  78 (3) 181-184
    CrossrefPubMedGoogle Scholar
  • 33 Cassarino D S, Quezado M M, Ghatak N R, Duray P H. Lyme-associated parkinsonism: a neuropathologic case study and review of the literature.  Arch Pathol Lab Med. 2003;  127 (9) 1204-1206
    PubMedGoogle Scholar
  • 34 Miklossy J. Alzheimer's disease—a spirochetosis?.  [see comments] Neuroreport. 1993;  4 (7) 841-848
    CrossrefPubMedGoogle Scholar
  • 35 Pappolla M A, Omar R, Saran B et al.. Concurrent neuroborreliosis and Alzheimer's disease: analysis of the evidence.  Hum Pathol. 1989;  20 (8) 753-757
    CrossrefPubMedGoogle Scholar
  • 36 Halperin J J, Krupp L B, Golightly M G, Volkman D J. Lyme borreliosis-associated encephalopathy.  Neurology. 1990;  40 (9) 1340-1343
    CrossrefPubMedGoogle Scholar
  • 37 Krupp L B, Masur D, Schwartz J et al.. Cognitive functioning in late Lyme borreliosis.  Arch Neurol. 1991;  48 (11) 1125-1129
    CrossrefPubMedGoogle Scholar
  • 38 Halperin J J, Heyes M P. Neuroactive kynurenines in Lyme borreliosis.  Neurology. 1992;  42 (1) 43-50
    CrossrefPubMedGoogle Scholar
  • 39 Luo N, Johnson J A, Shaw J W, Feeny D, Coons S J. 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) 1078-1086
    CrossrefPubMedGoogle Scholar
  • 40 Klempner M S, Hu L T, 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
    CrossrefPubMedGoogle Scholar
  • 41 Krupp L B, Hyman L G, Grimson R et al.. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial.  Neurology. 2003;  60 (12) 1923-1930
    CrossrefPubMedGoogle Scholar
  • 42 Fallon B A, Keilp J G, Corbera K M et al.. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy.  Neurology. 2008;  70 (13) 992-1003
    CrossrefPubMedGoogle Scholar
  • 43 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. 2007;  26 (8) 571-581
    CrossrefPubMedGoogle Scholar
  • 44 Wormser G P, Dattwyler R J, Shapiro E D 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 (9) 1089-1134
    CrossrefPubMedGoogle Scholar
  • 45 Halperin J J, Shapiro E D, Logigian E L Quality Standards Subcommittee of the American Academy of Neurology 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. 2007;  69 (1) 91-102
    CrossrefPubMedGoogle Scholar
  • 46 Lantos P M, Charini W A, Medoff G et al.. Final report of the Lyme disease review panel of the Infectious Diseases Society of America.  Clin Infect Dis. 2010;  51 (1) 1-5
    CrossrefPubMedGoogle Scholar
  • 47 Mygland A, Ljøstad U, Fingerle V, Rupprecht T, Schmutzhard E, Steiner I. European Federation of Neurological Societies . EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis.  Eur J Neurol. 2010;  17 (1) 8-16 e1-e4
    CrossrefPubMedGoogle Scholar
  • 48 Hollstrom E. Successful treatment of erythema migrans Afzelius.  Acta Derm Venereol. 1951;  31 (2) 235-243
    PubMedGoogle Scholar
  • 49 Halperin J J. Nervous system Lyme disease.  J R Coll Physicians Edinb. 2010;  40 (3) 248-255
    CrossrefPubMedGoogle Scholar

John J HalperinM.D. 

Chair, Department of Neurosciences, Overlook Hospital and Atlantic Neuroscience Institute

99 Beauvoir Avenue, Summit, NJ 07902

Email: john.halperin@atlantichealth.org

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