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
- 2
Scrimenti R J.
Erythema chronicum migrans.
Arch Dermatol.
1970;
102
(1)
104-105
- 3
Afzelius A.
Verhandlugen der dermatorischen Gesellshaft zu. Stockholm.
Arch Derm Syphiligr.
1910;
101
404
- 4
Garin C H, Bujadoux C.
Paralysie par les tiques.
J Med Lyon.
1922;
71
765-767
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 14
Halperin J J.
Facial nerve palsy associated with Lyme disease.
Muscle Nerve.
2003;
28
(4)
516-517
- 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
- 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
- 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
- 18
Sibony P, Halperin J, Coyle P K, Patel K.
Reactive Lyme serology in optic neuritis.
J Neuroophthalmol.
2005;
25
(2)
71-82
- 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
- 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
- 21
Halperin J J, Luft B J, Anand A K et al..
Lyme neuroborreliosis: central nervous system manifestations.
Neurology.
1989;
39
(6)
753-759
- 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
- 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
- 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
- 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
- 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
- 27
Hörstrup P, Ackermann R.
[Tick born meningopolyneuritis (Garin-Bujadoux, Bannwarth) (author's transl)].
Fortschr Neurol Psychiatr Grenzgeb.
1973;
41
(11)
583-606
- 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
- 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
- 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
- 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
- 32
Fredrikson S, Link H.
CNS-borreliosis selectively affecting central motor neurons.
Acta Neurol Scand.
1988;
78
(3)
181-184
- 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
- 34
Miklossy J.
Alzheimer's disease—a spirochetosis?.
[see comments]
Neuroreport.
1993;
4
(7)
841-848
- 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
- 36
Halperin J J, Krupp L B, Golightly M G, Volkman D J.
Lyme borreliosis-associated encephalopathy.
Neurology.
1990;
40
(9)
1340-1343
- 37
Krupp L B, Masur D, Schwartz J et al..
Cognitive functioning in late Lyme borreliosis.
Arch Neurol.
1991;
48
(11)
1125-1129
- 38
Halperin J J, Heyes M P.
Neuroactive kynurenines in Lyme borreliosis.
Neurology.
1992;
42
(1)
43-50
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 48
Hollstrom E.
Successful treatment of erythema migrans Afzelius.
Acta Derm Venereol.
1951;
31
(2)
235-243
- 49
Halperin J J.
Nervous system Lyme disease.
J R Coll Physicians Edinb.
2010;
40
(3)
248-255
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
