Nervous system Lyme disease
- John J Halperin, MD, FAAN, FACP
John J Halperin, MD, FAAN, FACP
- Professor of Neurology
- Mount Sinai School of Medicine
- Medical Director, Neurosciences
- Atlantic Health, NJ
- Section Editors
- Allen C Steere, MD
Allen C Steere, MD
- Section Editor — Lyme Disease
- Professor of Medicine
- Harvard Medical School
- Jeremy M Shefner, MD, PhD
Jeremy M Shefner, MD, PhD
- Section Editor — Neuromuscular Disease
- Professor and Chair of Neurology, Barrow Neurological Institute
- Professor of Neurology, University of Arizona, Phoenix
- Clinical Professor of Neurology, Creighton University
Lyme disease is a tick-borne illness caused by three pathogenic species of the spirochete Borrelia (B. burgdorferi, B. afzelii and B. garinii). B. burgdorferi is the sole cause of the disease in the United States. All three pathogenic species occur in Europe, and two (B. afzelii and B. garinii) have been identified in Asia. Lyme disease has a broad spectrum of clinical manifestations, and it also varies in severity due, in part, to differences in the infecting species.
The neurologic manifestations of Lyme disease will be reviewed here. Other aspects of Lyme disease are discussed separately. (See "Clinical manifestations of Lyme disease in adults" and "Lyme disease: Clinical manifestations in children" and "Diagnosis of Lyme disease" and "Treatment of Lyme disease".)
Borrelia burgdorferi, the organism responsible for the multisystem infectious disease known as Lyme disease, appears to preferentially affect several organ systems. Skin, the site of inoculation, is involved in 80 percent or more of infected individuals . Joint involvement occurs frequently in patients in the United States , but less commonly in Europe. The third most common site is the nervous system, which is involved in 10 to 15 percent of infected individuals in both Europe and the United States . (See "Clinical manifestations of Lyme disease in adults".)
Just as in neurosyphilis, nervous system involvement begins during early disseminated Lyme disease, when spread of the spirochetes can result in meningeal seeding . As in syphilis, untreated Borrelia infection probably subsides in some patients but becomes chronic in others. Also as in syphilis, appropriate antimicrobial treatment results in microbiologic cure in the overwhelming majority of patients, regardless of the duration of the infection.
Much of the confusion and controversy surrounding Lyme disease relates to misunderstandings about what does and does not constitute evidence of nervous system infection. Many patients with Lyme disease develop nonspecific symptoms, including headache, fatigue, cognitive slowing, and memory difficulty. However, these symptoms are not indicative of central nervous system infection and, moreover, are common in many other infectious and inflammatory states [4-6]. At any point in time, indistinguishable cognitive symptoms occur in as many as 2 percent of otherwise healthy people , in whom they can have a significant negative impact on the quality of life.
- Gerber MA, Shapiro ED, Burke GS, et al. Lyme disease in children in southeastern Connecticut. Pediatric Lyme Disease Study Group. N Engl J Med 1996; 335:1270.
- Centers for Disease Control and Prevention (CDC). Lyme disease--United States, 2001-2002. MMWR Morb Mortal Wkly Rep 2004; 53:365.
- Luft BJ, Steinman CR, Neimark HC, et al. Invasion of the central nervous system by Borrelia burgdorferi in acute disseminated infection. JAMA 1992; 267:1364.
- Ogrinc K, Lotrič-Furlan S, Maraspin V, et al. Suspected early Lyme neuroborreliosis in patients with erythema migrans. Clin Infect Dis 2013; 57:501.
- Wormser GP, Halperin JJ. Toward a better understanding of European lyme neuroborreliosis. Clin Infect Dis 2013; 57:510.
- Melia MT, Lantos PM, Auwaerter PG. Lyme disease: authentic imitator or wishful imitation? JAMA Neurol 2014; 71:1209.
- Luo N, Johnson JA, Shaw JW, et al. Self-reported health status of the general adult U.S. population as assessed by the EQ-5D and Health Utilities Index. Med Care 2005; 43:1078.
- Halperin JJ, Krupp LB, Golightly MG, Volkman DJ. Lyme borreliosis-associated encephalopathy. Neurology 1990; 40:1340.
- Halperin JJ, Heyes MP, Keller TL, Whitman M. Neuroborreliosis - encephalopathy vs encephalitis. Proceedings of the 5th International Conference on Lyme Borreliosis, Arlington, Virginia, May 1992. Abstr. 1. 1992:1.
- Halperin JJ, Pass HL, Anand AK, et al. Nervous system abnormalities in Lyme disease. Ann N Y Acad Sci 1988; 539:24.
- Halperin J, Luft BJ, Volkman DJ, Dattwyler RJ. Lyme neuroborreliosis. Peripheral nervous system manifestations. Brain 1990; 113 ( Pt 4):1207.
- England JD, Bohm RP Jr, Roberts ED, Philipp MT. Mononeuropathy multiplex in rhesus monkeys with chronic Lyme disease. Ann Neurol 1997; 41:375.
- Ramesh G, Borda JT, Gill A, et al. Possible role of glial cells in the onset and progression of Lyme neuroborreliosis. J Neuroinflammation 2009; 6:23.
- Garin C, Bujadoux A. Paralysis by ticks. 1922. Clin Infect Dis 1993; 16:168.
- Reik L, Steere AC, Bartenhagen NH, et al. Neurologic abnormalities of Lyme disease. Medicine (Baltimore) 1979; 58:281.
- Centers for Disease Control and Prevention (CDC). Lyme disease--United States, 2003-2005. MMWR Morb Mortal Wkly Rep 2007; 56:573.
- Halperin JJ, Golightly M. Lyme borreliosis in Bell's palsy. Long Island Neuroborreliosis Collaborative Study Group. Neurology 1992; 42:1268.
- Halperin JJ. Lyme disease and the peripheral nervous system. Muscle Nerve 2003; 28:133.
- Sibony P, Halperin J, Coyle PK, Patel K. Reactive Lyme serology in optic neuritis. J Neuroophthalmol 2005; 25:71.
- Rothermel H, Hedges TR 3rd, Steere AC. Optic neuropathy in children with Lyme disease. Pediatrics 2001; 108:477.
- Hörstrup P, Ackermann R. [Tick born meningopolyneuritis (Garin-Bujadoux, Bannwarth) (author's transl)]. Fortschr Neurol Psychiatr Grenzgeb 1973; 41:583.
- Rupprecht TA, Koedel U, Fingerle V, Pfister HW. The pathogenesis of lyme neuroborreliosis: from infection to inflammation. Mol Med 2008; 14:205.
- Reimers CD, Neubert U. Garin-Bujadoux-Bannwarth syndrome. Lancet 1990; 336:128.
- Stanek G, Strle F. Lyme disease: European perspective. Infect Dis Clin North Am 2008; 22:327.
- Logigian EL, Steere AC. Clinical and electrophysiologic findings in chronic neuropathy of Lyme disease. Neurology 1992; 42:303.
- Oey PL, Franssen H, Bernsen RA, Wokke JH. Multifocal conduction block in a patient with Borrelia burgdorferi infection. Muscle Nerve 1991; 14:375.
- Muley SA, Parry GJ. Antibiotic responsive demyelinating neuropathy related to Lyme disease. Neurology 2009; 72:1786.
- Garro AC, Rutman M, Simonsen K, et al. Prospective validation of a clinical prediction model for Lyme meningitis in children. Pediatrics 2009; 123:e829.
- Reik L Jr, Burgdorfer W, Donaldson JO. Neurologic abnormalities in Lyme disease without erythema chronicum migrans. Am J Med 1986; 81:73.
- Hansen K, Lebech AM. The clinical and epidemiological profile of Lyme neuroborreliosis in Denmark 1985-1990. A prospective study of 187 patients with Borrelia burgdorferi specific intrathecal antibody production. Brain 1992; 115 ( Pt 2):399.
- Ackermann R, Rehse-Küpper B, Gollmer E, Schmidt R. Chronic neurologic manifestations of erythema migrans borreliosis. Ann N Y Acad Sci 1988; 539:16.
- Halperin JJ, Volkman DJ, Wu P. Central nervous system abnormalities in Lyme neuroborreliosis. Neurology 1991; 41:1571.
- Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med 1990; 323:1438.
- Belman AL, Iyer M, Coyle PK, Dattwyler R. Neurologic manifestations in children with North American Lyme disease. Neurology 1993; 43:2609.
- Zemel L. Lyme disease and pseudotumor. Mayo Clin Proc 2000; 75:315.
- Halperin JJ. Lyme disease: neurology, neurobiology, and behavior. Clin Infect Dis 2014; 58:1267.
- Halperin JJ, Luft BJ, Anand AK, et al. Lyme neuroborreliosis: central nervous system manifestations. Neurology 1989; 39:753.
- Stoppe G, Wildhagen K, Seidel JW, et al. Positron emission tomography in neuropsychiatric lupus erythematosus. Neurology 1990; 40:304.
- Krupp LB, Masur D, Schwartz J, et al. Cognitive functioning in late Lyme borreliosis. Arch Neurol 1991; 48:1125.
- 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; 345:85.
- 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; 60:1923.
- 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.
- Halperin JJ. Prolonged Lyme disease treatment: enough is enough. Neurology 2008; 70:986.
- Feder HM Jr, Johnson BJ, O'Connell S, et al. A critical appraisal of "chronic Lyme disease". N Engl J Med 2007; 357:1422.
- Marques A. Chronic Lyme disease: a review. Infect Dis Clin North Am 2008; 22:341.
- Stiernstedt GT, Granström M, Hederstedt B, Sköldenberg B. Diagnosis of spirochetal meningitis by enzyme-linked immunosorbent assay and indirect immunofluorescence assay in serum and cerebrospinal fluid. J Clin Microbiol 1985; 21:819.
- Lakos A. CSF findings in Lyme meningitis. J Infect 1992; 25:155.
- Pachner AR, Steere AC. The triad of neurologic manifestations of Lyme disease: meningitis, cranial neuritis, and radiculoneuritis. Neurology 1985; 35:47.
- Steere AC, Berardi VP, Weeks KE, et al. Evaluation of the intrathecal antibody response to Borrelia burgdorferi as a diagnostic test for Lyme neuroborreliosis. J Infect Dis 1990; 161:1203.
- Blanc F, Jaulhac B, Fleury M, et al. Relevance of the antibody index to diagnose Lyme neuroborreliosis among seropositive patients. Neurology 2007; 69:953.
- Ljøstad U, Skarpaas T, Mygland A. Clinical usefulness of intrathecal antibody testing in acute Lyme neuroborreliosis. Eur J Neurol 2007; 14:873.
- Baig S, Olsson T, Hansen K, Link H. Anti-Borrelia burgdorferi antibody response over the course of Lyme neuroborreliosis. Infect Immun 1991; 59:1050.
- Hansen K, Cruz M, Link H. Oligoclonal Borrelia burgdorferi-specific IgG antibodies in cerebrospinal fluid in Lyme neuroborreliosis. J Infect Dis 1990; 161:1194.
- Nocton JJ, Bloom BJ, Rutledge BJ, et al. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in cerebrospinal fluid in Lyme neuroborreliosis. J Infect Dis 1996; 174:623.
- Tumani H, Cadavid D. Are high CSF levels of CXCL13 helpful for diagnosis of Lyme neuroborreliosis? Neurology 2011; 76:1034.
- Marra CM, Tantalo LC, Sahi SK, et al. CXCL13 as a cerebrospinal fluid marker for neurosyphilis in HIV-infected patients with syphilis. Sex Transm Dis 2010; 37:283.
- Schmidt C, Plate A, Angele B, et al. A prospective study on the role of CXCL13 in Lyme neuroborreliosis. Neurology 2011; 76:1051.
- Rupprecht TA, Pfister HW, Angele B, et al. The chemokine CXCL13 (BLC): a putative diagnostic marker for neuroborreliosis. Neurology 2005; 65:448.
- Halperin JJ. Nervous system Lyme disease. Infect Dis Clin North Am 2008; 22:261.
- Kalina P, Decker A, Kornel E, Halperin JJ. Lyme disease of the brainstem. Neuroradiology 2005; 47:903.
- Logigian EL, Johnson KA, Kijewski MF, et al. Reversible cerebral hypoperfusion in Lyme encephalopathy. Neurology 1997; 49:1661.
- Rupprecht TA, Pfister HW. What are the indications for lumbar puncture in patients with Lyme disease? Curr Probl Dermatol 2009; 37:200.
- 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 2007; 69:91.
- 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.
- Hansen K. Lyme neuroborreliosis: improvements of the laboratory diagnosis and a survey of epidemiological and clinical features in Denmark 1985-1990. Acta Neurol Scand Suppl 1994; 151:1.
- Kristoferitsch W. Neurological manifestations of Lyme borreliosis: clinical definition and differential diagnosis. Scand J Infect Dis Suppl 1991; 77:64.
- CLINICAL MANIFESTATIONS
- Peripheral nervous system
- - Cranial neuropathies
- - Radiculoneuritis
- - Bannwarth syndrome
- - Other forms of peripheral nerve involvement
- Central nervous system
- - Meningitis
- - Lyme encephalomyelitis
- - Benign intracranial hypertension
- - Encephalopathy
- Post-Lyme disease syndrome and chronic Lyme disease
- Serologic testing
- CSF analysis
- - CSF antibodies
- - Polymerase chain reaction
- - CXCL13
- Electrophysiologic testing
- Approach to diagnostic testing
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS