Neurologic complications of Lyme disease

0.5 CME. Many patients with Lyme disease develop neurological complications from the infection. This presentation focuses on small fiber neuropathy secondary to Lyme disease. It also discusses immune mechanisms implicated in the post-treatment Lyme disease syndrome (PTLDS) and reduced cerebral blood flow as a potential etiology for the cognitive complaints that are common in patients with PTLDS.


Peter Novak, MD, PhD
Associate Professor of Neurology
Director, Autonomic Laboratory
Brigham and Women’s Faulkner Hospital
Harvard Medical School


Many patients with Lyme disease develop neurological complications from the infection. This presentation focuses on small fiber neuropathy secondary to Lyme disease. It also discusses immune mechanisms implicated in the post-treatment Lyme disease syndrome (PTLDS) and reduced cerebral blood flow as a potential etiology for the cognitive complaints that are common in patients with PTLDS.

Learning objectives

  1. To be familiar with the neurological complications of Lyme Disease
  2. To understand the concept of PTLDS
  3. To understand the current status including immune mechanisms in PTLDS

This session, Neurologic complications of Lyme disease, is approved for 0.5 enduring AAFP Prescribed credits.

AAFP Prescribed credit is accepted by the American Medical Association as equivalent to AMA PRA Category 1 credit(s)™ toward the AMA Physician’s Recognition Award. When applying for the AMA PRA, Prescribed credit earned must be reported as Prescribed, not as Category 1.

The AAFP has reviewed One Health Medical Education for a Changing Climate and deemed it acceptable for AAFP credit. Term of approval is from 01/02/2024 to 01/01/2025. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Evidence-based bibliography for further study

Pachner AR, Steiner I. Lyme neuroborreliosis: infection, immunity, and inflammation. Lancet Neurol. 2007;6: 544–552. 10.1016/S1474-4422(07)70128-X [PubMed] [CrossRef] [Google Scholar]

 Koedel U, Fingerle V, Pfister H-W. Lyme neuroborreliosis-epidemiology, diagnosis and management. Nat Rev Neurol. 2015;11: 446–456. 10.1038/nrneurol.2015.121 [PubMed] [CrossRef] [Google Scholar]

 Cairns V, Godwin J. Post-Lyme borreliosis syndrome: a meta-analysis of reported symptoms. Int J Epidemiol. 2005;34: 1340–1345. 10.1093/ije/dyi129 [PubMed] [CrossRef] [Google Scholar]

Aucott JN. Posttreatment Lyme disease syndrome. Infect Dis Clin North Am. 2015;29: 309–323. 10.1016/j.idc.2015.02.012 [PubMed] [CrossRef] [Google Scholar]

 Aucott JN, Crowder LA, Kortte KB. Development of a foundation for a case definition of post-treatment Lyme disease syndrome. Int J Infect Dis. 2013;17: e443–449. 10.1016/j.ijid.2013.01.008 [PubMed] [CrossRef] [Google Scholar]

 Melia MT, Auwaerter PG. Time for a Different Approach to Lyme Disease and Long-Term Symptoms. N Engl J Med. 2016;374: 1277–1278. 10.1056/NEJMe1502350 [PubMed] [CrossRef] [Google Scholar]

Paules CI, Marston HD, Bloom ME, Fauci AS. Tickborne Diseases—Confronting a Growing Threat. N Engl J Med. 2018; 10.1056/NEJMp1807870 [PubMed] [CrossRef] [Google Scholar]

Novak P. Electrochemical Skin Conductance Correlates with Skin Nerve Fiber Density. Front Aging Neurosci. 2016;8: 199 10.3389/fnagi.2016.00199 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

 Birnbaum J, Bingham CO. Non-length-dependent and length-dependent small-fiber neuropathies associated with tumor necrosis factor (TNF)-inhibitor therapy in patients with rheumatoid arthritis: expanding the spectrum of neurological disease associated with TNF-inhibitors. Semin Arthritis Rheum. 2014;43: 638–647. 10.1016/j.semarthrit.2013.10.007 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

de Greef BTA, Hoeijmakers JGJ, Gorissen-Brouwers CML, Geerts M, Faber CG, Merkies ISJ. Associated conditions in small fiber neuropathy—a large cohort study and review of the literature. Eur J Neurol. 2018;25: 348–355. 10.1111/ene.13508 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Novak P. Quantitative autonomic testing. J Vis Exp. 2011; 10.3791/2502 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Novak P. Quantitative Scale for Grading of Cardiovascular Autonomic Reflex Tests and Small Fibers from Skin Biopsies (QASAT). Journal of Neurological Disorders. 2015; 10.4172/2329-6895.1000196 [CrossRef] [Google Scholar]

Novak P. Hypocapnic cerebral hypoperfusion: A biomarker of orthostatic intolerance. PLoS ONE. 2018;13: e0204419 10.1371/journal.pone.0204419 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Novak Peter. Autonomic Testing. Oxford University Press; 2019 [Google Scholar]

Low PA, Caskey PE, Tuck RR, Fealey RD, Dyck PJ. Quantitative sudomotor axon reflex test in normal and neuropathic subjects. Ann Neurol. 1983;14: 573–580. 10.1002/ana.410140513 [PubMed] [CrossRef] [Google Scholar]

Bastyr EJ, Price KL, Bril V, MBBQ Study Group. Development and validity testing of the neuropathy total symptom score-6: questionnaire for the study of sensory symptoms of diabetic peripheral neuropathy. Clin Ther. 2005;27: 1278–1294. 10.1016/j.clinthera.2005.08.002 [PubMed] [CrossRef] [Google Scholar]

Zilliox L, Peltier AC, Wren PA, Anderson A, Smith AG, Singleton JR, et al. Assessing autonomic dysfunction in early diabetic neuropathy: the Survey of Autonomic Symptoms. Neurology. 2011;76: 1099–1105. 10.1212/WNL.0b013e3182120147 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

England JD, Gronseth GS, Franklin G, Carter GT, Kinsella LJ, Cohen JA, et al. Practice Parameter: evaluation of distal symmetric polyneuropathy: role of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based review). Report of the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation. Neurology. 2009;72: 177–184. 10.1212/01.wnl.0000336345.70511.0f [PubMed] [CrossRef] [Google Scholar]

Lauria G, Hsieh ST, Johansson O, Kennedy WR, Leger JM, Mellgren SI, et al. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol. 2010;17: 903–912, e44-49. 10.1111/j.1468-1331.2010.03023.x [PubMed] [CrossRef] [Google Scholar]

Gibbons CH, Illigens BMW, Wang N, Freeman R. Quantification of sudomotor innervation: a comparison of three methods. Muscle Nerve. 2010;42: 112–119. 10.1002/mus.21626 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Novak P. Autonomic Disorders. Am J Med. 2018; 10.1016/j.amjmed.2018.09.027 [PubMed] [CrossRef] [Google Scholar]

Duray PH. Histopathology of clinical phases of human Lyme disease. Rheum Dis Clin North Am. 1989;15: 691–710. [PubMed] [Google Scholar]

Duray PH. Clinical pathologic correlations of Lyme disease. Rev Infect Dis. 1989;11 Suppl 6: S1487–1493. [PubMed] [Google Scholar]

Alaedini A, Latov N. Antibodies against OspA epitopes of Borrelia burgdorferi cross-react with neural tissue. J Neuroimmunol. 2005;159: 192–195. 10.1016/j.jneuroim.2004.10.014 [PubMed] [CrossRef] [Google Scholar]

Rupprecht TA, Koedel U, Fingerle V, Pfister H-W. The pathogenesis of lyme neuroborreliosis: from infection to inflammation. Mol Med. 2008;14: 205–212. 10.2119/2007-00091.Rupprecht [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Novak V, Novak P, Spies JM, Low PA. Autoregulation of cerebral blood flow in orthostatic hypotension. Stroke. 1998;29: 104–111. [PubMed] [Google Scholar]

Novak P. Orthostatic Cerebral Hypoperfusion Syndrome. Front Aging Neurosci. 2016;8: 22 10.3389/fnagi.2016.00022 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Novak V, Zhao P, Manor B, Sejdić E, Alsop D, Abduljalil A, et al. Adhesion Molecules, Altered Vasoreactivity, and Brain Atrophy in Type 2 Diabetes. Diabetes Care. 2011;34: 2438–2441. 10.2337/dc11-0969 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Chung C-C, Pimentel D, Jor’dan AJ, Hao Y, Milberg W, Novak V. Inflammation-associated declines in cerebral vasoreactivity and cognition in type 2 diabetes. Neurology. 2015;85: 450–458. 10.1212/WNL.0000000000001820 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Biesiada G, Czepiel J, Sobczyk-Krupiarz I, Salamon D, Garlicki A, Mach T. Levels of sVCAM-1 and sICAM-1 in patients with lyme disease. Pol Arch Med Wewn. 2009;119: 200–204. [PubMed] [Google Scholar]

Aucott JN, Soloski MJ, Rebman AW, Crowder LA, Lahey LJ, Wagner CA, et al. CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study. Clin Vaccine Immunol. 2016;23: 757–766. 10.1128/CVI.00071-16 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Novak V, Spies JM, Novak P, McPhee BR, Rummans TA, Low PA. Hypocapnia and cerebral hypoperfusion in orthostatic intolerance. Stroke. 1998;29: 1876–1881. [PubMed] [Google Scholar]

Ross AJ, Medow MS, Rowe PC, Stewart JM. What is brain fog? An evaluation of the symptom in postural tachycardia syndrome. Clin Auton Res. 2013;23: 305–311. 10.1007/s10286-013-0212-z [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Kanjwal K, Karabin B, Kanjwal Y, Grubb BP. Postural orthostatic tachycardia syndrome following Lyme disease. Cardiol J. 2011;18: 63–66. [PubMed] [Google Scholar]

Rauer S, Kastenbauer S, Fingerle V, Hunfeld K-P, Huppertz H-I, Dersch R. Lyme Neuroborreliosis. Dtsch Arztebl Int. 2018;115: 751–756. 10.3238/arztebl.2018.0751 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Fallon BA, Keilp JG, Corbera KM, Petkova E, Britton CB, Dwyer E, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008;70: 992–1003. 10.1212/01.WNL.0000284604.61160.2d [PubMed] [CrossRef] [Google Scholar]

Grill MF, Maganti RK. Neurotoxic effects associated with antibiotic use: management considerations. Br J Clin Pharmacol. 2011;72: 381–393. 10.1111/j.1365-2125.2011.03991.x [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Olsson R. Can doxycycline cause polyneuropathy? J Intern Med. 2002;251: 361–362. [PubMed] [Google Scholar]

Serrador JM, Picot PA, Rutt BK, Shoemaker JK, Bondar RL. MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis. Stroke. 2000;31: 1672–1678. [PubMed] [Google Scholar]

About Instructor

Not Enrolled

Course Includes

  • 1 Lesson
  • 2 Quizzes
  • Course Certificate