Review
Lyme Neuroborreliosis: Clinical Outcomes, Controversy, Pathogenesis, and Polymicrobial Infections
Juan Carlos Garcia-Monco MD, PhD, FAAN,
Jorge L. Benach PhD,
Corresponding Author
Juan Carlos Garcia-Monco MD, PhD, FAAN
Department of Neurology, University Hospital of Basurto, Bilbao, Vizcaya, Spain
Departments of Molecular Genetics and Microbiology, Stony Brook University School of Medicine, Stony Brook, NY
Address correspondence to Dr Garcia-Monco, Department of Neurology, Hospital Universitario de Basurto, Bilbao, Vizcaya, Spain. Email: [email protected]
Search for more papers by this authorJorge L. Benach PhD
Departments of Molecular Genetics and Microbiology, Stony Brook University School of Medicine, Stony Brook, NY
Pathology, Stony Brook University School of Medicine, Stony Brook, NY
Search for more papers by this authorJuan Carlos Garcia-Monco MD, PhD, FAAN,
Jorge L. Benach PhD,
Corresponding Author
Juan Carlos Garcia-Monco MD, PhD, FAAN
Department of Neurology, University Hospital of Basurto, Bilbao, Vizcaya, Spain
Departments of Molecular Genetics and Microbiology, Stony Brook University School of Medicine, Stony Brook, NY
Address correspondence to Dr Garcia-Monco, Department of Neurology, Hospital Universitario de Basurto, Bilbao, Vizcaya, Spain. Email: [email protected]
Search for more papers by this authorJorge L. Benach PhD
Departments of Molecular Genetics and Microbiology, Stony Brook University School of Medicine, Stony Brook, NY
Pathology, Stony Brook University School of Medicine, Stony Brook, NY
Search for more papers by this authorAbstract
Lyme borreliosis is the object of numerous misconceptions. In this review, we revisit the fundamental manifestations of neuroborreliosis (meningitis, cranial neuritis, and radiculoneuritis), as these have withstood the test of time. We also discuss other manifestations that are less frequent. Stroke, as a manifestation of Lyme neuroborreliosis, is considered in the context of other infections. The summary of the literature regarding clinical outcomes of neuroborreliosis leads to its controversies. We also include new information on pathogenesis and on the polymicrobial nature of tick-borne diseases. In this way, we update the review that we wrote in this journal in 1995. ANN NEUROL 2019;85:21–31.
Supporting Information
| Filename | Description |
|---|---|
| ana25389-sup-0001-TableS1.docxWord 2007 document , 53.7 KB | Supplementary Table 1 Unusual clinical conditions associated to Lyme neuroborreliosis. |
| ana25389-sup-0002-TableS2.docxWord 2007 document , 41.3 KB | Supplementary Table 2 List of patient series and case reports of patients with stroke, cerebral hemorrhage, and cerebral vasculitis due to Lyme neuroborreliosis. |
| ana25389-sup-0003-TableS3.docxWord 2007 document , 58.2 KB | Supplementary Table 3 List of studies on long term outcomes of Lyme neuroborreliosis; in chronological order with the most recent first. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Paules CI, Marston HD, Bloom ME, Fauci AS. Tickborne diseases—confronting a growing threat. N Engl J Med 2018; 379: 701–703.
- 2Rosenberg R, Lindsey NP, Fischer M, et al. Vital signs: trends in reported vectorborne disease cases—United States and territories, 2004-2016. MMWR Morb Mortal Wkly Rep 2018; 67: 496–501.
- 3Steere AC, Strle F, Wormser GP, et al. Lyme borreliosis. Nat Rev Dis Primers 2016; 2: 16090.
- 4Pachner AR, Steere AC. The triad of neurologic manifestations of Lyme disease: meningitis, cranial neuritis, and radiculoneuritis. Neurology 1985; 35: 47–53.
- 5Garcia-Monco JC, Benach JL. Lyme neuroborreliosis. Ann Neurol 1995; 37: 691–702.
- 6Kristoferitsch W. Neurological manifestations of Lyme borreliosis: clinical definition and differential diagnosis. Scand J Infect Dis Suppl 1991; 77: 64–73.
- 7Marques AR. Lyme neuroborreliosis. Continuum (Minneap Minn) 2015; 21(6 Neuroinfectious Disease): 1729–1744.
- 8Pachner AR, Steiner I. Lyme neuroborreliosis: infection, immunity, and inflammation. Lancet Neurol 2007; 6: 544–552.
- 9Stanek G, Wormser GP, Gray J, Strle F. Lyme borreliosis. Lancet 2012; 379: 461–473.
- 10Halperin JJ, Garcia-Monco JC. The human borreliosis: Lyme neuroborreliosis and relapsing fever. In: JC Garcia-Monco, ed. CNS infections: a clinical approach. London, UK: Springer, 2017.
- 11Knudtzen FC, Andersen NS, Jensen TG, Skarphedinsson S. Characteristics and clinical outcome of Lyme neuroborreliosis in a high endemic area, 1995-2014: a retrospective cohort study in Denmark. pp 233–249. Clin Infect Dis 2017; 65: 1489–1495.
- 12Ackermann R, Horstrup P, Schmidt R. Tick-borne meningopolyneuritis (Garin-Bujadoux, Bannwarth). Yale J Biol Med 1984; 57: 485–490.
- 13Kruger H, Reuss K, Pulz M, et al. Meningoradiculitis and encephalomyelitis due to Borrelia burgdorferi: a follow-up study of 72 patients over 27 years. J Neurol 1989; 236: 322–328.
- 14Kruger H, Kohlhepp W, Konig S. Follow-up of antibiotically treated and untreated neuroborreliosis. Acta Neurol Scand 1990; 82: 59–67.
- 15Camponovo F, Meier C. Neuropathy of vasculitic origin in a case of Garin-Boujadoux-Bannwarth syndrome with positive borrelia antibody response. J Neurol 1986; 233: 69–72.
- 16Vallat JM, Hugon J, Lubeau M, et al. Tick-bite meningoradiculoneuritis: clinical, electrophysiologic, and histologic findings in 10 cases. Neurology 1987; 37: 749–753.
- 17Ogrinc K, Lusa L, Lotric-Furlan S, et al. Course and outcome of early European Lyme neuroborreliosis (Bannwarth syndrome): clinical and laboratory findings. Clin Infect Dis 2016; 63: 346–353.
- 18Shah A, O'Horo JC, Wilson JW, et al. An unusual cluster of neuroinvasive Lyme disease cases presenting with Bannwarth syndrome in the Midwest United States. Open Forum Infect Dis 2018; 5:ofx276.
- 19Garcia-Monco JC, Beldarrain MG, Zabalza I. Infectious meningitis with atypical cerebrospinal fluid cells. Eur J Neurol 1997; 4: 188–191.
- 20Garcia-Monco JC, Gomez Beldarrain M, Estrade L. Painful lumbosacral plexitis with increased ESR and Borrelia burgdorferi infection. Neurology 1993; 43: 1269.
- 21Henriksson 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: 337–345.
- 22Garkowski A, Zajkowska J, Zajkowska A, et al. Cerebrovascular manifestations of Lyme neuroborreliosis—a systematic review of published cases. Front Neurol 2017; 8: 146.
- 23Lebas A, Toulgoat F, Saliou G, et al. Stroke due to Lyme neuroborreliosis: changes in vessel wall contrast enhancement. J Neuroimaging 2012; 22: 210–212.
- 24Ruisanchez A, Vicente-Olabarria I, Escalza-Cortina I, et al. Role of MRI in early detection of stroke secondary to neurosyphilis in an elderly patient coinfected with HIV. Neurol Clin Pract 2017; 7: e12–e15.
- 25Ionita CC, Siddiqui AH, Levy EI, et al. Acute ischemic stroke and infections. J Stroke Cerebrovasc Dis 2011; 20: 1–9.
- 26Traisk F, Lindquist L. Optic nerve involvement in Lyme disease. Curr Opin Ophthalmol 2012; 23: 485–490.
- 27Sibony P, Halperin J, Coyle PK, Patel K. Reactive Lyme serology in optic neuritis. J Neuroophthalmol 2005; 25: 71–82.
- 28Kristoferitsch W, Sluga E, Graf M, et al. Neuropathy associated with acrodermatitis chronica atrophicans. Clinical and morphological features. Ann N Y Acad Sci 1988; 539: 35–45.
- 29Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med 1990; 323: 1438–1444.
- 30Halperin JJ. Lyme disease and the peripheral nervous system. Muscle Nerve 2003; 28: 133–143.
- 31Wormser GP, Strle F, Shapiro ED, et al. A critical appraisal of the mild axonal peripheral neuropathy of late neurologic Lyme disease. Diagn Microbiol Infect Dis 2017; 87: 163–167.
- 32Halperin JJ, Little BW, Coyle PK, Dattwyler RJ. Lyme disease: cause of a treatable peripheral neuropathy. Neurology 1987; 37: 1700–1706.
- 33Ackermann R, Gollmer E, Rehse-Kupper B. Progressive Borrelia encephalomyelitis. Chronic manifestation of erythema chronicum migrans disease of the nervous system [in German]. Dtsch Med Wochenschr 1985; 110: 1039–1042.
- 34Mygland A, Ljostad U, Fingerle V, et al. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol 2010; 17: 8–16, e1–e4.
- 35Halperin JJ, Luft BJ, Anand AK, et al. Lyme neuroborreliosis: central nervous system manifestations. Neurology 1989; 39: 753–759.
- 36Halperin JJ, Krupp LB, Golightly MG, Volkman DJ. Lyme borreliosis-associated encephalopathy. Neurology 1990; 40: 1340–1343.
- 37Shadick NA, Phillips CB, Sangha O, et al. Musculoskeletal and neurologic outcomes in patients with previously treated Lyme disease. Ann Intern Med 1999; 131: 919–926.
- 38Cerar D, Cerar T, Ruzic-Sabljic E, et al. Subjective symptoms after treatment of early Lyme disease. Am J Med 2010; 123: 79–86.
- 39Branda JA, Strle K, Nigrovic LE, et al. Evaluation of modified 2-tiered serodiagnostic testing algorithms for early Lyme disease. Clin Infect Dis 2017; 64: 1074–1080.
- 40Moore A, Nelson C, Molins C, et al. Current guidelines, common clinical pitfalls, and future directions for laboratory diagnosis of Lyme disease, United States. Emerg Infect Dis 2016; 22(7).
- 41Marques AR. Laboratory diagnosis of Lyme disease: advances and challenges. Infect Dis Clin North Am 2015; 29: 295–307.
- 42Hammers-Berggren S, Hansen K, Lebech AM, Karlsson M. Borrelia burgdorferi-specific intrathecal antibody production in neuroborreliosis: a follow-up study. Neurology 1993; 43: 169–175.
- 43Steere 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: 1203–1209.
- 44Philipp MT, Wormser GP, Marques AR, et al. A decline in C6 antibody titer occurs in successfully treated patients with culture-confirmed early localized or early disseminated Lyme borreliosis. Clin Diagn Lab Immunol 2005; 12: 1069–1074.
- 45Halperin 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: 91–102.
- 46Eikeland R, Mygland A, Herlofson K, Ljostad U. Risk factors for a non-favorable outcome after treated European neuroborreliosis. Acta Neurol Scand 2013; 127: 154–160.
- 47Ljostad U, Mygland A. Remaining complaints 1 year after treatment for acute Lyme neuroborreliosis; frequency, pattern and risk factors. Eur J Neurol 2010; 17: 118–123.
- 48Berende A, ter Hofstede HJ, Vos FJ, et al. Randomized trial of longer-term therapy for symptoms attributed to Lyme disease. N Engl J Med 2016; 374: 1209–1220.
- 49Krupp 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: 1923–1930.
- 50Klempner MS, Baker PJ, Shapiro ED, et al. Treatment trials for post-Lyme disease symptoms revisited. Am J Med 2013; 126: 665–669.
- 51Feder HM Jr, Johnson BJ, O'Connell S, et al. A critical appraisal of “chronic Lyme disease”. N Engl J Med 2007; 357: 1422–1430.
- 52Pachner AR, Delaney E, O'Neill T, Major E. Inoculation of nonhuman primates with the N40 strain of Borrelia burgdorferi leads to a model of Lyme neuroborreliosis faithful to the human disease. Neurology 1995; 45: 165–172.
- 53Philipp MT, Aydintug MK, Bohm RP Jr, et al. Early and early disseminated phases of Lyme disease in the rhesus monkey: a model for infection in humans. Infect Immun 1993; 61: 3047–3059.
- 54Roberts ED, Bohm RP Jr, Cogswell FB, et al. Chronic lyme disease in the rhesus monkey. Lab Invest 1995; 72: 146–160.
- 55Roberts ED, Bohm RP Jr, Lowrie RC Jr, 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: 722–732.
- 56Garcia-Monco JC, Benach JL. A disconnect between the neurospirochetoses in humans and rodent models of disease. PLoS Pathog 2013; 9: e1003288.
- 57Garcia-Monco JC, Fernandez Villar B, Szczepanski A, Benach JL. Cytotoxicity of Borrelia burgdorferi for cultured rat glial cells. J Infect Dis 1991; 163: 1362–1366.
- 58Garcia-Monco JC, Fernandez-Villar B, Benach JL. Adherence of the Lyme disease spirochete to glial cells and cells of glial origin. J Infect Dis 1989; 160: 497–506.
- 59Garcia-Monco JC, Villar BF, Alen JC, Benach JL. Borrelia burgdorferi in the central nervous system: experimental and clinical evidence for early invasion. J Infect Dis 1990; 161: 1187–1193.
- 60Kuhlow CJ, Garcia-Monco JC, Coleman JL, Benach JL. Murine microglia are effective phagocytes for Borrelia burgdorferi. J Neuroimmunol 2005; 168: 183–187.
- 61Parthasarathy G, Philipp MT. Inflammatory mediator release from primary rhesus microglia in response to Borrelia burgdorferi results from the activation of several receptors and pathways. J Neuroinflammation 2015; 12: 60.
- 62Greenmyer JR, Gaultney RA, Brissette CA, Watt JA. Primary human microglia are phagocytically active and respond to Borrelia burgdorferi with upregulation of chemokines and cytokines. Front Microbiol 2018; 9: 811.
- 63Ramesh G, Alvarez AL, Roberts ED, et al. Pathogenesis of Lyme neuroborreliosis: Borrelia burgdorferi lipoproteins induce both proliferation and apoptosis in rhesus monkey astrocytes. Eur J Immunol 2003; 33: 2539–2550.
- 64Brissette CA, Kees ED, Burke MM, et al. The multifaceted responses of primary human astrocytes and brain microvascular endothelial cells to the Lyme disease spirochete, Borrelia burgdorferi. ASN Neuro 2013; 5: 221–229.
- 65Ramesh G, Benge S, Pahar B, Philipp MT. A possible role for inflammation in mediating apoptosis of oligodendrocytes as induced by the Lyme disease spirochete Borrelia burgdorferi. J Neuroinflammation 2012; 9: 72.
- 66Myers TA, Kaushal D, Philipp MT. Microglia are mediators of Borrelia burgdorferi-induced apoptosis in SH-SY5Y neuronal cells. PLoS Pathog 2009; 5: e1000659.
- 67Baig S, Olsson T, Link H. Predominance of Borrelia burgdorferi specific B cells in cerebrospinal fluid in neuroborreliosis. Lancet 1989; 2: 71–74.
- 68Lunemann JD, Gelderblom H, Sospedra M, et al. Cerebrospinal fluid-infiltrating CD4+ T cells recognize Borrelia burgdorferi lysine-enriched protein domains and central nervous system autoantigens in early Lyme encephalitis. Infect Immun 2007; 75: 243–251.
- 69Bockenstedt LK, Gonzalez DG, Haberman AM, Belperron AA. Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy. J Clin Invest 2012; 122: 2652–2660.
- 70Wormser GP, Nadelman RB, Schwartz I. The amber theory of Lyme arthritis: initial description and clinical implications. Clin Rheumatol 2012; 31: 989–994.
- 71Narayan K, Dail D, Li L, et al. The nervous system as ectopic germinal center: CXCL13 and IgG in Lyme neuroborreliosis. Ann Neurol 2005; 57: 813–823.
- 72Legler DF, Loetscher M, Roos RS, et al. B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5. J Exp Med 1998; 187: 655–660.
- 73Lalor SJ, Segal BM. Lymphoid chemokines in the CNS. J Neuroimmunol 2010; 224: 56–61.
- 74Rupprecht TA, Pfister HW, Angele B, et al. The chemokine CXCL13 (BLC): a putative diagnostic marker for neuroborreliosis. Neurology 2005; 65: 448–450.
- 75Wutte N, Berghold A, Loffler S, et al. CXCL13 chemokine in pediatric and adult neuroborreliosis. Acta Neurol Scand 2011; 124: 321–328.
- 76Schmidt C, Plate A, Angele B, et al. A prospective study on the role of CXCL13 in Lyme neuroborreliosis. Neurology 2011; 76: 1051–1058.
- 77Mullegger RR, Means TK, Shin JJ, et al. Chemokine signatures in the skin disorders of Lyme borreliosis in Europe: predominance of CXCL9 and CXCL10 in erythema migrans and acrodermatitis and CXCL13 in lymphocytoma. Infect Immun 2007; 75: 4621–4628.
- 78Eckman EA, Pacheco-Quinto J, Herdt AR, Halperin JJ. Neuroimmunomodulators in neuroborreliosis and Lyme encephalopathy. Clin Infect Dis 2018; 67: 80–88.
- 79Marra 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: 283–287.
- 80Rupprecht TA, Kirschning CJ, Popp B, et al. Borrelia garinii induces CXCL13 production in human monocytes through Toll-like receptor 2. Infect Immun 2007; 75: 4351–4356.
- 81Senel M, Rupprecht TA, Tumani H, et al. The chemokine CXCL13 in acute neuroborreliosis. J Neurol Neurosurg Psychiatry 2010; 81: 929–933.
- 82Fujimori J, Nakashima I, Kuroda H, et al. Cerebrospinal fluid CXCL13 is a prognostic marker for aseptic meningitis. J Neuroimmunol 2014; 273: 77–84.
- 83Kowarik MC, Cepok S, Sellner J, et al. CXCL13 is the major determinant for B cell recruitment to the CSF during neuroinflammation. J Neuroinflammation 2012; 9: 93.
- 84Leypoldt F, Hoftberger R, Titulaer MJ, et al. Investigations on CXCL13 in anti-N-methyl-D-aspartate receptor encephalitis: a potential biomarker of treatment response. JAMA Neurol 2015; 72: 180–186.
- 85Krumbholz M, Theil D, Cepok S, et al. Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain 2006; 129(pt 1): 200–211.
- 86Rubenstein JL, Wong VS, Kadoch C, et al. CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma. Blood 2013; 121: 4740–4748.
- 87Sellebjerg F, Bornsen L, Khademi M, et al. Increased cerebrospinal fluid concentrations of the chemokine CXCL13 in active MS. Neurology 2009; 73: 2003–2010.
- 88van Burgel ND, Bakels F, Kroes AC, van Dam AP. Discriminating Lyme neuroborreliosis from other neuroinflammatory diseases by levels of CXCL13 in cerebrospinal fluid. J Clin Microbiol 2011; 49: 2027–2030.
- 89Benach JL, Bosler EM, Hanrahan JP, et al. Spirochetes isolated from the blood of two patients with Lyme disease. N Engl J Med 1983; 308: 740–742.
- 90Burgdorfer W, Barbour AG, Hayes SF, et al. Lyme disease—a tick-borne spirochetosis? Science 1982; 216: 1317–1319.
- 91Steere AC, Grodzicki RL, Kornblatt AN, et al. The spirochetal etiology of Lyme disease. N Engl J Med 1983; 308: 733–740.
- 92Sonenshine DE. Range expansion of tick disease vectors in North America: implications for spread of tick-borne disease. Int J Environ Res Public Health 2018; 15. pii: E478.
- 93Fukunaga M, Takahashi Y, Tsuruta Y, et al. Genetic and phenotypic analysis of Borrelia miyamotoi sp. nov., isolated from the ixodid tick Ixodes persulcatus, the vector for Lyme disease in Japan. Int J Syst Bacteriol 1995; 45: 804–810.
- 94Molloy PJ, Telford SR III, Chowdri HR, et al. Borrelia miyamotoi disease in the northeastern United States: a case series. Ann Intern Med 2015; 163: 91–98.
- 95Platonov AE, Karan LS, Kolyasnikova NM, et al. Humans infected with relapsing fever spirochete Borrelia miyamotoi, Russia. Emerg Infect Dis 2011; 17: 1816–1823.
- 96Jiang BG, Jia N, Jiang JF, et al. Borrelia miyamotoi Infections in humans and ticks, northeastern China. Emerg Infect Dis 2018; 24: 236–241.
- 97Krause PJ, Fish D, Narasimhan S, Barbour AG. Borrelia miyamotoi infection in nature and in humans. Clin Microbiol Infect 2015; 21: 631–639.
- 98Boden K, Lobenstein S, Hermann B, et al. Borrelia miyamotoi-associated neuroborreliosis in immunocompromised person. Emerg Infect Dis 2016; 22: 1617–1620.
- 99Hovius JW, de Wever B, Sohne M, et al. A case of meningoencephalitis by the relapsing fever spirochaete Borrelia miyamotoi in Europe. Lancet 2013; 382: 658.
- 100Gugliotta JL, Goethert HK, Berardi VP, Telford SR III. Meningoencephalitis from Borrelia miyamotoi in an immunocompromised patient. N Engl J Med 2013; 368: 240–245.
- 101Dahlgren FS, Heitman KN, Drexler NA, et al. Human granulocytic anaplasmosis in the United States from 2008 to 2012: a summary of national surveillance data. Am J Trop Med Hyg 2015; 93: 66–72.
- 102Dahlgren FS, Heitman KN, Behravesh CB. Undetermined human ehrlichiosis and anaplasmosis in the United States, 2008-2012: a catch-all for passive surveillance. Am J Trop Med Hyg 2016; 94: 299–301.
- 103Park J, Choi KS, Grab DJ, Dumler JS. Divergent interactions of Ehrlichia chaffeensis- and Anaplasma phagocytophilum-infected leukocytes with endothelial cell barriers. Infect Immun 2003; 71: 6728–6733.
- 104Choi KS, Garyu J, Park J, Dumler JS. Diminished adhesion of Anaplasma phagocytophilum-infected neutrophils to endothelial cells is associated with reduced expression of leukocyte surface selectin. Infect Immun 2003; 71: 4586–4594.
- 105Dunn BE, Monson TP, Dumler JS, et al. Identification of Ehrlichia chaffeensis morulae in cerebrospinal fluid mononuclear cells. J Clin Microbiol 1992; 30: 2207–2210.
- 106Ratnasamy N, Everett ED, Roland WE, et al. Central nervous system manifestations of human ehrlichiosis. Clin Infect Dis 1996; 23: 314–319.
- 107Davis LE, Paddock CD, Childs JE. Ehrlichiosis and the nervous system. In: LE Davis, PGE Kennedy, eds. Infectious diseases of the nervous system. Oxford, UK: Butterworth-Heinemann, 2000: 499–520.
- 108McLean DM, Donohue WL. Powassan virus: isolation of virus from a fatal case of encephalitis. Can Med Assoc J 1959; 80: 708–711.
- 109Krow-Lucal ER, Lindsey NP, Fischer M, Hills SL. Powassan virus disease in the United States, 2006-2016. Vector Borne Zoonotic Dis 2018; 18: 286–290.
- 110Piantadosi A, Rubin DB, McQuillen DP, et al. Emerging cases of Powassan virus encephalitis in New England: clinical presentation, imaging, and review of the literature. Clin Infect Dis 2016; 62: 707–713.
- 111Telford SR III, Armstrong PM, Katavolos P, et al. A new tick-borne encephalitis-like virus infecting New England deer ticks, Ixodes dammini. Emerg Infect Dis 1997; 3: 165–170.
- 112Tavakoli NP, Wang H, Dupuis M, et al. Fatal case of deer tick virus encephalitis. N Engl J Med 2009; 360: 2099–2107.
- 113Solomon IH, Spera KM, Ryan SL, et al. Fatal Powassan encephalitis (deer tick virus, lineage II) in a patient with fever and orchitis receiving rituximab. JAMA Neurol 2018; 75: 746–750.
- 114Cavanaugh CE, Muscat PL, Telford SR III, et al. Fatal deer tick virus infection in Maine. Clin Infect Dis 2017; 65: 1043–1046.
- 115Dupuis AP Jr, Peters RJ, Prusinski MA, et al. Isolation of deer tick virus (Powassan virus, lineage II) from Ixodes scapularis and detection of antibody in vertebrate hosts sampled in the Hudson Valley, New York State. Parasit Vectors 2013; 6: 185.
- 116Frost HM, Schotthoefer AM, Thomm AM, et al. Serologic evidence of Powassan virus infection in patients with suspected Lyme disease. Emerg Infect Dis 2017; 23: 1384–1388.
- 117Cimperman J, Maraspin V, Lotric-Furlan S, et al. Concomitant infection with tick-borne encephalitis virus and Borrelia burgdorferi sensu lato in patients with acute meningitis or meningoencephalitis. Infection 1998; 26: 160–164.
- 118Cimperman J, Maraspin V, Lotric-Furlan S, et al. Double infection with tick borne encephalitis virus and Borrelia burgdorferi sensu lato. Wien Klin Wochenschr 2002; 114: 620–622.
- 119Holub M, Kluckova Z, Beran O, et al. Lymphocyte subset numbers in cerebrospinal fluid: comparison of tick-borne encephalitis and neuroborreliosis. Acta Neurol Scand 2002; 106: 302–308.
- 120Engman ML, Lindstrom K, Sallamba M, et al. One-year follow-up of tick-borne central nervous system infections in childhood. Pediatr Infect Dis J 2012; 31: 570–574.
Citing Literature
