Neuroimmunomodulators in neuroborreliosis and lyme encephalopathy

Elizabeth A. Eckman, Javier Pacheco-Quinto, Aimee R. Herdt, John Halperin

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background. Lyme encephalopathy, characterized by nonspecific neurobehavioral symptoms including mild cognitive difficulties, may occur in patients with systemic Lyme disease and is often mistakenly attributed to central nervous system (CNS) infection. Identical symptoms occur in many inflammatory states, possibly reflecting the effect of systemic immune mediators on the CNS. Methods. Multiplex immunoassays were used to measure serum and cerebrospinal fluid (CSF) cytokines in patients with or without Lyme disease to determine if there are specific markers of active CNS infection (neuroborreliosis), or systemic inflammatory mediators associated with neurobehavioral syndromes. Results. CSF CXCL13 levels were elevated dramatically in confirmed neuroborreliosis (n = 8), less so in possible neuroborreliosis (n = 11) and other neuroinflammatory conditions (n = 44). Patients with Lyme (n = 63) or non-Lyme (n = 8) encephalopathy had normal CSF findings, but had elevated serum levels of interleukins 7, 17A, and 17F, thymic stromal lymphopoietin and macrophage inflammatory protein-α. Conclusions. CSF CXCL13 is a sensitive and specific marker of neuroborreliosis in individuals with Borrelia-specific intrathecal antibody production. However, it does not distinguish individuals strongly suspected of having neuroborreliosis, but lacking confirmatory intrathecal antibodies, from those with other neuroinflammatory conditions. Patients with mild cognitive symptoms occurring during acute Lyme disease, and/or after appropriate treatment, have normal CSF but elevated serum levels of T-helper 17 markers and T-cell growth factors, which are also elevated in patients without Lyme disease but with similar symptoms. In the absence of CSF abnormalities, neurobehavioral symptoms appear to be associated with systemic inflammation, not CNS infection or inflammation, and are not specific to Lyme disease.

Original languageEnglish (US)
Pages (from-to)80-88
Number of pages9
JournalClinical Infectious Diseases
Volume67
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Lyme Neuroborreliosis
Brain Diseases
Lyme Disease
Cerebrospinal Fluid
Central Nervous System Infections
Interleukin-17
Serum
Inflammation
Borrelia
Macrophage Inflammatory Proteins
Interleukin-7
Neurobehavioral Manifestations
Acute Disease
Immunoassay
Antibody Formation
Interleukin-2
Central Nervous System
Cytokines
Antibodies

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Eckman, Elizabeth A. ; Pacheco-Quinto, Javier ; Herdt, Aimee R. ; Halperin, John. / Neuroimmunomodulators in neuroborreliosis and lyme encephalopathy. In: Clinical Infectious Diseases. 2018 ; Vol. 67, No. 1. pp. 80-88.
@article{65e0a37e5b2c4ec89d7d0b47b33424f9,
title = "Neuroimmunomodulators in neuroborreliosis and lyme encephalopathy",
abstract = "Background. Lyme encephalopathy, characterized by nonspecific neurobehavioral symptoms including mild cognitive difficulties, may occur in patients with systemic Lyme disease and is often mistakenly attributed to central nervous system (CNS) infection. Identical symptoms occur in many inflammatory states, possibly reflecting the effect of systemic immune mediators on the CNS. Methods. Multiplex immunoassays were used to measure serum and cerebrospinal fluid (CSF) cytokines in patients with or without Lyme disease to determine if there are specific markers of active CNS infection (neuroborreliosis), or systemic inflammatory mediators associated with neurobehavioral syndromes. Results. CSF CXCL13 levels were elevated dramatically in confirmed neuroborreliosis (n = 8), less so in possible neuroborreliosis (n = 11) and other neuroinflammatory conditions (n = 44). Patients with Lyme (n = 63) or non-Lyme (n = 8) encephalopathy had normal CSF findings, but had elevated serum levels of interleukins 7, 17A, and 17F, thymic stromal lymphopoietin and macrophage inflammatory protein-α. Conclusions. CSF CXCL13 is a sensitive and specific marker of neuroborreliosis in individuals with Borrelia-specific intrathecal antibody production. However, it does not distinguish individuals strongly suspected of having neuroborreliosis, but lacking confirmatory intrathecal antibodies, from those with other neuroinflammatory conditions. Patients with mild cognitive symptoms occurring during acute Lyme disease, and/or after appropriate treatment, have normal CSF but elevated serum levels of T-helper 17 markers and T-cell growth factors, which are also elevated in patients without Lyme disease but with similar symptoms. In the absence of CSF abnormalities, neurobehavioral symptoms appear to be associated with systemic inflammation, not CNS infection or inflammation, and are not specific to Lyme disease.",
author = "Eckman, {Elizabeth A.} and Javier Pacheco-Quinto and Herdt, {Aimee R.} and John Halperin",
year = "2018",
month = "1",
day = "1",
doi = "10.1093/cid/ciy019",
language = "English (US)",
volume = "67",
pages = "80--88",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "1",

}

Neuroimmunomodulators in neuroborreliosis and lyme encephalopathy. / Eckman, Elizabeth A.; Pacheco-Quinto, Javier; Herdt, Aimee R.; Halperin, John.

In: Clinical Infectious Diseases, Vol. 67, No. 1, 01.01.2018, p. 80-88.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neuroimmunomodulators in neuroborreliosis and lyme encephalopathy

AU - Eckman, Elizabeth A.

AU - Pacheco-Quinto, Javier

AU - Herdt, Aimee R.

AU - Halperin, John

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background. Lyme encephalopathy, characterized by nonspecific neurobehavioral symptoms including mild cognitive difficulties, may occur in patients with systemic Lyme disease and is often mistakenly attributed to central nervous system (CNS) infection. Identical symptoms occur in many inflammatory states, possibly reflecting the effect of systemic immune mediators on the CNS. Methods. Multiplex immunoassays were used to measure serum and cerebrospinal fluid (CSF) cytokines in patients with or without Lyme disease to determine if there are specific markers of active CNS infection (neuroborreliosis), or systemic inflammatory mediators associated with neurobehavioral syndromes. Results. CSF CXCL13 levels were elevated dramatically in confirmed neuroborreliosis (n = 8), less so in possible neuroborreliosis (n = 11) and other neuroinflammatory conditions (n = 44). Patients with Lyme (n = 63) or non-Lyme (n = 8) encephalopathy had normal CSF findings, but had elevated serum levels of interleukins 7, 17A, and 17F, thymic stromal lymphopoietin and macrophage inflammatory protein-α. Conclusions. CSF CXCL13 is a sensitive and specific marker of neuroborreliosis in individuals with Borrelia-specific intrathecal antibody production. However, it does not distinguish individuals strongly suspected of having neuroborreliosis, but lacking confirmatory intrathecal antibodies, from those with other neuroinflammatory conditions. Patients with mild cognitive symptoms occurring during acute Lyme disease, and/or after appropriate treatment, have normal CSF but elevated serum levels of T-helper 17 markers and T-cell growth factors, which are also elevated in patients without Lyme disease but with similar symptoms. In the absence of CSF abnormalities, neurobehavioral symptoms appear to be associated with systemic inflammation, not CNS infection or inflammation, and are not specific to Lyme disease.

AB - Background. Lyme encephalopathy, characterized by nonspecific neurobehavioral symptoms including mild cognitive difficulties, may occur in patients with systemic Lyme disease and is often mistakenly attributed to central nervous system (CNS) infection. Identical symptoms occur in many inflammatory states, possibly reflecting the effect of systemic immune mediators on the CNS. Methods. Multiplex immunoassays were used to measure serum and cerebrospinal fluid (CSF) cytokines in patients with or without Lyme disease to determine if there are specific markers of active CNS infection (neuroborreliosis), or systemic inflammatory mediators associated with neurobehavioral syndromes. Results. CSF CXCL13 levels were elevated dramatically in confirmed neuroborreliosis (n = 8), less so in possible neuroborreliosis (n = 11) and other neuroinflammatory conditions (n = 44). Patients with Lyme (n = 63) or non-Lyme (n = 8) encephalopathy had normal CSF findings, but had elevated serum levels of interleukins 7, 17A, and 17F, thymic stromal lymphopoietin and macrophage inflammatory protein-α. Conclusions. CSF CXCL13 is a sensitive and specific marker of neuroborreliosis in individuals with Borrelia-specific intrathecal antibody production. However, it does not distinguish individuals strongly suspected of having neuroborreliosis, but lacking confirmatory intrathecal antibodies, from those with other neuroinflammatory conditions. Patients with mild cognitive symptoms occurring during acute Lyme disease, and/or after appropriate treatment, have normal CSF but elevated serum levels of T-helper 17 markers and T-cell growth factors, which are also elevated in patients without Lyme disease but with similar symptoms. In the absence of CSF abnormalities, neurobehavioral symptoms appear to be associated with systemic inflammation, not CNS infection or inflammation, and are not specific to Lyme disease.

UR - http://www.scopus.com/inward/record.url?scp=85058650684&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058650684&partnerID=8YFLogxK

U2 - 10.1093/cid/ciy019

DO - 10.1093/cid/ciy019

M3 - Article

VL - 67

SP - 80

EP - 88

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 1

ER -