title: The effects of vagus nerve stimulation on pro- and anti-inflammatory cytokines in children with refractory epilepsy: an exploratory study.
abstract: OBJECTIVE
  The vagus nerve has important immunological and anti-inflammatory actions that might be relevant to the beneficial effects of vagus nerve stimulation (VNS). Therefore, we conducted an exploratory study on VNS effects on cytokine levels in plasma and cerebrospinal fluid of children suffering from refractory epilepsy. Moreover, as predictors of the response are lacking, we also aimed to determine if cytokine changes predict the clinical response.
  
  
  METHODS
  VNS was performed according to a randomized double-blind design: plasma levels were compared between patients who received 20 weeks of high output (therapeutic) (n = 21) or low output (active control) stimulation (n = 20). Thereupon, all patients received high output stimulation for another 19 weeks; levels during this period were compared to baseline. Interictal interleukin-1β, interleukin-6, and interleukin-10 were determined by ELISA.
  
  
  RESULTS
  No significant changes were found between high and low output groups and between the last 19 weeks of stimulation and baseline. Changes in interleukin-1β correlated with improved IQ (τ = 0.42, p < 0.01). Lower baseline plasma levels of interleukin-6 were associated with more seizure frequency reduction [R(2) = 0.105 (1, 35), p = 0.050].
  
  
  CONCLUSIONS
  Interictal cytokine levels were not altered by VNS but baseline interleukin-6 predicted the clinical response. In the future, patient selection may be aided by determination of the cytokine profile of the patient.
authors.affiliation: School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands. mwaalbers@gmail.com
authors.forename: Marlien Wilhelmina
authors.initials: MW
authors.lastname: Aalbers
authors.forename: Sylvia
authors.initials: S
authors.lastname: Klinkenberg
authors.forename: Kim
authors.initials: K
authors.lastname: Rijkers
authors.forename: Pauline
authors.initials: P
authors.lastname: Verschuure
authors.forename: Alfons
authors.initials: A
authors.lastname: Kessels
authors.forename: Albert
authors.initials: A
authors.lastname: Aldenkamp
authors.forename: Johan
authors.initials: J
authors.lastname: Vles
authors.forename: Marian
authors.initials: M
authors.lastname: Majoie
mesh_terms: D000293:Adolescent; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D004311:Double-Blind Method; D004827:Epilepsy / Q000276:immunology / Q000628:therapy*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D008297:Male; D016896:Treatment Outcome; D055536:Vagus Nerve Stimulation / Q000379:methods*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators