title: Central Autonomic Dysfunction Delays Recovery of Fingolimod Induced Heart Rate Slowing.
abstract: BACKGROUND
  In multiple sclerosis (MS) patients, Fingolimod may induce prolonged heart-rate slowing which might be caused by MS-related central autonomic lesions.
  
  
  OBJECTIVE
  To evaluate whether MS-patients with prolonged heart-rate slowing (> six hours) upon Fingolimod show cardiovascular-autonomic dysfunction before Fingolimod-initiation.
  
  
  METHODS
  Before Fingolimod-initiation, we recorded electrocardiographic RR-intervals (RRIs) and blood-pressure (BP) at rest, upon standing-up, during metronomic deep-breathing, Valsalva-maneuver, and "sustained-handgrip-exercise" in 21 patients with relapsing-remitting MS, and 20 healthy persons. We calculated sympathetic and parasympathetic cardiovascular parameters, including low- (LF) and high-frequency (HF) powers of RRI- and BP-oscillations, RRI-RMSSDs, RRI- and BP-changes during handgrip-exercise, parasympathetic heart-rate-slowing in relation to BP-overshoot after Valsalva-strain-release. We compared values of healthy persons and patients with and without prolonged heart-rate slowing after Fingolimod-initiation (ANOVA; significance: p<0.05).
  
  
  RESULTS
  Upon Fingolimod-initiation, 7/21 patients had prolonged HR-slowing. Before Fingolimod, these patients had higher resting BP and higher BP increase during handgrip-exercise than had the other participants (p<0.05). They did not reduce parasympathetic HR-parameters upon standing-up. After Valsalva-strain-release, their parasympathetic HR-slowing in response to BP-overshoot was four times higher than in the other participants (p<0.05).
  
  
  CONCLUSIONS
  The autonomic cardiovascular dysfunction in MS-patients with delayed HR-re-acceleration upon Fingolimod-initiation suggests that MS-related central autonomic lesions compromise HR-re-acceleration upon Fingolimod.
  
  
  BACKGROUND
  German Clinical Trial Register DRKS00004548 http://drks-neu.uniklinik-freiburg.de/drks_web/setLocale_EN.do.
authors.affiliation: Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Max J
authors.initials: MJ
authors.lastname: Hilz
authors.affiliation: Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Tassanai
authors.initials: T
authors.lastname: Intravooth
authors.affiliation: Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Moeller
authors.affiliation: Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Ruihao
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: De-Hyung
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Koehn
authors.affiliation: Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Linker
mesh_terms: D000328:Adult; D001341:Autonomic Nervous System / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001919:Bradycardia / Q000139:chemically induced* / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D018737:Hand Strength / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000503:physiopathology; D014636:Valsalva Maneuver
chemical_list: D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride