title: The mixed blessing of treating symptoms in acute vestibular failure--evidence from a 4-aminopyridine experiment.
abstract: Early symptomatic treatment of acute unilateral vestibulopathy is thought to impede the course of ensuing central vestibular compensation (VC). Despite the great clinical importance of this hypothesis there is no experimental evidence of its validity. The present study addressed this question by investigating the direct effect of 4-aminopyridine (4-AP) on ocular motor and postural symptoms in acute unilateral vestibulopathy as well as its long-term consequences for VC in a rat model of chemical unilateral labyrinthectomy (UL). After UL, one group of Sprague-Dawley rats was treated with 4-AP p.o. (1mg/kg/day), another with 0.9% NaCl solution p.o. for 3days. Behavioural testing for symptoms of vestibular tone imbalance was done 1day before and 1, 2, 3, 5, 7, 9, 15, 21, and 30days after UL. In addition, sequential whole-brain [(18)F]-FDG-μPET was performed before and 1, 3, 7, 15, and 30days after UL to examine and visualize 4-AP-induced modulation of VC. Administration of 4-AP on days 1-3 significantly improved postural imbalance 2h after administration compared to that in controls. This effect was only transient. Remarkably, the 4-AP group had a prolonged and impaired course of postural compensation compared to that of controls. The μPET revealed a significant increase of regional cerebral glucose metabolism (rCGM) in the vestibulocerebellum 2h after administration of 4-AP. However, the 4-AP group exhibited a persistent asymmetry of rCGM after day 3 in the vestibular nuclei and posterolateral thalami. In conclusion, this study confirms the hypothesis that early pharmacological abatement of vestibular symptoms impedes VC.
authors.affiliation: German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University of Munich, Germany; Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Germany.
authors.forename: Roswitha
authors.initials: R
authors.lastname: Beck
authors.affiliation: German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University of Munich, Germany; Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Günther
authors.affiliation: German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University of Munich, Germany; Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Germany.
authors.forename: Guoming
authors.initials: G
authors.lastname: Xiong
authors.affiliation: Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University of Munich, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Potschka
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Böning
authors.affiliation: German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University of Munich, Germany; Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Germany; Munich Cluster of Systems Neurology, SyNergy, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.affiliation: German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University of Munich, Germany; Institute for Clinical Neuroscience, Ludwig-Maximilians-University of Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brandt
authors.affiliation: German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University of Munich, Germany; Department of Neurology, Ludwig-Maximilian-University of Munich, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Jahn
authors.affiliation: German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University of Munich, Germany; Munich Cluster of Systems Neurology, SyNergy, Munich, Germany; Department of Neurology, Ludwig-Maximilian-University of Munich, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Dieterich
authors.affiliation: German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University of Munich, Germany; Department of Neurology, Ludwig-Maximilian-University of Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Strupp
authors.affiliation: German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University of Munich, Germany; Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Germany; Department of Nuclear Medicine, Eberhard Karls University of Tübingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: la Fougère
authors.affiliation: German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University of Munich, Germany; Department of Neurology, Ludwig-Maximilian-University of Munich, Germany. Electronic address: andreas.zwergal@med.uni-muenchen.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zwergal
mesh_terms: D015761:4-Aminopyridine / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D019788:Fluorodeoxyglucose F18; D008297:Male; D009759:Nystagmus, Pathologic / Q000188:drug therapy* / Q000209:etiology; D049268:Positron-Emission Tomography; D004856:Postural Balance / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012678:Sensation Disorders / Q000209:etiology / Q000517:prevention & control*; D012720:Severity of Illness Index; D013223:Statistics as Topic; D013997:Time Factors; D015837:Vestibular Diseases / Q000150:complications* / Q000209:etiology / Q000473:pathology; D014722:Vestibule, Labyrinth / Q000601:surgery
chemical_list: D026902:Potassium Channel Blockers; D019788:Fluorodeoxyglucose F18; D015761:4-Aminopyridine
keywords: Pharmacological treatment; Positron emission tomography; Unilateral labyrinthectomy; Vestibular compensation