The mixed blessing of treating symptoms in acute vestibular failure — Evidence from a 4-aminopyridine experiment

• Published in: Experimental neurology 2014-11, Vol.261, p.638-645
• Main Authors: Beck, Roswitha, Günther, Lisa, Xiong, Guoming, Potschka, Heidrun, Böning, Guido, Bartenstein, Peter, Brandt, Thomas, Jahn, Klaus, Dieterich, Marianne, Strupp, Michael, la Fougère, Christian, Zwergal, Andreas
• Format: Article
• Language: English
• Subjects: 4-Aminopyridine - therapeutic use; Animals; Brain - diagnostic imaging; Disease Models, Animal; Drug Administration Schedule; Fluorodeoxyglucose F18; Male; Nystagmus, Pathologic - drug therapy; Nystagmus, Pathologic - etiology; Pharmacological treatment; Positron emission tomography; Postural Balance - drug effects; Potassium Channel Blockers - therapeutic use; Rats; Rats, Sprague-Dawley; Sensation Disorders - etiology; Sensation Disorders - prevention & control; Severity of Illness Index; Statistics as Topic; Time Factors; Unilateral labyrinthectomy; Vestibular compensation; Vestibular Diseases - complications; Vestibular Diseases - etiology; Vestibular Diseases - pathology; Vestibule, Labyrinth - surgery
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2014.08.013

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 [18F]-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. •4-Aminopyridine (4-AP) improves postural control in acute unilateral vestibulopathy.•However, early treatment with 4-AP impedes ensuing vestibular compensation (VC).•Early 4-AP treatment induces prolonged asymmetries in cerebral vestibular networks.•Individual symptomatic pressure in acute vestibulopathy drives subsequent VC.•Symptomatic treatment should only be given on demand and for a short time.