title: Neurologic abnormalities and cerebrospinal fluid changes in horses administered fumonisin B1 intravenously.
abstract: The objective of this experiment was to characterize a dose-dependent toxic effect of fumonisin B1 (FB1) and to document initial neurologic signs, clinical progression, and terminal cerebrospinal fluid (CSF) changes in horses administered FB1 IV. Seventeen healthy horses were administered 0.00 (n = 4), 0.01 (n = 3), 0.05 (n = 3), 0.10 (n = 3), or 0.20 mg (n = 4) of purified FB1 IV q24h. When neurologic abnormalities observed by a masked observer became severe, atlanto-occipital CSF taps were performed and CSF pressure, cell count, cytology, protein, albumin and glucose concentrations, and creatine kinase activity were measured. Changes in CSF and number of days to 1st observation of neurologic abnormalities were compared between doses by ANOVA, with the level of significance set at P < .05. Control horses and low-dose horses (0.01 mg/kg) remained neurologically normal. In higher dose FB1-treated horses (n = 10), initial clinical signs (days 4-10) included hindlimb ataxia, delayed forelimb placing, and decreased tongue tone and movement. Hindlimb and trunkal ataxia, depression, hyperesthesia, and intermittent dementia gradually became apparent. When data from all horses with neurologic abnormalities were pooled (0.05-0.20 mg/kg FB1), mild clinical signs (mean day 6.3) occurred significantly earlier than did more severe (mean day 8.9) clinical signs (P = .009). Neurologic horses had high CSF protein, albumin, and IgG concentrations and increased albumin quotients (P < .05). It was concluded that FB1-induced neurologic and CSF changes in a dose-dependent manner, with a no-observable-limit of 0.01 mg FB1/kg IV q24h for 28 days. The neurologic and CSF changes were consistent with vasogenic cerebral edema.
authors.affiliation: University of Illinois at Urbana-Champaign, College of Veterinary Medicine, Department of Veterinary Clinical Medicine, 1008 W Hazelwood Drive, Urbana, IL 61802, USA. jforeman@cvm.uiuc.edu
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Foreman
authors.forename: Peter D
authors.initials: PD
authors.lastname: Constable
authors.forename: Amy L
authors.initials: AL
authors.lastname: Waggoner
authors.forename: Michel
authors.initials: M
authors.lastname: Levy
authors.forename: R M
authors.initials: RM
authors.lastname: Eppley
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Smith
authors.forename: Mike E
authors.initials: ME
authors.lastname: Tumbleson
authors.forename: Wanda M
authors.initials: WM
authors.lastname: Haschek
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004678:Encephalomalacia / Q000139:chemically induced / Q000503:physiopathology / Q000662:veterinary*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D037341:Fumonisins / Q000008:administration & dosage / Q000633:toxicity*; D006734:Horse Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000503:physiopathology*; D006736:Horses; D007262:Infusions, Intravenous / Q000662:veterinary; D008297:Male; D009183:Mycotoxins / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D004791:Enzyme Inhibitors; D037341:Fumonisins; D009183:Mycotoxins; C056933:fumonisin B1