Neurologic abnormalities and cerebrospinal fluid changes in horses administered fumonisin B₁ intravenously

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 FB ₁-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.