MEDICINE POTPOURRI: NEUROLOGY, FOALS, MUSCLES, AND THE GUT


that previously reported7,9 and equivalent to use of a nose net in this study, although 20% fewer respon- dents had tried them. Again, adverse effects not previously reported such as “spookiness” and stum- bling due to presumed reduced vision were frequent and observed in over 1


⁄5 of horses using face masks.


Whereas observed less frequently than with use of a nose net, these reported adverse effects were of a more disruptive nature. A surprisingly large percentage of horses (21%;


18/84) were reported to derive some benefit from the use of fly control, in contrast to only 2% previously described.7 The current study population may have comprised more mildly affected horses than the aforementioned study,7 despite 2


⁄3 of owners describ-


ing their horse’s headshaking as “severe” or “very severe.” It is likely that a positive outcome rate of approximately 20% is heavily influenced by re- sponse bias, as no treatment achieved lower than 18% positive outcome. Such bias may have arisen from multiple sources including the difficulty in ob- jective assessment of headshaking and any treat- ment response, a proxy-placebo effect, the phenomena of spontaneous and seasonal remission, fluctuation of clinical signs, regression to the mean, any contemporaneous treatments, and recall bias. Whereas such bias limits interpretation of all ob- served responses to treatments, the variability in reported outcomes gives confidence that a genuine treatment effect, above and beyond any bias, was noted for some treatments. The positive response of over 50% (17/31) of head- shakers to corticosteroid therapy was also unex- pected given the documented aberrant trigeminal nerve activity5 and the failure of a recent blinded, clinical trial of pulsed high dose dexamethasone therapy to have any effect on idiopathic headshak- ing.15 Whereas not a first-line treatment for neu- ropathic pain, corticosteroids have been shown to reduce spontaneous discharge in injured nerves and might be useful as adjunct therapy.16 Although nerve injury is not suspected in idiopathic head- shaking, a reduced threshold for activation of the trigeminal nerve has been documented5 and cortico- steroids might act to decrease such aberrant activ- ity. It is also possible that, in the responding subset of headshaking horses, there was a degree of low grade inflammation or allergy contributing to clinical signs observed by owners. As prolonged, ongoing management of headshaking is usually re- quired, corticosteroids are unlikely to be useful as a therapeutic option due to the risk of serious adverse effects such as laminitis. One-third of owners reported general antihista-


mine treatment improved their horse’s headshaking (12/36). Such improvement may suggest an aller- gic component to headshaking in these horses; how- ever, the reported effect may be largely due to bias as previously discussed. A positive response to cy- proheptadine treatment was observed in approxi- mately 50% of horses (14/29). Cyproheptadine is a


first generation antihistamine with additional anti- cholinergic, antiserotonergic, calcium channel block- ing, and local anesthetic activity,17 which is used to treat human vascular headaches. Previous reports describing the response of headshaking to cyprohep- tadine treatment has varied widely, from no im- provement4,18 to 70%.7 Such variation in efficacy is difficult to explain. The percentage of horses with a photic component to their headshaking is variable across these studies (none4; 39%, current study; 60%7), which may be relevant in responsiveness to cyproheptadine. Inappropriate dosage may have affected treatment outcome with cyproheptadine in the current study as, whereas only 2 owners re- ported using an inadequate dosage, many owners reported they did not know or omitted administra- tion details. Adverse effects such as lethargy and drowsiness were noted in almost 50% of horses treated with cyproheptadine, which is likely to limit its use in ridden horses. Carbamazepine, an anticonvulsant, which stabi-


lizes voltage-gated sodium channels, had one of the lowest positive outcome rates of all treatments (25%; 2/8) and, therefore, does not appear to be an effica- cious treatment for headshaking. Additionally, negative side effects were reported in 1


⁄3 of treated


horses. Although carbamazepine is the treatment of choice for human trigeminal neuralgia,19 the pharmacokinetics of this drug in horses is unknown, which may explain its lack of effect. Additionally, recent trigeminal electrophysiological data suggests the etiopathogenesis of equine headshaking and hu- man trigeminal neuralgia may differ.5 NSAIDs were also poorly efficacious (22%; 4/22) as would be expected in the treatment of a neuropathic condi- tion. The noted response in 4 horses may be due to the aforementioned biases. Melatonin reduced headshaking in almost half


(47%; 8/17) of horses in this study. The hypothesis for melatonin treatment of headshaking is that a late afternoon (5 PM) dose of melatonin artificially manipulates photoperiod such that, biologically, the horse remains in winter. Approximately 40% of treated horses did not shed their coat due to this phenomenon. Therapy is proposed to be most suc- cessful when melatonin is started before the onset of spring for seasonal headshakers7and, therefore, ini- tiation of therapy when the horse was already head- shaking may have reduced efficacy. A positive outcome in the two horses given melatonin inappro- priately and the fact that suppression of the vernal increase in gonadotropins did not reduce headshak- ing20 may question the proposed rationale. How- ever, melatonin is also able to modulate pain, including neuropathic pain, via various antinocice- ptive effects including activation of opioid receptors, inhibition of pro-inflammatory cytokine production,


modulation of GABAA receptor function and acting as a free radical scavenger.21 Melatonin receptors have been identified in the trigeminal ganglion and trigeminal nucleus of mammals22 and interestingly,


AAEP PROCEEDINGS  Vol. 60  2014 181


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