Episodic Events - Frightening to the Owner But Often Not Seen by the Veterinarian

True episodic events wherein the horse is totally normal between events are not so common in equine practice, and, because they are often not witnessed by veterinarians, they conjure up hobgoblin and wacky diagnoses – strokes and brain tumors in particular. The principal disorders covered here will be epilepsy [recurrent seizures] and sleep disorders in horses. As with other species, video capture of events is a powerful tool in making the diagnosis. Therapies are available but should only be undertaken after careful considerations. The potential confounding influences of third parties such as Insurance Companies on clinical management must not be underestimated.

Introduction

Seizures, abnormal sleep patterns and syncope, can be difficult to distinguish apart. The last of these, occurring in the absence of heart failure, is incredibly rare but the first 2 are quite distinguishable if observed. A [24-hour] video recording can be useful to capture suspected episodes of sleep and seizures when they are not overt.

Sleep Disorders

Sleep disorders in humans can been divided into narcolepsy [with cataplexy], narcolepsy without cataplexy and idiopathic hypersomnia. Narcolepsy occurs in 0.02-0.15% of the population and patients typically demonstrate excessive diurnal sleep, flaccid paralysis with somatic areflexia [cataplexy], sleep paralysis, sleep-onset hallucinations and nocturnal disrupted sleep. Strict EEG and EOG criteria, including the early onset of rapid eye movement (REM) at the beginning instead of the middle of a sleep cycle, are in place for confirming the diagnosis and distinguishing narcolepsy from narcolepsy without cataplexy and from idiopathic hypersomnia. A familial form occurs in dogs and humans and in the latter it is associated with the genetic allele HLA-DQβ1-0602. Narcolepsy without cataplexy shares the same electrophysiological abnormalities and associated signs but there is no demonstrable cataplexy. Purely excessive daytime sleep attacks [also referred to as “unwanted siestas”] occur in idiopathic hypersomnia.

Over the past few years great strides have been made in unraveling the pathophysiology of narcolepsy in humans, mice and dogs. Two novel neuropeptides, hypocretins [orexins] 1 and 2, were found to be specifically expressed in certain hypothalamic neurons and defective hypocretin signaling was related to both familial and sporadic narcolepsy. A mutation in the hypocretin receptor-2 gene was present in dogs with familial narcolepsy although they had normal levels of hypocretins in their CSF and hypothalamus. Neurotransmission through hypocretin-1 was likely to be intact indicating that defective hypocretin-2 function is more important in producing narcolepsy in that model. In contrast, dogs with sporadic narcolepsy had no expressed hypocretins in the CSF or brain tissue.

In the sporadic and some familial forms of the disease various pieces of evidence indicate that there may be an autoimmune attack on hypocretin-producing neurons and decreased hypocretin- expressing neurons in the hypothalamus have been reported. Attempts to identify a neural autoantibody in canine and human narcolepsy have been unsuccessful. Recently, evidence for the presence of a functional, IgG autoantibody, that upregulates cholinergic activity [being a characteristic of narcolepsy], being present in serum of narcoleptic humans and not in controls, has been presented . Further evidence that the immune system plays a role in canine genetically dependant narcolepsy has been published. This study found that immunosuppressive and anti-inflammatory drugs delayed the onset and severity of narcolepsy and cataplexy in treated dogs compared to controls. Results of attempts at treating narcolepsy in dogs with predisolone and systemic and intrathecal hypocretin-1 have been poor, perhaps because of depleted hypothalamic neurons. Although using immipramine for the narcolepsy and yohimbine [an α-2 antagonist to activate adrenergic transmission] for the cataplexy showed promise. [...]