Seizures are typically unpredictable and unprovoked. In humans, provoked seizures that occur in response to specific sensory stimuli have been termed reflex seizures, sensory-evoked epileptic seizures, stimulus-triggered seizures, provoked seizures, and triggered seizures.1–5 Visually induced (ie, photosensitive) seizures, such as those occurring in response to video games, strobe lights, and computer visual displays, are the most commonly described form of reflex seizures in human patients.1,6–8 However, other forms of reflex epilepsy have been described, including seizures triggered by reading, performing mathematical calculations, eating, smelling specific odors, hearing specific sounds, and performing specific movements.2,9,10
Reflex seizures have a short duration from stimulus to seizure onset (seconds), and the stimulus is specific.2,3 In humans, they are considered true epileptic, rather than psychogenic, seizures. Whereas reflex seizures do not usually occur in the absence of the stimulus, some affected individuals with a concurrent diagnosis of another form of epilepsy may have unprovoked or nonreflex seizures in addition to reflex seizures.11 As is the case for unprovoked or nonreflex seizures, reflex seizures can be focal or generalized in nature.
Reflex epilepsy is rarely discussed in veterinary medicine. Webb et al12 describe auditory and visual stimuli as triggers for seizures in a dog with Lafora disease, an inherited, late-onset form of progressive myoclonic epilepsy. One mistitled report was actually a review of reflex epilepsy.13 In a 2010 review, Thomas14 indicated that reflex seizures in dogs could be triggered by sounds (eg, lawnmower engine), automobile rides, and visits to veterinary offices. He defined reflex seizures as those “that can be provoked by specific stimuli or events.”
Given the paucity of information on reflex seizures and reflex epilepsy in dogs, the objective of the study reported here was to identify dogs with reflex epilepsy (ie, dogs with seizure activity triggered by specific situations, events, or locations) and determine the outcome of any treatments for such seizures.
Materials and Methods
Clinical cases were identified through a review of discussions by veterinarians participating in the Veterinary Information Network online community15 for the years 2000 through 2014. To identify potential cases, archived discussions were searched by species (dog) and by the following keywords or phrases: reflex epilepsy, reflex seizure, situational seizure, location seizure, seizure veterinary clinic, seizure groomers, and seizure boarding.
Data obtained for dogs considered for inclusion in the study consisted of signalment (including age at the onset of reflex epilepsy), seizure stimulus or stimuli (veterinary clinic, grooming facility, boarding facility, or other), how often the stimulus had triggered seizure activity, the time period over which reflex epilepsy had been present, whether the dog had seizures not induced by a specific location or situation, whether there was evidence of other neurologic signs or other diseases that might explain the seizures, and how the reflex epilepsy was managed (medications, avoidance of stimuli, or other). Case material was independently reviewed by 2 investigators (LS and RS) to determine that sufficient information was present and that the dog experienced a seizure consistently when exposed to the stimulus. Disagreements were resolved by consensus following joint review of the case material and discussion.
Results
Forty-three dogs were included in the study. Review of discussion threads indicated that these cases had been discussed by participants in the Veterinary Information Network online community either because the veterinarian was unaware of stimulus-sensitive or reflex seizures or because attempts to prevent the seizures had been ineffective.
Of the 43 dogs included in the study, 36 (83.7%) were purebreds and 5 (11.6%) were of mixed breeding. For the remaining 2 (4.7%) dogs, the breed description was incomplete (“pit bull”; n = 1) or unrecorded (1). Represented breeds included Cocker Spaniels (n = 4), Dachshunds (4), Siberian Huskies (4), Labrador Retrievers (4), Beagles (2), Brittanys (2), Chihuahuas (2), Keeshonds (2), Miniature Pinschers (2), Shih Tzus (2), and 1 each of Border Collie, American Eskimo Dog, German Shepherd Dog, Havanese, Newfoundland, Shetland Sheepdog, unspecified (English or Welsh) Springer Spaniel, and Yorkshire Terrier.
Age at onset of reflex epilepsy ranged from 3 months to 11 years (mean, 5.38 years; median, 5 years). Of the 43 dogs, 23 (53.5%) were female (17 spayed, 2 sexually intact, and 4 with unknown reproductive status) and 17 (39.5%) were male (11 castrated, 4 sexually intact, and 2 with unknown reproductive status). Sex was not recorded for the remaining 3 (7.0%) dogs. All dogs were described as having seizure activity when exposed to a specific stimulus. Twenty-one of 43 dogs had manifested such seizure activity for > 1 year (range, 1 to 4 years), and 10 had manifested such activity for < 1 year. For 9 dogs, duration of seizure activity was reported as months to years, and for the remaining 3 dogs, duration of seizure activity was not specified. Concurrent neurologic signs or abnormalities were not described for any of the dogs. However, 8 of the 43 (18.6%) dogs reportedly had seizures at times with no known trigger stimulus; such seizures were stated or presumed to be primary or idiopathic epilepsy on the basis of an absence of interictal neurologic signs. No dogs underwent brain imaging or CSF analysis although 1 was referred to a neurologist for examination.
The number of specific situations described as triggering a seizure varied. Nineteen of the 43 (44%) dogs were reported to experience seizures in response to only 1 specific stimulus, an additional 19 (44%) dogs were reported to experience seizures in response to 2 different stimuli, and 5 (12%) dogs were reported to experience seizures in response to > 3 stimuli. Five dogs that had seizures triggered by 1 specific stimulus subsequently developed seizures triggered by a different stimulus.
Most of the stimuli that triggered reflex seizures were visits to a specific location such as a veterinary clinic (35 dogs), a grooming facility (24 dogs), a boarding facility (13 dogs), a pet store (2 dogs), or a friend's home (1 dog). Other specific stimuli that triggered seizures included car rides (3 dogs), putting the dog in a bathtub (2 dogs), having visitors in the house (1 dog), or approaching the driveway or vehicles (1 case). Unspecified fearful or stressful situations were noted to trigger seizures in 4 dogs.
Eight (18.6%) dogs had a history of seizures occurring at times unassociated with stimuli-specific seizures. Seven of these dogs were receiving a variety of maintenance AEDs (phenobarbital [n = 4], zonisamide [1], bromide [1], and bromide and phenobarbital [1]), which were described as adequately controlling the presumed primary (idiopathic) epilepsy but which did not prevent reflex seizures. Specific drug dosages were generally not provided. Five of 43 additional dogs were receiving maintenance AEDs (phenobarbital [n = 2], zonisamide [2], and phenobarbital and bromide [1]) to specifically treat the reflex epilepsy. However, the AEDs were described as ineffective in preventing reflex seizures in all 5 dogs. Thus, maintenance AEDs were administered to 12 of the 43 dogs and reportedly failed to prevent stimulus-specific seizures in all 12 dogs.
Dogs were reported to have received a variety of drugs immediately prior to encountering the seizure stimulus or situation, although specific drug dosages were not provided in most instances. Diazepam was administered PO to 16 of 43 dogs prior to exposure and was reportedly unsuccessful in preventing the reflex seizure in 15 dogs and moderately successful in 1 dog. Diazepam was administered per rectum to 1 dog on 1 occasion and apparently prevented the reflex seizure but caused the dog to become overly anxious. Alprazolam was administered PO to 5 dogs and was effective in 1, but alprazolam administration was combined with a change in entrance to the veterinary clinic (the stimulus) for this dog. Levetiracetam was administered PO to 1 dog for 2 days prior to exposure to the specific stimulus and was believed to reduce the severity of the seizure but not prevent it. Clorazepate was administered PO prior to exposure to the specific stimulus on 2 occasions in 1 dog and was reportedly successful at preventing seizures. Phenobarbital, acepromazine, and levetiracetam were each administered once by mouth prior to stimulus exposure in 1 dog and were ineffective in preventing reflex seizures.
Various environmental maneuvers to prevent seizures were also reported for 5 of the 43 dogs, including having veterinarians perform examinations in the owner's car or in the veterinary clinic parking lot. This was apparently effective initially; however, 1 dog eventually developed seizures in the parking lot. Use of a different entrance to the grooming building was successful in 1 dog. Home veterinary visits were successful in 2 dogs, but 1 of these subsequently developed seizures during home examinations.
Discussion
Results of the present retrospective case series conducted over a 15-year period (2000 through 2014) suggested that stimulus-specific seizures occur in dogs and that, as is the case for human patients with reflex epilepsy, the triggers may be fairly specific. Certain situations (eg, visit to veterinary clinic, bathing in tub, or entering grooming facility or other buildings) were described as repeatedly provoking seizures in affected dogs of the present study.
Whereas the exact cause of reflex seizures is unknown, stress, anxiety, fatigue, sleep deprivation, and fear have been cited as common provocations of seizures in human patients with an established diagnosis of epilepsy16–18 and in particular in people with photosensitive reflex epilepsy.1,19 Thus, we suggest it is not surprising that entry into veterinary clinics and grooming or boarding facilities was reported to trigger seizure activity in the dogs of this report, as these are likely places for dogs to experience stress or anxiety. A significant increase in the urinary glucocorticoid-to-creatinine ratio, an indicator of stress, has previously been documented in hospitalized dogs.20 Panting, also common in excited or stressed dogs, could result in hypocapnia, which has also been reported to occasionally trigger seizure activity in human patients with epilepsy.21
Although a recent report by the International League Against Epilepsy22 categorizes reflex epilepsy as an electroclinical syndrome, an etiologic classification by Shorvon5 maintains that reflex epilepsy should be categorized as “provoked epilepsy.” That report5 defined provoked epilepsy as that in which a specific or environmental factor is the predominant cause of the seizure and in which there is no gross neuroanatomic or neuropathologic alteration. By use of this definition, the reflex seizures reported in a dog with Lafora disease would not be classified as reflex seizures because of the underlying neuropathologic changes associated with that disease.12 Although the dogs in the present study reportedly did not undergo extensive neurologic diagnostic testing to exclude underlying neuroanatomic or neuropathologic changes, concurrent neurologic signs were not described for these dogs, and almost half (21/43) of the affected dogs had apparently manifested clinical signs of reflex epilepsy for > 1 year without developing other neurologic or clinical signs.
Environmental sensory factors, such as sights, odors, or sounds, may have been possible triggers for the seizures that the dogs of the present study experienced. Visual stimulation is considered the most common trigger of reflex epilepsy in human patients, comprising 5% of the total of 6% of reflex seizure cases.1 Possible explanations are centered around the large size of the human visual cortex and the common environmental light patterns (eg, television screens, computer screens, and strobe or flickering lights) that often serve as the trigger.1 Because olfaction is considered the dog's most powerful sense,23 occupying much of the dog's brain space, environmental odors should be considered more likely triggers than visual cues.
In the present study, attempts to treat reflex seizures through the use of maintenance AEDs were apparently unsuccessful. We recognize that our case series has an inherent bias because veterinarians were likely reporting and discussing cases that could not be successfully managed. We do not know how many cases, if any, might be successfully managed with maintenance AEDs.
Given that benzodiazepines are frequently administered IV to treat patients with active seizures, it is reasonable to assume that oral or rectal administration prior to stimulus exposure might be preventive. However, in the present study, oral administration of diazepam (dose unknown) apparently failed to prevent such seizures from occurring in 15 of 16 dogs. Clorazepate was administered PO twice to 1 dog and apparently prevented reflex seizures on both occasions. Dogs that are successfully managed with orally administered benzodiazepines might exist but might not have been accessible and retrieved as part of our source of cases for this retrospective study. As such, we would caution that further studies are indicated before concluding that oral benzodiazepine treatment is ineffective for prophylaxis in dogs with reflex epilepsy.
The most effective means of preventing stimulus-specific epilepsy may be avoidance of the trigger, as suggested by the 5 dogs of this study in which seizures were circumvented by avoiding entry into the veterinary clinic, grooming facility, or boarding facility. However, 24 of 43 (56%) dogs in this study had > 1 seizure trigger, suggesting that reflex seizures may develop in response to other specific stimuli. One dog initially experienced seizures upon entering the veterinary clinic and later apparently manifested seizures during home visits by the veterinarian.
The present study did not attempt to evaluate whether dogs with reflex epilepsy have seizures in response to other environmental stimuli (eg, vacuum cleaner sounds, train whistles, busy streets, or walking or exercising in parks). However, it is possible that other anxiety-inducing circumstances could trigger seizures in dogs, as has been documented in humans.1,16–19 Additional studies are necessary to further elucidate the characteristics of reflex epilepsy in dogs and to determine the most effective means of managing these patients. Such information may also be of value in treating reflex epilepsy in humans.24
Acknowledgments
Supported in part by the Ross University School of Veterinary Medicine Center for Integrative Mammalian Research.
Presented in abstract form at the 27th Annual European Society of Veterinary Neurology and European College of Veterinary Neurology Symposium, Madrid, September 2014.
ABBREVIATIONS
| AED | Antiepileptic drug |
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