Epilepsy in Cavalier King Charles Spaniels
See also: Flycatcher's Syndrome
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Epilepsy refers to repeated seizures. A form of epilepsy, called "idiopathic epilepsy', is inheritable and is prevalent in cavalier King Charles spaniels. It is caused by a mutation in a specific gene which the dogs have inherited from their parents.
According to a report in the June 2004 issue of the Journal of Veterinary Internal Medicine, idiopathic epilepsy has been found to occur more frequently in descendants from bloodlines originating from whole-colored CKCS ancestors from the late 1960s, especially from matings of blood relatives, such as half-siblings. See also a follow up report in July 2005.
In a 2012 report, UK neurology researchers C.J. Driver, K. Chandler, G. Walmsley, N. Shihab, and H.A. Volk examined the MRIs of 85 cavalier King Charles spaniels, looking for a relationship between Chiari-like malformation (CM), ventriculomegaly, and seizures in the dogs. The 85 CKCSs all had CM; 27 of them also had had seizures. They found no association between CM, ventriculomegaly, and the seizures. The seizures were classified as having partial onset -- meaning that they occur in in one area of the brain, unlike generalized seizures which typically affect nerve cells throughout the brain -- in 61% of the dogs. They also stated that "Another cause of recurrent seizures in CKCS (such as familial epilepsy) is suspected, as previously reported."
There are many different types of seizures in dogs. The most common is the generalized major motor seizure, characterized by paddling of the limbs. The dog may cry, bark or whine during the seizure, and it may snap or bite, not quite fully aware of its surroundings. Urination and defecation are common during a generalized seizure. Post seizural signs may last from a few minutes to an hour.
The onset of epilepsy in cavaliers is most common between the ages of six months and five years.
Diagnosing epilepsy in dogs is difficult. It begins by attempting to rule out other causes for the seizures. The electroencephalogram (EEG) is a frequently used device in diagnosing epilepsy, but has serious drawbacks in animals. Advanced imaging, such as magnetic resonance imaging (MRI) or CT scans, is necessary to be able to actually see the brain. By imaging the brain, veterinarians are able to diagnose diseases such as brain tumors or hydrocephalus (water on the brain) which can cause seizures. Apart from the EEG or MRI or CT scans, there is no health test for epilepsy.
Immediately after a seizure, the dog should be handled with caution. The dog likely will pant after a seizure, due to heat generated by the intense brain activity and seizure. Cool, wet compresses place at the base of the skull and in the groin area will help decrease the body temperature. The dog should be offered a drink of water, but should not be left unattended with a water bowl.
In a 2004 article, Dr. H. C. Gurney of Colorado reports success in treating dogs during epileptic seizures by applying ice directly to the dogs' backs at T10 to L4 of the spine. See the article citation for details and a diagram.
All dogs should be examined by a veterinarian after their first seizure for determination of the cause. Anti-convulsant therapy (usually oral phenobarbital [Solfoton, Luminal, Phenoleptil] and/or potassium bromide) may be started once the seizures recur frequently. The owner should keep a calendar noting the frequency of the seizures, and the dog that seizures more than once a month should treated long term with anti-convulsants.
The anti-convulsant gabapentin (Neurontin, Gabarone) is being prescribed, following a study which has shown that between 41% and 55% of dogs have responded to it. Gabapentin works through a receptor on the membranes of brain and peripheral nerve cells. It binds to calcium channels and modulates calcium influx as well as influences GABergic neurotransmission. In humans, gabapentin reportedly does not interact with any other medications, and it is not metabolized, so it is fully excreted in the urine and has no affect upon the liver. However, in dogs, gabapentin is partially metabolized in the liver, and therefore the prescribing neurologist may be expected to order periodic blood tests to check the liver enzymes.
A newer anti-convulsant, pregabalin (Lyrica), is being prescribed by some neurologists. Dr. Curtis Dewey, board certified veterinary neurologist at Cornell University's college of veterinary medicine, has reported that 78% of dogs responded to pregabalin, and that there was a 57% mean reduction in seizures for the participants who finished the study; all had been diagnosed with difficult-to-control seizures. For more details, go here.
Pregabalin is closely related to gabapentin and was developed by Pfizer, which also developed gabapentin. Pfizer reports that pregabalin is more potent than gabapentin and achieves its effect at lower doses. Doses of pregabalin also reportedly have a longer lasting effect than gabapentin. No generic version is available, and as an exclusive brand, Lyrica is quite expensive in comparison to generic gabapentin.
A recent study of the use of acepromazine maleate (i.e., acetylpromazine), which is a common sedative administered to dogs, involved administered it for tranquilization during hospitalization to 36 dogs with a prior history of seizures and to 11 other dogs to decrease seizure activity. No seizures were observed within 16 hours of its administration in the 36 dogs that received the drug for tranquilization, and seizures abated for from 1.5 to 8 hours or did not recur in 8 of 10 of the 11 dogs that had been actively seizing. Also, excitement-induced seizure frequency was reduced for 2 months in one dog.
Imepitoin (Pexion) became available in the UK and Europe in 2012. Imepitoin is a centrally acting antiepileptic substance which inhibits seizures by acting on a specific receptor in the brain cells to reduce the amount of excessive electrical activity present, in order to reduce the number of seizures the dog experiences.. In addition, imepitoin has a weak calcium-channel-blocking effect.
Zonisamide (Zonegram) is an anticonvulsant which in clinical trials appears to be effective for generalized seizures in dogs. It’s anti-seizure effect is believed to work through sodium and calcium channels. Dr. Curtis Dewey has conducted studies of this drug.
Levetiracetam (Keppra) is an anticonvulsant which can also be used in conjunction with phenobarbital and/or potassium bromide. it appears to be relatively safe for dogs, and reportedly rarely has any adverse side effects and does not appear to affect the liver or liver enzymes.
Other anti-convulsants, such as topiramate (Topamax), lamotrigine (Lamictal), oxcarbazepine (Trileptal), or tiagabine (Gabitril), may be prescribed.
Medication will usually eliminate seizures entirely, and is considered effective if a seizure occurs no more than every four to six weeks. Any time the dog exhibits a cluster of seizures, the veterinarian should be consulted, and may require immediate emergency treatment by the veterinarian, due to the possibility of permanent brain damage.
The Canine Inherited Disorders Database (www.upei.ca/~cidd/intro.htm) recommends that cavaliers which have had seizures should not be bred, nor should their parents and siblings.
►May 2013: UK's Royal Veterinary College needs dogs with idiopathic epilepsy for study. The Royal Veterinary College of the University of London still is seeking dogs suspected of suffering idiopathic epilepsy for a study of the influence of a diet on improving seizure control. Details are available here. See our June 2012 item below for more information.
►July 2012: UK researchers find no connection between Chiari-like malformation and epilepsy in cavaliers. In a 2012 report in the Veterinary Journal, UK neurology researchers C.J. Driver, K. Chandler, G. Walmsley, N. Shihab, and H.A. Volk examined the MRIs of 85 cavalier King Charles spaniels, looking for a relationship between Chiari-like malformation (CM), ventriculomegaly, and seizures in the dogs. The 85 CKCSs all had CM; 27 of them also had had seizures. They found no association between CM, ventriculomegaly, and the seizures. The seizures were classified as having partial onset -- meaning that they occur in in one area of the brain, unlike generalized seizures which typically affect nerve cells throughout the brain -- in 61% of the dogs. They also stated that "Another cause of recurrent seizures in CKCS (such as familial epilepsy) is suspected, as previously reported."
►June 2012: Royal Veterinary College (RVC) conducts study of the influence of diet on improving seizure control. The RVC is working with a small animal health and wellness company to confirm the efficacy and safety of a novel diet in the management of dogs with idiopathic epilepsy being treated with phenobarbitone and/or potassium bromide. To confirm the efficacy of this new diet, RVC seeks to recruit dogs which are suspected of having idiopathic epilepsy, with these qualifications: (a) dogs which have a seizure frequency of at least three seizures in the last three months; and (b) dogs receiving phenobarbitone and/or potassium bromide treatment. For more information, contact RVC by clicking here, and/or downloading this brochure.
►March 2012: Intravenous levetiracetam is reported to be safe and potentially effective for treatment of epileptic dogs. University of Minnesota veterinary researchers report in a March 2012 article that intravenous levetiracetam. in addition to IV diazepam treatment, showed a trend toward superiority over placebo and IV diazepam for the treatment of epilepsy and acute repetitive seizures in dogs.
►December 2009: Pregabalin (Lyrica) is being studied to treat epileptic dogs. Dr. Curtis Dewey, board certified veterinary neurologist at Cornell University's college of veterinary medicine, reports that 78% of dogs respond to pregabalin (Lyrica) and that there was a 57% mean reduction in seizures for the participants who finished the study; all had been diagnosed with difficult-to-control seizures. For more details, go here.
►The Canine Epilepsy Project, led by Dr. Ned Patterson, of the University of Minnesota's College of Veterinary Medicine, and by Dr. Gary Johnson, of the University of Missouri's College of Veterinary Medicine, is a collaborative study into the causes of epilepsy in dogs. Its goal is to find the genes responsible for epilepsy in dogs so that wise breeding can decrease the incidence of the disease in dogs, and that, knowing what genes regulate epilepsy in dogs may help better tailor therapy to the specific cause. Participation by owners of affected dogs and their relatives is essential to the success of this project. Researchers need DNA samples from dogs who have experienced seizures, and immediate relatives, both normal and affected. Specifically, they need samples from all available siblings, parents, and grandparents. If the affected dog has been bred, all offspring and mates should be sampled as well. Useful research families are explained in more detail here. Participation in this research project is confidential - the names of individual owners or dogs will not be revealed. Data and DNA sample collection instructions and sample submission forms are available on www.canine-epilepsy.net, or the packet will be mailed or faxed upon request. Contact Liz Hansen, at the Animal Molecular Genetics Laboratory, University of Missouri - College of Veterinary Medicine, email email@example.com Go to the Canine Epilepsy Network website for more information.
►October 2004: New anti-epileptic drug ELB138. Profs. Chris Rundfeldt, Andrea Tipold, Wolfgang Loscher, and others, of the Department of Small Animal Medicine and Surgery, University of Veterinary Medicine, and Center for Systems Neuroscience, Hannover, Germany, have researched, developed, and have been studying the efficacy of a new antiepileptic and anxiolytic drug, ELB138, which is a low-affinity partial BZD-receptor agonist, formerly called AWD 131-138; 1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one. They and others hold a U.S.patent (20050070537) for this drug. They report in their October 2004 veterinary journal article that "the reduction in seizure frequency using ELB138 in dogs with newly diagnosed idiopathic epilepsy was comparable to the reduction in dogs treated either with phenobarbital or primidone. In dogs with chronic epilepsy and add-on therapy with either ELB138 or potassium bromide, such supplementation reduced the seizure frequency and the duration and severity of seizures" with reportedly rare side effects.
►June 2004: Clare Rusbridge finds epilepsy is inheritable in CKCSs, especially whole-colors. UK's Clare Rusbridge reports that idiopathic epilepsy is an inheritable disease in the cavalier King Charles spaniel and is seen imore frequently in lines originating from whole-colored ancestors from the late 1960s, especially where there were half-brother/sister matings.
Control of Canine Genetic Diseases. Padgett, G.A., Howell Book House 1998, pp. 198-199, 235.
A Simple, Effective Technique for Arresting Canine Epileptic Seizures. H. C. Gurney, Janice Gurney. J. Amer. Holistic Vet. Med. Assn. Jan 2004; 22(4):17-18. Quote: "Fifty-one epileptic canine patients were successfully treated during an epileptic seizure with a technique involving the application of ice on the back (T10 to L4). This technique was found to be effective in aborting or shortening the duration of ictus. ... Ice is applied as soon as the seizure is observed. The application itself is either a block of ice (i.e., water frozen in a metal ice tray, with the tray applied directly to the seizing patient), or ice (cubes or crushed ice in a plastic bag). The ice is held firmly to the dog’s back, on the area superior to the spinal process from T10 (palpable at the 'low spot' on the canine spine) to L4 (Figure at right). The size of a given ice application is sufficient to cover the described area. Maintain firm pressure in that location until the patient spontaneously recovers sternal recumbency and makes efforts to rise and walk. If the patient is prone to 'chain' episodes or displays evidence of returning to ictus after removal of the ice, the ice should once again be applied until the patient regains sternal recumbence (when chain seizures occur, aggressive medical intervention is necessary). Clients have used bags or boxes of frozen vegetables, but such applications are reported to be less effective. ... The sooner ice was applied during an epileptic event, the more effective the intervention was in stopping or abbreviating the seizure. Also of note was the observation that the canines’ post-ictus recovery time was shorter, and recovery appeared to be augmented."
Inheritance of occipital bone hypoplasia (Chiari type I malformation) in Cavalier King Charles spaniels. Rusbridge C., Knowler S. P. J Vet Intern Med 2004;18:673–678. Quote: "Occipital bone hypoplasia with foramen magnum obstruction and secondary syringomyelia (SM) is a common condition in the Cavalier King Charles Spaniel (CKCS) that is similar to human Chiari type I malformation. A worldwide family tree of more than 5,500 CKCSs spanning a maximum of 24 generations was established by obtaining pedigree information from 120 dogs diagnosed with SM secondary to occipital bone hypoplasia. The ongoing study showed 6 of 8 great grandparents of all affected dogs could be traced back to 2 female ancestors so that all 8 were descended from one or the other or both. The disease appears to be more severe and have an earlier onset with increased inbreeding, especially when breeding from affected dogs. The family tree of idiopathic epilepsy (IE) appears to be a different subset of the CKCS population, although some overlap was observed. Idiopathic epilepsy is more frequent in lines originating from whole-color dogs. Selection for coat color is believed to have influenced the development of both occipital hypoplasia with secondary SM and IE. In addition, breeding guidelines to reduce the incidence of mitral valve disease have placed further pressures on the gene pool."
"Seizures" (Podell, M.) in: Manual of Small Animal Neurology, 3d ed. Editors Olby N., Platt S., British Small Animal Vety Assn (2004). pp 97-112.
Alternative anticonvulsant drugs for dogs with seizure disorders. Curtis W. Dewey, Georgina Barone, Kerry Smith, Gregg D. Kortz. DVM360.com. Sept. 2004.
Anticonvulsant efficacy of the low-affinity partial benzodiazepine receptor agonist ELB 138 in a dog seizure model and in epileptic dogs with spontaneously recurrent seizures. Loscher W, Potschka H, Rieck S, Tipold A, Rundfeldt C. Epilepsia. 2004 Oct;45(10):1228-39. Quote: "Results: ELB 138 was shown to increase potently the pentylenetetrazole (PTZ) seizure threshold in dogs. Prolonged oral administration with twice-daily dosing of ELB 138 with either 5 or 40 mg/kg over a 5-week period was not associated with loss of anticonvulsant efficacy in the PTZ dog model. To study whether physical dependence developed during long-term treatment, the BZD antagonist flumazenil was injected after 5 weeks of treatment with ELB 138. Compared with prolonged treatment with DZP, only relatively mild abstinence symptoms were precipitated in dogs treated with ELB 138, particularly at the lower dosage (5 mg/kg, b.i.d.). In a prospective trial in dogs with newly diagnosed epilepsy, ELB 138 markedly reduced seizure frequency and severity without significant difference to standard treatments (phenobarbital or primidone) but was much better tolerated than the standard drugs. In dogs with chronic epilepsy, most dogs exhibited a reduction in seizure frequency and severity during add-on treatment with ELB 138. Conclusions: The data demonstrate that the partial BZD receptor agonist ELB 138 exerts significant anticonvulsant efficacy without tolerance in a dog seizure model as well as in epileptic dogs with spontaneously recurrent seizures. These data thus substantiate that partial agonism at the BZD site of GABAA receptors offers advantages versus full agonism and constitutes a valuable approach for treatment of seizures."
Neurological diseases of the Cavalier King Charles spaniel. Rusbridge, C. J Small Animal Practice, June 2005, 46(6): 265-272(8). "Idiopathic epilepsy is a inheritable disease in the CKCS and is seen in all colour varieties but is more frequent in lines originating from whole-coloured ancestors from the late 1960s, especially where there were half-brother/sister matings (Rusbridge and Knowler 2004). Diagnosis is by ruling out other causes of seizures; for example, using haematology and biochemistry to rule out reactive causes such as hepatic encephalopathy, and MRI and CSF analysis to rule out structural and inflammatory disease such as GME. The author’s firstline therapy is phenobarbital or bromide monotherapy, progressing to a combination of both drugs if the seizures are not adequately controlled. Some cases of CKCS epilepsy are difficult to control and novel anticonvulsants such as levetiracetam (Keppra; UCB Pharma) or topiramate (Topamax; Janssen-Cilag) may be useful. For a more extensive review of the management of epilepsy see Podell (2004)."
Anticonvulsant activity and tolerance of ELB138 in dogs with epilepsy: A clinical pilot study. Rieck S, Rundfeldt C, Tipold A. Vet J. 2005 May 16.
A Retrospective Study on the Use of Acepromazine Maleate in Dogs With Seizures. Karen M. Tobias, Katia Marioni-Henry, and Rebecca Wagner. J. Am.An. Hosp. Assn. (2006) 42:283-289.Epil-K9's Canine Epilepsy Resources website: www.canine-epilepsy.com/Resources.html
Pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with suspected idiopathic epilepsy. Curtis W. Dewey, Sofia Cerda-Gonzalez, Jonathan M. Levine, Britton L. Badgley, Julie M. Ducoté, Gena M. Silver, Jocelyn J. Cooper, Rebecca A. Packer, and James A. Lavely. JAVMA, Dec 2009; 235(12):1442-1449, Quote: "Objective—To assess tolerability and short-term efficacy of oral administration of pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with poorly controlled suspected idiopathic epilepsy. ... Animals—11 client-owned dogs suspected of having idiopathic epilepsy that was inadequately controlled with phenobarbital, potassium bromide, or a combination of these 2 drugs. ... Results—Seizures were significantly reduced (mean, 57%; median, 50%) after pregabalin administration in the 9 dogs that completed the study; 7 were considered responders with mean and median seizure reductions of 64% and 58%, respectively. Adverse effects for pregabalin were reported in 10 dogs. Mean and median plasma pregabalin concentrations for all dogs were 6.4 and 7.3 μg/mL, respectively. Conclusions and Clinical Relevance—Pregabalin may hold promise as a safe and effective adjunct anticonvulsant drug for epileptic dogs poorly controlled with the standard drugs phenobarbital or potassium bromide. Adverse effects of pregabalin appeared to be mild. Additional studies with larger numbers of dogs and longer follow-up intervals are warranted."
Breed Predispositions to Disease in Dogs & Cats (2d Ed.). Alex Gough, Alison Thomas. 2010; Wiley-Blackwell Publ. 53.
The association between Chiari-like malformation, ventriculomegaly and seizures in cavalier King Charles spaniels. C.J. Driver, K. Chandler, G. Walmsley, N. Shihab, H.A. Volk. Vety.J. Feb. 2013;195(2):235-237. Quote: "Cavalier King Charles spaniels (CKCSs) with Chiari-like malformation (CM) and associated seizures are frequently diagnosed with idiopathic epilepsy. There could be an association between ventriculomegaly (V) or caudal fossa overcrowding (CCFP) and seizures. A retrospective case-control study was performed using MRI to investigate the possible association between these morphological abnormalities and seizures. Seizure semiology and, where possible, electroencephalographic (EEG) abnormalities were documented. Eighty-five CKCS with CM were included, 27 with seizures. There was no association between V or CCFP and seizures (P = 0.10 and 0.71, respectively). Seizures were classified as having partial onset [meaning that they occur in in one area of the brain, unlike generalized seizures which typically affect nerve cells throughout the brain] in 61% of individuals in the study population (95% CI 42.41–76.43%). Another cause of recurrent seizures in CKCS (such as familial epilepsy) is suspected, as previously reported."
Double-Masked, Placebo-Controlled Study of Intravenous Levetiracetam for the Treatment of Status Epilepticus and Acute Repetitive Seizures in Dogs. B.T. Hardy, E. E. Patterson, J.M. Cloyd, R.M. Hardy, I.E. Leppik. J.Vet.Inter.Med. March 2012;26(2):334-340. Quote: "Background: Status epilepticus (SE) and acute repetitive seizures (ARS) are common canine neurologic emergencies. No evidence-based studies are available to guide treatment in veterinary patients. Parenteral levetiracetam (LEV) has many favorable properties for the emergency treatment of seizures, but its safety and efficacy in dogs for SE and ARS are unknown. Hypothesis: Intravenous LEV is superior to placebo in controlling seizures in dogs with SE or ARS after treatment with IV diazepam. Animals: Nineteen client-owned dogs admitted for SE or ARS. Methods: Randomized, placebo-controlled, double-masked study. Dogs with SE or ARS were randomized to receive IV LEV (30 or 60 mg/kg using an adaptive dose-escalation approach) or placebo, in addition to standard of care treatment. They were monitored for at least 24 hours after admission for additional seizures. Results: The responder rate (defined as dogs with no additional seizures after administration of the study medication) after LEV was 56% compared with 10% for placebo (P = .06). Dogs in the placebo group required significantly more boluses of diazepam compared with the LEV group (P < .03). Seizure etiologies identified were idiopathic epilepsy (n = 10), inflammatory central nervous system disease (n = 4), intracranial neoplasia (n = 2), hepatic encephalopathy (n = 1), and 2 dogs had no cause determined. No serious adverse effects were attributable to LEV administration. Conclusions and Clinical Importance: LEV was safe and potentially effective for the treatment of SE and ARS in these client-owned dogs. Larger, controlled clinical trials are needed to confirm this preliminary observation."
Prevalence of Lateral Ventricle Asymmetry in Brain MRI Studies of Neurologically Normal Dogs and Dogs with Idiopathic Epilepsy. Mauro Pivetta, Luisa De Risio, Richard Newton, Ruth Dennis. Vet.Radiology&Ultrasound. Sept. 2013;54(5):516-521. Quote: "Asymmetry of the cerebral lateral ventricles is a common finding in cross-sectional imaging of otherwise normal canine brains and has been assumed to be incidental. The purpose of this retrospective study was to compare the prevalence of ventricular asymmetry in brain MRI studies of normal dogs and dogs with idiopathic epilepsy. Brain MRI archives were searched for 100 neurologically normal dogs (Group 1) and 100 dogs with idiopathic epilepsy (Group 2). For each dog, asymmetry of the lateral ventricles was subjectively classified as absent, mild, moderate, and severe based on a consensus of two observers who were unaware of group status. ... The prevalence of asymmetry was 38% in Group 1 dogs and 44% in Group 2 dogs. Asymmetry was scored as mild in the majority of Group 2 dogs. There was no significant association between presence/absence and degree of ventricular asymmetry vs. dog group, age, gender, or skull conformation. Findings from the current study supported previously published assumptions that asymmetry of the lateral cerebral ventricles is an incidental finding in MRI studies of the canine brain."
Pediatric Seizure Disorders in Dogs and Cats. James A. Lavely. Vet. Clinics of No. America: Small Animal Prac. Dec. 2013. Quote: "Seizure disorders in young animals pose different considerations as to cause and therapeutic decisions compared with adult animals. Infectious diseases of the nervous system are more likely in puppies and kittens compared with adults. The diagnosis of canine distemper is often based on clinical signs. Idiopathic epilepsy typically occurs in dogs between 1 and 5 years of age; however, inflammatory brain diseases such as necrotizing encephalitis and granulomatous meningoencephalomyelitis also commonly occur in young to middle-aged small-breed dogs. The choice of which anticonvulsant to administer for maintenance therapy is tailored to each individual patient. ... A 6-month-old Cavalier King Charles spaniel was reported to have seizures secondary to a hexanoylglycine aciduria."