Epilepsy in Cavalier King Charles Spaniels


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.

* See Neurological diseases of the Cavalier King Charles spaniel.

It is to be distinguished from Flycather's Syndrome, which is a separate disorder of the CKCS.

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."

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Symptoms

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 YouTube video of epileptic seizurebite, 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. A brief seizure, called the "absence seizure", may last for only seconds, during which the dog may just seem to be staring into space. See this YouTube video of a Tibetan spaniel experiencing a seizure.

The onset of epilepsy in cavaliers is most common between the ages of six months and five years.

The most common form of hereditary epilepsy in cavaliers is flycatcher's syndrome which is discussed on its own webpage.

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Diagnosis

EEG HeadsetDiagnosing epilepsy in dogs is difficult. It begins by attempting to rule out other causes for the seizures. Some cases of epileptic seizures have a specific structural cause. The age of onset, breed, weight, historical findings, and neurological exam findings are important in estimating the likelihood that there is a structural problem and therefore a specific treatment and prognosis.

The electroencephalogram (EEG) (right) is a frequently used device in diagnosing epilepsy. Electroencephalography uses electrodes that detect the flow of  electrical current between the cells of the brain, spinal cord, heart, and other organs, to view brain function. However, EEG has some serious drawbacks in animals.

MRI scan of CKCSAdvanced imaging, such as magnetic resonance imaging (MRI) (left) 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.

 In a September 2015 article, the International Veterinary Epilepsy Task Force issued a consensus proposal on diagnosing epilepsy in dogs. They outlined "two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause." They then described a three-tier system for the diagnosis of idiopathic epilepsy (IE):

"Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis.

Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis.

Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset <6 months or >6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose. This consensus article represents the basis for a more standardised diagnostic approach to the seizure patient. These recommendations will evolve over time with advances in neuroimaging, electroencephalography, and molecular genetics of canine epilepsy."
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Treatment

Epileptic seizure -- Tibetan spanielImmediately 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.

-- conventional drugs

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. Unfortunately, however, less than 50% of dogs treated with these anti-convulsants become seizure-free without significant side-effects. In an April 2014 report, a cavalier suffered loss of muscle control and repetitive leg twitching due to an overdose of potassium bromide. Also, 30% of dogs treated with these drugs still will demonstrate poor seizure control or chronic resistance to the drugs.

In a February 2016 report, an international panel of veterinary neurologists and other specialists published a "2015 ACVIM Consensus Statement" on seizure management in dogs based on current literature and clinical expertise, authorized by the American College of Veterinary Internal Medicine (ACVIM). In that report,  they rated phenobarbital, "High recommendation and likely be effective treatment." They gave potassium bromide a "Moderate recommendation and most likely to be effective treatment."

The anti-convulsant gabapentin (Neurontin, Gabarone) is being prescribed, following an October 2010 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, see this December 2009 report.

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.

Oddly, the 2015 ACVIM Consensus Statement does not mention either gabapentin or pregabalin.

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. See this April 2015 report discussing its safety and effectiveness. In the 2015 ACVIM Consensus Statement, the panel gave imepitoin a "High recommendation and likely be effective treatment."

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. The 2015 ACVIM Consensus Statement rated zonisamide, "Low recommendation and may not be effective treatment."

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. In a July 2014 study, researchers found that the adding phenobarbital to a dosage of Levetiracetam significantly altered the disposition of the levetiracetam. See, also, this February 2015 study. The 2015 Consensus Statement rated levetiracetam, "Low recommendation and may not be effective treatment."

In a November 2015 article, six of twelve affected dogs were treated solely with  levetiracetam and six were treated solely with phenobarbital. The researchers found that, in the levetiracetam treated dogs, there was no significant difference in the monthly number of seizures before and after treatment, whereas in the phenobarbital treated dogs, there were "significantly fewer seizures after treatment". They concluded that: "In this study levetiracetam was well tolerated but was not effective at the given doses as mono-therapy in dogs with idiopathic epilepsy."

Other anti-convulsants, such as topiramate (Topamax), lamotrigine (Lamictal), oxcarbazepine (Trileptal), tiagabine (Gabitril),  primidone, sodium valproate, and felbamate 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.

In an October 2014 report, UK researchers UK researchers Marios Charalambous, David Brodbelt, and Holger A. Volk found evidence to support the efficacy of oral phenobarbital and imepitoin and a "fair level of evidence" to support the efficacy of oral potassium bromide and levetiracetam. However, for zonisamide, primidone, gabapentin, pregabalin, sodium valproate, felbamate, and topiramate, they found "insufficient evidence to support their use due to lack of bRCTs [blinded randomized clinical trials]". They concluded that "there is a need for greater numbers of adequately sized bRCTs evaluating the efficacy of AEDs [antiepileptic drugs] for IE."

-- natural alternative remedies

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.

Holistic veterinarians who practice Traditional Chinese Medicine use acupuncture, Chinese and Western herbal therapy, nutrition, veterinary chiropractic, homeopathy, and homotoxicology as treatment therapies which may be highly beneficial for treating epileptic conditions and other seizures, where a conventional approach either fails to provide relief or produces unacceptable side effects.

Traditional Chinese herbal medicines (TCM) and other holistic supplements should be taken only if prescribed by a licensed veterinarian who also is holistically trained in TCM. Search webpages for finding holistic veterinarians in the United States are located here and here.

-- dietary remedies

In a September 2015 article, a team of UK researchers fed 21 dogs suspected to have idiopathic epilepsy, including a cavalier King Charles spaniel (CKCS), a dry food kibble which was either a ketogenic medium-chain TAG (triacylglycerol) diet (MCTD) or a placebo diet, for three months. Then the dogs were switched from the one diet to the other for another three months. The results overall showed that seizure frequencies were "significantly lower when dogs were fed the MCTD in comparison with the placebo diet. The CKCS's seizure frequency was reduced from 10 per month on the placebo diet to 5 per month while on the MCTD. The researchers concluded:

"In conclusion, the data show antiepileptic properties associated with ketogenic diets and provide evidence for the efficacy of the MCTD used in this study as a therapeutic option for epilepsy treatment."

In a February 2016 report, the same team studied 21 dogs affected with idiopathic epilepsy (IE), feeding them a ketogenic MCTD for three months and then a placebo diet for three months. They were looking for attention-deficit/hyperactivity disorder (ADHD) behaviors in the dogs -- excitability, chasing, and trainability. They found that their "data support the supposition that dogs with IE may exhibit behaviors that resemble ADHD symptoms seen in humans and rodent models of epilepsy and that a MCTD may be able to improve some of these behaviors, along with potentially anxiolytic effects."

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Breeders' Responsibilities

The Canine Inherited Disorders Database recommends that cavaliers which have had seizures should not be bred, nor should their parents and siblings.

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What You Can Do

Canine Epilepsy NetworkThe 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 hansenl@missouri.edu  Go to the Canine Epilepsy Network website for more information.

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Research News

February 2016: ACVIM issues a Consensus Statement on treating dogs for seizures. Dr. Michael PodellIn a February 2016 report, an international panel of veterinary neurologists and other specialists (M. Podell [right], H.A. Volk, M. Berendt, W. Löscher, K. Muñana, E.E. Patterson, S.R. Platt) published a "Consensus Statement" on seizure management in dogs based on current literature and clinical expertise, authorized by the American College of Veterinary Internal Medicine (ACVIM). The report is divided into a series of questions much like an FAQ format and focuses primarily upon drug treatments and also touches upon alternative care methods.

Their first question is "When Should Treatment Be Started?" They conclude:

"The panel recommendations to initiate AED [antiepileptic drugs] treatment are summarized as follows: (i) Identifiable structural lesion present or prior history of brain disease or injury; (ii) Acute repetitive seizures or, status epilepticus (ictal event ≥5 minutes or ≥3 or more generalized seizures within a 24-hour period); (iii) ≥2 or more seizure events within a 6-month period; and (iv) Prolonged, severe, or unusual postictal periods."

Then they pose this question and analyze in detail five specific drugs: "Which Drug Should Be Used First?" Their list:

    • Phenobarbital: High recommendation and likely be effective treatment.
    • Potassium Bromide: Moderate recommendation and most likely to be effective treatment.
    • Primidone: Not recommended for treatment and may be ineffective and/or dangerous to the patient.
    • Imepitoin: High recommendation and likely be effective treatment.
    • Levetiracetam: Low recommendation and may not be effective treatment.
    • Zonisamide: Low recommendation and may not be effective treatment.

They fail to mention the anti-convulsants such as gabapentin or pregabalin or the sedative acepromazine maleate, presumably because of a lack of much published evidentiary research on these treatments.

They next discuss: "How Should Monitoring Be Performed?" and "What Are The Risks Of Treatment?" and "When Should a Second AED Be Started and Which Should be Used?", Then they turn their attention to "What Alternative Nonpharmacologic Treatments Are Available?" They list four categories of alternative treatments: Vagal nerve stimulation (VNS), dietary alteration treatment, acupuncture, and homeopathy, thereby ignoring other holistic remedies such as Chinese and Western herbal therapy, nutrition, veterinary chiropractic, and homotoxicology.

January 2016: UK study of epileptic dogs also finds attention-deficit/hyperactivity disorder (ADHD) behaviors, and that a ketogenic medium chain triglyceride diet (MCTD) improved the ADHD activities. Dr. Yuanlong PanIn a February 2016 report, a team of UK researchers (Rowena M.A. Packer, Tsz Hong Law, Emma Davies, Brian Zanghi, Yuanlong Pan [right], Holger A. Volk) studied 21 dogs affected with idiopathic epilepsy (IE), feeding them a ketogenic medium chain triglyceride diet (MCTD) for three months and then a placebo diet for three months. They were looking for attention-deficit/hyperactivity disorder (ADHD) behaviors in the dogs -- excitability, chasing, and trainability. They found that their "data support the supposition that dogs with IE may exhibit behaviors that resemble ADHD symptoms seen in humans and rodent models of epilepsy and that a MCTD may be able to improve some of these behaviors, along with potentially anxiolytic effects."

Dr. Nadia Fredsø AndersenDecember 2015: Danish research concludes levetiracetam was not effective as mono-therapy for idiopathic epilepsy. In a November 2015 article, a team of Danish researchers (Nadia Fredsø [Andersen] [right], A. Sabers, N. Toft, A. Møller, M. Berendt) treated six of twelve affected dogs solely with  levetiracetam and treated the other six solely with phenobarbital. The researchers found that, in the levetiracetam treated dogs, there was "no significant difference" in the monthly number of seizures before and after treatment, whereas in the phenobarbital treated dogs, there were "significantly fewer seizures after treatment". They concluded that: "In this study levetiracetam was well tolerated but was not effective at the given doses as mono-therapy in dogs with idiopathic epilepsy."

October 2015: UK researchers find anti-epileptic properties in ketogenic diets reduce seizure frequencies in epileptic dogs. Dr. Holger VolkIn a September 2015 article by a team of UK researchers (Tsz Hong Law, Emma S. S. Davies, Yuanlong Pan, Brian Zanghi, Elizabeth Want, Holger A. Volk [right]), they fed 21 dogs suspected to have idiopathic epilepsy, including a cavalier King Charles spaniel (CKCS), a dry food kibble which was either a ketogenic medium-chain TAG (triacylglycerol) diet (MCTD) or a placebo diet, for three months. Then the dogs were switched from the one diet to the other for another three months. The results overall showed that seizure frequencies were "significantly lower when dogs were fed the MCTD in comparison with the placebo diet. The CKCS's seizure frequency was reduced from 10 per month on the placebo diet to 5 per month while on the MCTD. The researchers concluded:

"In conclusion, the data show antiepileptic properties associated with ketogenic diets and provide evidence for the efficacy of the MCTD used in this study as a therapeutic option for epilepsy treatment."

September 2015: International Veterinary Epilepsy Task Force issues a consensus proposal on diagnosing idiopathic epilepsy. International Veterinary Epilepsy Task ForceIn a September 2015 article, the International Veterinary Epilepsy Task Force, consisting of neurologists and other veterinary specialists from the US, UK, and throughout Europe (Velia-Isabel Hülsmeyer, Andrea Fischer, Paul J.J. Mandigers, Luisa DeRisio, Mette Berendt, Clare Rusbridge, Sofie F.M. Bhatti, Akos Pakozdy, Edward E. Patterson, Simon Platt, Rowena M.A. Packer, Holger A. Volk) issues their consensus proposal on diagnosing epilepsy in dogs. They outline "two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause." They then describe a three-tier system for the diagnosis of idiopathic epilepsy (IE):

"Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis.

Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis.

Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset <6 months or >6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose. This consensus article represents the basis for a more standardised diagnostic approach to the seizure patient. These recommendations will evolve over time with advances in neuroimaging, electroencephalography, and molecular genetics of canine epilepsy."

September 2015: International Veterinary Epilepsy Task Force reports on epilepsy in cavaliers. In a September 2015 article, the International Veterinary Epilepsy Task Force, consisting of neurologists and other veterinary specialists from the US, UK, and throughout Europe (Velia-Isabel Hülsmeyer, Andrea Fischer, Paul J.J. Mandigers, Luisa DeRisio, Mette Berendt, Clare Rusbridge, Sofie F.M. Bhatti, Akos Pakozdy, Edward E. Patterson, Simon Platt, Rowena M.A. Packer, Holger A. Volk) issues their massive "current understanding of idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs", including, of course, the cavalier King Charles spaniel. Their primary findings regarding the CKCS:

• Idiopathic epilepsy may occur independently of Chiari-like malformation (CM), but an overlapping of the two diseases cannot be excluded.
• Epilepsy was found more frequently in lines originating from whole-color dogs.
• No detailed data regarding potential modes of inheritance are available.
• Potential breed-specific diseases that may mimic idiopathic epilepsy: episodic falling ("In contrast to epileptic seizures, consciousness usually is not affected during these episodes."); myoclonus [spasmodic jerky contraction of groups of muscles] ("Older Cavalier King Charles spaniels (>5 years old) have a high prevalence of myoclonus, which manifests most commonly as a brief jerking of the head and forelimbs when the dog is standing or sitting. Initially the syndrome is relatively benign but can be progressive with affected dogs suffering frequent jerks which may interfere with function, for example cause the dog to fall or stumble. The syndrome can be confused with focal epileptic seizures but generally does not respond to AEDs [antiepileptic drugs] licenced for dogs although may respond to levetiracetam.")

February 2015: NC State researchers find adding phenobarbital and bromide increases Levetiracetam's movement through epileptic dogs. In a February 2015 study, a team of researchers at North Carolina State University report that the concurrent administration of phenobarbital alone or with bromide increased the clearance of Levetiracetam in epileptic dogs. See, also, this team's July 2014 report on the same topic.

February 2015: UK's Royal Veterinary College's research team finds levetiracetam to effectively reduce seizures. In a February 2015 report by UK's Royal Veterinary College's canine epilepsy research team, it found that in a study of 52 affected dogs, the epilepsy drug levetiracetam was effective and well-tolerated for reducing seizures -- 69% of the dogs had a 50% or greater reduction in seizure frequency while 15% of all the dogs were completely free from seizures.

January 2015: UK's Royal Veterinary College's new Epilepsy & Stress study needs affected dogs. The Royal Veterinary College's Canine Epilepsy Research team (Rowena Packer, Holger Volk, and Rob Fowkes) is seeking saliva samples from dogs affected with idiopathy epilepsy and information from their owners about the dogs' quality of life, including their seizure frequency, type, severity, and how well their seizures are controlled by medication. They assure that all information will be kept secure and anonymous. No visit to RVC will be necessary, as all samples and data will be collected remotely.

If you live in the UK and have an eligible dog (must not be affected by any known endocrine disorder, such as Cushing's, hypothyroidism or hyperthyroidism and not taking any steroids), contact Dr. Packer at rpacker@rvc.ac.uk with this information: (a) name, age, breed, sex, and neuter status of the dog; (b) whether you and your dog meet the inclusion criteria; (c) how often your dog has seizures per month; and (d) where in the UK you are located.

October 2014: UK researchers find oral phenobarbital, imepitoin, potassium bromide, and levetiracetam likely are effective to treat idiopathic epilepsy, with a big BUTDr. Hogler Volk. UK researchers Marios Charalambous, David Brodbelt, and Holger A. Volk (right) examined various antiepileptic drugs (AEDs) used for the management of canine idiopathic epilepsy (IE). In an October 2014 report, they found evidence to support the efficacy of oral phenobarbital and imepitoin and a "fair level of evidence" to support the efficacy of oral potassium bromide and levetiracetam. However, for the remaining AEDs (zonisamide, primidone, gabapentin, pregabalin, sodium valproate, felbamate, and topiramate), they found "insufficient evidence to support their use due to lack of bRCTs [blinded randomized clinical trials]". They concluded that "there is a need for greater numbers of adequately sized bRCTs evaluating the efficacy of AEDs for IE."

April 2014: Epileptic CKCS has leg twitching and loss of muscle control reactions to potassium bromide treatment. In an April 2014 report, a spayed female cavalier diagnosed with idiopathic epilepsy was treated with potassium bromide and phenobarbital. Eight days later, the veterinarians found her suffering from a lack of muscle control and repetitive twitching of the limbs. They concluded she was overdosed with the bromide solution. She had no similar episodes following a reduction in the dosing.

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."

Royal Veterinary College (RVC)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. In a December 2009 study, an international panel of neurologists (Curtis W. Dewey, Sofia Cerda-Gonzalez, Jonathan M. Levine, Britton L. Badgley, Julie M. Ducoté, Gena M. Silver, Jocelyn J. Cooper, Rebecca A. Packer, James A. Lavely)  report 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.

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.

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Related Links

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Veterinary Resources

Extramedullary Hematopoiesis in the Choroid Plexus of Five Dogs. D. Bienzle, J. M. Kwiecien, J. M. Parent. Vet.Pathol. 1995;32:437-440. Quote: "Five dogs euthanatized because of refractory seizures were found to have hematopoietic elements in the interstitium of the choroid plexus at the level of the fourth ventricle. None of the dogs had significant hematologic or cerebrospinal fluid abnormalities. Dog No. 4 was a 3-year-old male Cavalier King Charles Spaniel with seizures since the age of 7 months. Five months of phenobarbital therapy had not affected the clinical status, and addition of KBr and dexamethasone yielded no improvement. Relevant laboratory findings consisted of mild hyperglycemia and a mild leukocytosis due to a mature neutrophilia (Table 1). CSF analysis disclosed blood contamination and several small clumps of meningeal cells (Table 2). Based on clinical examination and magnetic resonance imaging, a diagnosis of genetic epilepsy was established, and euthanasia was elected. Dog No. 4 had swollen, vacuolated hepatocytes attributed to recent glucocorticoid and barbiturate therapy and a cystic craniopharyngeal duct considered an incidental finding. Individual small foci of gliosis were present throughout the white matter of the frontal cortex, the internal capsule, and the substantia nigra. The temporal cortex had several ectopic islands of gray matter. Immature myelocytic cells, ranging from myeloblasts to band neutrophils, and scattered rubricytes were present in the stroma of the choroid plexus of the fourth ventricle. The xtramedullary hematopoiesis was confined to the central nervous system and consisted of megakaryocytes, immature granulocytes, and rubricytes in two dogs and of one predominant cell population in each of the other three dogs. These findings are unique, and factors possibly contributing to the formation of a hematopoietic inductive microenvironment in the choroid plexus are cytokine neurokine homologies, locally altered vascular supply, and aberrant functioning of bone marrow-derived central nervous system macrophages."

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 Epilepsy Ice Treatmentseizure 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.

From Gold Beads to Keppra: Update on Anticonvulsant Therapy. Gregg Kortz. 2d Ann. Vet. Neurology Symposium. Univ. Calif.-Davis. 2005.

Improving seizure control in dogs with refractory epilepsy using gabapentin as an adjunctive agent. M. Govendir, M. Perkins, R. Malik. Australian Vet. October 2005;83(10):602-608. Quote: "Objective: To assess whether there is a change in seizure activity in dogs with refractory epilepsy that are receiving appropriate doses of phenobarbitone and/or potassium bromide, when gabapentin is added to the therapeutic regimen. Design: A prospective study of 17 dogs with a refractory seizure disorder, 16 of which have idiopathic epilepsy. Procedure: Patients were stabilised using phenobarbitone and/or potassium bromide to produce tolerable therapeutic serum concentrations and dosed additionally with gabapentin at 35 to 50 mg/kg/d (divided twice or three times daily) for 4 months. Owners recorded seizure activity and side effects during this period in a standardised diary. Patients underwent monthly physical examinations and venepuncture to assess selected serum biochemical analytes, as well as phenobarbitone and bromide concentrations. Patients were further monitored for long-term response to adjunctive gabapentin therapy. Results: There was no significant decrease in the number of seizures over the studyperiod for the entire cohort, however three dogs stopped seizuring completely. There was a significant increase in the number of patients who showed an increase in the interictal period (P > 0.001). Serum alkaline phosphatase activity and triglyceride concentrations were elevated at baseline. There were no significant changes in biochemical analytes during the course of the study period. Side effects observed initially on addition of gabapentin included sedation and hind limb ataxia. The former resolved spontaneously after a few days; the latter after a slight reduction in bromide dose. Long-term, a further two patients became seizure free and ten patients remained on gabapentin indefinitely. No long-term side effects have become apparent. Conclusion: Addition of gabapentin to phenobarbitone and/or potassium bromide increased the interictal period and shortened the post-seizure recovery in some canine epileptics. In some dogs, seizures were prevented completely, while in others there was an increase in interictal period. The short-half life of gabapentin has advantages for seizure control, however its present high cost may prohibit therapy in large dogs."

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.

Treatment with gabapentin of 11 dogs with refractory idiopathic epilepsy. Platt, S. R.; Adams, V.; Garosi, L. S.; Abramson, C. J.; Penderis, J.; De Stefani, A.; Matiasek, L. Vet.Rec. December 2006;159(26):881-884. Quote: "Eleven dogs diagnosed with refractory idiopathic epilepsy were treated orally with gabapentin for a minimum of three months at an initial dose of 10 mg/kg every eight hours. They were all experiencing episodes of generalised tonic-clonic seizures and had been treated chronically with a combination of phenobarbital and potassium bromide at doses sufficient to reach acceptable therapeutic serum levels without causing significant side effects. In each dog, the number of seizures per week, the average duration of the seizures and the number of days on which seizures occurred were compared for the three months before and after they were treated with gabapentin. A minimum 50 per cent reduction in the number of seizures per week was interpreted as a positive response to gabapentin, and six of the dogs showed a positive response. After the addition of gabapentin, both the number of seizures per week (P = 0.005) and the number of days with any seizures in a one-week period (P = 0.03) were significantly reduced. Mild side effects of ataxia and sedation were observed in five of the dogs, but they were not severe enough to warrant the treatment being discontinued during the trial."

Epil-K9's Canine Epilepsy Resources website.

The efficacy and tolerability of Levetiracetam in pharmacoresistant epileptic dogs. Holger A. Volk, Lara A. Matiasek, Alejandro Luján Feliu-Pascual, Simon R. Platt, Kate E. Chandler. Vet. J. June 2008;176(3):310-319. Quote: "Twenty-two dogs with idiopathic epilepsy which were pharmacoresistant to phenobarbitone and bromide were treated with levetiracetam as an add-on medication. Records of eight dogs were used retrospectively to determine a safe, efficient levetiracetam dosage. Fourteen dogs were entered into a prospective, open label, non-comparative study. After 2 months of levetiracetam oral treatment (10 mg/kg TID), 8/14 dogs responded significantly to the treatment and seizure frequency was reduced by ⩾50%. In dogs that remained refractory, the dosage was increased to 20 mg/kg TID for 2 months. One further dog responded to levetiracetam treatment. Levetiracetam responders had a significant decrease in seizure frequency of 77% (7.9 ± 5.2 to 1.8 ± 1.7 seizures/month) and a decrease in seizure days per month of 68% (3.8 ± 1.7 to 1.2 ± 1.1 seizure days/month). However, 6/9 responders experienced an increase in seizure frequency and seizure days after 4–8 months continuing with the levetiracetam treatment at the last effective dosage. Levetiracetam was well tolerated by all dogs and sedation was the only side-effect reported in just one of the 14 dogs."

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."

 Dietary supplementation with medium-chain TAG has long lasting cognition-enhancing effects in aged dogs. Pan Y, Larson B, Araujo JA. British J. Nutr. June 2010;103:1746–54. Quote: "The present study focused on the hypothesis that dietary supplementation with medium-chain TAG (MCT) will improve cognitive function in aged dogs by providing the brain with energy in the form of ketones. Aged Beagle dogs were subjected to a baseline battery of cognitive tests, which were used to establish cognitively equivalent control or treatment groups. The dogs in the treatment group were maintained on a diet supplemented with 5·5 % MCT. After an initial wash-in period, all the dogs were tested with a battery of cognitive test protocols, which assessed sequentially landmark discrimination learning ability, egocentric visuospatial function and attention. The groups were maintained on the diets for 8 months. The MCT-supplemented group showed significantly better performance in most of the test protocols than the control group. The group differences also varied as a function of task difficulty, with the more difficult task showing greater supplementation effects than the easier tasks. The group given the MCT supplement showed significantly elevated levels of β-hydroxybutyrate, a ketone body. These results indicate, first, that long-term supplementation with MCT can have cognition-improving effects, and second, that MCT supplementation increases circulating levels of ketones. The results support the hypothesis that brain function of aged dogs can be improved by MCT supplementation, which provides the brain with an alternative energy source."

Seizure Management in Dogs: Going Beyond Standard Therapy. C.W. Dewey. October 2010. Quote: "A common misconception concerning seizure management is that the achievement of no more than one seizure per month should be the goal of therapy. Such a goal would be of little benefit to the dog presenting with a history of monthly seizure activity. Alternatively, a dog that seizures daily prior to drug intervention and experiences two seizures per month afterwards would be incorrectly considered a treatment failure, using such arbitrary criteria. Concerns over potential side effects of drug therapy are based primarily on the use of phenobarbital and bromide. With the advent of the newer anticonvulsant drugs to be discussed in this presentation, improved seizure control is often possible without concurrent adverse side effects. There are a number of so-called “new” drugs for dogs with epilepsy, and they are discussed below in order of my perception of most to least effective. I will also briefly discuss a drug called pregabalin for which we recently reported the results of a clinical trial in refractory epileptics. My opinion is that pregabalin is often an effective drug. ... Gabapentin is a structural analog of GABA. Gabapentin is thought to exert its antiseizure effects via binding to the α2δ subunit of voltage-gated neuronal calcium channels. Long-term toxicity trials for gabapentin have not been reported in dogs. However, the drug seems to be very well tolerated by this species, usually with no side-effects. Sedation does not appear to be a common problem with gabapentin use in dogs, but occasionally occurs. There are two clinical reports of gabapentin use as an add-on drug for dogs with refractory epilepsy. Overall, the responder rate of these dogs was between 41% and 55%. In the author’s experience, gabapentin is moderately effective as an anticonvulsant drug in dogs. ... My colleagues and I have completed an oral pharmacokinetic study of pregabalin in both dogs and cats, and a clinical trial of pregabalin in refractory epileptic dogs. The median seizure reduction in the clinical study was approximately 50%."

Idiopathic Epilepsy in Dogs and Cats. William B. Thomas. Vet. Clin. Small. Anim. 2010;40:161–179. Quote: "Gabapentin binds to neuronal voltage-gated calcium channels, inhibiting calcium flow. A major advantage of this drug in people is that it is excreted unchanged by the kidneys, is not metabolized by the liver, and has little or no potential for drug interactions. In dogs, however, gabapentin is partially metabolized to N-methyl-gabapentin, with an elimination half life of 3 to 4 hours. Gabapentin improves seizure control when added to phenobarbital and/or bromide. A recommended starting dose is 10 mg/kg every 8 hours. Mild sedation and ataxia are the most common side effects."

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 and risk factors for canine epilepsy of unknown origin in the UK. L. Kearsley-Fleet, D. G. O’Neill, H. A. Volk, D. B. Church, D. C. Brodbelt. Vet. Rec. January 2013;172(13):338. Quote: "Epidemiological evaluation of canine epilepsy is an under-researched area. The objectives of this study were to estimate prevalence and investigate risk factors for epilepsy of unknown origin (EUO) among dogs attending primary veterinary practices in the UK. The clinical data analysed spanned a two-year period and included all dogs attending 92 primary veterinary clinics participating in the VetCompass project. Five hundred and thirty-nine EUO cases were identified giving a prevalence of 0.62% (95% CI 0.57% to 0.67%). Males were over 1.5 times as likely to have EUO compared with females (95% CI 1.44 to 2.06; P < 0.001). Of purebred dogs, the border terrier had 2.70 (95% CI 1.57 to 4.62; P < 0.001) and the German shepherd dog had 1.90 (95% CI 1.28 to 2.80; P=0.001) times increased odds of EUO compared with crossbred dogs. [Cavalier King Charles spaniel had 0.88 times.] In addition, the West Highland white terrier had reduced odds (OR 0.23; 95% CI 0.08 to 0.62; P=0.004) of EUO compared with crossbred dogs (likelihood ratio test P < 0.0001). ... No association was found with neuter status, colour or weight. ... Idiopathic epilepsy (IE) has also been seen more frequently in solid coat-colour Cavalier King Charles spaniels indicating that the number of colours may have some association with the disease (Rusbridge 2005). ... The current study highlights the clinical importance of epilepsy as a canine disorder in the UK. Increased awareness of sex and breed predispositions may assist clinicians with diagnosis. Further research is merited to evaluate the specific breed associations identified."

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."

Unusual manifestation of bromide toxicity (bromism) in an idiopathic epileptic dog already treated with phenobarbital. Fabio Stabile, Alberta de Stefani, and Luisa De Risio. Veterinary Record Case Report. April 2014;2(1). Quote: "A three-year seven-month-old female spayed Cavalier King Charles spaniel was diagnosed with idiopathic epilepsy. Because of poor seizure control, the dog was started on oral treatment with potassium bromide as adjunctive treatment to phenobarbital. The dog presented eight days following bromide loading, having developed sedation, general proprioceptive ataxia and generalised appendicular repetitive myoclonus [twitching of the limbs]. The serum bromide concentration was 15.9 mg/ml (target range 1 mg/ml to 2.5 mg/ml), which was suggestive of a bromide overdose. The dog improved after reduction of bromide dosing and no similar episodes were reported by the owners at a follow up of 26 months. To the authors’ knowledge this is the first report describing generalised repetitive myoclonus related to bromide toxicity."

Validation of the diagnosis canine epilepsy in a Swedish animal insurance database against practice records. Linda Heske, Mette Berendt, Karin Hultin Jäderlund, Agneta Egenvall, Ane Nødtvedt. Preventive Vet. Med. June 2014;114(3-4):145-150. Quote: "Canine epilepsy is one of the most common neurological conditions in dogs but the actual incidence of the disease remains unknown. A Swedish animal insurance database has previously been shown useful for the study of disease occurrence in companion animals. The dogs insured by this company represent a unique population for epidemiological studies, because they are representative of the general dog population in Sweden and are followed throughout their life allowing studies of disease incidence to be performed. The database covers 50% of all insured dogs (in the year 2012) which represents 40% of the national dog population. Most commonly, dogs are covered by both veterinary care insurance and life insurance. Previous studies have shown that the general data quality is good, but the validity of a specific diagnosis should be examined carefully before using the database for incidence calculations. The aim of the current study was therefore to validate the information contained in the insurance database regarding canine epilepsy. The validation focused on the positive predictive value and the data-transfer from the veterinary practice records to the insurance database. The positive predictive value was defined as the proportion of recorded cases that actually had the disease in question. The quality of the data-transfer was assessed by comparing the diagnostic codes in practice records to the codes in the insurance database. The positive predictive value of the diagnostic codes for canine epilepsy (combining “epileptic convulsions” and “idiopathic epilepsy”) in the insurance database was validated in a cross-sectional study where insurance claims for canine epilepsy were compared to diagnostic information in practice records. A random sample of dogs with a reimbursed insurance claim during 2006 was included in the study sample (n = 235). Practice records were requested by mail from attending veterinarians. Two independent examiners scrutinized all the records. All 235 dogs were coded correctly in the database as they really had suffered seizures with or without convulsions, and the quality of the data-transfer was therefore excellent. In total, 167 dogs (71%) were classified as cases of canine epilepsy according to pre-defined criteria, and the positive predictive value was therefore considered relatively high. The most common breeds were mongrel (n = 26), Labrador retriever (n = 26), Cavalier King Charles spaniel (n = 11), Golden retriever (n = 10) and and German shepherd (n = 10). Based on these results, it was concluded that the data regarding canine epilepsy in the insurance database can be used for further population studies."

Pharmacokinetics of levetiracetam in epileptic dogs when administered concurrently with phenobarbital, bromide, or phenobarbital and bromide in combination. K.R. Muñana, J.A. Nettifee-Osborne, M.G. Papich. J.Vet.Int.Med. July 2014;28(4):1358. Quote: "Levetiracetam (LEV) is a common add-on antiepileptic medication (AED) for dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs. The objective of this study was to evaluate the pharmacokinetics of LEV in epileptic dogs when administered concurrently with conventional AEDs. Eighteen client-owned dogs on maintenance therapy with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB-BR group, n = 6) were enrolled. All AEDs had attained steady state concentrations. Blood samples were collected at 0, 1, 2, 4 and 6 hours after a morning dose of LEV. Plasma LEV concentrations were determined by high-pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations using a noncompartmental method, and AUC calculated using the trapezoidal method. Compared to the PB and PB-BR groups, the BR group had significantly higher Cmax (70.6 ± 24.0 μg/mL, versus 35.5 ± 13.7 μg/mL and 25.3 ± 9.0 μg/mL, respectively) and AUC0-Cn (314.2 ± 114.3 h*μg/mL versus 127.0 ± 64.7 h*μg/mL and 91.0 ± 42.2 h*μg/mL, respectively), and significantly lower CL/F (68.9 ± 22.1 mL/h/kg versus 172.1 ± 81.9 mL/h/kg and 247.6 ± 126.9 mL/h/kg, respectively). Concurrent administration of phenobarbital alone or in combination with bromide significantly alters the disposition of LEV in epileptic dogs compared to concurrent administration of bromide alone. These findings warrant consideration when utilizing LEV for add-on therapy in dogs with epilepsy."

A cohort study of epilepsy among 665,000 insured dogs: Incidence, mortality and survival after diagnosis. L. Heske, A. Nødtvedt, K. Hultin Jäderlund, M. Berendt, A. Egenvall. Vet.J. October 2014. Quote: "The main objective of this study was to estimate the incidence and mortality rates of epilepsy in a large population of insured dogs and to evaluate the importance of a variety of risk factors. Survival time after a diagnosis of epilepsy was also investigated. The Swedish animal insurance database used in this study has previously been helpful in canine epidemiological investigations. More than 2,000,000 dog-years at-risk (DYAR) were available in the insurance database. In total, 5013 dogs had at least one veterinary care claim for epilepsy [including 173 cavalier King Charles spaniels], and 2327 dogs were euthanased or died because of epilepsy. Based on veterinary care claims the incidence rate of epilepsy (including both idiopathic and symptomatic cases) was estimated to be 18 per 10,000 DYAR. Dogs were followed up until they were 10 (for life insurance claims) or 12 years of age (veterinary care claims). Among the 35 most common breeds in Sweden, the Boxer was at the highest risk of epilepsy with 60.3 cases per 10,000 DYAR, and also had the highest mortality rate of 46.7 per 10,000 DYAR (based on life insurance claims). Overall, males were at a higher risk than females (1.4:1). Median survival time (including euthanasia and death) after diagnosis was 1.5 years. In general, breeds kept solely for companionship lived longer after diagnosis than those kept for dual-purposes, such as hunting and shepherd and working breeds. The study demonstrates marked breed differences in incidence and mortality rates, which are assumed to reflect genetic predisposition to epilepsy."

Treatment in canine epilepsy - a systematic review. Marios Charalambous, David Brodbelt, Holger A Volk. BMC Vet. Research. Oct. 2014;10:257. Quote: "Background: Various antiepileptic drugs (AEDs) are used for the management of canine idiopathic epilepsy (IE). Information on their clinical efficacy remains limited. A systematic review was designed to evaluate existing evidence for the effectiveness of AEDs for presumptive canine IE. Electronic searches of PubMed and CAB Direct were carried out without date or language restrictions. Conference proceedings were also searched. Peer-reviewed full-length studies describing objectively the efficacy of AEDs in dogs with IE were included. Studies were allocated in two groups, i.e. blinded randomized clinical trials (bRCTs), non-blinded randomized clinical trials (nbRCTs) and non-randomized clinical trials (NRCTs) (group A) and uncontrolled clinical trials (UCTs) and case series (group B). Individual studies were evaluated based on the quality of evidence (study design, study group sizes, subject enrolment quality and overall risk of bias) and the outcome measures reported (in particular the proportion of dogs with ≥50% reduction in seizure frequency). Results: Twenty-six studies, including two conference proceedings, reporting clinical outcomes of AEDs used for management of IE were identified. Heterogeneity of study designs and outcome measures made meta-analysis inappropriate. Only four bRCTs were identified in group A and were considered to offer higher quality of evidence mong the studies. A good level of evidence supported the efficacy of oral phenobarbital and imepitoin and fair level of evidence supported the efficacy of oral potassium bromide and levetiracetam. For the remaining AEDs, favorable results were reported regarding their efficacy, but there was insufficient evidence to support their use due to lack of bRCTs. Conclusions: Oral phenobarbital and imepitoin in particular, as well as potassium bromide and levetiracetam are likely to be effective for the treatment of IE. However, variations in baseline characteristics of the dogs involved, significant differences between study designs and several potential sources of bias preclude definitive recommendations. There is a need for greater numbers of adequately sized bRCTs evaluating the efficacy of AEDs for IE."

Clinical efficacy and safety of imepitoin in comparison with phenobarbital for the control of idiopathic epilepsy in dogs. Tipold, A., Keefe, T. J., Loscher, W., Rundfeldt, C., de Vries, F. Vet. Pharm. & Therapeutics. April 2015;38(2):160-168. Quote: "The anticonvulsant activity and safety of imepitoin, a novel antiepileptic drug licensed in the European Union, were evaluated in a multicentre field efficacy study as well as in a safety study under laboratory conditions. Efficacy of imepitoin was compared with phenobarbital in 226 client-owned dogs in a blinded parallel group design. The administration of imepitoin twice daily in incremental doses of 10, 20 or 30 mg/kg demonstrated comparable efficacy to phenobarbital in controlling seizures in dogs. The frequency of adverse events including somnolence/sedation, polydipsia and increased appetite was significantly higher in the phenobarbital group. In phenobarbital-treated dogs, significantly increased levels of alkaline phosphatase, gamma-glutamyl-transferase and other liver enzymes occurred, while no such effect was observed in the imepitoin group. In a safety study under laboratory conditions, healthy beagle dogs were administered 0, 30, 90 or 150 mg/kg imepitoin twice daily for 26 weeks. A complete safety evaluation including histopathology was included in the study. A no-observed-adverse-event level of 90 mg/kg twice daily was determined. These results indicate that imepitoin is a potent and safe antiepileptic drug for dogs."

Assessment into the usage of levetiracetam in a canine epilepsy clinic. Rowena MA Packer, George Nye, Sian Elizabeth Porter, holger A Volk. BMC Vet. Research. February 2015. Quote: "Background: The purpose of this retrospective study was to describe the use of LEV in a canine epilepsy clinic and determine the long-term efficacy and tolerability of LEV in veterinary clinical practice. The electronic database of a UK based referral hospital was searched for LEV usage in dogs with seizures. Information and data necessary for the evaluation were obtained from a combination of electronic and written hospital records, the referring veterinary surgeons? records and telephone interviews with dog owners. Only dogs that were reportedly diagnosed with idiopathic epilepsy were included in the study. Results: Fifty-two dogs [including one cavalier King Charles spaniel] were included in this retrospective study. Two treatment protocols were recognised; 29 dogs were treated continuously with LEV and 23 dogs received interval or pulse treatment for cluster seizures. LEV treatment resulted in 69% of dogs having a 50% or greater reduction of seizure frequency whilst 15% of all the dogs were completely free from seizures. Seizure frequency reduced significantly in the whole population. No dog was reported to experience life-threatening side effects. Mild side effects were experienced by 46% of dogs and a significantly higher number of these dogs were in the pulse treatment group. The most common side-effects reported were sedation and ataxia. Conclusions: LEV appears to be effective and well tolerated for reduction of seizures."

Effect of Chronic Administration of Phenobarbital, or Bromide, on Pharmacokinetics of Levetiracetam in Dogs with Epilepsy. K.R. Muñana, J.A. Nettifee-Osborne, M.G. Papich. J.Vet. Int. Med. February 2015. Quote: "Background: Levetiracetam (LEV) is a common add-on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs. Hypothesis/Objectives: To evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs. Animals: Eighteen client-owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB–BR group, n = 6). Methods: Prospective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high-pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area-under-the-curve (AUC) calculated to the last measured time point. Results: Compared to the PB and PB–BR groups, the BR group had significantly higher peak concentration (Cmax) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 μg/mL, respectively, P < .001) and AUC (329 ± 114 versus 140 ± 64.7 and 98.7 ± 42.2 h*μg/mL, respectively, P < .001), and significantly lower clearance (CL/F) (71.8 ± 22.1 versus 187 ± 81.9 and 269 ± 127 mL/h/kg, respectively, P = .028). Conclusions and Clinical Importance: Concurrent administration of PB alone or in combination with bromide increases LEV clearance in epileptic dogs compared to concurrent administration of bromide alone. Dosage increases might be indicated when utilizing LEV as add-on treatment with phenobarbital in dogs."

International Veterinary Epilepsy Task Force’s current understanding of idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs. Velia-Isabel Hülsmeyer, Andrea Fischer, Paul J.J. Mandigers, Luisa DeRisio, Mette Berendt, Clare Rusbridge, Sofie F.M. Bhatti, Akos Pakozdy, Edward E. Patterson, Simon Platt, Rowena M.A. Packer, Holger A. Volk. BMC Vet. Res. September 2015;11:175. Quote: "Canine idiopathic epilepsy is a common neurological disease affecting both purebred and crossbred dogs. Various breed-specific cohort, epidemiological and genetic studies have been conducted to date, which all improved our knowledge and general understanding of canine idiopathic epilepsy, and in particular our knowledge of those breeds studied. However, these studies also frequently revealed differences between the investigated breeds with respect to clinical features, inheritance and prevalence rates. Awareness and observation of breed-specific differences is important for successful management of the dog with epilepsy in everyday clinical practice and furthermore may promote canine epilepsy research. The following manuscript reviews the evidence available for breeds which have been identified as being predisposed to idiopathic epilepsy with a proven or suspected genetic background, and highlights different breed specific clinical features (e.g. age at onset, sex, seizure type), treatment response, prevalence rates and proposed inheritance reported in the literature. In addition, certain breed-specific diseases that may act as potential differentials for idiopathic epilepsy are highlighted. --- Cavalier King Charles Spaniel: For several years it has been suggested that idiopathic epilepsy may occur as an independent disease in this breed and may not be the consequence of the frequently occurring Chiari-like malformation. This hypothesis was supported by a study from 2013 that did not find a significant association between the degree of the Chiari-like malformation, (such as degree of ventriculomegaly) and the occurrence of epileptic seizures. However, an overlapping of the two diseases cannot be entirely excluded. According to the findings of the study published in 2013 the seizure type was defined as (primary) generalised epileptic seizures in 39% of the dogs, as focal epileptic seizures in 36% and as focal epileptic seizures evolving into generalised seizures in 25% of dogs. No detailed data regarding potential modes of inheritance are available; however, epilepsy was found more frequently in lines originating from whole-colour dogs. Potential breed-specific diseases that may mimic idiopathic epilepsy: Cavalier King Charles Spaniels are also known to suffer from Episodic Falling (paroxysmal exercise-induced dyskinesia). Episodic falling is a movement disorder that typically manifests between the age of 4 months and four years. Falling episodes are induced by physical activity, stress and excitement and manifest with hypertonicity of the limbs resulting in inability to move or even complete collapse. In contrast to epileptic seizures, consciousness usually is not affected during these episodes. A gene test is available for episodic falling that is based on evidence of a BCAN (brevican) mutation. Older Cavalier King Charles spaniels (>5 years old) have a high prevalence of myoclonus [spasmodic jerky contraction of groups of muscles], which manifests most commonly as a brief jerking of the head and forelimbs when the dog is standing or sitting. Initially the syndrome is relatively benign but can be progressive with affected dogs suffering frequent jerks which may interfere with function, for example cause the dog to fall or stumble. The syndrome can be confused with focal epileptic seizures but generally does not respond to AEDs [antiepileptic drugs] licenced for dogs although may respond to levetiracetam (personal communication Clare Rusbridge February 2015). The pathogenesis of the myoclonus is as yet undetermined."

International veterinary epilepsy task force consensus proposal: diagnostic approach to epilepsy in dogs. Luisa De Risio, Sofie Bhatti, Karen Muñana, Jacques Penderis, Veronika Stein, Andrea Tipold, Mette Berendt, Robyn Farqhuar, Andrea Fischer, Sam Long, Paul JJ. Mandigers, Kaspar Matiasek, Rowena MA Packer, Akos Pakozdy, Ned Patterson, Simon Platt, Michael Podell, Heidrun Potschka, Martí Pumarola Batlle, Clare Rusbridge, Holger A. Volk. BMC Vet. Res. September 2015;11:148. Quote: "This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause. Differentiation of epileptic seizures from other non-epileptic episodic paroxysmal events can be challenging. ... Certain movement disorders are breed-specific, generally occur in young dogs and their phenotype may be well characterised. To date the associated genetic defect (e.g., deletion in the gene BCAN) has been identified only in Cavalier King Charles spaniels with paroxysmal exercise-induced dyskinesia (also known as episodic falling). ... Criteria that can be used to make this differentiation are presented in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset <6 months or >6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose. This consensus article represents the basis for a more standardised diagnostic approach to the seizure patient. These recommendations will evolve over time with advances in neuroimaging, electroencephalography, and molecular genetics of canine epilepsy."

International veterinary epilepsy task force consensus proposal: outcome of therapeutic interventions in canine and feline epilepsy. Heidrun Potschka, Andrea Fischer, Wolfgang Löscher, Ned Patterson, Sofie Bhatti, Mette Berendt, Luisa De Risio, Robyn Farquhar, Sam Long, Paul Mandigers, Kaspar Matiasek, Karen Muñana, Akos Pakozdy, Jacques Penderis, Simon Platt, Michael Podell, Clare Rusbridge, Veronika Stein, Andrea Tipold, Holger A Volk. BMC Vet. Res. September 2015;11:177. Quote: "Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered."

A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy. Tsz Hong Lawa1a, Emma S. S. Daviesa, Yuanlong Pana, Brian Zanghia, Elizabeth Wanta, Holger A. Volk. Brit. J. Nutrition. September 2015. Quote: "Despite appropriate antiepileptic drug treatment, approximately one-third of humans and dogs with epilepsy continue experiencing seizures, emphasising the importance for new treatment strategies to improve the quality of life of people or dogs with epilepsy. A 6-month prospective, randomised, double-blinded, placebo-controlled cross-over dietary trial was designed to compare a ketogenic medium-chain TAG diet (MCTD) with a standardised placebo diet in chronically antiepileptic drug-treated dogs with idiopathic epilepsy. Dogs were fed either MCTD or placebo diet for 3 months followed by a subsequent respective switch of diet for a further 3 months. Seizure frequency, clinical and laboratory data were collected and evaluated for twenty-one dogs completing the study. ... This study included twenty-one dogs of seventeen different breeds including the following: American bulldog, two Beagles, two Border Collies, Boxer, Cavalier King Charles Spaniel, English Bull Terrier, English Springer Spaniel, German Shepherd, Golden Retriever, Lhasa Apso, Mastiff, Rhodesian Ridgeback, Saint Bernard, Siberian Husky, Slovakian Rough Haired Pointer, Welsh Springer Spaniel, and three cross breeds. ... Seizure frequency was significantly lower when dogs were fed the MCTD (2·31/month, 0–9·89/month) in comparison with the placebo diet (2·67/month, 0·33–22·92/month, P=0·020); three dogs achieved seizure freedom, seven additional dogs had ≥50 % reduction in seizure frequency, five had an overall <50 % reduction in seizures (38·87 %, 35·68–43·27 %) and six showed no response. Seizure day frequency were also significantly lower when dogs were fed the MCTD (1·63/month, 0–7·58/month) in comparison with the placebo diet (1·69/month, 0·33–13·82/month, P=0·022). Consumption of the MCTD also resulted in significant elevation of blood β-hydroxybutyrate concentrations in comparison with placebo diet (0·041 (sd 0·004) v. 0·031 (sd 0·016) mmol/l, P=0·028). There were no significant changes in serum concentrations of glucose (P=0·903), phenobarbital (P=0·422), potassium bromide (P=0·404) and weight (P=0·300) between diet groups. In conclusion, the data show antiepileptic properties associated with ketogenic diets and provide evidence for the efficacy of the MCTD used in this study as a therapeutic option for epilepsy treatment."

A single-blinded phenobarbital-controlled trial of levetiracetam as mono-therapy in dogs with newly diagnosed epilepsy. N. Fredsø, A. Sabers, N. Toft, A. Møller, M. Berendt. Vet. J. November 2015. Quote: "Treatment of canine epilepsy is problematic. Few antiepileptic drugs have proven efficacy in dogs and undesirable adverse effects and pharmacoresistance are not uncommon. Consequently, the need for investigation of alternative treatment options is ongoing. The objective of this study was to investigate the efficacy and tolerability of levetiracetam as mono-therapy in dogs with idiopathic epilepsy. The study used a prospective single-blinded parallel group design. Twelve client-owned dogs were included and were randomised to treatment with levetiracetam (30 mg/kg/day or 60 mg/kg/day divided into three daily dosages) or phenobarbital (4 mg/kg/day divided twice daily). Control visits were at days 30, 60 and then every 3 months for up to 1 year. Two or more seizures within 3 months led to an increase in drug dosage (levetiracetam: 10 mg/kg/day, phenobarbital: 1 mg/kg/day). Five of six levetiracetam treated dogs and one of six phenobarbital treated dogs withdrew from the study within 2–5 months due to insufficient seizure control. In the levetiracetam treated dogs there was no significant difference in the monthly number of seizures before and after treatment, whereas in the phenobarbital treated dogs there were significantly (P=0.013) fewer seizures after treatment. Five phenobarbital treated dogs were classified as true responders (≥50% reduction in seizures/month) whereas none of the levetiracetam treated dogs fulfilled this criterion. Adverse effects were reported in both groups but were more frequent in the phenobarbital group. In this study levetiracetam was well tolerated but was not effective at the given doses as mono-therapy in dogs with idiopathic epilepsy."

Effects of a ketogenic diet on ADHD-like behavior in dogs with idiopathic epilepsy. Rowena M.A. Packer, Tsz Hong Law, Emma Davies, Brian Zanghi, Yuanlong Pan, Holger A. Volk. Epilepsy & Behavior. February 2016;55:62-68. Quote: "Objectives: Epilepsy in humans and rodent models of epilepsy can be associated with behavioral comorbidities including an increased prevalence of attention-deficit/hyperactivity disorder (ADHD). Attention-deficit/hyperactivity disorder symptoms and seizure frequency have been successfully reduced in humans and rodents using a ketogenic diet (KD). The aims of this study were (i) to describe the behavioral profile of dogs with idiopathic epilepsy (IE) while on a standardized nonketogenic placebo diet, to determine whether ADHD-like behaviors [excitability, chasing, and trainability] are present, and (ii) to examine the effect of a ketogenic medium chain triglyceride diet (MCTD) on the behavioral profile of dogs with idiopathic epilepsy (IE) compared with the standardized placebo control diet, including ADHD-like behaviors. Methods: A 6-month prospective, randomized, double-blinded, placebo-controlled, crossover dietary trial comparing the effects of the MCTD with a standardized placebo diet on canine behavior was carried out. Dogs diagnosed with IE, with a seizure frequency of at least 3 seizures in the past 3 months (n=21), were fed the MCTD or placebo diet for 3 months andwere then switched to the alternative diet for 3 months. Owners completed a validated behavioral questionnaire to measure 11 defined behavioral factors at the end of each diet period to report their dogs' behavior, with three specific behaviors hypothesized to be related to ADHD: excitability, chasing, and trainability. Results: The highest scoring behavioral factors in the placebo and MCTD periods were excitability (mean ± SE: 1.910 ± 0.127) and chasing (mean ± SE: 1.824 ± 0.210). A markedly lower trainability score (mean ± SE: 0.437±0.125) than that of previously studied canine populations was observed. The MCTD resulted in a significant improvement in the ADHD-related behavioral factor chasing and a reduction in stranger-directed fear (p b 0.05) compared with the placebo diet. The latter effect may be attributed to previously described anxiolytic effects of a KD. Conclusions: These data support the supposition that dogs with IE may exhibit behaviors that resemble ADHD symptoms seen in humans and rodent models of epilepsy and that a MCTD may be able to improve some of these behaviors, along with potentially anxiolytic effects."

Risk factors for cluster seizures in canine idiopathic epilepsy. Rowena M.A. Packer, Nadia K. Shihaba, Bruno B.J. Torres, Holger A. Volk. Research in Vet. Sci. February 2016. Quote: "Cluster seizures (CS), two or more seizures within a 24-hour period, are reported in 38–77% of dogs with idiopathic epilepsy (IE). Negative outcomes associated with CS include a reduced likelihood of achieving seizure freedom, decreased survival time and increased likelihood of euthanasia. Previous studies have found factors including breed, sex and neuter status are associated with CS in dogs with IE; however, only one UK study in a multi-breed study of CS in IE patients exists to the author's knowledge, and thus further data is required to confirm these results. Data from 384 dogs treated at a multi-breed canine specific epilepsy clinic were retrospectively collected from electronic patient records. 384 dogs were included in the study, of which nearly half had a history of CS (49.1%). Dogs with a history of CS had a younger age at onset than those without (p = 0.033). In a multivariate model, three variables predicted risk of CS: a history of status epilepticus (p = 0.047), age at seizure onset (p = 0.066) and breed (German Shepherd Dog) (p < 0.001). Dogs with a history of status epilepticus and dogs with an older age at seizure onset were less likely to be affected by cluster seizures. German Shepherd Dogs (71% experiencing CS) were significantly more likely to suffer from CS compared to Labrador Retrievers (25%) (p < 0.001). ... The occurrence of CS [cluster seizures] in each individual breed was compared with the Labrador Retriever. GSDs (71% CS, p<0.001), Boxers (67%, p=0.001), Cavalier King Charles Spaniels (67%, p=0.002), Staffordshire Bull Terriers (62%, p=0.007) and Border Collies (62%, p=0.001) were significantly more likely to suffer from CS compared to Labrador Retrievers (25% CS) at the univariate level. No significant association was found between CS and size (48% large, 38% medium, 14% small; p>0.05). ... Although GSDs and Boxers were found to be more affected by CS than Labrador Retrievers in both studies, three further breeds, the Cavalier King Charles Spaniel, Staffordshire Bull Terriers and Border Collie were identified in this study at the univariate level. ... There was no association between sex, neuter status, body size and CS. Further studies into the pathophysiology and genetics of CS are required to further understand this phenomenon."

2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs. M. Podell, H.A. Volk, M. Berendt, W. Löscher, K. Muñana, E.E. Patterson, S.R. Platt. J. Vet. Internal Med. February 2016. Quote: "This report represents a scientific and working clinical consensus statement on seizure management in dogs based on current literature and clinical expertise. The goal was to establish guidelines for a predetermined, concise, and logical sequential approach to chronic seizure management starting with seizure identification and diagnosis (not included in this report), reviewing decision-making, treatment strategies, focusing on issues related to chronic antiepileptic drug treatment response and monitoring, and guidelines to enhance patient response and quality of life. Ultimately, we hope to provide a foundation for ongoing and future clinical epilepsy research in veterinary medicine. ... When Should Treatment Be Started? ... The panel recommendations to initiate AED [antiepileptic drugs] treatment are summarized as follows: (i) Identifiable structural lesion present or prior history of brain disease or injury; (ii) Acute repetitive seizures or, status epilepticus (ictal event ≥5 minutes or ≥3 or more generalized seizures within a 24-hour period); (iii) ≥2 or more seizure events within a 6-month period; and (iv) Prolonged, severe, or unusual postictal periods. ... Which Drug Should Be Used First? ... Phenobarbital: High recommendation and likely be effective treatment. Potassium Bromide: Moderate recommendation and most likely to be effective treatment. Primidone: Not recommended for treatment and may be ineffective and/or dangerous to the patient. Imepitoin: High recommendation and likely be effective treatment. Levetiracetam: Low recommendation and may not be effective treatment. Zonisamide: Low recommendation and may not be effective treatment. ... How Should Monitoring Be Performed? ... What Are The Risks Of Treatment? ... When Should a Second AED Be Started and Which Should be Used? ... What Alternative Nonpharmacologic Treatments Are Available? ... ."

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