Summery :
- Diagnosis, causes and classification of canine epilepsy
- Genetics of Canine Epilepsy
- Etiology of epilepsy
- Medical Management Options: How to Treat Canine Epilepsy?
- Future prospects
- Bibliography
1-General
Epilepsy is the most common neurological disorder seen in dogs and is estimated to affect approximately 0.75% of the canine population.
The term epilepsy refers to a heterogeneous disease , characterized by the presence of recurrent and unprovoked epileptic seizures resulting from an anomaly of the brain .
The condition may be inherited (genetic or idiopathic epilepsy), caused by structural problems in the brain ( structural epilepsy ), or arise from unknown causes (epilepsy of unknown cause).
Determining an appropriate treatment regimen for canine epilepsy depends on an accurate diagnosis of the type and cause of seizures, after which more effective options can be identified.
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2- Diagnosis, causes and classification of canine epilepsy
There is no universally accepted classification system for seizures in dogs.
The biggest problem is the subjective recognition of symptoms. Dog owners may notice a specific behavior that typically precedes an epileptic seizure , making it indicative of a behavioral change. On the other hand, there is no direct way to determine the presence of a pre-seizure event, as is the case in humans.
Recently, the International Task Force on Veterinary Epilepsy proposed a classification scheme for veterinary seizures, which is similar, but not identical, to the current human classification system.
Using this method, the seizure is classified primarily based on where in the brain it begins, also using specific features to characterize the event.
Recognizing and observing the epileptic event is important!
The description of the seizures is the most important information in the diagnosis of canine epilepsy.
There are two basic types of seizures: generalized and focal .
Generalized epileptic seizures
Generalized seizures initially involve both cerebral hemispheres and are characterized by clinical signs evident on both sides of the body.
Most generalized seizures manifest with bilateral involuntary muscle movements or sudden losses or increases in muscle tone .
During a generalized epileptic seizure, the individual’s awareness of the environment is usually impaired and salivation , urination , and/or defecation may occur .
Focal epileptic seizures
Focal seizures originate in a distinct area of the brain and are characterized by signs that affect a single side or a specific part of the body.
Focal seizures may present with abnormal motor activity (facial twitching , chewing movements, movement of a limb), behavioral signs (fear, attention seeking), and/or changes in autonomic functions (pupil dilation , salivation, vomiting ).
Awareness may or may not be impaired during focal seizures.
A focal seizure can spread to both cerebral hemispheres and become generalized.
The observation continues even after the epileptic event: what happens to the dog?
When observing seizures, it is important to keep a diary containing detailed information, including:
- affected body parts;
- when seizures occur;
- how often do seizures occur;
- how long they last (see the attached diary template for recording retention).
The veterinarian and owner should also pay close attention to how the dog behaves immediately after a seizure. Although some animals return to normal quickly during the post-ictal period , others have difficulty standing or moving.
They may also experience blindness , sedation , anxiety , or other changes in behavior.
These symptoms can last for a variable length of time and may influence the choice of treatment.
In some cases, seizures may result from exposure to a specific stimulus , such as a disease, a toxin, or problems with metabolism (reactive seizures).
Any potentially implicated event should be brought to the attention of your veterinarian, as such reactive seizures are not generally treated with standard antiepileptic drugs.
Reflex seizures , which are seizures that consistently occur after a particular exposure, such as a loud noise, a flashing light, or a more complex movement or behavior, have also been reported in dogs.
Classification of Canine Epilepsy by Cause
It is not always possible to identify the cause of epileptic seizures in dogs; however, canine epilepsies can generally be classified into one of three categories , based on etiology .
Idiopathic epilepsy is defined as epilepsy without an identifiable structural cause and having a presumed genetic origin .
The presentation of repetitive seizures in dogs between the ages of 1 and 5 years with a normal neurological examination, in which there are no known structural brain abnormalities, metabolic diseases, or exposure to toxins , is often considered a form of idiopathic epilepsy.
The definition of idiopathic epilepsy suggests that the exact cause of the seizures is unknown , although the condition is assumed to be inherited.
However, it can sometimes be determined, for example when the seizures are the result of a specific genetic defect known to be present in some breeds.
Structural epilepsy is the diagnosis for seizures that occur due to observable damage or malformations of the brain. For example, structural epilepsy may occur after an inflammatory disease , the growth of an intracranial tumor , or after trauma to the head. It may also be the result of congenital malformations or a vascular event , such as a stroke .
Brain abnormalities seen in structural epilepsies can sometimes be detected using an MRI scan or by analyzing cerebrospinal fluid .
Testing for structural epilepsy may be recommended if the dog exhibits neurological abnormalities between seizures, or if the dog is outside the typical age range for idiopathic epilepsy. Interictal changes are less common in dogs with idiopathic epilepsy.
Conditions in which a structural cause is suspected, but has not been identified in the diagnostic evaluation, are considered to be of unknown cause.
Reactive seizures , those that occur in response to specific stimuli (such as a metabolic imbalance or a toxin), are not considered a form of epilepsy, because they are not caused by an abnormality in the brain.
3- Genetics of Canine Epilepsy
A large number of genetic mutations have been associated with epilepsy, both in humans and in mice.
In humans, the inheritance of epilepsy is generally complex, involving interactions of one or more genes with each other and, potentially, with the interaction of environmental factors; this is probably also true for dogs. However, the extent of inbreeding within specific dog breeds has allowed the identification of increased risk of developing seizures. At least 26 dog breeds have shown some signs of inherited epilepsy.
Genetic mutations have been identified, many of which include a group of diseases known as neuronal ceroid lipofuscinoses . These are storage disorders in which mutations lead to the abnormal accumulation of a product within cells , ultimately leading to neuronal dysfunction or death .
A gene for an inherited epilepsy has been identified in Lagotto Romagnolo dogs . That gene, LGI2, is similar to the previously identified human epilepsy gene LGI1, and scientists believe that a number of inherited epilepsies may have similar causes in humans and dogs.
Research into potential similarities between canine and human epilepsy has also led to the identification of several candidate genes that may predict the effectiveness of antiepileptic treatment in certain breeds.
4- Etiology of epilepsy
The specific biochemical mechanisms that cause seizures are not yet fully understood in either dogs or humans, although it is known that seizures result from a dysfunction in the electrical activity of the brain .
Seizures are generally thought to be caused by an imbalance between excitatory and inhibitory activity in specific areas of the brain, leading to either excessive brain activity or unusually depressed activity.
However, in the absence of structural damage or metabolic insults, the causes of this dysfunction are unclear.
There is some evidence to suggest that abnormal excitatory processes may be caused by functional abnormalities in neurons, particularly mutations in ion channels, which are essential for the electrical function of cells, but this explanation is likely to apply only to a subset of idiopathic epilepsies. Further research is needed into the specific causes of the various forms of epilepsy; current understanding is incomplete.
5- Medical Management Options: How to Treat Canine Epilepsy?
The information provided below is for informational purposes only and is not a substitute for the advice of your veterinarian. Do not give any medication to your dog without a prescription from your veterinarian.
Antiepileptic drugs ( AEDs ) work primarily by inhibiting the action of excitatory neurotransmitters , stimulating inhibitory pathways , or altering the function of ion channels in the brain .
Not all drugs work the same way in all animals and their safety profiles are quite variable.
A single isolated seizure is not usually considered a reason to initiate treatment with AEDs.
Treatment with these drugs is usually indicated when:
- multiple generalized seizures occurred within 24 hours ;
- a dog has had at least two epileptic seizures in a six-month period ;
- a dog exhibits unusual or severe signs during the post-ictal period.
Once treatment has been declared necessary, the process of choosing the right drug requires a balance between efficacy and tolerability.
Although many short-term side effects can be managed by titrating drug dosages, some antiepileptic drugs have the potential to cause significant adverse effects .
Therefore, it is important to choose and test drugs carefully and to recognize that not all epilepsies are amenable to drug treatment.
Canine Anti-Epilepsy Drugs: Effectiveness and Side Effects
Phenobarbital , a first-generation AED, is one of the most widely used drugs in veterinary patients because it is effective, relatively inexpensive, well tolerated, and easily dosed .
Serious side effects include loss of blood cells (cytopenias) and liver toxicity.
Other side effects include sedation, ataxia , and increased appetite and water consumption.
Dogs can also develop tolerance to phenobarbital over time and are susceptible to withdrawal effects as physical dependence can develop .
Potassium bromide is another first-generation AED used to treat canine epilepsy. When used in combination with phenobarbital and other liver-metabolized AEDs , dosages may be reduced to decrease the risk of liver damage.
Bromide may also be useful in resolving some cases of epilepsy that do not respond to phenobarbital monotherapy.
Side effects of bromide include sedation, ataxia, vomiting, and increased appetite and water consumption.
Second-generation AEDs used in dogs include levetiracetam , zonisamide , felbamate , gabapentin , pregabalin , and topiramate . Of these, levetiracetam and zonisamide are the most commonly used.
Levetiracetam is considered a particularly safe treatment option across a wide range of doses, however its efficacy remains unclear.
Side effects are considered mild, with sedation and ataxia reported most commonly.
Additionally, co- administration with phenobarbital may influence the length of time it remains in the bloodstream.
Zonisamide is metabolised by the liver and may cause liver toxicity, although this is rarely observed .
Other adverse effects include sedation, ataxia, vomiting, and loss of appetite.
It is well absorbed, works through multiple mechanisms, and has been shown to be effective against a variety of types of seizures in humans.
Because it interacts with phenobarbital, doses of zonisamide should be increased when the two drugs are used in combination.
Lamotrigine , a second – generation human epilepsy drug, is not recommended for use in dogs because it can cause cardiac arrhythmias .
In recent years, several third-generation AEDs have been marketed for human use that may prove useful in the treatment of canine epilepsy.
Lacosamide has been shown to be well tolerated in humans and there are some dog-specific data to support its use.
Rufinamide , a new AED unlike any other, may also have some potential for treating dogs.
Finally, several other types of drugs to treat epilepsy are also being studied, including drugs that reduce inflammation , alter connections between neurons, and address other brain health issues, but they are not yet ready for general use.
Pharmacological dosage
Determining the appropriate dose for an AED is a lengthy process .
Although the initial indication is determined by weight , different dogs metabolize these drugs differently. Therefore, a series of blood tests are often needed to evaluate serum drug levels over time to ensure that levels remain high enough to be therapeutic, but low enough to not be toxic.
While measuring serum AED levels is a useful monitoring tool , it is not a substitute for clinical judgment in determining the appropriate type and dose of drug for an individual dog.
Drug-resistant epilepsy
Drug-resistant, or refractory , epilepsy presents a therapeutic problem both in terms of dosage and choice of drug.
Refractory epilepsy is diagnosed when treatment with at least two appropriate antiepileptic drugs fails and occurs in 30-40% of all dogs with epilepsy.
Occasionally, it can be treated with the addition of second- or third-generation drugs, such as gabapentin, zonisamide, levetiracetam, or pregabalin in a multidrug regimen.
In some cases, crisis management may remain uncontrolled.
6- Future prospects
Researchers continue to study the causes of canine epilepsy, both inherited and acquired, and new therapies to more safely and effectively treat canine seizures. Epilepsy in dogs and humans is similar enough that canine epilepsy research not only has a direct impact on the health of dogs, but also has the potential to improve the lives of human epileptic populations.
Elements of translational research, those that bridge the gap between species, can be seen in a wide range of clinical areas. Many of the types of familial epilepsy seen in dogs are similar to those that cause inherited seizures in humans, and drug research has been shown to be beneficial for both species.
Canine epilepsies have also been used as a testing ground for new treatment options that could help both dogs and humans. For example, preliminary research using intracranial electroencephalography (iEEG) in dogs suggests that the technique could be a way to predict epileptic seizures, which could be incredibly useful for people who currently suffer from seemingly random epileptic events.
There are limitations, of course. Canine epilepsy is not identical to human epilepsy, and several drugs have already been shown to have differential toxicity in dogs and humans. Additionally, owners have limited ability to monitor their dogs’ seizures, especially when compared to people’s ability to report their own seizures. However, the extent to which naturally occurring epilepsy in dogs is similar to epilepsy in humans presents a unique opportunity to study canine epilepsy as a model to help both dogs and their owners.
7- Bibliography
Potschka, H., Fischer, A., von Rüden, E.-L., Hülsmeyer, V., Baumgärtner, W. 2013. Canine epilepsy as a translational model? Epilepsia. 54:571-579.
Berendt M, Farquhar RG, Mandigers PJ, Pakzody A, Bhatti SF, De Risio L, Fischer A, Long S, Matsiasek K, Munana K, Patterson EE, Penderis J, Platt S, Podell M, Potschka H, Pumarola MB, Rusbridge C, Stein VM, Tipold A, Volk HA. International Veterinary Epilepsy Task Force consensus report on epilepsy definition, classification and terminology in companion animals. 2015. BMC Vet Res 11:182.
Ekenstedt, KJ and Oberbauer, AM Inherited Epilepsy in Dogs. 2013. Topics in Compan An Med. 28:51-58.
Heske L, Nodvedt A, Jaderlund KH, Berendt M, Egenvall A. A cohort study of epilepsy among 665,000 insured dogs: incidence, mortality and survival. 2014. Vet J; 202:471-6.
Howbert, J.J., Patterson, E.E., Stead, S.M., Brinkmann, B., Vasoli, V., et al. 2014. Forecasting seizures in dogs with naturally occurring epilepsy. PLOS One. 9:e81920.
Moore, S.A. 2013. A clinical and diagnostic approach to the patient with seizures. Topics in Compan An Med. 28:46-50.
Muñ ana , KR 2013. Management of refractory epilepsy. Topics in Compan An Med. 28:67-71.
Patterson, E.E. 2013. Epileptogenesis and companion animals. Topics in Compan An Med. 28:42-45.
Podell M. 2013. Antiepileptic drug therapy and monitoring. Topics in Compan An Med. 28:59-66.
Podell, M, Volk HA, Berendt M, Löscher W, Muñana K, Patterson EE, Platt SR. 2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs. 2016. J Vet Intern Med 30:477-80.
