19 Apr 2022
Simona Radaelli
Job Title
Image © Dvorakova Veronika / Adobe Stock
Epilepsy is the most common neurological disorder seen in dogs. Up to 0.75% of the dog population is estimated to suffer from epilepsy.
Seizure classification has been evolving over the years in human and animal medicine, as terminology is key for an informed and informative communication between practitioners and pet owners:
Epileptic seizures can be divided into three major groups, based on their aetiology:
The recognition of a seizure and its description can be challenging for its witness, which is often the owner.
The ubiquitous presence of mobile phones with an integrated camera has been very helpful in this transition, and it is important to educate the owners to video record any paroxysmal event occurring to their pets.
Differentiating seizures from vestibular attacks, other movement disorders or even cardiovascular disease is very important for the diagnostic and therapeutic approach.
During focal epileptic seizures, abnormal electrical activity arises in a localised group of neurons in one hemisphere.
The clinical signs reflect the functions of the areas involved, and they are characterised by lateralised and/or regional signs (motor, autonomic and/or behavioural signs).
Generalised epileptic seizures normally present as tonic, clonic or tonic-clonic epileptic seizures, and they are characterised by bilateral involvement of the cerebral hemispheres.
Animals lose consciousness during convulsive epileptic seizures, and salivation, urination and/or defecation often also occur.
Myoclonic seizures are characterised by jerking movements usually affecting both sides of the body without loss of consciousness.
Atonic seizures (drop attacks) are non-convulsive, and they are characterised by sudden and general loss of muscle tone, which usually causes the animal to collapse.
Generalised epileptic seizures last less than five minutes, occur at rest or during sleep, and are usually followed by post-ictal signs such as disorientation, restlessness, lethargy, deep sleep, hunger, thirst, ataxia, proprioceptive deficits and, less commonly, aggressive behaviour and blindness.
During the ictus, the animal cannot be distracted and the owner cannot alter the course of the event.
Focal epileptic seizures with secondary generalisation is the most common seizure type observed in the dog.
The onset is often very short (seconds to minutes) and it may be difficult to detect; the secondary generalisation follows rapidly with convulsions.
The seizure starts with focal signs (regional motor, autonomic and/or behavioural), rapidly spreads and is followed by a convulsive stage (bilateral tonic, clonic or tonic-clonic activity and loss of consciousness).
Collecting accurate descriptions of seizures from the owners is very important to recognise this type.
The main criteria for the diagnosis of epileptic seizures are:
IE is diagnosed by exclusion – it is based on the age at onset; normal inter-ictal physical and neurological examinations; and on exclusion of metabolic, toxic and structural cerebral disorders through diagnostic investigations.
The criteria for the diagnosis of IE have been grouped in three tiers of confidence levels:
As an average, 70% of epileptic dogs respond well to anti-epileptic drugs (AEDs). The aim of daily treatment is to reduce the frequency and/or severity of the seizures, as seizure-free status is very difficult to achieve.
Seizure control depends on several factors such as the breed of the animal, the owner’s compliance and the correct dosage of AEDs (as well as serum levels within the therapeutic range).
When to begin AED treatment in dogs is decided based on different factors, but no evidence-based guidelines exist (Panel 1).
It is recommended to start anti-epileptic drug treatment when:
Long-term seizure management seems to be most successful when therapy is started early – especially in dogs with a high seizure frequency and in breeds known to suffer from a severe form of epilepsy (such as the Australian shepherd dog, border collie, Italian spinone, German shepherd dog and Staffordshire bull terrier).
The choice of AED is based on the animal’s health, the type of seizures, specific factors of the AED, and the owner’s compliance and lifestyle, as in many cases the AED treatment has a potential lifelong duration. AED treatment is always decided for each individual: we don’t treat epilepsy, we treat epileptic patients.
Monotherapy is the initial goal when treating epilepsy, to reduce possible drug-to-drug interactions and adverse effects.
Drugs such as phenobarbital and potassium bromide are broadly used, but new drugs such as gabapentin, levetiracetam, felbamate, topiramate, pregabalin and zonisamide are becoming very popular as an add-on therapy in refractory cases and/or to reduce the side effects of the other AEDs.
The main downsides of some of the newer drugs are their shorter half-lives (requiring more frequent administrations), reduced scientific data and costs.
A seizure diary is very useful for monitoring the response to treatment.
This should include dates, frequency, duration and description of the episodes. Once therapy is initiated, dates of dosage changes and blood monitoring should be added.
Epilepsy treatment can be challenging. In some cases, despite the use of multiple medications, seizure control is not achieved.
Genetic factors play a role in refractory cases (patients that do not respond to anti-epileptic treatment), but other controllable factors may also be involved.
Poor owner compliance and drug discontinuation can be avoided by assessing the owner’s lifestyle and by explaining the negative consequences associated with drug discontinuation.
Inadequate blood levels and inadequate dosage, as well as drug interaction/malabsorption, can be responsible for failure of seizure control.
To achieve a successful treatment of the epileptic dog, owners need to be educated thoroughly on the management of their animals and expectations (Panel 2).
To achieve a successful treatment, dog owners should be educated on (Bhatti et al, 2015):
Discontinuation of an AED is justified in cases of remission of seizures or life-threatening adverse effects. Treatment for idiopathic epilepsy involves lifelong AED administration in most cases.
Remission has been reported in dogs with rates between 15% to 30%.
The decision to gradually taper the dose of an AED should be taken on an individual basis in cases of seizure freedom of at least one to two years.
In case of life-threatening adverse effects, immediate cessation of AED administration and 24-hour observation are necessary; loading with an alternative AED should be initiated promptly.
Cluster seizures are a common neurological emergency. They are defined as two or more seizures in 24 hours. Clusters of up to three seizures are generally not a significant problem; however, the frequency can be unpredictable, and they can lead to status epilepticus, which requires more aggressive treatment .
Rectal diazepam should be available to the owner for emergency treatment at home and it should be administered after the second seizure in 24 hours.
Application should be carefully discussed to avoid injury to the patient.
The aim is to stop seizure activity in prolonged episodes or, in cases where clusters are the recognised pattern, to try to reduce the number of seizures.
The recommended dose is 0.5mg/kg to 2mg/kg to a maximum of three applications within 24 hours.
Rectal absorption (10 minutes) is faster than oral or IM injection, although the absorption rate can be variable.
Intranasal diazepam could be a suitable alternative option, but no appropriate preparation is available.
Oral diazepam is not a choice for seizure management.
Pulse protocol with levetiracetam can also be used as emergency home treatment for cluster seizures.
Breed predisposition has been recognised in idiopathic epilepsy; therefore, some authors have also suggested to name it genetic epilepsy.
Studies are ongoing to prove a genetic predisposition in some breeds (such as the border collie and the Italian spinone, although the author notes no data is published to confirm this yet).
Idiopathic epilepsy with a proven or suspected genetic background has been reported for some purebred dogs, but most studies have not yet identified causative gene mutations.
Some studies have reported genetic mutations associated with idiopathic epilepsy in the lagotto Romagnolo (focal, juvenile remitting epilepsy) the Belgian shepherd dog and the Rhodesian ridgeback (photosensitive myoclonic epilepsy), but the hypothesis is that epilepsy represents a complex disease with interaction of multiple genes and environmental factors.
Lafora disease in miniature wirehaired dachshunds belongs to a group of structural disorders, as the gene defect (mutation in the EPM2 gene) results in a storage disease that causes seizures and other neurological deficits.
Genetic testing to investigate pharmacoresistance to AEDs is also under way – particularly in individuals that show resistance to most AEDs, raising the suspicion of a more complex cause than simple drug metabolism (multi-drug transporter hypothesis and drug target hypothesis of pharmacoresistance).
One study has shown the benefit of a ketogenic medium-chain TAG diet (MCTD) as an adjunctive method in dogs on anti-epilepsy treatment.
The MCTD resulted in a reduction in seizure frequency per month compared to the placebo-standardised diet (Law et al, 2015).
The beneficial effects of MCTD are supposed to be due to:
A commercial diet is now available, or medium-chain triglyceride oil can be added to the normal diet at 1tsp/10kg bodyweight of the dog twice a day.
Vagal stimulation is used in humans that are refractory to AED treatment. A pacemaker-like device, implanted subcutaneously, can be activated to stimulate the vagus nerve in the neck.
This will stimulate the solitary nucleus, and several cortical and subcortical areas, to interfere with the seizure activity.
It can be a treatment option for the future in refractory dogs, but further studies are required and the device is still very expensive for veterinary use.
Surgery to resect the corpus callosum or focal cortical areas (seizure focus, identified by EEG) in refractory patients has been described in human medicine, but its use in veterinary medicine still needs large-scale reports.
Acupuncture is based on the implantation of gold bead implants or acupuncture needles in specific locations (acupoints) to stimulate the nervous system. This practice is rarely used in veterinary medicine.
Canine epilepsy has attracted the attention and efforts of neurologists and scientists alike, as it is the most common neurologic disorder, and its clinical manifestation can be traumatic.
Common comprehensive classification, accurate diagnostic process and effective treatment are the key aspects of epilepsy management, and they are constantly evolving with the studies carried out in human and animal medicine.
At present, several studies are ongoing to improve our understanding of the pathophysiology of seizures, and of the potential genetic involvement in their occurrence and pharmacoresistance.
The results of these studies should favour the development of more targeted and new therapeutic approaches. The results of genetic studies could also ultimately benefit breeding regulations through screening and prevention of diseases.
While studies are ongoing, it is key that the clinician recognises, diagnoses and intervenes promptly when dealing with seizures, and that the owner’s education and compliance are given priority and value.
