Idiopathic epilepsy is the benchmark against which all canine seizure cases are evaluated. Establishing a differential diagnosis hinges significantly on the dog’s signalment and seizure pattern. Key factors include the animal’s age at onset, the type and frequency of seizures, the medical history, and the findings from physical and neurological examinations. Idiopathic epilepsy, characterized by recurrent seizures without an identifiable underlying structural brain lesion or other neurological deficits, is presumed to be genetic and often age-dependent. Understanding the typical signalment and seizure patterns of this condition is crucial as it serves as a reference point for diagnosing other seizure disorders.
In typical cases of idiopathic epilepsy, seizures are generalized tonic-clonic, often preceded by an aura. The frequency of seizures typically progresses gradually, with initial seizures occurring weeks to months apart, varying by breed. Larger breeds may exhibit progressive epilepsy that becomes refractory to treatment, sometimes experiencing cluster seizures every 10 to 30 days. If more than two seizures occur within the first week of onset, idiopathic epilepsy should be questioned, and a thorough diagnostic workup is warranted. Seizures typically begin in dogs between 6 months and 5 years of age. Earlier onset within this range generally indicates more severe and difficult-to-control epilepsy. While any dog can be affected, certain breeds have a lower incidence or lack documented cases of idiopathic epilepsy. In breeds like Dobermans and sight hounds, alternative causes for seizures should always be investigated, irrespective of the seizure pattern or age at onset. Breeds predisposed to severe epilepsy include German Shepherd Dogs, Golden Retrievers, Springer Spaniels, Border Collies, and Siberian Huskies. Other commonly affected breeds include Shelties, Welsh Corgis, Nova Scotia Duck Tolling Retrievers, Belgian Sheepdogs, Cocker Spaniels, and Poodles of all sizes.
Other Characteristics of the Idiopathic Epileptic Dog
Dogs diagnosed with idiopathic epilepsy typically present with unremarkable findings on physical, neurological, and funduscopic examinations. Hematology, biochemical profiles, and urinalysis are generally within normal reference ranges. Further diagnostic tests, such as cerebrospinal fluid (CSF) analysis and magnetic resonance imaging (MRI), are also usually unremarkable in these cases.
In most instances of idiopathic epilepsy, a CSF collection is not essential for diagnosis, as the history, signalment, and seizure pattern are highly characteristic.
Differential Diagnosis Based on Dog’s Age
0-6 Months Group
- Epilepsy of the Young Dog (Juvenile Epilepsy): The etiology is often unknown, likely multifactorial, and related to the young brain’s propensity to seize. Onset typically occurs at or before 16 weeks of age. Approximately 25% of affected puppies have affected littermates. Seizures can be generalized tonic-clonic, focal with secondary generalization, or complex focal. The onset is usually acute, with no other clinical signs. Seizures can be frequent, progressing to status epilepticus. Database results are typically normal or show mild changes suggestive of self-limiting viral infection. Phenobarbital is administered at 5 mg/kg every 12 hours, with dosage adjustments until serum levels reach 100-120 µmol/L. Serum levels should be monitored every five days. Puppies have a different drug metabolism requiring higher oral doses. After six months seizure-free, the animal can be gradually weaned off phenobarbital over 6 to 18 months. The prognosis is good with controlled seizures, allowing affected puppies to become normal, seizure-free, and drug-free dogs. Cocker Spaniels appear to be predisposed to this condition.
- Inflammatory Diseases: This category includes viral diseases (excluding canine distemper), protozoal (Neospora caninum), fungal, and rickettsial diseases (Ehrlichia canis), as well as bacterial infections.
- Toxicities: Ingestion of slug bait, spoiled dairy products, or compost (mycotoxins) can cause seizures, particularly in young dogs with poor eating habits. Treatment follows protocols for status epilepticus, potentially involving intravenous diazepam followed by a constant rate infusion.
- Trauma: Physical injury can lead to seizures.
- Hypoglycemia: Primarily observed in miniature breeds.
- Hydrocephalus: While sometimes listed as a cause of seizures, significant neurological signs related to the thalamocortex and cerebellum are usually present concurrently.
- Hepatic Encephalopathy: Seizures, typically generalized tonic-clonic, are rare with portosystemic shunts but can occur. Marked neurological signs often precede and follow seizures. Seizures may increase post-surgical correction.
6 Months to 5 Years Old
- Idiopathic/Genetic Epilepsy: The most common cause in this age group.
- Inflammatory Diseases (Encephalitis):
- Infectious: Viral (non-Canine Distemper and Canine Distemper), Bacterial, Rickettsial (ehrlichiosis, Rocky Mountain Spotted Fever), Protozoal (Neospora, Toxoplasmosis), Fungal, Parasitic. Systemic signs are often present.
- Non-infectious: Granulomatous meningoencephalomyelitis (GME), immune-mediated diseases, and breed-specific chronic inflammatory diseases (e.g., Yorkshire Terrier, Maltese, Pug).
- Thalamocortical Tumors: Intracranial tumors are usually primary. Metastatic involvement is rare. Clinical signs typically have a short course with possible subtle behavioral changes.
Over 5 Years Old
- Likely Symptomatic Epilepsy (unknown etiology): Seizures with no clear underlying cause.
- Inflammatory Diseases: As described above.
- Thalamocortical Tumors: Brain tumors can cause seizures in older dogs.
- Encephalopathy (unknown cause): Age-related changes can lead to seizures.
- Beta Cell Tumors: Pancreatic tumors can sometimes be associated with seizures.
Age-Based Prognosis (<10 months): Dogs with normal neurological examinations and databases that begin seizing before 16 weeks of age have a high probability of becoming seizure and drug-free. This probability decreases to 50% for onset between 16 weeks and 6 months, and the prognosis is guarded for onset between 6 and 10 months of age.
Diagnostic Workup of a Dog with Recurrent Seizures
The diagnostic process involves a thorough history, consideration of signalment, documentation of seizure patterns, physical, neurological, and funduscopic examinations, and a minimum database (CBC, chemistry, urinalysis). Advanced diagnostics like MRI and CSF analysis may also be indicated.
When comparing a patient’s presentation to the model of idiopathic epilepsy, a differential diagnosis is established. Laboratory data serve to confirm suspicions rather than being the sole diagnostic focus. It’s a common misconception that normal blood work automatically confirms idiopathic epilepsy; however, it primarily indicates that the disease is confined to the central nervous system.
Antiepileptic Treatment
The primary antiepileptic drugs (AEDs) accepted for use in dogs are potassium bromide (KBr), phenobarbital (PB), and benzodiazepines.
Potassium Bromide (KBr)
KBr is often considered a first-line AED, with efficacy comparable to phenobarbital for generalized seizures. It is safe, inexpensive, and excreted unchanged in the urine, bypassing the liver. No significant organ toxicity or hematologic/biochemical abnormalities have been reported with long-term use. Falsely elevated chloride levels may occur due to laboratory equipment limitations. When combined with phenobarbital, hind limb incoordination can occur at serum bromide levels above 20 mmol/L. KBr is available in flavored syrups and chewable tablets. It’s typically administered once daily due to its long half-life, though twice-daily dosing may be necessary to prevent vomiting. Dietary salt intake significantly impacts bromide levels, requiring a consistent diet for stable concentrations.
Recommendations:
- Dose: 20-40 mg/kg once daily, or divided twice daily.
- Therapeutic Serum Levels: 17-22 mmol/L. Monotherapy may allow for levels of 20-30 mmol/L with minimal side effects.
- Half-life: 22-38 days.
- Monitoring: Levels measured at 6 weeks (target 8-12 mmol/L) and again at 4-5 months (target >17 mmol/L).
Disadvantages: Long half-life, hind limb ataxia (especially with phenobarbital), polyuria/polydipsia, weight gain, increased risk of pancreatitis, dietary considerations, and occasional aggression.
Phenobarbital (PB)
Phenobarbital is a potent AED but is often used as a second-line treatment after KBr. It induces the cytochrome P450 system, increasing the body’s capacity to clear substances, including itself. This can lead to progressively lower serum levels despite regular dosing, especially within the first six months. Phenobarbital is habit-forming and requires regular dose adjustments. Hepatotoxicity is a significant concern with chronic use and high serum levels (>140 µmol/L), though it can be avoided with adequate monitoring.
Recommendations:
- Baseline blood work: Prior to treatment.
- Initial dose: 2-5 mg/kg divided twice daily, potentially increasing to >8 mg/kg to reach therapeutic range.
- Therapeutic Serum Levels: 100-120 µmol/L.
- Half-life: 45-80 hours, but shortens with use due to auto-induction.
- Monitoring: Serum levels measured at four weeks, then adjusted and re-evaluated every four weeks until the optimal range is reached. Monitor liver enzymes (SAP, ALT), albumin, and AED levels every 6-8 months if levels are >120 µmol/L, and yearly if within the optimal range.
Disadvantages: Shortening half-life with use, habit-forming, hepatotoxicity, weight gain, polydipsia/polyuria, potential for pancreatitis, and rare idiosyncratic bone marrow suppression.
Benzodiazepines
Benzodiazepines (e.g., clonazepam, clorazepate) are generally not recommended for long-term maintenance due to the development of refractoriness. However, diazepam is crucial for treating cluster seizures and status epilepticus. Rectal diazepam can be used at home for cluster seizures. Clonazepam may be added to KBr and/or phenobarbital therapy for partial or generalized seizures refractory to conventional drugs. Gabapentin and levetiracetam are newer add-on therapies, though their cost can be a deterrent.
When to Start and Stop Treatment?
Treatment should be initiated:
- After the second generalized seizure, especially if the animal is under three years old at onset.
- With more than one generalized seizure per day at first occurrence.
- For convulsive status epilepticus.
Treatment should generally not be stopped once a diagnosis of epilepsy is made, or after two years seizure-free. In structural disorders with successful treatment, discontinuation may be considered after 6 months seizure-free.
Stopping Phenobarbital or Potassium Bromide: This must be done very gradually to avoid withdrawal seizures. If serum levels are within the therapeutic range, a minimum of 16 weeks (often 6-18 months) is necessary for tapering.
If epilepsy remains uncontrolled despite phenobarbital and potassium bromide, consultation with a veterinary neurologist is recommended.
