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Basics ⬇

Basics

Definition

Syndrome that is only epilepsy, with no demonstrable underlying brain lesion or other neurologic signs or symptoms; age-related; assumed genetic. The term ‘idiopathic’ replaced by ‘genetic’ according to the ILAE classification. (See Appendix VIII.)

Pathophysiology

  • Exact mechanism unknown.
  • Likely different mechanisms between breeds.

Systems Affected

Nervous

Genetics

Genetic basis suspected in Australian shepherd, beagle, Belgian shepherd (Groenendael and Tervuren), Bernese mountain dog, border collie, dachshund, English springer spaniel, Finnish Spitz, German shepherd, golden retriever, Keeshond, Irish wolfhound, Italian spinone, Labrador retriever, Shetland sheepdog, standard poodle, vizsla.

Incidence/Prevalence

0.5–2.3% of all dogs

Geographic Distribution

Widespread

Signalment

Species

Dog

Breed Predilections

Beagles; all shepherds (German, Australian, Belgian); Bernese mountain dogs; boxers; cocker spaniels; border collies; dachshunds; golden retrievers; Irish setters; Labrador retrievers; poodles (all sizes); Saint Bernards; Shetland sheepdogs; Siberian huskies; springer spaniels; Welsh corgis; wirehaired fox terriers. Can occur in any breed.

Mean Age and Range

  • Mean age 10 months–3 years
  • Range 6 months–5 years

Predominant Sex

Male predisposition in Bernese mountain dog.

Signs

General Comments

  • Seizures may be generalized (convulsive) from onset, or have a short aura (focal onset) with rapid secondary generalization.
  • An aura (animal appears frightened, dazed, seeks attention, or hides, etc.) frequently precedes the generalized seizure.
  • Focal seizures reported in the border collie, Finnish spitz dog, English springer spaniel, Labrador retriever, viszla, Belgian shepherd, standard poodle.

Historical Findings

  • First seizure-between 6 months and 5 years.
  • Seizures-often when patient is resting or asleep; often at night or early morning; frequency tends to increase if left untreated; affected animal falls on its side, becomes stiff, chomps its jaw, salivates profusely, urinates, defecates, vocalizes, and paddles with all limbs in varying combinations. Short duration (30–90 seconds).
  • Postictal behavior-confusion, disorientation; aimless, compulsive, blind, pacing; frequent polydipsia and polyphagia; recovery immediate or may take up to 24 hours.
  • Dogs with established epilepsy might have clustered generalized seizures at intervals of 1–4 weeks.
  • No asymmetry should be observed during seizure, e.g., twitching more pronounced on one side, limb contractions on one side, compulsive circling just prior or after the seizure.
  • Stimulus-induced seizures: seizures only upon specific stimulus (sound, event).

Physical Examination Findings

  • Patients often have recovered at time of presentation.
  • Patients may have postictal behavior.

Causes

Genetic in some breeds; of unknown cause in others.

Risk Factors

Known epilepsy in the family line

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • Seizure pattern (breed, age at onset, type and frequency of seizures)-most important factor toward diagnosis.
  • Acute onset of cluster seizures or status epilepticus-rule out toxicity or structural brain disease.
  • >2 seizures within the first week of onset-consider diagnosis other than genetic epilepsy.
  • Seizures at <6 months or >5 years of age-consider metabolic, or intracranial structural disease; rule out hypoglycemia in older dogs.
  • Focal seizures, or presence of neurologic deficits-rule out intracranial structural disease.

CBC/Biochemistry/Urinalysis

  • Usually normal
  • Perform before initiating drug therapy as baseline data.

Other Laboratory Tests

Bile acids to rule out hepatic encephalopathy unnecessary in dogs with seizures without accompanying episodic abnormal behavior.

Imaging

MRI-if seizure pattern does not fit genetic (idiopathic) epilepsy, neurologic deficits are present, or intracranial structural disease is suspected.

Diagnostic Procedures

  • CSF-for suspected structural intracranial diseases.
  • Electroencephalography-may see interictal spikes, polyspikes, and spike slow wave complexes.

Pathologic Findings

  • No primary lesion.
  • Secondary neuronal loss and gliosis from prolonged seizures.

Treatment ⬆ ⬇

Treatment

Appropriate Health Care

  • Outpatient-recurrence of isolated seizures.
  • Inpatient-for cluster seizures (>1 seizure q24h) or status epilepticus.

Nursing Care

Inpatients with seizure disorders require constant monitoring.

Diet

  • Dogs on chronic PB and KBr treatment often become overweight; weight-reducing program as necessary.
  • KBr treatment-insure steady levels of salt in diet; an increase in salt causes an increase in bromide excretion preferentially over chloride, with subsequent decreased serum KBr levels. Alternatively, a decrease salt content increases KBr serum level.
  • Trial with high-fat, low-carbohydrate diet-no improvement in seizure control.

Client Education

  • Severe cluster seizures and status epilepticus are life-threatening emergencies requiring immediate medical attention.
  • Keep a seizure calendar noting date, time, length, and severity of seizures to assess response to treatment.
  • Once treatment instituted, medication is life-long in most cases.
  • Abrupt drug withdrawal may cause seizures.

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

  • Initiate treatment at second generalized seizure if dog <2 years; when interictal period gradually shortens in the others.
  • Antiepileptic treatment-decreases frequency, severity, and length of seizures; perfect control rarely achieved.
  • Tolerance and refractoriness to treatment may develop.

Phenobarbital

  • Most efficacious AED in the dog.
  • Traditional first-line drug; initial dosage 3–5 mg/kg PO q12h; steady-state reached at 12–15 days but levels decrease significantly in the first 6 months owing to activation of lysosomal enzymes.
  • Optimal therapeutic serum levels-100–120 µmol/L or 23–28 µg/mL.
  • Oral loading dose (if needed)-6–10 mg/kg PO q12h for 2–3 days to reach therapeutic range rapidly.

Zonisamide

  • First-line drug when seizure frequency allows (<1/week); 5 mg/kg PO q12h; 10 mg/kg PO q12h as add-on to PB; half-life 15 hours; steady state 4 days; therapeutic range in human 10–45 µg/mL.

Levetiracetam

  • First-line drug when seizures have focal onset; <1 seizure/week; 20 mg/kg PO q8h; must be given q8h to reach adequate levels; no hepatic metabolism; safe; steady state 3 days; therapeutic range in human 10–40 µg/mL.

Potassium Bromide

  • Traditional first-line drug; initial dosage 30 mg/kg PO q24h or divided q12h; half-life 24–46 days; steady-state 3–4 months; varies with salt concentration in diet; bioavailability differs between dogs.
  • Optimal therapeutic serum levels-20–25 mmol/L or 1.6–2 mg/mL; if sole antiepileptic drug, 25–32 mmol/L or 2–2.25 mg/mL can be safely used.
  • Add-on to PB if seizures uncontrolled with optimal PB level-beneficial and synergistic effect.
  • Loading dose-may cause vomiting, diarrhea, profound longstanding sedation; if needed, double daily PO doses for 2 weeks.
  • Renal insufficiency decreases bromide elimination; half initial dosage.

Diazepam (At-Home Use)

  • To abort ongoing seizures-dogs with cluster seizures or status epilepticus.
  • Insert 0.5–1 mg/kg injectable drug in rectum via 1-inch teat cannula as soon as a seizure occurs; repeat 20 and 40 minutes later for a total of 3 insertions within 40 minutes; can be safely repeated once more in a 24-hour period.
  • Given early in the course of ongoing seizures, help abort subsequent seizures.

Contraindications

Aminophylline, theophylline

Precautions

-adrenergic agonists (e.g., phenylpropanolamine)-central nervous system excitation

Possible Interactions

  • Cimetidine and chloramphenicol-interfere with PB metabolism; may cause toxic PB levels.
  • PB lowers serum levels of zonisamide and levetiracetam.
  • PB may lower T4 and cause an upward trend in TSH without signs of hypothyroidism.
  • PB does not interfere with low-dose dexamethasone suppression tests regardless of dose and treatment.
  • Zonisamide decreases total T4.
  • Whenever animals on lifetime medication, refer to manufacturer's drug profile or to a pharmacist for interaction information.

Alternative Drug(s)

  • With polypharmacy, initiate add-on gradually to avoid sedation.
  • Gabapentin 10–20 mg/kg PO q8h; low efficacy as add-on. Newer analog pregabalin may be more efficacious (2–4 mg/kg q8h PO).
  • Clorazepate 0.5–1 mg/kg PO q8h.
  • Felbamate 30–70 mg/kg q12h–8h.
  • Topiramate 2–10 mg/kg PO q12h.
  • Phenytoin, valproic acid, carbamazepine, and ethosuximide-unsuitable pharmacokinetics in dogs.
  • Others-acupuncture, vagal nerve stimulation, transcranial magnetic motor stimulation.

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

  • Serum drug levels-preferentially at trough, at same time for each sampling; use same laboratory.
  • Phenobarbital-measure PB level 4 weeks after initiating therapy; adjust dose as needed; then repeat level every 2 weeks until optimal levels reached; with chronic use perform CBC, biochemistry, and PB level every 6–12 months; tabulate albumin, liver enzymes and serum drug levels to monitor trend; drug essentially hepatotoxic; most dogs eventually develop hepatotoxicity if serum levels >140 µmol/L (>33 µg/mL) for long time (>6–8 months). If hepatotoxicity suspected, perform bile acids.
  • KBr-serum level (along with PB level) 4–6 weeks after initiating (should be 8–12 mmol/L or 0.5–1 mg/mL) and at 3–4 months. If diet change required, consider diet salt content; monitor level accordingly. Monitor KBr level closely if renal insufficiency (isosthenuria or azotemia).
  • Zonisamide-measure level at 1 week. Monitor electrolytes and acid-base status to check for renal tubular acidosis.
  • Levetiracetam-measure level at 4 days.

Prevention/Avoidance

  • Abrupt discontinuation of medication may precipitate seizures.
  • Avoid salty treats in dogs treated with KBr.

Possible Complications

  • Recurrent episodes of cluster seizures and status epilepticus.
  • PB and KBr-polyuria, polydipsia, polyphagia, weight gain.
  • Phenobarbital-induced C-AP occurs frequently; may be an early sign of hepatotoxicity but of less concern if ALT is within reference range.
  • Phenobarbital-induced hepatotoxicity-after chronic treatment at high serum levels (>140 µmol/L or >33 µg/mL); often insidious in onset; only biochemical abnormality may be a decreased albumin.
  • Higher incidence of pancreatitis in patients treated with PB and/or KBr; once pancreatitis develops, recurrence is frequent.
  • Phenobarbital-rare bone marrow suppression with severe neutropenia (± sepsis) early in the course of treatment; discontinue drug.
  • Paradoxical hyperexcitability; discontinue drug. Risk factor for superficial necrolytic dermatitis.
  • KBr-when levels are >22 mmol/L or >1.8 mg/mL, owners may complain of patient's unsteadiness while managing stairs.
  • Zonisamide-mild sedation, decreased appetite, gastrointestinal signs.
  • One case of renal tubular acidosis and one case of acute idiosyncratic hepatic necrosis reported.
  • Levetiracetam-transient sedation.

Expected Course and Prognosis

  • Treatment for life.
  • Some dogs are well controlled with same drug and dosage for years; others remain poorly controlled despite polypharmacy.
  • Patient may develop status epilepticus and die.
  • Early treatment does not decrease occurrence of status epilepticus.
  • Normal expected lifespan but survival time shorter if episodes of status epilepticus.
  • Treatment with 2 AEDs not linked to poor prognosis.
  • Increased risk of premature death.
  • Marked breed differences in incidence and mortality rates.
  • Prognosis depends on combined veterinary expertise, therapeutic success, and owner's motivation.

Miscellaneous ⬆

Miscellaneous

Associated Conditions

Idiopathic epilepsy can be a reason for euthyroid sick syndrome in dogs.

Age-Related Factors

If onset <2 years of age, epilepsy more likely to be difficult to control; condition may becomes intractable.

Pregnancy/Fertility/Breeding

  • Avoid breeding affected animals.
  • Reported association between estrus and onset of seizures in intact bitches with presumptive ‘idiopathic’ epilepsy; two hormonally based patterns recognized: (1) during heat and (2) during a specific time point at the end of diestrus.

Abbreviations

  • AED = antiepileptic drug
  • ALT = alanine aminotransferase
  • C-AP = corticosteroid alkaline phosphatase
  • CSF = cerebrospinal fluid
  • KBr = potassium bromide
  • ILAE = International League Against Epilepsy
  • MRI = magnetic resonance imaging
  • PB = phenobarbital
  • TSH = thyroid stimulating hormone

Internet Resources

http://www.canine-epilepsy.net/

Author Joane M. Parent

Consulting Editor Joane M. Parent

Client Education Handout Available Online

Suggested Reading

Muñana KR.Management of refractory epilepsy. Top Companion Anim Med 2013, 28:67–71.

Podell M.Antiepileptic drug therapy and monitoring. Top Companion Anim Med 2013, 28:59–66.