Disease progression and treatment response of idiopathic epilepsy in Australian Shepherd dogs.

BACKGROUND: Idiopathic epilepsy (IE) in Australian Shepherds (ASs) occurs worldwide but there is a lack of description of the epilepsy syndrome in this breed. The ABCB1-1Δ mutation is more prevalent in ASs than in many other dog breeds. HYPOTHESIS: Australian Shepherds suffer from a poorly controlled IE syndrome with prevailing severe courses. Seizure control and ABCB1-1Δ mutation might be related in this breed. ANIMALS: Fifty ASs diagnosed with IE and 50 unaffected ASs. METHODS: Predominant study design is a longitudinal cohort study. Pedigrees, medical records, seizure, and treatment data of ASs with IE were analyzed descriptively. Sex, color, and the ABCB1-1Δ genotype were compared between case and control groups and ASs with poorly or well-controlled seizures. Differences in survival times were assessed by logrank tests and Cox regression analysis. RESULTS: Idiopathic epilepsy in ASs is dominated by moderate and severe clinical courses with the occurrence of cluster seizures and status epilepticus and a high seizure frequency. Poor seizure control and a high initial seizure frequency (≥10 seizure days/first 6 months) are associated with shorter survival times (P < .05). Poor seizure control, unrelated to the ABCB1(MDR1) genotype, is evident in 56% of epileptic ASs. Pedigree analysis suggests a genetic basis. CONCLUSION AND CLINICAL IMPORTANCE: Frequent severe clinical courses, poor seizure control unrelated to the ABCB1(MDR1) genotype, and a young age at death compromise animal welfare and warrant further genetic studies to unravel the underlaying molecular mechanisms of IE and seizure control in the breed.

Polymorphisms in the ABCB1 gene in phenobarbital responsive and resistant idiopathic epileptic Border Collies.

BACKGROUND: Variation in the ABCB1 gene is believed to play a role in drug resistance in epilepsy. HYPOTHESIS/OBJECTIVES: Variation in the ABCB1 gene encoding the permeability-glycoprotein could have an influence on phenobarbital (PB) resistance, which occurs with high frequency in idiopathic epileptic Border Collies (BCs). ANIMALS: Two hundred and thirty-six client-owned BCs from Switzerland and Germany including 25 with idiopathic epilepsy, of which 13 were resistant to PB treatment. METHODS: Prospective and retrospective case-control study. Data were collected retrospectively regarding disease status, antiepileptic drug (AED) therapy, and drug responsiveness. The frequency of a known mutation in the ABCB1 gene (4 base-pair deletion in the ABCB1 gene [c.296_299del]) was determined in all BCs. Additionally, the ABCB1 coding exons and flanking sequences were completely sequenced to search for additional variation in 41 BCs. Association analyses were performed in 2 case-control studies: idiopathic epileptic and control BCs and PB-responsive and resistant idiopathic epileptic BCs. RESULTS: One of 236 BCs (0.4%) was heterozygous for the mutation in the ABCB1 gene (c.296_299del). A total of 23 variations were identified in the ABCB1 gene: 4 in exons and 19 in introns. The G-allele of the c.-6-180T > G variation in intron 1 was significantly more frequent in epileptic BCs resistant to PB treatment than in epileptic BCs responsive to PB treatment (P(raw) = .0025). CONCLUSIONS AND CLINICAL IMPORTANCE: A variation in intron 1 of the ABCB1 gene is associated with drug responsiveness in BCs. This might indicate that regulatory mutations affecting the expression level of ABCB1 could exist, which may influence the reaction of a dog to AEDs.

Epilepsy in Border Collies: clinical manifestation, outcome, and mode of inheritance.

BACKGROUND: There is a lack of data on idiopathic epilepsy (IE) in Border Collies (BCs) in the veterinary literature. HYPOTHESIS: Genetic epilepsy occurs in BCs and is frequently characterized by a severe clinical course and poor response to medical treatment. ANIMALS: Forty-nine BCs diagnosed with IE. METHODS: Medical records, seizure data, treatment data, and pedigree information of affected dogs were collected. Cases were classified phenotypically as affected or not affected; mild, moderate, or severe clinical course; active epilepsy (AE) or remission; and drug resistant or not drug resistant. RESULTS: Clinical manifestations were classified as having a moderate (33%) or severe clinical course (49%), characterized by a high prevalence of cluster seizures and status epilepticus. Survival time was significantly decreased in dogs < 2 years of age at seizure onset, and in dogs with a severe clinical course. Drug resistance was apparent in 71% of 24 dogs treated with > 2 antiepileptic drugs. The epilepsy remission rate was 18%. Median age at onset was significantly higher and initial seizure frequency was significantly lower in dogs with remission compared with dogs with AE. Pedigree analyses indicated a strong genetic founder effect in the appearance of epilepsy, resembling autosomal recessive inheritance. CONCLUSION AND CLINICAL IMPORTANCE: The present study confirms the occurrence of genetically mediated epilepsy with a frequent severe clinical course and drug resistance in BCs. The results provide information about the long-term prognosis of IE in BCs for veterinarians and concerned owners, and may benefit breeders as well.

Canine status epilepticus due to acute intoxication.

OBJECTIVES: The purpose of this study was to describe the type of toxin ingested, clinical presentation and outcome of dogs with status epilepticus (SE) due to acute poisoning presented to a large referral veterinary hospital. MATERIALS AND METHODS: Retrospective case series. Medical records of all dogs suffering from SE were reviewed (Jan 1, 2002 to April 30, 2009). RESULTS: Fourteen dogs with SE due to acute intoxication were identified. Toxicological analyses (qualitative analysis with gas chromatography/mass spectrometry; n=11) detected poisonings with carbofuran, crimidine, paraoxone, metaldehyde, strychnine and diazinon. In the other three cases the uptake of a known poison was observed (zink phosphide, metaldehyde). None of the dogs showed evidence of neurological disease up to the day of presentation. The dogs were hospitalised for 2-10 days (median 5 days). The survival rate was 85.7%. None of the dogs experienced any more seizures after discharge (median observation period 2.6 years). CONCLUSION AND CLINICAL RELEVANCE: Ancillary to the acute clinical presentation, preliminary reports (possible uptake of poisonous material) and an inconspicuous medical history may suggest a tentative diagnosis. Managed adequately, these patients can have a high survival rate. Clinicians should also keep uncommon intoxications in mind.

Status epilepticus and epileptic seizures in dogs.

BACKGROUND: A special form of epileptic seizures (ES) is the life-threatening condition of status epilepticus (SE), which requires immediate and specific treatment based on a correct diagnosis of the underlying disease condition. HYPOTHESIS/OBJECTIVES: The objectives of this retrospective study were to determine prevalence of ES and SE in dogs presenting at a veterinary teaching hospital, to identify the etiology and relative risk (RR) for SE in general and at the onset of seizures. Furthermore the outcome for dogs suffering from SE was to be evaluated. ANIMALS: Three hundred and ninety-four dogs that were admitted to a veterinary teaching hospital (January 1, 2002 to March 31, 2008) with ES. METHODS: All medical records of dogs with ES were identified by screening the clinical documentation system and evaluated for inclusion in this retrospective study. RESULTS: Dogs with reactive seizures caused by poisoning had a significantly higher risk of developing SE (P < .001; RR = 2.74), particularly as 1st manifestation of a seizure disorder (P = .001; RR = 1.97). After SE, dogs with symptomatic epilepsy had a significantly lower probability of survival than dogs with idiopathic epilepsy (P < .001) and reactive ESs (P= .005). CONCLUSION AND CLINICAL IMPORTANCE: In dogs showing SE as the 1st manifestation of a seizure disorder, intoxication should always be considered and appropriate investigations undertaken. Dogs with SE owing to toxicosis have more favorable outcomes than dogs with symptomatic epilepsy (P < .001).