Focal epilepsy in the Belgian shepherd: evidence for simple Mendelian inheritance

Objectives : To establish the mode of inheritance and describe the clinical features of epilepsy in the Belgian shepherd, taking the outset in an extended Danish dog family (199 individuals) of Groenendael and Tervueren with accumulated epilepsy. Methods : Epilepsy positive individuals (living and deceased) were ascertained through a telephone interview using a standardised questionnaire regarding seizure history and phenomenology. Living dogs were invited to a detailed clinical evaluation. Litters more than five years of age, or where epilepsy was present in all offspring before the age of five, were included in the calculations of inheritance. Results : Out of 199 family members, 66 dogs suffered from epilepsy. The prevalence of epilepsy in the family was 33%. Fifty‐five dogs experienced focal seizures with or without secondary generalisation, while four dogs experienced primary generalised seizures. In seven dogs, seizures could not be classified. The mode of inheritance of epilepsy was simple Mendelian. Clinical Significance : This study identified that the Belgian shepherd suffers from genetically transmitted focal epilepsy. The seizure phenomenology expressed by family members have a strong resemblance to what has been reported for familial partial (focal) epilepsy in humans with variable foci with suggestion of linkage to chromosome 2 and chromosome 22q12.     

Leukopenia in six healthy Belgian Tervuren.

A healthy 6.5-year-old sexually intact female Belgian Tervuren was found to be persistently leukopenic during preoperative evaluation for routine ovariohysterectomy. Abnormalities of the erythroid or myeloid series were not detected during bone marrow analysis. Blood samples for CBC were collected from 8 additional healthy Belgian Tervuren of both sexes and of various ages. Six of the 9 dogs were leukopenic, with WBC counts between 2.38 and 5.42 x 10(3) WBC/microl (mean +/- SD, 4.13 +/- 1.04 x 10(3) WBC/microl). Leukopenia was a persistent finding in the 3 dogs from which multiple blood samples were collected. All dogs were otherwise clinically normal. Leukopenia, as defined by a WBC count < 6.00 x 10(3) WBC/microl, may be a common finding in the Belgian Tervuren breed.     

Investigation of physiologic leukopenia in Belgian Tervuren dogs

BACKGROUND: Physiologic leukopenia in Tervuren dogs was reported in North America with a higher frequency in aged Tervurens. If not recognized, physiologic leukopenia can provoke unnecessary clinical investigations. HYPOTHESIS: The primary objective was to compare Tervurens and control dogs in Belgium with respect to the numbers of dogs with physiologic leukopenia. The secondary objectives were to compare Tervurens with control dogs and age classes within Tervurens and controls for parameters related to physiologic leukopenia. ANIMALS: Tervurens (n = 94) and control dogs (n = 48, maximum of 5 dogs per breed and 5 mixed breed dogs) were entered into the study. Dogs were 1-11 years old and healthy on routine physical examination. Dogs had no history of disease or drug administration in the previous 2 months. METHODS: Hematologic analyses were performed by an automated device within 30 hours of sampling. Blood smears were evaluated for cellular morphologic anomalies. RESULTS: Only 1 of the 94 Tervuren dogs had physiologic leukopenia (1.06%; 95% confidence interval, 0.05-5.22). Furthermore, the white blood cell (WBC) count in Tervuren dogs (median, 10.00 x 109/L; range, 5.90-20.80) was not significantly different (P = .55) from that of control dogs (median, 9.75 x 109/L; range, 5.20-20.90). The WBC count decreased significantly (P < .001) with age in Tervuren dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Physiologic leukopenia is uncommon in the Belgian Tervuren dog. Differences with earlier data published in North America might be due to genetic or environmental differences.     

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).     

Effectiveness of breeding guidelines for reducing the prevalence of syringomyelia

Several toy breed dogs are predisposed to syringomyelia (SM), a spinal cord disorder, characterised by fluid-filled cavitation. SM is a complex trait with a moderately high heritability. Selective breeding against SM is confounded by its complex inheritance, its late onset nature and high prevalence in some breeds. This study investigated the early outcome of existing SM breeding guidelines. Six hundred and forty-three dogs, 550 Cavalier King Charles spaniels (CKCS) and 93 Griffon Bruxellois (GB), were identified as having either one (454 dogs) or both parents (189 dogs) with MRI-determined SM status. Offspring without SM were more common when the parents were both clear of SM (SM-free; CKCS 70 per cent, GB 73 per cent). Conversely, offspring with SM were more likely when both parents had SM (SM-affected; CKCS 92 per cent, GB 100 per cent). A mating of one SM-free parent with an SM-affected parent was risky for SM affectedness with 77 per cent of CKCS and 46 per cent of GB offspring being SM-affected. It is recommended that all breeding dogs from breeds susceptible to SM be MRI screened; that the SM status at five years old is established; and all results submitted to a central database that can be used by dog breeders to better enable mate selection based on estimated breeding values.     

Investigation of breeding strategies to increase the probability that German shepherd dog and Labrador retriever dog guides would attain optimum size

An optimum-sized dog guide weighs 18 to 32 kg and measures 53 to 64 cm in height at the withers when mature body size is attained. Effects of selection index with and without restrictions, independent trait selection, directional selection, stabilizing selection, and negative assortative mating were modeled using data from German shepherd dogs and Labrador retrievers raised by the Seeing Eye, Inc., Morristown, NJ from 1979 to 1997. The selection goals were to decrease mature weight and mature height in German shepherd dogs and to decrease mature weight and increase mature height in Labrador retrievers. Mature weights were recorded for 1,333 German shepherd dog offspring and their 69 dams and 17 sires, and 1,081 Labrador retriever offspring and their 51 dams and 13 sires. Mature heights also were recorded for offspring and parents, including 871 German shepherd dogs from 70 dams and 15 sires, and 793 Labrador retrievers from 40 dams and 13 sires. Selecting on mature weight alone produced the highest aggregate genetic-economic gain for German shepherd dogs compared with the selection indices with and without restrictions, generating a 2.10-kg decrease in mature weight and a correlated 0.36-cm decrease in mature height. In Labrador retrievers, selecting for mature height alone produced the highest aggregate genetic-economic gain but caused an increase in mature weight. Weighting the two traits equally but in the opposite direction without restrictions was the only index that produced the desired effect of decreasing mature weight and increasing mature height in Labrador retrievers. Response to selection for one generation of directional selection for a single trait included a 0.50-kg decrease in mature weight for German shepherd dogs, a 0.59-kg decrease in mature weight for Labrador retrievers, a 0.18-cm decrease in mature height for German shepherd dogs, and a 0.91-cm increase in mature height for Labrador retrievers. Increasing the percentage of dogs attaining optimum size may decrease the cost of production for the Seeing Eye, Inc., because fewer dogs would need to be raised and trained to provide assistance to the same number of blind individuals.     

Focal loss of pigment in the Belgian Tervuren dog.

Hypopigmentation most commonly affecting the face and mouth of the Belgian Tervuren dog was characterized by an absence of melanocytes in the epidermis. Pigment loss usually occurred during young adulthood, and although there was partial repigmentation in some dogs, complete repigmentation did not occur. Treatment with vitamin and mineral supplements was unrewarding. The condition appeared to have some degree of heritability and to be similar to vitiligo in man.     

Bromide Therapy in Refractory Canine Idiopathic Epilepsy

On a retrospective basis, the response to adding chronic oral bromide (BR) to phenobarbital (PB) administration in 23 refractory canine idiopathic epileptics between 1986 and 1991 was studied. The mean age for an observed first seizure was 24 months (range 7 to 72) for all dogs. Thirteen (57%) dogs were males with no breed predisposition observed. All dogs were diagnosed as having idiopathic epilepsy based on normal metabolic and neurologic diagnostic evaluations. Dogs were evaluated before BR therapy for a mean time of 22 months (range 5 to 75 months). Seventeen dogs (74%) received multiple antiepileptic drugs (AEDs) before BR therapy. All animals were maintained on PB at least 4 months before the onset of BR therapy, with a mean trough serum concentration of 37.8 mcg/mL and no improvement in seizure severity or recurrence. Twelve dogs presented with generalized isolated seizures and 11 with generalized cluster seizures (two or more seizures within 24 hours) as their first seizure. The effects of BR therapy were evaluated for a mean time of 15 months (range 4 to 33), with 17 dogs (74%) followed for 12 or more months. The mean BR serum concentration for the 0 to 4 months time period was 117 mg/dL compared with 161 mg/dL for the greater than 4 months period. Overall, response to BR therapy was associated with a reduction in the total number of seizures in 83% of the dogs when compared with their respective pre-BR period. For those followed for 1 year after BR, there was a 53% reduction in the number of seizures compared with the previous 12 months. Furthermore, owners reported a decrease in seizure intensity (65% of dogs) and change to a less severe seizure type (22% of dogs) in those dogs that continued to have seizures. Seizure-free status was obtained in 26% of the dogs with protection continuing up to 31 months in one dog. No correlations could be determined between response to BR and either age of onset of the first seizure or interval from the first AED therapy to BR therapy. Adverse effects of concomitant BR and PB therapy were polydipsia (56% of dogs), polyphagia (30% of dogs), excessive sedation (30% of dogs), and generalized ataxia (17% of dogs). As a result of BR treatment, the PB dosage was reduced in eight dogs (35%). In conclusion, concomitant BR and PB was well tolerated in dogs of this study and was effective in treating refractory canine idiopathic epilepsy, regardless of prior interval of seizure activity or previous treatment. (Journal of Veterinary Internal Medicine 1993; 7:318–327. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

Electroencephalographic examination of epileptic dogs under propofol restraint

The main aim of this study was to identify interictal epileptiform discharges in a group of dogs with seizures of known aetiology (symptomatic epilepsy, SE) and in dogs with idiopathic epilepsy (IE). Propofol was used for chemical restraint in all dogs. We found electroencephalographic (EEG) changes that could be considered epileptiform discharges (EDs) in 5 out of 40 dogs (12.5%). The EEG changes identified were spikes in four cases and periodic epileptiform discharges in one case. All EDs were seen in the SE group. We conclude that the interictal electroencephalographic examinations of propofolanaesthetised dogs suffering from IE and SE rarely show epileptic discharges and that the diagnostic value of such EEGs in the work-up for epilepsy seems to be low as epileptic discharges were unlikely to be detected. However, positive findings are more likely to be connected with SE. We found frequent, transient EEG phenomena (spindles, K-complexes, vertex waves, positive occipital sharp transients of sleep, cyclic alternating patterns), which are non-epileptic but their differentiation from epileptic phenomena is challenging.     

A retrospective study on the use of acepromazine maleate in dogs with seizures

Use of acepromazine (i.e., acetylpromazine) maleate in dogs with a history of seizures is reportedly contraindicated because of the risk of decreasing the seizure threshold in these animals. In this retrospective study, acepromazine was administered for tranquilization to 36 dogs with a prior history of seizures and to decrease seizure activity in 11 dogs. No seizures were seen within 16 hours of acepromazine administration in the 36 dogs that received the drug for tranquilization during hospitalization. After acepromazine administration, seizures abated for 1.5 to 8 hours (n=6) or did not recur (n=2) in eight of 10 dogs that were actively seizing. Excitement-induced seizure frequency was reduced for 2 months in one dog.     

Influence of anesthetic regimen on the frequency of seizures after cervical myelography in the dog

We examined the influence of various anesthetic drug combinations on the frequency of seizures in dogs after cervical myelography with metrizamide. Over a 12-month period, 78 dogs admitted to the teaching hospital for cervical myelography were assigned randomly to 1 of 6 anesthetic protocols. Myelography was performed, and the dogs were observed for signs of seizure activity after recovery from anesthesia. The person making the decision as to whether or not a dog had had a seizure was unaware of the anesthetic protocol that had been used. Preanesthetic treatment with pentobarbital (5.0 mg/kg) and maintenance of anesthesia with methoxyflurane significantly reduced the frequency of seizures (P less than 0.05). No reduction in seizure frequency was seen with any anesthetic protocol using halothane as the maintenance agent.     

Seizure activity in dogs is associated with enhanced TIMP-2 expression of microglia

In the pathogenesis of epilepsy aberrant synaptic plasticity plays an important role. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are responsible for nervous tissue remodelling resulting in synaptic plasticity in the central nervous system (CNS) and might therefore be crucially involved in epileptogenesis. To assess the potential pathogenetic role of microglial MMPs and TIMPs in seizure induction, twenty-four dogs suffering from different intracranial diseases with and without seizure activity were comparatively examined. Microglial cells were isolated by density gradient centrifugation and their expression profiles of MMP-2, MMP-9, MMP-12, MMP-13, MMP-14, TIMP-1, TIMP-2, and RECK (reversion-inducing cysteine-rich protein with Kazal motifs) were examined via quantitative real-time PCR (qPCR). Interestingly, a significant up-regulation of TIMP-2 expression was found for the first time in dogs suffering from seizures. In conclusion, microglial TIMP expression might be involved in seizure generation.     

Magnetic resonance imaging findings in Finnish Spitz dogs with focal epilepsy

Eleven Finnish Spitz dogs with focal seizures and 3 healthy controls were evaluated. General clinical and neurological examinations, blood examination, urinalysis, cerebrospinal fluid examination, electroencephalography (EEG), and magnetic resonance imaging (MRI) of the brain were performed on all dogs. On EEG examination, focal epileptic activity was found in 7 of 11 dogs (64%), and generalized epileptic activity was observed in 4 of 11 dogs (36%). MRI (performed with 1.5 T equipment) detected changes in 1 epileptic dog. Mild contrast enhancement after gadolinium injection was identified in this dog's right parietal cortex. However, no such changes were observed in repeated magnetic resonance images. Special emphasis was given to seizure history to determine any correlations between seizure intervals and MRI findings. Our results indicate that Finnish Spitz dogs with focal seizures suffer from focal idiopathic epilepsy and have nondetectable findings on MRI or pathology. MRI showed poor sensitivity in detecting epileptogenic areas in our patients with focal seizures. Reversible MRI changes in 1 dog could have been caused by seizures.     

A cross-sectional study of epilepsy in Danish Labrador Retrievers: prevalence and selected risk factors

The purpose of this study was to investigate the prevalence and selected risk factors of epilepsy, the proportion of dogs with epilepsy in remission, and the types of seizures in Danish Labrador Retrievers. A prospective cross-sectional study of epilepsy was conducted in 1999-2000. The study was carried out in 2 phases in a reference population consisting of 29,602 individuals. In phase 1, 550 dogs were selected by random sampling stratified by year of birth. A telephone interview was used to identify dogs with possible epilepsy. In phase 2, dogs judged during phase 1 as possibly suffering from epilepsy were further subjected to physical and neurologic examination, CBC, blood chemistry, and a questionnaire on seizure phenomenology. Seventeen dogs were diagnosed with epilepsy, yielding a prevalence of 3.1% (95% CI 1.6-4.6%) in the Danish population of Labrador Retrievers. A diagnosis of epilepsy was 6 times more probable in dogs >4 years (born before 1995) than in younger dogs (born between 1995 and 1999) (P = .004, relative risk = 6.5). No significant difference in risk between genders was observed, nor could any effect of neutering be proven statistically. The frequencies of primary generalized seizures and partial seizures (with or without secondary generalization) were 24 and 70%, respectively. The type of seizures could not be classified in 6%. In conclusion, the 3.1% prevalence of epilepsy in Danish Labrador Retrievers is higher than the 1% prevalence of epilepsy described in the general canine population, establishing that this breed is at increased risk.     

Metabolic and toxic causes of canine seizure disorders: A retrospective study of 96 cases

A wide variety of intoxications and abnormal metabolic conditions can lead to reactive seizures in dogs. Patient records of dogs suffering from seizure disorders (n = 877) were reviewed, and 96 cases were associated with an underlying metabolic or toxic aetiology. These included intoxications by various agents, hypoglycaemia, electrolyte disorders, hepatic encephalopathy, hypothyroidism, uraemic encephalopathy, hypoxia and hyperglycaemia. The incidence of the underlying diseases was determined.The most common causes of reactive seizures were intoxications (39%, 37 dogs) and hypoglycaemia (32%, 31 dogs). Hypocalcaemia was the most frequent electrolyte disorder causing reactive seizures (5%) and all five of these dogs had ionised calcium concentrations ?0.69 mmol/L. Eleven per cent of dogs with seizures had metabolic or toxic disorders and this relatively high frequency emphasises the importance of a careful clinical work-up of cases presented with seizures in order to reach a correct diagnosis and select appropriate treatment options.     

Administration of acepromazine maleate to 31 dogs with a history of seizures

Objective: To retrospectively evaluate the incidence of seizures in dogs presenting with a history of seizures that were treated with acepromazine (ACE) during hospitalization. Design: Retrospective study. Setting: Privately owned emergency and referral hospital. Animals: Thirty‐one client‐owned dogs. Interventions: Administration of ACE. Measurements and main results: The medical records from dogs with an acute or chronic seizure history that received ACE were reviewed. Factors evaluated included presenting complaint, seizure history, ACE dosage, duration of observation, seizure activity, and other medications used. Thirty‐one dogs qualified for the study: 20 males and 11 females. Age range was 3 months to 14.9 years. Presenting complaint was seizure in 28/31 dogs. There was a prior history of seizures in 22/31 dogs, and 15/22 were currently on antiseizure medication. ACE was given 1–5 times per dog. Mean ACE dose was 0.029 mg/kg IV (range: 0.008–0.057 mg/kg; n=46), 0.036 mg/kg IM (range: 0.017–0.059 mg/kg; n=14), 0.53 mg/kg PO (n=2). Twenty‐seven dogs did not seizure after administration of ACE within the observation period (mean: 16.4 hours, range: 0.25–66 hours). Twenty‐five dogs received antiseizure medication before ACE. Eight seizure episodes occurred in 4 dogs (all of whom presented for seizures) within 0.3–10 hours after ACE administration. Conclusions: There was no observed correlation between ACE administration in dogs with a seizure history and the recurrence of seizure activity during hospitalization. The time from ACE administration to seizure activity was greater than expected for measurable effects to be seen in 1 dog (10 hour). Further studies with a larger group and alternative ACE doses are needed to more thoroughly evaluate the safety of short‐term ACE use in dogs with a seizure history.     

Epilepsy and seizure classification in 63 dogs: a reappraisal of veterinary epilepsy terminology

The human definitions of epilepsy and seizure classification were applied rigidly to epileptic dogs to investigate whether the distribution of the seizure types and epilepsies of dogs is comparable to that of human beings. Sixty-three dogs were referred because of recurrent (> 2) epileptic seizures. Only dogs without previous or ongoing antiepileptic treatment were included. All dogs had a physical and neurologic examination and blood work that included a CBC and a biochemical profile. All owners were asked to complete a questionnaire, focusing on seizure development. In addition, video recordings of suspected seizure episodes were analyzed if available. In the majority of dogs where an intracranial lesion was suspected, a computerized tomography scan was performed. Sixty-five percent of the dogs experienced partial seizures with or without secondary generalization and 32% exhibited primary generalized seizures; in 3% of the dogs the seizures could not be classified. Twenty-five percent of these cases were classified as idiopathic, 16% as symptomatic, and 45% as cryptogenic epilepsy; in 14% of these a classification was not possible. Applying human definitions, the distribution of seizure types and epilepsy classifications in these dogs differed widely from those in previous reports of canine epilepsy, where generalized seizures and idiopathic epilepsy were most frequently reported. However, our findings are consistent with the results of several large studies of human epilepsy patients. In dogs with epilepsy, closer attention must be given to the detection of a partial onset of seizures. In this study, detailed questioning of the owners and when possible analysis of video recorded seizures, proved to be sufficient for diagnosing seizures with a partial onset in a significant number of dogs. Partial onset of seizures may be an indication of underlying cerebral pathology. Some adjustments of veterinary epilepsy terminology are suggested.     

Low concentrations of cerebrospinal fluid GABA correlate to a reduced response to phenobarbital therapy in primary canine epilepsy

In this study, we investigated whether pretreatment cerebrospinal fluid (CSF) neurotransmitter concentrations of gamma-aminobutyric acid (GABA) and glutamate (GLU) were correlated with response to phenobarbital treatment in dogs with primary epilepsy. Eleven untreated dogs, 6 males and 5 females, with a median age of onset of seizures of 3 years (range: 0.5-5 years) were selected for therapy based on progressive or serious seizure patterns. The median interval between the first observed seizure and start of phenobarbital therapy was 485 days (range: 101-1,765 days). All dogs were purebred, with the exception of I male dog. Oral phenobarbital was started at 2.5 mg/kg every 12 hours. Trough serum phenobarbital concentrations were measured at 15, 45, 90, 180, 360, 540, and 720 days after the start of treatment. There was no difference in the mean trough serum concentration or in the mean number of seizures recorded between each time period of phenobarbital measurement over the 2-year evaluation. No correlation was found between CSF GLU, GABA, or GLU: GABA ratio and the total number of seizures recorded before or after initiation of phenobarbital therapy. Lower CSF GABA concentration, however, was correlated with a lower seizure frequency difference (the total number of seizures before phenobarbital therapy minus the total number of seizures after phenobarbital therapy for an identical time period of evaluation) and lower percentage reduction in seizures: ([total number of seizures before phenobarbital therapy minus the total number of seizures after phenobarbital therapy] divided by the total number of seizures before phenobarbital therapy) x 100. There was no correlation between CSF GLU and the seizure frequency difference and percentage reduction in seizures. A negative correlation between the CSF GLU:GABA ratio and seizure frequency difference was found. Thus, dogs with an initial lower CSF GABA concentration before phenobarbital therapy did not respond as well as did dogs with a higher CSF GABA concentration.