Clinical and genetic investigations of idiopathic epilepsy in the Bernese mountain dog

A study was conducted to investigate the clinical aspects and to define the mode of inheritance of idiopathic epilepsy in the Bernese mountain dog. Pedigree analyses were carried out on an open, non-preselected population of 4005 dogs. Five different subpopulations with 50 epileptic dogs from 13 generations were included. Almost all epileptic patients showed generalised seizures of the grand-mal type with a well-defined prodromal and postictal phase. The majority (62 per cent) of the epileptic dogs had had their first seizures at between one and three years of age and it was found that the age at first seizure was significantly (P < 0.05) lower in dogs from affected parental animals than in dogs from healthy parental animals. A clear predisposition for males was also noted. Additionally, there was no correlation between inbreeding coefficient and age at first seizure or incidence rate of seizures. The increased occurrence of the disease in different subpopulations and different families of the same sires or dams showed that there was a genetic basis for the condition in the Bernese mountain dog. Furthermore, the results of the pedigree analyses and binomial test support the hypothesis that idiopathic epilepsy has a polygenic, recessive mode of inheritance in the breed. Additional objective test-mating programmes would however be necessary to define the exact mode of inheritance.     

Clinical, epidemiological and treatment results of idiopathic epilepsy in 54 labrador retrievers: a long-term study

The records of 54 labrador retrievers with idiopathic epilepsy were reviewed. Exogenous factors played a minor role in the transmission of the epilepsy. Prodromal phase and aura were present in the majority of the dogs with generalised seizures. The ictal phase was characterised by long-lasting automatisms. Approximately half of the dogs had seizures more than once a month; the remainder ranged from one every two months to one every 12 months. The average frequency in dogs with generalised seizures (n = 49) was one every 65 days and in dogs with partial seizures (n 5) one every 205 days. Long-term follow-up was performed in 46 dogs, 37 of which followed a strict treatment protocol. Possible causes for the large variations in treatment results were analysed. One goal was identify objective aspects enabling a realistic prognosis prior to treatment. Animals with a high age at onset of seizure (mean, four years) showed an excellent outcome, even if treatment began late. Dogs with low frequency rates and low total numbers of seizures responded well to therapy if treated as early as possible.     

Potassium bromide‐associated panniculitis

Two cases of panniculitis associated with administration of potassium bromide in dogs are reported. Both dogs were treated with potassium bromide for idiopathic epilepsy for over 1 year. Dose increases in both cases were associated with panniculitis, characterised by painful subcutaneous nodules in a generalised distribution over the trunk. Nodule eruption waxed and waned in one dog and was persistent in the other. In both cases, panniculitis was accompanied by lethargy and pyrexia. Panniculitis, lethargy and pyrexia resolved and failed to recur after discontinuation of potassium bromide. No other cause of panniculitis could be determined for either dog. Panniculitis has been reported after administration of potassium bromide in humans and may be a form of drug‐induced erythema nodosum. To the authors’ knowledge, these are the first reports of potassium bromide‐associated panniculitis in dogs.     

Electroencephalographic recordings in dogs suffering from idiopathic and symptomatic epilepsy: diagnostic value of interictal short time EEG protocols supplemented by two activation techniques

The diagnostic value of interictal short time electroencephalographic (EEG) recordings in epileptic dogs under general anaesthesia with propofol and the muscle relaxant rocuronium bromide was investigated. Two activation techniques, namely photic stimulation and hyperventilation, were evaluated for their potential to enhance the diagnostic validity of these recordings. Sixty-one dogs suffering from idiopathic epilepsy and 28 dogs suffering from symptomatic epilepsy were included. Electroencephalograms were recorded using five subdermal EEG electrodes (F3, F4, Cz, O1 and O2). All 89 EEGs were analysed visually and 61 were also evaluated quantitatively with fast Fourier transformation. Interictal paroxysmal epileptiform activity was found in 25% of idiopathic and in 29% of symptomatic epileptic dogs. Quantitative analysis of the EEGs (qEEGs) detected significant differences of frequency analysis in single reading points without any continuous changes of frequency bands. A comparison between healthy and affected brain hemispheres in seven dogs with focal lesions of one hemisphere did not show any significant differences in qEEG analysis. qEEG was not more sensitive than visual evaluation. Despite the use of activation techniques, the results showed that short time EEG recordings in epileptic dogs can detect interictal epileptic activity in less than one third of all seizuring dogs and is not a useful screening method.     

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.     

PREVALENCE OF LATERAL VENTRICLE ASYMMETRY IN BRAIN MRI STUDIES OF NEUROLOGICALLY NORMAL DOGS AND DOGS WITH IDIOPATHIC EPILEPSY

Asymmetry of the cerebral lateral ventricles is a common finding in cross‐sectional imaging of otherwise normal canine brains and has been assumed to be incidental. The purpose of this retrospective study was to compare the prevalence of ventricular asymmetry in brain MRI studies of normal dogs and dogs with idiopathic epilepsy. Brain MRI archives were searched for 100 neurologically normal dogs (Group 1) and 100 dogs with idiopathic epilepsy (Group 2). For each dog, asymmetry of the lateral ventricles was subjectively classified as absent, mild, moderate, and severe based on a consensus of two observers who were unaware of group status. Ventricular areas were measured from transverse T1W images at the level of the interthalamic adhesion. An asymmetry ratio was calculated as the ratio of the larger to smaller ventricular transverse area. There was excellent agreement between subjective assessments of ventricular asymmetry and quantitative assessments using asymmetry ratios (k = 0.995). The prevalence of asymmetry was 38% in Group 1 dogs and 44% in Group 2 dogs. Assymmetry was scored as mild in the majority of Group 2 dogs. There was no significant association between presence/absence and degree of ventricular asymmetry vs. dog group, age, gender, or skull conformation. Findings from the current study supported previously published assumptions that asymmetry of the lateral cerebral ventricles is an incidental finding in MRI studies of the canine brain.     

Canine status epilepticus: a retrospective study of 50 cases

The medical records of 50 dogs that exhibited generalised convulsive tonic-clonic (GCTC) status epilepticus (SE) were reviewed and compared with the records of 50 dogs that exhibited non-SE GCTC seizures. The mean age, bodyweight and gender of the patients in both groups were not significantly different. Dogs in the non-SE group were two times more likely to be an idiopathic epileptic than to have secondary epileptic seizures. The SE group was more likely to have abnormalities on cerebrospinal fluid analysis, but not more likely to have abnormalities detected on computed tomography, when compared with the non-SE group. SE was 1.57 times more likely if the cause for the seizures was secondary or reactive epilepsy rather than idiopathic or primary epilepsy. In conclusion, dogs that exhibit SE should be thoroughly investigated for secondary causes.     

Treatment with gabapentin of 11 dogs with refractory idiopathic epilepsy

Eleven dogs diagnosed with refractory idiopathic epilepsy were treated orally with gabapentin for a minimum of three months at an initial dose of 10 mg/kg every eight hours. They were all experiencing episodes of generalised tonic-clonic seizures and had been treated chronically with a combination of phenobarbital and potassium bromide at doses sufficient to reach acceptable therapeutic serum levels without causing significant side effects. In each dog, the number of seizures per week, the average duration of the seizures and the number of days on which seizures occurred were compared for the three months before and after they were treated with gabapentin. A minimum 50 per cent reduction in the number of seizures per week was interpreted as a positive response to gabapentin, and six of the dogs showed a positive response. After the addition of gabapentin, both the number of seizures per week (P= 0.005) and the number of days with any seizures in a one-week period (P=0.03) were significantly reduced. Mild side effects of ataxia and sedation were observed in five of the dogs, but they were not severe enough to warrant the treatment being discontinued during the trial.     

Implantable loop recorders: a viable diagnostic tool in veterinary medicine

Objective : The purpose of this study was to investigate whether implantable loop recorders could be used in the diagnosis of unexplained collapse in dogs. Methods : The medical records of six dogs presented to the University of Liverpool Small Animal Teaching Hospital between May 2003 and October 2006 for further evaluation of intermittent syncopal episodes, collapse or episodic weakness, were reviewed. All these dogs underwent standard investigations and had implantable loop recorders placed. Results : A provisional diagnosis of supraventricular tachycardia was made in one dog, and diagnoses of exclusion of arrhythmogenic right ventricular cardiomyopathy and idiopathic epilepsy was made in two dogs. One dog suffered no further syncopal episodes, a diagnosis was not reached in another dog and the final dog was lost to follow‐up. Clinical Significance : The implantable loop recorder can be used successfully for the diagnosis of unexplained collapse in dogs.     

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.     

Idiopathic epilepsy in dogs: owners' perspectives on management with phenobarbitone and/or potassium bromide

OBJECTIVES: To explore seizure management from the perspective of the owners of dogs with idiopathic epilepsy. METHODS: Questionnaires were mailed to owners of 29 dogs under management for suspected or diagnosed idiopathic epilepsy through the clinics of the Small Animal Hospital of the University of Glasgow Veterinary School, using either phenobarbitone or potassium bromide alone or in combination. RESULTS: The postal survey had an 86 per cent response rate. Analysis of the responses demonstrated that "the dog's quality of life", "adequate seizure frequency" and "acceptable side effects of antiepileptic drugs" were the three greatest concerns for owners; 52 per cent of owners strongly agreed that the seizure management for their dog was adequate, though the seizure frequency reported varied within this group; the majority of owners did not consider the administration of medication a nuisance. However, approximately 60 per cent of owners reported that caring for an epileptic dog had an effect on the organisation of their free time, though this was not dependent on perception of seizure control. Opinions as to the value of further diagnostic procedures, in particular intracranial imaging, were significantly affected by having pet health insurance. CLINICAL SIGNIFICANCE: From the owners' perspective, adequacy of seizure control is determined by the balance between "the dog's quality of life", "adequate seizure frequency" and "acceptable side effects of antiepileptic drugs". A frequency of less than one seizure every three months is associated with the perception by owners of adequate seizure control.     

Idiopathic phenobarbital‐responsive hypersialosis in the dog: an unusual form of limbic epilepsy?

Three unusual cases of salivary gland enlargement and hypersialosis in the dog that responded to anticonvulsant therapy are reported. Presenting complaints included weight loss, hypersalivation, retching and vomiting of several weeks' duration. Two dogs were presented with enlarged painful mandibular salivary glands. The third dog exhibited bizarre behaviour (including jaw chattering) and developed enlarged painful mandibular salivary glands during hospitalisation. Fine needle aspirate cytology and biopsies from the enlarged salivary glands revealed no significant pathological changes. In one dog, an electroencephalogram revealed changes consistent with epilepsy. Hypersialism and salivary gland enlargement resolved completely during phenobarbital administration in all cases. Two dogs were successfully weaned off treatment six months after diagnosis. The remaining dog relapsed after eight months, but normalised with the addition of oral potassium bromide. It is hypothesised that the syndrome idiopathic hypersialosis may in fact be an unusual form of limbic epilepsy.     

Electroencephalography findings in healthy and Finnish Spitz dogs with epilepsy: visual and background quantitative analysis

BACKGROUND: Qualitative and quantitative electroencephalography (EEG) parameters of healthy and Finnish Spitz dogs with epilepsy have not been determined. OBJECTIVE: To determine if EEG can provide specific characteristics to distinguish between healthy dogs and dogs with epilepsy. ANIMALS: Sixteen healthy and 15 Finnish Spitz dogs with epilepsy. METHODS: A prospective clinical EEG study performed under medetomidine sedation. Blinded visual and quantitative EEG analyses were performed and results were compared between study groups. RESULTS: Benign epileptiform transients of sleep and sleep spindles were a frequent finding in a majority of animals from both groups. The EEG analysis detected epileptiform activity in 3 Finnish Spitz dogs with epilepsy and in 1 healthy Finnish Spitz dog. Epileptiform activity was characterized by spikes, polyspikes, and spike slow wave complexes in posterior-occipital derivation in dogs with epilepsy and with midline spikes in control dog. The healthy dogs showed significantly less theta and beta activity than did the dogs with epilepsy (P < .01), but the only significant difference between healthy dogs and dogs with untreated epilepsy was in the alpha band (P < .001). Phenobarbital treatment increased alpha, beta (P < .001), and theta (P < .01), and decreased delta (P < .001) frequency bands compared with dogs with untreated epilepsy. CONCLUSIONS AND CLINICAL IMPORTANCE: Benign epileptiform transients of sleep could be easily misinterpreted as epileptiform activity. Epileptiform activity in Finnish Spitz dogs with epilepsy seems to originate from a posterior-occipital location. The EEG of dogs with epilepsy exhibited a significant difference in background frequency bands compared with the control dogs. Phenobarbital treatment markedly influenced all background activity bands. Quantitative EEG analysis, in addition to visual analysis, seems to be a useful tool in the examination of patients with epilepsy.     

CEREBRAL GLUCOSE UTILIZATION MEASURED WITH HIGH RESOLUTION POSITRON EMISSION TOMOGRAPHY IN EPILEPTIC FINNISH SPITZ DOGS AND HEALTHY DOGS

In human epileptic patients, changes in cerebral glucose utilization can be detected 2‐deoxy‐2‐[¹⁸F] fluoro‐d ‐glucose positron emission tomography (FDG‐PET). The purpose of this prospective study was to determine whether epileptic dogs might show similar findings. Eleven Finnish Spitz dogs with focal idiopathic epilepsy and six healthy dogs were included. Dogs were examined using electroencephalography (EEG) and FDG‐PET, with epileptic dogs being evaluated during the interictal period. Visual and semi‐quantitative assessment methods of FDG‐PET were compared and contrasted with EEG findings. Three independent observers, unaware of dog clinical status, detected FDG‐PET uptake abnormalities in 9/11 epileptic (82%), and 4/8 healthy dogs (50%). Occipital cortex findings were significantly associated with epileptic status (P = 0.013). Epileptic dogs had significantly lower standardized uptake values (SUVs) in numerous cortical regions, the cerebellum, and the hippocampus compared to the control dogs. The lowest SUVs were found in the occipital lobe. White matter normalized and left‐right asymmetry index values for all pairs of homologous regions did not differ between groups. Visual evaluation of the EEGs was less sensitive (36%) than FDG‐PET. Both diagnostic tests were consensual and specific (100%) for occipital findings, but EEG had a lower sensitivity for detecting lateralized foci than FDG‐PET. Findings supported the use of FDG‐PET as a diagnostic test for dogs with suspected idiopathic epilepsy. Visual and semiquantitative analyses of FDG‐PET scans provided complementary information. Findings also supported the theory that epileptogenesis may occur in multiple brain regions in Finnish Spitz dogs with idiopathic epilepsy.     

Clinical, epidemiologic and therapeutic aspects of idiopathic epilepsy in 25 golden retrievers: results of a long term study]

The records of 25 Golden Retrievers with idiopathic epilepsy were reviewed. One goal was to identify objective aspects enabling a realistic prognosis prior to treatment. In half the dogs seizures occurred for the first time at the age of one to three years and were mostly generalised. The character, feeding habits and confinement of the dogs played a minor role in the clinical manifestation of the fits, but they were seen mostly during sleep in two thirds of the dogs. Because of the long follow-up period some important findings were made. At the beginning of the standardized long-term therapy with phenobarbital a success was observed in two thirds of the dogs, while after four years the symptoms worsened significantly in about half the dogs. We found no better success rate in castrated dogs. Dogs responded well to therapy if treated as early as possible.     

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.     

Severe haemoptysis associated with seizures in a dog

CASE HISTORY: A 7-year-old, sterilised male German Shepherd dog was presented with a history of three episodes of severe haemoptysis and associated dyspnoea within a 3-week period. A generalised tonic-clonic seizure was witnessed preceding the third episode. CLINICAL FINDINGS: Thoracic radiographs revealed a severe bilateral alveolar lung pattern of the caudodorsal lung fields; extension into the left cranial lung lobe was present but pulmonary vessels were within normal size limits. Frank blood was the only abnormality present at bronchoscopy. A coagulation profile, parasitological screening, thoracic and brain computed tomography (CT), and cerebrospinal fluid (CSF) cytological analysis did not identify any abnormalities. DIAGNOSIS: Haemoptysis due to either severe neurogenic pulmonary oedema or rupture of the pulmonary capillaries secondary to seizures was considered a possible diagnosis. The primary generalised seizures were attributed to late-onset idiopathic epilepsy diagnosed by exclusion of other causes. CLINICAL RELEVANCE: This is the first known case report describing severe haemoptysis associated with seizures in a dog.     

Aetiology and long-term outcome of juvenile epilepsy in 136 dogs

The aetiology and outcome of dogs with juvenile-onset seizures were investigated. One hundred and thirty-six dogs whose first seizure occurred before the age of one year were investigated. One hundred and two dogs were diagnosed with idiopathic epilepsy (IE), 23 with symptomatic epilepsy (SE), nine with reactive seizures (RS) and two with probable symptomatic epilepsy (pSE). The outcome was known in 114 dogs; 37 per cent died or were euthanased as a consequence of seizures. The mean survival time of this population of dogs was 7.1 years. Factors that were significantly associated with survival outcome included the diagnosis of SE and the number of antiepileptic drugs (AEDs) used before investigation. The use of one AED before investigation and a diagnosis of SE were associated with a negative outcome, whereas receiving no AED medications before referral was associated with a longer survival. For dogs with IE, survival time was shortened if the dog was a border collie or with a history of status epilepticus;receiving no AEDs before referral in the IE group was associated with a positive outcome. Seizure-free status was achieved in 22 per cent of dogs diagnosed with IE. While the survival times were longer than previously reported in canine epilepsy, similar remission rates to those reported in childhood epilepsy, where a 70 per cent remission rate is documented, were not seen in the canine juvenile population.     

Transient neuromyopathy after bromide intoxication in a dog with idiopathic epilepsy

A seven-year old Australian Shepherd, suffering from idiopathic epilepsy under treatment with phenobarbitone and potassium bromide, was presented with generalised lower motor neuron signs. Electrophysiology and muscle-nerve biopsies revealed a neuromyopathy.The serum bromide concentration was increased more than two-fold above the upper reference value.Clinical signs disappeared after applying diuretics and reducing the potassium bromide dose rate. This is the first case report describing electrophysiological and histopathological findings associated with bromide induced lower motor neuron dysfunction in a dog.     

Clinical Effects of Longitudinal Division of the Corpus Callosum in Normal Dogs

Longitudinal division of the corpus callosum was performed in six normal beagles to determine surgical morbidity. The corpus callosum was divided sagittally on the midline and the effect on neurological function was determined. Five of six dogs were clinically normal within 14 days or less after surgery. One dog had persistent but improving clinical signs consistent with a forebrain disturbance at 30 days after surgery. Overall, minimal morbidity and no mortality was associated with this surgical procedure. Further study is indicated to determine the efficacy of this surgical treatment for seizure control in dogs with idiopathic epilepsy.