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.     

Idiopathic epilepsy in 125 dogs: a long-term study. Clinical and electroencephalographic findings

Well-documented cases of confirmed idiopathic epilepsy in 125 dogs were evaluated retrospectively. Forty-six breeds (each with no sex predisposition) were examined. Although dogs of all ages were affected, the peak value for the onset of first seizure was between one and five years. Approximately 75 per cent of animals had generalised grand mal type seizures with loss of consciousness. Preictal and postictal phases were present in the majority of dogs. Interictal electroencephalographic recordings of 37 anaesthetised dogs were statistically analysed. High frequency and low amplitude paroxysmal discharges with either a focal or generalised distribution were found in the majority of these dogs. Possible causes for this variation from dog to dog were analysed. It was concluded that, despite anaesthesia, electroencephalographic features were consistent and unique in dogs with idiopathic epilepsy.     

The efficacy and tolerability of levetiracetam in pharmacoresistant epileptic dogs

Twenty-two dogs with idiopathic epilepsy which were pharmacoresistant to phenobarbitone and bromide were treated with levetiracetam as an add-on medication. Records of eight dogs were used retrospectively to determine a safe, efficient levetiracetam dosage. Fourteen dogs were entered into a prospective, open label, non-comparative study. After 2 months of levetiracetam oral treatment (10 mg/kg TID), 8/14 dogs responded significantly to the treatment and seizure frequency was reduced by 50%. In dogs that remained refractory, the dosage was increased to 20 mg/kg TID for 2 months. One further dog responded to levetiracetam treatment. Levetiracetam responders had a significant decrease in seizure frequency of 77% (7.9+/-5.2 to 1.8+/-1.7 seizures/month) and a decrease in seizure days per month of 68% (3.8+/-1.7 to 1.2+/-1.1 seizure days/month). However, 6/9 responders experienced an increase in seizure frequency and seizure days after 4-8 months continuing with the levetiracetam treatment at the last effective dosage. Levetiracetam was well tolerated by all dogs and sedation was the only side-effect reported in just one of the 14 dogs.     

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.     

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.     

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.     

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.     

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.     

Neurological dysfunction in dogs following attenuation of congenital extrahepatic portosystemic shunts

Eleven of 89 dogs (12 per cent) developed neurological signs within six days of surgical attenuation of a congenital extrahepatic portosystemic shunt. Neurological signs were not associated with hepatic encephalopathy or hypoglycaemia. Signs varied in severity from non-progressive ataxia (three dogs) to generalised motor seizures (four dogs), progressing to status epilepticus (three dogs). In a further four cases, ataxia and disorientation were treated vigorously with anticonvulsant medication, presumably preventing the development of seizures. Two dogs that developed status epilepticus died or were eventually euthanased. All other animals survived, although some had persistent neurological deficits. Postligation neurological complications were not prevented by gradual shunt attenuation. Prophylactic treatment with phenobarbitone (5 to 10 mg/kg preoperatively, followed by 3 to 5 mg/kg every 12 hours for three weeks) did not significantly reduce the incidence of neurological sequelae (2/31 [6 per cent] dogs with phenobarbitone vs 9/58 [16 per cent] without phenobarbitone; P = 0.2). However, no animal receiving phenobarbitone experienced generalised motor seizures or status epilepticus. In conclusion, these observations suggest that postligation neurological syndrome comprises a spectrum of neurological signs of variable severity. Perioperative treatment with phenobarbitone may not reduce the risk of neurological sequelae, but may reduce their severity.     

Absence Seizures as a Feature of Juvenile Myoclonic Epilepsy in Rhodesian Ridgeback Dogs

Myoclonic epilepsy in Rhodesian Ridgeback (RR) dogs is characterized by myoclonic seizures occurring mainly during relaxation periods, a juvenile age of onset and generalized tonic‐clonic seizures in one‐third of patients. An 8‐month‐old female intact RR was presented for myoclonic seizures and staring episodes that both started at 10 weeks of age. Testing for the DIRAS1 variant indicated a homozygous mutant genotype. Unsedated wireless video‐electroencephalography (EEG) identified frequent, bilaterally synchronous, generalized 4 Hz spike‐and‐wave complexes (SWC) during the staring episodes in addition to the characteristic myoclonic seizures with generalized 4–5 Hz SWC or 4–5 Hz slowing. Photic stimulation did not evoke a photoparoxysmal response. Repeat video‐EEG 2 months after initiation of levetiracetam treatment disclosed a >95% decrease in frequency of myoclonic seizures, and absence seizures were no longer evident. Absence seizures represent another seizure type in juvenile myoclonic epilepsy (JME) in RR dogs, which reinforces its parallels to JME in humans.     

Treatment of partial seizures and seizure-like activity with felbamate in six dogs

Six dogs with partial seizures or partial seizure-like activity were treated with the antiepileptic drug felbamate between 1993 and 1998. All dogs had a history and results of diagnostic testing suggestive of either primary (idiopathic) or occult secondary epilepsy. Dogs ranged between four months and eight years of age at the onset of seizure activity. The median time period between onset of the first seizure and the start of felbamate therapy was 3.8 months (range 0.75 to 36 months). Median duration of therapy was nine months (range two to 22 months). All dogs experienced a reduction in seizure frequency after felbamate administration. Median total number of seizures post-treatment was two (range 0 to 9). Two dogs had an immediate and prolonged cessation of seizure activity. Steady-state trough serum felbamate concentrations measured at two weeks, and one, 12 and 22 months after the commencement of therapy in four dogs ranged between 13 and 55 mg/litre (median 35 mg/litre). Reversible haematological adverse effects were detected in two dogs, with one dog developing concurrent keratoconjunctivitis sicca. These results suggest that felbamate can be an effective antiepileptic drug without life-threatening complications when used as monotherapy for partial seizures in the dog.     

Field efficacy of moxidectin in dogs and rabbits naturally infested with Sarcoptes spp., Demodex spp. and Psoroptes spp. mites

The efficacy of moxidectin 1% injectable for cattle was evaluated in dogs and rabbits with naturally acquired sarcoptic, demodectic or psoroptic mites. Twenty-two dogs with generalised demodicosis were orally treated with 0.4mg/kg moxidectin daily. Forty-one dogs suffering from sarcoptic mange were treated with 0.2-0.25mg/kg moxidectin either orally or subcutaneously every week for three to six times. Seven rabbits were treated orally with 0.2mg/kg moxidectin twice 10 days apart. Of the 22 dogs with demodicosis, 14% were stopped treatment because of side effects, 14% were lost and of the remaining 72% all were cured (mean therapy duration 2.4 months). Thirty-seven of the sarcoptic mange-infected dogs finished treatment and were cured. In 17% of dogs, side effects were noted. All seven rabbits treated for psoroptic mange were cured and did not show any side effect. Our results indicate that moxidectin is effective and a good alternative for the treatment of demodicosis and scabies in dogs and psoroptic mange in rabbits. Side effects seem to occur more frequently if applied subcutaneously, therefore the oral route should be preferred.     

Treatment of Trombicula autumnalis infestation in dogs and cats with a 0·25 per cent fipronil pump spray

To evaluate the efficacy of fipronil in controlling tromblculid infestations, 18 dogs and three cats Infested with Trombicula autumnalis larvae were treated monthly from examination to the end of the Trombicula season (range one to four months) with a 0–25 per cent fipronil spray applied to the whole body, with particular emphasis on the feet, face, ears, perineum and tail. No other antlparasite measures were used. Follow-up was by clinical examination and telephone interview until the end of the Trombicula season (range one to four months). No adverse effects were seen. Monthly treatment controlled trombicuiids in 15 dogs. In two dogs localised pedal reinfestations were controlled with additional local application of fipronil to the feet every 14 days. In one dog therapy was of no benefit. In the three cats, treatment was Initially effective, but generalised Infestations recurred after seven to 10 days. Fipronil is a safe and effective treatment for tromblculid infestations in dogs. Residual activity lasts for 14 to 30 days. Further studies are required to examine the apparent short duration of efficacy in cats.     

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.     

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.     

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.     

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.     

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.)     

Association between Estrus and Onset of Seizures in Dogs with Idiopathic Epilepsy

Background

Catamenial epilepsy in humans is defined as changes in seizure frequency over the course of the menstrual cycle. Three hormonally based patterns of seizure exacerbation have been determined.

Objectives

The aim of this study was to evaluate whether there is an association between onset of seizures and the estrous cycle in intact bitches with presumptive idiopathic epilepsy and whether a pattern to the onset of seizures could be recognized.

Animals

Forty‐five intact female dogs from a hospital population with a presumptive diagnosis of idiopathic epilepsy.

Methods

In a retrospective study, the database of a small animal hospital in Sweden was searched for medical records of intact female dogs diagnosed with epilepsy or seizures. The stage of the estrous cycle as reported either by the owner or the veterinarian at the time of the first seizure was noted.

Results

Of the 45 dogs with idiopathic epilepsy, 17 (38%) had their first seizure when in heat and six dogs (13%) had their first seizure 1–3 months after heat. Nine dogs (20%) had seizures reoccurring in relation to their estrous cycle.

Conclusions and Clinical Importance

These findings suggest an association between estrus and onset of seizures in intact bitches with presumptive idiopathic epilepsy. Two hormonally based patterns could be recognized: one during heat and one during a specific time point at the end of diestrus. This could be explained by the proconvulsive effects of estrogen or loss of protective effect against seizures of progesterone, respectively.     

Premature death, risk factors, and life patterns in dogs with epilepsy

BACKGROUND: Epilepsy in dogs is often difficult to medically control, resulting in premature death of dogs with epilepsy. However, the risks of premature death are not known. HYPOTHESIS: Dogs with epilepsy have an increased risk of premature death as compared to a general population of dogs. ANIMALS: Sixty-three dogs diagnosed with epilepsy between 1993 and 1996 were included in this study. METHODS: A prospective longitudinal study of the population was performed from the diagnosis of epilepsy until the time of euthanasia, death, or a maximum of 12 years to investigate mortality and risk factors. Information about sex, onset, type, frequency, and control of seizures, remission of epilepsy, death, cause of death, and owner's perspective was collected and analyzed. RESULTS: The median age at death of dogs was 7.0 years. The life span of dogs in which euthanasia or death was directly caused by their epileptic condition was significantly shorter as compared with epileptic dogs that were euthanized because of other causes (P = .001). The median number of years that a dog lived with epilepsy was 2.3 years. Females lived longer with epilepsy than males (P = .036). Seizure type (primary generalized versus focal seizures) was not significantly associated with survival time. The remission rate of epilepsy (spontaneous remission and remission with treatment) was 15%. CONCLUSION AND CLINICAL IMPORTANCE: The diagnosis of epilepsy implies an increased risk of premature death. The prognosis for dogs with epilepsy is dependent on a combination of veterinary expertise, therapeutic success, and the owner's motivation.