Therapeutic serum concentrations of primidone and its metabolites, phenobarbital and phenylethylmalonamide in epileptic dogs

Fifteen dogs with idiopathic epilepsy were included in a 9-month clinical trial to determine the therapeutic serum concentrations of primidone and its active metabolites, phenobarbital and phenylethylmalonamide. Dogs with a seizure frequency greater than 1/mo or with a record of multiple seizures greater than 1/day were chosen for the study. Each dog was given primidone 3 times daily at dosages intended to maximize seizure control and to minimize undesired side effects. Maintenance period blood samples were taken from fasted dogs 7 hours after dosing in the 3rd, 5th, 7th, and 9th months of the trial to determine therapeutic serum concentrations of primidone and its metabolites. Two blood samples also were taken from all dogs 7 hours after dosing, during an enforced drowsy period, to establish upper limits of desirable serum concentrations of the drug. Seizure frequencies during the trial were controlled in 13 dogs, 7 of which had no seizures during the 9-month trial. The mean percentage reduction in seizure frequency from pretrial frequency was 85%. Two dogs appeared refractory to primidone therapy. Serum phenobarbital was the best metabolite of primidone to use to assess therapeutic serum concentrations. The therapeutic antiepileptic serum concentration of phenobarbital was found to be between 25 and 40 micrograms/ml of serum. Serum phenobarbital concentrations greater than 40 micrograms/ml resulted in side effects in most dogs.     

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.     

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.     

Disposition and clinical use of bromide in cats

OBJECTIVE: To establish a dosing regimen for potassium bromide and evaluate use of bromide to treat spontaneous seizures in cats. DESIGN: Prospective and retrospective studies. ANIMALS: 7 healthy adult male cats and records of 17 cats with seizures. PROCEDURE: Seven healthy cats were administered potassium bromide (15 mg/kg [6.8 mg/lb], p.o., q 12 h) until steady-state concentrations were reached. Serum samples for pharmacokinetic analysis were obtained weekly until bromide concentrations were not detectable. Clinical data were obtained from records of 17 treated cats. RESULTS: In the prospective study, maximum serum bromide concentration was 1.1 +/- 0.2 mg/mL at 8 weeks. Mean disappearance half-life was 1.6 +/- 0.2 weeks. Steady state was achieved at a mean of 5.3 +/-1.1 weeks. No adverse effects were detected and bromide was well tolerated. In the retrospective study, administration of bromide (n = 4) or bromide and phenobarbital (3) was associated with eradication of seizures in 7 of 15 cats (serum bromide concentration range, 1.0 to 1.6 mg/mL); however, bromide administration was associated with adverse effects in 8 of 16 cats. Coughing developed in 6 of these cats, leading to euthanasia in 1 cat and discontinuation of bromide administration in 2 cats. CONCLUSIONS AND CLINICAL RELEVANCE: Therapeutic concentrations of bromide are attained within 2 weeks in cats that receive 30 mg/kg/d (13.6 mg/lb/d) orally. Although somewhat effective in seizure control, the incidence of adverse effects may not warrant routine use of bromide for control of seizures in cats.     

Anticonvulsant activity and tolerance of ELB138 in dogs with epilepsy: a clinical pilot study

A new antiepileptic and anxiolytic drug, ELB138, was evaluated in a clinical pilot study in dogs with newly diagnosed or chronic idiopathic epilepsy. The purpose was to verify clinically the anticonvulsant effectiveness of this substance, which had already been demonstrated experimentally. Data from 29 dogs treated with ELB138 were compared with results obtained retrospectively from 82 dogs treated with conventional antiepileptic medication. The reduction in seizure frequency using ELB138 in dogs with newly diagnosed idiopathic epilepsy was comparable to the reduction in dogs treated either with phenobarbital or primidone. In dogs with chronic epilepsy and add-on therapy with either ELB138 or potassium bromide, such supplementation reduced the seizure frequency and the duration and severity of seizures. The most obvious difference between ELB138 treatment and conventional medications became clear in the evaluation of side effects, which in those dogs treated with ELB138 were rare, and consisted mostly of transient polyphagia. This pilot study confirmed that ELB138 has a potent anticonvulsant effect in dogs with idiopathic epilepsy. These results will form the basis for a multicentre, blinded study.     

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.     

Alternative therapeutic options for medical management of epilepsy in apes

Phenobarbital has been the primary antiepileptic drug used in primates, but the dosage required for seizure control is frequently associated with significant side effects. Newer antiepileptic drugs and adjunctive therapies currently being used in human medicine provide additional options for treatment of nonhuman primates. This report describes different drug regimes used for control of epileptic seizures in apes at the Milwaukee County Zoo (Milwaukee, Wisconsin, U.S.A.), including the addition of acetazolamide to phenobarbital, levetiracetam, carbamazepine, and the use of extended cycle oral contraceptives to assist seizure control in female apes with catamenial epilepsy.     

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.     

Zonisamide therapy for refractory idiopathic epilepsy in dogs

Twelve dogs with poorly controlled idiopathic epilepsy were entered into a prospective, open-label, noncomparative study. Oral zonisamide was administered as an additional therapy at a dosage adequate to achieve serum drug concentrations of 10 to 40 microg/mL. Seizure frequency before and after initiation of zonisamide therapy was recorded. A dosing interval of q 12 hours was sufficient to maintain serum zonisamide concentrations within the therapeutic range. The mean dosage of zonisamide required was 8.9 mg/kg q 12 hours. Seven (58%) dogs responded favorably, experiencing a mean reduction in seizures of 81.3%. Five dogs had an increase in seizure frequency. Mild side effects (e.g., transient sedation, ataxia, vomiting) occurred in six dogs.     

Euthyroid sick syndrome in dogs with idiopathic epilepsy before treatment with anticonvulsant drugs

Euthyroid sick syndrome is a common finding in dogs and is attributable to nonthyroidal illness or treatment with any of a variety of drugs such as phenobarbital. In dogs with epilepsy, treatment with anticonvulsant drugs can lead to subnormal plasma thyroid hormone concentrations despite normal thyroid function. One-hundred thirteen dogs with seizure activity were retrospectively evaluated to determine the influence of idiopathic epilepsy (IE) on thyroid hormone concentrations. Blood samples were taken from 60 dogs with IE before initiation of anticonvulsant therapy. Control groups consisted of 34 dogs with IE and receiving anticonvulsants and 19 dogs with secondary epilepsy. Thyroid concentrations consistent with euthyroid sick syndrome were diagnosed in 38% of dogs with untreated IE without clinical signs of hypothyroidism or concomitant diseases. There was a significant correlation (r = 0.363, P = .01) between seizure frequency and plasma thyroid hormone concentrations: the longer the interval between 2 seizure events, the higher the serum total thyroxine concentration. There was no correlation between the degree of alteration of thyroid hormone concentrations and the time span between the most recent seizure event and blood collection, the type of the most recent seizure event, the duration of the complete seizure history, or the predominant seizure type. These results suggest that IE can be a reason for euthyroid sick syndrome in dogs. The effect of phenobarbital on plasma thyroid hormone concentrations must be investigated in future studies, as it might be less pronounced than expected.     

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.)     

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.     

Pharmacokinetics of phenobarbital in the cat following intravenous and oral administration.

Phenobarbital was administered to eight healthy cats as a single intravenous dose of 10 mg/kg. Serum phenobarbital concentrations were determined using an immunoassay technique. The intravenous data were fitted to one-, two- and three-compartment models. After statistical comparison of the three models, a two-compartment model was selected. Following intravenous administration, the drug was rapidly distributed (distribution half-life = 0.046 +/- 0.007 h) with a large apparent volume of distribution (931 +/- 44.8 mL/kg). Subsequent elimination of phenobarbital from the body was slow (elimination half-life = 58.8 +/- 4.21 h). Three weeks later, a single oral dose of phenobarbital (10 mg/kg) was administered to the same group of cats. A one-compartment model with an input component was used to describe the results. After oral administration, the initial rapid absorption phase (absorption half-life = 0.382 +/- 0.099 h) was followed by a plateau in the serum concentration (13.5 +/- 0.148 micrograms/mL) for approximately 10 h. The half-life of the terminal elimination phase (76.1 +/- 6.96 h) was not significantly different from the half-life determined for the intravenous route. Bioavailability of the oral drug was high (F = 1.20 +/- 0.120). Based on the pharmacokinetic parameters determined in this study, phenobarbital appears to be a suitable drug for use as an anticonvulsant in the cat.     

Pharmacokinetics of phenobarbital in the cat following multiple oral administration.

Phenobarbital was administered orally to seven healthy cats at a dose of 5 mg/kg once a day for 21 days. Serum phenobarbital concentrations were determined using a commercial immunoassay technique. A one-compartment model was used to describe the final elimination curve. The elimination half-life (t1/2 b) after the final day of treatment was 43.3 +/- 2.92 h. The large apparent volume of distribution of 695.0 +/- 43.9 mL/kg suggests that the drug was widely distributed within the body. The t1/2 b following multiple oral administration was significantly shorter than previously reported for a single oral dose of phenobarbital in the cat. Analysis of pharmacokinetic results after days 1 and 21 of treatment suggested that the elimination kinetics of phenobarbital did not change significantly with multiple oral administration. It appears that differences in elimination kinetics can exist between populations of cats. These differences emphasize the need for individual monitoring of cats receiving phenobarbital.     

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.     

Owner perception of the care of long-term phenobarbital-treated epileptic dogs

A study was undertaken to evaluate owners' perception of the effect that epilepsy and long-term phenobarbital therapy had on the quality of pet and owner lifestyle. Selected owners who participated in a prospective, longitudinal clinical epilepsy study were sent a questionnaire at the end of the two-year study. Inclusion criteria were dogs with a history of seizures without previous medical attention or therapy by any veterinarian before enrolment, subsequent determination of seizure aetiology using a standardised diagnostic protocol and treatment with phenobarbital for a minimum period of six months. A relatively equal distribution of the respondents' dogs had a determined (secondary, 47 per cent) or undetermined (primary, 53 per cent) seizure aetiology, and the vast majority of owners agreed that they would choose to treat their epileptic pet again rather than opt for other alternatives. Most owners disagreed that their pet was leading a poor quality of life after the start of phenobarbital therapy. A significant negative correlation existed between an owner's perception of the pet's quality of life and the amount of work required to care for the pet during the two-year study period. This study demonstrates that many owners are willing to care for epileptic dogs on long-term phenobarbital treatment, regardless of the underlying cause.     

Clinical findings, treatment, and outcome of dogs with status epilepticus or cluster seizures: 156 cases (1990-1995)

OBJECTIVE: To report clinical findings, treatments, and outcomes of dogs admitted to the hospital for status epilepticus or cluster seizures and evaluate factors associated with outcome. DESIGN: Retrospective study. ANIMALS: 156 dogs admitted for status epilepticus or cluster seizures. PROCEDURE: Medical records were reviewed for seizure and medication history, diagnostic test results, types of treatment, hospitalization costs, and outcome of hospital visits. RESULTS: Dogs were admitted for seizures on 194 occasions. Of 194 admissions, 128 (66%), 2 (1%), 32 (16.5%), 2 (1%), and 30 (15.5%) were of dogs with a history of clusters of generalized seizures, clusters of partial complex seizures, convulsive status epilepticus, partial status epilepticus, and > 1 type of seizure, respectively. Underlying causes of seizures were primary epilepsy (26.8%; 52/194), secondary epilepsy (35.1%; 68), reactive epileptic seizures (6.7%; 13), primary or secondary epilepsy with low serum antiepileptic drug concentrations (5.7%; 11), and undetermined (25.8%; 50). One hundred and eighty-six hospital visits resulted in admission to the intensive care unit (ICU). Treatments with continuous i.v. infusions of diazepam or phenobarbital were initiated during 66.8% (124/186) and 18.7% (35) of ICU hospital stays for 22.3 +/- 16.1 hours (mean +/- SD) and 21.9 +/- 15.4 hours, respectively. Of 194 admissions, 74.7% (145) resulted in discharge from the hospital, 2.1% (4) in death, and 23.2% (45) in euthanasia. A poor outcome (death or euthanasia) was significantly associated with granulomatous meningoencephalitis, loss of seizure control after 6 hours of hospitalization, and the development of partial status epilepticus. CONCLUSIONS AND CLINICAL RELEVANCE: Granulomatous meningoencephalitis, loss of seizure control after 6 hours of hospitalization, or the development of partial status epilepticus may indicate a poor prognosis for dogs with seizures.     

Clinical signs, underlying cause, and outcome in cats with seizures: 17 cases (1997-2002)

OBJECTIVE: To determine clinical signs, results of diagnostic testing, underlying cause, and outcome in cats with seizures. DESIGN: Retrospective study. ANIMALS: 17 cats with seizures. PROCEDURE: Only those cats in which an underlying metabolic abnormality causing the seizures had been identified, diagnostic imaging of the brain and CSF analysis had been done, or a necropsy had been performed were included. Seizures were classified as being a result of metabolic disease, symptomatic epilepsy (ie, epilepsy resulting from a structural lesion of the brain), or probably symptomatic epilepsy (ie, epilepsy without any extracranial or identifiable intracranial disease that is not suspected to be genetic in origin). RESULTS: 3 cats had seizures associated with an underlying metabolic disease (hepatic encephalopathy), 7 had symptomatic epilepsy (3 with neoplasia and 4 with meningoencephalitis), and 7 had probably symptomatic epilepsy. Six of the 7 cats with symptomatic epilepsy died or were euthanatized within 3 months after the diagnosis was made, whereas 6 of the 7 cats with probably symptomatic epilepsy survived for at least 12 months after the diagnosis was made. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that cats with probably symptomatic epilepsy may have a good long-term prognosis.     

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.     

The Use of Diazepam Per Rectum at Home for the Acute Management of Cluster Seizures in Dogs

The use of diazepam per rectum (RDZ) in the home to control generalized cluster seizures in 11 dogs diagnosed with idiopathic epilepsy was evaluated over a 16-month period. All dogs had a prior history of clusters of generalized seizures and were treated with multiple antiepileptic drugs. Owners were instructed to administer diazepam injectable solution (5 mg/mL) per rectum to their dogs at a dose of 0.5 mg/kg when an initial generalized seizure occurred and when a second or third generalized seizure occurred within 24 hours of the first seizure. Seizure activity was recorded by owners in a daily log before the onset of RDZ use and for the duration of RDZ use, which ranged from 57 to 464 days (median = 157 days). The median age at which the first seizure occurred and the median age at the time of enrollment in the study were 19 and 42 months, respectively. All 11 dogs were treated with phenobarbital, with 10 dogs receiving concomitant bromide therapy. No significant correlation between the duration of the first, second, or third antiepileptic drug therapy and the change in the number of cluster seizure events before or after use of RDZ was found. Comparisons of seizure activity were done for the same time interval before and after the onset of RDZ availability. A significant decrease in the total number of seizure events and the total number of cluster seizures events was found after RDZ availability. Similarly, a significant difference in the average number of seizures per cluster seizure event and the total number of isolated seizure events occurred before and after RDZ therapy. Eight of the 11 dogs (73%) that received RDZ for 1 or more times after the first or second seizure had a 100% success rate in prevention of further seizure activity after the first dose. In 3 dogs, success and compliance rates were both equal at 100%, thus suggesting 100% efficacy of RDZ in blocking further seizure activity over the next 24 hours in these dogs. Owners had a large cost-savings because of the decrease in emergency clinic visits after initiating treatment with RDZ. Before RDZ use, the average number of emergency clinic visits was 3, with an average cost of $308 per dog. After RDZ use, the average number of emergency clinic visits was 1, with an average cost of $81 per dog. The results of this study suggest that RDZ may be an effective method of home treatment of generalized cluster seizures in dogs with idiopathic epilepsy, regardless of prior antiepileptic drug history.