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).     

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.     

Case Series: Continuous electroencephalographic monitoring of status epilepticus in dogs and cats: 10 patients (2004–2005)

Objective – To describe the use of continuous electroencephalographic (EEG) monitoring for management of status epilepticus (SE) in dogs and cats. Design – Retrospective study. Setting – University teaching hospital. Animals – Ten patients (7 dogs, 3 cats) with SE of differing etiology (idiopathic epilepsy, n=3; toxicity, n=4; meningoencephalitis, n=2; undefined, n=1). Interventions – The EEG was recorded continuously from 5 stainless‐steel needle electrodes inserted SC. Animals were treated with diazepam and phenobarbital followed by either propofol (n=3) or pentobarbital (n=7) as a continuous rate of infusion. Measurements and Main Results – Clinical seizures stopped after induction of anesthesia in each animal. The EEG, however, still showed distinct epileptiform patterns (spikes, polyspikes) in all animals. Paroxysms were suppressed by increasing the infusion rate of either pentobarbital or propofol. A burst‐suppression pattern was achieved in 5 animals. EEG epileptiform activity reappeared in 4 animals when attempting to taper the dose after >6 hours of anesthesia. This was interpreted as ongoing EEG seizure activity and an increased risk for clinical seizures, and the anesthetic dosage was adjusted accordingly. Conclusion – Continuous EEG monitoring appears to be a useful tool for therapeutic monitoring of SE in dogs and cats. It allows the detection of EEG seizures without the appearance of clinical seizures. Further investigations with blinded investigators and homogeneous animal groups to define therapeutic endpoints are warranted.     

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.     

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.     

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.     

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.)     

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.     

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.     

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.     

Risk factors for development of status epilepticus in dogs with idiopathic epilepsy and effects of status epilepticus on outcome and survival time: 32 cases (1990-1996)

OBJECTIVE: To identify risk factors for episodes of status epilepticus (SE) in dogs with idiopathic epilepsy and determine how SE affects long-term outcome and survival time. DESIGN: Retrospective study. ANIMALS: 32 dogs with idiopathic epilepsy. PROCEDURE: Information on signalment, seizure onset, initiation of treatment, anticonvulsants administered, number of episodes of SE, overall seizure control, and long-term outcome was obtained from medical records and through telephone interviews. Differences between dogs that did and did not have episodes of SE were evaluated statistically. RESULTS: 19 (59%) dogs had 1 or more episodes of SE. Body weight was the only variable significantly different between dogs that did and did not have episodes of SE. Thirteen dogs (9 that did not have episodes of SE and 4 that did) were still alive at the time of the study and were > or = 10 years old. Six of the 19 (32%) dogs that had episodes of SE died of causes directly attributed to the seizure disorder. Mean life spans of dogs that did and did not have episodes of SE were 8.3 and 11.3 years, respectively. Survival time was significantly different between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that a substantial percentage of dogs with idiopathic epilepsy will have episodes of SE. Dogs with greater body weights were more likely to have episodes of SE, and early appropriate seizure treatment did not appear to decrease the risk that dogs would have episodes. Most dogs with idiopathic epilepsy had an expected life span, but survival time was shorter for dogs that had episodes of SE.     

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.     

Placebo Effect in Canine Epilepsy Trials

Background: The placebo effect is a well-recognized phenomenon in human medicine; in contrast, little information exists on the effect of placebo administration in veterinary patients.
Hypothesis: Nonpharmacologic therapeutic effects play a role in response rates identified in canine epilepsy trials.
Animals: Thirty-four dogs with epilepsy.
Methods: Meta-analysis of the 3 known prospective, placebo-controlled canine epilepsy trials. The number of seizures per week was compiled for each dog throughout their participation in the trial. Log-linear models were developed to evaluate seizure frequency during treatment and placebo relative to baseline.
Results: Twenty-two of 28 (79%) dogs in the study that received placebo demonstrated a decrease in seizure frequency compared with baseline, and 8 (29%) could be considered responders, with a 50% or greater reduction in seizures. For the 3 trials evaluated, the average reduction in seizures during placebo administration relative to baseline was 26% ( P = .0018), 29% ( P = .17), and 46% ( P = .01).
Conclusions and Clinical Importance: A positive response to placebo administration, manifesting as a decrease in seizure frequency, can be observed in epileptic dogs. This is of importance when evaluating open label studies in dogs that aim to assess efficacy of antiepileptic drugs, as the reported results might be overstated. Findings from this study highlight the need for more placebo-controlled trials in veterinary medicine.     

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.     

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.     

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.     

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.     

Inhibitory and excitatory neurotransmitters in the cerebrospinal fluid of epileptic dogs

OBJECTIVE: To determine concentrations of excitatory and inhibitory amino acids in CSF of a large number of dogs with idiopathic epilepsy or genetic epilepsy and to evaluate changes in CSF amino acid concentration with regard to drug treatment and sex. ANIMALS: 35 Labrador Retrievers with genetic epilepsy (20 male and 15 female), 94 non-Labrador Retrievers with idiopathic epilepsy (71 male and 23 female), and 20 control dogs (10 male and 10 female). PROCEDURE: Collection of CSF was performed > 72 hours after the occurrence of seizures. Cerebrospinal fluid concentrations of gamma-aminobutyric acid (GABA), glutamate (GLU), aspartate (ASP), serine, and glycine were determined by use of high performance liquid chromatography with electrochemical detection. RESULTS: CSF concentrations of GABA and GLU were significantly lower in Labrador Retrievers with genetic epilepsy (LR-group dogs) than in control-group dogs or in non-Labrador Retrievers with idiopathic epilepsy (non-LR-group dogs). The GLU-to-GABA ratio was significantly higher in LR-group dogs than in non-LR-group dogs. CSF concentrations of GLU and ASP were significantly lower when all dogs with epilepsy (non-LR- and LR-group dogs combined) were compared with control-group dogs. CONCLUSIONS AND CLINICAL RELEVANCE: A decrease in CSF concentrations of GABA appears to play a role in the pathogenesis of genetically determined epilepsy in Labrador Retrievers. However, this decrease in CSF concentrations of GABA may also be a consequence of seizure activity. The GLU-to-GABA ratio may prove to be a useful indicator of genetic epilepsy in Labrador Retrievers.     

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.