potassium-bromide and Seizures

To critically evaluate and summarize available information on the safety of potassium bromide in dogs.. Systematic review.. 111 references reporting safety information relevant to potassium bromide published between 1938 and 2011.. PubMed searches without date limitations were conducted with the terms "potassium bromide" and "sodium bromide" in December 2009 and October 2011. Additional articles were identified through examination of article reference lists and book chapters on seizures in dogs and pharmacology.. Reversible neurologic signs were the most consistently reported toxicoses and were generally associated with adjunctive potassium bromide treatment or high serum bromide concentrations. Dermatologic and respiratory abnormalities were rare in dogs. Insufficient information was available to assess the effects of potassium bromide on behavior or to determine the incidence of vomiting, weight gain, polyphagia, pancreatitis, polyuria, polydipsia, or reproductive abnormalities associated with potassium bromide administration. Evidence suggested that administration of potassium bromide with food may alleviate gastrointestinal irritation and that monitoring for polyphagia, thyroid hormone abnormalities, and high serum bromide concentrations may be beneficial.. Results suggested that potassium bromide is not an appropriate choice for treatment of every dog with seizures and that practitioners should tailor therapeutic regimens and clinical monitoring to each dog. Abrupt dietary changes or fluid therapy may compromise seizure control or increase the likelihood of adverse events. Availability of an appropriately labeled, approved potassium bromide product could provide better assurance for veterinarians and their clients of the quality, safety, and effectiveness of the product for veterinary use.

Topics: Animals; Anticonvulsants; Bromides; Dog Diseases; Dogs; Potassium Compounds; Seizures

A 5-month-old boy with migrating partial seizures in infancy acquired bromoderma 4 weeks after initiating potassium bromide (KBr) therapy (60mg/kg/day). Erythematous pustules appeared on the forehead within a few days of attaching electroencephalography electrodes, and on the cheek at the site of nasogastric tube fixation. These later developed into vegetant plaques. Bromoderma aggravated at the site of skin biopsy that was performed 4 weeks after KBr termination. Bromoderma tuberosum should be recognized widely, considering the increasing use of KBr for treating intractable childhood epilepsy.

Topics: Bromides; Dermatitis, Exfoliative; Drug Eruptions; Epilepsies, Partial; Humans; Infant; Male; Potassium Compounds; Seizures

In women with epilepsy, seizures can be influenced by variations in sex hormone secretion during the menstrual cycle. The proconvulsant effects of estrogen have been demonstrated in both animals and humans, whereas progesterone has been found to have anticonvulsant properties. Catamenial epilepsy affects approximately one-third of women with epilepsy. This type of epilepsy has generally been defined as an increase in seizure frequency beginning immediately before or during menses. However, three distinct patterns of catamenial epilepsy have been described: perimenstrual, periovulatory, and luteal. The diagnosis of catamenial epilepsy can be made through careful assessment of menstrual and seizure diaries and characterization of cycle type and duration. A variety of therapies for catamenial epilepsy have been proposed, including acetazolamide, cyclical use of benzodiazepines or conventional antiepileptic drugs (AEDs), and hormonal therapy. However, evidence for the effectiveness of these treatment approaches comes from small, unblinded series or anecdotal reports. Larger multicenter trials, as well as further investigation of the pathophysiology of the disorder, are needed to identify the most effective treatment for women with catamenial epilepsy.

Topics: Acetazolamide; Adolescent; Adult; Animals; Anticonvulsants; Brain Edema; Bromides; Contraceptives, Oral, Hormonal; Convulsants; Epilepsy; Estradiol; Estrogen Receptor Modulators; Female; Gonadal Steroid Hormones; Humans; Incidence; Menstrual Cycle; Middle Aged; Models, Biological; Periodicity; Potassium Compounds; Pregnanolone; Progesterone; Pyramidal Cells; Rats; Seizures

Successful treatment of seizure disorders in small animals requires proper patient assessment, understanding the principles of antiepileptic drug (AED) therapy, designing a strategy for pharmacotherapy, and plans for emergency treatment. Several levels of assessment are needed in managing an epileptic patient to include the diagnosis, effectiveness of therapy, and health-related quality of life assessments. Three levels of diagnosis are important in determining the appropriate AED therapy: 1) confirmation that an epileptic seizure has occurred, and if so, the seizure type(s) manifested; 2) diagnosis of the seizure etiology; and 3) determination of an epileptic syndrome. Monotherapy is the initial goal of treating any cat or dog with epilepsy to reduce possible drug-drug interactions and adverse effects. Unfortunately, many of the AEDs useful in people cannot be prescribed to small animals either due to inappropriate pharmacokinetics (too rapid of an elimination), and potential hepatotoxicity. Thus, the most commonly used AEDs in veterinary medicine are from the same mechanistic category, that of enhancing inhibition of the brain. Antiepileptic drugs can be classified into three broad mechanistic categories: 1) enhancement of inhibitory processes via facilitated action of gamma amino-butyric acid (GABA); 2) reduction of excitatory transmission; and 3) modulation of membrane cation conductance. Pharmacotherapy strategies should be designed based on the decision when to start treatment, choice of the appropriate AED, and proper AED monitoring and adjustment. Information is presented for the current AEDs of choice, phenobarbital and bromide. Additional guidelines are provided for administration of newer AEDs, felbamate and gabapentin. All owners should be aware that emergency therapy may be necessary if recurrent or severe seizures occur in their pet. A rapid, reliable protocol is presented for the emergency management of seizuring cats and dogs in the hospital and at home. Home treatment with per rectal administration of diazepam in the dog has proven to be an effective means of reducing seizure frequency and owner anxiety. Treating each animal as an individual, applying the philosophy that seizure prevention is better than intervention, and consulting specialists to help formulate or revise treatment plans will lead to improved success in treating seizure disorders in the cat and dog.

Topics: Acetates; Amines; Animals; Anticonvulsants; Bromides; Cat Diseases; Cats; Cyclohexanecarboxylic Acids; Diazepam; Dog Diseases; Dogs; Drug Resistance; Emergency Treatment; Epilepsy; Felbamate; Gabapentin; gamma-Aminobutyric Acid; Phenobarbital; Phenylcarbamates; Potassium Compounds; Propylene Glycols; Seizures

Imepitoin has recently been approved in Europe for the management of dogs with idiopathic epilepsy. Currently, there is no evidence-based information available on the efficacy of antiepileptic drugs used as additions to the therapeutic regimen in dogs with idiopathic epilepsy that are not well controlled with imepitoin. The goal of this study was to evaluate the efficacy of phenobarbital or potassium bromide (KBr) as add-on antiepileptic drugs for controlling dogs refractory to a maximum dose of imepitoin (30 mg/kg twice daily). The study was performed as a prospective, randomised, controlled clinical trial. The efficacy of phenobarbital and KBr was evaluated by comparing monthly seizure frequency (MSF), monthly seizure day frequency (MSDF), the presence of cluster seizures during a retrospective 2-month period with a prospective follow-up of 6 months, and the overall responder rate. Twenty-seven dogs were included in the study, 14 dogs in the phenobarbital group and 13 dogs in the KBr group. Both median MSF and MSDF decreased in the phenobarbital group (both P = 0.001) and in the KBr group (P = 0.004 and P = 0.003, respectively). Overall, the number of dogs with cluster seizures decreased (P = 0.0005). The responder rate was 79% vs. 69% in the phenobarbital and KBr groups, respectively. We conclude that phenobarbital or KBr add-on treatment decreases median MSF and MSDF in epileptic dogs refractory to a maximum dose of imepitoin. Combination therapy was generally well tolerated and resulted in an improvement in seizure management in the majority of the dogs.

Topics: Animals; Anticonvulsants; Belgium; Bromides; Dog Diseases; Dogs; Epilepsy; Imidazoles; Phenobarbital; Potassium Compounds; Prospective Studies; Retrospective Studies; Seizures

Despite appropriate antiepileptic drug treatment, approximately one-third of humans and dogs with epilepsy continue experiencing seizures, emphasising the importance for new treatment strategies to improve the quality of life of people or dogs with epilepsy. A 6-month prospective, randomised, double-blinded, placebo-controlled cross-over dietary trial was designed to compare a ketogenic medium-chain TAG diet (MCTD) with a standardised placebo diet in chronically antiepileptic drug-treated dogs with idiopathic epilepsy. Dogs were fed either MCTD or placebo diet for 3 months followed by a subsequent respective switch of diet for a further 3 months. Seizure frequency, clinical and laboratory data were collected and evaluated for twenty-one dogs completing the study. Seizure frequency was significantly lower when dogs were fed the MCTD (2·31/month, 0-9·89/month) in comparison with the placebo diet (2·67/month, 0·33-22·92/month, P=0·020); three dogs achieved seizure freedom, seven additional dogs had ≥50 % reduction in seizure frequency, five had an overall <50 % reduction in seizures (38·87 %, 35·68-43·27 %) and six showed no response. Seizure day frequency were also significantly lower when dogs were fed the MCTD (1·63/month, 0-7·58/month) in comparison with the placebo diet (1·69/month, 0·33-13·82/month, P=0·022). Consumption of the MCTD also resulted in significant elevation of blood β-hydroxybutyrate concentrations in comparison with placebo diet (0·071 (sd 0·035) v. 0·053 (sd 0·028) mmol/l, P=0·028). There were no significant changes in serum concentrations of glucose (P=0·903), phenobarbital (P=0·422), potassium bromide (P=0·404) and weight (P=0·300) between diet groups. In conclusion, the data show antiepileptic properties associated with ketogenic diets and provide evidence for the efficacy of the MCTD used in this study as a therapeutic option for epilepsy treatment.

Topics: 3-Hydroxybutyric Acid; Animals; Anticonvulsants; Blood Glucose; Bromides; Cross-Over Studies; Diet, Ketogenic; Dogs; Double-Blind Method; Epilepsy; Female; Male; Phenobarbital; Potassium Compounds; Prospective Studies; Quality of Life; Seizures; Treatment Outcome; Triglycerides

Seizure threshold-2 (SZT2) gene variants have been associated with a decrease in seizure threshold resulting in variable phenotypic expressions ranging from mild-moderate intellectual disabilities without seizures, to an early-onset epileptic encephalopathy with severe cognitive impairment. In addition, hypotonia and distinctive facial dysmorphism, including a high forehead and to a lesser extent ptosis and down-slanting palpebral fissures, were present in the majority. We herein report a novel SZT2 variant in one of two siblings both diagnosed with epilepsy of infancy with migrating focal seizures (EIMFS). This report is the fourth to document a possible familial case in EIMFS, a condition that was not previously associated with SZT2 variant. This report expands the phenotypic expression of SZT2, corroborates the importance of genetic counseling in some cases of EIMFS, and highlights the efficacy of potassium bromide in controlling the seizures associated with this condition.

Topics: Bromides; Consanguinity; Electroencephalography; Epileptic Syndromes; Fatal Outcome; Female; Humans; Infant; Infant, Newborn; Nerve Tissue Proteins; Phenotype; Potassium Compounds; Seizures; Spasms, Infantile; Twins

We evaluated potassium bromide's (KBr's) efficacy and tolerability for pediatric refractory epilepsy.. We retrospectively reviewed the records of 42 patients treated with KBr in our hospital between 2008 and 2016 (age: 4 months to 19 years; mean: 6.2 years). Thirteen of them had 2 seizure types. The treatment durations ranged from 1 month to 6 years (mean: 15.0 months).. KBr had an excellent effect (seizure-free status) in 3 patients (7.1%), a moderate effect (>50% reduction in seizure frequency from the pretreatment baseline) in 21 patients (50.0%), and no effect (<50% reduction in seizure frequency from the pretreatment baseline) in 18 patients (42.9%). The effective daily doses ranged from 20 to 80 mg/kg (mean: 50.0 mg/kg). KBr was effective in 59.1% patients with generalized epilepsy (n = 22), 55.6% patients with focal epilepsy (n = 18), and both patients with Dravet syndrome. An excellent or moderate effect was found in 72.2% patients with tonic seizures (n = 18), 66.6% patients with generalized tonic-clonic seizures (n = 6), 75.0% patients with secondary generalized seizures (n = 4), 46.2% patients with focal seizures (n = 13), and 20% patients with infantile spasms (n = 10) but no patients with myoclonic seizures (n = 2). Adverse effects including drowsiness, excitement, and rashes were reported in 13 patients (31.0%).. These findings suggest that KBr is particularly effective for tonic seizures, generalized tonic-clonic seizures, and secondary generalized seizures. Although the adverse effects need further attention, KBr should be considered for pediatric refractory epilepsy.

Topics: Adolescent; Anticonvulsants; Bromides; Child; Child, Preschool; Drug Resistant Epilepsy; Epilepsies, Partial; Epilepsy, Generalized; Female; Humans; Infant; Male; Potassium Compounds; Retrospective Studies; Seizures; Treatment Outcome; Young Adult

Phenobarbital or potassium bromide (KBr) add-on treatment decreases the average monthly seizure frequency in dogs with idiopathic epilepsy resistant to a maximum dose of imepitoin. The importance of continued administration of imepitoin in these dogs is currently unknown. The goal of this study was to assess whether imepitoin withdrawal would destabilize epileptic seizure control. In this prospective clinical trial epileptic seizure control was evaluated by comparing the monthly seizure frequency of 13 dogs with well-controlled idiopathic epilepsy receiving a combination of imepitoin and phenobarbital (n=4), imepitoin and KBr (n=7), and imepitoin, phenobarbital and KBr (n=2) during a period of 3-6 months (pre-withdrawal period), with a follow-up period of 9-12 months after withdrawal of imepitoin (post-withdrawal period). Adverse effects were also recorded before and after withdrawal of imepitoin. Imepitoin was tapered off over 3 months as follows: 20mg/kg twice daily for 1 month, then 10mg/kg twice daily for 1 month, then once daily for 1 month. Withdrawal of imepitoin did not increase monthly seizure frequency (P=0.9). Moreover, all owners reported improvement in the adverse effects experienced by their dog after withdrawal of imepitoin. Imepitoin withdrawal in epileptic dogs that were well-controlled with imepitoin and phenobarbital and/or KBr did not worsen epileptic seizure control, and possibly decreased antiepileptic treatment-related adverse effects. However, a worsening of seizure frequency could occur in individual cases.

Topics: Animals; Anticonvulsants; Bromides; Dog Diseases; Dogs; Drug Therapy, Combination; Epilepsy; Female; Imidazoles; Male; Phenobarbital; Potassium Compounds; Seizures; Treatment Outcome

A girl with mild psychomotor developmental delay developed right or left hemiclonic convulsion at 10months of age. One month later, clusters of hemiclonic or bilateral tonic seizures with eyelid twitching emerged, resulting in status epilepticus. Treatment with phenobarbital and potassium bromide completely terminated the seizures within 10days. Ictal electroencephalography revealed a migrating focus of rhythmic 3-4Hz waves from the right temporal to right frontal regions and then to the left frontal regions. Genetic analysis was conducted based on the characteristic facial appearance of the patient, which identified a 2.1-Mb terminal deletion on chromosome 4p. This is the first case of Wolf-Hirschhorn syndrome complicated by epilepsy with migrating partial seizures.

Topics: Anticonvulsants; Brain; Bromides; Chromosome Deletion; Chromosomes, Human, Pair 4; Comparative Genomic Hybridization; Electroencephalography; Epilepsy; Female; Humans; Infant; Phenobarbital; Potassium Compounds; Seizures; Wolf-Hirschhorn Syndrome

To clarify the effect of levetiracetam (LEV) for acute and chronic seizure control in acute encephalitis with refractory, repetitive partial seizures (AERRPS).. We retrospectively reviewed the clinical course of six AERRPS cases treated with LEV, and explored the acute phase termination by withdrawal from barbiturate-induced coma under artificial ventilation, and the reduction in seizure frequency during the chronic phase. LEV was administrated orally or via nasogastric tubes as an add-on agent during acute (n=3; age 8-10 years) and chronic (n=3; age 19-30 years) AERRPS.. In the acute phase, administration of LEV (50-60 mg/kg/d) in combination with phenobarbital (n=3; peak 57.9-76.1 μg/ml) and potassium bromide (n=2; 30-36 mg/kg/d)) resulted in successful reduction of intravenous barbiturate dosage and withdrawal from artificial ventilation. In the chronic phase, seizure frequency reduced by >75% for 5-18 months with LEV 750-1500 mg/d.. LEV may affect seizure control in AERRPS, particularly during the chronic phase, through its unique action of inhibition of excitatory neurotransmitter release. The regimen of oral barbiturate, potassium bromide and LEV would be worth for trial during the acute phase of AERRPS.

Topics: Acute Disease; Adolescent; Adult; Anticonvulsants; Bromides; Child; Chronic Disease; Encephalitis; Female; Humans; Levetiracetam; Male; Phenobarbital; Piracetam; Potassium Compounds; Retrospective Studies; Seizures; Status Epilepticus; Young Adult

Topics: Anticonvulsants; Bromides; Child; Diagnosis, Differential; Drug Eruptions; Humans; Leg Dermatoses; Male; Potassium Compounds; Seizures; Treatment Outcome

Dravet syndrome is a catastrophic pediatric epilepsy with severe intellectual disability, impaired social development and persistent drug-resistant seizures. One of its primary monogenic causes are mutations in Nav1.1 (SCN1A), a voltage-gated sodium channel. Here we characterize zebrafish Nav1.1 (scn1Lab) mutants originally identified in a chemical mutagenesis screen. Mutants exhibit spontaneous abnormal electrographic activity, hyperactivity and convulsive behaviours. Although scn1Lab expression is reduced, microarray analysis is remarkable for the small fraction of differentially expressed genes (~3%) and lack of compensatory expression changes in other scn subunits. Ketogenic diet, diazepam, valproate, potassium bromide and stiripentol attenuate mutant seizure activity; seven other antiepileptic drugs have no effect. A phenotype-based screen of 320 compounds identifies a US Food and Drug Administration-approved compound (clemizole) that inhibits convulsive behaviours and electrographic seizures. This approach represents a new direction in modelling pediatric epilepsy and could be used to identify novel therapeutics for any monogenic epilepsy disorder.

Topics: Animals; Anticonvulsants; Benzimidazoles; Bromides; Diazepam; Dioxolanes; Drug Evaluation, Preclinical; Epilepsies, Myoclonic; Gene Expression Profiling; Mutation; NAV1.1 Voltage-Gated Sodium Channel; Potassium Compounds; Seizures; Valproic Acid; Voltage-Gated Sodium Channel beta-1 Subunit; Zebrafish; Zebrafish Proteins

Two cases that involve drug compounding errors are described. One dog exhibited increased seizure activity due to a compounded, flavored phenobarbital solution that deteriorated before the expiration date provided by the compounder. The other dog developed clinical signs of hyperkalemia and bromine toxicity following a 5-fold compounding error in the concentration of potassium bromide (KBr).

Topics: Animals; Anticonvulsants; Bromides; Dog Diseases; Dogs; Drug Compounding; Male; Medication Errors; Phenobarbital; Potassium Compounds; Seizures

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

Topics: Animals; Anticonvulsants; Bromides; Dog Diseases; Dogs; Drug Therapy, Combination; Epilepsy; Phenobarbital; Potassium Compounds; Quality of Life; Seizures; Surveys and Questionnaires; Treatment Outcome

To assess whether there is a change in seizure activity in dogs with refractory epilepsy that are receiving appropriate doses of phenobarbitone and/or potassium bromide, when gabapentin is added to the therapeutic regimen.. A prospective study of 17 dogs with a refractory seizure disorder, 16 of which have idiopathic epilepsy.. Patients were stabilised using phenobarbitone and/or potassium bromide to produce tolerable therapeutic serum concentrations and dosed additionally with gabapentin at 35 to 50 mg/kg/d (divided twice or three times daily) for 4 months. Owners recorded seizure activity and side effects during this period in a standardised diary. Patients underwent monthly physical examinations and venepuncture to assess selected serum biochemical analytes, as well as phenobarbitone and bromide concentrations. Patients were further monitored for long-term response to adjunctive gabapentin therapy.. There was no significant decrease in the number of seizures over the study period for the entire cohort, however three dogs stopped seizuring completely. There was a significant increase in the number of patients who showed an increase in the interictal period (P > 0.001). Serum alkaline phosphatase activity and triglyceride concentrations were elevated at baseline. There were no significant changes in biochemical analytes during the course of the study period. Side effects observed initially on addition of gabapentin included sedation and hind limb ataxia. The former resolved spontaneously after a few days; the latter after a slight reduction in bromide dose. Long-term, a further two patients became seizure free and ten patients remained on gabapentin indefinitely. No long-term side effects have become apparent.. Addition of gabapentin to phenobarbitone and/or potassium bromide increased the interictal period and shortened the post-seizure recovery in some canine epileptics. In some dogs, seizures were prevented completely, while in others there was an increase in interictal period. The short-half life of gabapentin has advantages for seizure control, however its present high cost may prohibit therapy in large dogs.

Topics: Amines; Animals; Anticonvulsants; Bromides; Chemotherapy, Adjuvant; Cyclohexanecarboxylic Acids; Dog Diseases; Dogs; Drug Therapy, Combination; Epilepsy; Female; Gabapentin; gamma-Aminobutyric Acid; Male; Phenobarbital; Potassium Compounds; Prospective Studies; Seizures; Treatment Outcome

Human seizure disorders are a major health concern due to the large number of affected individuals, the potentially devastating consequences of untreated seizure occurrences, and the lack of an effective treatment for all patients. Although anticonvulsants have proven very helpful in treating seizures and remain the best option available for treatment, not all afflicted individuals respond to medication and many only do so in unique drug combinations or at the cost of adverse side-effects. Therefore, new and more effective anticonvulsants are continually sought after to combat this illness. In this study, we present results which offer the possibility of using Drosophila bang-sensitive (BS) mutants as a tool to screen anticonvulsants. By feeding the BS mutants a known anticonvulsant, potassium bromide, we have demonstrated that the drug dramatically reduces the seizures of bang senseless, the most severe of the BS mutants. This methodology suggests that the Drosophila system can potentially be a powerful instrument for assaying and testing new compounds with anticonvulsant properties.

Topics: Administration, Oral; Animals; Anticonvulsants; Bromides; Disease Models, Animal; Drosophila; Drosophila Proteins; Drug Evaluation, Preclinical; Electrophysiology; Mutation; Paralysis; Potassium Compounds; Refractory Period, Electrophysiological; Seizures; Species Specificity

Ataxia, sedation, amnesia, ethanol and barbiturate potentiation, loss of efficacy (tolerance), development of dependence, and the potential for drug abuse limit the clinical use of benzodiazepines (BZDs) for long-term treatment of epilepsy or anxiety. BZD ligands that are in current use act as full allosteric modulators of gamma-aminobutyric acid (GABA)-gated chloride channels and, on long-term administration, trigger a functional uncoupling between the GABAA and BZD recognition sites. Partial allosteric modulators, which have a low intrinsic activity at the BZD recognition site of the GABAA receptor, might eventually overcome the limitations of full agonists such as diazepam (DZP).. In the present study, the new low-affinity partial BZD-receptor agonist ELB 138 [former name AWD 131-138; 1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one] was evaluated in a dog seizure model and in epileptic dogs with spontaneously recurrent seizures.. ELB 138 was shown to increase potently the pentylenetetrazole (PTZ) seizure threshold in dogs. Prolonged oral administration with twice-daily dosing of ELB 138 with either 5 or 40 mg/kg over a 5-week period was not associated with loss of anticonvulsant efficacy in the PTZ dog model. To study whether physical dependence developed during long-term treatment, the BZD antagonist flumazenil was injected after 5 weeks of treatment with ELB 138. Compared with prolonged treatment with DZP, only relatively mild abstinence symptoms were precipitated in dogs treated with ELB 138, particularly at the lower dosage (5 mg/kg, b.i.d.). In a prospective trial in dogs with newly diagnosed epilepsy, ELB 138 markedly reduced seizure frequency and severity without significant difference to standard treatments (phenobarbital or primidone) but was much better tolerated than the standard drugs. In dogs with chronic epilepsy, most dogs exhibited a reduction in seizure frequency and severity during add-on treatment with ELB 138.. The data demonstrate that the partial BZD receptor agonist ELB 138 exerts significant anticonvulsant efficacy without tolerance in a dog seizure model as well as in epileptic dogs with spontaneously recurrent seizures. These data thus substantiate that partial agonism at the BZD site of GABAA receptors offers advantages versus full agonism and constitutes a valuable approach for treatment of seizures.

Topics: Animals; Anticonvulsants; Bromides; Chronic Disease; Disease Models, Animal; Dog Diseases; Dogs; Drug Therapy, Combination; Epilepsy; Flumazenil; GABA Agonists; GABA-A Receptor Agonists; Imidazoles; Pentylenetetrazole; Phenobarbital; Potassium Compounds; Primidone; Receptors, GABA-A; Seizures; Substance Withdrawal Syndrome; Treatment Outcome

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.. Retrospective study.. 156 dogs admitted for status epilepticus or cluster seizures.. Medical records were reviewed for seizure and medication history, diagnostic test results, types of treatment, hospitalization costs, and outcome of hospital visits.. 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.. 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.

Topics: Animals; Anticonvulsants; Bromides; Cerebrospinal Fluid; Diazepam; Dog Diseases; Dogs; Female; Male; Phenobarbital; Potassium Compounds; Records; Retrospective Studies; Seizures; Status Epilepticus; Treatment Outcome

Topics: Animals; Bromides; Dog Diseases; Dogs; Drug Therapy, Combination; Phenobarbital; Potassium; Potassium Compounds; Seizures

A 4-year-old German Shepherd Dog was evaluated because of chronic hind limb lameness and recurrent seizures. Diagnostic evaluation of the dog confirmed rheumatoid arthritis and idiopathic epilepsy. The rheumatoid arthritis was treated with prednisone and piroxicam. The seizures were treated with phenobarbital plus clonazepam. The seizures were refractory and potassium bromide was substituted for clonazepam. The dog was reevaluated 4 months after initiation of potassium bromide treatment because of recurrence of arthritis signs. During hospitalization, the dog had neurologic signs, which progressed from depression to recumbency and stupor. Anisocoria, muscle pain, and hyporeflexia were noticed. Bromide toxicosis was diagnosed on the basis of toxic serum bromide concentration (2.7 mg/ml; therapeutic range, 1.0 to 2.0 mg/ml). Following cessation of potassium bromide treatment, the neurologic signs resolved. The seizures recurred 6 weeks after potassium bromide was discontinued. Bromide treatment was reinitiated at half the initial dosage. After 6 weeks, the serum bromide concentration was 1.9 mg/ml, and no seizures had been reported by the dog's owners. Therapeutic serum bromide concentrations in dogs has been reported to be 0.5 to 2.3 mg/ml. The serum bromide concentration at which toxic signs are expected is variable in human beings because individuals differ in their tolerance of the drug. Clinical trials are necessary to determine the toxic serum bromide concentrations in dogs. This case of bromism in a dog suggests that the dosage of potassium bromide should be based on serial measurement of serum bromide concentrations.

Topics: Animals; Bromides; Dog Diseases; Dogs; Lameness, Animal; Male; Potassium; Potassium Compounds; Seizures