Seizures In Dogs Research Articles

Abstract

Treatment of seizures in 12 dogs and a cat with propofol Steffen, F. & Grasmueck, S. (2000) Propofol ftor treatment of refractory seizures in dogs and cats with intracranial disorders....

Comparison of plasma benzodiazepine concentrations following intranasal and intravenous administration of diazepam to dogs

To determine whether plasma concentrations of benzodiazepines (BDZ) in dogs following intranasal (IN) administration of diazepam are comparable to concentrations following IV administration. 6 (4 male, 2 female) healthy adult Greyhounds. Dogs were randomly assigned to 2 groups of 3 dogs in a crossover design. Diazepam (0.5 mg/kg of body weight) was administered intravenously to dogs in group 1 and intranasally to dogs in group 2. Blood was collected from the jugular vein of each dog into tubes containing lithium heparin before and 3, 6, 9, 12, 15, 20, 30, 60, 120, 240, and 480 minutes following diazepam administration. After a 4-day washout period, dogs in group 1 received diazepam intranasally, dogs in group 2 received diazepam intravenously, and blood was again collected. Plasma concentration of BDZ was determined by use of a fluorescence polarization immunoassay. Mean (+/- SD) peak plasma concentration of BDZ following IV administration (1,316 +/- 216 microg/L) was greater than that following IN administration (448 +/- 41 microg/L). Time to peak concentration was < or = 3 minutes following IV administration and 4.5 +/- 1.5 minutes following IN administration. Mean bioavailability of BDZ following IN administration was 80 +/- 9%. Diazepam is rapidly and efficiently absorbed following IN administration of the parenteral formulation. Plasma concentrations match or exceed the suggested therapeutic concentration (300 microg/L). Intranasal administration of diazepam may be useful for treatment of seizures in dogs by owners or when intravenous access is not readily available.

Vagus nerve stimulation: a new tool for brain research and therapy∗

Biological psychiatry has a long history of using somatic therapies to treat neuropsychiatric illnesses and to understand brain function. These methods have included neurosurgery, electroconvulsive therapy, and, most recently, transcranial magnetic stimulation. Fourteen years ago researchers discovered that intermittent electrical stimulation of the vagus nerve produces inhibition of neural processes, which can alter brain electrical activity and terminate seizures in dogs. Since then, approximately 6000 people worldwide have received vagus nerve stimulation for treatment-resistant epilepsy. We review the neurobiology and anatomy of the vagus nerve and provide an overview of the vagus nerve stimulation technique. We also describe the safety and potential utility of vagus nerve stimulation as a neuroscience research tool and as a putative treatment for psychiatric conditions. Vagus nerve stimulation appears to be a promising new somatic intervention that may improve our understanding of brain function and has promise in the treatment of neuropsychiatric disorders.

Inflammatory diseases of the central nervous system in dogs

Inflammatory diseases of the central nervous system (CNS) are important causes of seizures in dogs. Specific diseases include canine distemper, rabies, cryptococcosis, coccidioidomycosis, toxoplasmosis, neosporosis, Rocky Mountain spotted fever, ehrlichiosis, granulomatous meningoencephalomyelitis, and pug dog encephalitis. Inflammatory disorders should be considered when a dog with seizures has persistent neurological deficits, suffers an onset of seizures at less than 1 or greater than 5 years of age, or exhibits signs of systemic illness. A thorough history, examination, and analysis of cerebrospinal fluid are important in the diagnosis of inflammatory diseases. However, even with extensive diagnostic testing, a specific etiology is identified in less than two thirds of dogs with inflammatory diseases of the CNS.

Surgical Treatments for Seizure: Adaptability for Dogs

Surgical treatments are often used for human epileptics who are refractory to more conventional anticonvulsant therapies. The goals of surgery are to decrease seizure morbidity or, ideally, bring about a cure to the seizure disorder. As a sizable subpopulation of dogs with seizures are also refractory to currently available anticonvulsant therapies, consideration has been given to evaluating alternative treatments for seizures in dogs. This article discusses the adaptability of surgical treatments used in humans for use in seizure control in affected dogs.

Seizures in Dogs

Epileptic seizures are the most common neurologic problem of the dog. The ability of a clinician to start proper management does not require elaborate equipment or specialized skills. What is needed is a thorough assessment of the history and examination findings. Dogs with a history of seizures at less than 1 or greater than 7 years of age, a history of behavioral changes, an initial interictal interval of less than 4 weeks, or an initial partial seizure should be suspected of having an identifiable underlying cause for the seizures. As such, an appropriate diagnostic evaluation should be done. Once a cause has been determined, PB is the AED of choice for dogs without underlying liver disease. Factors that enhance successful PB therapy are early initiation of therapy and proper monitoring of trough serum concentrations. Dogs that develop functional tolerance to PB should be given oral potassium bromide as the second AED. Diazepam per rectum can be used as an at-home therapy to stop cluster seizure activity. Overall, improved seizure control can be achieved by establishing a well-thought out therapeutic monitoring schedule. This approach will lead to improved quality of life for the patient, resulting in greater client satisfaction and less clinician frustration.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional Changes in Central Nervous System Thyrotropin-Releasing Hormone after Pentylenetetrazol-Induced Seizures in Dogs

Regional Changes in Central Nervous System Thyrotropin-Releasing Hormone after Pentylenetetrazol-Induced Seizures in Dogs

Regional changes in central nervous system thyrotropin-releasing hormone after pentylenetetrazol-induced seizures in dogs.

We have recently shown that seizures induce significant and sustained elevations of thyrotropin-releasing hormone (TRH) in specific extrahypothalamic rat brain regions associated with epileptic foci including amygdala, hippocampus, pyriform cortex, and anterior cortex. Seizures were induced in dogs to further study the effect on central nervous system TRH in a species known to show epileptiform seizures. Adult mongrel beagles were given pentylenetetrazol (PTZ) to induce generalized tonic-clonic seizures. Two groups of dogs were given either PTZ or saline every other day for four intravenous injections. Major motor seizures were observed visually and by electroencephalography with each PTZ injection, and these lasted from 3 to 10 minutes. Forty-eight hours after the fourth seizure, the dogs were killed and brains were removed, dissected, and stored at -90 degrees. After acetic acid extraction, extracts were assayed for TRH content by specific radioimmunoassay. Significant (P < 0.05) postictal TRH increases were seen in frontal cortex (1.5-fold), dorsal hippocampus (2.2-fold), pyriform cortex (2.5-fold), and amygdala (2.1-fold). Cerebellum, medulla, thalamus, hypothalamus, and septum showed no postictal changes in TRH. This report is the first to demonstrate TRH elevations in specific central nervous system regions associated with epileptic foci in the dog. Our results continue to stress the importance of the pyriform/periamygdaloid region as a key limbic region of endogenous TRH action in response to seizures and provides further evidence that TRH is either directly or indirectly involved in seizure modulation. Additional recent data from our laboratory and others suggest that this modulation is intrinsic to the hippocampus and may be anticonvulsant in nature.

Trans-2-en-valproate: reevaluation of its anticonvulsant efficacy in standardized seizure models in mice, rats and dogs

The anticonvulsant potency of the Irans isomer of 2-en-valproate (trans-2-en-VPA) was determined in standardized models for different seizure types in rodents and dogs. In mice and rats, adverse effects were quantified by the rotarod and chimney tests. Clinically established antiepileptic drugs (valproate, ethosuximide, phenobarbital, carbamazepine, phenytoin, diazepam) were used for comparison. Based on time course studies, drug potencies were determined and compared at the individual time of peak anticonvulsant effect. Potency comparisons were based on administered dosages and, in the case of trans-2-en-VPA and valproate, also on plasma levels determined after administration of anticonvulsant doses. The data show that trans-2-en-VPA exerts anticonvulsant effects against different seizure types i.e., myoclonic, clonic, and tonic seizures in rodents and (myo)clonic seizures in dogs. In most seizure models, trans2-en-VPA was more potent than valproate, when both compounds were compared at their individual times of peak effect. Time course and pharmacokinetic studies showed that duration of action and pharmacokinetic characteristics of trans-2-en-VPA and valproate are similar. In the rotarod and chimney tests in mice and rats, trans-2-en-VPA was more potent than valproate. However, because of the higher anticonvulsant potency of trans-2-en-VPA, protective indices calculated from rodent models were similar to those of valproate. Similarly, in dogs trans-2-en-VPA exerted anticonvulsant effects at doses below those which induced sedation and ataxia. In view of the previously reported advantages of trans-2-en-VPA compared to valproate with respect to teratogenic and hepatotoxic effects, the present data substantiate that trans-2-en-VPA might be a valuable alternative to valproate in antiepileptic therapy.

Vagal Stimulation Reduces the Severity of Maximal Electroshock Seizures in Intact Rats: Use of a Cuff Electrode for Stimulating and Recording

J. Zabara showed that repetitive vagal stimulation (VS) prevents or ameliorates convulsive seizures in dogs. We have studied the effects of VS on maximal electroshock seizures (MES) in intact rats: (1) A 5 wire cuff electrode was developed for stimulating and recording from the vagus. Compound action potentials (AP) were recorded and strength-duration curves obtained for A and C fibers. There is a monotonic relationship with a negative slope between heart rate (HR) and AP amplitude. C fibers remain excitable for 25 days after cuff implant. (2) The anticonvulsant efficacy of VS is directly related to the fraction of vagal C fibers stimulated and the frequency of stimulation. (3) The anticonvulsant efficacy of VS has been established using two rat models of human epilepsy. VS abolishes the extensor component of the tonic phase of a MES and shortens or prevents tonic seizures induced by pentylenetetrazol (PTZ). (4) VS appears to act via release of large quantities of the inhibitory mediators GABA and glycine throughout large volumes of the brain. (5) It is rational to test VS in man as a treatment for intractable seizures.

Effects of Vagal Stimulation on Experimentally Induced Seizures in Rats

Repetitive stimulation of the vagus nerve inhibits chemically induced seizures in dogs. We report here the results and conclusions from studies designed to answer some of the immediate questions raised by this finding. (1) Maximal stimulation of vagal C fibers at frequencies greater than 4 Hz prevents or reduces chemically and electrically induced seizures in young male rats. (2) Antiepileptic potency is directly related to the fraction of vagal C fibers stimulated. (3) Vagal stimulation shortens but does not shut down a chemical seizure once it has begun. (4) In rats, optimal stimulus frequency is approximately 10-20 Hz; duration of stimulus, 0.5-1 ms; and stimulus strength, 0.2-0.5 mA/mm2 of nerve cross-section. These results, when taken together with similar results obtained from dogs, monkeys, and humans, strongly suggest that periodic stimulation of the vagus nerve using appropriate stimulation parameters is a powerful method for preventing seizures. The data from the literature suggest that the antiepileptic actions of vagal stimulation are largely mediated by widespread release of GABA and glycine in the brainstem and cerebral cortex. The probable pathway is via projections from the nucleus of the solitary tract to the reticular formation and thence by diffuse projections to the cortex and other areas. Intermittent vagal stimulation has the potentiality of reducing the number and/or the intensity of seizures in patients with intractable epilepsy. These results indicate that feasibility studies in humans should be continued and expanded.

Medical Management of Recurrent Seizures in Dogs and Cats

The problem of recurrent seizures is a common and challenging one in veterinary medical practice. The pathophysiology and pharmacologic suppression of focal seizure activity have been studied extensively in basic research settings, yet little is known of the genesis, modulation, and termination of generalized seizures, the most common form of seizures noted to occur in companion animals. Knowledge concerning the pharmacokinetic fate of anticonvulsant drugs currently used in veterinary medicine is adequate, though prospective clinical studies of the efficacy of these drugs in the treatment of various types of seizures are lacking. This study will review the available literature regarding the pharmacology, use, and side effects of anticonvulsant drugs currently available for control of recurrent seizures in companion animals. Alternative anticonvulsant drugs will also be described.

Intra-arterial valium: its safety and effectiveness.

Diazepam (Valium) was injected directly into the renal and mesenteric arteries of 10 dogs. There was no histologic evidence of vascular or end-organ toxicity. Spinal seizures due to selective spinal cord arteriography in monkeys were completely suppressed with intra-arterial diazepam. The volume of contrast agent required to induce spinal seizures in dogs was doubled by a preliminary intra-arterial infusion of diazepam. Potential clinical applications are discussed.

Recovery after procaine-induced seizures in dogs

1. 1. Generalized convulsions can be produced in most dogs by the i.v. administration of procaine hydrochloride 100 mg/kg. 2. 2. In paralyzed mechanically ventilated dogs this dose of procaine produces repetitive EEG seizure discharges similar in timing to the generalized motor convulsions seen in unparalyzed dogs. 3. 3. Maintenance of good ventilation is a major factor in recovery after such seizures regardless of their duration. Room air is adequate for this purpose. 4. 4. Both generalized convulsions in unparalyzed dogs and repetitive EEG seizure discharges in paralyzed dogs can be terminated by the injection of thiopental 100 mg i.v. 5. 5. In paired experiments in the same dog, recovery times were similar whether seizures were suppressed promptly with thiopental or allowed to terminate spontaneously, provided good ventilation was maintained.

Intrathecal aminopterin therapy of meningeal leukemia.

Meningeal leukemia is an important complication of acute leukemia. 3 While chemotherapy has resulted in prolongation of survival, 4 the effective antimetabolites do not reach therapeutic levels in the cerebrospinal fluid. 5,6 As a result, meningeal leukemia has become the major therapeutic problem in patients with acute leukemia in remission, as well as being a serious complication encountered in patients with active leukemia. 3 Intrathecal methotrexate (Amethopterin) has been used for the treatment of meningeal leukemia. 7-9 At dosages usually employed, this therapy has often been adequate to control symptoms. However, in cases which do not respond, further increments in dosage have been limited by concern regarding neurotoxicity. Wollner et al. described seizures in dogs following 1.0-1.5 mg. per kilogram of methotrexate administered by cisternal injection. 10 Moreover, neurotoxicity of folic acid antagonists related to the quantity of pteroylglutamic acid, not to the antifolic activity of the compound. 10 Therefore,

Cerebral Effects of Induced Electro-encephalographic Seizures in Dogs

Cerebral Effects of Induced Electro-encephalographic Seizures in Dogs

A SUGGESTION ON THE MECHANISM HOW ELECTRIC CURRENT EXCITES THE NERVOUS SYSTEM

1. If the faradization of a certain strength and duration was applied to the motor cortex of a dog, the epileptic seizure was produced which continued after the cessation of the application, and when the motor cortex was excised, the attack was suddenly ceased.2. When a minute quantity of nicotine, picrotoxine, pentamethylentetrazol in its diluted solution was introduced into the grey matter of the motor area of a dog, the epileptic seizure was produced and continued, and as soon as when the site of its application was excised, the attack was suddenly ceased.3. Acetylcholine in its rather high concentration which was applied to the motor area could produce the epileptic fit as the above chemicals in dogs as well as in human beings.4. Sodium glutamate if pure in its appropriate concentration also could produce from the motor cortex the fit of epileptic seizure in dogs as well as in human beings, but when it was mixed with proteinoids, those motor action was inhibited.5. When sodium glutamate was not pure, it was inactive in the above motor effect, but if it was treated for a few second in vitro by the electric current, direct or induced, it was suddenly disinhibited and produces the motor effect. The sodium glutamate was the only substance which would be activated by current in vitro.6. A model experiment was introduced and discussed by the author which suggested how electric current excited the motor nerve cells of extrapyramidal system. At the same time, a hypothesis on aetiological origin of epilepsy was offered.