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.     

Feline Temporal Lobe Epilepsy: Review of the Experimental Literature

Accumulating evidence suggests that epileptic seizures originating from the temporal lobe (TL) occur in cats. Typically, affected animals have clinically focal seizures with orofacial automatisms including salivation, facial twitching, lip smacking, chewing, licking, and swallowing. Motor arrest and autonomic and behavioral signs also may occur. Many affected cats have magnetic resonance imaging (MRI) changes within the hippocampus or histopathologically confirmed hippocampal sclerosis or necrosis. From the 1950s to the 1980s, cats frequently were used as animal models for neurophysiological experiments and electrophysiological studies, from which important basic knowledge about epilepsy originated, but which has been rarely cited in clinical veterinary studies. These studies were reviewed. Experimental research on cats showed the widespread anatomical connections among TL structures. The ictal clinical signs originating from the hippocampus, amygdala, or lateral temporal cortex are similar, because of their dense interconnections. The ictal signs can be divided into autonomic, somatic, and behavioral. For research purposes, a 6‐stage system was established, reflecting the usual sequential progression from focal to generalized seizure: attention response (1), arrest (2), salivation, licking (3), facial twitching (4), head turning or nodding (5), and generalized clonic convulsions (6). Knowledge of this data may help in recognizing low‐stage (stage 1 or stage 2) epileptic seizures in clinical practice. Early experimental research data are in accordance with recent clinical observations regarding ictal clinical signs of TL epileptic seizures in cats. Furthermore, the research data supports the idea that TL epilepsy represents a unique clinical entity with a specific seizure type and origin in cats.     

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).     

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.     

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.     

The pharmacologic spectrum of furosemide

Objective: To review the clinical spectrum and mechanisms of action of furosemide in human and small animal veterinary patients. Data sources: Review of human and veterinary literature. Data synthesis: Furosemide is used primarily for its properties as a loop diuretic; however, it has many other actions that may be clinically applicable. Furosemide has a vasodilatory effect that precedes diuresis that may confer its immediate benefit in patients with volume overload. Furosemide can be inhaled to relieve dyspnea in patients with bronchospasm. Furosemide also shows promise as an adjunct to antiseizure therapy to help control epilepsy, status epilepticus, and acute ischemic damage related to seizures. It has activity as an antioxidant, iodine depletive, and may increase thoracic lymph duct flow. Reported furosemide side effects include altered drug metabolism, electrolyte depletion, ototoxicity, mucociliary impairment, endocrine and exocrine pancreatic effects, delayed wound healing, sulfonamide toxicity, and thyroid binding interference. It is worthwhile to consider the implications of these effects when using furosemide either alone or in combination with other drugs. Conclusions: Despite the research in animal models that demonstrates a wide spectrum of pharmacologic activity, furosemide has not been widely recognized or used clinically in veterinary medicine except as a loop diuretic.     

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.     

Nonhuman primate dermatology: a literature review

In general, veterinary dermatologists do not have extensive clinical experience of nonhuman primate (NHP) dermatoses. The bulk of the published literature does not provide an organized evidence-based approach to the NHP dermatologic case. The veterinary dermatologist is left to extract information from both human and veterinary dermatology, an approach that can be problematic as it forces the clinician to make diagnostic and therapeutic decisions based on two very disparate bodies of literature. A more cohesive approach to NHP dermatology – without relying on assumptions that NHP pathology most commonly behaves similarly to other veterinary and human disease – is required. This review of the dermatology of NHP species includes discussions of primary dermatoses, as well as diseases where dermatologic signs represent a significant secondary component, provides a first step towards encouraging the veterinary community to study and report the dermatologic diseases of nonhuman primates.     

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.     

Classification of Involuntary Movements in Dogs: Myoclonus and Myotonia

Myoclonus is a sudden brief, involuntary muscle jerk. Of all the movement disorders, myoclonus is the most difficult to encapsulate into any simple framework. On the one hand, a classification system is required that is clinically useful to aid in guiding diagnosis and treatment. On the other hand, there is need for a system that organizes current knowledge regarding biological mechanisms to guide scientific research. These 2 needs are distinct, making it challenging to develop a robust classification system suitable for all purposes. We attempt to classify myoclonus as “epileptic” and “nonepileptic” based on its association with epileptic seizures. Myotonia in people may be divided into 2 clinically and molecularly defined forms: (1) nondystrophic myotonias and (2) myotonic dystrophies. The former are a group of skeletal muscle channelopathies characterized by delayed skeletal muscle relaxation. Many distinct clinical phenotypes are recognized in people, the majority relating to mutations in skeletal muscle voltage‐gated chloride (CLCN1) and sodium channel (SCN4A) genes. In dogs, myotonia is associated with mutations in CLCN1. The myotonic dystrophies are considered a multisystem clinical syndrome in people encompassing 2 clinically and molecularly defined forms designated myotonic dystrophy types 1 and 2. No mutation has been linked to veterinary muscular dystrophies. We detail veterinary examples of myotonia and attempt classification according to guidelines used in humans. This more precise categorization of myoclonus and myotonia aims to promote the search for molecular markers contributing to the phenotypic spectrum of disease. Our work aimed to assist recognition for these 2 enigmatic conditions.     

Myasthenia gravis in dogs with an emphasis on treatment and critical care management

Objective – To review the human and veterinary literature on the pathophysiology of myasthenia gravis (MG) and describe treatment options for clinical use in people and animals. Data Sources – Human and veterinary clinical reports, studies and reviews, textbooks, and recent research findings in MG from 1996 present, with a focus on treatment and patient management. Human Data Synthesis – MG is a well‐described condition in people with new research and treatment options available. Many of the newest therapeutic options available in veterinary medicine for MG are based on current strategies used in people with this condition. Seronegative MG is well described in people and provides insight to clinical cases encountered in veterinary medicine when the index of suspicion is high though serologic tests are negative. Veterinary Data Synthesis – Previous studies in veterinary medicine focused on the use of acetylcholinesterase inhibitors as the main form of treatment in canine MG. Recent studies, mainly case series and case reports, emphasize the use of immunomodulatory treatments as an alternative for long‐term treatment. However, there are no randomized, controlled studies on treatment with immunomodulatory therapy for MG in dogs available to assess the efficacy of this treatment strategy. Conclusions – Although early recognition of clinical signs is most important in the outcome of patients with MG, further understanding the pathophysiology of MG may lead to earlier diagnosis and novel treatment strategies. The discovery of additional autoantibodies against striated muscle proteins in dogs, should enhance our understanding of diseases affecting the neuromuscular junction. In addition, clinical data for canine MG could be applied to other autoimmune disorders.     

Absence of temporal lobe epilepsy pathology in dogs with medically intractable epilepsy

Epilepsy is a common neurological problem in dogs. In some dogs, seizures cannot be controlled adequately with anticonvulsant medication. Temporal lobe epilepsy is the most common type of epilepsy in adult humans, it is frequently resistant to anticonvulsant therapy, and it is commonly associated with characteristic neuropathological abnormalities in the hippocampal dentate gyrus. We sought to test the hypothesis that dogs with medically intractable epilepsy have temporal lobe epilepsy. The hippocampi of 6 dogs that were euthanized because of chronic, recurrent seizures were compared with those of 8 nonepileptic controls. In control and epileptic dogs, stereological cell counting showed similar numbers of neurons in the hilus of the dentate gyrus, somatostatin immunoreactivity identified numerous immunopositive neurons in the hilus, and Timm staining showed the normal pattern of granule cell axon projections. These findings demonstrate a lack of hilar neuron loss and granule cell axon reorganization, suggesting that temporal lobe epilepsy is not a common cause of medically intractable epilepsy in dogs.     

Clinical and genetic investigations of idiopathic epilepsy in the Bernese mountain dog

A study was conducted to investigate the clinical aspects and to define the mode of inheritance of idiopathic epilepsy in the Bernese mountain dog. Pedigree analyses were carried out on an open, non-preselected population of 4005 dogs. Five different subpopulations with 50 epileptic dogs from 13 generations were included. Almost all epileptic patients showed generalised seizures of the grand-mal type with a well-defined prodromal and postictal phase. The majority (62 per cent) of the epileptic dogs had had their first seizures at between one and three years of age and it was found that the age at first seizure was significantly (P < 0.05) lower in dogs from affected parental animals than in dogs from healthy parental animals. A clear predisposition for males was also noted. Additionally, there was no correlation between inbreeding coefficient and age at first seizure or incidence rate of seizures. The increased occurrence of the disease in different subpopulations and different families of the same sires or dams showed that there was a genetic basis for the condition in the Bernese mountain dog. Furthermore, the results of the pedigree analyses and binomial test support the hypothesis that idiopathic epilepsy has a polygenic, recessive mode of inheritance in the breed. Additional objective test-mating programmes would however be necessary to define the exact mode of inheritance.     

Canine status epilepticus: a retrospective study of 50 cases

The medical records of 50 dogs that exhibited generalised convulsive tonic-clonic (GCTC) status epilepticus (SE) were reviewed and compared with the records of 50 dogs that exhibited non-SE GCTC seizures. The mean age, bodyweight and gender of the patients in both groups were not significantly different. Dogs in the non-SE group were two times more likely to be an idiopathic epileptic than to have secondary epileptic seizures. The SE group was more likely to have abnormalities on cerebrospinal fluid analysis, but not more likely to have abnormalities detected on computed tomography, when compared with the non-SE group. SE was 1.57 times more likely if the cause for the seizures was secondary or reactive epilepsy rather than idiopathic or primary epilepsy. In conclusion, dogs that exhibit SE should be thoroughly investigated for secondary causes.     

Electroencephalographic examination of epileptic dogs under propofol restraint

The main aim of this study was to identify interictal epileptiform discharges in a group of dogs with seizures of known aetiology (symptomatic epilepsy, SE) and in dogs with idiopathic epilepsy (IE). Propofol was used for chemical restraint in all dogs. We found electroencephalographic (EEG) changes that could be considered epileptiform discharges (EDs) in 5 out of 40 dogs (12.5%). The EEG changes identified were spikes in four cases and periodic epileptiform discharges in one case. All EDs were seen in the SE group. We conclude that the interictal electroencephalographic examinations of propofolanaesthetised dogs suffering from IE and SE rarely show epileptic discharges and that the diagnostic value of such EEGs in the work-up for epilepsy seems to be low as epileptic discharges were unlikely to be detected. However, positive findings are more likely to be connected with SE. We found frequent, transient EEG phenomena (spindles, K-complexes, vertex waves, positive occipital sharp transients of sleep, cyclic alternating patterns), which are non-epileptic but their differentiation from epileptic phenomena is challenging.     

Review cutaneous lesions of the canine scrotum

Scrotal lesions are uncommon and often present a diagnostic challenge. In the veterinary literature there are no texts devoted to this subject. This study reviews and illustrates canine scrotal lesions following an aetiological layout with the aim of facilitating clinical identification and diagnosis. Infectious, immune-mediated, endocrinological and neoplastic conditions are the most commonly reported causes of scrotal lesions in the dog. They may affect the scrotum only or other parts of the body as well. The clinical presentation of the lesions, the presence of primary or secondary lesions and the presence of clinical signs of systemic disease may help in obtaining a diagnosis. In some cases further investigations are necessary to reach a definitive diagnosis. Histopathology aids in understanding pathological reactions of the scrotal skin but unfortunately this is not commonly carried out and few reports in the literature include histopathology. The list of conditions given in this review is not exhaustive and other, more rare, diseases may be encountered.     

Non-pharmacological treatment options for refractory epilepsy: An overview of human treatment modalities and their potential utility in dogs

Refractory epilepsy is a common disorder both in humans and dogs and treatment protocols are difficult to optimise. In humans, different non-pharmacological treatment modalities currently available include surgery, the ketogenic diet and neurostimulation. Surgery leads to freedom from seizures in 50–75% of patients, but requires strict patient selection. The ketogenic diet is indicated in severe childhood epilepsies, but efficacy is limited and long-term compliance can be problematic. In the past decade, various types of neurostimulation have emerged as promising treatment modalities for humans with refractory epilepsy. Currently, none of these treatment options are used in routine daily clinical practice to treat dogs with the condition. Since many dogs with poorly controlled seizures do not survive, the search for alternative treatment options for canine refractory epilepsy should be prioritised. This review provides an overview of non-pharmacological treatment options for human refractory epilepsy. The current knowledge and limitations of these treatments in canine refractory epilepsy is also discussed.