Andrea Fischer

International veterinary epilepsy task force consensus report on epilepsy definition, classification and terminology in companion animals

Dogs with epilepsy are among the commonest neurological patients in veterinary practice and therefore have historically attracted much attention with regard to definitions, clinical approach and management. A number of classification proposals for canine epilepsy have been published during the years reflecting always in parts the current proposals coming from the human epilepsy organisation the International League Against Epilepsy (ILAE). It has however not been possible to gain agreed consensus, “a common language”, for the classification and terminology used between veterinary and human neurologists and neuroscientists, practitioners, neuropharmacologists and neuropathologists. This has led to an unfortunate situation where different veterinary publications and textbook chapters on epilepsy merely reflect individual author preferences with respect to terminology, which can be confusing to the readers and influence the definition and diagnosis of epilepsy in first line practice and research studies.In this document the International Veterinary Epilepsy Task Force (IVETF) discusses current understanding of canine epilepsy and presents our 2015 proposal for terminology and classification of epilepsy and epileptic seizures. We propose a classification system which reflects new thoughts from the human ILAE but also roots in former well accepted terminology. We think that this classification system can be used by all stakeholders.

Etiologic classification of seizures, signalment, clinical signs, and outcome in cats with seizure disorders: 91 cases (2000–2004)

OBJECTIVE To evaluate associations among etiologic classifications of seizures and signalment, clinical signs, and outcome in cats with various seizure disorders. STUDY DESIGN Retrospective case series. ANIMALS 91 cats evaluated for seizure disorders at a veterinary teaching hospital from 2000 through 2004. PROCEDURES Data regarding characteristics of the cats and their seizures were obtained from medical records. Seizures were classified as reactive, symptomatic, or idiopathic. Survival times were displayed as Kaplan-Meier curves, and differences between etiologic classifications were assessed by log-rank test. RESULTS Over the 5-year period, the incidence of seizures among all cats evaluated at the hospital was 2.1%. Etiology was classified as reactive in 20 (22%) cats, symptomatic in 45 (50%), idiopathic or presumptive idiopathic in 23 (25%), and cardiac syncope in 3 (3%). Focal seizures with or without secondary generalization were recorded for 47 (52%) cats, and primary generalized seizures with or without status epilepticus were recorded for 44 (48%). Etiology was not associated with seizure type. However, mean age of cats with idiopathic seizures (3.5 years) was significantly lower than that of cats with reactive seizures (8.2 years) or symptomatic seizures (8.1 years). The 1-year survival rate for cats with idiopathic seizures (0.82) was longer than that for cats with reactive (0.50) or symptomatic (0.16) seizures. CONCLUSIONS AND CLINICAL RELEVANCE Seizure etiology was symptomatic or reactive in most cats. Underlying disease was not associated with seizure type. Cats with idiopathic seizures lived longer than did cats with reactive or symptomatic seizures but were also younger.

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).

Canine epilepsy as a translational model

Dogs with spontaneous diseases can exhibit a striking similarity in etiology, clinical manifestation, and disease course when compared to human patients. Therefore, dogs are intensely discussed as a translational model of human disease. In particular, genetic studies in selected dog breeds serve as an excellent tool to identify epilepsy disease genes. In addition, canine epilepsy is discussed as a translational platform for drug testing. On one hand, epileptic dogs might serve as an interesting model by allowing the evaluation of drug efficacy and potency under clinical conditions with a focus on chronic seizures resistant to standard medication, preventive strategies, or status epilepticus. On the other hand, several limitations need to be considered including owner‐based seizure monitoring, species differences in pharmacokinetics and drug interactions, as well as cost‐intensiveness. The review gives an overview on the current state of knowledge regarding the etiology, clinical manifestation, pathology, and drug response of canine epilepsy, also pointing out the urgent need for further research on specific aspects. Moreover, the putative advantages, the disadvantages, and limitations of antiepileptic drug testing in canine epilepsy are critically discussed.

Disease Progression and Treatment Response of Idiopathic Epilepsy in Australian Shepherd Dogs

BACKGROUND Idiopathic epilepsy (IE) in Australian Shepherds (ASs) occurs worldwide but there is a lack of description of the epilepsy syndrome in this breed. The ABCB1-1Δ mutation is more prevalent in ASs than in many other dog breeds. HYPOTHESIS Australian Shepherds suffer from a poorly controlled IE syndrome with prevailing severe courses. Seizure control and ABCB1-1Δ mutation might be related in this breed. ANIMALS Fifty ASs diagnosed with IE and 50 unaffected ASs. METHODS Predominant study design is a longitudinal cohort study. Pedigrees, medical records, seizure, and treatment data of ASs with IE were analyzed descriptively. Sex, color, and the ABCB1-1Δ genotype were compared between case and control groups and ASs with poorly or well-controlled seizures. Differences in survival times were assessed by logrank tests and Cox regression analysis. RESULTS Idiopathic epilepsy in ASs is dominated by moderate and severe clinical courses with the occurrence of cluster seizures and status epilepticus and a high seizure frequency. Poor seizure control and a high initial seizure frequency (≥10 seizure days/first 6 months) are associated with shorter survival times (P < .05). Poor seizure control, unrelated to the ABCB1(MDR1) genotype, is evident in 56% of epileptic ASs. Pedigree analysis suggests a genetic basis. CONCLUSION AND CLINICAL IMPORTANCE Frequent severe clinical courses, poor seizure control unrelated to the ABCB1(MDR1) genotype, and a young age at death compromise animal welfare and warrant further genetic studies to unravel the underlaying molecular mechanisms of IE and seizure control in the breed.

Disseminated angiostrongylosis with fatal cerebral haemorrhages in two dogs in Germany: A clinical case study

Canine angiostrongylosis is a nematode infection in domestic dogs and wild carnivores. Few single case reports describing the occurrence of this disease in Germany exist and until recently angiostrongylosis has not been considered endemic in this country. The present report focuses on clinical, pathological and parasitological findings in two cases of fatal disseminated canine angiostrongylosis associated with multifocal haemorrhages in the central nervous system. Both animals, which lived in Germany, presented with rapidly progressive neurological signs including depression, ataxia, unilateral central blindness and epileptic seizures. Blood work revealed grossly elevated D-dimers and mild thrombocytopenia. Both animals were subsequently euthanised due to progressive clinical aggravation. Necropsy showed cerebral and lung haemorrhages in both animals. Multiple sections of nematode larvae consistent with Angiostrongylus vasorum were identified on histopathological sections of the brain, heart, kidney and lung in both animals and a predominantly granulomatous inflammation with the occurrence of multinucleated giant cells was observed. Adult nematodes were found in the larger lung arteries of one dog and Angiostrongylus infection was subsequently confirmed by PCR-analysis and sequencing in both dogs. A. vasorum larvae were not detected by faecal Baermann examination performed in one of the dogs. It was concluded that canine angiostrongylosis should be considered as differential diagnosis in dogs in Germany, even if faecal examination is negative. There is currently still a lack of studies investigating the occurrence of angiostrongylosis in dogs and intermediate hosts in Germany which would be necessary to survey the endemic realities of this disease.

Sensitivity and specificity of fasting ammonia and serum bile acids in the diagnosis of portosystemic shunts in dogs and cats.

BACKGROUND Portosystemic shunt (PSS) is the most common cause of hepatic encephalopathy in dogs and cats. Fasting ammonia and serum bile acids (SBA) are used to diagnose PSS, but their true sensitivity and specificity have not been fully evaluated, especially in cats. OBJECTIVES The purpose of this study was to determine the diagnostic accuracy of fasting ammonia and SBA concentrations in the diagnosis of PSS in dogs and cats and to compare diagnostic accuracy between species. METHODS A retrospective analysis of data from 373 dogs and 85 cats presented to the clinic from 1996 to 2006 was carried out. Based on clinical, laboratory, and imaging findings, animals were grouped as having PSS, parenchymal hepatic disease, or extrahepatic disease. The sensitivity and specificity of ammonia and SBA concentrations for the diagnosis of PSS were calculated and receiver-operating characteristic analysis was used to optimize cut-offs. RESULTS Using the upper limit of laboratory reference intervals (ammonia, 59 micromol/L; SBA, 20 micromol/L), the sensitivity and specificity of ammonia was 85% and 86% in dogs, and 83% and 76% in cats, respectively. The sensitivity and specificity of SBA was 93% and 67% in dogs, and 100% and 71% in cats, respectively. Using optimal cut-off points for ammonia (dogs, 57 micromol/L; cats, 94 micromol/L) the sensitivity and specificity was 91% and 84% in dogs and 83% and 86% in cats, respectively. Using optimal cut-off points for SBA (dogs, 58 micromol/L; cats, 34 micromol/L) the sensitivity and specificity was 78% and 87% in dogs and 100% and 84% in cats. CONCLUSION Increased fasting ammonia and SBA concentrations are accurate indicators of PSS. An improvement in diagnostic accuracy can be achieved by using defined optimal cut-off points for the selective diagnosis of PSS.

Electrophysiologic assessment of sciatic nerve regeneration in the rat: surrounding limb muscles feature strongly in recordings from the gastrocnemius muscle.

Striking inconsistencies between the results of morphometric and electrophysiologic examinations of the regenerating nerve were observed in a previous study featuring the bridging of a 14 mm gap in the rat sciatic nerve. To shed light on this dichotomy, seven further rats were subjected to permanent sciatic nerve transection and assessed electrophysiologically, histologically and by retrograde axonal tracing at various postoperative intervals (1 h to 8 weeks). The results of the histological examinations and retrograde tracing revealed that in spite of the fact that compound muscle action potentials could be recorded in the gastrocnemius muscle, no reinnervation of the gastrocnemius muscle, either physiological or aberrant, had actually taken place. Furthermore, it was established that the electrical activity recorded in the gastrocnemius muscle after stimulation of the proximal or distal stump is generated by surrounding hind limb muscles unaffected by denervation. These are stimulated either directly, or indirectly due to spreading of the impulse. It is therefore strongly recommended that caution should be exercised when interpreting recordings from the gastrocnemius muscle after stimulation of a regenerating sciatic nerve in laboratory rodents.

International Veterinary Epilepsy Task Force consensus proposal: medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible.

Hereditary Ataxia in the Jack Russell Terrier– Clinical and Genetic Investigations

Hereditary ataxia in the Jack Russell Terrier (JRT) is characterized by a gait disturbance with symmetric generalized ataxia and hypermetric and spastic movements. Histopathology shows a disease of the entire central nervous system, predominantly an axonopathy. In the present study, 35 clinically affected dogs were examined. Gait abnormalities began at 2-9 months of age. Generalized seizures occurred in 13 dogs in addition to the ataxia, and 7 dogs developed respiratory distress. Brain stem auditory-evoked potentials (BAEPs) were abnormal in 4 of 8 examined dogs, in which only waves I and II were detected. Abnormal BAEPs suggest the possibility of hereditary ataxia in the JRT. Investigations regarding the mode of inheritance were performed by complex segregation analyses on 3 pedigrees with a total of 115 JRTs (27 clinically affected dogs and 88 unaffected littermates and ancestors). Different modes of inheritance were tested, including monogenic, mixed, and polygenic models, as well as a model with environmental effects only. Models with genetic effects explained the data significantly better than the environmental model. The monogenic model had to be rejected in this study because of an insufficient match of data when compared to that of the most general model. The polygenic and mixed major gene models explained the pedigree data best and therefore have to be regarded as possible hypotheses for the mode of inheritance of hereditary ataxia in the JRT. The polygenic model proved best suited to explain the segregation pattern in the JRT, because it had the fewest number of parameters.