International Veterinary Epilepsy Task Force’s current understanding of idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs

Hülsmeyer et al. BMC Veterinary Research (2015) 11:175 DOI 10.1186/s12917-015-0463-0 CORRESPONDENCE Open Access International Veterinary Epilepsy Task Force’s current understanding of idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs Velia-Isabel Hülsmeyer1*, Andrea Fischer1, Paul J.J. Mandigers2, Luisa DeRisio3, Mette Berendt4, Clare Rusbridge5,6, Sofie F.M. Bhatti7, Akos Pakozdy8, Edward E. Patterson9, Simon Platt10, Rowena M.A. Packer11 and Holger A. Volk11 Abstract Canine idiopathic epilepsy is a common neurological disease affecting both purebred and crossbred dogs. Various breed-specific cohort, epidemiological and genetic studies have been conducted to date, which all improved our knowledge and general understanding of canine idiopathic epilepsy, and in particular our knowledge of those breeds studied. However, these studies also frequently revealed differences between the investigated breeds with respect to clinical features, inheritance and prevalence rates. Awareness and observation of breed-specific differences is important for successful management of the dog with epilepsy in everyday clinical practice and furthermore may promote canine epilepsy research. The following manuscript reviews the evidence available for breeds which have been identified as being predisposed to idiopathic epilepsy with a proven or suspected genetic background, and highlights different breed specific clinical features (e.g. age at onset, sex, seizure type), treatment response, prevalence rates and proposed inheritance reported in the literature. In addition, certain breed-specific diseases that may act as potential differentials for idiopathic epilepsy are highlighted. Keywords: Idiopathic epilepsy, Dog, Breed, Epilepsy prevalence, Epileptic seizure Introduction Canine idiopathic epilepsy is a common neurological disease and has been recently defined as two or more unprovoked seizures at least 24 h apart with no identifiable underlying etiology other than a suspected genetic origin. Idiopathic epilepsy still represents a diagnosis of exclusion and an appropriate diagnostic workup is essential as a correct diagnosis impacts treatment and breeding decisions [1]. Affected dogs most often require life-long antiepileptic medication and regular control visits. Consequently, the daily lives of many owners are affected by concerns related to their pet’s seizures and the changes in daily routine [1–4]. Furthermore, canine idiopathic epilepsy is a disease, which is characterised by a broad array of clinical signs, age of onset, and at least * Correspondence: 1 Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-University, Veterinärstr. 13, 80539 Munich, Germany Full list of author information is available at the end of the article in part underlying genetic backgrounds (see also Tables 1 and 2) [5, 6]. In recent years, idiopathic epilepsy with a proven or suspected genetic background has been reported for a number of purebred dogs with most studies focusing on clinical characteristics and genetic aspects. However, most studies have not yet identified causative gene mutations, suggesting that, either the research group in question did not have resources or availability to go from clinical to genetic identification of monogenic epilepsy-causing genes or that inheritance may be complex, involving several or many susceptibility genes, and be reflective of additional environmental interactions similar to what is proposed for many human genetic epilepsies [5–7]. The individual dog's response to antiepileptic treatment may also be complex and in some individuals, successful antiepileptic drug treatment presents a time- and cost-consuming challenge with an increased risk for poor quality of life, premature death or euthanasia when seizures cannot be adequately © 2015 Hülsmeyer et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Hülsmeyer et al. BMC Veterinary Research (2015) 11:175 Page 2 of 28 Table 1 Depicting breed-specific data regarding age of seizure onset Breed Age at seizure onset Reference Australian Shepherd 2.5 years (median) Weissl et al. 2012 [9] Belgian Shepherd 3.3 years (mean) Berendt et al. 2008 [23] 3.3 years (mean) Seppala et al. 2012 [34] Bernese Mountain dog 26.5 months (mean) Kathmann et al. 1999 [45] Border Collie 2.5 years (median) Hülsmeyer et al. 2010 [8] Border Terrier 3.2 years (mean) Kloene et al. 2008 [56] Dalmatian 2.9 years (median), 3.2 years (mean) Licht et al. 2002 [65] English Springer Spaniel 3 years (median) Patterson et al. 2005 [74] Finnish Spitz 3 years (median) Viitmaa et al. 2013 [82] Golden Retriever 27.5 months (mean) Srenk et al. 1994 [84] 24.9 months (mean) Lengweiler&Jaggy 1999 [86] Hungarian (Magyar) Vizsla 3 years (median) Patterson et al. 2003 [87] Irish Wolfhound by the age of 3 years in 73 % of dogs Casal et al. 2006 [24] Italian Spinone 38 months (mean) De Risio et al. 2015 [93] Labrador Retriever 30.6 months (mean) Jaggy et al. 1998 [95] 34 months for males and 28 months for females (mean) Heynold et al. 1997 [94] by the age of 4 years in 76 % of dogs Berendt et al. 2002 [26] Lagotto Romganolo 6.3 weeks (mean) Jokinen et al. 2007 [105] Petit Basset Griffon Vendeen 2 years (median) Gulløv et al. 2011 [25] Shetland Sheepdog predominantly between 1 and 1.5 years Morita et al. 2002 [109] Standard Poodle 3.7 years (median) Licht et al. 2007 [113] 2.4 years (median), 2.8 years (mean) Licht et al. 2002 [65] controlled [8–13]. Estimated prevalence data among the general dog population have been reported with variable results [14–17]. The true prevalence of epilepsy in dogs is unknown and has been estimated to be 0.6–0.75 % in general dog population [16, 18]. However, prevalence rates may differ considerably when looking at hospital populations with prevalence rates of 0.5 − 5 % in nonreferral population and of 1–2.6 % in referral hospital population [14–17, 19–22]. In breeds, which are predisposed to idiopathic epilepsy, considerable higher prevalence rates are reported [23–26] than the prevalence estimated for the general dog population (see Table 3.), which is one of the reasons a genetic component is suspected in certain canine breeds. Current data show that the clinical courses, seizure semiology, treatment responses and heritability may differ substantially between dog breeds and also between geographically distinct populations of the same breed, which further highlights the complexity of the disease. In summary, knowledge and consi (...truncated)