Review Non-pharmacological treatment options for refractory epilepsy: An overview of human treatment modalities and their potential utility in dogs Valentine Martlé a,⇑ , Luc Van Ham a , Robrecht Raedt b , Kristl Vonck b , Paul Boon b , Sofie Bhatti a a Department of Small Animal Medicine and Clinical Biology, Faculty of Veterinary Medicine, Ghent University, Merelbeke 9820, Belgium b Laboratory for Clinical and Experimental Neurophysiology, Department of Neurology, Ghent University Hospital, Ghent 9000, Belgium article info Article history: Available online xxxx Keywords: Diet Dog Epilepsy surgery Neurostimulation Refractory epilepsy abstract 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 epilep- sies, 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 pro- vides 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. Ó 2013 Elsevier Ltd. All rights reserved. Introduction Epilepsy is one of the most common chronic neurological disor- ders both in humans (Sander and Shorvon, 1996; Brodie et al., 1997) and dogs (Bielfelt et al., 1971; Cunningham and Farnbach, 1988; Schwartz-Porsche, 1994; Knowles, 1998). Most dogs have idiopathic epilepsy (Schwartz-Porsche, 1994; Jaggy and Bernardini, 1998) and they are often managed successfully with standard anti- epileptic drugs (AEDs; Schwartz-Porsche et al., 1985; Schwartz- Porsche and Jurgens, 1991), but approximately 30% of cases are refractory to treatment (Lane and Bunch, 1990). Interestingly, the prevalence of refractory epilepsy is similar in humans (Kwan and Brodie, 2000). Unfortunately, although a substantial number of new AEDs have become available (Beghi, 2004), several long-term studies have demonstrated that few human patients became sei- zure free after initiating a third AED when two AEDs have failed (Kwan and Brodie, 2000; Mohanraj and Brodie, 2005, 2006). There- fore, non-pharmacological treatment options are becoming increasingly important in humans. Only a limited number of the newer treatment strategies in hu- mans have been investigated in canine epilepsy. Currently, many dogs with refractory epilepsy are eventually euthanased or die dur- ing uncontrollable seizures (Arrol et al., 2012; Monteiro et al., 2012). Dietary treatment of refractory epilepsy The ketogenic diet and human epilepsy The antiepileptic effect of fasting was noted almost 100 years ago (Geyelin, 1921) and the ketogenic diet (KD) was introduced in that same year for the treatment of epilepsy (Wilder, 1921). Over the next 20 years, the KD became a popular treatment for both children and adults with epilepsy, but with the development of different AEDs, the popularity and use of the KD diminished (Kossoff et al., 2009a). A renewed interest and research into the efficacy of the KD was initiated around 1994, due to the successful treatment of the refractory seizures of a famous American film pro- ducer’s son (Kossoff et al., 2009a). This diet is used mainly for the treatment of refractory childhood epilepsy (Kossoff et al., 2009b) and is high in fat (80%), low in carbohydrates (5%) and has ade- quate amounts of protein (15%), based on minimum daily require- ments (Kossof, 2004). The classic KD is also called the ‘long-chain triglyceride’ diet or the ‘4:1 fat:non-fat’ diet (Kossoff et al., 2009a). Despite much in vitro and in vivo investigation, the precise anti- epileptic mechanism of action (MOA) of the KD still remains un- known (Schwartzkroin, 1999; McNally and Hartman, 2012). It 1090-0233/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tvjl.2013.09.055 ⇑ Corresponding author. Tel.: +32 9 2647700. E-mail address: Valentine.Martle@UGent.be (V. Martlé). The Veterinary Journal xxx (2013) xxx–xxx Contents lists available at ScienceDirect The Veterinary Journal journal homepage: www.elsevier.com/locate/tvjl Please cite this article in press as: Martlé, V., et al. Non-pharmacological treatment options for refractory epilepsy: An overview of human treatment modalities and their potential utility in dogs. The Veterinary Journal (2013), http://dx.doi.org/10.1016/j.tvjl.2013.09.055