International veterinary epilepsy task force consensus proposal: outcome of therapeutic interventions in canine and feline epilepsy

BMC Veterinary Research

Holger A Volk⁸  Andrea Tipold^1,15  Veronika Stein^1,15  Clare Rusbridge^1,13  Michael Podell^1,18  Simon Platt^1,16  Jacques Penderis^1,12  Akos Pakozdy^1,14  Karen Muñana⁶  Kaspar Matiasek⁵  Paul Mandigers⁴  Sam Long^1,19  Robyn Farquhar³  Luisa De Risio²  Mette Berendt^1,11  Sofie Bhatti^1,17  Ned Patterson⁹  Wolfgang Löscher¹  Andrea Fischer^1,10  Heidrun Potschka⁷ 

[1] Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Bünteweg 17, Hannover, 30559, Germany;Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU, UK;Fernside Veterinary Centre, 205 Shenley Road, Borehamwood SG9 0TH, Hertfordshire, UK;Department of Clinical Sciences of Companion Animals, Utrecht University, Yalelaan 108, Utrecht, 3583 CM, The Netherlands;Section of Clinical & Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-University, Veterinärstr. 13, Munich, 80539, Germany;Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1052 William Moore Drive, Raleigh 27607, NC, USA;Department of Pharmacology, Toxicology and Pharmacy, Ludwig-Maximillians-University, Königinstr. 16, Munich, 80539, Germany;Department of Clinical Science and Services, Royal Veterinary College, Hatfield AL9 7TA, Hertfordshire, UK;University of Minnesota College of Veterinary Medicine, D426 Veterinary Medical Center, 1352 Boyd Avenue, St. Paul 55108, MN, USA;Service Neurology at the Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-University, Veterinärstr. 13, Munich, 80539, Germany;Department of Veterinary and Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark;Vet Extra Neurology, Broadleys Veterinary Hospital, Craig Leith Road, Stirling FK7 7LE, Stirlingshire, UK;School of Veterinary Medicine, Faculty of Health & Medical Sciences, University of Surrey, Guildford GU2 7TE, Surrey, UK;Clinical Unit of Internal Medicine Small Animals, University of Veterinary Medicine, Veterinärplatz 1, Vienna, 1210, Austria;Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Bünteweg 9, Hannover, 30559, Germany;College of Veterinary Medicine, University of Georgia, 501 DW Brooks Drive, Athens 30602, GA, USA;Department of Small Animal Medicine and Clinical Biology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke 9820, Belgium;Chicago Veterinary Neurology and Neurosurgery, 3123 N. Clybourn Avenue, Chicago 60618, IL, USA;University of Melbourne, 250 Princes Highway, Weibee 3015, VIC, Australia

关键词: Treatment;    Epilepsy;    Epileptic seizure;    Dog;   

Others  :  1224261
DOI  :  10.1186/s12917-015-0465-y

 received in 2015-06-05, accepted in 2015-06-29,  发布年份 2015

【 摘 要 】

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered.

【 授权许可】

   
2015 Potschka et al.

【 图 表 】

Fig. 1.

【 参考文献 】

• [1]Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G et al.. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010; 51(6):1069-1077.
• [2]Tellez-Zenteno JF, Hernandez-Ronquillo L, Buckley S, Zahagun R, Rizvi S. A validation of the new definition of drug-resistant epilepsy by the International League Against Epilepsy. Epilepsia. 2014; 55(6):829-834.
• [3]Balosso S, Liu J, Bianchi ME, Vezzani A. Disulfide-containing high mobility group box-1 promotes N-methyl-D-aspartate receptor function and excitotoxicity by activating Toll-like receptor 4-dependent signaling in hippocampal neurons. Antioxid Redox Signal. 2014; 21(12):1726-1740.
• [4]Balosso S, Maroso M, Sanchez-Alavez M, Ravizza T, Frasca A, Bartfai T et al.. A novel non-transcriptional pathway mediates the proconvulsive effects of interleukin-1beta. Brain. 2008; 131(Pt 12):3256-3265.
• [5]Librizzi L, Noe F, Vezzani A, de Curtis M, Ravizza T. Seizure-induced brain-borne inflammation sustains seizure recurrence and blood-brain barrier damage. Ann Neurol. 2012; 72(1):82-90.
• [6]Wilcox KS, Vezzani A. Does brain inflammation mediate pathological outcomes in epilepsy? Adv Exp Med Biol. 2014; 813:169-183.
• [7]Ryvlin P, Nashef L, Lhatoo SD, Bateman LM, Bird J, Bleasel A et al.. Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study. Lancet Neurol. 2013; 12(10):966-977.
• [8]Shankar R, Cox D, Jalihal V, Brown S, Hanna J, McLean B. Sudden unexpected death in epilepsy (SUDEP): development of a safety checklist. Seizure. 2013; 22(10):812-817.
• [9]Fredso N, Koch BC, Toft N, Berendt M. Risk factors for survival in a university hospital population of dogs with epilepsy. J Vet Intern Med. 2014; 28(6):1782-1788.
• [10]Berendt M, Gredal H, Ersboll AK, Alving J. Premature death, risk factors, and life patterns in dogs with epilepsy. J Vet Intern Med. 2007; 21(4):754-759.
• [11]Gullov CH, Toft N, Berendt M. A longitudinal study of survival in Belgian Shepherds with genetic epilepsy. J Vet Intern Med. 2012; 26(5):1115-1120.
• [12]Hülsmeyer V, Zimmermann R, Brauer C, Sauter-Louis C, Fischer A. Epilepsy in Border Collies: clinical manifestation, outcome, and mode of inheritance. J Vet Intern Med. 2010; 24(1):171-178.
• [13]Scorza CA, Calderazzo L, Cavalheiro EA, Scorza FA, Cysneiros RM. Sudden unexpected death in dogs with epilepsy: risks versus benefits of omega-3 fatty acid supplementation for man’s best friend. Epilepsy Behav. 2013; 27(3):508-509.
• [14]Berendt M, Gredal H, Pedersen LG, Alban L, Alving J. A cross-sectional study of epilepsy in Danish Labrador Retrievers: prevalence and selected risk factors. J Vet Intern Med. 2002; 16(3):262-268.
• [15]Chang Y, Mellor DJ, Anderson TJ. Idiopathic epilepsy in dogs: owners’ perspectives on management with phenobarbitone and/or potassium bromide. J Small Anim Pract. 2006; 47(10):574-581.
• [16]Callaghan B, Schlesinger M, Rodemer W, Pollard J, Hesdorffer D, Allen Hauser W et al.. Remission and relapse in a drug-resistant epilepsy population followed prospectively. Epilepsia. 2011; 52(3):619-626.
• [17]Neligan A, Bell GS, Elsayed M, Sander JW, Shorvon SD. Treatment changes in a cohort of people with apparently drug-resistant epilepsy: an extended follow-up. J Neurol Neurosurg Psychiatry. 2012; 83(8):810-813.
• [18]Sillanpaa M, Schmidt D. Is incident drug-resistance of childhood-onset epilepsy reversible? A long-term follow-up study. Brain. 2012; 135(Pt 7):2256-2262.
• [19]Rundfeldt C, Loscher W. The pharmacology of imepitoin: the first partial benzodiazepine receptor agonist developed for the treatment of epilepsy. CNS Drugs. 2014; 28(1):29-43.
• [20]Tipold A, Keefe TJ, Loscher W, Rundfeldt C, de Vries F. Clinical efficacy and safety of imepitoin in comparison with phenobarbital for the control of idiopathic epilepsy in dogs. J Vet Pharmacol Ther. 2015; 38(2):160-8.
• [21]Cross HJ, Kurlemann G. Current Recommendations for Children. UNI-MED Verlag AG, Bremen; 2013.
• [22]Klamer S, Singh A, Gil-Nagel A, Krämer G, French J, Lerche H. Current Recommendations, Guidlines, and Expert Views of Practical Anticonvusant Therapy. UNI-MED Verlag AG, Bremen; 2013.
• [23]Bhatti S, De Risio L, Muñana KR, Penderis J, Stein V, Tipold A, et al. International Veterinary Epilepsy Task Force consensus proposal: medical treatment of canine epilepsy in Europe. BMC Vet Res. 2015.
• [24]Tang V, Michaelis R, Kwan P. Psychobehavioral therapy for epilepsy. Epilepsy Behav. 2014; 32:147-155.
• [25]Stafstrom CE. Epilepsy comorbidities: how can animal models help? Adv Exp Med Biol. 2014; 813:273-281.
• [26]Shihab N, Bowen J, Volk HA. Behavioral changes in dogs associated with the development of idiopathic epilepsy. Epilepsy Behav. 2011; 21(2):160-167.
• [27]Wessmann A, Volk HA, Parkin T, Ortega M, Anderson TJ. Evaluation of quality of life in dogs with idiopathic epilepsy. J Vet Intern Med. 2014; 28(2):510-514.
• [28]Rutherford L, Wessmann A, Rusbridge C, McGonnell IM, Abeyesinghe S, Burn C et al.. Questionnaire-based behaviour analysis of Cavalier King Charles spaniels with neuropathic pain due to Chiari-like malformation and syringomyelia. Vet J. 2012; 194(3):294-298.
• [29]Olmez I, Moses H, Sriram S, Kirshner H, Lagrange AH, Pawate S. Diagnostic and therapeutic aspects of Hashimoto’s encephalopathy. J Neurol Sci. 2013; 331(1-2):67-71.
• [30]Pancotto T, Rossmeisl JH, Panciera DL, Zimmerman KL. Blood-brain-barrier disruption in chronic canine hypothyroidism. Vet Clin Pathol. 2010; 39(4):485-493.
• [31]von Klopmann T, Boettcher IC, Rotermund A, Rohn K, Tipold A. Euthyroid sick syndrome in dogs with idiopathic epilepsy before treatment with anticonvulsant drugs. J Vet Intern Med. 2006; 3:516-522.
• [32]Yilmaz U, Yilmaz TS, Akinci G, Korkmaz HA, Tekgul H. The effect of antiepileptic drugs on thyroid function in children. Seizure. 2014; 23(1):29-35.
• [33]Eddy CM, Rickards HE, Cavanna AE. Behavioral adverse effects of antiepileptic drugs in epilepsy. J Clin Psychopharmacol. 2012; 32(3):362-375.
• [34]Zaccara G, Franciotta D, Perucca E. Idiosyncratic adverse reactions to antiepileptic drugs. Epilepsia. 2007; 48(7):1223-1244.
• [35]Steinmetz S, Tipold A, Bilzer T, Schenk HC. Transient neuromyopathy after bromide intoxication in a dog with idiopathic epilepsy. Ir Vet J. 2012; 65(1):19. BioMed Central Full Text
• [36]Baird-Heinz HE, Van Schoick AL, Pelsor FR, Ranivand L, Hungerford LL. A systematic review of the safety of potassium bromide in dogs. J Am Vet Med Assoc. 2012; 240(6):705-715.
• [37]Kube SA, Vernau KM, LeCouteur RA. Dyskinesia associated with oral phenobarbital administration in a dog. J Vet Intern Med. 2006; 20(5):1238-1240.
• [38]Gaskill CL, Cribb AE. Pancreatitis associated with potassium bromide/phenobarbital combination therapy in epileptic dogs. Can Vet J. 2000; 41(7):555-558.
• [39]Dewey CW, Cerda-Gonzalez S, Levine JM, Badgley BL, Ducote JM, Silver GM et al.. Pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with suspected idiopathic epilepsy. J Am Vet Med Assoc. 2009; 235(12):1442-1449.
• [40]Bersan E, Volk HA, Ros C, De Risio L. Phenobarbitone-induced haematological abnormalities in idiopathic epileptic dogs: prevalence, risk factors, clinical presentation and outcome. Vet Rec. 2014; 175(10):247.
• [41]Jacobs G, Calvert C, Kaufman A. Neutropenia and thrombocytopenia in three dogs treated with anticonvulsants. J Am Vet Med Assoc. 1998; 212(5):681-684.
• [42]Schwartz M, Munana KR, Olby NJ. Possible drug-induced hepatopathy in a dog receiving zonisamide monotherapy for treatment of cryptogenic epilepsy. J Vet Med Sci. 2011; 73(11):1505-1508.
• [43]Miller ML, Center SA, Randolph JF, Lepherd ML, Cautela MA, Dewey CW. Apparent acute idiosyncratic hepatic necrosis associated with zonisamide administration in a dog. J Vet Intern Med. 2011; 25(5):1156-1160.
• [44]March PA, Hillier A, Weisbrode SE, Mattoon JS, Johnson SE, DiBartola SP et al.. Superficial necrolytic dermatitis in 11 dogs with a history of phenobarbital administration (1995-2002). J Vet Intern Med. 2004; 18(1):65-74.
• [45]Neuman MG, Cohen L, Nanau RM, Hwang PA. Genetic and immune predictors for hypersensitivity syndrome to antiepileptic drugs. Transl Res. 2012; 159(5):397-406.
• [46]The World Health Organization Quality Of Life Assessment (WHOQOL): position paper from the World Health Organization. Soc Sci Med. 1995; 41(10):1403-1409.
• [47]Lord LK, Podell M. Owner perception of the care of long-term phenobarbital-treated epileptic dogs. J Small Anim Pract. 1999; 40(1):11-15.
• [48]Munana KR, Thomas WB, Inzana KD, Nettifee-Osborne JA, McLucas KJ, Olby NJ et al.. Evaluation of levetiracetam as adjunctive treatment for refractory canine epilepsy: a randomized, placebo-controlled, crossover trial. J Vet Intern Med. 2012; 26(2):341-348.
• [49]Levitski RE, Trepanier LA. Effect of timing of blood collection on serum phenobarbital concentrations in dogs with epilepsy. J Am Vet Med Assoc. 2000; 217(2):200-204.
• [50]Monteiro R, Anderson TJ, Innocent G, Evans NP, Penderis J. Variations in serum concentration of phenobarbitone in dogs receiving regular twice daily doses in relation to the times of administration. Vet Rec. 2009; 165(19):556-558.
• [51]Munana KR, Nettifee-Osborne JA, Papich MG. Pharmacokinetics of levetiracetam in epileptic dogs when administered concurrently with phenobarbital, bromide, or phenobarbital and bromide in combination. J Vet Intern Med. 2014; 28:1358.
• [52]Moore SA, Munana KR, Papich MG, Nettifee-Osborne JA. The pharmacokinetics of levetiracetam in healthy dogs concurrently receiving phenobarbital. J Vet Pharmacol Ther. 2011; 34(1):31-4.
• [53]Orito K, Saito M, Fukunaga K, Matsuo E, Takikawa S, Muto M et al.. Pharmacokinetics of zonisamide and drug interaction with phenobarbital in dogs. J Vet Pharmacol Ther. 2008; 31(3):259-264.
• [54]Chung JY, Hwang CY, Chae JS, Ahn JO, Kim TH, Seo KW et al.. Zonisamide monotherapy for idiopathic epilepsy in dogs. N Z Vet J. 2012; 60(6):357-359.
• [55]Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting zero numerators. JAMA. 1983; 249(13):1743-1745.
• [56]Jovanovic BD, Levy PS. A look at the rule of three. Am Stat. 1997; 51:137-139.
• [57]Westover MB, Cormier J, Bianchi MT, Shafi M, Kilbride R, Cole AJ et al.. Revising the “Rule of Three” for inferring seizure freedom. Epilepsia. 2012; 53(2):368-376.
• [58]Volk HA, Matiasek LA, Lujan Feliu-Pascual A, Platt SR, Chandler KE. The efficacy and tolerability of levetiracetam in pharmacoresistant epileptic dogs. Vet J. 2008; 176(3):310-319.
• [59]Von Klopmann T, Rambeck B, Tipold A. Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs. J Small Anim Pract. 2007; 48(3):134-138.
• [60]Potschka H, Fischer A, von Ruden EL, Hulsmeyer V, Baumgartner W. Canine epilepsy as a translational model? Epilepsia. 2013; 54(4):571-579.
• [61]Rossmeisl JH, Inzana KD. Clinical signs, risk factors, and outcomes associated with bromide toxicosis (bromism) in dogs with idiopathic epilepsy. J Am Vet Med Assoc. 2009; 234(11):1425-1431.
• [62]Weissl J, Hulsmeyer V, Brauer C, Tipold A, Koskinen LL, Kyostila K et al.. Disease progression and treatment response of idiopathic epilepsy in Australian Shepherd dogs. J Vet Intern Med. 2012; 26(1):116-125.
• [63]Charalambous M, Brodbelt D, Volk HA. Treatment in canine epilepsy–a systematic review. BMC Vet Res. 2014; 10:257. BioMed Central Full Text
• [64]Munana KR, Zhang D, Patterson EE. Placebo effect in canine epilepsy trials. J Vet Intern Med. 2010; 24(1):166-170.
• [65]Ben-Menachem E, Sander JW, Privitera M, Gilliam F. Measuring outcomes of treatment with antiepileptic drugs in clinical trials. Epilepsy Behav. 2010; 18(1-2):24-30.
• [66]Faught E. Antiepileptic drug trials: the view from the clinic. Epileptic Disord. 2012; 14(2):114-123.
• [67]Löscher W, Schmidt D. Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma. Epilepsia. 2011; 52(4):657-678.
• [68]French JA, Cabrera J, Emir B, Whalen E, Lu F. Designing a new proof-of-principle trial for treatment of partial seizures to demonstrate efficacy with minimal sample size and duration-a case study. Epilepsy Res. 2013; 106(1-2):230-236.
• [69]International Conference on Harmonisation of Technocal Requirement of Pharmaceuticals for Human Use (ICH) Topic E10 Note for Guidance on Choice of Control Group in Clinical Trials, vol. 96. CPMP/ICH, London; 2001.
• [70]Boothe DM, Dewey C, Carpenter DM. Comparison of phenobarbital with bromide as a first-choice antiepileptic drug for treatment of epilepsy in dogs. J Am Vet Med Assoc. 2012; 240(9):1073-1083.
• [71]French JA, Wang S, Warnock B, Temkin N. Historical control monotherapy design in the treatment of epilepsy. Epilepsia. 2010; 51(10):1936-1943.
• [72]Perucca E. When clinical trials make history: demonstrating efficacy of new antiepileptic drugs as monotherapy. Epilepsia. 2010; 51(10):1933-1935.
• [73]Glauser T, Ben-Menachem E, Bourgeois B, Cnaan A, Chadwick D, Guerreiro C et al.. ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia. 2006; 47(7):1094-1120.
• [74]Glauser T, Ben-Menachem E, Bourgeois B, Cnaan A, Guerreiro C, Kalviainen R et al.. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia. 2013; 54(3):551-563.
• [75]Packer RM, Shihab NK, Torres BB, Volk HA. Clinical risk factors associated with anti-epileptic drug responsiveness in canine epilepsy. PLoS ONE. 2014; 9(8):e106026.