Читать книгу Canine and Feline Epilepsy - Luisa De Risio - Страница 53

The definition of pharmacoresistant epilepsy has been a matter of debate in human medicine. Formerly, epilepsy was considered responsive to medical treatment if seizures were reduced by ≥50% to one or two adequate AED which achieved therapeutic serum concentration and steady state (Regesta and Tanganelli, 1999). Most current epilepsy drug trials in veterinary medicine have used this definition to determine AED efficacy (Dewey et al., 2004, 2009; Platt et al., 2006; von Klopmann et al., 2007; Volk et al., 2008; Muñana et al., 2010, 2012b). However, this does not take into account that even a reduction of seizure frequency by more than 50% may still entail a high seizure frequency, which negatively impacts on the animal’s and the owner’s quality of life (Chang et al., 2006; Wessmann et al., 2012). A good quality of life is however best improved by seizure freedom, one of the main outcome measures nowadays in epilepsy trials in human medicine (Elsharkawy et al., 2009).

A task force of the International League against Epilepsy (ILAE) has recently agreed on a global consensus on granted outcome measures for therapeutic interventions (Level 1) and definition of pharmacoresistant epilepsy (Level 2) taking the occurrence of drug-induced side effects and seizure control into account (Kwan et al., 2010):

• Level 1 categorizes the outcome of each medical treatment as either free of seizures or treatment failure, if not seizure free. The ILAE recommends a follow-up time of three times the longest interictal period for therapeutic trials; e.g. if the period in between seizures is 1 month then the follow-up time should be at least 3 months. However, as this is not always practical, seizure freedom is usually defined as an absence of seizures for a 12-month period. Level 1 does not only consider efficacy, but also the occurrence of drug-induced side effects, which will contribute significantly to the overall impact on the patient’s quality of life.

• Level 2 defines pharmacoresistant epilepsy as a failure to achieve freedom from seizures despite adequate trials of two (or more) well-tolerated, correctly chosen and used AED regimens (whether administered as monotherapies or in combination) (Kwan et al., 2010). The number of AED trialled has been restricted to ‘two’ based on the observation that successful seizure control is very unlikely once the patient has not responded to two correctly chosen AED (Kwan and Brodie, 2000; Arts et al., 2004).

It needs to be considered that drug non-responsiveness is not a fixed state but rather a dynamic process, which can be altered by fluctuation of the underlying pathophysiology (Kwan et al., 2010). The seizure frequency can vary over time (Berg et al., 2009; Muñana et al., 2010) and the state of drug non-responsiveness is dependent on the time-point of assessment (Kwan et al., 2010).

Taking into consideration the revised ILAE classification of pharmacoresistant epilepsy, a high proportion of dogs would be classified as pharmacoresistant. Spontaneous and drug-induced epilepsy remission rate in people is around 63% (Kwan and Brodie, 2000), which is markedly higher than that reported in veterinary medicine, which usually ranges between 15 and 24% (Heynold et al., 1997; Berendt et al., 2007; Arrol et al., 2012). However, in a recent study comparing the efficacy and tolerability of phenobarbitone with potassium bromide as a first line treatment, seizures ceased in 85% and 52% of the treated dogs, respectively (Boothe et al., 2012). The study period was only 6 months long and thus it is likely that the percentage of dogs being seizure free would have been less with a longer follow-up period. Lagotto Romagnolo dogs have a documented ‘childhood’ or juvenile epilepsy, which starts when they are around 6 weeks of age (Jokinen et al., 2007). Of the affected dogs, 96% become seizure free at the age of 10 weeks generally without receiving AED treatment. Future, long-term epidemiological studies are necessary to determine prevalence of drug response more accurately in the general epileptic dog population, in addition to the effect of patient age and duration of seizure history on this response.