國(guó)際獸醫(yī)癲癇工作組共識(shí)建議：歐洲犬癲癇的藥物治療

Sofie F.M. Bhatti1*, Luisa De Risio2 , Karen Mu?ana3 , Jacques Penderis4 , Veronika M. Stein5 , Andrea Tipold5 , Mette Berendt6 , Robyn G. Farquhar7 , Andrea Fischer8 , Sam Long9 , Wolfgang L?scher10, Paul J.J. Mandigers11, Kaspar Matiasek12, Akos Pakozdy13, Edward E. Patterson14, Simon Platt15, Michael Podell16, Heidrun Potschka17, Clare Rusbridge18,19 and Holger A. Volk20?

When to recommend maintenance AED treatment?

Definitive, evidence-based data on when to start AED therapy in dogs based on seizure frequency and type is lacking. As such, extrapolation from human medicine may be possible to provide treatment guidelines. Clinicians should consider the general health of the patient, as well as the owner’s lifestyle, financial limitations, and comfort with the proposed therapeutic regimen. Individualized therapy is paramount for choosing a treatment plan. As a general rule, the authors recommend initiation of longterm treatment in dogs with idiopathic epilepsy when any one of the following criteria is present:

對(duì)于各種抽搐發(fā)作頻率和類型的犬，什么時(shí)候開始抗癲癇藥物治療，準(zhǔn)確和循證的相關(guān)數(shù)據(jù)并不充分。

因此，從人類醫(yī)學(xué)的推斷可能能提供一些治療指南。

臨床醫(yī)生應(yīng)考慮病患的整體健康狀況，以及寵主的生活方式、經(jīng)濟(jì)限制和對(duì)擬議治療方案的舒適度。

個(gè)體化治療對(duì)于選擇治療方案至關(guān)重要。

一般情況下，作者建議患有特發(fā)性癲癇的犬出現(xiàn)以下任何一種情況時(shí)，應(yīng)進(jìn)行長(zhǎng)期治療:

– Interictal period of ≤ 6 months (i.e. 2 or more epileptic seizures within a 6 month period)?

– Status epilepticus or cluster seizures

– The postictal signs are considered especially severe (e.g. aggression, blindness) or last longer than 24 hours

– The epileptic seizure frequency and/or duration is increasing and/or seizure severity is deteriorating over 3 interictal periods

-發(fā)作間期**≤6個(gè)月（即6個(gè)月內(nèi)癲癇性抽搐發(fā)作2次及以上）?

-癲癇持續(xù)狀態(tài)或叢集性抽搐發(fā)作

-發(fā)作后期癥狀被認(rèn)為特別嚴(yán)重（例如攻擊性、失明）或持續(xù)時(shí)間超過24小時(shí)

-癲癇性抽搐發(fā)作頻率和/或發(fā)作時(shí)長(zhǎng)增加和/或抽搐發(fā)作嚴(yán)重程度在3個(gè)發(fā)作周期內(nèi)惡化

In humans, the decision regarding when to recommend AED treatment is based on a number of risk factors (e.g. risk of recurrence, seizure type, tolerability, adverse ?effects) [42, 115]. In people, clear proof exists that there is no benefit initiating AED treatment after a single unprovoked seizure [42], but there is evidence to support starting treatment after the second seizure [43, 108]. In dogs, long-term seizure management is thought to be most successful when appropriate AED therapy is started early in the course of the disease, especially in dogs with a high seizure density and in dog breeds known to suffer from a severe form of epilepsy [12?14]. A total number of ≥ 10 seizures during the first 6 months of the disease appeared to be correlated with a poor outcome in Australian Shepherds with idiopathic epilepsy [132]. Furthermore, recent evidence exists that seizure density is a crucial risk factor, experiencing cluster seizures, and being male is associated with poor AED response [84].

在人類中，關(guān)于什么時(shí)候推薦抗癲癇藥物治療的決定是基于許多風(fēng)險(xiǎn)因素來(lái)下的（如復(fù)發(fā)風(fēng)險(xiǎn)、抽搐發(fā)作類型、耐受性、不良反應(yīng)）[42,115]。

在人類中，有明確的證據(jù)表明，在單次非誘發(fā)性抽搐發(fā)作后開始抗癲癇藥物治療沒有任何益處[42]，但有證據(jù)支持在第二次抽搐發(fā)作后開始治療有益[43,108]。

在犬類中，如果在發(fā)病早期就開始適當(dāng)?shù)目拱d癇藥物治療，長(zhǎng)期的抽搐發(fā)作管理被認(rèn)為是最成功的，特別是對(duì)于抽搐發(fā)作頻率高的犬和已知會(huì)有嚴(yán)重癲癇的某些犬的品種[12?14]。

發(fā)病起初6個(gè)月抽搐發(fā)作次數(shù)≥10次，似乎與澳大利亞牧羊犬特發(fā)性癲癇的預(yù)后不良存在相關(guān)性[132]。

此外，最近有證據(jù)表明，抽搐發(fā)作頻率是一個(gè)關(guān)鍵的危險(xiǎn)因素，經(jīng)歷叢集性抽搐發(fā)作，雄性均與抗癲癇藥物治療反應(yīng)差有關(guān)[84]。

A strong correlation exists in epileptic people between a high seizure frequency prior to AED treatment and poor AED response [16, 34, 59]. Historically, this has been attributed to kindling, in which seizure activity leads to intensification of subsequent seizures [117]. However, there is little clinical evidence that kindling plays a role in either dogs [54] or humans [111] with recurrent seizures. In humans, a multifactorial pathogenesis is suggested [14, 52]. Recent epidemiologic data suggest that there are differences in the intrinsic severity of epilepsy among individuals, and these differences influence a patient’s response to medication and long-term outcome. Additionally, evidence for seizure-associated alterations that affect the pharmacodynamics and pharmacokinetics of AEDs have been suggested [99]. Breed-related differences in epilepsy severity have been described in dogs, with a moderate to severe clinical course reported in Australian Shepherds [132], Border Collies [49, 84], Italian Spinoni [24], German Shepherds and Staffordshire Bull Terriers [84], whereas a less severe form of the disease has been described in a different cohort of Collies (mainly rough coated) [77], Labrador Retrievers [7] and Belgian Shepherds [45]. Consequently, genetics may affect the success of treatment and may explain why some breeds are more predisposed to drug resistant epilepsy [3, 77].

癲癇人類病患在抗癲癇藥物治療前抽搐頻繁發(fā)作與抗癲癇藥物反應(yīng)差之間存在很強(qiáng)的相關(guān)性[16,34,59]。

在過去，這認(rèn)為是由于點(diǎn)燃機(jī)制（kindling）的原因，抽搐發(fā)作活動(dòng)導(dǎo)致隨后的抽搐發(fā)作加劇（intensification）[117]。

然而，很少有臨床證據(jù)表明點(diǎn)燃機(jī)制在復(fù)發(fā)性抽搐發(fā)作的犬[54]或人[111]中起作用。

在人類中，可能存在多因素發(fā)病機(jī)制[14,52]。

最近的流行病學(xué)數(shù)據(jù)表明，個(gè)體之間癲癇發(fā)作的嚴(yán)重程度存在差異，這些差異影響病患對(duì)藥物的反應(yīng)和長(zhǎng)期預(yù)后。

此外，有證據(jù)表明抽搐發(fā)作相關(guān)的改變會(huì)影響抗癲癇藥物的藥效學(xué)和藥代動(dòng)力學(xué)[99]。

犬的癲癇嚴(yán)重程度的品種相關(guān)差異已有描述，澳大利亞牧羊犬[132]、邊境牧羊犬[49,84]、意大利斯皮諾尼犬[24]、德國(guó)牧羊犬和斯塔福德郡牛頭梗犬[84]的臨床病程為中度至重度，而不同的牧羊犬(主要是粗毛犬)[77]、拉布拉多尋回獵犬[7]和比利時(shí)牧羊犬[45]的疾病的嚴(yán)重形式較輕。

因此，基因可能會(huì)影響治療的成功可能性，或許可能解釋為什么某些品種更容易發(fā)生耐藥性癲癇（drug resistant epilepsy）[3,77]。