國際獸醫(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?

翻譯 By @蘇蘇蘇蘇喬

校正 By @寵物神經(jīng)科醫(yī)生高健??

Discontinuation of AEDs
抗癲癇藥物的停減

Two main reasons for discontinuation of an AED are remission of seizures or life-threatening adverse effects.Generally, treatment for idiopathic epilepsy involves lifelong AED administration. However, remission has been reported in dogs. Remission rates between 15?30 % have been described in hospital based populations [6, 7, 47, 49]. In a study by Packer et al. (2014) 14 % of dogs were in remission on PB [84]. When ≥50 % reduction in seizure frequency was used as the outcome measure, success rates were markedly higher with 64,5 % of dogs achieving this level of seizure reduction. Several factors were associated with an increased likelihood of achieving remission, namely: being female, neutered, no previous experience of cluster seizures and an older age at onset of seizures. The same four factors were associated with an increased likelihood of achieving a ≥50 % reduction in seizure frequency [84]. The breed least likely to go into remission or have an ≥50 % reduction in seizure frequency was the Border Collie (0 and 40 %, respectively), the German Shepherd (11 and 35 %, respectively) and Staffordshire Bull Terrier (0 and 57 %, respectively) [84]. In a study by Hülsmeyer et al. (2010) the remission rate was 18 % in Border Collies independent of disease severity [49]. The decision to gradually taper the dose of an AED should be taken on a case-by-case basis, but seizure freedom of at least 1?2 years is advised. In people with prolonged seizure remission (generally 2 or more years), the decision to discontinue AED treatment is done on an individual basis considering relative risks and benefits. Individuals with the highest probability of remaining seizure-free are those who had no structural brain lesion, a short duration of epilepsy, few seizures before pharmacological control, and AED monotherapy [81, 109]. In dogs, however, little information on risk factors associated with seizure relapse exist, thus the pet owner must be aware that seizures may recur anytime during AED dose reduction of after discontinuation. To prevent withdrawal seizures or status epilepticus it is advised to decrease the dose with 20 % or less on a monthly basis.

抗癲癇藥物的停減的兩個(gè)主要原因是抽搐發(fā)作完全解除或用藥出現(xiàn)危及生命的不良反應(yīng)。一般來說，特發(fā)性癲癇的治療需要終身使用抗癲癇藥物。然而，有報(bào)道稱有些犬的病情完全解除。據(jù)報(bào)道，在以醫(yī)院為基礎(chǔ)的群體中，解除率在15-30%之間[6,7,47,49]。Packer等人（2014）的一項(xiàng)研究顯示，14%的犬在苯巴比妥治療后病情解除[84]。當(dāng)以抽搐發(fā)作頻率降低≥50%作為結(jié)果測量時(shí)，成功率明顯更高，64.5%的犬達(dá)到了這一標(biāo)準(zhǔn)的抽搐發(fā)作減少。有多個(gè)因素與病情解除的可能性增加有關(guān)，如：雌性，已絕育，以前沒有叢集性抽搐發(fā)作的經(jīng)歷，以及癲癇發(fā)作時(shí)的年齡較大。同樣的四個(gè)因素與抽搐發(fā)作頻率降低≥50%的可能性增加相關(guān)[84]。最不可能解除或抽搐發(fā)作頻率降低≥50%的品種是邊境牧羊犬（分別為0%和40%），德國牧羊犬（分別為11%和35%）和斯塔福德郡牛頭?（分別為0%和57%）[84]。 Hülsmeye等人（2010）的一項(xiàng)研究顯示，邊境牧羊犬的解除率為18%，與疾病嚴(yán)重程度無關(guān)[49]。逐漸減少抗癲癇藥物劑量的決定應(yīng)根據(jù)具體情況而定，但建議至少1-2年的抽搐未發(fā)作的情況下再?zèng)Q定。對(duì)于抽搐發(fā)作解除時(shí)間較長的人類病患（通常為2年或更長時(shí)間），停止抗癲癇藥物治療的決定應(yīng)根據(jù)個(gè)人情況考慮相對(duì)風(fēng)險(xiǎn)和益處。無抽搐發(fā)作可能性最高的個(gè)體是那些沒有結(jié)構(gòu)性腦損傷、癲癇持續(xù)時(shí)間短、藥物控制前抽搐發(fā)作少、抗癲癇藥物單藥治療的個(gè)體[81,109]。然而，在犬，與抽搐發(fā)作復(fù)發(fā)相關(guān)的風(fēng)險(xiǎn)因素的信息很少，因此寵物主人必須意識(shí)到抽搐發(fā)作可能在抗癲癇藥物劑量減少期間或停藥后的任何時(shí)候都有可能復(fù)發(fā)。為了防止戒斷性抽搐發(fā)作或癲癇持續(xù)狀態(tài)，建議每月減少20%或更少的劑量來逐漸減量停藥。

In case of life-threatening adverse effects, instant cessation of AED administration under 24h observation is necessary. In these cases, loading with an alternative AED should be initiated promptly in order to achieve target serum concentrations before serum PB concentration decreases. Loading with KBr (see section on KBr) or levetiracetam (see section on levetiracetam) is possible. If hepatic function is normal, starting imepitoin or zonisamide at the recommended oral starting dose may be another alternative.

如出現(xiàn)危及生命的不良反應(yīng)，有些病例需在24小時(shí)觀察下立即停用抗癲癇藥物。在這些情況下，應(yīng)立即開始負(fù)荷劑量給予替代的抗癲癇藥物，以便在血清苯巴比妥濃度下降之前達(dá)到目標(biāo)血清藥物濃度?？梢载?fù)荷劑量給予溴化鉀（參見溴化鉀一節(jié)）或左乙拉西坦（參見左乙拉西坦一節(jié)）。如果肝功能正常，以推薦的口服起始劑量開始服用伊匹妥因或唑尼沙胺，可能是另外的選擇。