国际抗癫痫联盟癫痫新定义解读

1,癫痫新定义解读,桂林医学院附属医院 俸军林,2018/2/4,2,一、癫痫定义,癫痫定义：是多种原因导致的脑部神经元高度同步化异常放电的临床综合征，临床表现具有发作性、短暂性、重复性、刻板性。（第7版教科书）癫痫的概念性定义（ILAE，2005） ：癫痫是一种脑部疾患，其特点是持续存在的能产生癫痫发作的易感性，并出现相应的神经生物、认知、心理以及社会等方面的后果。诊断癫痫至少需要一次癫痫发作。,2018/2/4,3,癫痫定义（2005）的三大要素,至少一次癫痫发作的病史脑部持续存在反复发作的易感性发作伴发的神经生化、认知、心理及社会功能障碍。,核心要素是反复癫痫发作的易感性，如：家族史，EEG显示癫痫样放电，脑部有确切而不易根除的癫痫病因。,2018/2/4,4,存在问题：,未能区分诱发发作和非诱发发作通常认为非诱发发作方可考虑诊断为癫痫，反射性癫痫系诱发发作所致，按照定义不可诊断为癫痫，显然与事实不符。中风、CNS感染、脑外伤急性期出现的发作不应诊断为癫痫，但急性期过后患者出现一次非诱发发作可否诊断为癫痫？癫痫是否终生存在？若患者停药后不再发作，应考虑为癫痫缓解？不活动性癫痫？癫痫治愈？还是其他？,2018/2/4,5,二、癫痫的新定义,国际抗癫痫联盟（ILAE）最近扩展了癫痫定义 2014年4月14日在线发表的一篇Epilepsia杂志文章描述了上述新的癫痫定义。实用性定义与概念性定义,2018/2/4,6,根据新的定义，癫痫是由以下标准定义的脑部疾病：1. 间隔超过24小时发生的、至少2次的非诱发性（或反射性）痫性发作；2. 未来10年内，与2次非诱发性痫性发作总体再发风险（至少60%）有近似再发可能性的、单次非诱发性（或反射性）痫性发作；3. 诊断为癫痫综合征。,2018/2/4,7,三、新定义的解读,（一）癫痫是一种脑部疾病（disease）而非疾患（disorder）Disorder: 通常指身体某一部位的失调、紊乱，常引发长期疾病。Disease: 意为通常指持续时间较长的、比较严重的疾病，常影响身体特定的部位。 Epilepsy has traditionally been referred to as a disorder or a family of disorders, rather than a disease, to emphasize that it is comprised of many different diseases and conditions. The term disorder implies a functional disturbance, not necessarily lasting; whereas, the term disease may (but not always) convey a more lasting derangement of normal function.,2018/2/4,8,（二）关注癫痫的早期诊断,新定义强调“一次发作即应考虑癫痫的可能”，充分体现了ILAE和IBE的癫痫早期诊断的关注。但和我们已经普遍接受的癫痫“反复性”特征看起来不一致。“至少一次癫痫发作” + “反复发作的易感性”，意即“反复性”“一次发作”虽然也可诊断癫痫，但必须有充分证据，应注意避免癫痫诊断扩大化。Fisher博士：这些改变并非激进，这不过是对现有定义范围的一种修正，而非根本上的变化。多数时候，我们仍然将反复发生的非诱发性痫性发作视为癫痫。Fisher博士：有些病人虽然仅为首发非诱发性痫性发作，但因 MRI 或其它检查结果显示异常，所以再发痫性发作风险很大，将其视为“癫痫”有助于对其良好管理。,2018/2/4,9,（三）强调非诱发发作,新定义强调“相隔24h以上、至少两次非诱发发作”强调“诱发发作”和“非诱发发作”的区别诱发发作“反应性发作”或“急性症状性发作”，常见于疾病的急性期。非诱发发作缺乏短暂性或可逆性诱因，是对慢性、稳定性病因的一种反应。,2018/2/4,10,（四）强调“两次发作相隔24h以上”,新定义强调“两次发作相隔24h以上”基于流行病学资料和临床实际，工作组认为应将24h内成簇的非诱发发作视为一次非诱发发作。对第二次非诱发发作，新定义未明确给出一个外部的时间限制。在有些特殊情况下，两个不同时间点的发作其病因可能并不相同，如果是这样，就不能诊断为癫痫。,2018/2/4,11,（五）关于两次非诱发发作的特殊情况,新定义对不符合两次非诱发发作的特殊情况进行了补充说明流行病学资料显示，两次非诱发发作的再发风险为60-90。中风、CNS感染、脑外伤等远期脑损伤后，可能会出现一次非诱发发作。一次非诱发发作后，如果存在较高的再发风险，多数专家认同癫痫会复发。临床医生难以评估具体每一位患者的一次非诱发发作的再发风险。Schachter博士：首次癫痫发作后未来癫痫发作风险的评估仍不明确。复发风险尚需进一步的研究以确定这些风险随着时间的推移能否达到新定义的阈值。,2018/2/4,12,（六）反射性癫痫,新定义涵盖了反射性癫痫反射性癫痫为即时、短暂的刺激所诱发，如闪光刺激，因而不属于非诱发性。但刺激诱发发作的倾向符合癫痫的概念性定义，因为反射性癫痫与导致发作的持久异常的易感性相关，因此新定义认可反射性癫痫为癫痫。Fisher 博士：我们都认为这种情况就是癫痫；但是旧标准没有将其定义，因此我们做出了相应改变。,2018/2/4,13,（七）新定义涵盖了癫痫综合征,如果存在癫痫综合征的证据，即使再发痫性发作的风险很低，新定义认为也应成立癫痫诊断。众所周知，伴中央-颞区棘波的儿童良性癫痫、慢波睡眠中持续棘慢波的癫痫和LandauKleffner综合征等特殊类型的癫痫综合征临床上几乎很少出现行为学上的发作，其发作风险很低，按照新定义的第一和第二条款似乎不应该考虑为癫痫，这显然有悖于常识。Fisher博士：如果说你患有癫痫综合征，但却不是癫痫，这是非常可笑的。 反对意见：Tan博士癫痫综合征可能不会大幅度增加未来癫痫发作的风险，所以将它们一致定义为癫痫可能为过度诊断。,2018/2/4,14,（八）癫痫已控制,新定义特别提出一个新术语癫痫已控制 / 不再发（epilepsy resolved）癫痫一直会再发么？失神发作儿童已停药数十年、无发作，还会再发么？内侧颞叶癫痫患者在切除硬化的海马后停药无发作十余年，还会在发吗？长时间无发作可能来自不同的情况：非诱发发作的易感性可能仍然存在，但发作已被控制；儿童癫痫患者到一定年龄不再发作，如伴中央-颞区棘波的良性癫痫；外科手术对一些患者而言可带来长期无发作。对于上述情况，是“癫痫缓解”还是“治愈”？“resolved”，“remission” or “no longer present” 在新定义中，工作组使用了“癫痫已控制（resolved）”这一简单的术语。癫痫已控制，意味着患者目前已经无癫痫了，尽管不能保证未来不再现。,2018/2/4,15,新定义未能明确使用多长的时间间隔来定义“癫痫已控制”，因为再发风险影响因素众多。新定义允许病情缓解患者排除癫痫诊断，即近10年无发作且近5年未服用抗癫痫药物的患者。Fisher 博士举例说：“如果你在 2 岁时出现痫性发作并在 3 岁再发，根据旧定义，直到 80 岁你仍然被视为癫痫患者。（新定义则不会）”,2018/2/4,16,（九）新定义的影响,如果内科医生能正确地对一次非诱发发作后再发的风险进行分析，新定义将会改善癫痫预后，对某些非诱发发作，内科医生能更轻松地启动初始治疗。新定义允许早期诊断，鉴于发作再发的风险较高，新定义将对发作再发所致的不必要的身体损害或造成社会后果有积极的预防价值。新定义如何影响癫痫的患病率尚不能预测。经济、立法方面的影响。新定义旨在临床诊断，而不适用于研究。诊断不一定立即治疗Fisher博士强调“治疗应与诊断定义分开”。治疗决策与诊断不同，需要根据患者的需求、个体风险获益比和可供选择的方案进行个体化制定。医生应权衡再次发作的可能性与药物相关副作用导致再次发作风险和患者费用之间的联系。,2018/2/4,17,2018/2/4,18,Case 1：Two seizures,A 25-year-old woman has two unprovoked seizures, 1year apart.Epilepsy：Yes_ or No_Comment: This person has epilepsy, according to both the old and new definitions.,2018/2/4,19,Case 2: Stroke and seizure,A 65-year-old man had a left middle cerebral artery stroke 6weeks ago and now presented with an unprovoked seizure. Epilepsy：Yes_ or No_Comment: With a seizure in this time relation to a stroke (or brain infection or brain trauma) the literaturesuggests a high (70%) risk of another unprovoked seizure. Therefore, in the new (but not the old) definition, this man would have epilepsy.,2018/2/4,20,Case 3: Photic seizures,A 6-year-old boy has had two seizures 3days apart while playing a videogame involving flashing lights. There have been no other seizures. EEG shows an abnormal photoparoxysmal response.Epilepsy：Yes_ or No_Comment: This boy has epilepsy according to the new definition (but not the old), even though the seizures are provoked by lights, since there is an abnormal enduring predisposition to have seizures with light flashes.,2018/2/4,21,Case 4:Benign Epilepsy with Centrotemporal Spikes (BECTS),A 22-year-old man had seizures with face twitching when falling asleep at ages 9, 10, and 14years; he has had none since. EEG at age 9years demonstrated centrotemporal spikes. Medications were discontinued at age 16.Epilepsy：Yes_ or No_Comment: For this young man, epilepsy is resolved, because of passing the relevant age range of an age-dependent syndrome. The old definition has no provision for considering epilepsy to be resolved.,2018/2/4,22,Case 5: Single seizure and dysplasia,A 40-year-old man had a focal seizure characterized by left hand twitching that progressed to a tonicclonic seizure. This was his only seizure. Magnetic resonance imaging (MRI) shows a probable transmantle dysplasia in the right frontal lobe and EEG shows right frontotemporal interictal spikes.Epilepsy：Yes_ or No_Comment: Although many clinicians would reasonably treat this man with antiseizure medications, the recurrence risk for seizures is not precisely known, and therefore epilepsy cannot yet be said to be present according to either definition. Future epidemiologic studies might clarify this situation.,2018/2/4,23,Case 6: Two seizures long ago,An 85-year-old man had a focal seizure at age 6 and another at age 8years. EEG, MRI, blood tests, and family history were all unrevealing. He received antiseizure drugs from age 8 to age 10years, when they were discontinued. There have been no further seizures.Epilepsy：Yes_ or NoComment: According to the new definition, epilepsy is resolved, since he has been seizure-free for 10years and off seizure medication for at least the last 5 years. This is not a guarantee against future seizures, but he has a right to be viewed as someone who does not currently have epilepsy.,2018/2/4,24,Case 7: Long-interval seizures,A 70-year-old woman had unprovoked seizures at ages 15 and 70. EEG, MRI, and family history are unremarkable.Epilepsy：Yes_ or NoComment: Both old and new definitions consider this woman to have epilepsy. Despite the diagnosis, many clinicians would not treat because of the low frequency of seizures. Should investigations somehow show that the causes of the two seizures were different, then epilepsy would not be considered to be present.,2018/2/4,25,Case 8: