Alvarez N, Besag F, Iivanainen M
Harvard, Medical School, Boston, Massachusetts, USA.
J Intellect Disabil Res. 1998 Dec;42 Suppl 1:1-15.
The main principles of antiepileptic drug treatment of epilepsy in patients with intellectual disability are basically the same as for other patients with epilepsy. However, some specific issues need to be taken into account These are primarily associated with the diagnostic difficulties of epilepsy in this population. In addition, a number of other relevant issues, including the degree and location of brain lesion, the nature of the underlying disease, the higher frequency of difficult-to-treat epilepsies, the additional intellectual impairment caused by inappropriate antiepileptic medication, or by frequent and prolonged seizures, the appropriate use of monotherapy versus rational polytherapy, and the use of broad-spectrum antiepileptic drugs will be discussed in the present paper. Although the goals of treatment are to keep the patient seizure-free and alert while preventing possible mental deterioration, we have to accept compromises between these primary goals in many cases. Some people with epilepsy and intellectual disability are very vulnerable to insidious neurotoxic effects; for example, sedative effects caused by phenobarbital, or cognitive and/or cerebellar dysfunction caused by long-term phenytoin, especially together with other drugs. Because of the adverse effects of phenobarbital and phenytoin, these drugs are no longer recommended as a first-choice drugs when long-term antiepileptic medication is required. In primary generalized tonic-clonic seizures, valproate, oxcarbazepine/carbamazepine and lamotrigine are recommended in this order of preference. The corresponding recommendations are: in typical absences, valproate, ethosuximide and lamotrigine; in atypical absences, valproate and lamotrigine; in juvenile myoclonic epilepsy, valproate, lamotrigine and clobazam; in infantile spasms vigabatrin, ACTH and valproate; in Lennox-Gastaut syndrome, valproate, lamotrigine and vigabatrin; in atonic seizures, valproate and lamotrigine; in simple and complex partial seizures with or without secondary generalization, oxcarbazepine/carbamazepine, valproate/ vigabatrin and lamotrigine; and in status epilepticus lorazepam, diazepam and clonazepam together with phenytoin or fosphenytoin. In cases of poor response to the monotherapy recommended above, the following combinations may be indicated: in primary generalized tonic-clonic epilepsy, valproate and oxcarbazepine/ carbamazepine, or valproate and lamotrigine; in typical absences, valproate and lamotrigine, or valproate and ethosuximide; in juvenile myolonic epilepsy, valproate and lamotrigine, or valproate and clonazepam; and in partial epilepsies, add to the monotherapy one of the following drugs, vigabatrin, lamotrigine, gabapentin, tiagabine, topiramate, zonisamide or clobazam. So far, the order of preference of these new drugs remains undetermined. More data are needed on the efficacy and adverse effects of the new drugs based on controlled studies on patients with intellectual disability and epilepsy.
智力残疾患者癫痫的抗癫痫药物治疗的主要原则与其他癫痫患者基本相同。然而，需要考虑一些特定问题。这些主要与该人群癫痫的诊断困难相关。此外，本文还将讨论一些其他相关问题，包括脑损伤的程度和位置、基础疾病的性质、难治性癫痫的较高发生率、不适当的抗癫痫药物治疗或频繁和长期发作导致的额外智力损害、单药治疗与合理联合治疗的恰当使用以及广谱抗癫痫药物的使用。尽管治疗目标是使患者无癫痫发作且保持警觉，同时防止可能的智力衰退，但在许多情况下我们不得不接受这些主要目标之间的折衷。一些癫痫和智力残疾患者极易受到潜在神经毒性作用的影响；例如，苯巴比妥引起的镇静作用，或长期使用苯妥英钠尤其是与其他药物合用时引起的认知和/或小脑功能障碍。由于苯巴比妥和苯妥英钠的不良反应，当需要长期抗癫痫药物治疗时，不再推荐将这些药物作为首选药物。在原发性全面性强直阵挛发作中，推荐丙戊酸盐、奥卡西平/卡马西平以及拉莫三嗪，优先顺序依次为上述顺序。相应的推荐如下：在典型失神发作中，丙戊酸盐、乙琥胺和拉莫三嗪；在非典型失神发作中，丙戊酸盐和拉莫三嗪；在青少年肌阵挛癫痫中，丙戊酸盐、拉莫三嗪和氯巴占；在婴儿痉挛症中，氨己烯酸、促肾上腺皮质激素和丙戊酸盐；在伦诺克斯 - 加斯东综合征中，丙戊酸盐、拉莫三嗪和氨己烯酸；在失张力发作中，丙戊酸盐和拉莫三嗪；在伴有或不伴有继发性全面发作的简单和复杂部分性发作中，奥卡西平/卡马西平、丙戊酸盐/氨己烯酸和拉莫三嗪；在癫痫持续状态中，劳拉西泮、地西泮和氯硝西泮以及苯妥英钠或磷苯妥英钠。在对上述推荐的单药治疗反应不佳的情况下，可考虑以下联合用药：在原发性全面性强直阵挛癫痫中，丙戊酸盐和奥卡西平/卡马西平，或丙戊酸盐和拉莫三嗪；在典型失神发作中，丙戊酸盐和拉莫三嗪，或丙戊酸盐和乙琥胺；在青少年肌阵挛癫痫中，丙戊酸盐和拉莫三嗪，或丙戊酸盐和氯硝西泮；在部分性癫痫中，在单药治疗基础上加用以下药物之一，氨己烯酸、拉莫三嗪、加巴喷丁、噻加宾、托吡酯、唑尼沙胺或氯巴占。到目前为止，这些新药的优先顺序尚未确定。需要基于对智力残疾和癫痫患者的对照研究，获取更多关于新药疗效和不良反应的数据。
