Park Kang Min, Shin Kyong Jin, Ha Sam Yeol, Park JinSe, Kim Si Eun, Kim Sung Eun
Department of Neurology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.
Department of Neurology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.
Clin Neurol Neurosurg. 2014 Aug;123:64-8. doi: 10.1016/j.clineuro.2014.04.029. Epub 2014 May 14.
Although partial epilepsy with structural lesions on MRI (lesional epilepsy) is less favorably responsive to antiepileptics than those without structural lesions on MRI, the response to antiepileptics in lesional epilepsy is a heterogeneous condition. There is growing evidence that the extent of epileptic network beyond the visible lesion on MRI may be related with the response to antiepileptics. The aims of this study are to clarify whether (1) the epilepsy network beyond the visible lesion on MRI, or (2) duration of lesional epilepsy on MRI are related with the response to antiepileptics or not.
The inclusion criteria for this study were (1) having structural lesions on MRI, (2) taking antiepileptics for at least 1 year, and (3) age ≥13 years old. The definition for drug-resistance epilepsy was a failure of adequate trials of two tolerated, appropriately chosen and used antiepileptics to achieve sustained seizure freedom. The duration was defined as the interval between the start of antiepileptics and the last follow-up. We defined the lesion-plus group as the structural lesions on MRI that has wider spread of epileptic network beyond the visible lesions on MRI, such as hippocampal sclerosis and malformation of cortical development. Lesion-restriction group was defined as the epileptic network being believed to be limited on the structural lesions.
We found 234 patients with lesional epilepsy, who met the inclusion criteria. Of these 234 patients, 115 patients were male (49%) and 119 patients were female (51%). The median age was 22 years old (range 13-78 years old) and the median duration was 131 months (range 12-516 months). Forty percent (90/234 patients) were intractable to antiepileptics. Of the structural lesions on MRI, hippocampal sclerosis was most frequent (N=90). Other structural lesions were malformation of cortical development (N=38), cerebromalatic lesions related with trauma (N=34), tumor (N=19), cystic lesion (N=15), cerebral infarction (N=11), vascular malformation (N=10), and other miscellaneous lesion (N=24). Lesion-plus group had significantly higher drug-resistance epilepsy than cystic lesions on MRI (60/128 vs. 2/15, p=0.013 by Fisher's exact test). There was a tendency of having more drug-resistance epilepsy in the lesion-plus group than the lesion-restriction group (56/121 vs. 30/89, p=0.09 by Chi-square test). The median duration in drug-resistance epilepsy was significantly longer than that of medically controlled epilepsy (178 months (range 23-516 months) vs 102 months (range 12-479 months), p<0.0001 by Mann-Whitney test). In addition, duration was only the significant variable associated with drug-resistance epilepsy in lesional epilepsy by multiple logistic regression analysis (p=0.02 for overall model fit).
In lesional epilepsy, hippocampal sclerosis and malformation of cortical development are more intractable to antiepileptics, reflecting wider epileptic network beyond the visible lesion. In addition, the response to antiepileptics may be expected to decrease when the duration is prolonged.
尽管磁共振成像(MRI)显示有结构损伤的部分性癫痫(损伤性癫痫)对抗癫痫药物的反应不如MRI无结构损伤的癫痫,但损伤性癫痫对抗癫痫药物的反应存在异质性。越来越多的证据表明,MRI上可见损伤之外的癫痫网络范围可能与对抗癫痫药物的反应有关。本研究的目的是明确:(1)MRI上可见损伤之外的癫痫网络,或(2)MRI上损伤性癫痫的病程,是否与对抗癫痫药物的反应相关。
本研究的纳入标准为:(1)MRI有结构损伤;(2)服用抗癫痫药物至少1年;(3)年龄≥13岁。耐药性癫痫的定义为:充分试用两种耐受、适当选择和使用的抗癫痫药物后仍未能实现持续无癫痫发作。病程定义为开始服用抗癫痫药物至最后一次随访的时间间隔。我们将损伤加组定义为MRI上的结构损伤,其癫痫网络在MRI可见损伤之外有更广泛的扩散,如海马硬化和皮质发育畸形。损伤局限组定义为癫痫网络被认为局限于结构损伤。
我们发现234例符合纳入标准的损伤性癫痫患者。在这234例患者中,115例为男性(49%),119例为女性(51%)。中位年龄为22岁(范围13 - 78岁),中位病程为131个月(范围12 - 516个月)。40%(90/234例患者)对抗癫痫药物难治。在MRI上的结构损伤中,海马硬化最为常见(N = 90)。其他结构损伤包括皮质发育畸形(N = 38)、与创伤相关的脑软化病变(N = 34)、肿瘤(N = 19)、囊性病变(N = 15)、脑梗死(N = 11)、血管畸形(N = 10)和其他杂类病变(N = 24)。损伤加组的耐药性癫痫显著高于MRI上的囊性病变(60/128 vs. 2/15,Fisher精确检验p = 0.013)。损伤加组的耐药性癫痫有多于损伤局限组的趋势(56/121 vs. 30/89,卡方检验p = 0.09)。耐药性癫痫的中位病程显著长于药物控制的癫痫(178个月(范围23 - 516个月)vs 102个月(范围12 - 479个月),Mann-Whitney检验p < 0.0001)。此外,通过多因素逻辑回归分析,病程是损伤性癫痫中与耐药性癫痫相关的唯一显著变量(总体模型拟合p = 0.02)。
在损伤性癫痫中,海马硬化和皮质发育畸形对抗癫痫药物更难治,反映出可见损伤之外有更广泛的癫痫网络。此外,病程延长时,对抗癫痫药物的反应可能会降低。