药物难治性癫痫外科治疗展望

癫痫是危害较大的神经系统疾病,其发病率在4‰～6‰.在我国有近600万癫痫患者,其中20%～30%患者对内科药物治疗效果不佳,是癫痫外科治疗的主要目标[1,2].近二十年来,随着神经电生理技术和神经影像学的飞速发展,药物难治性癫痫患者的术前定位和评估取得了明显的突破,外科手术已成为癫痫治疗的一种重要手段[2].同时,随着外科麻醉和手术技巧的不断改进,尤其是显微神经外科技术的应用,使癫痫的外科治疗越来越安全有效,外科治疗已成为治疗药物难治性癫痫患者的主要手段[2,3].     

难治性癫痫的放射外科治疗

难治性癫痫 ,又称顽固性癫痫 ,指癫痫发作频繁、应用适当的第一线抗癫痫药物正规治疗且药物血浓度在有效范围内两年以上、仍不能控制发作且影响日常生活。约有 2 0 %的癫痫病人随着病情发展或治疗不当 ,可能转变为难治性癫痫。容易导致难治性癫痫的因素有 :(1)复杂部分性发作、婴儿痉挛及 L ennox- Gastaut综合征等 ;(2 )发作频繁 ,每天数次 ;(3)出现过癫痫持续状态 ;(4 )对发作频率判断错误 ;(5 )起病后延误治疗 ;(6 )不适当的多种药物联合应用 (包括中药 ) ;(7)同一期间内在几个医疗单位应用不同的治疗计划 ;(8)对合并的精神心理障碍认识…     

难治性癫痫状态的外科治疗

难治性癫痫状态(refractory status epilepticus,RSE)是一种对足够疗程足够大剂量抑制性治疗(high-dose Suppressive therapy,HDST)治疗效果不佳的癫痫状态。目前大多数情况下药物难治性癫痫状态的治疗,主要凭借医生个人经验,HDST是RSE治疗的主要方法,而外科手术切除致痫病灶亦是很有效的治疗手段之一。目前外科治疗RSE相关文献仅限于病例报告及小样本分析。本文就目前外科治疗RSE的现状、手术适应证、手术时机、手术方式、手术并发症和预后进行综述。     

伽玛刀治疗颞叶癫痫的长期随访

目的 探讨颞叶癫痫的伽玛刀治疗的疗效。方法 用PET、SPECT、MRI、EEG检查痫灶位置，应用瑞典ELEKTA公司伽玛刀治疗系统行杏仁核毁损术(90～100Gy)加颞叶内侧或外侧低剂量(中心20Gy，边缘10Gy)伽玛射线照射38例。结果 本组38例经伽玛刀治疗后随访5．1～7．2年，满意26例，显著改善及良好各3例，无效6例，有效率84．2％。其中癫痫完全消失23例，占61％；1例3个月后出现精神症状，经激素、甘露醇治疗第六个月后症状消失；6例(在满意26例中)2年后癫病症状同治疗前。无病残及死亡。结论 伽玛刀行杏仁核毁损术加颞叶内侧或外侧低剂量照射，对颞叶癫痫具有明确的疗效，并发症少见。部分病例的复发可能与杏仁核毁损剂量不足有关。     

难治性癫痫的外科治疗及术前评估

癫痫是危害较大的神经系统常见病,其中约30%~40%属于难治性癫痫,近年来随着术前评估及外科手术技巧不断改进,特别是显微外科技术的应用,外科治疗尤其是对颞叶内侧癫痫的治疗疗效满意。癫痫的术前评估至关重要,手术效果与术前致痫灶定位准确与否密切相关。癫痫术前评估包括非侵袭性评估(I期)和侵袭性评估(II期),随着新的诊断技术的飞速发展,术前评估通过脑电图、脑磁图、CT、MRI、磁共振波谱、功能MRI成像、单光子发射计算机断层扫描和正电子发射计算机断层扫描等以确定病人致痫灶。癫痫手术方式主要有颞叶切除术、选择性杏仁核海马切除术、胼胝体切开术、大脑半球切除术等。本文就癫痫手术适应证、术前评估、手术方式等予以综述。     

小儿难治性癫痫早期外科治疗探讨

长期反复发作的难治性癫痫可严重影响患者的生活质量,尤其是处于发育阶段的小儿患者,可导致患者智力低下和精神衰退,影响正常的生长发育。随着临床诊疗技术的进步,癫痫患者的早期外科治疗已得到广泛的认同。成人患者已有完善的手术标准作为其治疗指导,而目前对于小儿难治性癫痫的认识及早期手术治疗尚处于探索阶段。本文主要就小儿难治性癫痫早期外科治疗的必要性及术后疗效进行探讨。     

小儿难治性癫痫综合征的外科治疗

目的总结外科手术治疗27例小儿难治性癫痫综合征病人的经验。方法术前评估和术中脑电检查显示为局灶性改变者行致痫灶切除、脑叶切除或多软膜下横纤维切断(MST)。检查提示一侧半球为主多灶性改变者,术中行多脑叶切除联合MST或(和)胼胝体部分切开。结果本组随访1-8年,平均4.5年。27例病人中有14例获得Ⅰ级(Engel分级),8例获得Ⅱ级,3例为Ⅲ级。平均智商(IQ)从术前的61.4分提高到75.0分,癫痫病程和术前药物难治的时间越短,智商改善越明显。本组4例病人出现暂时性的并发症,无手术死亡。结论对小儿难治性癫痫综合征进行早期外科干预,可以有效地控制癫痫发作、改善智力损害和避免生活残疾。     

难治性癫痫手术治疗进展

磁共振成像技术与电生理技术为难治性癫痫的诊断提供了有力的技术支持。神经导航技术、手术中磁共振成像技术等提高了操作的准确性。其他新技术例如软膜下多重横切术、迷走神经直接或间接刺激术也有效应用于临床。通过研究经典神经外科切除手术与采用新技术在治疗上的差异,分析了目前难治性癫痫手术的治疗结果,证实手术治疗对于药物难治性癫痫患者是安全有效的。     

额叶癫痫的外科治疗

额叶癫痫是外科手术治疗的一种常见类型癫痫,约占癫痫外科手术病例的10%～20%.额叶位于大脑前部,包括中央沟以前的全部皮质区.额叶癫痫的外科治疗成败的关键在于如何准确定位致痫灶.额叶癫痫的外科治疗较颞叶癫痫复杂,其手术方式可分为两种:切除性手术和功能性手术.目前额叶癫痫外科治疗的有效率,各家报道不一,一般可达到50%～80%.     

Long-term seizure outcome and antiepileptic drug treatment in surgically treated temporal lobe epilepsy patients: a controlled study

PURPOSE: To evaluate the long-term impact of surgical treatment on seizure outcome and antiepileptic drug (AED) use in patients with pharmacoresistant temporal lobe epilepsy (TLE). METHODS: Comparison of seizure outcome and AED us in operated-on TLE patients (n=148) and nonsurgically treated TLE patients (n=94) at a baseline visit and a follow-up visit after a mean period of 4.8 years. RESULTS: At follow-up, 44.6% of the surgical patients and 4.3% of the nonsurgical patients had been continuously seizure- free since the baseline visit (including the immediate postoperative period). A further 17.6% of the operated-on and 3.2% of the not operated-on patients had been seizure-free for at least the previous year; 37.8% of the surgical and 92.5% of the nonsurgical patients had had seizures during the previous 12 months (p < 0.001). Of the surgical patients, 8.8% versus none of the nonsurgical patients were AED free at follow-up; 55.4% versus 20.2% were receiving monotherapy, and 35.8% versus 79.8% were receiving polytherapy (p < 0.001). Mean number of AEDs and mean change in number of AEDs were significantly more favorable in operated-on than in non-operated-on patients. Further subgroup analysis revealed that not only the continuously seizure-free surgical patients, but also the operated-on patients with ongoing seizures took fewer AEDs than their respective non-operated-on counterparts. CONCLUSIONS: This controlled study for the first time provides comprehensive information on long-term seizure outcome and AED use in surgical TLE patients. It shows a more favorable seizure outcome and AED use in the surgically treated patients. The latter holds true even for the not seizure-free patient subgroup.     

Long-term epilepsy surgery outcomes in patients with MRI-negative temporal lobe epilepsy

Purpose: The outcome of surgery in patients with temporal lobe epilepsy (TLE) and normal high‐resolution magnetic resonance imaging (MRI) has been significantly worse than in patients with unilateral hippocampal damage upon MRI. The purpose of this study was to determine the long‐term outcomes of consecutive true MRI‐negative TLE patients who all underwent standardized preoperative evaluation with intracranial electroencephalography (EEG) electrodes. Methods: In this study we present all adult MRI‐negative TLE surgery candidates evaluated between January 1990 and December 2006 at Kuopio Epilepsy Center in Kuopio University Hospital, which provides a national center for epilepsy surgery in Finland. During this period altogether 146 TLE surgery candidates were evaluated with intracranial electrodes, of whom 64 patients with normal high‐resolution MRI were included in this study. Results: Among the 38 patients who finally underwent surgery, at the latest follow‐up (mean 5.8 years), 15 (40%) were free of disabling seizures (Engel class I) and 6 (16%) were seizure‐free (Engel class IA). Twenty‐one (55%) of 38 patients had poor outcomes (Engel class III–IV). Outcomes did not change compared to 12‐month follow‐up. Histopathologic examination failed to reveal any focal pathology in 68% of our MR‐negative cases. Only patients with noncongruent positron emission tomography (PET) results had worse outcomes (p = 0.044). Discussion: Our results suggest that epilepsy surgery outcomes in MRI‐negative TLE patients are comparable with extratemporal epilepsy surgery in general. Seizure outcomes in the long‐term also remain stable. Modern imaging techniques could further improve the postsurgical seizure‐free rate. However, these patients usually require chronic intracranial EEG evaluation to define epileptogenic areas.     

Long-term seizure outcome of surgery versus no surgery for drug-resistant partial epilepsy: A review of controlled studies

A majority of patients with formerly drug-resistant temporal lobe epilepsy become seizure-free after surgery. However, apart from one 12-month randomized trial, it is unclear how many become seizure-free because of surgery. To determine the net benefit of surgery, we performed a systematic review and meta-analysis of the published evidence of how many patients in similar studies become seizure-free without surgery. Of 155 potentially eligible articles reviewed in full text, 29 (19%) fulfilled eligibility criteria. After excluding 9 publications, 20 studies form the base of evidence. Overall, 719 of 1,621 (44%) of patients with mostly temporal lobe surgery were seizure-free compared to 139 of 1113 (12%) of nonoperated controls [pooled random effects relative risk (RR) 4.26, 95% confidence interval (CI) 3.03–5.98]. The pooled risk difference in favor of surgery was 42% (95% CI 32–51%). We found no comparative outcome data in patients with extratemporal lobe epilepsy only. The available evidence from mostly nonrandomized observational studies indicates that in appropriately selected patients with drug-resistant temporal lobe epilepsy, the combination of surgery with medical treatment is 4 times as likely as medical treatment alone to achieve freedom from seizures.     

Consideration of epilepsy surgery in adults should be independent of age

Objectives

Epilepsy surgery is performed less frequently in persons over 45 years of age than in younger individuals, probably reflecting biases among patients, referring physicians and neurologists.

Methods

We report on a clinically heterogenous cohort of patients aged 45 years or older who underwent epilepsy surgery for medically intractable epilepsy.

Results

Over a 15-year period, 42 patients with a mean duration of epilepsy of 27.3 years underwent elective surgery. The mean follow-up period was 48 months. Thirty-two patients had an Engel class I outcome, of which 23 were totally seizure-free (Ia). Six patients had a class II outcome (rare disabling seizures), one had a class III outcome (worthwhile improvement), and three had a class IV outcome (no worthwhile improvement). The majority of patients reported an improved quality of life and satisfaction with the epilepsy surgery. A subjective improvement in cognition was reported in 7 patients while a decline was reported in 10 patients. New neuropsychiatric difficulties were reported in three patients while three patients reported improved anxiety after surgery. Only one patient became newly employed after surgery while 23 returned to driving. Permanent complications occurred in four patients (thalamic infarct during a Wada test (n = 1) and asymptomatic visual field defect (n = 3)).

Conclusions

We report a favorable outcome from epilepsy surgery in a large series of older adults and conclude that age per se is not a contraindication to epilepsy surgery. We emphasize the lack of correlation between outcome from surgery and pre-operative duration of epilepsy.     

A survey of adult and pediatric epilepsy surgery in the United Kingdom

All consultant epilepsy neurosurgeons were asked to prospectively record all epilepsy surgery procedures carried out at their center between April 2010 and March 2011. Figures were compared to a previous survey completed in 2000. Of a total of 710 procedures, temporal lobe surgery was the most common resective surgery. Although extratemporal lesional surgery was less common, vagus nerve stimulator (VNS) implantation accounted for almost half the procedures. The numbers for all surgical procedures, with the exception of VNS implantations, had decreased. This decrease may represent a global rather than a regional phenomenon. Further longitudinal multinational data on epilepsy surgery is required to confirm or refute this theory.     

Levetiracetam efficacy in refractory partial-onset seizures,especially after failed epilepsy surgery

PURPOSE: We conducted a retrospective study to evaluate the efficacy of levetiracetam as adjunctive therapy in patients with localization-related epilepsy, and specifically in the subset of patients for whom epilepsy surgery failed. METHODS: Eighty-two patients with uncontrolled partial-onset seizures treated with levetiracetam were identified; epilepsy surgery had failed for 21 (25.6%; group I), and 61 (74.4%) had no prior surgery (group II). Group I and group II patients were comparable in age (mean, 40.7 vs. 41.5 years) and age at seizure onset (mean, 14.4 vs. 18.2 years). Patients who had >/=50% reduction in seizure frequency were considered responders; the remaining patients were considered nonresponders. RESULTS: In patients (group I) for whom surgery had failed, responder rate was 76.1% (16 of 21), including 10 (47.6%) patients who became seizure free. In nonsurgical patients (group II), responder rate was 34.3% (21 of 61), including nine (14.7%) patients who became seizure free. In group I, 11 (91.6%) of 12 temporal resection patients were responders, of whom eight were seizure free; of the remaining nine operated (extratemporal) patients, five (55.5%) were responders, and two were seizure free. In three responders, all in group I, a severe, delayed psychotic syndrome developed 4 to 9 months after levetiracetam introduction, leading to its discontinuation. CONCLUSIONS: These findings suggest that adjunctive levetiracetam therapy should be considered early after failed epilepsy surgery, especially after temporal resection, and may have implications for its use before surgical intervention. Patients should be under close psychiatric observation in this clinical setting.     

Long-term social outcomes for children with epilepsy

Summary   Children with epilepsy often grow into adults with significant social problems including decreased employment, marriage, social relationships, and independent living arrangements. These problems are noted in population-based longitudinal and cross-sectional studies from many countries. Learning disorder and mental handicap are the most consistent predictors of poor social outcome. Epilepsy variables, even remission, appear to have little effect. The influence of epilepsy on social outcome is greater than found in other childhood chronic disease control groups. More attention and research is needed to correct these unfortunate outcomes.