Effect of topiramate for patients with intractable epilepsy

The effects of topiramate (TPM) were evaluated in 51 patients with intractable epilepsy. Callosotomy and hemispherotomy were performed in 16 patients and one patient before the administration of TPM, respectively. The 50% responder rate (50%RR) was recorded in 39% of the total patient population and in 58% of patients with symptomatic location-related epilepsy (SLE). TPM was most effective for frontal lobe epilepsy (FLE), and the 50%RR was recorded in 88% of those patients. TPM (50%RR) was more effective in secondary generalized seizures (in 75%) and complex partial seizures (in 67%) in comparison to that of tonic-clonic seizures (in 44%) and drop attacks (in 29%). Seventy-one percent of the patients with atypical absence seizures increased seizure frequency. The 50%RR was recorded in 22% of the patients who underwent epilepsy surgery, and 29% of those patients also showed seizure aggravation due to TPM. These results suggest the efficacy of TPM for intractable epilepsy.     

Comparative cognitive effects of levetiracetam and topiramate in intractable epilepsy

Aim: Anti‐epileptic drugs (AED) may cause cognitive impairment. Because intractable epilepsy (IE) represents a distinct group, the purpose of the present study was to study the comparative cognitive effects of the two efficacious AED, levetiracetam (LEV) and topiramate (TPM), on IE. Methods: This was a non‐randomized, blinded cognitive assessment and parallel design. The cognitive effects of LEV and TPM on 79 demographically comparable patients with IE were assessed at baseline (T1) and after 1 year of treatment (T2) using the Cognitive Abilities Screening Instrument. Results: Forty patients took TPM and 39 took LEV. At T1, seizure frequency, number of AED, and epilepsy duration were not significantly different. There were no significant differences in cognition between the two groups at T1 or T2. T2 orientation scores were lower than T1 scores in the TPM group (P < 0.05). In the TPM subgroup with T1 cognitive abnormalities, T2 scores for recent memory improved (P < 0.05). Conclusion: For patients with IE, LEV might preserve cognition, TPM's effects for patients with baseline cognitive abnormalities are worth observation.     

托吡酯添加治疗难治性癫痫初步临床观察

目的　观察添加托吡酯 (TPM)对难治性癫痫 (IE)的临床效果与安全性。方法　IE 2 4例 ,以加用TPM前 3个月的月均发作频率为基准 ,并与加TPM后稳定期 3个月的月均发作频率进行比较。按常规计算有效率。并进行临床观察和实验室检查。原用抗癫痫药 (AED)基本保持不变 ,以测原用AED治疗前后的血浓度 ,协助观察病人用药的依从性。结果　病人用药依从性好 ,有效率为 67 9%～ 70 8% ,其中显效率达 5 0 % (4例未再发作 )。高级神经系统活动一时性副反应达16%。结论　加用TPM治疗IE是安全有效的方法之一。     

托吡酯添加治疗儿童难治性癫痫的开放性自身对照临床研究

目的 评价托吡酯添加治疗儿童难治性癫痫的疗效及安全性。方法 应用托吡酯对44例难治性癫痫患儿进行开放性自身对照临床研究,其中单纯部分性发作患儿14例次,复杂部分性发作患儿23例次,部分性发作继发全面性发作患儿16例次。于服药后6个月评价托吡酯的疗效和安全性,以及临床疗效与药物剂量关系。结果 托吡酯治疗总有效率为58.14％(25/43例次),以发作次数减少≥50％为界,单纯部分性发作患儿治疗总有效率为57.14％(8/14例次),复杂部分性发作63.64％(14/22例次),部分性发作继发全面性发作68.75％(11/16例次)。6例Lennox-Gastaut综合征患儿中仅2例有效。托吡酯治疗后的不良反应发生率为46.51％(20/43例次),主要为厌食(37.21％)和体重下降(27.91％)。托吡酯所致不良反应较轻微,部分患儿继续接受治疗可自行缓解。结论 尽管在服用托吡酯期间须行不良反应监测,但其作为添加剂治疗儿童难治性癫痫安全有效,且对患儿血尿常规、肝肾功能均无明显影响。     

难治性颞叶内侧癫痫术前评估方法再评价

目的 通过难治性颢叶内侧癫痫术后随访1年以上,术后效果达到Engel's Ⅰ级(无发作)的患者,探讨各种术前评估方法确定癫痫灶的可靠程度.方法 65名术后随访超过1年,术后达到Engel's Ⅰ级疗效的难治性颞叶内侧癫痫患者,患者的发作症状学、神经影像和头皮脑电图进行回顾性分析.结果 所有患者的发作间期正电子发射断层扫描(PET)显示与手术侧一致的颞叶低代谢改变;41例患者发作前存在典型的颞叶内侧常见先兆,所有患者发作起始表现为意识障碍;28例患者有手术侧颞叶影像异常(图1),8例患者存在双侧颞叶异常,8例患者存在多脑叶影像异常,21例患者核磁共振检查未发现明显异常;20%患者发作间期偶有异常、80%患者存在多灶棘波、尖波、棘慢波;发作期脑电放电早期显示:20例患者无法确定起源侧别,45例患者可以确定侧别(手术侧),只有21例患者可以清楚的显示手术侧蝶骨电极起源.结论 患者的发作症状学分析和PET检查是难治性颞叶内侧癫痫术前评估中基本和重要的评估手段.     

妥泰对West综合征患儿免疫功能的影响

目的：观察妥泰对West综合征患儿的免疫功能的调节作用。方法：采用流式细胞术对West综合征患儿妥泰治疗前后外周血淋巴细胞亚群比例和血清免疫球蛋白进行检测，观察其动态变化，并与25例正常婴儿比较。结果：经妥泰治疗后的T辅助细胞与治疗前比明显下降，接近对照组。治疗前后B细胞与对照组相比明显下降。治疗后NK细胞与治疗前相比明显上升。治疗前后的IgA与对照组比明显下降。治疗后IgG与治疗前比明显上升已接近对照组。结论：妥泰可能通过调节免疫功能的作用，达到控制West综合征发作。     

托吡酯添加治疗难治性癫痫的临床研究

目的观察托吡酯作为添加药物治疗难治性癫痫的疗效、用药方法、剂量及副作用.方法采用开放性试验的方法对50例难治性癫痫患者(其中成人30例,小儿20例)进行添加托吡酯治疗,观察其疗效.结果托吡酯作为添加药物治疗难治性癫痫,总有效率达58%,22%的患者发作停止.对复杂部分性发作有效率达69%,对其他发作类型亦有一定疗效.本组中成人的疗效好于儿童.平均有效剂量成人为(123.9±47.9)mg/d,小儿为(3.6±1.2)mg·kg     

皮质发育不良导致的难治性部分性癫癎临床特征分析

目的探讨病理表现为皮质发育不良的难治性部分性癫癎的临床特征。方法回顾分析46例手术切除癫癎灶后，病理证实为皮质发育不良的难治性癫癎病例的影像学和脑电图表现以及手术疗效等资料，分析此类癫癎的临床特征。结果在46例中，癫癎灶的病理类型为轻度皮质发育不良10例、Ⅰ型局灶性皮质发育不良25例、Ⅱ型局灶性皮质发育不良5例、伴有胚胎发育障碍性神经上皮瘤和神经节胶质瘤的分别为4例和2例。通过磁共振成像（MRI）扫描可以发现局灶性皮质异常的12例（26．1％），海马硬化10例（21．7％），未见明显异常的24例（52．2％）。在发作间期，60．9％的病例为区域性的癎性放电，45．7％的病例表现出节律性癎样电活动。手术切除癫癎灶后，69．6％的病例发作消失。结论皮质发育不良约占MRI阴性表现的难治性癫癎病例的50％，以Ⅰ型局灶性皮质发育不良最为常见，发作间期脑电图常常显示节律性癎样电活动。     

The effects of adjunctive topiramate on cognitive function in patients with epilepsy

PURPOSE: We investigated possible cognitive effects of topiramate (TPM) in polypharmacy on patients with intractable epilepsy. METHODS: Study 1 evaluated 22 consecutively admitted patients whose antiepileptic drugs (AEDs) on admission to the Montreal Neurological Hospital included TPM. Performance on neuropsychological tests administered on and subsequently off TPM was analyzed. Four patients also were tested before taking TPM, allowing comparisons off, then on, and then off the drug again. Measures included intellectual function, verbal and nonverbal memory, language, word and design fluency, somatosensory sensitivity, and motor skills. In Study 2, 16 patients at the Minnesota Epilepsy Group were tested first off, then on TPM with nine cognitive tasks that measured concentration, verbal fluency, language, and psychomotor speed. RESULTS: In Study 1, significant (p < or = 0.01) improvements were observed off TPM on 13 measures including verbal and nonverbal fluency and certain verbal and perceptual tasks. Notably, verbal learning and memory were unaffected; a limited effect was observed on nonverbal memory. Patients tested 3 times scored better in both tests off TPM compared with on this drug. In Study 2, declines on TPM were observed on all measures, significantly (p < or = 0.05) for tests of fluency, sustained concentration, and visual motor processing speed. CONCLUSIONS: TPM was associated with declines in fluency, attention/concentration, processing speed, language skills, and perception; working memory but not retention was affected. As the two studies used an opposite order of testing on versus off TPM, our results clearly show a performance decrement while patients are taking TPM, without respect to which condition is tested first.     

Clinical and electroencephalographic effects of topiramate in patients with epilepsy and healthy volunteers

Although topiramate, one of the newer drugs used in treating epilepsy, is effective in reducing seizure frequency and has a wide spectrum of action, it often induces intolerable adverse effects, predominantly related to the central nervous system. Information that would help document adverse reactions early, thus allowing topiramate doses to be adjusted during the drug titration and maintenance phases, could be obtained from electroencephalogram (EEG) studies. We studied the clinical effects and EEG changes induced by topiramate in patients with refractory partial epilepsy receiving the drug as add-on therapy. To exclude effects related to the other drugs and to epilepsy itself, we compared data from patients and healthy volunteers. After receiving topiramate, 22.6% of patients became seizure free and 29% had their seizures reduced by 50% or more. Topiramate nevertheless induced noteworthy adverse reactions, the main problems being sedative and cognitive changes. Also, in healthy volunteers, a single 100-mg dose of topiramate induced mild adverse reactions, mainly affecting concentration and attention, with difficulties in speech and writing. In patients with epilepsy, the EEG changes induced by topiramate consisted of increased delta and theta activities and decreased activity in the rapid bands. This recognizable topiramate-induced EEG pattern was again evident in the healthy volunteers, in whom we also detected a significant reduction in the alpha frequency rhythm. Our results confirm that topiramate needs to be introduced gradually while patients undergo close neuropsychologic and neurophysiologic monitoring to detect adverse sedative and cognitive reactions early. The EEG correlate of these events seems to be increased activity in the slower frequency bands.     

Combined treatment with vigabatrin and topiramate in West syndrome

The clinical and electroencephalographic (EEG) response to combined therapy with vigabatrin and topiramate was evaluated in five patients ages 7 to 15 months affected by West syndrome in an open-label trial. Four patients had cryptogenic and one patient had symptomatic (tuberous sclerosis) West syndrome. In cryptogenic patients who failed to respond to pyridoxine, vigabatrin was titrated to 80 to 100 mg/kg. Because control of infantile spasms or an EEG improvement was not obtained with vigabatrin treatment, topiramate was added (3-3.8 mg/kg/day). In all patients, the combined therapy with topiramate and vigabatrin achieved a rapid and complete normalization of infantile spasms, and in three patients with cryptogenic West syndrome, the EEG also became normal. In only one patient, transient anorexia was observed. This drug combination led to rapid neurodevelopmental normalization in cryptogenic patients. The results are promising and justify more trials in larger numbers of children with West syndrome.     

托吡酯治疗癫痫的临床疗效及安全性的观察

目的　观察及评价托吡酯对各型癫痫的临床疗效及安全性。方法　对 1998年 12月至2 0 0 0年 12月在我院确诊的 14 2例癫痫患者中的 93例采用托吡酯添加治疗、4 9例单药治疗 ,经 8周加量期和 12周稳定期观察后进行评价。结果　添加治疗组及单药治疗组总有效率分别为 79%和84 % ,完全控制率分别为 2 8%和 4 1%。成人有效剂量为 10 0～ 2 0 0mg/d ,儿童 3～ 5mg·kg-1·d-1。不良反应较轻 ,耐受性良好。结论　托吡酯是一种广谱、有效及安全的新型抗癫痫药 ,可作为一线抗癫痫药添加或单独使用。     

Experience with topiramate monotherapy in elderly patients with recent-onset epilepsy

OBJECTIVES: To evaluate the effect of topiramate in elderly patients with onset of epilepsy after the age of 60, treatment-naive or non-responding to an initial antiepileptic drug. METHODS:Analysis of patients with epilepsy diagnosed in the preceding 5 years, aged>/=65 years (n=43), enrolled in a larger open-label trial (n=692). After titration to topiramate 100 mg/day over 4 weeks, the dose was adjusted according to individual response (maximum 400 mg/day). Patients were followed up for at least 7 months. RESULTS: After 7 months, 79% of patients remained in the study. Seizure frequency decreased significantly vs baseline (P<0.001); >/=50% reduction in seizure frequency was achieved in 87% of patients, 64% remained seizure-free. Both previously treated and naive patients responded. Fourteen per cent dropped out because of insufficient tolerability. No unexpected or unusual adverse events were observed. CONCLUSIONS: The results indicate that elderly patients respond well to topiramate monotherapy. The high patient retention rate reflects a favourable tolerability profile in this population.     

A double-blind, placebo-controlled study of topiramate in adult patients with refractory partial epilepsy

PURPOSE: The efficacy and safety of topiramate (TPM) as adjunctive therapy in the treatment of adult Chinese patients with refractory partial epilepsy were investigated in a randomized, double-blind, placebo-controlled study. METHODS: A total of 46 patients who had four or more complex partial seizures with or without secondary generalization within an 8-week baseline phase were enrolled. Patients were assigned randomly to receive TPM (n = 23) or placebo (n = 23). TPM or placebo was titrated to target doses of 300 mg/d for 6 weeks and maintained at stabilized levels for another 8 weeks. Concomitant antiepileptic drugs remained at constant previous levels during the trial. RESULTS: In all, 41 patients completed the trial (TPM group, n = 20; placebo group, n = 21). The proportion of patients with a > or =50% reduction from baseline in complex partial seizures was 11 of 23 (47.8%) in the TPM group and 3 of 23 (13.0%) in the placebo group (p = 0.01). In addition, patients treated with TPM had significantly better investigator (p = 0.014) and patient (p = 0.0005) global assessment scores than patients in the placebo group. Adverse events were mostly mild and transient, with no significant differences between treatment groups. Two patients with TPM therapy complained of weight loss. Routine blood cell counts and other laboratory results showed no significant changes from baseline in either treatment group. CONCLUSIONS: TPM 300 mg/d is effective and well tolerated as treatment for refractory partial epilepsy in adults.     

托吡酯对慢性癫痫幼鼠神经元保护作用的实验研究

目的 研究托吡酯(TPM)单药对慢性癫痫幼鼠损伤神经元的影响.方法 将3～4周龄雄性Wistar大鼠72只采用随机数字表法分为6组,每组各12只,A组:阴性对照组;B组:阳性对照组;C组:TPM低剂量组(20 mg/kg);D组:TPM中等剂量组(40 mg/kg);E组:TPM高剂量组(80 mg/kg);F组:合药组(TPM 40 mg/kg+丙戊酸钠200 mg/kg),其中B～F组为慢性癫痫组,于给药前腹腔注射戊四氮.连续用药2个月,观察幼鼠体重、行为学表现、血清神经元特异性烯醇化酶(NSE)及病理改变.结果 (1)E组对幼鼠体重的影响比C组、F组显著.(2)D组、E组戊四氮诱发痫性发作的时间延长,痫性发作的程度减轻.(3)TPM各剂量组NSE水平显著低于B组,F组与TPM单药组无差异.(4)E组海马组织神经元的退行性变和胶质细胞的增生程度减轻明显.结论 TPM可减轻幼鼠痫性发作后的神经损伤程度,且存在剂量效应,但与丙戊酸钠联合可削弱其神经保护作用.     

Long-term developmental outcome in patients with West syndrome after epilepsy surgery

It has been hypothesized that early seizure control may prevent children with intractable epileptic spasms (ES) from developmental regression and may contribute to better developmental outcome. The effectiveness of surgery for ES has been reported. We investigated long-term post-operative outcomes of seizure control and development in patients with symptomatic West syndrome (S-WS) who underwent epilepsy surgery. Six children who underwent surgical intervention for intractable ES were retrospectively investigated. Cortical malformations were observed on pre-operative MRI in all patients, with hemispheric or multilobar involvement in four children and focal lesions in two. Following surgery, we measured motor function, developmental age (DA), language skills, and sociopsychological function for up to 7years (mean, 4.9years). Post-operative seizure outcome was Engel Class I (n=4) or III (n=2). Motor function and DA was increased following surgery in six and five patients, respectively. Two patients started to speak in sentences following focal resection. Autistic features were noted in four of the five examined patients post-operatively. None of the patients showed developmental regression following surgery. Epilepsy surgery for S-WS with ES may result in good seizure control and improvement in motor development. Improvement in cognitive function was modest in this small cohort of children and autistic features were noted post-operatively in a substantial proportion of the children. While seizure control can be obtained by epilepsy surgery, early intervention for sociopsychological comorbidities may be warranted in children with S-WS.     

A case of intractable epilepsy in a double cortex syndrome

This article describes a very rare case of a double cortex syndrome in a man aged 32 years old who started from the age of 14 years having seizures and many other epileptic manifestations that continue to the present age, being always intractable to various therapeutic regimes. The neuroimaging revealed cortical ectopias in the cingulum, the visual cortex, in the middle part of the superior temporal gyrus, in the frontal pole as well as in the middle area of precentral gyrus. This article attempts to underline the behavioral disturbances, the learning difficulties, the psychological fluctuations, and the multitude of the seizures that have been released during the clinical course of the patient. The article attempts to correlate the clinical phenomena of the patient and the resistance to therapeutical interventions with the morphological changes as they have been visualized by the neuroimaging techniques, reviewing in addition relevant cases from the literature.