Long-term safety and efficacy of zonisamide in patients with refractory partial-onset epilepsy

Objectives –  To investigate whether zonisamide remains effective and well tolerated in the treatment of refractory partial epilepsy during long-term treatment and with flexible dosing in clinical practice.
Materials and methods –  Patients with refractory partial epilepsy who completed a fixed-dose, randomized, double-blind clinical trial were recruited in an open-label extension study with adjustment of zonisamide and other antiepileptic drug dosage according to the treating physician's usual clinical practice.
Results –  An intention-to-treat analysis of 317 patients showed that zonisamide was well tolerated with a predictable safety profile. Patient retention rates at 1, 2 and 3 years were 65.3%, 44.5% and 28.8%, respectively. Zonisamide treatment was associated with a maintained reduction in seizure frequency, with some patients achieving prolonged periods of seizure freedom.
Conclusions –  Flexible dosing with zonisamide demonstrated a good safety profile and sustained efficacy in the long-term adjunctive treatment of refractory partial epilepsy.     

新型抗癫痫药唑尼沙胺对点燃的影响

目的研究唑尼沙胺对大鼠杏仁核点燃及戊四唑(PTZ)化学性点燃模型的抗癫痫作用。方法建立大鼠杏仁核电刺激点燃、化学性点燃模型,探讨唑尼沙胺的抗点燃作用;测定唑尼沙胺对小鼠最大电休克的影响。结果唑尼沙胺50~200mg·kg-1ig可抑制大鼠杏仁核点燃发作,降低Racine's分级唑尼沙胺50,100mg·kg-1ig抑制PTZ化学性点燃发作,降低Ono分级(P<0.01)与OnoⅣ级发作百分率(P<0.01)。ZNS10.0mg·kg-1ig降低小鼠最大电休克诱发的,惊厥发生率(P<0.01)。结论唑尼沙胺对点燃发作具有拮抗作用。     

Efficacy and tolerability of zonisamide as add‐on in brain tumor‐related epilepsy: preliminary report

Background –  Zonisamide (ZNS) is an antiepileptic drug (AED) with broad spectrum action that demonstrated a good efficacy in controlling seizures as add‐on in adult and pediatric epilepsy. To date there have been no studies on ZNS in patients with brain tumor‐related epilepsy (BTRE). Aim of the study –  To evaluate efficacy and tolerability of ZNS as add‐on in BTRE. Methods– We followed six patients suffering from BTRE who had already been treated with other AEDs and who had had not experienced adequate seizure control. Three patients underwent chemotherapy while being treated with ZNS. Mean duration of follow‐up was 8 months. Results –  Mean seizure number in the last month prior to the introduction of ZNS had been 27.7/month. ZNS mean dosage was of 283.3 mg/day. At last follow‐up, the mean seizure number was reduced to 8.8/month. Responder rate was 83.3%.Two patients discontinued the drug because of side effects. There were no other reported side effects. Conclusions –  Preliminary data on the use of ZNS in add‐on in patients with BTRE indicate that this drug may represent a valid alternative as add‐on in this particular patient population. However, larger samples are necessary to draw definitive conclusions.     

A pilot open‐label trial of zonisamide in Unverricht‐Lundborg disease

Action myoclonus frequently remains the primary cause of disability in Unverricht‐Lundborg disease (EPM1) patients. Pharmacological treatment of myoclonus in these patients continues to be challenging; indeed conventional AEDs may be poorly effective in monotherapy or even in combination. We carried out a pilot, open‐label trial of add‐on zonisamide (ZNS) in patients with EPM1. Twelve EPM1 patients with epilepsy and action myoclonus were included in the study. Oral ZNS was gradually titrated until the target dose of 6 mg/Kg/day. Unified Myoclonus Rating Scale was obtained in each subject before and after ZNS add‐on. A significant reduction of myoclonus severity was reached after ZNS introduction. ZNS was generally well tolerated and only two patients withdrew due to mild adverse effects. Our trial suggests that ZNS may be a valuable therapeutic option in EPM1 patients. © 2010 Movement Disorder Society     

颞叶癫痫的病理特点分析与手术方式探讨

目的探讨颞叶癫痫的发病基础以及如何选择手术方式。方法将53例行前颞叶切除术的颞叶新鲜标本按照统一的步骤和方法进行处理,详细描述皮层分层结构,细胞形态、数量、分布,海马结构及其他病变组织的病理特点,研究其在颞叶癫痫中所起的作用。结果病理改变可以分为8个主要类型,其中最常见的是海马硬化和皮质发育不良,共35例(66.0%),这两种改变伴随出现于24例中,其次常见的是肿瘤(8例)。结论颞叶癫痫病理改变最常见的是海马硬化和皮质发育不良,而且这两种改变常常伴随出现。目前仍以同时切除海马杏仁核的标准前颞叶切除术为主要术式。     

A double-blind placebo-controlled trial of zonisamide (zonegran) in the treatment of essential tremor.

Medical therapy for essential tremor (ET), a common movement disorder, is often inadequate. We performed a double-blind placebo-controlled randomized trial to evaluate the efficacy and tolerability of zonisamide (ZNS), an antiepileptic agent, in treating ET. Twenty patients (mean age, 60 +/- 15 years) with ET were randomized to receive ZNS or placebo. ZNS was initiated at a dosage of 100 mg/day and escalated to 200 mg/day at day 14. Patients were evaluated by accelerometry and the Fahn-Tolosa-Marin (FTM) rating scale at baseline and days 14 and 28, as well as the Clinical Global Impression (CGI-C) scale at day 28. At endpoint, subjects assigned to ZNS were taking a mean dosage of 160 +/- 50 mg/day. There were no significant improvements in the FTM total score or its subsections. Tremor amplitude as assessed by accelerometry significantly improved in the ZNS group compared to the placebo group at endpoint relative to baseline (-0.50 +/- 0.72 vs. 0.30 +/- 0.79 m/s(2); P = 0.03). On the CGI-C, 60% (n = 6) of patients in the ZNS group felt that their tremor was unchanged, while the remaining patients felt that their tremor was "minimally improved." Thirty percent (n = 3) of patients taking ZNS discontinued the study due to side effects (fatigue, headache, paresthesias) while taking 100 mg per day. ZNS did not provide significant improvements in clinical rating scales at study endpoint compared to placebo and was only modestly well tolerated. ZNS was effective in reducing tremor amplitude as measured by accelerometry.     

托吡酯添加治疗难治性癫癎的临床观察

目的　观察添加托吡酯对难治性癫的临床效果与副作用。方法　对 18例难治性癫患者 ,加用TPM后观察其发作频率并与加用前进行比较 ,计算总有效率。同时进行临床疗效和副作用观察。结果　病人加用托吡酯后总有效率为 5 0 % ,其中显效率达 2 2 2 % (3例未再发作 )。副反应以胃肠道反应及神经系统症状为主 ,发生率为 5 2 6%。结论　加用TPM治疗难治性癫安全有效。     

Multi-center study on post-ictal headache in patients with localization-related epilepsy

The nature of post-ictal headache (PIH) remains unclear. A multicenter study was conducted in order to evaluate frequency and risk factors for PIH. The subjects consisted of 97 patients with temporal lobe epilepsy (TLE), 65 patients with frontal lobe epilepsy (FLE) and 37 patients with occipital lobe epilepsy (OLE). The subjects were asked about PIH at each institute. Clinical factors of epilepsy were reviewed for each patient and correlated with PIH. Post-ictal headache occurred in 41% of TLE patients, 40% of FLE patients and 59% of OLE patients. Logistic regression analysis revealed that the risk of PIH was significantly higher in OLE than in FLE. In contrast, there were no significant differences in the incidence of PIH between TLE and either OLE or FLE patients. Post-ictal headache occurred significantly more frequently in subjects with generalized tonic-clonic seizure (GTCS) than in those without GTCS. Other clinical factors, such as sex, age, age at onset, duration of illness, seizure frequency, family history of headache and interictal headache were found to have no associations with PIH. A difference was found in the incidence of PIH depending on classification of epilepsy, but only to a relatively slight extent. It was also found that GTCS was significantly related to PIH. These results suggest that both the location of epileptogenic focus and the involvement of certain cerebral areas in the spread of seizure discharges may be closely related to PIH.     

前颞叶切除术对癫痫患者记忆功能影响的临床研究

目的评估前颞叶切除术对癫痫患者记忆功能的影响。方法对30例颞叶癫痫病例往术前、术后2周和术后6个月以上时分别进行记忆测评,比较患者记忆评分的变化;对24例患者进行1H-MRS成像,评估1H-MRS值与韦氏记忆评分之间的相关关系。结果术前MQ均值与术后2周时有显著性差异,术后6个月以上较术后2周时有显著改善;短时记忆在术前、术后无明显变化;非海马硬化组中患侧NAA/Cr与术前、术后短时记忆差值有相关性,患侧NAA/(Cr Cho)以及健侧与患侧NAA/(Cr Cho)之差与术前、术后MQ差值有相关性。结论术后早期多数患者MQ、长时记忆、瞬时记忆有较明显下降,6个月以后有明显恢复,而短时记忆下降不明显。患侧海马1H-MRS值与术前、术后韦氏记忆评分之间存在一定的相关关系。     

幕上脑膜瘤术后早期癫痫的临床分析

目的探讨影响幕上脑膜瘤术后早期癫痫发生的相关因素。方法回顾性分析2001年1月至2006年12月间经手术治疗的173例幕上脑膜瘤患者,分析其临床特征、外科手术情况、术后并发症、术后早期癫痫的发生情况及其关系。结果术后发生早期癫痫14例,占8.09%。其中全面性发作3例,局灶性发作11例。6例发生于术后24小时内,8例发生于术后2～7天。10例肿瘤次全或大部切除、30例术中发生皮层或皮层血管损伤、25例术后瘤腔出血、69例脑水肿、56例术后水电解质紊乱,各组中发生术后早期癫痫例数分别为2例、4例、5例、8例和9例。结论幕上脑膜瘤的术后早期癫痫的发生与瘤体大小、手术操作技巧、肿瘤切除程度、术后并发症等因素密切相关。     

Administration of zonisamide in three cases of dementia with Lewy bodies

Zonisamide (ZNS) add‐on administration was used to treat parkinsonian symptoms in three cases of dementia with Lewy bodies (DLB). ZNS was added after doses of the anti‐Parkinson's disease drugs were fixed for at least 4 weeks. A total of 25 mg of ZNS produced mild–moderate improvement of parkinsonian symptoms in two cases, but it did not affect the cognitive functions and behavioral or psychological symptoms. Caregiver burdens were decreased in two cases. Although dizziness and drowsiness were detected, these were improved by decreasing the dose. ZNS may be useful for the treatment of motor symptoms in DLB patients.