吡仑帕奈治疗局灶性癫痫的研究进展

吡仑帕奈为第三代新型抗癫痫发作药物,通过非竞争性抑制α-氨基-3-羟基-5-甲基-4-异恶唑啉丙酸受体来发挥其抗癫痫发作作用。多个国家已批准用于≥4岁局灶性癫痫患者(伴或不伴继发全面性发作)的单药及添加治疗。该文总结了吡仑帕奈治疗局灶性癫痫患者的作用机制、药代动力学、疗效及不良反应等的相关文献,以期为临床医师治疗局灶性癫痫提供更多的药物选择,从而更好地为临床上合理化用药提供依据。[国际神经病学神经外科学杂志,2023,50(4):85-89]     

局灶性皮质发育不良与难治性癫痫

局灶性皮质发育不良是难治性癫痫的重要病因,近年来,随着影像学和脑电生理学的发展,分子生物学和病理生理学在癫痫发病机制研究中的应用,人们对局灶性皮质发育不良的遗传和病理生理学特点的认识产生了浓厚的兴趣.本文对大脑皮质的发育过程、局灶性皮质发育不良的发病及致痫机制分类及影像学的特征、手术治疗进行综述.     

局灶性脑皮层发育不良致顽固性癫痫的外科治疗

目的总结局灶性脑皮层发育不良致顽固性癫痫的诊断、手术治疗方案及效果。方法选取28例局灶性脑皮层发育不良致顽固性癫痫患者,MRI、脑电图（EEG）及正电子发射断层成像（PET）提示癫痫病灶位于发育不良区域,在皮层脑电图监测下切除病灶并进行病理学检查,患者继续服药并随访1年以上。结果局灶性脑皮层发育不良区存在不同程度神经细胞缺失和胶质细胞增生。患者1年预后按Engel标准分级：Ⅰ级12例,Ⅱ级9例,Ⅲ级4例,Ⅳ级3例。结论局灶性脑皮层发育不良区的神经细胞减少和少枝/小胶质细胞增生可能是引起癫痫发作的病理学基础。建议在术中脑电图监测下进行癫痫灶切除术和软膜下横切术,术后1年内75%患者控制良好。     

局灶性皮质发育不良继发难治性癫痫的外科治疗进展

局灶性皮质发育不良(Focal Cortical Dysplasias,FCDs)是一种先天性皮质发育不良,也是儿童和成人难治性癫痫的一种常见病因。随着结构及功能神经影像学技术的发展,该类癫痫发作逐渐被证实为难治性癫痫患者需行手术治疗的重要原因之一。各种具有特征性表现的FCDs的病理分型可以帮助我们对其作为癫痫病因的理解。而对FCDs及相关的癫痫起源灶的全切除可以为绝大多数癫痫患者带来理想的治疗效果。     

局灶性癫痫与非酮性高血糖症

早在1965年Maccario等就强调局灶性癫痫可能是非酮性高血糖症的症状之一，但这并未引起临床医生对本病的重视。本文报告2例非酮性高血糖症并发局灶性癫痫的病倒，其癫痫发作与高血糖症相关，单纯的抗癫痫药物治疗无效，某些药物甚至可能有害，只在血糖降至正常或接近正常时癫痫发作才能得以控制，非酮性高血糖症所致的局灶性癫痫发作可能是一种特殊的神经内分泌综合征。     

伴全面放电的局灶性癫痫的临床特征及手术治疗

目的 探讨伴有全面性发作间期癫痫样放电（GIEDs）的局灶性癫痫患者的临床特征及手术疗效。方法 回顾性分析2011年1月至2014年6月收治的733例MRI显示有局部异常的癫痫患者的临床资料,发作间期出现全导联同步异常放电（包括同时有局灶性异常放电形式）60例（伴GIEDs组）,673例没有这种表现（不伴GIEDs组）。伴GIEDs组中,19例采用手术治疗。结果 伴GIEDs组起病年龄≤12岁比例（80.0%,48/60）明显高于不伴GIEDs组（46.2%,311/673;PPP<0.05）。19例手术治疗患者术后随访1年以上,无明显永久的神经功能损伤,发作控制效果按engel分级:ⅰ级13例,ⅱ级2例,ⅲ~ⅳ级4例。>结论 局灶性癫痫患者可伴有GIEDs,手术治疗或可为该类患者提供一定的获益。     

家族性局灶性癫痫伴可变灶1型一例并文献复习

<正>家族性局灶性癫痫伴可变灶1型(Familial focal epilepsy with variable foci,FFEVF)是一种较为罕见且发生率不明确的常染色体疾病,以临床表现复杂、不同家族成员可在不同皮质区发生局灶性癫痫、发作严重程度表现不一为特征,常见的基因变异为DEPDC5(Dishevelled.EGI,-10 and Pleck Strin Domain Containing 5)基因^[1]。目前关于FFEVF治疗还是以药物治疗为主,对于存在明确致痫灶的患者可考虑手术治疗,国内外关于钠通道阻滞剂治疗DEPDC5基因变异相关家族性局灶性癫痫伴可变灶的报道比较少。本文将介绍一例拉考沙胺添加治疗DEPDC5基因变异相关家族性局灶性癫痫伴可变灶1型,以及文献复习以供临床医生参考。     

局灶性皮质发育不良相关癫痫的诊疗进展

局灶性皮质发育不良（FCD）是临床中常见的局灶性癫痫的病理类型之一,多数FCD患者在癫痫起病后即表现出耐药性,成为难治性癫痫。2011年国际抗癫痫联盟提出了新的FCD病理分型后,让大家对FCD有了更进一步的认识。近几年随着医学检测技术、病理研究及神经影像技术的发展,针对不同病理亚型的研究使得临床医生对FCD致病机制及治疗措施的决策有了新的理解。该文综合近年相关文献,对FCD不同亚型临床特点、治疗方法及相关预后作一综述,以期为临床决策提供帮助。     

局灶性癫痫患者认知障碍的相关性分析

目的 通过神经心理评估探究局灶性癫痫患者可能产生认知障碍的相关因素.方法 收集2016年3月-2020年1月于天津医科大学总医院门诊及住院的癫痫病患者53例,其中男25例,女28例,平均年龄(23.58±13.24)岁,平均病程(6.49±7.39)年,均符合2017年国际抗癫痫联盟(ILEA)局灶性癫痫的诊断标准,无...     

拉考沙胺治疗44例局灶性癫痫的疗效分析

目的 观察拉考沙胺(lakosamine,LCM)治疗局灶性癫痫患者的临床疗效.方法 收集2019年3月-2020年7月昆明三博脑科医院和昆明医科大学第一附属医院服用拉考沙胺治疗局灶性癫痫患者53例,最终纳入44例,服用拉考沙胺时间超过6个月.2021年2月对44例患者发作情况及耐受性进行随访并分析.结果添加LCM药物...     

立体定向放射外科治疗功能区顽固性癫痫

目的　探讨脑重要功能区局部致痫灶顽固性癫痫的立体定向放射外科治疗新方法 ,提高手术疗效。方法　 1999年 12月～ 2 0 0 1年 2月 ,对 30例 (男 18例 ,女 12例 ,平均年龄 2 3.1岁 )顽固性癫痫病人术前借助EEG ,MRI和PET联合定位 ,致痫灶均位于脑重要功能区 ,并采用PET辅助引导、BrainScanX刀治疗系统以致痫灶为靶区进行立体定向放射外科治疗 ,周边剂量 9～ 11Gy。所有病人随访 12～ 2 4个月 ,定期比较治疗前后的EEG结果并观察疗效。结果　治疗组X刀治疗后 3月、6月、12月、2 4月复查EEG明显改善或正常 ,同时发作频率明显下降。按国际抗痫联盟Wieser外科手术疗效分类法进行疗效判定 ,1～ 2级 6 0 % ,3～ 4级 2 3.3% ,5～ 6级 16 .7%。结论　探讨了立体定向放射外科治疗功能区顽固性癫痫的方法和机理 ,并与多处软脑膜下横切术作比较后 ,提出这一治疗是脑重要功能区顽固性癫痫的有效的新方法     

Intraoperative ultrasound to define focal cortical dysplasia in epilepsy surgery

Focal cortical dyplasia (FCD) is a frequent cause of medication-resistant focal epilepsy. Patients with FCD may benefit from epilepsy surgery. However, it is difficult to intraoperatively define lesion boundaries. In this case report we present a novel tool to identify FCD intraoperatively. A patient with frontal lobe epilepsy underwent resection of a left frontomesial FCD. Image guidance was achieved by intraoperative ultrasound, which depicted the lesion with a higher resolution than preoperative MRI. Postoperatively the patient remained seizure free. Intraoperative ultrasound may be helpful in identifying and targeting subtle epileptogenic lesions, which are difficult to visualize.     

A population-based study of long-term outcomes of cryptogenic focal epilepsy in childhood: cryptogenic epilepsy is probably not symptomatic epilepsy

Purpose: To compare long‐term outcome in a population‐based group of children with cryptogenic versus symptomatic focal epilepsy diagnosed from 1980 to 2004 and to define the course of epilepsy in the cryptogenic group. Methods: We identified all children residing in Olmsted County, MN, 1 month through 17 years, with newly diagnosed, nonidiopathic focal epilepsy from 1980 to 2004. Children with idiopathic partial epilepsy syndromes were excluded. Medical records were reviewed to determine etiology, results of imaging and EEG studies, treatments used, and long‐term outcome. Children were defined as having symptomatic epilepsy if they had a known genetic or structural/metabolic etiology, and as cryptogenic if they did not. Key Findings: Of 359 children with newly diagnosed epilepsy, 215 (60%) had nonidiopathic focal epilepsy. Of these, 206 (96%) were followed for >12 months. Ninety‐five children (46%) were classified as symptomatic. Median follow‐up from diagnosis was similar in both groups, being 157 months (25%, 75%: 89, 233) in the cryptogenic group versus 134 months (25%, 75%: 78, 220) in the symptomatic group (p = 0.26). Of 111 cryptogenic cases, 66% had normal cognition. Long‐term outcome was significantly better in those with cryptogenic versus symptomatic etiology (intractable epilepsy at last follow‐up, 7% vs. 40%, p < 0.001; seizure freedom at last follow‐up, 81% vs. 55%, p < 0.001). Of those who achieved seizure freedom at final follow‐up, 68% of the cryptogenic group versus only 46% of the symptomatic group were off antiepileptic medications (p = 0.01). One‐third of the cryptogenic group had a remarkably benign disorder, with no seizures seen after initiation of medication, or in those who were untreated, after the second afebrile seizure. A further 5% had seizures within the first year but remained seizure‐free thereafter. With the exception of perinatal complications, which predicted against seizure remission, no other factors were found to significantly predict outcome in the cryptogenic group. Significance: More than half of childhood nonidiopathic localization‐related epilepsy is cryptogenic. This group has a significantly better long‐term outcome than those with a symptomatic etiology, and should be distinguished from it.     

Safety of focused ultrasound neuromodulation in humans with temporal lobe epilepsy

ObjectiveTranscranial Focused Ultrasound (tFUS) is a promising new potential neuromodulation tool. However, the safety of tFUS neuromodulation has not yet been assessed adequately. Patients with refractory temporal lobe epilepsy electing to undergo an anterior temporal lobe resection present a unique opportunity to evaluate the safety and efficacy of tFUS neuromodulation. Histological changes in tissue after tFUS can be examined after surgical resection, while further potential safety concerns can be assessed using neuropsychological testing.MethodsNeuropsychological functions were assessed in eight patients before and after focused ultrasound sonication of the temporal lobe at intensities up to 5760 mW/cm². Using the BrainSonix Pulsar 1002, tFUS was delivered under MR guidance, using the Siemens Magnetom 3T Prisma scanner. Neuropsychological changes were assessed using various batteries. Histological changes were assessed using hematoxylin and eosin staining, among others.ResultsWith respect to safety, the histological analysis did not reveal any detectable damage to the tissue, except for one subject for whom the histology findings were inconclusive. In addition, neuropsychological testing did not show any statistically significant changes in any test, except for a slight decrease in performance on one of the tests after tFUS.SignificanceThis study supports the hypothesis that low-intensity Transcranial Focused Ultrasound (tFUS) used for neuromodulation of brain circuits at intensities up to 5760 mW/cm² may be safe for use in human research. However, due to methodological limitations in this study and inconclusive findings, more work is warranted to establish the safety. Future directions include greater number of sonications as well as longer exposure at higher intensity levels to further assess the safety of tFUS for modulation of neuronal circuits.     

EEG-fMRI in children with pharmacoresistant focal epilepsy

PURPOSE: To evaluate the usefulness of EEG-combined functional magnetic resonance imaging (EEG-fMRI) to localize epileptogenic sources. METHODS: Six children (age 8-15 years) with lesional or nonlesional pharmacoresistant focal epilepsy were studied. RESULTS: We found significant activations in four children, activation and deactivation in one child, and widespread deactivation in another. In four children, activations colocalized with the presumed location of the epileptic focus, one of which was confirmed by intracranial EEG. CONCLUSIONS: EEG-fMRI is a promising tool to noninvasively localize epileptogenic regions in children with pharmacoresistant focal epilepsy.     

A novel technique of detecting MRI‐negative lesion in focal symptomatic epilepsy: Intraoperative ShearWave Elastography

Focal symptomatic epilepsy is the most common form of epilepsy that can often be cured with surgery. A small proportion of patients with focal symptomatic epilepsy do not have identifiable lesions on magnetic resonance imaging (MRI). The most common pathology in this group is type II focal cortical dysplasia (FCD), which is a subtype of malformative brain lesion associated with medication‐resistant epilepsy. We present a patient with MRI‐negative focal symptomatic epilepsy who underwent invasive electrode recordings. At the time of surgery, a novel ultrasound‐based technique called ShearWave Elastography (SWE) was performed. A 0.5 cc lesion was demonstrated on SWE but was absent on B‐mode ultrasound and 3‐T MRI. Electroencephalography (EEG), positron emission tomography (PET), and magnetoencephalography (MEG) scans demonstrated an abnormality in the right frontal region. On the basis of this finding, a depth electrode was implanted into the lesion. Surgical resection and histology confirmed the lesion to be type IIb FCD. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .     

Epileptogenesis due to peripheral injury as a cause of focal epilepsy

PURPOSE: To report three patients in whom focal epilepsy developed shortly after painful soft tissue injuries to their hands. METHODS: Case reports. RESULTS: The attacks started in the injured hand. No evidence was found of an underlying brain lesion by history or from imaging studies. CONCLUSIONS: These cases suggest the possibility that the injuries led to a plastic change in the sensory/motor cortex, leading to increased excitability and ultimately to seizures. This suggests that epileptogenesis can occur in response to painful peripheral stimuli in some individuals.