Intra-operative cortical motor mapping using subdural grid electrodes in children undergoing epilepsy surgery evaluation and comparison with the conventional extra-operative motor mapping

Objectives

The objective of this study was to review our experience with intra-operative “train of five” stimulation using subdural grid for motor mapping in children undergoing epilepsy surgery evaluation.

Investigation of subdural electrode displacement in invasive epilepsy surgery workup using neuronavigation and intraoperative MRI

Objectives: One of the main obstacles of electrode implantation in epilepsy surgery is the electrode shift between implantation and the day of explantation. We evaluated this possible electrode displacement using intraoperative MRI (iopMRI) data and CT/MRI reconstruction.

Methods: Thirteen patients (nine female, four male, median age 26 ± 9.4 years) suffering from drug-resistant epilepsy were examined. After implantation, the position of subdural electrodes was evaluated by 3.0 T-MRI and thin-slice CCT for 3D reconstruction. Localization of electrodes was performed with the volume-rendering technique. Post-implantation and pre-explantation 1.5 T-iopMRI scans were coregistered with the 3D reconstructions to determine the extent of electrode dislocation.

Results: Intraoperative MRI at the time of explantation revealed a relevant electrode shift in one patient (8%) of 10 mm. Median electrode displacement was 1.7 ± 2.6 mm with a coregistration error of 1.9 ± 0.7 mm. The median accuracy of the neuronavigation system was 2.2 ± 0.9 mm. Six of twelve patients undergoing resective surgery were seizure free (Engel class 1A, median follow-up 37.5 ± 11.8 months).

Conclusion: Comparison of pre-explantation and post-implantation iopMRI scans with CT/MRI data using the volume-rendering technique resulted in an accurate placement of electrodes. In one patient with a considerable electrode dislocation, the surgical approach and extent was changed due to the detected electrode shift.

Abbreviations: ECoG: electrocorticography; EZ: epileptogenic zone; iEEG: invasive EEG; iopMRI: intraoperative MRI; MEG: magnetoencephalography; PET: positron emission tomography; SPECT: single photon emission computed tomography; 3D: three-dimensional.     

Outcome and complications of chronically implanted subdural electrodes for the treatment of medically resistant epilepsy

Background

Surgery for medically resistant epilepsy is safe and effective. However, when noninvasive techniques are insufficient, then consideration is given to invasive electrocorticography (EcoG).

Objective

The aim of the study was to analyze results and complications of subdural electrodes placement in the treatment of intractable epilepsy.

Methods

Ninety-one consecutive patients who underwent placement of subdural electrodes (1999-2010) were considered for this study. All patients underwent a standardized pre-operative evaluation. Invasive subdural electrode placement was considered when there were inadequate ictal recordings, there was discordance between EEG and neuroimaging or the epileptogenic zone was localized near eloquent cortex.

Results

Resective epilepsy surgery was performed in 70/91 patients (76.9%). Twenty-four out of seventy (34.3%) who underwent surgical resection were seizure-free (CL-I) at last follow-up. A statistical evaluation revealed a very strong trend for patients with positive lesional pre-operative MRI to have improved outcomes compared to normal brain MRI population (p = .028). There were 10 surgical related complications (11%), but no mortality or permanent morbidity. Statistical analysis demonstrated that placement of a subdural grid in any combination was statistically significant (p = .01) for surgical complications.

Conclusions

Invasive monitoring is a useful and necessary technique for the surgical treatment of intractable epilepsy. Careful surveillance is required during the monitoring period especially when the patient has undergone large subdural grid placement. A good working hypothesis can minimize complications and achieve better outcomes.     

Risks and benefits of invasive epilepsy surgery workup with implanted subdural and depth electrodes

Purpose: In patients with pharmacoresistant focal‐onset seizures, invasive presurgical workup can identify epilepsy surgery options when noninvasive workup has failed. Yet, the potential benefit must be balanced with procedure‐related risks. This study examines risks associated with the implantation of subdural strip and grid, and intracerebral depth electrodes. Benefit of invasive monitoring is measured by seizure outcomes. Diagnostic procedures made possible by electrode implantation are described. Methods: Retrospective evaluation of invasive workups in 242 epilepsy surgery candidates and additional 18 patients with primary brain tumors implanted for mapping only. Complications are scaled in five grades of severity. A regression analysis identifies risk factors for complications. Outcome is classified according to Engel’s classification. Key Findings: Complications of any type were documented in 23% of patients, and complications requiring surgical revision in 9%. We did not find permanent morbidity or mortality. Major risk factor for complications was the implantation of grids and the implantation of electrode assemblies comprising strip and grid electrodes. Depth electrodes were significantly correlated with a lower risk. Tumors were not correlated with higher complication rates. Chronic invasive monitoring of 3–40 days allowed seizure detection in 99.2% of patients with epilepsy and additional extensive mapping procedures. Patients with epilepsy with follow‐up >24 months (n = 165) had an Engel class 1a outcome in 49.7% if epilepsy surgery was performed, but only 6.3% when surgery was rejected. Significance: The benefit of chronic invasive workup outweighs its risks, but complexity of implantations should be kept to a minimum.     

迷走神经刺激术治疗药物难治性癫痫的价值

尽管目前癫痫的药物治疗已取得较大进展,但仍有20％～30％的患者对癫痫药物治疗反应差,部分癫痫发作难以有效控制,即所谓的药物难治性癫痫。癫痫病灶切除术是治疗药物难治性癫痫的有效方法,但并非所有患者均能找到确切病灶,而且部分患者手术后效果不佳。1988年,迷走神经刺激术(vagus nerve stimulation,VNS)开始应用于治疗药物难治性部分性癫痫,为药物难治性癫痫提供了一种新的治疗方法。     

难治性癫痫侵袭性评估中颅内皮层电极的应用与并发症分析

目的探讨在难治性癫痫术前评估中颅内皮层电极埋藏的方法与安全性。方法回顾性分析湘雅医院功能神经外科2014年4月～2017年6月开展的65例颅内皮层电极埋置患者的临床资料,总结颅内皮层电极埋置在癫痫术前评估中的经验。结果 65例患者均采用开颅埋置皮层片状电极,其中38例辅助埋置深部电极。患者术后平均监测时间为10. 8天(2～28天)。术后颅内血肿8例,其中硬膜外血肿4例,硬膜下血肿4例,有3例患者因硬膜外血肿行手术清除血肿,术后伤口脑脊液漏12例,术后颅内感染3例,均为并发脑脊液漏患者,脑水肿1例,电极脱出1例。无因并发症放弃监测病例,无埋置手术长期并发症及神经功能受损病例。结论颅内皮层电极埋置在癫痫外科中是一项重要的安全有效的侵袭性术前评估方法,术后出血及感染是主要的并发症,适当的术中、术后处理将有助于避免相关并发症。     

伴顽固性癫痫的脑肿瘤的病理分析

目的 分析伴顽固性癫痫患者的脑肿瘤病理特点,探讨最适合的手术方式.方法 在符合顽固性癫痫并进行手术治疗的病例中,回顾分析45例病理证实存在脑肿瘤的病例资料.结果 癫痫灶位于额叶8例,颞叶34例,顶枕叶3例;病理证实神经元和混合性神经元-胶质肿瘤35例(78%).WHO Ⅰ级36例,WHO Ⅰ～Ⅱ4例,WHO Ⅱ级5例.术后随访1年以上的42例,全部生存.癫痫发作控制结果 显示Engel Ⅰ级32例(76%),Ⅱ级5例,Ⅲ级4例,Ⅳ级1例.结论 与顽固性癫痫相关的脑肿瘤是一类特殊的病理组群,手术切除包括肿瘤在内的癫痫灶,效果满意.     

The combination of subdural and depth electrodes for intracranial EEG investigation of suspected insular (perisylvian) epilepsy

Purpose: We present two methods of implantation for the investigation of suspected insular and perisylvian epilepsy that combine depth and subdural electrodes to capitalize on the advantages of each technique. Methods: Retrospective study of all intracranial EEG studies that included insular electrodes from 2004–2010. Patients were divided according to the implantation scheme. The first method (type 1) consisted of a craniotomy, insertion of insular electrodes after microdissection of the sylvian fissure, orthogonal implantation of mesiotemporal structures with neuronavigation, and coverage of the adjacent lobes with subdural electrodes. The second method (type 2) consisted of magnetic resonance imaging (MRI)–stereotactic frame‐guided depth electrode implantation into insula and hippocampus using sagittal axes, and insertion of subdural electrodes through burr holes to cover the adjacent lobes. The combined implantations were developed and performed by one neurosurgeon (AB). Key Findings: Nineteen patients had an intracranial study that sampled the insula, among other regions. Sixteen patients were implanted using the first method, which allowed a mean of 4, 5, 20, 15, and 42 contacts per patient to be positioned into/over the insular, mesial temporal, neocortical temporal, parietal, and frontal areas, respectively. The second method (three patients) allowed a mean of 8, 7, 16, 6, and 9 contacts per patient to sample the same areas, respectively. The four patients in whom transient neurologic deficits occurred were investigated with use of type 1 implantation. Significance: Combined depth and subdural electrodes can be used safely to investigate complex insular/perisylvian refractory epilepsy. Choice of implantation scheme should be individualized according to presurgical data and the need for functional localization.     

脑皮层电刺激对功能区和癫痫发作起始区的确定作用

目的评估皮层电刺激功能区的确定的可靠性和对癫痫发作起始区的辅助定位作用。方法19名患者,在最怀疑的区域进行颅内电极置入,条状电极和格子电极均采用。颅内电极置入后,手术后关闭手术切口,患者返回脑电监测室进行1~2周的长程视频颅内脑电监测,期间对患者的发作间期和发作期脑电图进行分析和进行脑皮层电刺激功能区测定。皮层电刺激方式本临床实验采用的脑皮层电刺激参数是50Hz,0.2ms电脉冲刺激。结果脑皮层功能区测定19例患者中,发作起源区与重要的皮质功能区(运动、感觉、语言、视觉)范围紧邻或有重叠的有7例。脑皮层电刺激癫痫发作诱发19名患者中,18名患者人为通过颅内电极电刺激诱发出患者的发作先兆或发作,诱发脑皮质位置均包含皮层脑电记录所确定的癫痫发作起始区,电刺激诱发先兆或发作的可重复率为94.7%。手术并发症1例患者发生永久性局限视野缺损(术后7个月复查仍未改善),缺损为左上视野区;1例患者电极埋藏术后出现一过性失语,2天后该症状缓解,切除术后未发生失语;1例患者术后3天内反应时有“星星闪光”样视幻觉,后未经特殊处理,自愈。所有其他患者经过检查,术后无神经功能和神经心理损害发生。结论皮层电刺激确定的神经功能区可靠性好,是避免手术并发症的保证,同时电刺激对癫痫发作起始区的确定有良好的辅助作用。     

The localizing value of auditory event-related potentials (P300) in patients with medically intractable temporal lobe epilepsy

The localizing value of postictal versus interictal event-related potentials (ERPs) was studied in patients with medically intractable TLE admitted for long-term video EEG monitoring. Ten patients with partial seizures and secondary generalization underwent preictal (upon hospital admission), postictal (6 h after seizure), and interictal (7–48 h after seizure) ERP recordings of an auditory oddball paradigm. Preictal ERPs were compared to postictal and interictal recordings. Intraclass correlations, transformed into z scores, were utilized to analyze amplitude differences between electrodes placed on the hemisphere ipsilateral versus contralateral to the epileptogenic focus. The results showed that in 9 out of 10 patients the ERP amplitude was reduced in postictal compared to preictal recordings for electrodes placed ipsilateral to the epileptogenic focus (P<0.0001). However, there was no difference in amplitude between ipsilateral and contralateral electrodes in preictal and interictal recordings. These findings suggest that postictal ERPs are of localizing value in patients with TLE while interictal ERPs are not.     

凋亡抑制蛋白XIAP在难治性癫痫大鼠脑内的表达

目的研究杏仁核电刺激点燃的难治性癫痫大鼠脑内凋亡抑制蛋白XIAP表达的情况。方法建立杏仁核电刺激点燃的难治性癫痫大鼠模型,通过药物筛选用出耐药大鼠和药物敏感大鼠,采用免疫组织化学及western blot的方法,分析比较凋亡抑制蛋白XIAP在耐药组与药物敏感组的表达。结果难治性癫痫大鼠脑内XIAP的表达明显高于药物敏感组。结论癫痫大鼠脑内凋亡抑制蛋白XIAP可能参与了难治性癫痫的耐药机制。     

Glial and neuronoglial malformative lesions associated with medically intractable epilepsy

In a large series of 116 cortical resections for treatment of medically intractable epilepsy, 10 glial hamartomas and 11 neuronoglial malformative lesions were found. Glial hamartomas were astrocytic in 3 cases, oligodendrocytic in 6 and mixed oligoastrocytic in 1. Neuronoglial lesions corresponded to focal cortical dysplasia in 6 patients and to microdysgenesis in 5 others. This study focuses on the various neuropathological presentations of these malformative epileptogenic lesions, and on correlations with neuro-imaging data.     

89例动态脑电图监测对诊断癫（癎）的意义

目的探讨动态脑电图(ambulatory electroencephalogram,AEEG)对癫鉴别诊断的意义。方法对89例临床可疑癫病人进行动态脑电图监测,并对监测结果分析。结果AEEG检查发现有样放电者69例,占77.5%,其中27例(30.3%)有临床发作,42例(47.2%)仅在AEEG检查发现样放电,20例(22.5%)排除癫。结论AEEG对癫的鉴别诊断具有重要作用。     

Potential role of drug transporters in the pathogenesis of medically intractable epilepsy

Summary:  The pathogenesis underlying pharmacoresistance in epilepsy is unclear. One of the candidate mechanisms that has attracted growing interest is the limitation of antiepileptic drug (AED) access to the seizure focus by a range of efflux transporters, the prototype of which is P-glycoprotein (P-gp). P-gp is encoded by the multidrug resistance ( MDR1 or ABCB1 ) gene. Predominantly expressed in organs with excretory functions and at blood–tissue barriers, P-gp is thought to act as a physiologic defense by extruding xenobiotics from mammalian cells and affording protection of sensitive organs. The high level of P-gp in the cerebrovascular endothelium is believed to contribute to the functionality of the blood–brain barrier. Overexpression of P-gp causes multidrug resistance in certain cancers. It has been hypothesized that overexpression of P-gp and other efflux transporters in the cerebrovascular endothelium, in the region of the epileptic focus, also may lead to drug resistance in epilepsy. This hypothesis is supported by the findings of elevated expression of efflux transporters in epileptic foci in patients with drug-resistant epilepsy, induction of expression by seizures in animal models, and experimental evidence that some commonly used AEDs are substrates. Conflicting reports suggest a possible association between variants of the MDR1 gene and medical intractability in epilepsy. Further studies to delineate the exact role, if any, of P-gp and other efflux transporters in drug-resistant epilepsy are warranted.     

药物难治性癫痫大鼠脑内Bax和Bcl-2表达的研究

目的研究杏仁核电刺激点燃的药物难治性癫痫大鼠脑内凋亡相关蛋白Bax和Bcl-2表达的情况。方法建立杏仁核电刺激点燃的难治性癫痫大鼠模型,通过药物筛选用出耐药大鼠和药物敏感大鼠,采用免疫组织化学及免疫蛋白印记（western blot）的方法,分析比较Bax和Bcl-2在耐药组与药物敏感组的表达。结果药物难治性癫痫大鼠组脑内Bax蛋白的表达显著高于药物敏感组（P〈0.01）,而Bcl-2蛋白的表达显著低于药物敏感组（P〈0.01）。结论癫痫大鼠脑内凋亡相关蛋白可能参与了难治性癫痫的耐药机制。     

难治性颞叶癫痫患者脑组织中Vav3的表达

目的研究难治性颞叶癫痫患者脑组织中Vav3的表达,探讨其在难治性颞叶癫痫形成中的意义。方法应用免疫组织化学法检测难治性颞叶癫痫患者脑组织和正常脑组织中Vav3蛋白的表达。光学显微镜下观察Vav3蛋白表达结果,并对免疫组织化学结果进行分析。结果免疫组化检测发现Vav3蛋白在难治性颞叶癫痫患者脑组织中阳性表达率明显高于正常脑组织,两组相比差异具有统计学意义（x^2=15．841,P〈0．015。实验组患者海马组中Vav3染色评分2分和3分占总体的76．93％（10／13）,而在颞叶组中Vav3染色评分1分和2分占总体的64．71％（11／17）,可见在难治性颞叶癫痫患者海马组织较颞叶组织神经元中Vav3的表达明显增强。结论Vav3在难治性颞叶癫痫患者的海马和颞叶脑组织中表达增强,提示其有可能参与了难治性颞叶癫痫的形成。     

Interictal PET and ictal subtraction SPECT: Sensitivity in the detection of seizure foci in patients with medically intractable epilepsy

Purpose: Interictal positron emission tomography (PET) and ictal subtraction single photon emission computed tomography (SPECT) of the brain have been shown to be valuable tests in the presurgical evaluation of epilepsy. To determine the relative utility of these methods in the localization of seizure foci, we compared interictal PET and ictal subtraction SPECT to subdural and depth electrode recordings in patients with medically intractable epilepsy. Methods: Between 2003 and 2009, clinical information on all patients at our institution undergoing intracranial electroencephalography (EEG) monitoring was charted in a prospectively recorded database. Patients who underwent preoperative interictal PET and ictal subtraction SPECT were selected from this database. Patient characteristics and the findings on preoperative interictal PET and ictal subtraction SPECT were analyzed. Sensitivity of detection of seizure foci for each modality, as compared to intracranial EEG monitoring, was calculated. Key Findings: Fifty‐three patients underwent intracranial EEG monitoring with preoperative interictal PET and ictal subtraction SPECT scans. The average patient age was 32.7 years (median 32 years, range 1–60 years). Twenty‐seven patients had findings of reduced metabolism on interictal PET scan, whereas all 53 patients studied demonstrated a region of relative hyperperfusion on ictal subtraction SPECT suggestive of an epileptogenic zone. Intracranial EEG monitoring identified a single seizure focus in 45 patients, with 39 eventually undergoing resective surgery. Of the 45 patients in whom a seizure focus was localized, PET scan identified the same region in 25 cases (56% sensitivity) and SPECT in 39 cases (87% sensitivity). Intracranial EEG was concordant with at least one study in 41 cases (91%) and both studies in 23 cases (51%). In 16 (80%) of 20 cases where PET did not correlate with intracranial EEG, the SPECT study was concordant. Conversely, PET and intracranial EEG were concordant in two (33%) of the six cases where the SPECT did not demonstrate the seizure focus outlined by intracranial EEG. Thirty‐three patients had surgical resection and >2 years of follow‐up, and 21 of these (64%) had Engel class 1 outcome. No significant effect of imaging concordance on seizure outcome was seen. Significance: Interictal PET and ictal subtraction SPECT studies can provide important information in the preoperative evaluation of medically intractable epilepsy. Of the two studies, ictal subtraction SPECT appears to be the more sensitive. When both studies are used together, however, they can provide complementary information.