Clinical application of spike averaging to dipole tracing method

Summary As part of our studies on localization of epileptic foci, dipole analysis using averaged spikes were compared with that using individual spikes for 25 patients with localization related epilepsy. Our results are as follows. 1) In the group which showed stable dipoles from individual spikes, dipole localization from averaged and individual spikes were similar, although the former showed a higher dipolarity and more stable location, for the entire spike discharge including the peak, trough and wave. The high dipolarity was due to improved signal to noise ratio obtained from averaging. 2) The cases with centrotemporal spike focus including benign childhood epilepsy with centrotemporal spikes showed more reliable dipoles. In the cases with frontal lobe epilepsy, reliable dipoles were rarely obtained even with averaged spikes. Each method provided independent information, so they are of complementary value.     

Dipole source analysis of rolandic spikes in benign rolandic epilepsy and other clinical syndromes

Summary Dipole source analysis of rolandic spike-and-wave complexes was performed in 48 children. The estimated source of the rolandic spike, of the trough between the spike and the following slow wave, and of the slow wave appeared to have the same position but had a small significant difference in orientation. Despite the heterogeneity of associated clinical syndromes, there were no clear differences between the clinical categories of patients regarding the localization and the orientation of the sources of the rolandic spike, trough and slow wave. The presence of a second source could explain the ascending phase of the rolandic spike in 19 children. This combination of two sources corresponded with the "double-spike phenomenon" that had been found previously by sequential brain mapping and which was associated with epilepsy. The preceding spike source and the source of the rolandic spike-and-wave complex were found to have the same position but a different orientation. A hypothetical explanation is proposed in which the presence of the rolandic spike-and-wave complex alone is insufficient to account for the clinical symptomatology. Both the preceding spike source and the source of the rolandic spike-and-wave complex, representing two separate, nearby but differently oriented populations of neurones in the inferior part of the rolandic cortex, is necessary for the development of epileptic manifestations.We like to thank the Netherlands Ophthalmic Research Institute (I.O.I) and B.W. van Dijk for the availability of and help with the TWDIP program.     

The Existence of Two Sources in Rolandic Epilepsy: Confirmation with High Resolution EEG, MEG and fMRI

In benign rolandic epilepsy seizure semiology suggests that the epileptic focus resides in the lower sensorimotor cortex. Previous studies involving dipole modeling based on 32 channel EEG have confirmed this localization. These studies have also suggested that two distinct dipole sources are required to adequately describe the typical interictal spikes. Since in benign epilepsy invasive validation is prohibited, this study tries to further establish these results using a multi-modal approach, involving 32 channel EEG, high resolution 84 channel EEG, 151 channel MEG and fMRI. From one patient interictal spikes were recorded and analyzed using the MUSIC algorithm in a realistic volume conductor model. In an fMRI experiment the same patient performed voluntary tongue movements, thus mimicking a typical seizure. Results show that EEG, MEG and fMRI localization converge on the same area in the lower part of the sensorimotor cortex, and that high resolution EEG clearly reveals two distinct sources, one in the post- and one in the pre-central cortex.     

Use of multiple dipole analysis for the classification of benign rolandic epilepsy

Summary The clinical literature has suggested that while the clinical features and presentation of benign rolandic epilepsy in children (BREC) are known, the neuronal mechanism of the epileptic focus is poorly understood. Classification of clinical subtypes is usually made by determining whether there are supplementary clinical signs of brain damage, in which case the epilepsy is classified as non-benign or "atypical". Studies of EEG findings in BREC have suggested that the source of the epilepsy is in the Rolandic fissure. We investigated dipole source modelling in 24 children, comparing the results of one and two dipole models. The results indicate that atypical BREC patients have a more complex distribution of dipoles and that single dipole fits may be more predictive of typical BREC than multiple dipole fits. The implications of these results are discussed.     

儿童失神癫痫240例治疗及预后随访报告：应用改良的1989年儿童失神癫诊断标准

目的总结儿童失神癫痫（CAE）的治疗和预后，为CAE的合理用药和评价远期预后提供依据。方法对1999年10月至2005年12月北京市3家医院为研究CAE易感基因收集的CAE患儿的治疗用药、疗效及预后进行随访。CAE诊断标准参考1989年国际抗癫痫联盟（ILAE）提出的癫痫及癫痫综合征分类诊断标准，并制定了统一的CAE纳入标准和排除标准。根据CAE的选药原则进行治疗，评估CAE患儿的远期预后。结果3家医院共收集符合ILAECAE诊断标准的患儿339例，其中296例符合本研究制定的CAE纳入标准。296例患儿中有56例患儿因失访未得到远期预后随访结果，有随访结果者240例（81．1％），其中男94例（39．2％），女146例（60．8％）。失神发作起病年龄为3岁3个月至12岁，其中4～8岁174例（72．5％）。39例（16．2％）有热性惊厥史，18例（7．5％）有热性惊厥家族史和（或）癫痫家族史，5例（2．1％）有失神癫痫家族史。失神癫痫发作频率为每日5～50次，其中每日发作10～30次占80％。出现失神持续状态1例。伴全面强直一阵挛发作12例（5．0％）。所有患儿发作期EEG均表现为双侧对称同步的3Hz棘慢波爆发，头颅影像学检查均未见异常。治疗首选丙戊酸234例，其中217例（92．7％）于服药后3d至6个月发作完全控制，15例加用另一种药物（其中氯硝西泮7例、硝西泮4例及拉莫三嗪4例）后发作控制，余2例单用丙戊酸2年后仍有发作，但发作次数明显减少；首选拉莫三嗪4例，其中3例发作控制，1例服药1年发作未控制，改用丙戊酸1周后发作控制。2例首选托吡酯治疗，其中1例发作控制，1例服药5个月效果不明显，改用丙戊酸2个月后发作控制。240例患儿随访时间为2～7年，158例（65．8％）已停用抗癫痫药物，其中停药1年以上者96例，停药后均无复发；82例尚未停用抗癫痫药物患儿中，80?     

BECT患儿录像脑电图表现和临床治疗的回顾性分析

目的：总结伴有中央颞区棘波的小儿良性癫痫（BECT）录像脑电图（视频脑电图,VEEG）和临床治疗的结果。方法：对139例BECT患儿的脑电图（EEG）表现和临床治疗进行回顾性分析。结果：本组发病年龄：2～12岁134例,占总数的96％,13～14岁5例,占总数的4％。只在睡眠中发作122例,清醒和睡眠均发作者15例,仅在白天觉醒时发作者2例。复杂部分性发作（CPS）34例,单纯部分性发作（SPS）34例,继发全身性发作（SGS）42例,全身强直阵挛发作（GTCS）1例,或兼有以上两种或两种以上发作类型合计22例,无法分类6例。剥夺睡眠后V-EEG描记发现：发作间期均有一侧或双侧中央颞区棘（尖）波。经过正规抗癫痫药物治疗2～5年后有69例临床完全不发作。结论：BECT临床发作和睡眠密切相关。发作间期EEG均有一侧或双侧中央和中颞区棘（尖）波。睡眠期EEG阳性率显著高于清醒期EEG。抗癫痫药物治疗反应良好,预后良好。     

Progressive myoclonus epilepsy: genetic and nosological aspects with special reference to 107 Finnish patients

In 107 Finnish patients with progressive myoclonus epilepsy (PME), belonging to 74 families, autosomal recessive inheritance was evident. The sex ratio was 48:51, the corrected proportion of affected sibs being 0.260. Of 68 marriages 15, or 22%, were consanguineous; several of the parents were related and the geographical distribution was of the uneven type typical of young, isolated populations in Finland. The incidence in Finland was estimated to exceed 1:20,000. The clinical picture in the Finnish PME patients was uniform, being identical with that of Unverricht's and Lundborg's patients, but clearly distinct from Lafora disease. The following classification of PME is proposed: (1) PME, Lafora type: onset of grand mal attacks and/or myoclonus around the 15th year of life; rapid and severe mental deterioration, often with psychotic symptoms; short survival; histological finding of Lafora bodies; autosomal recessive inheritance. (2) PME, Unverricht-Lundborg type: onset around the 10th year of life; severity variable, progressive invalidity from myoclonic features associated with mild mental symptoms, time of survival variable, "degenerative" histological changes; autosomal recessive inheritance. (3) Autosomal dominant or otherwise atypical cases of PME. The importance of accurate diagnosis is stressed.     

Clinical predictors of drug-resistant epilepsy in children

Background/aimIn up to 20% of epilepsy patients, seizures may not be controlled despite the use of antiepileptic drugs, either alone or in combination. These individuals are considered to have drug-resistant epilepsy. Drug-resistant epilepsy is usually associated with intellectual disability, psychiatric comorbidity, physical injury, sudden unexpected death, and low quality of life. Early detection and prediction of drug-resistant epilepsy are essential in determining the patient’s most appropriate treatment option. This retrospective study aimed to determine the clinical, electroencephalographic, and radiological factors associated with medically intractable childhood seizures.Materials and methods Data regarding 177 patients diagnosed with drug-resistant epilepsy were compared with 281 patients with drug-responsive epilepsy. Results Univariate analysis showed that age at seizure onset, having mixed seizure types, history of status epilepticus, history of neonatal seizures, history of both having febrile and afebrile seizures, daily seizures at the onset, abnormality on the first electroencephalogram, generalized epileptic abnormality on electroencephalogram, abnormal neurodevelopmental status, abnormal neuroimaging, and having symptomatic etiology were significant risk factors for the development of drug-resistant epilepsy (p < 0.05). In multivariable analysis, having mixed seizure types, history of status epilepticus, having multiple seizures in a day, intellectual disability, symptomatic etiology, and neuroimaging abnormality remained significant predictors for developing drug-resistant epilepsy.ConclusionsIn the course of childhood epilepsy, some clinical features may predict the outcome. Early identification of patients with high risk for drug-resistant epilepsy will help plan the appropriate treatment option. Further prospective studies should confirm these findings.     

儿童失神癫痫易感基因的研究

尽管近年来发现有少数非离子通道编码基因参与人类特发性癫痫（idiopathic eplepsies，IE），但更多的遗传学研究证实，离子通道在IE的遗传病理机制中起核心作用。离子通道基因突变是一些罕见类型的单基因遗传IE的常见病因，被称为通道病。但离子通道基因突变仅能解释IE的少数家系或散发病例，更大的难题来自于对复杂遗传IE的研究，它们未知的遗传模式、表型异质性和综合征亚型间不确定的遗传背景重叠限制了遗传图谱的绘制。失神癫痫是常见的IE亚型，呈复杂遗传方式。现共发现有11个基因与失神癫痫有关联，其中有4种编码神经元钙通道亚单位。因此钙通道基因是失神癫痫的重要候选基因。失神癫痫钙通道基因的遗传学研究可能是复杂遗传IE病因研究的最佳切入点，并有利于最终阐明失神癫痫的分子机制。     

Dipole Source Analysis May Differentiate Benign Focal Epilepsy of Childhood with Occipital Paroxysms from Symptomatic Occipital Lobe Epilepsy

The aim of the study was to distinguish Benign Focal Epilepsy of Childhood with Occipital Paroxysms (BEOP) from its symptomatic counterpart on the basis of the location of the sources of the interictal EEG spikes. Patients were classified into two groups: idiopathic BEOP and symptomatic occipital lobe epilepsy. Source analysis of the averaged occipital spikes was performed using a homogeneously conducting sphere as the volume conductor model. Results showed a statistically significant difference in the eccentricity, i.e., the distance of the occipital spike focus from the centre of the head. The dipole sources of the occipital spikes in the BEOP group were found to be located more superficially than in the symptomatic group, corresponding in six of the nine cases with a source position estimated to be within the cortical layer just below the skull. The eccentricity of the symptomatic occipital spikes suggests a location deeper than the cortical layer. The results were validated in two patients from the symptomatic group. In one patient the estimated deeper dipole source location corresponded with a deeper location of spike activity observed during ECoG; in the other patient's ECoG, spike activity was observed superficially but over an extended area. The discrepancy between estimated and real location may be explained by the method of dipole source analysis used. It is concluded that the finding of a superficial dipole source location of the occipital spikes provides an indication for the diagnosis BEOP (sensitivity: 67%; specificity: 74%).     

事件相关电位在检测失神癫(痫)儿童认知功能损伤中的应用

目的:应用事件相关电位(ERP) P300成分即P3波与神经心理学评分来研究失神发作患儿的认知功能并探讨其相关性.方法:选取确诊为失神发作的患儿22例,并设立正常对照组.应用ERP的P300检测,同时选用韦氏智力量表(C-WISC)测试对受试者言语智商(VIQ)和操作智商(PIQ)进行综合评估.通过统计学将病例组与对照组P300潜伏期、波幅及智商得分进行单因素方差分析,再将P300潜伏期、波幅与C-WISC各项测评分数进行相关性分析.结果:①失神发作患儿组P300潜伏期及波幅的均值明显长于对照组,其间差异有显著意义;②失神癫(痴)患儿组在C-WISC测试的各项得分均值均低于对照组,其间差异有显著意义;③P300潜伏期与VlQ、PIQ、总智商(FIQ)值呈负相关,而VlQ、PIQ、FIQ与P300波幅之间则不存在相关性.结论:①失神发作病例组的患儿P300各项参数均与同龄正常儿童存在差异,而且病例组患儿VIQ、PIQ及FIQ得分均低于同龄正常儿童,且存在显著差异;②失神癫(痫)伴认知损伤患儿ERP具有特征性,P300潜伏期明显长于同龄正常儿童,而P300波幅明显低于同龄正常儿童;③P300波幅与各智商(IQ)评分不存在相关性,P300潜伏期与IQ评分则呈负相关,IQ评分越高,其P300潜伏期越短.     

痫样放电偶极子对颞叶内侧型顽固性癫痫的定位价值

目的：探讨痫样放电偶极子分析结合临床特征和其它无创检查对颞叶内侧型顽固性癫痫的定位价值。方法：对21例发作间期主要在颞区存在痴样放电且每月致残性发作1次以上的顽固性癫痫患者,结合临床特征和其它无创检查确诊为颞叶内侧型癫病并定侧后,进行机器人辅助立体定向射频热凝毁损颞叶内侧结构治疗。结果：术后12～37个月,按照Engel分级系统：Ⅰ级6例（29％,其中Ⅰa级5例,Ⅰd级1例）,Ⅱb级3例（14％）,Ⅳa级4例（19％）,Ⅳb级7例（30％）,Ⅳc级1例（5％）。术后患者的神经功能均无明显下降。结论：机器人辅助立体定向系统射频热凝毁损术安全、有效、方便、快捷,部分颞叶内侧型顽固性癫痫患者对立体定向射频热凝治疗反应良好。     

伴有中央颞区棘波儿童良性癫(癎)的临床与EEG

目的:探讨伴中央-颢区棘波放电的儿童良性癫(癎)(BECT)的临床及脑电图(EEG)特征.方法:对46例BECT患儿的临床及EEG资料进行回顾性分析.结果:本组患儿发病年龄为2.5～12.5岁;31例(67%)的发作与睡眠密切相关,8例(17%)于睡眠和觉醒时均有发作,7例(15%)只在觉醒时发作;24例(52%)表现为部分性发作,13例(28%)为部分性发作继发全身性发作,9例(19%)表现为混合发作和不典型发作.发作间期EEG均有一侧或双侧中央和(或)中颢区尖波或棘波,清醒EEG阳性率为33%,睡眠EEG阳性率为85%.结论:BECT是与年龄相关的癫(癎)综合征,是一种预后较好的良性癫(癎),认识其临床和EEG演变的特点及规律,可提高对BECT的检出率.     

伴中央颞区棘波儿童良性癫癎脑电图分析

目的：分析伴中央颞区棘波儿童良性癫癎(BECT)患儿的脑电图表现。方法：对52例临床明确诊断的BECT患儿进行脑电图描记。结果：52例患者中,癫癎样波形出现在清醒描记时39例,出现在NREMⅠ—Ⅱ期13例。其中仅出现棘波者31例,尖波者16例,棘、尖波均出现者5例。癫癎样波形仅出现在中央和(或)颞区者43例,除见于中央、颞区外亦散在性出现于其他脑区者9例,其中双额区明显者1例,一侧枕区明显者1例。有2例在清醒描记时出现典型中央颞区棘波,过度换气时出现广泛性双侧同步性3～4 Hz棘慢波综合。结论：大多数BECT患儿有典型的特征性脑电图表现,但少数患儿可出现其它脑电图异常,应注意鉴别。     

头皮EEG偶极子定位在癫癎外科中的应用研究

目的：研究头皮EEG偶极子定位方法在癫痫手术病人中的应用价值及其准确性。方法：在80例难治性癫痫手术病人中．术前在发作间期头皮EEG上用偶极子定位方法定出致痫源放电位置．术中以皮质电图(ECoG)及脑深部电极记录确定致痫区．对比偶极子定位的准确性．按ECoG定出的位置直接对致痫区进行手术处理．术后随访手术效果。结果：在颞叶癫痫．偶极子定位与ECoG及脑深部电极定位完全一致；在额、顶、枕叶癫痫，偶极子位置误差为10～15mm。随访6～24个月(平均13个月)，80例中71％的病人无癫痫发作，25％的病人发作减少75％以上．手术有效率96%。结论：头皮EEG的偶极子定位方法无创、准确，相当于脑磁图，可避免创伤性检查而用于癫痫病人的术前定位。     

Ultrastructure of the spleens in childhood ITP with special reference to the foamy cells

We examined the spleens from four patients with childhood ITP. Numerous foamy cells were investigated in two cases, moderate number in one case, and a few in one case. PAP method using anti-human platelet antibody demonstrated the platelet antigen in the cytoplasms of these foamy cells, which were granular or reticular. Electron microscopically, many platelets in various stages of intracellular digestion from intact-appearing forms to myelin-like materials, were disclosed. Enzyme cytochemical electron microscopy revealed localization of acid phosphatase activity around the degrading platelets and vacuolated inclusions, but rarely in the myelin-like materials. We suggest that the mechanism of formation of the foamy cells in ITP is as follows; macrophages phagocytize many platelets, exhaust their lysosomal enzyme, and can not digest the engulfed platelets completely. Thus the partially degraded platelets remain as myelin-like materials in the cytoplasm of macrophages, which have foamy appearance in light microscopy.     

Localization of epileptic foci in Children with childhood absence epilepsy by magnetoencephalography combined with synthetic aperture magnetometry

This present study was aimed to investigate the localizable diagnostic value of magnetoencephalography (MEG) combined with synthetic aperture magnetometry (SAM) in childhood absence epilepsy (CAE).Thirteen CAE patients underwent MEG detection at resting state and after hyperventilation,and then the epileptic foci were located by SAM.In the thirteen CAE patients,epileptic foci were found in five cases (38.5%),and they were all located in the bilateral frontal lobe,suggesting that the frontal lobe in some CAE patients may serve as the epileptic foci.Our findings indicate that MEG combined with SAM could be of diagnostic value in localizing the epileptic foci in certain CAE patients.     

儿童失神性癫痫EEG放电昼夜规律的探讨

对３例原发性失神性癫痫患儿进行２４ｈ痫样放电的定量分析。结果表明，非快速眼动（ＮＲＥＭ）睡眠期痫样放电频度较醒觉期显著增多，而每次放电持续时间显著缩短，放电失去全导同步３Ｈｚ节律性爆发的特征，表现为不规则棘慢波、多棘慢波以杂乱无序的形式出现，以前头部为主，多种放电现象可出现于同一患儿的同一睡眠相。提示儿童原发性失神性癫痫可能系皮层多位点起源，并受到丘脑等皮层下结构的调控。其脑电的去同步化可能对皮层的放电有抑制作用。ＮＲＥＭ睡眠期可能在皮层水平触发多处放电。临床上，２４ｈＥＥＧ监测可定量检出临床发作及放电频率，正确判断睡眠中的异常放电，确定抗癫痫药物的治疗效果。     

Ultrastructural abnormalities and perifascicular atrophy in childhood dermatomyositis with special reference to transverse tubular system-sarcoplasmic reticulum junctions

Comparison of ultrastructural abnormalities between perifascicular and centrofascicular myofibers was made in the same muscle fascicles from six patients with childhood dermatomyositis. Consistent abnormalities are seen at the junctional sites between the transverse tubular system (TS) and sarcoplasmic reticulum (SR) as visualized by lanthanum staining. Early conical dilations at the TS-SR junctions have progressed to become connected with large cylindrical or spheroid channels representing SR. These TS-SR anastomoses are far more extensive in the perifascicular than in the centrofascicular myofibers. Honeycomb TS proliferations suggestive of a repair process occasionally occur at the sites of TS-SR anastomoses. These alterations precede myofibrillar derangements and they may be related to the primary pathogenetic process involved in dermatomyositis. It is postulated that leakage of degraded structural protein molecules through TS-SR anastomoses may lead to the perifascicular atrophy seen on light microscopy.