儿童良性癫痫伴中央颞区棘波患者的认知损害研究

目的探讨儿童良性癫痫伴中央颞区棘波(Benign epilepsy of childhood with centrotemporal spikes,BECTS)患者的认知损害特点。方法纳入2010年9月-2019年12月于首都医科大学宣武医院神经内科就诊的BECTS患者61例(BECTS组)。选取60名年龄、性别和教育程度相匹配的健康儿童和青少年作为对照组。对BECTS组及对照组进行神经心理学任务测试以评估其注意力、记忆力、计算力、语言功能、执行能力、视空间功能、视知觉及反应能力等多项认知功能。应用SPSS 20.0统计软件,对两组的认知任务测试得分进行独立样本t检验和秩和检验,对影响认知功能损害的各项临床因素进行多元线性回归分析。结果与对照组相比,BECTS组患者的配对联结学习平均(19.56±2.91)分,词语辨析测验的平均(23.67±9.50)分,物体数量认知的平均(61.45±13.14)分,言语工作记忆的平均(6.54±1.47)分,声音知觉测验的平均(5.79±5.90)分,Taylor复杂图形测验的平均(35.10±2.33)分,选择反应时的平均(700.34±493.05)分,均显著低于对照组(P<0.05)。在BECTS组中有36例起病<8岁,与起病≥8岁组相比,前者在视觉追踪任务、空间记忆任务、简单减法任务、数字数量大小比较、汉字押韵测试、词语辨析测试和视觉感知任务等大部分神经心理测试中得分均较低(P<0.05);34例接受单药治疗,27例接受两种及以上抗癫痫药物治疗,多药治疗组在注意力、记忆力、视知觉、反应力等方面均低于单药治疗组(P<0.05)。结论 BECTS患者存在注意力、记忆力、视知觉、声音知觉及反应速度的损害。起病年龄越小其认知损害的程度越重;多药治疗患者的认知损害程度较单药治疗重。     

EEG characteristics related to educational impairments in children with benign childhood epilepsy with centrotemporal spikes

PURPOSE: Learning and behavioral difficulties often occur in benign childhood epilepsy with centrotemporal spikes (BCECTS). In recent years, several electroencephalogram (EEG) characteristics have been related to the occurrence of learning and behavioral problems. METHODS: From 28 children medical, school and psychological reports were present and children were rated according to a 4-point scale for educational and behavioral impairment (Part 1). Thirty 24-h EEG recordings were reanalyzed for spike frequency, the presence of atypical EEG criteria, and the presence of a nondipole spike. EEGs were scored during wakefulness, first hour of sleep and whole night sleep (minus the first hour of sleep) separately (Part 2). RESULTS: The presence of I: an intermittent slow-wave focus during wakefulness, II: a high number of spikes in the first hour of sleep (and during whole night sleep), and III: multiple asynchronous bilateral spike-wave foci in the first hour of sleep correlates significantly with a sum score > or = 3 which indicates a complicated course with educational or behavioral impairment. It is sufficient to analyze an EEG during wakefulness and a sleep EEG for only the first hour of sleep instead of a whole night recording to demonstrate those EEG criteria. CONCLUSIONS: On basis of our reanalysis we can possibly conclude that the aforementioned EEG characteristics correlate with educational impairments, and that analysing an EEG recording during wake and the first hour of sleep is sufficient to look adequately for those EEG criteria in children with BCECTS.     

Distributed source localization of interictal spikes in benign childhood epilepsy with centrotemporal spikes: A standardized low-resolution brain electromagnetic tomography (sLORETA) study

Benign childhood epilepsy with centrotemporal spikes (BCECTS), also known as Rolandic epilepsy, is the most common benign childhood epilepsy. Centrotemporal spikes are characteristic findings on electroencephalography (EEG). Though the condition is considered benign, many studies have reported some degree of neuropsychological impairment in individuals with BCECTS. There is also growing evidence from neuroimaging studies that BCECTS may affect a larger portion of the brain than originally thought. We performed distributed source localization analysis of interictal spikes in BCECTS. Current-source density (CSD) of the maximal negative peak of the interictal spikes averaged from each of 20 EEG epochs in 11 patients with BCECTS was measured using standardized low-resolution brain electromagnetic tomography (sLORETA). Rolandic area was included in the distribution of the CSD in all of the patients. The significant CSD and its maximal point were distributed in multiple cortical regions over the Rolandic area. It is suggested that the widespread cortical distribution of interictal spikes seen in this study may be associated with atypical presentation and a variety of comorbidities of BCECTS. Our results imply that BCECTS represents a deviation from normal development during a critical period of brain maturation and that children with BECTS might be more likely to need special medical attention.     

The attention networks in benign epilepsy with centrotemporal spikes: A long-term follow-up study

PurposeTo evaluate the long-term prognosis of attention deficit in children with newly diagnosed benign childhood epilepsy with centrotemporal spikes (BECTS).MethodsAttention network test (ANT) was performed over a period of 7 years on 42 patients who were newly diagnosed with BECTS, in the Department of Neurology of Anhui Provincial Children's Hospital.ResultsIn the patients’ group, the accuracy of ANT was lower (P = 0.000), the total response time was longer (P = 0.000), and the efficiency of orienting (P = 0.000) and alerting (P = 0.041) networks was lower than that of the control group. Accuracy was positively correlated with age of onset (b = 1.184) and negatively correlated with number of seizures (b = −1.321). After 7 years, there was no significant difference in the accuracy (P = 0.385); total response time (P = 0.661); and alerting (P = 0.797), orienting (P = 0.709), and executive control (P = 0.806) network efficiencies between the patients and controls. Accuracy was positively correlated with age of onset (b = 0.8583) and negatively correlated with number of seizures (b = −1.017) and duration of antiepileptic drugs therapy (b = −3.203).ConclusionsIn our study, the newly diagnosed BECTS patients had impaired attention network, mainly in the alerting and orienting domains. Age of onset, number of seizures, and time of antiepileptic treatment may affect the attention networks. With the remission of BECTS, the attention network dysfunction was reversed.     

Benign epilepsy of childhood with centrotemporal spikes and unilateral developmental opercular dysplasia

The case of a 15-year-old right-handed girl with developmental delay, mild retardation, astereognosis, and tactile discrimination impairment in the left arm, is reported. During sleep, right partial simple motor seizures with sialorrhea and saliva pooling were present, sometimes followed by secondary generalization. Absences and drop attacks were also observed. Electroencephalography revealed left centrotemporal spike waves spreading to the homologous contralateral region, generalized 3-Hz spike-and-wave complexes enhanced by hyperventilation, and generalized polyspike-and-wave discharges during drowsiness. Magnetic resonance imaging showed right perisylvian (opercular) malformation. Benign epilepsy of childhood with centrotemporal spikes (BECCTS) is a focal idiopathic epilepsy presumed to be of genetic origin. Although brain damage is not expected, structural lesions including opercular macrogyria have been reported. This coexistence has been considered mainly casual and only exceptionally causal. The Foix-Chavany-Marie syndrome or operculum syndrome is the result of bilateral opercular damage. In our child the right structural and the left functional lesions appeared mutually activated, yielding a transient opercular syndrome. The concomitance of BECCTS and developmental opercular dysplasia is suggestive of a common genetic substratum.     

Striatal hypertrophy and its cognitive effects in new-onset benign epilepsy with centrotemporal spikes

Purpose: Benign epilepsy with centrotemporal spikes (BECTS), the most common childhood epilepsy syndrome, is a neurodevelopmental disorder with a genetic influence. Despite its signature electroencephalographic pattern and distinct focal motor seizure semiology, little is known about the underlying brain anatomic alteration and the corresponding cognitive consequences. Given the motor manifestations of seizures in BECTS, we hypothesize that anatomic networks in BECTS involve a distributed corticostriatal circuit. Methods: We investigated volumetric differences and shape deformities of caudate, putamen, pallidum, and thalamus in a group of children with new‐ and recent‐onset BECTS (N = 13) compared to healthy controls (N = 54). We correlated specific subcortical volumes in BECTS that were significantly different from those in healthy controls with performances in executive function. Key Findings: Children with BECTS demonstrated significantly hypertrophied putamen, which was selective among the subcortical regions examined. Shape analysis showed dorsoventral elongation of the left caudate and bilateral putamen, with subnuclei expansion in ventral and dorsal striatum. Larger putamen volumes were linked to better cognitive performances on two complementary executive function tests. Significance: Children with BECTS showed aberrant volume and shape in subcortical regions that are critical for both motor processing and executive function. It is of importance to note that the hypertrophy appears to be cognitively adaptive, as enlargement was associated with improved cognitive performances. The anatomic abnormalities and their cognitive effects are evident in a group of children with new‐ and recent‐onset epilepsy, suggesting that the structural brain anomalies occurred before the diagnosis of epilepsy.     

Interictal and ictal magnetoencephalographic study in patients with medial frontal lobe epilepsy

PURPOSE: To determine whether magnetoencephalography (MEG) has any clinical value for the analysis of seizure discharges in patients with medial frontal lobe epilepsy (FLE). METHODS: Four patients were studied with 74-channel MEG. Interictal and ictal electroencephalographic (EEG) and MEG recordings were obtained. The equivalent current dipoles (ECDs) of the MEG spikes were calculated. RESULTS: In two patients with postural seizures, interictal EEG spikes occurred at Cz or Fz. The ECDs of interictal MEG spikes were localized around the supplementary motor area. In the other two patients with focal motor or oculomotor seizures, interictal EEG spikes occurred at Fz or Cz. The ECDs of interictal MEG spikes were localized at the top of the medial frontal region. The ECDs detected at MEG ictal onset were also localized in the same area as those of the interictal discharges. CONCLUSIONS: In medial FLE patients, interictal and ictal MEG indicated consistent ECD localization that corresponded to the semiology of clinical seizures. Our findings demonstrate that MEG is a useful tool for detecting epileptogenic focus.     

额叶癫(癎)执行功能损害及磁共振弥散张量成像研究

目的用磁共振弥散张量成像技术研究额叶癫患者执行功能损害的相关脑区及病理改变,探讨其可能的发生机制。方法对32例成人额叶癫患者和75例正常健康对照者进行神经心理检查,并对18例常规影像无病灶的额叶癫患者和20例正常健康对照者进行弥散张量成像扫描及统计分析。结果额叶癫患者组语义流畅性明显差于对照组,数字广度测验得分和90min正确填写数字符号个数明显低于对照组。与对照组比较,额叶癫患者右侧额叶MD值明显高于对照组;右侧外囊、尾状核和双侧丘脑的FA值明显低于对照组,差异具有显著性意义。相关分析显示双侧内囊前肢、左侧外囊、左枕叶皮质下白质FA值与语义流畅性呈正相关。左侧内囊膝部、内囊后肢和丘脑MD值与MMSE呈负相关;双侧内囊前肢、左侧外囊、额叶、枕叶相应白质内FA值与MMSE呈正相关。结论DTI显示额叶癫患者右侧额叶MD值明显增高、右侧外囊、尾状核和双侧丘脑的FA值明显减低,提示额叶癫患者在上述区域可能存在细微病理改变,执行功能可能超出前额叶的范围。     

Prolonged Intermittent Drooling and Oromotor Dyspraxia in Benign Childhood Epilepsy with Centrotemporal Spikes

Prolonged isolated sialorrhea of epileptic origin was described by Penfield and Jasper (1954) in a patient with a lesional epilepsy. A child with prolonged but intermittent drooling, lingual dyspraxia, and other clinical and electroencephalographic (EEG) features compatible with benign childhood epilepsy with centrotemporal spikes (BCECS) is described. The fluctuant course of the symptomatology and correlation with the intensity of the paroxysmal discharges on EEG are consistent with an epileptic dysfunction located in the lower rolandic fissure. No lesion was demonstrated by magnetic resonance imaging (MRI). Our case bears analogies with the recently reported status epilepticus of BCECS and the "acquired aphasia-epilepsy syndrome."     

Changes in current-source density of interictal spikes in benign epilepsy of childhood with centrotemporal spikes following treatment with oxcarbazepine

PurposeThe aim of this study was to detect clinical variables associated with the extent of change of the irritative zone in benign epilepsy of childhood with centrotemporal spikes (BECTS) after oxcarbazepine monotherapy.MethodBECTS patients receiving oxcarbazepine monotherapy were retrospectively reviewed. Changes in current-source density (CSD) of the maximum negative points of interictal spikes prior to the start of oxcarbazepine treatment were compared with CSD following oxcarbazepine treatment for 6–12 months. CSD was measured using low-resolution brain electromagnetic tomography (LORETA). Patients were divided into two groups based on the change in CSD: increased-extent or decreased-extent. Comparisons were made between the groups based on the age of onset, seizure frequency before treatment, time interval between seizure onset and treatment start, time interval between the two EEGs, oxcarbazepine dosage at the follow-up electroencephalography, occurrence of daytime seizures, and seizure control.ResultsFourteen patients were enrolled. Seven patients were in the decreased-extent group and six in the increased-extent group; one patient was excluded because she did not demonstrate any change in CSD. We found that seizure control differed significantly between the two groups: seizures were well-controlled in six out of seven patients in the decreased-extent group (85.7%), but in only one of six patients (16.7%) in the increased-extent group (p = 0.03). The other variables did not differ between the groups.ConclusionSeizure control may be associated with the extent of changes in the neuronal irritative zones of BECTS patients. We suggest that changes of CSD extent may be used as an imaging modality to evaluate clinical improvement in BECTS patients.     

Deficit of endogenous spatial orienting of attention in children with benign epilepsy with centrotemporal spikes (BECTS)

Attention difficulties have been reported in children with benign epilepsy with centrotemporal spikes (BECTS) but have not yet been fully specified. The aim of this study was to evaluate the functions of exogenous and endogenous spatial orienting of attention and alerting in these children. Two versions of the spatial cueing paradigm and an alerting task, including trials with and without warning signal, were performed by 25 children with BECTS aged 6–12 years and 25 controls matched for age, gender and IQ. In these three tasks, patients were slower and made more omissions than controls. The alert effect amplitude was comparable in both groups at the longer SOAs (450 ms and 800 ms) while, at the shortest SOA (100 ms), it was greater in controls than in the BECTS group. In the first version of the spatial cueing task (peripheral cues and no probability information), the validity effect amplitude, measured by longer response times (RTs) in invalid trials compared to valid trials, was comparable in both groups. In the second version (central cues and a 75% probability that the target would appear at the cued location), the validity effect was larger in the BECTS group compared to controls because of a higher cost of invalid trials compared to neutral trials. These results suggest the existence of impairments in the endogenous orienting of attention in children with BECTS, in particular an attention disengagement deficit, while exogenous orienting of attention appears to be preserved.     

Educational problems related to quantitative EEG changes in benign childhood epilepsy with centrotemporal spikes

The relationship between educational problems and clinical/electroencephalographic aspects was assessed in 38 children with benign childhood epilepsy with centrotemporal spikes (BECTS). Children were assessed using the School Performance Test; questionnaires on learning difficulties administered to parents and teachers; the Wechsler Intelligence Scale for Children, Third Edition; and EEGs. Absolute and relative amplitudes in the classic bands (quantitative EEG) and characteristics of epileptiform activity on the EEG were examined. Educational problems were observed in 7 (18.4%) children with BECTS. In this subgroup, relative alpha amplitudes at the central and parietal electrodes were lower as compared with those of the BECTS subgroup with normal educational performance and a control group matched for age, gender, and socioeconomic status. The data indicated a possible relationship between alterations in background brain electrical activity and the tendency toward inferior educational performance in children with BECTS. This study suggested that quantitative EEGs are a possible physiological tool in the assessment of cognitive aspects in children with BECTS.     

儿童良性癫痫伴中央颞区棘波放电患者的GRIN2A突变筛查及遗传特征分析

目的对儿童良性癫痫伴中央颞区棘波放电(BECTS)患者进行GRIN2A基因突变筛查,分析其在BECTS患者中的致病性和遗传特征。方法收集2012年6月~2014年12月期间我院诊断的BECTS患者,采用PCR扩增和一代测序方法筛查GRIN2A基因突变。结果在收集的53例BECTS患者中,发现4例存在GRIN2A杂合突变,其中1例患者同时具有2个GRIN2A基因突变位点。突变包括4个错义突变(c.2627TC,p.I876T;c.1341TA,p.N447K;c.4322CA,p.T1441N;c.1271CT,p.P424L)和1个剪切位点突变(c.415-38CT),且均为未见报道的新突变位点。除c.1271CT为新生突变、c.1341TA未能验证突变来源外,其余3个突变均为遗传性突变。突变率为7.5%,外显率为75%。经保守性分析,发生错义突变的氨基酸变化位点均为高度保守。结论GRIN2A可能是BECTS的致病基因。GRIN2A突变存在不完全外显,临床进行遗传咨询时应引起高度重视。     

Correlation between scalp high-frequency oscillations and prognosis in patients with benign epilepsy of childhood with centrotemporal spikes

Aims

The study aimed to explore whether high-frequency oscillations (HFOs) can predict seizure risk and atypical manifestations of benign epilepsy of childhood with centrotemporal spikes (BECTS).

Methods

We recruited 60 patients and divided them into three groups: (1) seizure-free BECTS, (2) active typical BECTS, and (3) active atypical forms of BECTS. Electroencephalogram was used to record the number, location, average amplitude, and duration of spikes, and spike ripples were analyzed using time-frequency technology. Multivariable logistic regression analysis was used to investigate independent predictive factors for prognosis.

Results

The number of sleep spike ripples, rather than spikes, was an independent risk factor for the active period of the disease (odds ratio [OR] = 4.714, p = 0.003) and atypical forms of BECTS (OR = 1.455, p = 0.049); the optimal thresholds for the spike ripple rate were >0 (area under the curve [AUC] = 0.885, sensitivity = 96.15%, specificity = 73.33%) and >0.6/min (AUC = 0.936, sensitivity = 84.21%, specificity = 96.15%), respectively. Furthermore, in typical BECTS, the spike ripple rate showed significant negative correlations with time since the last seizure (ρ = −0.409, p = 0.009) and age (ρ = −0.379, p = 0.016), while the spike rate did not.

Conclusion

Spike ripple was a marker for distinguishing typical and atypical forms of BECTS and reflected the risk of seizure recurrence better than the spike alone. The present findings might assist clinicians in BECTS treatment.     

Peripheric smell regions in patients with temporal and frontal lobe epilepsies: An MRI evaluation

ObjectivesWe investigated peripheric smell regions of olfactory bulb (OB) volume and olfactory sulcus (OS) depth in temporal and frontal lobe epilepsy patients by cranial magnetic resonance imaging (MRI).MethodsIn this retrospective study, cranial MRI images of 150 adult patients were included. Group 1 was consisted of 50 adult patients with temporal lobe epilepsy (TLE). Group 2 was consisted of 50 adult patients with frontal lobe epilepsy (FLE). The control group (Group 3) was consisted of 50 healthy subjects without epilepsy. OB volume and OS depth were measured in all groups.ResultsOB volumes of the temporal and frontal epilepsy groups were significantly lower than those of the control group (p_adjusted < 0.0175). However, OS depths were not different between groups 1–3 (p > 0.05). In the temporal and frontal epilepsy groups, there were positive correlations between OB volumes; OS depths; left OB volume and bilateral OS depths p < 0.05). There were no significant correlations between OB volume and OS depth; and age and gender of the epilepsy group (p > 0.05).ConclusionWe concluded that temporal and frontal epilepsy maybe related to decrease in OB volume and may cause olfactory impairment. Olfactory deficit maybe related to central epileptic focus. Therefore, early diagnosis and appropriate treatment of epilepsy are important to prevent olfactory impairment.     

重性抑郁症首次发病患者额叶、海马磁共振质子波谱分析及其与认知功能的相关性

目的 探讨重性抑郁症首次发病(以下简称首发)患者生化物质改变与认知功能变化之间的关系.方法 利用质子磁共振波谱分析(1H-MRS)测量21例首发重性抑郁症患者(患者组)双侧额叶和海马N-乙酰天门冬氨酸(NAA)、谷氨酸复合物(Glx)、胆碱复合物(Cho)、肌酸(Cr)及肌醇(ml)水平,计算NAA/Cr、Glx/Cr、Cho/Cr、ml/Cr,并与21名正常对照者(对照组)作比较.此外,分别对两组进行神经心理学测试及比较.将1H-MRS所测异常生化物质与异常的认知功能测验项目进行相关性分析.结果 患者组左额叶NAA/Cr(1.8±0.6)低于对照组(2.6±1.0),且与修订韦氏成人智力量表手册中的相似分量表得分及威斯康星卡片分类测验分类数呈正相关(r=0.60,r=0.53);右侧额叶NAA/Cr(2.0±0.6)低于对照组(2.9±1.8),且与连线测验时间呈负相关(r=-0.52).上述差异均有统计学意义(P＜0.05).结论 首发重性抑郁症患者抽象思维能力下降、思维灵活度下降及执行功能障碍与左额叶NAA/Cr降低相关,注意力障碍与右额叶NAA/Cr降低相关.     

The topographic distribution of brain atrophy in frontal lobe dementia

Summary The topographic distribution of brain atrophy was quantified by image analysis of fixed brain slices from ten patients dying with dementia of frontal type (DFT) and from six other patients dying with dementia of frontal type with motor neurone disease (DFT+MND). In both groups the atrophy was maximal within frontal, anterior temporal and anterior parietal regions of cortex, although other structures such as the amygdala, caudate nucleus, thalamus and hippocampus were also affected. The magnitude of the atrophy was much greater, in all affected regions, in DFT alone than in DFT+MND. Grey and white matter were affected equally in DFT alone although in DFT+MND a preferential white matter involvement was noted. No differences in the topographic distribution of the atrophy was observed in cases of DFT showing a spongiform degeneration of the cortex compared to those showing a gliotic degeneration with, or without, Pick cells and Pick bodies.Supported by a studentship (to PWS) from the Zochonis Foundation