Landau-Kleffner综合征研究进展

Landau Kleffner综合征是年龄依赖性癫疒间 综合征 ,常发生于儿童期 ,病因不清 ,可能与免疫、脑神经元损伤、遗传因素有关。其临床特点为获得性失语、癫疒间 发作和脑电图颞区异常放电 ,失语多为言语听觉失认 ,患儿听力正常 ,但失去言语理解能力 ,表现为缄默 ,失语可持续 2周至数年 ,部分患儿终生语言障碍。大部分患儿有癫疒间 发作 ,常于 15岁前缓解 ,抗癫疒间 药可控制癫疒间 发作 ,但对于失语无明显治疗效果 ,肾上腺皮质激素可明显改善语言功能     

癫(癎)与孤独症共患相关综合征基因研究进展

癫(癎)与孤独症至今都尚未发现特异性的致病基因,但二者的共患率却达到约30％,提示二者可能存在共同的发病机制.癫(癎)与孤独症共患常表现在一些常见的综合征中,如Rett综合征、结节性硬化、脆性X综合征等,这些综合征的发生多与神经系统发育相关的基因突变有关,如ARX、MECP2基因,基因突变的结果往往使突触重塑发生异常,蛋白质调节失控,致大脑兴奋与抑制系统不平衡,最终患病.早期发生的癫(癎)和孤独症的发病机制是多水平的,基因突变可以造成细胞和分子水平的改变,最终造成智力和行为异常.该文研究探讨这些综合征的发病机制研究进展,有助于了解癫(癎)与孤独症共患的发病机制以及寻找治疗共患患儿的新方法.     

婴儿恶性游走性部分性癫癎综合征研究进展

婴儿恶性游走性部分性癫癎综合征是在婴儿期发病的一种严重的癫癎性脑病,1995年由Coppola等首次报道,目前世界共有近80例报道,国内暂无报道.目前该综合征病因不明,早期诊断困难,传统抗癫癎药物疗效不佳.该文就婴儿恶性游走性部分性癫癎综合征可能的病因、临床特点、诊断、治疗进行综述.     

Dravet综合征1例报告

患儿女,5岁,因反复惊厥4.5年,再次惊厥持续发作1h为主诉于2006-08-02入院.患儿G1P1,足月剖腹产,围生期无异常.4.5年前首次发作惊厥,表现为右侧肢体抽搐,迅速意识丧失,全身阵挛.体温38℃,     

癫(癎)患者认知功能障碍病因学研究进展

认知功能障碍是癫痫患者常见的伴随症状，严重影响患者的生活质量，已引起临床医师的广泛关注。癫痫患者出现认知功能障碍的机制一直是国内外的研究热点。本文就近几年来国内外对认知障碍产生的多方面原因的相关研究进展作一简要综述。     

抗癫癎药物治疗中值得注意的问题

~~抗癫癎药物治疗中值得注意的问题     

Landau-Kleffner综合征1例

患儿,男,10岁,右利手,第3胎,出生史正常,生后精神运动发育同同龄儿,家族史无异常。6岁时出现发作性摔倒,四肢抽搐伴意识丧失,发作频率为1、2次/d或2、3次/d,每次数分钟,脑电图有样放电,当地按癫治疗后抽搐控制,此后4年患儿无发作。6岁后其父母发现患儿渐对喊声无反应,仍可讲话,     

癫(癎)的免疫学研究进展

癫(癎)为临床常见综合征,近年来,关于癫(癎)的免疫学发病机制已逐渐被人们所认识,包括体液免疫和细胞免疫两个方面.体液免疫异常主要包括细胞因子、自身抗体及免疫球蛋白等的变化,细胞免疫异常则表现为淋巴细胞亚群、淋巴细胞增殖带及NK细胞等的变化.除外周血的异常,癫(癎)患者的脑脊液检查也可发现各项免疫指标的变化.抗癫癎药物...     

热性感染相关性癫(癎)综合征的研究进展

国外学者报道了一组既往正常的儿童,在发热后出现难治性部分性癫(癎)或癫(癎)持续状态,预后存在认知功能障碍以及药物抵抗性癫(癎)的临床病例,将其命名为热性感染相关性癫(癎)综合征.目前该病病因不明,病情危重,预后差,脑脊液、脑活检和神经影像学未见特异性改变,尚无明确有效的治疗方法,有报道生酮饮食可能有效.该文就热性感染相关性癫(癎)综合征的临床特点进行综述.     

获得性癫(癎)失语综合征4例

目的 探讨获得性癫(癎)失语综合征(LKS)的临床特征及治疗反应.方法 通过对4例LKS患儿临床表现、EEG特征、治疗效果观察,并通过电话及门诊复诊随访其预后.结果 4例患儿均予丙戊酸钠口服溶液及激素治疗,3～6个月抽搐发作控制,失语明显好转,EEG提示不同程度改善.结论 LKS是一少见的年龄依赖性癫(癎)综合征,以失语和癫(癎)发作为主要表现,可伴有行为异常,EEG以颞区为主的样放电,睡眠期可泛化全导,抗癫(癎)药物可控制癫(癎)发作,但对失语疗效欠佳,早期足量激素治疗对失语疗效明显.该病预后较好.     

Dravet syndrome: The main issues

Dravet syndrome (DS) is a severe form of infantile onset epilepsy characterized by multiple seizure types, prolonged convulsive seizures and frequent episodes of status epilepticus. Seizures precipitated by fever are a main characteristic. Affected children exhibit normal early development. Cognitive impairment, behavioral disturbances with hyperactivity and sometimes autistic traits occur after seizure onset. Seizures persist into adulthood but become less frequent. In about 85% of patients, a mutation of the SCN1A gene is present. DS fully illustrates the concept of epileptic encephalopathy. However, it is difficult to determine the causative role of the underlying sodium channel dysfunction and that of the consequent seizures in influencing cognitive outcome. An overwhelmingly high number of SCN1A mutations have been associated with DS. Intragenic or whole gene deletions, duplications and amplifications are additional rare molecular mechanisms. Most mutations are de novo, but familial mutations also occur. Somatic mosaic mutations should be considered when estimating the recurrence. MRI imaging is usually normal, and no neuropathologic signature of the condition seems to exist. In heterozygous Scn1a+/? mice, GABAergic interneurons exhibit substantially reduced sodium current density with reduced ability for sustained action potential firing. GABAergic output is reduced and excitability of downstream synaptic targets increased. Stiripentol was effective in combination with valproate and clobazam in two pivotal phase III trials. Phenytoin, carbamazepine, and lamotrigine can worsen seizures and should be avoided. Prospective studies will clarify to what extent earlier diagnosis and efforts at seizure control with the most appropriate drug combinations will reduce clinical deterioration.     

Diagnosis and long-term course of Dravet syndrome

Dravet syndrome is a severe infantile-onset epilepsy syndrome with a distinctive but complex electroclinical presentation. A healthy, developmentally normal infant presents at around 6 months of age with convulsive status epilepticus, which may be hemiclonic or generalized; seizures may be triggered by fever, illness or vaccination. The infant typically has further episodes of status epilepticus every month or two, often triggered by fever. Other seizure types including focal dyscognitive seizures, absence and myoclonic seizures develop between 1 and 4 years. Atonic drop attacks and episodes of non-convulsive status may occur. Early development is normal but slows in the second year. Developmental regression may occur, particularly with status epilepticus. EEG studies are initially normal, but after 2 years they show generalized spike-wave and polyspike-wave activity with multifocal discharges. Photosensitivity may be seen. Imaging is normal or shows non-specific findings such as atrophy.Dravet syndrome is associated with mutations of the gene encoding the alpha-1 subunit of the sodium channel, SCN1A, in >70% of patients. These include sequencing mutations and copy number variant anomalies; 90% of mutations arise de novo. PCDH19 mutational analysis is a second-tier test for girls with a Dravet-like picture who do not have SCN1A mutations.Outcome is poor, with intellectual disability in most patients and ongoing seizures. Intellectual impairment varies from severe in 50% patients, to moderate and mild intellectual disability each accounting for 25% cases. Rare patients have normal intellect. The long-term course involves ongoing, brief nocturnal convulsions and a characteristic deterioration in gait.     

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??Objective To evaluate the effect of ketogenic diet??KD?? in patients with Dravet syndrome??DS??. Methods The seizures??electroencephalogram??EEG?? and cognitive function of 46 DS patients receiving treatment of KD from January 2007 to November 2015 in Department of Pediatrics were analyzed retrospectively. Modified Johns Hopkins protocol was used to initiate KD??and urinary ketone bodies were daily monitored in the patients to maintain the state of ketosis. The effect was evaluated by Engel outcome scale. The EEG?? cognition??language??and motor function of the patients were assessed. Results Totally 46 DS patients??25 boys??21 girls?? received treatment of KD more than 12 weeks??and among them 29??63.0%?? patients were maintained on the diet more than 24 weeks??16??34.8%?? patients more than 48 weeks. Nine patients were seizure free. The seizures in 25 patients were reduced over 50%??and the KD effect was observed within 2 weeks in them.At the end of 12 weeks of treatment with KD??46 patients achieved ?? ?? ?? ?? grade effect??accounting for 19.6%??9/46 cases????13.0%??6/46 cases????21.7%??10/46 cases????and 45.7%??21/46 cases?? respectively according to Engel scale. The background rhythm of EEG showed obvious improvement in 6 patients??andinterictal seizure discharge frequency decreased significantly. Cognitive function of 15 patients was improved. Language was enhanced in 8 patients. Motor function was improved in 8 patients. The main adverse reactions of KD in the treatment process were mainly gastrointestinal symptoms and metabolic disorders. Conclusion KD treatment in Dravet syndrome has many advantages??such as fast acting?? being effective in more than half of the DS patients and tolerable adverse reactions. Drug resistant DS patients are suggested to receive KD treatment.     

Helping families cope with the devastation of Dravet syndrome

Dravet syndrome shakes family life to the core. Seizure control is rarely complete, and simply prescribing medication is inadequate to help families. Our suggestions are based on structured interviews with >25 Dravet families. In Stage 1 (up to 1–1½ years), a written protocol for an organized approach to status epilepticus is mandatory. In Stage 2 (age from 1½ to ～6–10 years), assistance in finding qualified baby sitters (extended family and others) is required. Equipment, rescue medication and protocols should accompany the child. Siblings may benefit from assigning one parent to be “on call”, and an Internet support group provides an invaluable lifeline. In Stage 3 (after ～10 years), family isolation may become extreme: respite care and personal time for parents are important.An epilepsy transition clinic that can effectively liaise with adult emergency services is optimal. Attention to these realities may improve the quality of life for the child and family.     

Gait abnormalities in people with Dravet syndrome: A cross-sectional multi-center study

ObjectiveTo quantify gait abnormalities in people with Dravet syndrome (DS).MethodsIndividuals with a confirmed diagnosis of DS were enrolled, and stratified according to knee flexion at initial contact (IC) and range of motion (ROM) during stance (atypical crouch: knee flexion >20° at IC and knee ROM >15° during stance; straight: knee flexion <20° at IC). A 1D ANOVA (α = 0.05) was used to test statistical differences among the joint kinematics and spatio–temporal parameters of the cohort and an age-matched control group. Clinical (neurological and orthopaedic evaluation) and anamnestic data (seizure type, drugs, genetic mutation) were collected; distribution between the two gait phenotypes was assessed with the Fisher exact test and, for mutation, with the chi-squared test (p < 0.05). Linear regression between maximum knee flexion and normalised walking speed was calculated.ResultsSeventy-one subjects were enrolled and evaluated with instrumented gait analysis. Fifty-two were included in final analysis (mean age 13.8 ± 7.3; M 26). Two gait patterns were detected: an atypical crouch gait (34.6%) with increased ankle, knee and hip flexion during stance, and reduced walking speed and stride length not associated with muscle-tendon retractions; and a pattern resembling those of healthy age-matched controls, but still showing reduced walking speed and stride length. No differences in clinical or anamnestic data emerged between the two groups.SignificanceObjectively quantified gait in DS shows two gait patterns with no clear-cut relation to clinical data. Kinematics abnormalities may be related to stabilization issues. These findings may guide rehabilitative and preventive measures.