促皮质素治疗前后婴儿痉挛患儿视频脑电图变化及其与预后的关系

目的 观察婴儿痉挛(IS)患儿促皮质素(ACTH)治疗前后视频脑电图(VEEG)变化并进行追踪随访,以了解其与预后的关系并评价影响预后的因素.方法 对2008年1月- 2011年1月在本科住院的52例IS患儿行VEEG长时间监测,对治疗前后VEEG进行分析,包括高峰失律、背景、睡眠纺锤波等;并对其临床随访资料进行回顾性研究.结果 ACTH患儿治疗4周后无论症状性IS还是隐源性IS,高峰失律均基本消失.随访6个月,无发作16例;发作未完全缓解36例,发作形式为痉挛发作、局限性发作和全面强直发作.病程≤2个月、隐源性IS、起病年龄＜8个月、ACTH近期疗效好及VEEG为典型高峰失律的患儿临床预后好;ACTH治疗前VEEG呈局灶性高峰失律者预后不良;ACTH满疗程时VEEG背景不正常、高峰失律不消失及睡眠纺锤波持续不出现者临床预后不良;随访6个月VEEG仍为高峰失律的患儿均为症状性IS,预后差.结论 ACTH治疗前后监测VEEG对评价IS临床预后具有重要作用.     

视频脑电图评估促肾上腺皮质激素治疗婴儿痉挛症的疗效

目的 分析促肾上腺皮质激素(adrenocorticotrophic hormone,ACTH)治疗婴儿痉挛症(infantile spasms,IS)前后视频脑电图变化的特点.方法 收集我院2005年1月至2009年12月住院的65例IS患儿的临床资料,分析其用ACTH治疗前后视频脑电图变化的特点.结果 65例患儿用ACTH治疗前IS发作间期脑电图背景均出现高峰失律现象;丛集性痉挛发作频繁出现,并可见同期特征性发作图形.ACTH治疗后,40例(61.5%,40/65)完全控制发作的患儿中,27例(67.5%,27/40)脑电图高峰失律背景消失或明显好转;另25例(38.5%,25/65)仍有发作的患儿中,仅5例(20.0%,5/25)脑电图高峰失律背景消失或明显好转.完全控制发作和仍有发作患儿的脑电图高峰失律背景消失或好转率比较差异有统计学意义(x2=13.888,P＜0.000).结论 IS患儿发作前视频脑电图监测是正确诊断IS的重要依据,ACTH治疗后视频脑电图监测是判断短期疗效的重要指标.     

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目的探讨晚发型癫痫性痉挛患儿的临床和脑电图(EEG)特征、治疗反应及预后。方法对北京大学第一医院儿科2000年6月至2007年8月59例晚发型癫痫性痉挛患儿的临床和EEG资料进行回顾性研究,其中37例有随访,随访时间13～90个月,末次随访年龄为2岁6个月至12岁2个月(中位数60个月)。结果59例患儿癫痫起病年龄为12～98个月,中位年龄22个月。以痉挛发作起病36例(61.0%),以其他发作类型起病23例(39.0%)。17例(28.8%)在病程中有部分性发作,22例(37.3%)合并其他全面性发作形式,20例(33.9%)病程中仅有痉挛发作。EEG14例(23.7%)为典型高度失律;2例(3.4%)为一侧性高度失律;43例(72.9%)无典型的高度失律。总计22例(37.3%)表现为局灶性或一侧性临床、影像学和(或)EEG异常。44例(74.6%)为症状性癫痫,围生期脑损伤、中枢神经系统感染、脑结构异常为主要病因。14例(23.7%)符合晚发型West综合征,7例(11.9%)符合Lennox-Gastaut综合征。促肾上腺皮质激素(ACTH)治疗后近期无发作率32.0%,有效率58.0%,复发率为61...     

A case of West syndrome with atypical massive gray matter heterotopia that is well controlled by ACTH therapy

A 4 month old female infant with atypical asymmetrical massive gray matter heterotopia diagnosed as West syndrome is described. Her seizure initially appeared as afebrile general tonic and clonic convulsion and progressed to typical West syndrome consisting of clusters of myoclonic spasms of the extremities, mainly on the left side, accompanied by head and eye deviation to the right side. Electroencephalogram (EEG) presented typical hypsarrhythmia and cranial computerized tomography (CT) and magnetic resonance imaging (MRI) showed massive heterotopic gray matter in the right hemisphere with the same density or intensity as cortical gray matter. Single photon emission computed tomography (SPECT), using N-isopropyl-p-¹²³I-iodoamphetamine (¹²³I-IMP), demonstrated decreased blood flow in the ectopic lesion. Although clinical response to several anti-epileptic drugs was poor, her seizures were well controlled by relatively low dose adrenocorticotropic hormone (ACTH) therapy of 0.015 mg/kg per day followed by a combination of valproic acid and clonazepam.     

利妥昔单抗治疗儿童及青少年成熟B细胞非霍奇金淋巴瘤疗效及安全性的Meta分析

目的 探讨促肾上腺皮质激素（adrenocorticotropic hormone,ACTH）首次治疗婴儿癫痫痉挛综合征（infantile epileptic spasms syndrome,IESS）短期（ACTH治疗28 d时）疗效、复发及预后的影响因素。 方法 收集2008年4月—2018年1月中南大学湘雅医院小儿神经专科首次接受ACTH治疗且随访时间≥2年的IESS患儿的临床资料,采用多因素logistic回归分析探讨ACTH治疗短期疗效、复发和远期预后的影响因素。 结果 ACTH治疗28 d时癫痫控制率为55.5%（111/200）,治疗后12个月持续控制无复发率为67.6%（75/111）。未合并局灶性发作的患儿在ACTH治疗28 d时癫痫控制的可能性是合并局灶性发作患儿的2.463倍（P<0.05）;ACTH治疗14 d时脑电图无高度失律的患儿在ACTH治疗28 d时癫痫控制的可能性是ACTH治疗14 d时脑电图有高度失律患儿的2.415倍（P<0.05）;ACTH治疗前病程每增加1个月,治疗后12个月内复发可能性增加11.8%（P<0.05）。ACTH治疗28 d癫痫未控制患儿中重度发育迟滞或死亡的可能性是癫痫控制患儿的8.314倍（P<0.05）,结构性病因患儿中重度发育迟滞或死亡的可能性是原因不明患儿的14.448倍（P<0.05）。 结论 是否合并局灶性发作、治疗14 d时脑电图高度失律是否消失可作为ACTH治疗短期疗效的预测指标,而治疗前病程可作为ACTH治疗癫痫控制后是否复发的预测指标。IESS患儿的预后与病因相关,而使用ACTH后早期控制癫痫发作,也可改善远期预后。     

Kabuki make-up syndrome associated with West syndrome

A Japanese boy with Kabuki make-up syndrome associated with West syndrome is reported. He developed periodic tonic spasms at 6 months of age while his electro-encephalogram also revealed hypsarrhythmia. Although only a few previously reported cases of Kabuki make-up syndrome have been associated with epilepsy, it is likely that epileptic seizures are another primary feature of Kabuki make-up syndrome.     

晚发型癫痫性痉挛患儿临床特征及生酮饮食近期疗效分析

目的 分析晚发型癫痫性痉挛患儿临床特征、诊断和治疗。方法 回顾性收集2012年3月至2013年12月在复旦大学附属儿科医院神经科收治的晚发型癫痫性痉挛患儿的临床资料、EEG及抗癫痫药物治疗情况,并评估生酮饮食（KD）的近期疗效。结果 ①18例晚发型癫痫性痉挛患儿进入分析,均经长程视频EEG监测到癫痫性痉挛发作,男13例,女5例,年龄2~10岁（中位年龄5.5岁）。癫痫起病年龄1~8岁（中位年龄3岁）;病程1~72个月（中位病程9个月）。②首次发作为癫痫性痉挛4例（22.2%）,其他发作类型14例（77.8%）。③发作间期EEG呈典型高度失律4例(22.2%)。④7例为症状性癫痫（病毒性脑炎后遗症4例,围生期脑损伤3例）,另11例病因不明,18例均有不同程度精神运动发育落后。⑤在电-临床综合征分类上,符合晚发型婴儿West综合征4例,Lennox-Gastaut综合征4例。⑥18例在抗癫痫药物治疗期间随访3~24个月,抗癫痫药物治疗末次随访时单药治疗2例,多种抗癫痫药物治疗16例;4例维持无发作,14例（77.8%）为药物难治性癫痫。8例药物难治性癫痫患儿接受KD治疗,治疗3个月末完全无发作3例,有效2例,无效3例,有效率62.5%(5/8),完全无发作率37.5%(3/8)。8例均能耐受KD且均未观察到明显的不良事件。结论 儿童晚发型癫痫性痉挛发作不仅见于West综合征,也可见于其他癫痫性脑病,EEG缺乏特征性高度失律,多为药物难治性癫痫,KD治疗安全且具有一定的近期疗效。     

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目的总结婴儿痉挛(infantile spasms,IS)临床特点,比较不同剂量促肾上腺皮质激素(ACTH)治疗IS短期疗效、副反应,探讨临床痉挛发作缓解的影响因素。方法对2005年1月至2010年12月北京大学第一医院儿科住院并首次行ACTH治疗的IS患儿病历资料进行回顾性研究。按起始ACTH治疗剂量不同分为大剂量组、小剂量组,比较两组临床及脑电图疗效、副反应,采用Logistic回归分析评价临床疗效的影响因素。结果共收集198例临床资料、脑电图特点及影像学特征。大剂量组IS患儿痉挛发作缓解率为37.3%(25/67),小剂量组45.0%(59/131),差异无统计学意义(P>0.05)。120例治疗结束后复查录像脑电图,大剂量组高度失律消失率42.2%(19/45),小剂量组58.7%(44/75),差异无统计学意义(P>0.05)。两组不同剂量应用ACTH期间副反应发生率分别为52.2%(35/67)和32.8%(43/131),差异有统计学意义(P<0.05)。ACTH治疗前病程(treatment lag,TL)是影响短期ACTH疗效的独立危险因素,TL≤1个月者痉挛发作缓解率59.0%(36/61),TL>1个月者痉挛发作缓解率34.8%(48/137),差异有统计学意义(P<0.05)。结论大剂量与小剂量ACTH对痉挛发作缓解率、脑电图高度失律消失率差异无统计学意义(P>0.05);大剂量ACTH副反应显著多于小剂量;TL是影响短期ACTH疗效的独立危险因素。     

Insulin-resistant diabetes during growth hormone therapy in a child with SHORT syndrome

We report the case of a 13-year-old boy with SHORT syndrome, including lipoatrophy and insulin resistance, who developed diabetes mellitus while receiving growth hormone therapy. The diabetes persisted after cessation of exogenous growth hormone but oral hypoglycaemic therapy was successful and could be discontinued eight months later.     

Therapeutic efficacy and adverse effects of adrenocorticotropic hormone therapy in west syndrome: differences in dosage of adrenocorticotropic hormone, onset of age, and cause

OBJECTIVES: To determine the dosage and factors influencing efficacy of adrenocorticotropic hormone (ACTH) for West syndrome. STUDY DESIGN: A retrospective study of 135 patients receiving ACTH therapy with a synthetic analogue for initial effect, seizure outcome 1 year after therapy, and adverse effects. Efficacy and adverse effects were compared among the groups divided by clinical factors: dosage, treatment lag, onset age, and cause. RESULTS: One hundred thirteen patients had seizure control with ACTH. For more than 1 year after ACTH, 59 remained seizure free. Adverse effects were observed in 57, and ACTH therapy was discontinued in 23. The lowest dosage group (0.0125 mg/kg/d) had fewer episodes of discontinuation (P<.05), whereas differences in efficacy between different dosages were insignificant. None of the clinical factors correlated with initial effect. The earlier-onset group (<4 months) showed unfavorable seizure outcome 1 year after ACTH (P<.01). The cryptogenic patients showed better seizure outcome (P<.05) compared with the symptomatic. CONCLUSION: Synthetic ACTH therapy at a lower dosage is as effective as natural ACTH therapy at a higher dosage. Considering the adverse effects and the benefits for seizure control, the ACTH dosage of 0.0125 mg/kg/d (synthetic analogue) is more favorable than larger dosage.     

West syndrome associated with Down syndrome: Case report and literature review

West syndrome is the most frequent cause of epilepsy in Down syndrome. West syndrome is often associated with poor long-term prognosis in most of children. We report a girl with West syndrome associated with Down syndrome which occurred at 8 months of age for repetitive flexor spasms and electroencephalography (EEG) showed hypsarrhythmia. She had Down syndrome facies, microcephaly, psychomotor development delay and axial hypotonia. Computed tomography of the brain was normal. Her karyotype was 47, XX, +21. Phenobarbital therapy was immediately effective with good clinical control of seizures, while the EEG monitored after one month was unchanged. At 2 years of age, the patient had hypertonic status epilepticus following a lung infection. The EEG showed a persistence of hypsarrhythmia. Sodium valproate and hydrocortisone therapy was effective with good seizure control but her psychomotor development was severely impaired. After a follow-up of 7 years, the patient presents growth retardation, microcephaly, severe psychomotor development delay, generalized hypotonia and tetraparesis. Knowledge of West syndrome in Down syndrome allows the early detection and prompt management of this neurological complication in order to optimize psychomotor development and improve the quality of life of these children.     

促肾上腺皮质激素治疗婴儿痉挛症作用机制研究进展

婴儿痉挛症是一种特发于婴儿期的难治性严重癫(癎)性脑病,促肾上腺皮质激素(ACTH)已成为治疗本病的主导药物.但目前对ACTH治疗婴儿痉挛的作用机制仍缺乏合理的解释.研究发现ACTH可能通过负反馈抑制促肾上腺皮质激素释放激素的过度合成和释放,调控神经类固醇、神经生长因子的合成和释放等多种途径发挥疗效.     

促皮质素与生酮饮食治疗新发婴儿痉挛症的随机对照研究

目的 通过促皮质素(ACTH)与生酮饮食(KD)治疗新发婴儿痉挛症(IS)的随机对照研究,比较二者的疗效、安全性、耐受性,证实KD能否作为IS的首选治疗方法.方法 将不同时间收治的30例IS新发病例随机分为2组,每组15例.分别给予KD及ACTH治疗,于治疗2周及1、3、6、12个月观察和对比二者的疗效、脑电图改善情况、不良反应及治疗保留率情况.结果 治疗2周,ACTH组与KD组无发作比例分别为71.4%(10/14例)与33.3%(5/15例),ACTH组优于KD组(P=0.039),ACTH治疗有效病例起效时间为(6.00±4.10) d,而KD治疗有效病例起效时间为(9.31±3.59) d,ACTH组起效快于KD组(P<0.05),但治疗3、6、12个月,ACTH组无发作比例分别为50.0%、35.7%、28.6%;KD组无发作比例分别为85.7%、81.8%、75.0%.KD组均优于ACTH组(P=0.045,0.025,0.043),同时脑电图的高峰节律紊乱背景的改善情况与发作控制情况基本平行.1 a后,ACTH组与KD组治疗保留率分别为26.7%(4/15例)及40%(6/15例),二者差异无统计学意义(P=0.227).观察期间,ACTH组与KD组分别出现19例次与16例次的不良反应,但经对症处理后均能很快好转.结论 ACTH治疗IS起效较KD快,近期疗效优于KD治疗,但其停药后复发率逐渐增高,远期疗效不及KD治疗,提示KD可考虑作为IS的首选治疗方案.     

Factors predictive of prognosis of infantile spasms. A retrospective study in a low-income country

Purpose

To describe the management of infants with epileptic spasms (ESs) in a low-income country and identify factors predictive of their prognosis.

Epileptic spasms: Experience with a high‐dose oral corticosteroid protocol

Aim: To audit clinical practice and assess early outcomes for infants with epileptic spasms after an agreed initial treatment protocol was adopted. Methods: We reviewed all cases of epileptic spasms diagnosed between July 2007 and June 2009 and assessed adherence to protocol, remission by day 14, spasm recurrence and side effects. The protocol required that infants be treated with high‐dose oral prednisolone except those with tuberous sclerosis complex (TSC) who were treated with vigabatrin. Results: Twenty‐eight infants (age 3–14 months, 17 male) were newly diagnosed. Six (21%) had no cause identified (cryptogenic), six (21%) had TSC and 16 (57%) had other non‐TSC symptomatic aetiologies. Twenty‐three were treated per protocol and five were not. The proportion with remission by day 14 of treatment was 100% in the cryptogenic group (all treated per protocol), 64% in those with non‐TSC symptomatic aetiologies treated per protocol, 20% in those with non‐TSC symptomatic aetiologies treated not per protocol and 17% in infants with TSC (all treated per protocol). Of 17 infants who received prednisolone, two were admitted for management of febrile illness. Conclusion: Our experience with high‐dose oral prednisolone for treatment of epileptic spasms suggests that it is effective and tolerable. The greater proportion of non‐TSC symptomatic patients with timely cessation of spasms when treated by this protocol supports the use of high‐dose oral prednisolone as the treatment of choice. Given the poor response of children with TSC to treatment with vigabatrin, early use of steroid therapy deserves consideration.     

婴儿痉挛症首次促肾上腺皮质激素治疗相关因素与痉挛控制时间的Cox比例风险回归模型分析

目的 探讨婴儿痉挛症患儿首次行促肾上腺皮质激素（ACTH）治疗中的相关因素对痉挛控制时间的影响,为临床治疗提供参考依据。方法 选择2008年1月至2013年10月收治的72例婴儿痉挛症患儿为研究对象,收集临床资料,选取婴儿痉挛症相关暴露因素,以痉挛控制时间分别对各因素进行Cox比例风险回归模型分析,评估各因素对痉挛控制时间的影响。结果 有无明确病因（已知病因或不明原因）、治疗前痉挛发作频率、是否联合治疗（ACTH单用或联合硫酸镁）3个因素对婴儿痉挛症患儿的痉挛控制时间具有显著性影响（P < 0.05）。已知病因的婴儿痉挛症患儿痉挛控制时间较短,而治疗前痉挛发作频率较低以及ACTH联合硫酸镁治疗的患儿痉挛控制时间较长（均P < 0.05）。结论 对于首诊的婴儿痉挛症患儿,应尽可能明确病因,有助于评估预后;及早应用ACTH联合硫酸镁治疗,可能改善预后。     

促皮质素对婴儿痉挛症脑电图改变的影响

目的探讨促皮质素(ACTH)治疗婴儿痉挛症(IS)前后脑电图的改变趋势,为病因学和治疗学研究提供依据。方法回顾性分析本院小儿神经科收治的44例经ACTH治疗的IS患儿临床资料、治疗前1、2 d及正规治疗14 d后的视频脑电图,对经ACTH治疗前后IS患儿脑电图的放电总数变化情况进行评估,并对其前额额区、中央顶区、枕区、中后颞区4个部位治疗后改善程度是否存在差异及哪个部位改善最明显进行研究。结果 ACTH治疗前后IS患儿脑电图的放电总数变化有统计学意义(Z=-5.217,P<0.05);前额额区、中央顶区、枕区、中后颞区4个部位治疗后较治疗前有改善(M=34.075,P<0.05);上述4个部位用SNK法分别进行两两比较,前额额区与其他部位比较差异均有统计学意义,中央顶区、枕区,中后颞区组两两比较差异均无统计学意义,前额额区的用药前后差值最小。结论 ACTH可明显改善IS的异常放电,其改善程度在各部位之间有差异,其中前额、额区较中央顶区、枕区、中后颞区差,可能与IS的病因和发病机制相关。     

Infantile spasms associated with theophylline toxicity

We report on a 6-month-old infant with asthma who developed spasms and hypsarrhythmia on the electroencephalogram (EEG) shortly after starting oral theophylline medication. Theophylline levels at that time were just above the upper normal range. The spasms stopped and the EEG normalized when theophylline was discontinued and nitrazepam therapy started. On follow-up over the next 3 years there was no recurrence of seizures and the chilďs neurodevelopment has been normal. Nitrazepam was stopped at 10 months and the waking and sleeping EEG were normal at 14 months. We believe that the infantile spasms were caused by theophylline.     

Cognitive behavioral therapy for children with autism spectrum disorder: A prospective observational study

Objective

To evaluate prospectively the effectiveness of cognitive behavioral therapy (CBT) in children with autism spectrum disorder (ASD).

Transcranial direct current stimulation and constraint-induced therapy in cerebral palsy: A randomized,blinded, sham-controlled clinical trial

We investigated the safety, feasibility, and efficacy of transcranial direct current stimulation (tDCS) combined with constraint-induced movement therapy (CIMT) in children and young adults with unilateral cerebral palsy. Twenty participants were randomized to receive active or sham tDCS. The intervention consisted of 10 consecutive weekday sessions of tDCS applied to the non-lesioned hemisphere (20 min) concurrently with CIMT (120 min). Participants, caregivers, and interventionists were blinded to group assignment. The primary safety outcome investigated adverse events. The primary behavioral outcome was the Assisting Hand Assessment. All 20 participants (mean age = 12.7 yrs, range = 7.4–21.6 years) were evaluated for the primary outcomes. No serious adverse events occurred, and the most commonly reported minor adverse events were headache and itchiness. Both groups demonstrated a significant improvement in hand function after the intervention, although no significant effect of tDCS was observed (between-group difference = ?2.18, 95% CI = [?6.48, 2.12], p = 0.30). Although hand function improved overall, no significant differences between intervention groups were found. Children with preserved corticospinal tract circuitry from the lesioned hemisphere, compared to those without, showed greater improvement in hand function (mean difference = 3.04, 95% CI = [?0.64, 6.72], p = 0.099). Our study demonstrates the safety and feasibility of serial sessions of tDCS, and presents preliminary evidence for the effect of CST circuitry on outcomes following tDCS/CIMT. Future work in children with unilateral cerebral palsy should focus on the optimal dosing and consider individual brain circuitry when describing response to combined interventions.