家族性发作性运动诱发性运动障碍六个家系的临床及遗传特点分析

目的探讨发作性运动诱发性运动障碍（paroxysmal kinesigenic dyskinesia，PKD）的临床特征及遗传特点。方法对6个中国汉族PKD家系共122名成员进行随访，包括患者26例，总结分析其临床表现、遗传特点、辅助检查及预后。结果本组6个家系共有患者26例，其中男性18例，女性8例（男：女=2．25：1）。患者发病年龄为4～30岁，均以突然运动诱发，表现为肢体的不能控制的肌张力障碍、舞蹈、投掷样动作等，每次发作约持续几秒到十几秒，持续时间最长不超过1min，平均每天发作数次，不伴意识障碍。神经系统检查、脑电图、头颅影像学检查等均无阳性发现。多数患者可自然缓解，抗癫痫药物治疗有效。6个家系中4个家系有连续2代以上发病，符合常染色体显性遗传；2个家系只有一代患者，且均为同胞兄弟／姐妹，符合常染色体隐性遗传。通过家系内比较，发现4个显性遗传家系均有子代较父代发病年龄提前、发作频率增加、病程延长等现象，提示存在遗传早现（anticipation）。结论PKD是一种神经系统的常染色体遗传病，既有显性遗传又有隐性遗传，具有遗传和临床异质性（heterogeneity）。中国汉族人群中显性遗传的PKD家系存在遗传早现现象。     

家族性发作性运动诱发性运动障碍三个家系的临床及遗传学特点

目的探讨家族性发作性运动诱发性运动障碍（paroxysmal kinesigenic dyskinesia，PKD）的临床及遗传学特点，提高临床医师对该病的认识。方法总结分析3个汉族家族性PKD家系患者的临床资料，并进行详细的家系调查。结果3个家系共有患者25例，其中男性16例，女性9例。起病年龄1～10岁，发作由运动诱发，发作时意识清楚，发作持续时间在30s以内。查体未见异常，无明显智能障碍。发作次数10～50次／d，随年龄增长发作次数减少，卡马西平可完全缓解症状。家系遗传方式均符合常染色体显性遗传模式。家系中男性患者的临床表现比女性严重，未经治疗时，女性患者症状自然缓解的年龄比男性患者早。结论家族性PKD的主要遗传方式为常染色体显性遗传，在临床及遗传上可能存在异质性。男性患者临床表现比女性严重，可能与不同种族的遗传异质性有关。女性患者比男性症状轻，自然缓解年龄早，可能导致多数女性患者不完全外显，使得女性发病相对较少。     

发作性运动诱发性舞蹈手足徐动症

目的探讨发作性运动诱发性舞蹈手足徐动症的发病机制、临床特征及电生理表现。方法回顾性分析18例发作性运动诱发性舞蹈手足徐动症（PKC）患者的临床资料并结合相关文献进行讨论。结果18例患者，男14例，女4例；均为青少年发病，1例有家族病史，其外祖母、母亲年青时（〈20岁）、妹妹均有类似发作史，1例25岁发病．后证实有原发性甲状旁腺功能低下。发病均由突然运动诱发，表现为一侧或双侧肢体及面部（眼肌、舌肌等）的不自主运动．多持续数秒钟自行缓解。发作中无意识障碍。发作间期无异常表现。18例患者神经系统检查均未见异常，均行头CT和（或）MRI检查，3例有影像学异常。所有患者均行脑电图（EEG）检查，其中3例有痫样放电，余正常。诊断为特发性发作性运动诱发性舞蹈手足徐动症（PKC／PKD），经服用卡马西平、丙戊酸钠等药物后发作均得到有效控制。结论PKC由突然运动诱发．表现为发作性不自主运动等锥体外系症状。可呈常染色体显性遗传，亦可散发；可为特发性，也可继发于多发性硬化、原发性甲状旁腺功能低下等疾病。部分患者EEG有痫样放电，抗癫痫药物治疗有效。提示PKC的发病机制可能与癫痫类似，但预后良好。     

发作性运动诱发性运动障碍一家系临床与遗传学特点

目的探讨家族性发作性运动诱发性运动障碍(paroxysmal kinesigenic dyskinesia,PKD)临床及遗传学特点。方法对1个PKD家系共14名成员进行PRRT2基因检测及调查随访,其中患病2例(1例住院治疗,另1例未治疗),总结分析其临床表现、遗传特点、药物治疗效果及预后。结果该家系2例患者均为男性,患病率14.3%,其中1例不治自愈,1例用卡马西平疗效显著,用拉莫三嗪也有效。该家系为单纯性PKD家系,PRRT2基因检测结果显示该家系中3例存在突变c.797GA(p.266RQ),其中1例无临床症状,符合常染色体显性遗传,伴不全外显,存在遗传早现;该家系合并存在多囊肾家族史。结论单纯家族性PKD抗癫痫药物疗效与突变类型及临床特征有关;治疗方案选择应以临床特点及突变类型为依据。     

发作性运动诱发性运动障碍36例临床及影像学研究

目的观察发作性运动诱发性运动障碍(PKD)的临床特征及影像学改变,探讨其发病机制。方法详细观察36例PKD的临床特征,影像学和脑电图改变,并综合文献,简述其发病机制及遗传规律。结果36例均由运动诱发,呈发作性运动诱发性肌张力障碍30例,发作性运动诱发性舞蹈手足徐动症6例,发作时意识清楚,影像学有异常者4例,脑电图1例放电。抗癫痫药疗效好。结论发作性运动障碍是一种少见的运动障碍疾病,临床表现类似癫痫,可能是一种离子通道病,与基底节区功能障碍关系密切,大部分抗癫痫药物治疗有效。     

发作性运动诱发性舞蹈指痉症

目的：探讨发作性运动诱发性舞蹈指痉症（PKC）的临床特点，进一步提高对该病的诊治水平。方法：对5例PKC患者的临床表现及实验室资料进行分析。结果：5例患者来自2个家系，发病年龄13-16岁；临床表现均在运动开始时出现不自主手足及面部异常运动，持续数秒后自行缓解，紧张、恐惧时易发，克制可避免发作。5例检查12例次脑电图，均未见癫痫样放电；3例头颅MRI及T3、T4，血沉、血钙均在正常范围。3例脬用妥泰（100mg/d），完全控制发作，2例间断服苯英钠，亦有效。结论：PKC可能为常染色体显性遗传。临床表现以开始运动时出现发作性锥体外系症状为特征。抗癫痫药治疗效果良好。     

发作性运动诱发性运动障碍研究进展

发作性运动诱发性运动障碍(PKD)又称发作性运动诱发性手足徐动症或发作性运动诱发性舞蹈指痉症(PKC),主要表现为突然运动诱发的发作性异常运动,具有临床表型和遗传异质性,发作持续时间短,发作频率不等,发作期意识清楚,发作间期无神经系统阳性体征,抗癫痫药物治疗有效,预后良好。临床工作中误诊率高,需与癫痫等多种疾病相鉴别,本文就PKD的流行病学特点、疾病发生机制、临床表现、诊断标准、鉴别诊断、治疗及预后研究进展进行综述,重点更新了发病机制中遗传学说的国内外最新研究进展以及疾病的鉴别诊断。     

12例发作性运动诱发性肌张力障碍的临床、脑电图特点及文献复习

目的观察发作性运动诱发性肌张力障碍(PKD)的临床表现、脑电图特征,提高对本病的认识及选择有效的治疗药物。方法回顾性分析12例PKD患者的临床资料、脑电及影像学改变,并结合文献进行总结分析。结果临床症状表现为发作性运动诱发性手足扭转、肢体僵直、舞蹈手足徐动征等,有明确的运动诱发因素,同步脑电记录无异常,正确选择抗癫痫药物可有效控制其发作。结论 PKD是一种少见的运动障碍疾病,应与癫痫、假性发作、TIA、部分性发作等相鉴别。对抗癫痫药物敏感,早期诊断早期治疗预后较好。     

发作性运动诱发性运动障碍临床分析

目的探讨发作性运动诱发性运动障碍的临床特点。方法对23例PKD患者的临床资料进行分析,归纳其特点。结果 23例患者起病年龄6~18岁,病程1~27a,男性占大多数,男女比例为3.6∶1。突发启动的自主运动诱发,以单侧肢体舞蹈样手足徐动多见,部分表现为双侧,持续10s左右,无意识障碍,脑电图、头颅MRI、CT正常。小剂量卡马西平控制发作。结论 PKD是一种发作性运动诱发的、短暂的局部或全身不随意运动,卡马西平治疗有效。     

发作性运动诱发性舞蹈指痉症

目的 对发作性运动诱发性舞蹈指痉症的临床特点、电生理表现及发病机制等进行分析。方法 对2001-2003年收治的4例发作性运动诱发性舞蹈指痉症患的临床资料进行分析并复习近年献。结果 4例患均为青年，无家族遗传史，临床表现均为在运动开始时突然出现一侧或双侧肢体及面部的不自主运动，持续数秒钟后可自行缓解，发作期间无意识障碍，发作后无任何不适。4例患神经系统检查、脑电图以及头部CT和(或)MRI检查均无异常发现，诊断为特发性发作性运动诱发性舞蹈指痉症。经服用卡马西平等药物后发作均得到有效控制。结论 发作性运动诱发性舞蹈指痉症可呈常染色体显性遗传，亦可散发；可为特发性，也可继发于多发性硬化、特发性甲状旁腺功能减退症等其他疾病。发作性运动诱发性舞蹈指痉症的发病机制尚不清楚，其临床特征为运动诱发的一侧或双侧上下肢及面部的不自主运动，对抗癫痫药物敏感，预后良好。     

发作性运动障碍10例临床分析

目的:探讨发作性运动障碍的临床特点、诊断、治疗及误诊原因。方法:回顾性分析发作性运动障碍患者的临床表现、影像学与EEG/video-EEG(视频脑电图)检查及治疗。结果:本组10例,男8例,女2例,起病年龄6~14岁,病程半年~9年;9例由突然的运动诱发,1例为自发发生;临床表现为姿势性肌张力障碍6例,舞蹈样动作2例,投掷样运动1例,手足徐动样动作1例,均为单侧受累;发作时间多为10余秒;6例患者每日有发作,最多1d可发作30余次;CT/MRI均正常,EEG/video-EEG大多正常(9/10);9例卡马西平治疗有效,1例氯硝西泮部分有效。结论:9例为发作性运动障碍中的阵发性运动诱发性运动异常,1例为阵发性非运动诱发性运动异常,前者抗癫药治疗能全部控制发作,后者仅部分有效。     

Paroxysmal kinesigenic dyskinesia: cortical or non-cortical origin

Paroxysmal kinesigenic dyskinesia (PKD) is characterized by involuntary dystonia and/or chorea triggered by a sudden movement. Cases are usually familial with an autosomal dominant inheritance. Hypotheses regarding the pathogenesis of PKD focus on the controversy whether PKD has a cortical or non-cortical origin. A combined familial trait of PKD and benign familial infantile seizures has been reported as the infantile convulsions and paroxysmal choreoathetosis (ICCA) syndrome. Here, we report a family diagnosed with ICCA syndrome with an Arg217STOP mutation. The index patient showed interictal EEG focal changes compatible with paroxysmal dystonic movements of his contralateral leg. This might support cortical involvement in PKD.     

发作性肌张力障碍38例临床分析

目的提高对发作性肌张力障碍临床特征的认识,以引起临床重视,减少误诊。方法对发作性肌张力障碍的类型、临床特征、电生理表现、治疗转归以及发病机制等进行总结、分析。结果发作性肌张力障碍临床可分三型,不同类型有不同的诱因;患者多为青少年男性,发作表现为舞蹈样手足徐动、躯体扭转及扮鬼脸等肌张力障碍,形式多样,发作时无意识丧失;发作期及发作间期脑电图均无特异性异常,其余多项辅助检查也无异常。结论发作性肌张力障碍是一种不同于癫癎的独立的疾病。     

发作性运动障碍（附8例临床报道）

目的 :总结发作性运动障碍中PKC的临床特征 ,并对其发病机制加以探讨。方法 :对 8例PKC患者临床表现及实验室资料进行分析。结果 :本组中 8例患者发病年龄 8～ 14岁 ,病程 1～ 10年 ,87%为男性。临床表现均由突发运动诱发 ,由久坐、久立后突然改变体位 ,表现为一侧或双侧不自主肢体舞动、躯干扭动和面部异常运动 ,持续数秒钟自行缓解 ,发作时意识清楚 ,2例EEG轻度异常 ,6例正常EEG中有 2例 2 4h动态脑电图示样放电 ,8例服用少量卡马西平完全控制发作。结论 :PKC是发作性运动障碍中一类疾病 ,以开始运动时出现发作性锥体外系症状为特点 ,发作范围局部或全身 ,是可以治愈的 ,抗癫药治疗效果良好     

发作性运动诱发性运动障碍临床表型分析

研究背景发作性运动诱发性运动障碍是一组由突然动作诱发的非随意性运动障碍性疾病,表现为反复发作的短暂性肌张力障碍或舞蹈样动作,具有高度临床和遗传异质性。本研究旨在总结中国发作性运动诱发性运动障碍临床表型特点。方法采集195例原发性发作性运动诱发性运动障碍患者临床资料,采用自行设计的发作性运动诱发性运动障碍登记表记录并整理,分析和总结发作性运动诱发性运动障碍临床表型特点,并比较家族性与散发性患者临床表型差异。结果 195例发作性运动诱发性运动障碍患者男女比例为4.42∶1,平均发病年龄为(12.32±3.49)岁,单纯型162例(83.08%)、复杂型33例(16.92%),16例(8.21%)合并特发性震颤,144例(73.85%)发作前有先兆,发作形式包括肌张力障碍(134例,68.72%)、舞蹈样动作(8例,4.10%)和二者混合形式(53例,27.18%),134例(68.72%)发作时面部受累,115例(58.97%)发作频率10次/d、54例(27.69%)10~20次/d、26例(13.33%)20~30次/d,117例(60%)发作持续时间10 s、58例(29.74%)10~30 s、20例(10.26%)30~60 s,散发性131例(67.18%)、家族性64例(32.82%),78例(40%)未服用药物,117例(60%)服用抗癫药物患者中106例症状完全控制、8例偶有发作、3例未见明显缓解。其中,家族性组发病年龄低于(t=2.376,P=0.019)、发作持续时间短于(χ~2=7.731,P=0.021)散发性组。结论通过大样本临床数据分析和总结中国发作性运动诱发性运动障碍临床表型特点,以期为临床诊断与治疗提供帮助。     

Paroxysmal kinesigenic dyskinesia: a channelopathy? Study of 19 cases

INTRODUCTION: Paroxysmal kinesigenic dyskinesia (PKD) is characterized by brief episodes of dystonia and choreoathetosis triggered by sudden voluntary movements. Disease onset is seen in the first or second decade. The attacks typically last less than one minute. Three autosomal dominant PKD loci are identified: EKD1, EKD2 and EKD3. EKD1 has an overlap with the locus of the "Infantile Convulsion and Choreoathetosis (ICCA) syndrome". The favorable natural history, the episodic nature of the symptoms and their sensitivity to anticonvulsant therapy suggest channelopathy as a mechanism of PKD. PATIENTS AND METHODS: We reviewed the clinical features, the family history, the treatment response, the evolution and the technical investigations in 19 affected individuals. RESULTS: All cases were idiopathic. Ten patients had a positive familial history. Three patients suffered from ICCA syndrome. Some atypical features were seen, such as the association of kinesigenic and nonkinesigenic attacks and the presence of migraine, ataxia, seizures and myoclonus. Acetazolamide responsiveness was seen in two patients. CONCLUSION: The coexistence of PKD and nonkinesigenic dyskinesia in several patients confirms the earlier described presence of intermediary forms, nonrepresented in the current classification of paroxysmal dyskinesias. Our study results suggest channel dysfunction and basal ganglia involvement in the pathophysiology of PKD.     

Les dyskinésies paroxystiques kinésigéniques : une « canalopathie » ? Étude de 19 cas

Introduction

Paroxysmal kinesigenic dyskinesia (PKD) is characterized by brief episodes of dystonia and choreoathetosis triggered by sudden voluntary movements. Disease onset is seen in the first or second decade. The attacks typically last less than one minute. Three autosomal dominant PKD loci are identified: EKD1, EKD2 and EKD3. EKD1 has an overlap with the locus of the “Infantile Convulsion and Choreoathetosis (ICCA) syndrome”. The favorable natural history, the episodic nature of the symptoms and their sensitivity to anticonvulsant therapy suggest channelopathy as a mechanism of PKD.

Patients and methods

We reviewed the clinical features, the family history, the treatment response, the evolution and the technical investigations in 19 affected individuals.

Results

All cases were idiopathic. Ten patients had a positive familial history. Three patients suffered from ICCA syndrome. Some atypical features were seen, such as the association of kinesigenic and nonkinesigenic attacks and the presence of migraine, ataxia, seizures and myoclonus. Acetazolamide responsiveness was seen in two patients.

Conclusion

The coexistence of PKD and nonkinesigenic dyskinesia in several patients confirms the earlier described presence of intermediary forms, nonrepresented in the current classification of paroxysmal dyskinesias. Our study results suggest channel dysfunction and basal ganglia involvement in the pathophysiology of PKD.     

Clinical manifestations of 20 Taiwanese patients with paroxysmal kinesigenic dyskinesia

Introduction - We compared the clinical manifestations and response to medications between familial and sporadic patients with paroxysmal kinesigenic dyskinesia (PKD), and also between patients with autosomal dominant (AD) and autosomal recessive (AR) inheritance. Material and methods - This retrospective cohort study included 9 familial and 11 sporadic Taiwanese patients with PKD diagnosed during a 10-year period at one of two hospitals. The mean duration of follow-up was 2.7 years. Each patient was interviewed and their medical records, as well as videotape recordings of PKD attacks in 6 patients, were used for analysis. Patients were treated with either carbamazepine or phenytoin, and the efficacy of sodium valproate was tested in 5 patients. Results - No single distinguishing feature in terms of clinical manifestations or therapeutic response was found to differentiate among familial, and sporadic cases, or between AD and AR inheritance. Carbamazepine and phenytoin were superior to sodium valproate in treating both familial and sporadic PKD patients, and both drugs resulted in almost complete remission of attacks. Conclusion - Our findings indicate that the sporadic and familiar forms of PKD, as well as the AR and AD inherited types, are similar in terms of clinical manifestations and response to treatment. The functional status and prognosis of our Taiwanese patients suggest that PKD is a relatively benign entity.     

Ictal (99m)Tc ECD SPECT in paroxysmal kinesigenic choreoathetosis

Paroxysmal kinesigenic choreoathetosis is a rare neurologic disorder characterized by sudden attacks of brief involuntary dyskinetic movement that are precipitated by voluntary movement. A 14-year-old male who presented with frequent brief attacks of hemidystonia triggered by sudden movement is reported. Investigations, including video electroencephalogram and magnetic resonance imaging of brain, were normal. There was excellent and sustained response to carbamazepine. Ictal single-photon emission computed tomography using (99m)Tc ethyl cysteinate dimer revealed increased perfusion of the contralateral basal ganglia, which is associated with onset of choreoathetosis attacks. Our findings provide evidence that hyperactivity of the basal ganglia is associated with the dyskinetic attacks in paroxysmal kinesigenic choreoathetosis.