原发性震颤的诊断和治疗指南

原发性震颤(essential tremor,ET)也称特发性震颤,是一种常见的运动障碍性疾病,临床上以上肢远端的姿势性或动作性震颤为特点,可伴有头部、口面部或声音震颤,30%～50%的ET患者有家族史.传统观点认为ET是良性、家族遗传性、单症状性疾病,但目前认为ET是缓慢进展的、可能与家族遗传相关的复杂性疾病[1].     

原发性震颤的遗传学及治疗进展

原发性震颤（essential tremor，ET）是一种临床最常见的运动障碍性疾病，多发于40岁以上的中老年人群，临床表现以震颤为主。传统观点认为，原发性震颤是良性、家族性、轻微的单症状性疾病，随着研究的深入，目前认为原发性震颤为缓慢进展、可能与家族遗传相关的复杂性疾病（complex disease）。近年来，其遗传特点和治疗理念、方法都有了新的进展，笔者将围绕上述两方面的研究进展简要综述。     

原发性震颤的发病机制及治疗进展

原发性震颤(ET)是较为常见的神经系统疾病之一,有30%～50%患者被误诊为帕金森病或其他震颤性疾病.传统观点认为,原发性震颤是良性、家族性、单一症状性疾病,以上肢的姿势性或动作性震颤为主要特征.随着相关研究的深入,学术界对这一观点提出了质疑.     

原发性震颤的外科治疗

原发性震颤 (essentialtremor ,ET)是一种常见的发病原因和机理不明的运动障碍病 ,又称良性震颤或家族性震颤 ,约 6 0 %的患者有家族史 ,呈常染色体显性遗传特征。临床上ET主要表现为执行动作时出现震颤 ,症状单一。多数累及上肢、下颌和头颈 ,可以不对称 ,罕见下肢和躯干受累。药物治疗ET疗效不佳。症状严重的患者影响工作和生活 ,甚至失去自理生活能力。一、原发性震颤的流行病学和遗传学ET在老年人群中发病率的报道从 1 %到 2 2 %不等。最保守的估计 ,在 70岁以上人群中ET的发病率也有 1 .2 %到 2 %。一项研究证实 ,ET的发病率比PD…     

家族性原发性震颤2例报告

家族性原发性震颤２例报告于代君，陈宁原发性震颤是一种病因未明、具有常染色体显性遗传特征的病症，在临床上常被误诊为帕金森病。其实，这两种疾病在病因、病理、发病机理、临床症状以及治疗方面均有明显不同。目前，药物治疗效果国内尚未有报道。现将两例原发性震颤的...     

不同亚型帕金森病患者多导睡眠图的临床观察

目的评价不同亚型原发性帕金森病(PD)患者多导睡眠图(PSG)的变化指标,分析PD患者睡眠障碍的临床特点。方法选取原发性PD患者90例[震颤为主型40例,姿势异常步态障碍(PIGD)为主型50例]以及50名健康对照者,进行全夜PSG监测,并对结果进行比较。结果与震颤为主型相比,PIGD为主型总睡眠时间、卧床时间、睡眠中觉醒次数及睡眠效率明显下降,快速眼动(REM)睡眠时间明显减少,差异有统计学意义(均P0.05);睡眠潜伏期、S1(min)、S1(%)、S2(min)、S2(%)、S3+S4(min)、S3+S4(%)差异无统计学意义(均P0.05)。与对照组相比,震颤为主型总睡眠时间、卧床时间明显下降,差异有统计学意义(均P0.05);睡眠中觉醒次数、睡眠效率、REM睡眠时间、睡眠潜伏期、S1(min)、S1(%)、S2(min)、S2(%)、S3+S4(min)、S3+S4(%),差异无统计学意义(均P0.05)。结合视频监测录像观察,PIGD为主型原发性PD患者70%出现REM睡眠行为障碍(RBD)异常,而震颤为主型原发性PD患者2.5%出现RBD异常。结论 PIGD为主型较震颤为主型原发性PD患者更易出现睡眠障碍及RBD异常表现,可能与PD不同亚型的临床异质性相关。     

阿尔马尔治疗原发性震颤30例临床观察

目的 观察阿尔马尔治疗原发性震颤的疗效和安全性。方法 采用多中心开放试验，对30例原发性震颤患者给予阿尔马尔10mg，每日一次，共4周。对疗效不好者，从第3周开始增加剂量至15mg每日一次，总计6周。于治疗前及治疗后第2，4，6周进行症状评分。结果 阿尔马尔治疗原发性震颤的总有效率为73．4％，而且对正常的血压和心率无明显影响，不良反应轻微。结论 阿尔马尔是治疗原发性震颤的有效药物，服用方便而且安全。     

家族性特发性震颤合并痉挛性斜颈的临床特点(附2例报告)

目的探讨家族性特发性震颤(ET)合并痉挛性斜颈的临床特点。方法对2例家族性ET合并痉挛性斜颈患者的临床资料进行回顾性分析。结果 2例患者均为中年女性,表现为双上肢或四肢不自主颤抖27年、14年,缓慢加重;头颈向右歪斜10年、2个月。1例患者家系中有上肢不自主颤抖3例,另1例患者家系中有头部或上肢不自主颤抖3例及头颈肌张力障碍1例。EMG示胸锁乳突肌、颈部肌肉有成组运动单位电位阵发性发放。经A型肉毒素局部注射治疗及心得安、苯海索、乙哌立松、扑米酮等口服治疗,症状明显好转。结论家族性ET合并痉挛性斜颈患者在青年期出现ET,十多年后出现痉挛性斜颈;有家族遗传史;EMG有自发运动单位电位;A型肉毒素局部注射治疗有效。     

脑深部电刺激术治疗震颤

目的探讨脑深部电刺激术（brain deep stimulation,DBS）治疗各种震颤的疗效、术中手术靶点确定以及术后程控策略.方法采用微电极记录下丘脑腹中间核和丘脑底核电刺激术,对4例原发性震颤（essentialtremor,ET）（其中1例合并帕金森病患者靶点选择丘脑底核）和1例窒息后震颤症患者进行治疗.结果4例ET患者经过2～4次调试,双侧上肢症状控制满意（改善率在75%～90%）,其中1例头部震颤和发音震颤患者症状显著改善（改善率分别为82%和84%）.1例缺氧后震颤患者经多次调试症状改善不明显.其中1例行双侧DBS治疗的ET患者,手术后2个月出现慢性硬膜下血肿,经手术清除后痊愈,且开启DBS后症状控制满意.5例患者均没有出现永久性并发症.结论DBS是治疗ET双侧症状的首选方法,相对于丘脑毁损术（尤其是双侧）有较高的安全性.     

微电极引导苍白球腹后部毁损术治疗帕金森病震颤

目的分析微电极引导苍白球毁损术对帕金森病震颤的治疗效果,为震颤型帕金森病外科手术方法的选择提供依据.方法79例震颤型帕金森病患者进行了苍白球毁损术,术前及术后3个月采用VAS(Visual Analog Scale)对患者震颤严重程度进行评估.运用多针道寻找并毁损震颤同步细胞,微电极刺激验证靶点提高手术对震颤的治疗效果.结果79例患者中,术前重度震颤者38例(48.1%)、术后重度震颤2例(2.5%),其中16例(20.3%)震颤完全消除;术中包含震颤同步细胞者68例(86.6%),其中术前重度震颤者33例(48.5%)、术后重度震颤1例(1.5%);79例患者术后震颤改善显著68例(86.1%),在包含震颤同步细胞68例中,震颤改善显著62例(91.2%),P＜0.05,有统计学意义.结论微电极引导腹后苍白球毁损术对帕金森病震颤有很好的疗效,显著改善率为86.1%.震颤同步细胞的毁损对震颤的疗效起重要作用,3微电极引导腹后苍白球毁损术应该作为治疗震颤型帕金森病的首选.     

Essential tremor centralized brain repository: diagnostic validity and clinical characteristics of a highly selected group of essential tremor cases.

We studied essential tremor (ET) cases enrolled in the Essential Tremor Centralized Brain Repository to (1) assess the validity of their diagnoses and (2) characterize the clinical features in a group of highly selected cases who might reflect a far end of the disease spectrum. Our over-arching goal was to provide a perspective of ET that complements that derived from population-based and clinic-based studies. Based on a history and videotaped examination, 94 of 100 ET cases had their diagnoses confirmed; most of the remainder had Parkinson's disease. When compared with ET cases ascertained through populations and clinics, a large proportion had been prescribed medication for tremor (87.2%), had a family history of tremor (88.3%), had rest tremor (33.0%), or had neck tremor (60.6%). One patient had facial tremor, which has not been reported previously. As has been reported once before, a large proportion wore hearing aids (26.9% of the 67 participants age>or=70). In summary, diagnostic validity was high. In terms of their clinical characteristics, the high proportion of cases with severe tremor and varied disease manifestations (neck tremor, rest tremor) make these cases a valuable resource in pathological studies; the high proportion with familial tremor would provide an enriched sample for genetic studies.     

Clinical and genetic study of essential tremor in the Italian population

Essential tremor (ET) is one of the most common movement disorders. The pathogenesis is as yet unknown, although a genetic cause has long been recognised. Clinical and molecular evidence suggested that the ET gene contains a CAG expanded region. We examined a cohort of 240 Italian ET patients, classified as familial (193 cases) and sporadic (47 cases). The clinical manifestations of ET patients confirmed that the disorder is characterised by a large phenotypic variability. Repeat expansion detection (RED) approach did not demonstrate large CAG expansions. Six families were genotyped with 12 microsatellites markers of 2p and 3q regions and analysed according to parametrical methods. Lod scores values obtained in these families excluded the association of ET with 2p and 3q loci. Our findings confirm the presence of genetic heterogeneity and suggest that at least a third locus is involved in the pathogenesis of familial essential tremor.     

Isolated tremor and disruption of the nigrostriatal dopaminergic system: an 18F-dopa PET study.

We measured striatal 18F-dopa influx constants (Ki) for 20 patients with isolated, predominantly postural, tremor (eight familial, 12 sporadic) and 11 with predominantly rest tremor. Results were compared with 30 controls and 16 Parkinson's disease (PD) patients. The eight familial essential tremor (ET) patients had normal striatal 18F-dopa uptake. Two of the 12 sporadic postural tremor patients had subnormal putamen 18F-dopa Ki, one (who later became akinetic) falling in the PD range. The mean putamen 18F-dopa uptake of the 11 rest tremor patients was reduced to PD levels (51% of normal). Our findings argue against an association between ET and PD, but support the existence of a "benign" tremulous variant of PD. The presence of low-amplitude rest tremor, cogwheel rigidity, reduced arm swing, and short tremor duration was not a useful predictor of nigral dysfunction in patients with postural tremor. In contrast, patients with predominantly rest tremor, particularly with onset in the leg, consistently showed reduced putamen 18F-dopa uptake.     

特发性震颤的临床和电生理学特点

目的 探讨特发性震颤(EI)的临床和电生理学特点.方法 回顾性分析并比较33例ET患者(ET组)和30例生理性震颤患者(对照组)的震颤类型、程度、幅度和负重对其的影响,以总结ET的临床和电生理学特点.结果 ET组患者动作性震颤(KT)的震颤程度明显高于对照组,震颤幅度明显大于对照组(均P＜0.01);而姿势性震颤(PT...     

Familial essential tremor is not associated with SCA-12 mutation in southern Italy.

We investigated 30 patients with familial essential tremor (ET) for spinocerebellar ataxia type 12 (SCA-12) mutations. No patient presented a CAG repeat larger than 19, suggesting that familial ET and SCA-12 are distinct diseases.     

特发性震颤的临床特点

目的　探讨特发性震颤 (ET)的临床特点。方法　对 80例 ET患者的临床资料进行分析。结果80例 ET中男 5 0例 ,女 30例 ,发病年龄 3～ 70岁 ,平均 34.6± 16 .3岁 ,病程 6个月～ 6 0年 ,平均 14.2± 9.9年。45例 (5 6 .3% )患者有阳性家族史 ,多呈常染色体显性遗传。临床主要表现为单症状的姿势性震颤 ,累及部位依次为手 (92 .5 % )、咽喉部 (2 1.3% )、头 (2 0 % )、下颏 (17.5 % )等。 17.5 %患者因震颤致日常生活困难。 34例饮酒患者中 ,91.2 %显示对酒精有反应性。 6 .3%患者并发帕金森病 (PD)。 6 1%患者小剂量心得安治疗有效。结论　本组 ET患者男多于女 ,发病年龄轻 ,呈单峰模式 ,临床表现为单症状姿势性震颤 ,部分病例可伴发PD,小剂量心得安治疗大多有效。     

合并静止性震颤的原发性震颤患者临床特点分析

目的了解北京地区社区中老年人原发性震颤(essential tremor,ET)的临床特征及其与预后的关系。方法2000年在北京城区、近郊平原、远郊山区调查了2835名55岁以上中老年人,采用筛查和临床诊断两步法确诊患者。发现ET患者135例,对其中合并静止性震颤的患者进行分析,并于2004年对其进行随访。结果其中合并上肢静止性震颤患者17例,占12.6%,合并静止性震颤组震颤总分、头部震颤的比例、肢体震颤总分均明显高于对照组。两组年龄、性别组成、病史无显著性差异,姿势性震颤和动作性震颤的程度差异不明显。4年后随访到13例(13/17),其中3例死亡,实际调查的10例中有9例仍诊断为ET,另1例诊断为临床很可能ET。结论有相当部分社区ET患者可以合并静止性震颤,合并静止性震颤的患者提示病情较重。     

Update on genetics of essential tremor

Despite the research, few advances in the etiopathogenesis on essential tremor (ET) have been made to date. The high frequency of positive family history of ET and the observed high concordance rates in monozygotic compared with dizygotic twins support a major role of genetic factors in the development of ET. In addition, a possible role of environmental factors has been suggested in the etiology of ET (at least in non‐familial forms). Although several gene variants in the LINGO1 gene may increase the risk of ET, to date no causative mutated genes have been identified. In this review, we summarize the studies performed on families with tremor, twin studies, linkage studies, case–control association studies, and exome sequencing in familial ET.     

Jaw tremor: prevalence and clinical correlates in three essential tremor case samples.

The spectrum of involuntary movements seen in essential tremor (ET) is limited. Jaw tremor is one such movement. The prevalence and clinical correlates of jaw tremor have not been studied in detail. The objective of this study was to estimate the prevalence and examine the clinical correlates of jaw tremor in ET using ET cases from three distinct settings (population, tertiary-referral center, brain repository). All ET cases underwent a videotaped tremor examination in which tremors (including limb, head, voice, and jaw) were assessed. The prevalence [95% confidence interval (CI)] of jaw tremor was lowest in the population sample (7.5%; 3.9%-14.2%), intermediate in the tertiary-referral center (10.1%; 6.8%-14.7%), and highest in the brain repository (18.0%; 12.3%-25.5%; P = 0.03). Jaw tremor was associated with older age (P < 0.001), more severe action tremor of the arms (P < 0.001), and presence of head and voice tremor (P < 0.001). Jaw tremor was present in 4/14 (28.6%) ET cases with consistent rest tremor vs. 15/193 (7.8%) cases without rest tremor (odds ratio = 4.8; 95% CI = 1.3-7.0; P = 0.009). The prevalence of jaw tremor was 7.5% to 18.0% and was dependent on the mode of ascertainment, being least prevalent in a population-based sample. ET cases with jaw tremor had a more clinically severe and more topographically widespread disorder. The association in our study between jaw tremor and rest tremor, along with the published observation that jaw tremor can occur in Parkinson's disease (PD), raises the question whether jaw tremor in ET is a marker for subsequent conversion to PD.     

A clinical study of non-parkinsonian and non-cerebellar tremor at a specialty movement disorders clinic

BACKGROUND: No Indian studies have focused on the clinical aspects of tremor. AIMS: To study the distribution of various etiological types of tremor disorders at a Movement Disorders clinic of a large, tertiary care hospital in India and to study the clinical characteristics of essential tremor [ET]. SETTING AND DESIGN: Prospective cross-sectional study at a tertiary care specialty clinic. MATERIAL AND METHODS: Patients presenting with tremor as the chief complaint, with no features suggestive of parkinsonism, cerebellar disorder or acute central nervous system disorder, were included. Patients were classified into different etiological categories from detailed history. All patients diagnosed as ET, were further interrogated for a detailed family history and examined for characteristics of tremor. These patients were then classified into 'definite', 'probable' and 'possible' ET. RESULTS: One hundred and six patients (mean age 44.4 + 15.1 years) were examined during the study period. ET (59.4%) and dystonic tremor (21.7%) were the commonest types. Only 43% patients of ET reported progression; response to alcohol was seen in only a single patient, a positive family history was present in 52.4% and in 36.4% the inheritance was of an autosomal dominant pattern. CONCLUSION: ET and dystonic tremor are the commonest causes of tremor presenting to a specialty Movement Disorders clinic. Most patients with ET have high-frequency tremor, with mild asymmetry in 40% cases. Alcohol responsiveness may not be a useful tool in the diagnosis of ET.