多巴反应性肌张力障碍临床分析

目的回顾性分析多巴反应性肌张力障碍患者的临床特点和治疗原则。方法选择2005年3月-2010年7月门诊或住院治疗且诊断明确的多巴反应性肌张力障碍患者,面对面采集临床资料并门诊或电话随访,对其性别、年龄、发病年龄、家族史、首发症状、就诊症状、诊断延误时间及治疗过程进行分析。结果共21例患者入组,男4例、女17例,平均发病年龄(7.19±3.40)岁,平均诊断延误时间(13.76±11.38)年。均以肢体肌张力障碍为首发症状,20例(95.24%)呈现晨轻暮重现象,6例(28.57%)伴帕金森样症状,2例(9.52%)伴痉挛性截瘫;经小剂量左旋多巴/多巴丝肼治疗后症状显著缓解。随访l 8例患者,仅1例治疗后仍遗留肢体残疾;3例失访。随访期间左旋多巴/多巴丝肼平均维持剂量(175.35±113.51)mg/d,3例患者辅助应用盐酸苯海索(4～6 mg/d)治疗。结论多巴反应性肌张力障碍患者多于儿童期以肢体肌张力障碍发病,小剂量左旋多巴/多巴丝肼治疗效果显著。因此,对于儿童肌张力障碍或青年帕金森样症状患者应行小剂量左旋多巴/多巴丝肼诊断性治疗,以降低多巴反应性肌张力障碍的误诊率。     

多巴反应性肌张力障碍

目的探讨多巴反应性肌张力障碍的临床特点、诊断和治疗方法.方法回顾性分析10例多巴反应性肌张力障碍患者的临床表现、诊断方法和治疗效果.结果多巴反应性肌张力障碍发病年龄较早,多见于女孩,表现为肌张力障碍或合并帕金森综合征,呈昼间波动,应用左旋多巴治疗有明显疗效.结论对幼年起病的肌张力障碍或帕金森综合征患者,应首先使用左旋多巴治疗,以筛选出多巴反应性肌张力障碍,使患者能够保持正常生活质量.     

多巴反应性肌张力障碍

目的：探讨多巴反应性肌张力障碍的临床特点、诊断和治疗方法。方法：回顾性分析10例多巴反应性肌张力障碍患的临床表现、诊断方法和治疗效果。结果：多巴反应性肌张力障碍发病年龄较早,多见于女孩,表现为肌张力障碍或合并帕金森综合征,呈昼间波动,应用左旋多巴治疗有明显疗效。结论：对幼年起病的肌张力障碍或帕金森综合征患,应首先使用左旋多巴治疗,以筛选出多巴反应性肌张力障碍,使患能够保持正常生活质量。     

酪氨酸羟化酶基因新型突变所致多巴反应性肌张力障碍1例

多巴反应性肌张力障碍临床罕见，发病率低。本文报告1例酪氨酸羟化酶（tyrosine hydroxylase, TH基因新型突变致多巴反应性肌张力障碍患者的临床资料，为临床诊治提供参考。患者为29岁女性，肢体震颤伴手足姿势异常19年，儿童期急性起病，慢性加重，主要表现为四肢震颤，行走时足尖着地及双手肌肉痉挛，症状存在昼夜波动性特点。查体可见双上肢轻微姿势性及静止性震颤。基因检测提示患者TH基因EXON9 C.943G>A错义突变（遗传自父亲）及TH基因EXON8 C.851A>G错义突变（遗传自母亲）的杂合突变，C.851A>G位点既往未见报告。予小剂量左旋多巴治疗，患者症状明显改善。分析该病例特点及文献回顾表明，多巴反应性肌张力障碍患者诊断主要依赖于基因检测，且不同的临床表型对左旋多巴反应不同。     

多巴反应性肌张力障碍的临床特点

目的探讨多巴反应性肌张力障碍（DRD）的病因、临床特点及治疗方法，加强对该病的认识。方法对13例确诊的DRD患者的临床资料进行回顾性分析。结果本组发病年龄为（14．69±4．01）岁（10～27岁），病程6月～16年。最常见的临床表现为步态、姿势异常及震颤，症状日间波动明显，容易误诊为脑瘫、帕金森病、神经症等。服用小剂量多巴制剂有显著而持久的疗效。结论DRD患者具有症状多样及日间波动的特点。对儿童及青壮年本病患者可首选小剂量左旋多巴试验性治疗。     

多巴反应性肌张力障碍36例临床分析

目的探讨多巴反应性肌张力障碍的病因、临床特点和治疗。方法回顾性分析36例多巴反应肌张力障碍患者的临床资料。结果 36例中男8例,女28例,其中包含2个家系。发病年龄平均9.5岁。均为缓慢起病,首发症状为始自下肢的肌张力障碍者32例,4例以帕金森病样表现起病。症状均呈晨轻暮重。头颅CT、MRI、神经电生理等检查均正常。小剂量多巴制剂治疗有明显疗效。结论本病临床特征显著,只要认识到位,诊断不难,小剂量多巴制剂治疗效果好。     

多巴反应性肌张力障碍32例临床分析

目的 探讨多巴反应性肌张力障碍(dopa-responsive dystonia, DRD)的临床特点.方法 对32例DRD患者从发病年龄,临床症状与体征及其治疗等方面进行回顾性分析.结果 32例患者,男10例,女22例,发病年龄为2-37岁.未成年发病多以肌张力障碍为首发症状,成年期发病多以帕金森综合征起病.未成年发病患者表现日间症状波动性大且腱反射亢进的发生率较高,而成年期发病患者姿势性震颤发生率较高.未成年发病患者中有家族史者占50%,而在成年期起病患者有家族史者占75%.以性别分组后,男性多以肌张力障碍起病,女性这一表现并不明显.对32例患者进行小剂量左旋多巴治疗,有持续明显的疗效.结论 DRD患者具有临床表现多样化的特点,临床表现与年龄密切相关.小剂量左旋多巴对DRD患者具有显著而持久的疗效.     

一个遗传性多巴反应性肌张力障碍家系的临床特点及GCH-Ⅰ基因突变分析

目的 探讨一遗传性多巴反应性肌张力障碍(dopa-responsive dystonia,DRD)家系临床特点和相关基因突变.方法 收集一个多巴反应性肌张力障碍家系全部家庭成员临床资料并随访,采集家系成员静脉血,常规提取基因组DNA,利用PCR技术扩增三磷酸鸟苷环化水解酶Ⅰ(guanosine triphosphate cyclohydrolase 1,GCH-Ⅰ)基因全部6个外显子,进行DNA直接测序并分析.结果 该家系患病成员临床主要表现为肌张力障碍和帕金森综合征,但症状严重程度个体差异大,所以患者对多巴丝肼治疗均有较好反应,1例患者长期大剂量不规律使用左旋多巴后出现异动症.基因测序显示4例患病成员GCH-Ⅰ第四外显子102号碱基由胸腺嘧啶替换为腺嘌呤(T →A),并导致176位丝氨酸(Ser)转变为精氨酸(Arg) Arg176 Ser,该突变类型尚未见文献报道.其余家系成员未发现GCH-Ⅰ基因突变.结论 多巴反应性肌张力障碍临床表现在同一家系不同个体之间可有较大差异,部分患者长期大量不规律使用左旋多巴亦可导致异动症产生.GCH-Ⅰ基因第四外显子102号碱基 (T →A)突变是DRD患病的分子遗传学原因之一.     

多巴反应性肌张力障碍12例分析

目的:分析多巴反应性肌张力障碍(dopa-responsive dystonia,DRD)的临床特点。方法:对12例DRD患者进行临床分析。结果:12例患者,男4例,女8例,发病年龄6～30岁,平均发病年龄13岁,首发症状均为肌张力障碍,下肢起病者10例,上肢起病2例,全部病人均有晨轻暮重的现象,服用小剂量美多巴疗效显著。结论:多巴反应性肌张力障碍具有独特的临床表现和有效的治疗。     

多巴反应性肌张力障碍七例报告

目的加强对多巴反应性肌张力障碍的认识和重视。方法描述我院收治的来自５个家庭７例患者的临床表现、辅助检查及治疗情况。结果男１例,女６例,其中４例为２对姐妹。发病年龄３个月至８岁,平均３１岁,治疗前平均病程１２３年,均表现为缓慢起病的四肢僵硬、活动困难,部分患者伴有肢体震颤、构音不清、吞咽困难,症状均呈晨轻暮重。体检：均有四肢肌张力铅管样或齿轮样增高,多以左侧明显,双下肢腱反射活跃至亢进,部分患者病理征阳性,病程长者可有脊柱和足部畸形。辅助检查除部分患者血清酶增高外,头颅ＣＴ、ＭＲＩ、单光子发射断层扫描、神经电生理检查均正常。小剂量多巴制剂对７例患者均有明显疗效,左旋多巴平均剂量为８４８ｍｇ／ｄ（美多巴或帕金宁控释片）,使用最长者已达１５年,无需增大剂量。结论本病是一种较为罕见的遗传性运动障碍疾病,临床诊断不难,小剂量多巴制剂有显著、持续疗效,早期治疗效果好。     

Dystonia in untreated parkinsonism

While parkinsonism and dystonia generally are distinct clinical syndromes, both may be prominent features even prior to the use of antiparkinsonian medications. In 10 patients with typical parkinsonism, coincident dystonic features included neck, upper extremity, oromandibular, unilateral upper-lower extremity, and unilateral foot dystonia. Six patients were first affected before the age of 45. For some, dystonia preceded parkinsonism (for 1/2 to 20 years). Limb symptoms tended to be unilateral; in seven patients, parkinsonism also was limited to that side. While levodopa was adequate for improvement of parkinsonism, dystonic symptoms benefited from the combination of levodopa with a dopaminergic ergot. The dystonic features (which also can result from parkinsonian therapy) often add pain and disability to the deficits in parkinsonism. The coexistence of dystonia may constitute a distinctive syndrome of parkinsonism and points to possible etiologic mechanisms shared by these two extrapyramidal disorders.     

多巴反应性肌张力障碍

目的：探讨多巴反应性肌张力障碍的临床特点及治疗。方法：观察6例来自4个家族患者的临床表现,辅检查及对左旋多巴治疗的反应。结果：1例儿童期、2例少年期起病者,首发症状均为下肢肌张力异常、足跟着地困难;3例青年起病者表现为震颤、本例题硬;3例出现病理征阳性;6例症状均呈晨轻暮重。服用多巴制剂1－6天内有明显疗效,用药最长者（2例）达7年,未增加剂量。结论：该病临床特点较明显,多巴制剂对其有快速、显著、持续的疗效。     

The long-term response to levodopa in dopa-responsive dystonia

We report the long-term response to levodopa in 20 patients with dopa-responsive dystonia (DRD). We found an inverse correlation between the daily dose of levodopa and duration of treatment (r=-0.59, P<0.01). Mild dyskinesias were present in 20% of our patients. Dyskinetic patients were on a higher dose of levodopa than non-dyskinetics. Dyskinesias responded to a reduction in levodopa, with no deterioration in motor function. We propose that the dopamine turnover might decrease with time, which would lead to a decrease in the requirement for levodopa and the occurrence of dyskinesias late in the course of DRD.     

多巴反应性肌张力障碍15例临床分析

目的 探讨多巴反应性肌张力障碍(DRD)的病因、临床特点及治疗，加强对该病的认识。方法对15例DRD患者的临床资料进行回顾性分析。结果平均发病年龄11．5岁，平均病程8．9年，均为慢性起病，首发症状多从下肢肌张力障碍开始，症状有明显的昼间波动，有晨轻暮重现象。小剂量多巴制剂有显著而持久的疗效。结论本病是一种较为罕见的遗传性运动障碍性疾病，小剂量多巴制剂疗效显著；对儿童期起病的肌张力障碍性患者，应考虑DRD的可能性，早期诊治，预后良好。     

Effect of histamine H2 receptor antagonism on levodopa–induced dyskinesia in the MPTP‐macaque model of Parkinson's disease

Levodopa‐induced motor complications, including dyskinesia and wearing off, are troublesome side effects of treatment and impair quality of life in Parkinson's disease (PD) patients. The use of nondopaminergic agents as adjuncts to levodopa are potential options for managing these problems. Here, we asses the ability of the clinically available, selective histamine H₂ antagonist, famotidine (1, 3, and 30 mg/kg) to treat levodopa‐induced dyskinesia and wearing off in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐macaque model of PD. Famotidine (3 mg/kg) increased peak activity, enhanced peak anti‐parkinsonian action (1 and 3 mg/kg), and extended duration of action (3 mg/kg, by 38%) of a low dose of levodopa (compared to low dose levodopa alone). Enhancement of anti‐parkinsonian actions of low dose levodopa by famotidine (3 mg/kg) was associated with only mild, nondisabling dystonia. Famotidine had no effect on the anti‐parkinsonian actions of high dose levodopa (compared to high dose levodopa alone). However, famotidine (1, 3, and 30 mg/kg) had a significant effect on chorea, but not dystonia, induced by high dose levodopa (compared to high dose levodopa alone). Famotidine increased high dose levodopa–induced “good quality” on time, i.e., on time not associated with disabling dyskinesia, by up to 28% (compared to high dose levodopa alone). In conclusion, famotidine, a drug currently available for use in the clinic, can enhance the peak‐dose anti‐parkinsonian actions and extend total duration of action of a low dose of levodopa, without producing disabling dyskinesia. Furthermore, in combination with a higher dose of levodopa, famotidine can reduce peak‐dose levodopa‐induced chorea and improve the quality of on‐time. © 2010 Movement Disorder Society     

Dystonia in multiple system atrophy

OBJECTIVE: To delineate the frequency and nature of dystonia in multiple system atrophy (MSA). METHODS: A cohort of 24 patients with clinically probable MSA over the past 10 years were prospectively followed up. Motor features were either dominated by parkinsonism (MSA-P subtype, n=18) or cerebellar ataxia (MSA-C, n=6). Classification of dystonic features and their changes with time was based on clinical observation during 6-12 monthly follow up visits. Parkinsonian features and complications of drug therapy were assessed. Most patients (22/24) died during the observation period. Neuropathological examination was confirmatory in all of the five necropsied patients. RESULTS: At first neurological visit dystonia was present in 11 (46%) patients all of whom had been levodopa naive at this time point. Six patients (25%) exhibited cervical dystonia (antecollis) (MSA-P n=4, MSA-C n=2), five patients (21%) showed unilateral limb dystonia (MSA-P n=4; MSA-C n=1). A definite initial response to levodopa treatment was seen in 15/18 patients with MSA-P, but in none of the six patients with MSA-C. A subgroup of 12 patients with MSA-P developed levodopa induced dyskinesias 2.3 years (range 0.5-4) after initiation of levodopa therapy. Most patients had peak dose craniocervical dystonia; however, some patients experienced limb or generalised dystonia. Isolated peak dose limb chorea occurred in only one patient. CONCLUSION: The prospective clinical study suggests that dystonia is common in untreated MSA-P. This finding may reflect younger age at disease onset and putaminal pathology in MSA-P. Levodopa induced dyskinesias were almost exclusively dystonic affecting predominantly craniocervical musculature. Future studies are required to elucidate the underlying pathophysiology of dystonia in MSA.     

Are dopa-responsive dystonia and Parkinson’s disease related disorders? A case report

Objectivel-Dopa-responsive dystonia (DRD) is a hereditary dystonia characterized by an excellent response to low dosages of levodopa. DRD patients may also develop Parkinsonism which resembles idiopathic Parkinson’s disease. In classical DRD no changes in the dopaminergic uptake have been observed.MethodsA 65-year old woman presented with clinically remarkably slowly progressing Parkinson’s disease (PD) without any dystonic signs and excellent response to dopaminergic medications. We obtained a [¹²³I] FP-CIT-SPECT (DaTSCAN?) in order to elucidate a striatal dopaminergic deficit.ResultsWe found a reduced uptake in the [¹²³I] FP-CIT-SPECT (DaTSCAN?) contralateral to the more affected body side. Additionally, the patient showed a heterozygous deletion of the GHC1 gene.ConclusionsPatients with mild parkinsonian symptoms, excellent response to low dosages of dopaminergic drugs and a reduced dopamine-transporter uptake in [¹²³I] FP-CIT-SPECT might more commonly be GCH1 mutation carriers than has previously been supposed. PD patients with a positive family history of DRD and combination of these clinical symptoms should be offered genetic counselling and testing for GCH1.     

Dystonia in progressive supranuclear palsy.

OBJECTIVES: To document the nature, distribution, and frequency of dystonic symptoms in progressive supranuclear palsy (PSP). METHODS: Charts and videotapes of all clinically diagnosed patients with PSP seen between 1983 and 1993 were reviewed and the occurrence, nature, and distribution of all dystonic symptoms were recorded. RESULTS: Of 83 identified cases 38 had some dystonic features. Twenty (24%) had blepharospasm (one was induced by levodopa), 22 (27%) had limb dystonia (one was induced by electroconvulsive therapy and another by levodopa), 14 (17%) had axial dystonia in extension, one had oromandibular dystonia induced by levodopa, and two had other cranial dystonias. Six patients had limb dystonia as an early or presenting feature, sometimes leading to misdiagnosis of cortical-basal ganglionic degeneration. All three patients who had postmortem confirmation of the diagnosis had other concurrent disease. One patient with bilateral limb dystonia and blepharospasm had evidence of previous hydrocephalus and severe arteriosclerotic changes. One with arm dystonia also had cerebrovascular disease and one with hemidystonia also had rare swollen chromatolytic neurons in the frontotemporal cortex. CONCLUSIONS: Dystonia is a common manifestation of PSP. Limb dystonia is particularly common and may indicate the presence of concurrent disease. When dystonia occurs in PSP, dopaminergic medication should be cautiously reduced or discontinued to rule out the possibility of treatment induced symptoms.     

Comparison of lisuride and bromocriptine in the treatment of advanced Parkinson''s disease

Twenty patients with advanced idiopathic Parkinson's disease were studied, all having a deteriorating response to levodopa and suffering from daily fluctuations in disability. A double-blind randomized cross-over study was conducted. Basic levodopa and anticholinergic treatment was continued unchanged in all patients. The dose increment period of 4-8 weeks was followed by a 4 week treatment period on a fixed optimal dose. In both treatment groups the mean optimal daily dose of lisuride was 1.3 mg (range 0.2-2.4 mg) and that of bromocriptine about 15 mg (range 3.75-30.0), without any significant differences between the treatment groups. The addition of lisuride or bromocriptine to levodopa treatment resulted in a significant and equal further improvement of parkinsonian disability. The therapeutic profiles of both lisuride and bromocriptine were similar. There was significantly more improvement in tremor than in other parkinsonian symptoms. Both lisuride and bromocriptine elicited a significant improvement in fluctuations of disability. No significant differences between the treatments were observed. The occurrence of clinical side effects seemed to be similar with both treatment regimens. In advanced parkinsonian patients the therapeutic efficacy of lisuride seems to be equal to that of bromocriptine as far as parkinsonian disability and fluctuations in disability are concerned.