dyskinesia

运动障碍
  • 文章类型: Systematic Review
    背景和目的:主要是药物引起的垂直节律性运动障碍运动,仅影响下颌,嘴,和不涉及舌头的嘴唇在历史上被描述为“兔子”综合征(RS)。关于这种疾病的独特特征和含义的证据仍然有限。这篇文献综述旨在评估临床流行病学概况,病理机制,以及这种运动障碍的管理。材料和方法:两名审核员在1972年至2024年之间发表的没有语言限制的六个数据库中确定并评估了相关报告。结果:共发现85篇文献,包含146例RS。精神病医院成年人中RS的平均频率为1.2%(范围为0-4.4%)。受影响患者的平均年龄为49.2(SD:17.5),63.6%为女性。精神分裂症是最常见的共病,占47.6%,其次是双相情感障碍(17.8%),抑郁症(10.3%),强迫症(3.7%)。5例为特发性。与RS相关的最常见药物是氟哌啶醇(17%),利培酮(14%),阿立哌唑(7%),三氟拉嗪(5%),和舒必利(5%)。RS前药物治疗的平均持续时间为21.4周(SD:20.6)。RS与药物诱发的帕金森病(DIP)的发生率为27.4%,与迟发性运动障碍(TD)的发生率为8.2%。抗精神病药修饰和/或抗胆碱能药物在几乎所有报告的处方病例中都能完全或部分康复。结论:RS是一种独特的药物诱发综合征,主要但并非仅与抗精神病药有关。区分RS与TD很重要,因为这两种疾病的治疗选择完全不同。相比之下,RS可能是具有相似病程的DIP症状谱的一部分,治疗结果,和病理生理学。
    Background and Objectives: Vertical rhythmic dyskinetic movements that are primarily drug-induced and affect solely the jaw, mouth, and lips without involving the tongue have been historically described as \"rabbit\" syndrome (RS). Evidence on the unique features and implications of this disorder remains limited. This literature review aims to evaluate the clinical-epidemiological profile, pathological mechanisms, and management of this movement disorder. Materials and Methods: Two reviewers identified and assessed relevant reports in six databases without language restriction published between 1972 and 2024. Results: A total of 85 articles containing 146 cases of RS were found. The mean frequency of RS among adults in psychiatric hospitals was 1.2% (range 0-4.4%). The mean age of affected patients was 49.2 (SD: 17.5), and 63.6% were females. Schizophrenia was the most frequent comorbidity found in 47.6%, followed by bipolar disorder (17.8%), major depressive disorder (10.3%), and obsessive-compulsive disorder (3.7%). Five cases were idiopathic. The most common medications associated with RS were haloperidol (17%), risperidone (14%), aripiprazole (7%), trifluoperazine (5%), and sulpiride (5%). The mean duration of pharmacotherapy before RS was 21.4 weeks (SD: 20.6). RS occurred in association with drug-induced parkinsonism (DIP) in 27.4% and with tardive dyskinesia (TD) in 8.2% of cases. Antipsychotic modification and/or anticholinergic drugs resulted in full or partial recovery in nearly all reported cases in which they were prescribed. Conclusions: RS occurs as a distinct drug-induced syndrome associated primarily but not exclusively with antipsychotics. Distinguishing RS from TD is important because the treatment options for the two disorders are quite different. By contrast, RS may be part of a spectrum of symptoms of DIP with similar course, treatment outcomes, and pathophysiology.
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  • 文章类型: Journal Article
    背景:延迟使用左旋多巴治疗是否可以预防帕金森病(PD)的运动并发症,一直存在争议。
    目的:我们对随机临床试验(RCTs)进行了荟萃分析,比较了左旋多巴在PD中的早期和延迟开始治疗。
    方法:在PubMed,EMBASE,和WebofScience数据库从成立到2023年7月1日。仅包括比较PD中早期和延迟左旋多巴治疗的RCT。来自随访研究的非随机比较也包括在内。我们的主要结果是整体运动并发症的发生,电机波动,和运动障碍。
    结果:我们的分析包括7项研究,共1149例患者(早期启动组636例,延迟启动组513例)。两组之间在运动并发症(OR1.39;95%CI:0.68-1.72;P=0.37)或运动障碍(OR1.52;95%CI:0.90-2.57;P=0.11)方面没有差异。早期启动组的运动波动发生率较低(OR0.70;95%CI:0.52-0.95;P=0.02)。尽管如此,关于多巴胺激动剂的亚组分析,延迟启动组的运动障碍发生率较低(OR1.82;95%CI:1.08-3.07;P=0.03).
    结论:延迟使用左旋多巴治疗似乎不能预防PD患者左旋多巴相关运动并发症。多巴胺激动剂的辅助治疗可以减少对高剂量左旋多巴的需要,从而降低运动障碍的风险,但这种做法通常与多巴胺激动剂相关的不良反应的频率更高。
    BACKGROUND: There has been a long debate whether delaying treatment with levodopa prevents motor complications in Parkinson\'s disease (PD).
    OBJECTIVE: We performed a meta-analysis on randomized clinical trials (RCTs) that compared early- versus delayed-start treatment with levodopa in PD.
    METHODS: A systematic review was conducted in PubMed, EMBASE, and Web of Science databases from inception to July 1, 2023. Only RCTs that compared early and delayed levodopa treatment in PD were included. Non-randomized comparisons from follow-up studies were included as well. Our primary outcomes were occurrence of overall motor complications, motor fluctuations, and dyskinesias.
    RESULTS: Seven studies with a total of 1149 patients (636 in the early-start group and 513 in the delayed-start) were included in our analysis. There was no difference between groups regarding motor complications (OR 1.39; 95% CI: 0.68-1.72; P = 0.37) or dyskinesias (OR 1.52; 95% CI: 0.90-2.57; P = 0.11). Motor fluctuations occurred less frequently in the early-start group (OR 0.70; 95% CI: 0.52-0.95; P = 0.02). Nonetheless, on subgroup analysis of dopamine agonists, rate of dyskinesias was smaller in the delayed-start group (OR 1.82; 95% CI: 1.08-3.07; P = 0.03).
    CONCLUSIONS: Delaying treatment with levodopa does not seem to prevent levodopa-related motor complications in PD. Adjunct treatment with dopamine agonists may reduce the need for higher doses of levodopa and thus reduce the risk for dyskinesias but this practice is often associated with a higher frequency of adverse effects related to dopamine agonists.
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  • 文章类型: Journal Article
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  • 文章类型: Case Reports
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  • 儿童满足综合征(CGS)是指儿童的自我刺激或自慰行为,可能早在婴儿期(IGS)就开始发作。
    这篇综述的目的是了解CGS/IGS的各种临床表现及其与通常误诊的神经和身体疾病的临床区别,并制定其诊断和治疗的初步方法。
    这篇叙述性评论是基于对过去50年(1972-2022年)三个在线数据库(PubMed/Medline,Embase,和谷歌学者)。
    行为是偶发的,发生在短暂的时期,涉及姿势,刻板的肢体运动,耻骨压力与自主神经活动过度,和postepisocial嗜睡。它们模仿癫痫发作,运动障碍,腹痛,和Tics。本文还强调了当前知识的差距,以指导该领域的未来研究。CGS通常代表童年的非病理性“寻求快乐”习惯,但有时,这可能会给孩子和他的家人带来问题。对事件的仔细历史和录像带分析证实了以父母放心为主要治疗手段的诊断和行为治疗。
    必须更好地了解和了解CGS,以防止误诊和延迟适当的干预措施。
    UNASSIGNED: Childhood gratification syndrome (CGS) refers to self-stimulatory or masturbatory behaviors in children, which may have an onset as early as in infancy (IGS).
    UNASSIGNED: The aim of this review is to understand the various clinical manifestations of CGS/IGS and their clinical differentiation from commonly misdiagnosed neurological and physical illnesses and to formulate a preliminary approach to their diagnosis and management.
    UNASSIGNED: This narrative review is based on a search of literature over the past 50 years (1972-2022) in three online databases (PubMed/Medline, Embase, and Google Scholar).
    UNASSIGNED: The behaviors are episodic, occurring for brief periods, involving posturing, stereotypical limb movements, pubic pressure with autonomic hyperactivity, and postepisodic lethargy. They mimic seizures, movement disorders, abdominal pain, and tics. The paper also highlights the gap in the current knowledge to guide future research in the area. CGS usually represents nonpathological \"pleasure-seeking\" habits of childhood, but at times, it may become problematic for the child and his family. A careful history and videotape analysis of the events confirms the diagnosis and behavioral therapy with parental reassurance as the mainstay of treatment.
    UNASSIGNED: A better understanding and clinical awareness of the CGS are necessary to prevent misdiagnosis and delay in appropriate intervention.
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  • 文章类型: Journal Article
    NLX-112(即,F13640,贝非拉多)表现出纳摩尔亲和力,对5-羟色胺5-HT1A受体具有特殊的选择性和完全的激动剂功效。NLX-112在大鼠中显示出功效,帕金森病中L-DOPA诱导的运动障碍(LID)的mar猴和猕猴模型,并在该适应症的2a期概念验证研究中显示出临床疗效。在这里我们调查过,在老鼠身上,它的药效学,药代动力学(PK)和脑5-HT1A受体占据谱,及其在不存在和存在L-DOPA的情况下的PK特性。NLX-112在血浆中的总暴露量和游离暴露量,CSF和纹状体ECF在测试范围内与剂量成比例(0.04、0.16和0.63mg/kgi.p.)。NLX-112暴露迅速增加(Tmax0.25-0.5h),并且在大脑中的半衰期比血浆中长约三倍(1.1和3.6h,分别)。在药物相关剂量为0.16mg/kg腹膜内注射,先前显示在帕金森病大鼠中引起抗LID活性,从0.15到1h,NLX-112的脑浓度为51-63ng/g。在microPET成像实验中,NLX-112显示18F-F13640的剂量依赖性降低(即,18F-NLX-112)扣带皮质和纹状体中的脑5-HT1A受体标记,与运动控制和情绪相关的区域,在0.63mg/kg的剂量下几乎完全抑制标记。L-DOPA的共同给药(6mg/kgs.c.,用于在帕金森病大鼠中引起LID的剂量)与NLX-112(0.16mg/kg腹膜内)一起未改变NLX-112或L-DOPA的大鼠血浆和大脑中的PK参数。这里,我们证明了NLX-112的配置文件与中枢神经系统适应症的“可用药”参数兼容,并且结果提供了与化合物的抗运动障碍活性相关的脑浓度和5-HT1A受体结合参数的测量。
    NLX-112 (i.e., F13640, befiradol) exhibits nanomolar affinity, exceptional selectivity and full agonist efficacy at serotonin 5-HT1A receptors. NLX-112 shows efficacy in rat, marmoset and macaque models of L-DOPA induced dyskinesia (LID) in Parkinson\'s disease and has shown clinical efficacy in a Phase 2a proof-of-concept study for this indication. Here we investigated, in rats, its pharmacodynamic, pharmacokinetic (PK) and brain 5-HT1A receptor occupancy profiles, and its PK properties in the absence and presence of L-DOPA. Total and free NLX-112 exposure in plasma, CSF and striatal ECF was dose-proportional over the range tested (0.04, 0.16 and 0.63 mg/kg i.p.). NLX-112 exposure increased rapidly (Tmax 0.25-0.5h) and exhibited approximately threefold longer half-life in brain than in plasma (1.1 and 3.6h, respectively). At a pharmacologically relevant dose of 0.16 mg/kg i.p., previously shown to elicit anti-LID activity in parkinsonian rats, brain concentration of NLX-112 was 51-63 ng/g from 0.15 to 1h. In microPET imaging experiments, NLX-112 showed dose-dependent reduction of 18F-F13640 (i.e., 18F-NLX-112) brain 5-HT1A receptor labeling in cingulate cortex and striatum, regions associated with motor control and mood, with almost complete inhibition of labeling at the dose of 0.63 mg/kg i.p.. Co-administration of L-DOPA (6 mg/kg s.c., a dose used to elicit LID in parkinsonian rats) together with NLX-112 (0.16 mg/kg i.p.) did not modify PK parameters in rat plasma and brain of either NLX-112 or L-DOPA. Here, we demonstrate that NLX-112\'s profile is compatible with \'druggable\' parameters for CNS indications, and the results provide measures of brain concentrations and 5-HT1A receptor binding parameters relevant to the anti-dyskinetic activity of the compound.
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  • 文章类型: Journal Article
    关键时期是神经发育过程中可塑性增强的窗口。在这些时期神经活动的改变会导致结构的持久变化,连通性,和神经元的内在兴奋性,这可能有助于神经发育障碍的病理学。然而,关键时期的内生调节因子仍然定义不清。这里,我们使用由BK钾通道功能增益(BKGOF)引起的早发性运动障碍的果蝇(果蝇)模型研究了这个问题。采用遗传方法将GOFBK通道的稳健表达置于时空控制下,我们表明,成年期神经元表达的GOFBK通道对果蝇运动的干扰最小。相比之下,在晚期神经发育过程中,将GOFBK通道的神经元表达限制在短窗口内,会严重损害成年果蝇的运动和肢体运动学。在这个关键时期,BKGOF扰乱活性区蛋白Bruchpilot的突触定位并减少兴奋性神经传递。相反,特别是在发育过程中增强神经活动可以挽救BKGOF果蝇的运动缺陷。总的来说,我们的结果揭示了果蝇肢体控制的关键发育时期,该时期受BK通道的影响,并表明BKGOF通过破坏突触发育的活动依赖性方面而引起运动障碍。
    Critical periods are windows of heightened plasticity occurring during neurodevelopment. Alterations in neural activity during these periods can cause long-lasting changes in the structure, connectivity, and intrinsic excitability of neurons, which may contribute to the pathology of neurodevelopmental disorders. However, endogenous regulators of critical periods remain poorly defined. Here, we study this issue using a fruit fly (Drosophila) model of an early-onset movement disorder caused by BK potassium channel gain of function (BK GOF). Deploying a genetic method to place robust expression of GOF BK channels under spatiotemporal control, we show that adult-stage neuronal expression of GOF BK channels minimally disrupts fly movement. In contrast, limiting neuronal expression of GOF BK channels to a short window during late neurodevelopment profoundly impairs locomotion and limb kinematics in resulting adult flies. During this critical period, BK GOF perturbs synaptic localization of the active zone protein Bruchpilot and reduces excitatory neurotransmission. Conversely, enhancing neural activity specifically during development rescues motor defects in BK GOF flies. Collectively, our results reveal a critical developmental period for limb control in Drosophila that is influenced by BK channels and suggest that BK GOF causes movement disorders by disrupting activity-dependent aspects of synaptic development.
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  • 文章类型: Case Reports
    肚皮舞者运动障碍,一种罕见的疾病,可能经常被忽略为常规的非特异性腹痛,因此,要避免误诊,需要高度的临床怀疑。
    Belly dancer dyskinesia, a rare disease, may often be overlooked as a regular nonspecific abdominal pain, and therefore, high index of clinical suspicion is required to avert misdiagnosis.
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  • 文章类型: Journal Article
    肚皮舞者的运动障碍(BDD)的特征是不自主的有节奏的腹壁运动,重复,和运动障碍。本研究旨在回顾BDD的病因,病理生理学,和管理。我们搜索了六个数据库,以查找1990年至2023年10月以电子形式发布的有关BDD的现有报告。共发现47篇文章,包含59个案例。受BDD影响的大多数患者是女性,占病例的61.01%(36/59)。平均年龄和中位数分别为49.8岁(标准偏差:21.85)和52岁(范围:7-85),分别。BDD仅占3.38%(2/59)。与BDD相关的最常见原因是17种特发性,11药物诱导,11术后手术,5次怀孕,和4维生素B12缺乏。BDD是一种排斥诊断,和其他具有类似表现的更常见的病理最初应该被排除。鉴别诊断推理应包括膈肌阵挛症,心脏病,躯干肌张力障碍,腹部运动性癫痫发作,固有脊髓肌阵挛症,和功能或精神疾病。
    Belly dancer\'s dyskinesia (BDD) is characterized by involuntary abdominal wall movements that are rhythmic, repetitive, and dyskinetic. The present study aims to review BDD\'s etiology, pathophysiology, and management. We searched six databases to locate existing reports on BDD published from 1990 to October 2023 in electronic form. A total of 47 articles containing 59 cases were found. The majority of the patients affected by BDD were female, accounting for 61.01% (36/59) of the cases. The mean and median ages were 49.8 (standard deviation: 21.85) and 52 years (range: 7-85), respectively. The BDD was unilateral in only 3.38% (2/59). The most commonly reported causes associated with BDD were 17 idiopathic, 11 drug-induced, 11 postsurgical procedures, 5 pregnancies, and 4 Vitamin B12 deficiencies. BDD is a diagnosis of exclusion, and other more common pathologies with similar presentation should be ruled out initially. Differential diagnostic reasoning should include diaphragmatic myoclonus, cardiac conditions, truncal dystonia, abdominal motor seizures, propriospinal myoclonus, and functional or psychiatric disorders.
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  • 文章类型: Case Reports
    迟发性运动障碍(TD)是一种严重且通常是永久性的并发症,通常在长期使用抗精神病药物后出现。据报道,多种其他类型的药物会导致TD或TD样综合征。TD可以影响身体的任何部位,但它最常见的影响口腔,嘴唇,和舌头。我们介绍了一名86岁女性长期使用左乙拉西坦治疗癫痫发作的口腔-颊-舌运动障碍病例。患者在入院前四年开始服用左乙拉西坦,并注意到急性发作的口腔-口腔-舌运动障碍非常严重,中断了患者的言语和进食。患者的运动障碍在每天两次使用丙戊酸每天750mg交叉减量左乙拉西坦500mg后完全解决。此外,在交叉锥度后,患者的情绪和精神病得到了全球恢复。我们的病例强调了左乙拉西坦对运动障碍运动和神经精神症状的潜在影响,它需要密切监测服用这种药物的患者,尤其是患有多种合并症和肾功能受损的老年人。此外,该病例提示神经精神症状和运动障碍的可逆性。
    Tardive dyskinesia (TD) is a serious and often permanent complication usually seen after the long-term use of antipsychotic medications, and multiple other classes of medications have been reported to cause TD or TD-like syndromes. TD can affect any part of the body, but it most commonly affects the mouth, lips, and tongue. We present a case of oral-buccal-lingual dyskinesia in an 86-year-old female from the long-term use of levetiracetam for a seizure disorder. The patient was started on levetiracetam four years before admission and was noted to have an acute onset of oral-buccal-lingual dyskinesia that was so severe it interrupted the patient\'s speech and feeding. The patient\'s dyskinesias are completely resolved after cross-tapering levetiracetam 500 mg twice a day with valproic acid 750 mg daily. Additionally, there was a global recovery of the patient\'s mood and psychosis after the cross-taper. Our case highlights the potential implications of levetiracetam in dyskinetic movements and neuropsychiatric symptoms, and it warrants close monitoring of patients taking this medication especially elderly with multiple comorbidities and compromised renal function. Moreover, the case suggests the reversible nature of both neuropsychiatric symptoms and dyskinesias.
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