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Ischemia/reperfusion injury in acute human and experimental stroke: focus on thrombo-inflammatory mechanisms and treatments. 急性人类中风和实验性中风的缺血再灌注损伤:关注血栓-炎症机制和治疗方法。
Q2 Medicine Pub Date : 2024-11-25 DOI: 10.1186/s42466-024-00355-y
Guido Stoll, Bernhard Nieswandt, Michael K Schuhmann

Background: Despite high recanalization rates of > 90% after endovascular thrombectomy (EVT) clinical outcome in around 50% of treated acute ischemic stroke (AIS) patients is still poor. Novel treatments augmenting the beneficial effects of recanalization are eagerly awaited, but this requires mechanistic insights to explain and overcome futile recanalization.

Main body: At least two mechanisms contribute to futile recanalization after cerebral large vessel occlusions (LVO): (i) the no reflow phenomenon as evidenced by randomly distributed areas without return of blood flow despite reperfusion of large cerebral arteries, and (ii) ischemia/reperfusion (I/R) injury, the paradoxically harmful aspect of blood flow return in transiently ischemic organs. There is accumulating evidence from experimental stroke models that platelets and leukocytes interact and partly obstruct the microvasculature under LVO, and that platelet-driven inflammation (designated thrombo-inflammation) extends into the reperfusion phase and causes I/R injury. Blocking of platelet glycoprotein receptors (GP) Ib and GPVI ameliorated inflammation and I/R injury providing novel therapeutic options. Recently, MRI studies confirmed a significant, up to 40% infarct expansion after recanalization in AIS thereby proofing the existance of I/R injury in the human brain. Moreover, analysis of minute samples of ischemic arterial blood aspirated directly from the pial cerebral collateral circulation under LVO during the routine EVT procedure confirmed platelet activation and platelet-driven leukocyte accumulation in AIS and, thus, the principal transferability of pathophysiological stroke mechanisms from rodents to man. Two recently published clinical phase 1b/2a trials targeted (thrombo-) inflammation in AIS: The ACTIMIS trial targeting platelet GPVI by glenzocimab provided encouraging safety signals in AIS similar to the ApTOLL trial targeting toll-like receptor 4, a central receptor guiding stroke-induced innate immunity. However, both studies were not powered to show clinical efficacy.

Conclusions: The fact that the significance of I/R injury in AIS has recently been formally established and given the decisive role of platelet-leukocytes interactions herein, new avenues for adjunct stroke treatments emerge. Adjusted study designs to increase the probability of success are of outmost importance and we look forward from what can be learned from the so far unpublished, presumbably negative ACTISAFE and MOST trials.

背景:尽管血管内血栓切除术(EVT)后的再通率超过 90%,但约 50%的急性缺血性卒中(AIS)患者的临床疗效仍然不佳。人们热切期待能增强再通效果的新疗法,但这需要从机理上解释和克服无效再通:至少有两种机制导致脑大血管闭塞(LVO)后再通无果:(i) 无回流现象,表现为随机分布的区域,尽管对大脑血管进行了再灌注,但血流仍未恢复;(ii) 缺血/再灌注(I/R)损伤,即短暂缺血器官中血流恢复的矛盾有害方面。越来越多的实验性中风模型证据表明,血小板和白细胞相互作用,部分阻塞了低血容量状态下的微血管,血小板驱动的炎症(称为血栓炎症)延伸到再灌注阶段并导致 I/R 损伤。阻断血小板糖蛋白受体(GP)Ib和GPVI可改善炎症和I/R损伤,为治疗提供了新的选择。最近,核磁共振成像研究证实,AIS 再通畅后梗死面积显著扩大,最高可达 40%,从而证明了人脑中存在 I/R 损伤。此外,在常规 EVT 过程中,对直接从 LVO 下的大脑侧支循环抽取的微量缺血动脉血样本进行分析,证实了 AIS 中的血小板活化和血小板驱动的白细胞聚集,从而证实了中风的病理生理机制可从啮齿动物转移到人类。最近发表的两项针对 AIS(血栓)炎症的 1b/2a 期临床试验:格伦佐西单抗针对血小板 GPVI 的 ACTIMIS 试验与针对收费样受体 4 的 ApTOLL 试验相似,都为 AIS 提供了令人鼓舞的安全性信号,收费样受体 4 是引导中风诱导的先天性免疫的中心受体。然而,这两项研究均未达到显示临床疗效的水平:结论:I/R损伤在AIS中的重要性最近已被正式确定,鉴于血小板-白细胞相互作用在其中的决定性作用,卒中辅助治疗的新途径应运而生。调整研究设计以提高成功概率至关重要,我们期待着从迄今为止尚未公布的、可能是负面的 ACTISAFE 和 MOST 试验中汲取经验。
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引用次数: 0
Letter to the editor in response to Professor Josef Finsterer. 致编辑的信,回应约瑟夫-芬斯特尔教授。
Q2 Medicine Pub Date : 2024-11-18 DOI: 10.1186/s42466-024-00337-0
Sreelakshmi V, Amrita Pattanaik, Srilatha Marate, Reeta S Mani, Aparna R Pai, Chiranjay Mukhopadhyay
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引用次数: 0
MS brain health quality standards: a survey on the reality in clinical practice in Germany. 多发性硬化症脑健康质量标准:德国临床实践现状调查。
Q2 Medicine Pub Date : 2024-11-18 DOI: 10.1186/s42466-024-00333-4
Isabel Voigt, Katja Akgün, Hernan Inojosa, Judith Haas, Herbert Temmes, Sven G Meuth, Gavin Giovannoni, Tjalf Ziemssen

Background: The quality of treatment is especially critical in the context of complex and chronic diseases such as multiple sclerosis (MS). The Brain Health Initiative, an independent international consortium of neurologists, reached a consensus on time-based quality standards prioritizing brain health-focused care for people with MS.

Objectives: To gain deeper insights into the transferability of these quality standards to a specific area, we conducted a survey among MS experts across various MS centers in Germany.

Methods: Participants were asked about time frames considered high standards and those currently being implemented in daily routine based on their experience.

Results: The results reveal a large gap between ideal conceptions and their adaptation in the real world, mostly due to a lack of resources.

Conclusions: Nevertheless, these guidelines and recommendations can be aspired to as ideals. Consensual and inclusive clinical pathways complemented by measurable quality indicators are needed to improve care and approach these ideals. Neither exists in the current management of MS.

背景:治疗质量对于多发性硬化症(MS)等复杂的慢性疾病尤为重要。脑健康倡议(Brain Health Initiative)是一个由神经科医生组成的独立国际联盟,该联盟就以时间为基础的质量标准达成了共识,即优先考虑为多发性硬化症患者提供以脑健康为重点的治疗:为了深入了解这些质量标准在特定领域的可移植性,我们对德国各多发性硬化症中心的多发性硬化症专家进行了一项调查:方法:我们向参与者询问了被认为是高标准的时间框架,以及根据他们的经验目前在日常工作中实施的标准:结果:调查结果显示,理想构想与现实世界的适应性之间存在巨大差距,主要原因是缺乏资源:尽管如此,这些指南和建议仍可作为理想来追求。为了改善护理并接近这些理想,需要有一致的、包容性的临床路径,并辅以可衡量的质量指标。而在目前的多发性硬化症管理中,两者都不存在。
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引用次数: 0
Chikungunya-related Guillain-Barre syndrome is most commonly demyelinating and affects multiple cranial nerves. 与基孔肯雅病毒相关的格林-巴利综合征最常见的症状是脱髓鞘,会影响多个颅神经。
Q2 Medicine Pub Date : 2024-11-18 DOI: 10.1186/s42466-024-00336-1
Josef Finsterer
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引用次数: 0
Prevalence of comorbid autoimmune diseases and antibodies in newly diagnosed multiple sclerosis patients. 新诊断的多发性硬化症患者合并自身免疫性疾病和抗体的患病率。
Q2 Medicine Pub Date : 2024-11-12 DOI: 10.1186/s42466-024-00351-2
Konstantin Fritz Jendretzky, Lisa-Marie Lezius, Thea Thiele, Franz Felix Konen, André Huss, Lena Heitmann, Yunus Emre Güzeloglu, Philipp Schwenkenbecher, Kurt-Wolfram Sühs, Jelena Skuljec, Mike Peter Wattjes, Torsten Witte, Christoph Kleinschnitz, Refik Pul, Hayrettin Tumani, Stefan Gingele, Thomas Skripuletz

Background: Diagnosing multiple sclerosis (MS) is challenging due to diverse symptoms and the absence of specific biomarkers. Concurrent autoimmune diseases (AID) or non-specific antibodies further complicate diagnosis, progression monitoring, and management. Data on AID prevalence in MS patients are sparse. This study aims to identify concurrent AIDs alongside MS.

Methods: In this retrospective single-center study, we analyzed patient records at our university hospital from 2010 to 2017, focusing on cases suspected of inflammatory demyelinating disease. The 2017 McDonald criteria were applied. Additionally, we measured neurofilament light (NfL) levels from available CSF samples in our biobank.

Results: We identified a total of 315 patients, of whom 66% were women. In total, 13.7% of all patients had concurrent AID, while 20.3% had isolated antibody findings without AID. The most common AID was autoimmune thyroiditis (8.9%), followed by chronic inflammatory skin diseases (1.6%), arthritis (1%), type 1 diabetes (1%), Sjögren's syndrome (0.6%), and inflammatory bowel diseases (0.6%). Cardiolipin antibodies were the most frequent isolated antibody finding (8.6%). Our data showed that, from the perspective of the initial demyelinating event, neither comorbid AID nor isolated antibodies significantly influenced relapses or MS progression over a median follow-up of 9 months. Standard CSF parameters and NfL levels were similar between the groups at the time of MS diagnosis.

Conclusion: Our study shows that AIDs, particularly autoimmune thyroiditis, frequently occur at the onset of MS. The proportion of AIDs commonly treated with immunomodulatory therapy in our cohort was similar to that observed in the general population. Comorbid AID did not affect NfL levels, indicating similar disease activity. Future research should explore new AID emergence during the course of MS, especially considering the increased incidence of rheumatic diseases later in life.

背景:由于多发性硬化症(MS)症状多样且缺乏特异性生物标志物,因此诊断多发性硬化症(MS)极具挑战性。并发自身免疫性疾病(AID)或非特异性抗体使诊断、病情进展监测和管理更加复杂。有关多发性硬化症患者中 AID 患病率的数据非常稀少。本研究旨在确定多发性硬化症并发的自身免疫性疾病:在这项回顾性单中心研究中,我们分析了本大学医院 2010 年至 2017 年的患者病历,重点关注疑似炎症性脱髓鞘疾病的病例。采用了2017年麦克唐纳标准。此外,我们还测量了生物库中现有脑脊液样本的神经丝光(NfL)水平:我们共发现了 315 名患者,其中 66% 为女性。在所有患者中,13.7%的人同时患有自身免疫性疾病,20.3%的人有孤立的抗体发现,但没有自身免疫性疾病。最常见的自身免疫性甲状腺炎(8.9%),其次是慢性炎症性皮肤病(1.6%)、关节炎(1%)、1 型糖尿病(1%)、斯约格伦综合征(0.6%)和炎症性肠病(0.6%)。心磷脂抗体是最常见的分离抗体(8.6%)。我们的数据显示,从最初脱髓鞘事件的角度来看,在中位随访9个月期间,合并AID或孤立抗体都不会对复发或多发性硬化症的进展产生显著影响。在确诊多发性硬化症时,两组患者的标准脑脊液参数和NfL水平相似:我们的研究表明,AID,尤其是自身免疫性甲状腺炎,经常在多发性硬化症发病时出现。在我们的队列中,接受免疫调节治疗的自身免疫性甲状腺炎患者比例与普通人群相似。并发的AID并不影响NfL水平,这表明疾病活动性相似。未来的研究应探索多发性硬化症病程中新出现的 AID,尤其是考虑到晚年风湿性疾病发病率的增加。
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引用次数: 0
Prevalence, diagnosis and management of intracranial atherosclerosis in White populations: a narrative review. 白种人颅内动脉粥样硬化的患病率、诊断和管理:叙述性综述。
Q2 Medicine Pub Date : 2024-11-11 DOI: 10.1186/s42466-024-00341-4
Evangelos Panagiotopoulos, Maria-Ioanna Stefanou, George Magoufis, Apostolos Safouris, Odysseas Kargiotis, Klearchos Psychogios, Sofia Vassilopoulou, Aikaterini Theodorou, Maria Chondrogianni, Eleni Bakola, Frantzeska Frantzeskaki, Tatiana Sidiropoulou, Stavros Spiliopoulos, Georgios Tsivgoulis

Background: Intracranial atherosclerotic disease (ICAD) represents a leading cause of ischemic stroke worldwide, conferring increased risk of recurrent stroke and poor clinical outcomes among stroke survivors. Emerging evidence indicates a paradigm shift, pointing towards increasing detection rates of ICAD among White populations and an evolving epidemiological profile across racial and ethnic groups. The present review aims to provide a comprehensive overview of ICAD, focusing on its pathophysiology, diagnostic approach, and evolving epidemiological trends, including underlying mechanisms, advanced neuroimaging techniques for diagnostic evaluation, racial disparities in prevalence, and current and emerging management strategies.

Main body: Atherosclerotic plaque accumulation and progressive arterial stenosis of major intracranial arteries comprise the pathophysiological hallmark of ICAD. In clinical practice, the diagnosis of intracranial artery stenosis (ICAS) or high-grade ICAS is reached when luminal narrowing exceeds 50% and 70%, respectively. Advanced neuroimaging, including high-resolution vessel wall MRI (HRVW-MRI), has recently enabled ICAD detection before luminal stenosis occurs. While earlier studies disclosed significant racial disparities in ICAS prevalence, with higher rates among Asians, Hispanics, and Blacks, recent evidence reveals rising detection rates of ICAD among White populations. Genetic, environmental and epigenetic factors have been suggested to confer an increased susceptibility of certain ethnicities and races to ICAD. Nevertheless, with improved accessibility to advanced neuroimaging, ICAD is increasingly recognized as an underlying stroke etiology among White patients presenting with acute ischemic stroke and stroke of undetermined etiology. While conventional management of ICAS entails risk factor modification, pharmacotherapy, and endovascular treatment in selected high-risk patients, substantial progress remains to be made in the management of ICAD at its early, pre-stenotic stages.

Conclusion: ICAD remains a critical yet underappreciated risk factor for ischemic stroke across all populations, highlighting the need for increased awareness and improved diagnostic strategies. The emerging epidemiological profile of ICAD across racial groups necessitates a reassessment of risk factors, screening protocols and preventive strategies. Future research should focus on refining the diagnostic criteria and expanding the therapeutic options to cover the full spectrum of ICAD, with the aim of improving patient outcomes and reducing the global burden of intracranial atherosclerosis and stroke.

背景:颅内动脉粥样硬化性疾病(ICAD)是全球缺血性中风的主要病因,增加了中风幸存者复发中风的风险和不良的临床预后。新出现的证据表明模式发生了转变,白人群体中 ICAD 的检出率不断上升,不同种族和民族群体的流行病学特征也在不断变化。本综述旨在全面概述 ICAD,重点关注其病理生理学、诊断方法和不断变化的流行病学趋势,包括其潜在机制、用于诊断评估的先进神经影像学技术、发病率的种族差异以及当前和新兴的管理策略:颅内主要动脉的动脉粥样硬化斑块堆积和进行性动脉狭窄是 ICAD 的病理生理学特征。在临床实践中,颅内动脉狭窄(ICAS)或高级别 ICAS 的诊断标准是管腔狭窄分别超过 50%和 70%。最近,包括高分辨率血管壁磁共振成像(HRVW-MRI)在内的先进神经成像技术已能在管腔狭窄发生之前检测出 ICAD。早期的研究显示,ICAS 的发病率存在明显的种族差异,亚洲人、西班牙裔人和黑人的发病率较高,但最近的证据显示,白人中 ICAD 的检出率在不断上升。遗传、环境和表观遗传因素被认为是导致某些种族和人种更容易患上 ICAD 的原因。然而,随着先进神经影像学技术的普及,越来越多的急性缺血性卒中和病因不明卒中的白人患者认识到 ICAD 是卒中的潜在病因。虽然 ICAS 的传统治疗方法包括改变危险因素、药物治疗和对选定的高危患者进行血管内治疗,但在 ICAD 早期、狭窄前阶段的治疗方面仍有待取得重大进展:ICAD仍然是所有人群中缺血性卒中的一个重要风险因素,但却未得到足够重视,这凸显了提高认知和改进诊断策略的必要性。ICAD 在不同种族群体中新出现的流行病学特征要求对风险因素、筛查方案和预防策略进行重新评估。未来的研究应侧重于完善诊断标准和扩大治疗方案,以涵盖 ICAD 的所有病因,从而改善患者的预后,减轻颅内动脉粥样硬化和中风的全球负担。
{"title":"Prevalence, diagnosis and management of intracranial atherosclerosis in White populations: a narrative review.","authors":"Evangelos Panagiotopoulos, Maria-Ioanna Stefanou, George Magoufis, Apostolos Safouris, Odysseas Kargiotis, Klearchos Psychogios, Sofia Vassilopoulou, Aikaterini Theodorou, Maria Chondrogianni, Eleni Bakola, Frantzeska Frantzeskaki, Tatiana Sidiropoulou, Stavros Spiliopoulos, Georgios Tsivgoulis","doi":"10.1186/s42466-024-00341-4","DOIUrl":"10.1186/s42466-024-00341-4","url":null,"abstract":"<p><strong>Background: </strong>Intracranial atherosclerotic disease (ICAD) represents a leading cause of ischemic stroke worldwide, conferring increased risk of recurrent stroke and poor clinical outcomes among stroke survivors. Emerging evidence indicates a paradigm shift, pointing towards increasing detection rates of ICAD among White populations and an evolving epidemiological profile across racial and ethnic groups. The present review aims to provide a comprehensive overview of ICAD, focusing on its pathophysiology, diagnostic approach, and evolving epidemiological trends, including underlying mechanisms, advanced neuroimaging techniques for diagnostic evaluation, racial disparities in prevalence, and current and emerging management strategies.</p><p><strong>Main body: </strong>Atherosclerotic plaque accumulation and progressive arterial stenosis of major intracranial arteries comprise the pathophysiological hallmark of ICAD. In clinical practice, the diagnosis of intracranial artery stenosis (ICAS) or high-grade ICAS is reached when luminal narrowing exceeds 50% and 70%, respectively. Advanced neuroimaging, including high-resolution vessel wall MRI (HRVW-MRI), has recently enabled ICAD detection before luminal stenosis occurs. While earlier studies disclosed significant racial disparities in ICAS prevalence, with higher rates among Asians, Hispanics, and Blacks, recent evidence reveals rising detection rates of ICAD among White populations. Genetic, environmental and epigenetic factors have been suggested to confer an increased susceptibility of certain ethnicities and races to ICAD. Nevertheless, with improved accessibility to advanced neuroimaging, ICAD is increasingly recognized as an underlying stroke etiology among White patients presenting with acute ischemic stroke and stroke of undetermined etiology. While conventional management of ICAS entails risk factor modification, pharmacotherapy, and endovascular treatment in selected high-risk patients, substantial progress remains to be made in the management of ICAD at its early, pre-stenotic stages.</p><p><strong>Conclusion: </strong>ICAD remains a critical yet underappreciated risk factor for ischemic stroke across all populations, highlighting the need for increased awareness and improved diagnostic strategies. The emerging epidemiological profile of ICAD across racial groups necessitates a reassessment of risk factors, screening protocols and preventive strategies. Future research should focus on refining the diagnostic criteria and expanding the therapeutic options to cover the full spectrum of ICAD, with the aim of improving patient outcomes and reducing the global burden of intracranial atherosclerosis and stroke.</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"6 1","pages":"54"},"PeriodicalIF":0.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Restless legs syndrome: abbreviated guidelines by the German sleep society and the German neurological society. 不宁腿综合征:德国睡眠学会和德国神经学会的简略指南。
Q2 Medicine Pub Date : 2024-11-06 DOI: 10.1186/s42466-024-00353-0
Claudia Trenkwalder, Ambra Stefani, Cornelius G Bachmann, Christian Maihöfner, Johannes Mathis, Lucia Muntean, Julian Mollin, Joachim Paulus, Anna Heidbreder
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引用次数: 0
Iatrogenic botulism after intragastric botulinum neurotoxin injections - a major outbreak. 胃内注射肉毒杆菌神经毒素后的先天性肉毒中毒--一次大爆发。
Q2 Medicine Pub Date : 2024-10-29 DOI: 10.1186/s42466-024-00350-3
Tsepo Goerttler, Martin B Dorner, Christina van der Linden, Ricardo Kienitz, Stephan Petrik, Stephan Blechinger, Jonah Spickschen, Iris R Betz, Carl Hinrichs, David Steindl, Frederike Weber, Thomas Musacchio, Gilbert Wunderlich, Maria Adele Rueger, Michael T Barbe, Haidar Dafsari, Seda Demir, Sriramya Lapa, Pia S Zeiner, Adam Strzelczyk, Peter Tinnemann, Christian Kleine, Andreas Totzeck, Stephan Klebe, Agata Mikolajewska, Brigitte G Dorner, Elisabeth Fertl, Christian Grefkes-Hermann, Gereon Fink, Christoph Kleinschnitz, Tim Hagenacker

Background: Intragastric botulinum neurotoxin injections (IBNI) are offered off-label in the private medical sector in a few European countries as a safe and effective weight-loss measure. In February and March 2023, an outbreak of iatrogenic botulism occurred in several European countries following IBNI treatment in Turkey. This case series describes the clinical features of severe iatrogenic botulism after IBNI.

Methods: We retrospectively summarize the clinical course and emergency department and intensive care unit interventions in ten cases of severe iatrogenic botulism that occurred after receiving IBNI in this sudden outbreak in Austria and Germany.

Results: Seven out of ten cases initially showed characteristic symptoms of botulism with diplopia, dysphagia, dysarthria, dysarthrophonia, and descending paralysis. All patients were hospitalized, six in an intensive care unit and partially requiring mechanical ventilation. All patients recovered and were discharged without relevant permanent deficits.

Conclusion: Our study highlights ten clinical cases in this iatrogenic botulism outbreak, representing the largest reported outbreak worldwide. Clinicians should be aware of the risks associated with medical procedures involving botulinum neurotoxins and ensure measures to minimize the risk of iatrogenic botulism.

背景:在一些欧洲国家,胃内肉毒杆菌神经毒素注射(IBNI)作为一种安全有效的减肥措施,在私人医疗部门被标示外提供。2023 年 2 月和 3 月,在土耳其接受 IBNI 治疗后,欧洲多个国家爆发了先天性肉毒中毒事件。本系列病例描述了 IBNI 治疗后严重先天性肉毒中毒的临床特征:我们回顾性总结了在奥地利和德国突然爆发的肉毒中毒事件中,接受 IBNI 治疗后发生的 10 例重症先天性肉毒中毒病例的临床过程以及急诊科和重症监护室的干预措施:结果:10例患者中有7例最初表现出肉毒中毒的特征性症状,包括复视、吞咽困难、构音障碍、发音障碍和下肢瘫痪。所有患者均住院治疗,其中六人住在重症监护室,部分患者需要机械通气。所有患者均已康复出院,没有出现相关的永久性缺陷:我们的研究突出显示了这起先天性肉毒中毒疫情中的十个临床病例,这是全球报告的最大一起疫情。临床医生应了解涉及肉毒杆菌神经毒素的医疗程序的相关风险,并确保采取措施将先天性肉毒中毒的风险降至最低。
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引用次数: 0
Large-fiber neuropathy in Parkinson's disease: a narrative review. 帕金森病的大纤维神经病变:叙述性综述。
Q2 Medicine Pub Date : 2024-10-28 DOI: 10.1186/s42466-024-00354-z
Eun Hae Kwon, Julia Steininger, Raphael Scherbaum, Ralf Gold, Kalliopi Pitarokoili, Lars Tönges

Background: Numerous studies reported a higher prevalence of polyneuropathy (PNP) in patients with Parkinson's disease (PD) compared to the general population. Importantly, PNP symptoms can aggravate both motor and sensory disturbances in PD patients and negatively impact the disease course. Recent analyses indicate distinct PNP patterns in PD.

Main text: This review aims to provide an overview of the current insights into etiological factors, diagnostic methods, and management strategies of large fiber neuropathy in PD. Despite the higher prevalence, the causes of PNP in PD are still not fully understood. A genetic predisposition can underlie PNP onset in PD. Main research attention is focused on long-term levodopa exposure which is suggested to increase PNP risk by depletion of methylation cofactors such as vitamin B12 and accumulation of homocysteine that altogether can alter peripheral nerve homeostasis. Beyond a potential "iatrogenic" cause, alpha-synuclein deposition has been detected in sural nerve fibers that could contribute to peripheral neuronal degeneration as part of the systemic manifestation of PD. Whereas mild axonal sensory PNP predominates in PD, a considerable proportion of patients also show motor and upper limb nerve involvement. Intriguingly, a correlation between PNP severity and PD severity has been demonstrated. Therefore, PNP screening involving clinical and instrument-based assessments should be implemented in the clinical routine for early detection and monitoring. Given the etiological uncertainty, therapeutic or preventive options remain limited. Vitamin supplementation and use of catechol-O-methyltransferase-inhibitors can be taken into consideration.

Conclusion: PNP is increasingly recognized as a complicating comorbidity of PD patients. Long-term, large-scale prospective studies are required to elucidate the causative factors for the development and progression of PD-associated PNP to optimize treatment approaches. The overall systemic role of "idiopathic" PNP in PD and a putative association with the progression of neurodegeneration should also be investigated further.

背景:许多研究报告显示,帕金森病(PD)患者的多发性神经病(PNP)发病率高于普通人群。重要的是,多发性神经病症状会加重帕金森病患者的运动和感觉障碍,并对病程产生负面影响。最近的分析表明,帕金森病患者的 PNP 模式各不相同:本综述旨在概述目前对帕金森病大纤维神经病变的病因、诊断方法和管理策略的认识。尽管帕金森病的发病率较高,但其病因仍未完全明了。遗传易感性可能是帕金森病大纤维神经病发病的基础。研究的主要关注点集中在长期左旋多巴暴露上,这被认为会增加 PNP 风险,因为甲基化辅助因子(如维生素 B12)的消耗和同型半胱氨酸的积累会共同改变周围神经的稳态。除了潜在的 "先天性 "原因外,α-突触核蛋白沉积已在硬神经纤维中检测到,这可能会导致外周神经元变性,成为脊髓灰质炎全身表现的一部分。虽然轻度轴索感觉型帕金森病在帕金森病中占主导地位,但也有相当一部分患者表现为运动神经和上肢神经受累。耐人寻味的是,PNP 的严重程度与帕金森病的严重程度之间存在相关性。因此,应在临床常规中实施包括临床和仪器评估在内的 PNP 筛查,以便及早发现和监测。鉴于病因的不确定性,治疗或预防方案仍然有限。可以考虑补充维生素和使用儿茶酚-O-甲基转移酶抑制剂:PNP越来越多地被认为是帕金森病患者的并发症之一。需要进行长期、大规模的前瞻性研究,以阐明与帕金森病相关的 PNP 发生和发展的致病因素,从而优化治疗方法。此外,还应进一步研究 "特发性 "PNP 在帕金森病中的整体系统性作用以及与神经退行性病变进展之间的假定关联。
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引用次数: 0
Cognitive recovery of post critical care patients with and without COVID-19: differences and similarities, an observational study. 一项观察性研究:有 COVID-19 和没有 COVID-19 的重症监护后患者的认知恢复:异同。
Q2 Medicine Pub Date : 2024-10-22 DOI: 10.1186/s42466-024-00349-w
Anna Gorsler, Christiana Franke, Anneke Quitschau, Nadine Külzow

Background: Coronavirus disease (COVID-19) patients treated in an intensive care unit (ICU) are at high risk of developing cognitive impairments of a "post-intensive care syndrome" (PICS). We explored whether critically ill COVID-19 and non-COVID-19 survivors differ in their post-ICU recovery course in terms of severity and affected cognitive domains.

Methods: An observational prospective study was conducted in a German post-acute neurological early rehabilitation clinic. Critically ill patients with or without SARS-CoV-2 infection (at least mechanically ventilated for one week) underwent repeated standardized assessments during their subsequent inpatient rehabilitation stay. Cognitive functions (information processing speed, learning, recognition, short-term and working-memory, word fluency, flexibility) assigned to different domains (attention, memory, executive functions) were assessed as primary outcome. Secondary outcomes included mental (depression, anxiety) and physical (Barthel index, modified ranking scale) state.

Results: Out of 92 eligible patients (screened between June 2021 and August 2023), 34 were examined, and 30 were available for analysis (15 per group). Both groups were ventilated for a similar period (COVID-19 vs. Non-COVID-19: median: 48 vs. 53 days). Patients of COVID-19 group spend on average 10 days longer at ICU and developed slightly more complications, but subsequent inpatient rehabilitation was of comparable duration (median: 36.5 vs. 37 days). On the group-level both groups showed similar cognitive dysfunctions with striking impairments (normative T-scores < 41) in information processing speed, word fluency, flexibility, and recognition memory on admission. Significant gains until discharge were only revealed for information processing speed in both groups (main effect visit, mean difference [95%CI] - 7.5 [- 13.1, - 2.0]). Physical and mental state were also similarly affected in both groups on admission, but improved over time, indicating that overall recovery for higher-order cognitive functions is slowest. Interestingly, majority of patients stated correctly being still physically disabled, while a discrepancy was found between subjective and objective evaluation of cognitive health.

Conclusions: Results suggest a substantial overlap of cognitive, mental and physical dysfunction in post-acute recovery of ICU survivors independent of SARS-CoV-2 infection which warrants further monitoring to reduce the risk of long-term burden and enable a return to previous functionality.

Trial registration: Retrospectively registered at https://drks.de/search/de/trial/DRKS00025523 , 21.06.2021.

背景:在重症监护室(ICU)接受治疗的冠状病毒病(COVID-19)患者极有可能出现 "重症监护后综合征"(PICS)的认知障碍。我们探讨了 COVID-19 重症患者和非 COVID-19 重症患者在重症监护室后的恢复过程中在严重程度和受影响的认知领域方面是否存在差异:一项前瞻性观察研究在德国一家急性期后神经系统早期康复诊所进行。感染或未感染 SARS-CoV-2 的重症患者(至少机械通气一周)在随后的住院康复期间接受了重复的标准化评估。认知功能(信息处理速度、学习能力、识别能力、短期记忆和工作记忆、文字流畅性、灵活性)被分配到不同的领域(注意力、记忆力、执行功能),作为主要结果进行评估。次要结果包括精神(抑郁、焦虑)和身体(巴特尔指数、改良等级量表)状态:在 92 名符合条件的患者(筛选时间为 2021 年 6 月至 2023 年 8 月)中,34 人接受了检查,30 人可用于分析(每组 15 人)。两组患者的通气时间相近(COVID-19 组与非 COVID-19 组:中位数:48 天与 53 天)。COVID-19 组患者在重症监护室的平均住院时间长 10 天,并发症略多,但随后的住院康复时间相当(中位数:36.5 天对 37 天)。在组别层面上,两组患者的认知功能障碍相似,都有显著的损伤(常模 T-评分结论):结果表明,ICU 幸存者在急性恢复期后的认知、精神和身体功能障碍有很大的重叠,与 SARS-CoV-2 感染无关,值得进一步监测,以降低长期负担的风险,并使其恢复到以前的功能:回顾性注册:https://drks.de/search/de/trial/DRKS00025523 , 21.06.2021。
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Neurological research and practice
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