Pub Date : 2024-11-25DOI: 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.
{"title":"Ischemia/reperfusion injury in acute human and experimental stroke: focus on thrombo-inflammatory mechanisms and treatments.","authors":"Guido Stoll, Bernhard Nieswandt, Michael K Schuhmann","doi":"10.1186/s42466-024-00355-y","DOIUrl":"10.1186/s42466-024-00355-y","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Main body: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"6 1","pages":"57"},"PeriodicalIF":0.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18DOI: 10.1186/s42466-024-00337-0
Sreelakshmi V, Amrita Pattanaik, Srilatha Marate, Reeta S Mani, Aparna R Pai, Chiranjay Mukhopadhyay
{"title":"Letter to the editor in response to Professor Josef Finsterer.","authors":"Sreelakshmi V, Amrita Pattanaik, Srilatha Marate, Reeta S Mani, Aparna R Pai, Chiranjay Mukhopadhyay","doi":"10.1186/s42466-024-00337-0","DOIUrl":"10.1186/s42466-024-00337-0","url":null,"abstract":"","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"6 1","pages":"58"},"PeriodicalIF":0.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649816","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}
Pub Date : 2024-11-18DOI: 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。
{"title":"MS brain health quality standards: a survey on the reality in clinical practice in Germany.","authors":"Isabel Voigt, Katja Akgün, Hernan Inojosa, Judith Haas, Herbert Temmes, Sven G Meuth, Gavin Giovannoni, Tjalf Ziemssen","doi":"10.1186/s42466-024-00333-4","DOIUrl":"10.1186/s42466-024-00333-4","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>Participants were asked about time frames considered high standards and those currently being implemented in daily routine based on their experience.</p><p><strong>Results: </strong>The results reveal a large gap between ideal conceptions and their adaptation in the real world, mostly due to a lack of resources.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"6 1","pages":"59"},"PeriodicalIF":0.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649818","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}
Pub Date : 2024-11-18DOI: 10.1186/s42466-024-00336-1
Josef Finsterer
{"title":"Chikungunya-related Guillain-Barre syndrome is most commonly demyelinating and affects multiple cranial nerves.","authors":"Josef Finsterer","doi":"10.1186/s42466-024-00336-1","DOIUrl":"10.1186/s42466-024-00336-1","url":null,"abstract":"","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"6 1","pages":"56"},"PeriodicalIF":0.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649836","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}
Pub Date : 2024-11-12DOI: 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.
{"title":"Prevalence of comorbid autoimmune diseases and antibodies in newly diagnosed multiple sclerosis patients.","authors":"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","doi":"10.1186/s42466-024-00351-2","DOIUrl":"10.1186/s42466-024-00351-2","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"6 1","pages":"55"},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635172","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}
Pub Date : 2024-11-11DOI: 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.
{"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}
Pub Date : 2024-11-06DOI: 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
{"title":"Restless legs syndrome: abbreviated guidelines by the German sleep society and the German neurological society.","authors":"Claudia Trenkwalder, Ambra Stefani, Cornelius G Bachmann, Christian Maihöfner, Johannes Mathis, Lucia Muntean, Julian Mollin, Joachim Paulus, Anna Heidbreder","doi":"10.1186/s42466-024-00353-0","DOIUrl":"10.1186/s42466-024-00353-0","url":null,"abstract":"","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"6 1","pages":"53"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584994","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}
Pub Date : 2024-10-29DOI: 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。
{"title":"Iatrogenic botulism after intragastric botulinum neurotoxin injections - a major outbreak.","authors":"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","doi":"10.1186/s42466-024-00350-3","DOIUrl":"https://doi.org/10.1186/s42466-024-00350-3","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"6 1","pages":"52"},"PeriodicalIF":0.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549870","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}
Pub Date : 2024-10-28DOI: 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.
{"title":"Large-fiber neuropathy in Parkinson's disease: a narrative review.","authors":"Eun Hae Kwon, Julia Steininger, Raphael Scherbaum, Ralf Gold, Kalliopi Pitarokoili, Lars Tönges","doi":"10.1186/s42466-024-00354-z","DOIUrl":"10.1186/s42466-024-00354-z","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Main text: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"6 1","pages":"51"},"PeriodicalIF":0.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515554","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}
Pub Date : 2024-10-22DOI: 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.
{"title":"Cognitive recovery of post critical care patients with and without COVID-19: differences and similarities, an observational study.","authors":"Anna Gorsler, Christiana Franke, Anneke Quitschau, Nadine Külzow","doi":"10.1186/s42466-024-00349-w","DOIUrl":"https://doi.org/10.1186/s42466-024-00349-w","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Trial registration: </strong>Retrospectively registered at https://drks.de/search/de/trial/DRKS00025523 , 21.06.2021.</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"6 1","pages":"50"},"PeriodicalIF":0.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515553","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}