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Individuals and Families Affected by RYR1-Related Diseases: The Patient/Caregiver Perspective. 受 RYR1 相关疾病影响的个人和家庭--患者/护理者的视角。
IF 3.2 4区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-01-01 DOI: 10.3233/JND-240029
Sanne A J H van de Camp, Lizan Stinissen, Andrew Huseth, Brentney Simon, Jennifer Ryan, Anna Sarkozy, Filip Van Petegem, Michael F Goldberg, Heinz Jungbluth, Johann Böhm, Wija Oortwijn, Robert T Dirksen, Nicol C Voermans

Background and objective: Pathogenic variants of RYR1, the gene encoding the principal sarcoplasmic reticulum calcium release channel (RyR1) with a crucial role in excitation-contraction coupling, are among the most common genetic causes of non-dystrophic neuromuscular disorders. We recently conducted a questionnaire study focusing on functional impairments, fatigue, and quality of life (QoL) in patients with RYR1-related diseases (RYR1-RD) throughout the recognized disease spectrum. In this previous questionnaire study the medical perspective was taken, reflective of a study protocol designed by neurologists and psychologists. With this present study we wanted to specifically address the patient perspective.

Methods: Together with affected individuals, family members, and advocates concerned with RYR1-RD, we developed an online patient survey that was completed by 227 patients or their parents/other caretakers (143 females and 84 males, 0-85 years). We invited 12 individuals, representing most of the patient group based on age, sex, race, and type and severity of diagnosis, to share their personal experiences on living with a RYR1-RD during an international workshop in July 2022. Data were analyzed through a mixed-methods approach, employing both a quantitative analysis of the survey results and a qualitative analysis of the testimonials.

Results: Data obtained from the combined quantitative and qualitative analyses provide important insights on six topics: 1) Diagnosis; 2) Symptoms and impact of the condition; 3) Physical activity; 4) Treatment; 5) Clinical research and studies; and 6) Expectations.

Conclusions: Together, this study provides a unique patient perspective on the RYR1-RD spectrum, associated disease impact, suitable physical activities and expectations of future treatments and trials, and thus, offers an essential contribution to future research.

背景和目的:RYR1 是编码主要肌质网钙释放通道(RyR1)的基因,在兴奋-收缩耦合中起着至关重要的作用,RYR1 的致病变体是导致非肌营养不良性神经肌肉疾病的最常见遗传原因之一。我们最近进行了一项问卷调查研究,重点调查了RYR1相关疾病(RYR1-RD)患者在整个公认疾病谱中的功能障碍、疲劳和生活质量(QoL)。在之前的问卷调查中,我们从医学角度出发,采用了由神经学家和心理学家共同设计的研究方案。在本项研究中,我们希望特别从患者的角度出发:我们与受影响的个人、家庭成员以及关注 RYR1-RD 的倡导者共同开发了一项在线患者调查,共有 227 名患者或其父母/其他看护人(143 名女性和 84 名男性,0-85 岁)完成了调查。在 2022 年 7 月的一次国际研讨会上,我们邀请了 12 位代表了大部分患者群体(根据年龄、性别、种族、诊断类型和严重程度)的人士分享他们与 RYR1-RD 患者共同生活的个人经历。数据分析采用混合方法,既对调查结果进行定量分析,又对证言进行定性分析:结果:综合定量和定性分析所获得的数据为以下六个主题提供了重要启示:1) 诊断;2) 症状和病情影响;3) 体力活动;4) 治疗;5) 临床研究;6) 期望:总之,这项研究提供了一个独特的患者视角,让我们了解 RYR1-RD 病谱、相关疾病的影响、适合的身体活动以及对未来治疗和试验的期望,从而为未来研究做出重要贡献。
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引用次数: 0
Findings from the Longitudinal CINRG Becker Natural History Study. 纵向CINRG贝克尔自然历史研究的发现。
IF 3.3 4区 医学 Q2 Medicine Pub Date : 2024-01-01 DOI: 10.3233/JND-230178
Paula R Clemens, Heather Gordish-Dressman, Gabriela Niizawa, Ksenija Gorni, Michela Guglieri, Anne M Connolly, Matthew Wicklund, Tulio Bertorini, Jean Mah, Mathula Thangarajh, Edward C Smith, Nancy L Kuntz, Craig M McDonald, Erik Henricson, S Upadhyayula, Barry Byrne, Georgios Manousakis, Amy Harper, Susan Iannaccone, Utkarsh J Dang

Background: Becker muscular dystrophy is an X-linked, genetic disorder causing progressive degeneration of skeletal and cardiac muscle, with a widely variable phenotype.

Objective: A 3-year, longitudinal, prospective dataset contributed by patients with confirmed Becker muscular dystrophy was analyzed to characterize the natural history of this disorder. A better understanding of the natural history is crucial to rigorous therapeutic trials.

Methods: A cohort of 83 patients with Becker muscular dystrophy (5-75 years at baseline) were followed for up to 3 years with annual assessments. Muscle and pulmonary function outcomes were analyzed herein. Age-stratified statistical analysis and modeling were conducted to analyze cross-sectional data, time-to-event data, and longitudinal data to characterize these clinical outcomes.

Results: Deletion mutations of dystrophin exons 45-47 or 45-48 were most common. Subgroup analysis showed greater pairwise association between motor outcomes at baseline than association between these outcomes and age. Stronger correlations between outcomes for adults than for those under 18 years were also observed. Using cross-sectional binning analysis, a ceiling effect was seen for North Star Ambulatory Assessment but not for other functional outcomes. Longitudinal analysis showed a decline in percentage predicted forced vital capacity over the life span. There was relative stability or improved median function for motor functional outcomes through childhood and adolescence and decreasing function with age thereafter.

Conclusions: There is variable progression of outcomes resulting in significant heterogeneity of the clinical phenotype of Becker muscular dystrophy. Disease progression is largely manifest in adulthood. There are implications for clinical trial design revealed by this longitudinal analysis of a Becker natural history dataset.

背景:贝克肌营养不良症是一种x连锁的遗传性疾病,引起骨骼肌和心肌的进行性变性,具有广泛可变的表型。目的:对经证实的贝克肌营养不良症患者提供的3年纵向前瞻性数据集进行分析,以表征该疾病的自然史。更好地了解自然历史对严格的治疗试验至关重要。方法:83例贝克肌营养不良患者(基线年龄5-75岁)随访3年,每年进行一次评估。本文分析了肌肉和肺功能的结果。进行年龄分层统计分析和建模,分析横截面数据、事件发生时间数据和纵向数据,以表征这些临床结果。结果:肌营养不良蛋白外显子45-47和45-48缺失突变最为常见。亚组分析显示,基线时运动结果的两两相关性大于这些结果与年龄的相关性。与18岁以下的人相比,成年人的结果之间的相关性更强。通过横断面分箱分析,在北极星门诊评估中发现了天花板效应,但在其他功能结果中没有。纵向分析显示,在整个生命周期中,预测的强迫肺活量百分比下降。运动功能结果的中位功能在儿童期和青春期相对稳定或改善,之后随着年龄的增长功能下降。结论:贝克肌营养不良症的临床表型存在显著的异质性,结果的进展是可变的。疾病进展主要表现在成年期。对贝克尔自然历史数据集的纵向分析揭示了临床试验设计的启示。
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引用次数: 0
Real-World Outcomes in Patients with Spinal Muscular Atrophy Treated with Onasemnogene Abeparvovec Monotherapy: Findings from the RESTORE Registry. 脊髓肌肉萎缩症患者接受 Onasemnogene Abeparvovec 单一疗法的实际疗效:RESTORE 登记研究结果。
IF 3.3 4区 医学 Q2 Medicine Pub Date : 2024-01-01 DOI: 10.3233/JND-230122
Laurent Servais, John W Day, Darryl C De Vivo, Janbernd Kirschner, Eugenio Mercuri, Francesco Muntoni, Crystal M Proud, Perry B Shieh, Eduardo F Tizzano, Susana Quijano-Roy, Isabelle Desguerre, Kayoko Saito, Eric Faulkner, Kamal M Benguerba, Dheeraj Raju, Nicole LaMarca, Rui Sun, Frederick A Anderson, Richard S Finkel

Background: Long-term, real-world effectiveness and safety data of disease-modifying treatments for spinal muscular atrophy (SMA) are important for assessing outcomes and providing information for a larger number and broader range of SMA patients than included in clinical trials.

Objective: We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy in the real-world setting.

Methods: RESTORE is a prospective, multicenter, multinational, observational registry that captures data from a variety of sources.

Results: Recruitment started in September 2018. As of May 23, 2022, data were available for 168 patients treated with onasemnogene abeparvovec monotherapy. Median (IQR) age at initial SMA diagnosis was 1 (0-6) month and at onasemnogene abeparvovec infusion was 3 (1-10) months. Eighty patients (47.6%) had two and 70 (41.7%) had three copies of SMN2, and 98 (58.3%) were identified by newborn screening. Infants identified by newborn screening had a lower age at final assessment (mean age 11.5 months) and greater mean final (SD) CHOP INTEND score (57.0 [10.0] points) compared with clinically diagnosed patients (23.1 months; 52.1 [8.0] points). All patients maintained/achieved motor milestones. 48.5% (n = 81/167) experienced at least one treatment-emergent adverse event (AE), and 31/167 patients (18.6%) experienced at least one serious AE, of which 8/31 were considered treatment-related.

Conclusion: These real-world outcomes support findings from the interventional trial program and demonstrate effectiveness of onasemnogene abeparvovec over a large patient population, which was consistent with initial clinical data and published 5-year follow-up data. Observed AEs were consistent with the established safety profile of onasemnogene abeparvovec.

背景:脊髓性肌萎缩症(SMA)疾病修饰治疗的长期、真实世界的有效性和安全性数据对于评估疗效和提供比临床试验中更多和更广泛的 SMA 患者的信息非常重要:我们试图描述在现实世界中接受onasemnogene abeparvovec单药治疗的SMA患者的情况:RESTORE是一项前瞻性、多中心、跨国、观察性登记,从多种来源获取数据:招募始于2018年9月。截至2022年5月23日,共有168名接受onasemnogene abeparvovec单药治疗的患者数据可用。最初诊断为SMA时的中位(IQR)年龄为1(0-6)个月,输注onasemnogene abeparvovec时的中位(IQR)年龄为3(1-10)个月。80名患者(47.6%)有两个SMN2拷贝,70名患者(41.7%)有三个SMN2拷贝,98名患者(58.3%)是通过新生儿筛查确定的。与临床诊断的患者(23.1 个月;52.1 [8.0] 分)相比,通过新生儿筛查确定的婴儿接受最终评估的年龄较小(平均年龄为 11.5 个月),CHOP INTEND 最终平均得分(标清)较高(57.0 [10.0] 分)。所有患者都保持/达到了运动里程碑。48.5%(n = 81/167)的患者至少出现过一次治疗突发不良事件(AE),31/167 的患者(18.6%)至少出现过一次严重不良事件,其中 8/31 被认为与治疗有关:这些真实世界的结果支持了介入试验项目的研究结果,并证明了onasemnogene abeparvovec对大量患者的有效性,这与最初的临床数据和已公布的5年随访数据一致。观察到的不良反应与onasemnogene abeparvovec已建立的安全性特征一致。
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引用次数: 0
Upper Limbs Muscle Co-Contraction Changes Correlate With The Physical Motor Impairments in CMT. 上肢肌肉共收缩变化与 CMT 患者的身体运动障碍有关。
IF 3.2 4区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-01-01 DOI: 10.3233/JND-240006
Tiziana Lencioni, Virginia Bandini, Cristina Schenone, Maria Lagostina, Alessia Aiello, Angelo Schenone, Maurizio Ferrarin, Carlo Trompetto, Laura Mori

Background: Subjects with Charcot-Marie-Tooth (CMT) disease show hands impairment which is a relevant problem affecting the quality of life. This symptom is related to muscle weakness and reduced motor coordination of the upper limb. However, most studies focus on lower limb impairment, therefore the investigation of upper limb disability is necessary to identify biomarkers able to monitor disease-specific features and to tailor rehabilitation.

Objective: This study aimed at characterizing upper limb muscle co-contraction using the co-contraction index (CCI) in CMT population.

Methods: Upper limb kinematic and electromyography (EMG) data were collected from fourteen CMT subjects (6-CMT1A and 8-CMT1X) during motor tasks typical of daily living activities. Rudolph's CCI was used to quantify muscle co-contraction of four muscle pairs acting on shoulder, elbow and wrist. All CMT subjects underwent clinical examination. Thirteen healthy subjects served as the normative reference (HC).

Results: CMT1X and CMT1A showed a significant reduction in CCI for distal and proximal muscle pairs compared to HC. Furthermore, CMT1A showed greater values of CCI compared to CMT1X mainly for the axial and axial-to-proximal muscle pairs. Movement speed and smoothness were not altered compared to HC. In addition, EMG metrics showed moderate-to-strong significant correlations with clinical outcomes.

Conclusions: CCI was able to quantify disease-specific deficits with respect to the normative reference, highlighting motor control alterations even before motor output impairment. CCI was also sensitive in detecting CMT subtypes-based differences and adopted compensatory strategies. Our findings suggest that CCI can be an outcome measure for CMT disease monitoring and interventional studies.

背景:患有 Charcot-Marie-Tooth (CMT) 疾病的患者会出现手部功能障碍,这是影响生活质量的一个相关问题。这种症状与上肢肌肉无力和运动协调能力下降有关。然而,大多数研究都集中在下肢功能障碍方面,因此有必要对上肢残疾进行调查,以确定能够监测疾病特异性特征的生物标记物,并为康复量身定制:本研究旨在利用共收缩指数(CCI)描述 CMT 患者上肢肌肉共收缩的特征:方法:收集了 14 名 CMT 受试者(6 名 CMT1A 和 8 名 CMT1X)在典型的日常生活运动任务中的上肢运动学和肌电图(EMG)数据。鲁道夫 CCI 用于量化作用于肩、肘和腕的四对肌肉的肌肉协同收缩。所有 CMT 受试者均接受了临床检查。13名健康受试者作为常模参照(HC):结果:与 HC 相比,CMT1X 和 CMT1A 远端和近端肌肉对的 CCI 显著降低。此外,与 CMT1X 相比,CMT1A 的 CCI 值更高,主要体现在轴向和轴向至近端肌肉对上。与 HC 相比,运动速度和平稳性没有改变。此外,EMG指标与临床结果显示出中度到高度的显著相关性:结论:CCI 能够量化与常模参照物相比的疾病特异性缺陷,甚至在运动输出受损之前就能突出运动控制的改变。CCI 还能灵敏地检测出基于 CMT 亚型的差异和所采取的补偿策略。我们的研究结果表明,CCI 可以作为 CMT 疾病监测和干预研究的结果测量指标。
{"title":"Upper Limbs Muscle Co-Contraction Changes Correlate With The Physical Motor Impairments in CMT.","authors":"Tiziana Lencioni, Virginia Bandini, Cristina Schenone, Maria Lagostina, Alessia Aiello, Angelo Schenone, Maurizio Ferrarin, Carlo Trompetto, Laura Mori","doi":"10.3233/JND-240006","DOIUrl":"10.3233/JND-240006","url":null,"abstract":"<p><strong>Background: </strong>Subjects with Charcot-Marie-Tooth (CMT) disease show hands impairment which is a relevant problem affecting the quality of life. This symptom is related to muscle weakness and reduced motor coordination of the upper limb. However, most studies focus on lower limb impairment, therefore the investigation of upper limb disability is necessary to identify biomarkers able to monitor disease-specific features and to tailor rehabilitation.</p><p><strong>Objective: </strong>This study aimed at characterizing upper limb muscle co-contraction using the co-contraction index (CCI) in CMT population.</p><p><strong>Methods: </strong>Upper limb kinematic and electromyography (EMG) data were collected from fourteen CMT subjects (6-CMT1A and 8-CMT1X) during motor tasks typical of daily living activities. Rudolph's CCI was used to quantify muscle co-contraction of four muscle pairs acting on shoulder, elbow and wrist. All CMT subjects underwent clinical examination. Thirteen healthy subjects served as the normative reference (HC).</p><p><strong>Results: </strong>CMT1X and CMT1A showed a significant reduction in CCI for distal and proximal muscle pairs compared to HC. Furthermore, CMT1A showed greater values of CCI compared to CMT1X mainly for the axial and axial-to-proximal muscle pairs. Movement speed and smoothness were not altered compared to HC. In addition, EMG metrics showed moderate-to-strong significant correlations with clinical outcomes.</p><p><strong>Conclusions: </strong>CCI was able to quantify disease-specific deficits with respect to the normative reference, highlighting motor control alterations even before motor output impairment. CCI was also sensitive in detecting CMT subtypes-based differences and adopted compensatory strategies. Our findings suggest that CCI can be an outcome measure for CMT disease monitoring and interventional studies.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11307089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IMPatienT: An Integrated Web Application to Digitize, Process and Explore Multimodal PATIENt daTa. IMPatienT:用于数字化、处理和探索多模态患者数据的综合网络应用程序。
IF 3.2 4区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-01-01 DOI: 10.3233/JND-230085
Corentin Meyer, Norma Beatriz Romero, Teresinha Evangelista, Brunot Cadot, Jocelyn Laporte, Anne Jeannin-Girardon, Pierre Collet, Ali Ayadi, Kirsley Chennen, Olivier Poch

Medical acts, such as imaging, lead to the production of various medical text reports that describe the relevant findings. This induces multimodality in patient data by combining image data with free-text and consequently, multimodal data have become central to drive research and improve diagnoses. However, the exploitation of patient data is problematic as the ecosystem of analysis tools is fragmented according to the type of data (images, text, genetics), the task (processing, exploration) and domain of interest (clinical phenotype, histology). To address the challenges, we developed IMPatienT (Integrated digital Multimodal PATIENt daTa), a simple, flexible and open-source web application to digitize, process and explore multimodal patient data. IMPatienT has a modular architecture allowing to: (i) create a standard vocabulary for a domain, (ii) digitize and process free-text data, (iii) annotate images and perform image segmentation, (iv) generate a visualization dashboard and provide diagnosis decision support. To demonstrate the advantages of IMPatienT, we present a use case on a corpus of 40 simulated muscle biopsy reports of congenital myopathy patients. As IMPatienT provides users with the ability to design their own vocabulary, it can be adapted to any research domain and can be used as a patient registry for exploratory data analysis. A demo instance of the application is available at https://impatient.lbgi.fr/.

成像等医疗行为会产生各种描述相关发现的医疗文本报告。因此,多模态数据已成为推动研究和改进诊断的核心。然而,由于分析工具的生态系统根据数据类型(图像、文本、遗传学)、任务(处理、探索)和感兴趣的领域(临床表型、组织学)的不同而支离破碎,因此患者数据的利用存在问题。为了应对这些挑战,我们开发了 IMPatienT(集成数字多模态患者数据),这是一个简单、灵活和开源的网络应用程序,用于数字化、处理和探索多模态患者数据。IMPatienT 采用模块化结构,可以IMPatienT具有模块化架构,允许:(i) 创建一个领域的标准词汇表,(ii) 数字化和处理自由文本数据,(iii) 注释图像和执行图像分割,(iv) 生成一个可视化仪表板并提供诊断决策支持。为了展示 IMPatienT 的优势,我们在一个包含 40 份先天性肌病患者模拟肌肉活检报告的语料库中介绍了一个用例。由于 IMPatienT 允许用户设计自己的词汇表,因此可以适用于任何研究领域,并可用作探索性数据分析的患者登记册。该应用程序的演示实例可在 https://impatient.lbgi.fr/ 上获取。
{"title":"IMPatienT: An Integrated Web Application to Digitize, Process and Explore Multimodal PATIENt daTa.","authors":"Corentin Meyer, Norma Beatriz Romero, Teresinha Evangelista, Brunot Cadot, Jocelyn Laporte, Anne Jeannin-Girardon, Pierre Collet, Ali Ayadi, Kirsley Chennen, Olivier Poch","doi":"10.3233/JND-230085","DOIUrl":"10.3233/JND-230085","url":null,"abstract":"<p><p>Medical acts, such as imaging, lead to the production of various medical text reports that describe the relevant findings. This induces multimodality in patient data by combining image data with free-text and consequently, multimodal data have become central to drive research and improve diagnoses. However, the exploitation of patient data is problematic as the ecosystem of analysis tools is fragmented according to the type of data (images, text, genetics), the task (processing, exploration) and domain of interest (clinical phenotype, histology). To address the challenges, we developed IMPatienT (Integrated digital Multimodal PATIENt daTa), a simple, flexible and open-source web application to digitize, process and explore multimodal patient data. IMPatienT has a modular architecture allowing to: (i) create a standard vocabulary for a domain, (ii) digitize and process free-text data, (iii) annotate images and perform image segmentation, (iv) generate a visualization dashboard and provide diagnosis decision support. To demonstrate the advantages of IMPatienT, we present a use case on a corpus of 40 simulated muscle biopsy reports of congenital myopathy patients. As IMPatienT provides users with the ability to design their own vocabulary, it can be adapted to any research domain and can be used as a patient registry for exploratory data analysis. A demo instance of the application is available at https://impatient.lbgi.fr/.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11307071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Self-Reported Health-Related Quality of Life of Children with Spinal Muscular Atrophy: Preliminary Insights from a Nationwide Patient Registry in Germany. 脊髓性肌肉萎缩症患儿自述的健康相关生活质量:来自德国全国患者登记处的初步见解。
IF 3.3 4区 医学 Q2 Medicine Pub Date : 2024-01-01 DOI: 10.3233/JND-230071
Erik Landfeldt, Berenike Leibrock, Justine Hussong, Simone Thiele, Sophia Abner, Maggie C Walter, Eva Moehler, Michael Zemlin, Ulrich Dillmann, Marina Flotats-Bastardas

Background: Spinal muscular atrophy (SMA) is a rare, severely debilitating neuromuscular disease characterized by a wide spectrum of progressive muscular atrophy and weakness.

Objectives: The objective of this pilot study was to estimate self-assessed health-related quality of life (HRQoL) of children with SMA.

Methods: Children with SMA were recruited via the German national TREAT-NMD SMA patient registry and asked to self-complete the following rating-scales: KIDSCREEN-27, KINDL, the PedsQL 3.0 Neuromuscular Module (PedsQL 3.0 NMM), EQ-5D-5L, and the Health Utilities Index (HUI). Estimates were stratified by current best motor function of the lower limb and trunk (i.e., non-sitter, sitter, and walker) and SMA type (i.e., type I, II, and III).

Results: In total, 17 children with SMA (mean age: 9.88 years, SD: 4.33 years, range: 5-16 years; 59% female) participated in the study. Across examined strata, the mean KIDSCREEN-27 total score was estimated at between 48.24 and 83.81; the mean KINDL total score at between 60.42 and 76.73; the mean PedsQL 3.0 NMM total score at between 58.00 and 83.83; the mean EQ-5D-5L utility at between 0.31 and 0.99; and the mean HUI-derived utility at between -0.02 and 0.96.

Conclusions: The results from this pilot study show that German children with SMA, despite significant physical disability, have surprisingly good HRQoL as assessed using KIDSCREEN-27. Yet, many reside in health states associated with low utility. The disease burden was generally higher among non-sitters compared with walkers, and SMA type I compared with type III, but more research is needed to further delineate this variability. Our preliminary findings contribute to the understanding of HRQoL in pediatric patients with SMA and should be helpful to inform the design of future studies of this patient population.

背景:脊髓性肌萎缩症(SMA脊髓性肌萎缩症(SMA)是一种罕见、严重致残的神经肌肉疾病,其特征是广泛的进行性肌肉萎缩和无力:本试验性研究的目的是评估SMA患儿自我评估的健康相关生活质量(HRQoL):方法:通过德国国家 TREAT-NMD SMA 患者登记处招募 SMA 儿童,要求他们自我填写以下评分量表:KIDSCREEN-27、KINDL、PedsQL 3.0 神经肌肉模块(PedsQL 3.0 NMM)、EQ-5D-5L 和健康效用指数(HUI)。根据目前下肢和躯干的最佳运动功能(即非坐姿、坐姿和步行)和 SMA 类型(即 I 型、II 型和 III 型)进行分层估算:共有 17 名 SMA 患儿(平均年龄:9.88 岁,SD:4.33 岁,年龄范围:5-16 岁;59% 为女性)参加了研究。在所有接受检查的分层中,KIDSCREEN-27 总分的平均值估计在 48.24 和 83.81 之间;KINDL 总分的平均值估计在 60.42 和 76.73 之间;PedsQL 3.0 NMM 总分的平均值估计在 58.00 和 83.83 之间;EQ-5D-5L 实用性的平均值估计在 0.31 和 0.99 之间;HUI 衍生实用性的平均值估计在 -0.02 和 0.96 之间:这项试点研究的结果表明,德国 SMA 患儿尽管有严重的肢体残疾,但在 KIDSCREEN-27 评估的 HRQoL 方面却出人意料地好。然而,许多儿童的健康状况与低效用有关。与步行者相比,不坐立者的疾病负担普遍较重;与 III 型 SMA 患者相比,I 型 SMA 患者的疾病负担普遍较重。我们的初步研究结果有助于人们了解 SMA 儿童患者的 HRQoL,并有助于设计未来针对该患者群体的研究。
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引用次数: 0
Parental Experiences with Newborn Screening and Gene Replacement Therapy for Spinal Muscular Atrophy. 新生儿筛查和脊髓性肌肉萎缩症基因替代疗法的父母经验。
IF 3.3 4区 医学 Q2 Medicine Pub Date : 2024-01-01 DOI: 10.3233/JND-230082
Alayne P Meyer, Anne M Connolly, Kathryn Vannatta, Natasha Hacker, Andrea Hatfield, Abigail Decipeda, Patricia Parker, Ava Willoughby, Megan A Waldrop

Background: Spinal muscular atrophy (SMA) is a genetic neurodegenerative disorder with onset predominantly in infants and children. In recent years, newborn screening and three treatments, including gene replacement therapy (Onasemnogene abeparvovec-xioi), have become available in the United States, aiding in the diagnosis and treatment of children with SMA.

Objective: To evaluate parents' experiences with newborn screening and gene replacement therapy and to explore best practices for positive newborn screen disclosure and counseling of families.

Methods: We conducted semi-structured interviews (n = 32) and online surveys (n = 79) of parents whose children were diagnosed with SMA (on newborn screening or symptomatically) and treated with gene replacement therapy.

Results: Gene replacement therapy was most parents' first treatment choice, although concerns regarding long term efficacy (65%) and safety (51%) were common. Information provided during the newborn screening disclosure was quite variable. Only 34% of parents reported the information provided was sufficient and expressed need for more information about treatment. Although many parents experienced denial of the diagnosis at initial disclosure, 94% were in favor of inclusion of SMA on newborn screening. Parents were almost universally anxious following diagnosis and over half remained anxious at the time of study participation with uncertainty of the future being a key concern. Many parents had difficulty processing information provided during their first clinic appointment due to its complexity and their emotional state at the time.

Conclusions: Utilizing this data, we provide a recommendation for the information provided in newborn screening disclosure, propose adjustments to education and counseling during the first clinic visit, and bring awareness of parents' mental health difficulties.

背景:脊髓性肌萎缩症(SMA)是一种遗传性神经退行性疾病,主要在婴儿和儿童中发病。近年来,新生儿筛查和包括基因替代疗法(Onasemnogene abeparvovec-xioi)在内的三种治疗方法已在美国上市,有助于诊断和治疗 SMA 患儿:评估父母在新生儿筛查和基因替代疗法方面的经验,并探讨新生儿筛查阳性信息披露和家庭咨询的最佳做法:我们对其子女被诊断为 SMA(新生儿筛查或无症状)并接受基因替代疗法治疗的家长进行了半结构化访谈(32 人)和在线调查(79 人):基因替代疗法是大多数家长的首选治疗方法,但他们普遍担心长期疗效(65%)和安全性(51%)。新生儿筛查披露的信息差异很大。只有 34% 的家长表示所提供的信息足够充分,并表示需要更多有关治疗的信息。虽然许多家长在初次披露时否认诊断,但 94% 的家长赞成将 SMA 纳入新生儿筛查。确诊后,家长们几乎普遍感到焦虑,超过半数的家长在参与研究时仍然感到焦虑,对未来的不确定性是他们关注的主要问题。由于信息的复杂性和当时的情绪状态,许多家长在处理首次门诊提供的信息时遇到困难:利用这些数据,我们对新生儿筛查披露的信息提出了建议,对首次就诊时的教育和咨询提出了调整建议,并使人们意识到父母的心理健康问题。
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引用次数: 0
'A novel TRIP4 Variant Associated with Peripheral Neuropathy: Expanding the Clinical and Genetic Spectrum of ASC1-Related Myopathy'. 与周围神经病相关的新型 TRIP4 变异:扩展 ASC1 相关肌病的临床和遗传范围
IF 3.3 4区 医学 Q2 Medicine Pub Date : 2024-01-01 DOI: 10.3233/JND-230110
Ivana Frongia, Carlotta Spagnoli, Susanna Rizzi, Daniele Frattini, Alberta Leon, Stefano Giuseppe Caraffi, Marzia Pollazzon, Livia Garavelli, Francesco Pisani, Carlo Fusco

Activating Signal Cointegrator 1 complex (ASC-1 complex) is a ribonucleoprotein tetramer participating in transcriptional coactivation and RNA processing, consisting of four subunits: ASCC1-ASCC3 and ASC-1. Pathogenic variants in the TRIP4 and ASCC1 genes, encoding the ASC-1 and ASCC1 subunits, were recently described in congenital myopathic conditions without signs of motor neuron involvement, and Spinal Muscular Atrophy-like (SMA-like) phenotype with prenatal bone fractures. We present a novel pathogenic TRIP4 variant in two siblings with severe phenotype and mixed sensory-motor polyneuropathy. The reviewed phenotypic spectrum is broad, but sensory-motor polyneuropathy is so-far unreported. We thus expand ASC-1 related myopathy phenotype.

激活信号结合子 1 复合物(ASC-1 复合物)是一种参与转录共激活和 RNA 处理的核糖核蛋白四聚体,由四个亚基组成:ASCC1-ASCC3 和 ASC-1。编码 ASC-1 和 ASCC1 亚基的 TRIP4 和 ASCC1 基因中的致病变体最近在无运动神经元受累迹象的先天性肌病和伴有产前骨折的脊髓性肌肉萎缩症(SMA)表型中得到了描述。我们发现了一种新的致病性 TRIP4 变体,该变体出现在两个具有严重表型和感觉-运动混合型多发性神经病的兄弟姐妹中。所审查的表型范围很广,但感觉-运动多发性神经病迄今尚未报道。因此,我们扩展了与 ASC-1 相关的肌病表型。
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引用次数: 0
Patient-Reported Outcome Measures in Neuromuscular Diseases: A Scoping Review. Neuromuscular.Diseases: Patient-Reported Outcome Measures in Neuromuscular!Diseases:范围综述》。
IF 3.3 4区 医学 Q2 Medicine Pub Date : 2024-01-01 DOI: 10.3233/JND-240003
Nicoline Voet, Ronne Pater, Joana Garmendia, Andone Sistiaga, Garazi Labayru, Benjamin Gallais, Ingrid de Groot, Samar Muslemani, Cynthia Gagnon, Christopher Graham

 Patient-reported outcome measures (PROMs) are valuable in comprehensively understanding patients' health experiences and informing healthcare decisions in research and clinical care without clinicians' input. Until now, no central resource containing information on all PROMS in neuromuscular diseases (NMD) is available, hindering the comparison and choice of PROMs used to monitor NMDs and appropriately reflect the patient's voice. This scoping review aimed to present a comprehensive assessment of the existing literature on using PROMs in children and adults with NMD. A scoping methodology was followed using Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines to assess the literature on PROMs in NMDs. Eligibility criteria encompassed articles describing psychometric development or evaluation of generic or disease-specific PROM-based instruments for adults and children with specific NMDs. The data charting process involved extracting measurement properties of included PROMs, comprising validity, reliability, responsiveness, and interpretability information. The review identified 190 PROMs evaluated across 247 studies in individuals with NMDs. The majority of PROMs were disease specific. The physical functioning domain was most assessed. Validity was the most frequently investigated measurement property, with a limited number of PROMs sufficiently evaluated for a range of psychometric characteristics. There is a strong need for further research on the responsiveness and interpretability of PROMs and the development of PROMs on social functioning in NMD.

患者报告的结果测量(PROMs)对于全面了解患者的健康体验以及在没有临床医生参与的情况下为研究和临床护理中的医疗决策提供信息非常有价值。迄今为止,还没有包含所有神经肌肉疾病(NMD)PROMS 信息的中央资源,这阻碍了用于监测 NMD 并适当反映患者心声的 PROMs 的比较和选择。本范围界定综述旨在全面评估关于在儿童和成人 NMD 患者中使用 PROMs 的现有文献。范围界定方法采用了系统性综述和荟萃分析的首选报告项目(PRISMA-ScR)和基于共识的健康测量工具选择标准(COSMIN)指南,以评估有关在 NMD 中使用 PROMs 的文献。资格标准包括描述针对特定 NMD 成人和儿童的通用或特定疾病 PROM 工具的心理测量开发或评估的文章。数据制图过程包括提取所纳入的 PROM 的测量属性,包括有效性、可靠性、响应性和可解释性信息。研究发现,在 247 项针对 NMD 患者的研究中评估了 190 个 PROM。大多数 PROM 都是针对特定疾病的。身体功能领域的评估最多。有效性是最常被调查的测量属性,而对一系列心理测量特征进行充分评估的 PROM 数量有限。我们亟需进一步研究 PROM 的响应性和可解释性,并开发有关 NMD 社会功能的 PROM。
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引用次数: 0
Genetic Landscape of Amyotrophic Lateral Sclerosis in Czech Patients. 捷克肌萎缩侧索硬化症患者的基因状况
IF 3.2 4区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-01-01 DOI: 10.3233/JND-230236
Daniel Baumgartner, Zuzana Mušová, Jana Zídková, Petra Hedvičáková, Eva Vlčková, Lubica Joppeková, Tereza Kramářová, Lenka Fajkusová, Viktor Stránecký, Jan Geryk, Pavel Votýpka, Radim Mazanec

Background: Genetic factors are involved in the pathogenesis of familial and sporadic amyotrophic lateral sclerosis (ALS) and constitute a link to its association with frontotemporal dementia (FTD). Gene-targeted therapies for some forms of ALS (C9orf72, SOD1) have recently gained momentum. Genetic architecture in Czech ALS patients has not been comprehensively assessed so far.

Objective: We aimed to deliver pilot data on the genetic landscape of ALS in our country.

Methods: A cohort of patients with ALS (n = 88), recruited from two Czech Neuromuscular Centers, was assessed for hexanucleotide repeat expansion (HRE) in C9orf72 and also for genetic variations in other 36 ALS-linked genes via next-generation sequencing (NGS). Nine patients (10.1%) had a familial ALS. Further, we analyzed two subgroups of sporadic patients - with concomitant FTD (n = 7) and with young-onset of the disease (n = 22).

Results: We detected the pathogenic HRE in C9orf72 in 12 patients (13.5%) and three other pathogenic variants in FUS, TARDBP and TBK1, each in one patient. Additional 7 novel and 9 rare known variants with uncertain causal significance have been detected in 15 patients. Three sporadic patients with FTD (42.9%) were harbouring a pathogenic variant (all HRE in C9orf72). Surprisingly, none of the young-onset sporadic patients harboured a pathogenic variant and we detected no pathogenic SOD1 variant in our cohort.

Conclusion: Our findings resemble those from other European populations, with the highest prevalence of HRE in the C9orf72 gene. Further, our findings suggest a possibility of a missing genetic variability among young-onset patients.

背景:遗传因素参与了家族性和散发性肌萎缩性脊髓侧索硬化症(ALS)的发病机制,并与额颞叶痴呆症(FTD)密切相关。针对某些形式 ALS(C9orf72、SOD1)的基因靶向疗法近来势头强劲。迄今为止,捷克 ALS 患者的基因结构尚未得到全面评估:我们旨在提供有关我国 ALS 遗传结构的试验数据:从捷克两家神经肌肉中心招募的一组 ALS 患者(n = 88)通过新一代测序(NGS)评估了 C9orf72 的六核苷酸重复扩增(HRE)以及其他 36 个 ALS 相关基因的遗传变异。九名患者(10.1%)患有家族性 ALS。此外,我们还分析了散发性患者的两个亚组--伴有FTD(7例)和年轻发病(22例):我们在12名患者(13.5%)中检测到了C9orf72中的致病性HRE,并在一名患者中检测到了FUS、TARDBP和TBK1中的其他三个致病性变异。另外还在 15 名患者中检测到了 7 个新变异和 9 个已知的罕见变异,但其因果关系尚不确定。3名FTD散发性患者(42.9%)携带致病变体(均为C9orf72中的HRE)。令人惊讶的是,在年轻发病的散发性患者中,没有人携带致病变异体,我们在队列中也没有检测到致病的SOD1变异体:结论:我们的研究结果与其他欧洲人群的研究结果相似,C9orf72 基因的 HRE 患病率最高。此外,我们的研究结果表明,年轻发病患者中可能存在基因变异的缺失。
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引用次数: 0
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Journal of neuromuscular diseases
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