Amyotrophic lateral sclerosis & frontotemporal degeneration最新文献

{"title":"How to measure person-centred care in people living with ALS: development and validation of the patient experience PEMALS questionnaire.","authors":"Ann Katrin Schmidt, Eline W M Scholten, Ruben P A van Eijk, Conny van der Meijden, Charlotte van Esch, Johanna M A Visser-Meily, Leonard H van den Berg, Anita Beelen","doi":"10.1080/21678421.2026.2640128","DOIUrl":"10.1080/21678421.2026.2640128","url":null,"abstract":"<p><p><i>Objective:</i> Person-centredness is a fundamental aspect of care for people with amyotrophic lateral sclerosis (plwALS). Systematic assessment of patient experiences is essential to reflect their perspectives and needs in care. This study aimed to develop and evaluate the psychometric properties of the Patient Experience Measure in ALS care (PEMALS), and to assess the care experience of Dutch plwALS. <i>Methods:</i> We developed a preliminary questionnaire based on literature and input from two representatives, each from a different patient association and three healthcare professionals. In an online survey study, plwALS from the population-based national registry were invited to complete the Dutch questionnaire twice within a 3-day interval. We evaluated test-retest reliability, structural validity, and internal consistency. After item reduction, a total PEMALS score was computed and analyzed for reliability, measurement error, and associations with demographic and clinical patient characteristics. <i>Results:</i> The preliminary questionnaire included 28 items and was completed by 245 plwALS. After item reduction, the final PEMALS contained 16 items. Factor analysis confirmed unidimensionality, with a Cronbach's α of 0.97. Test-retest reliability had an ICC of 0.81 (95% CI 0.72-0.87), and a measurement error of 0.43 points (scale 1 to 10). There was no systematic difference between test-retest (mean difference 0.02, 95% CI 0.05-0.10, <i>p</i> = 0.510). PlwALS rated ALS care with a median score of 9.6 (IQR 8.7-10); 31.4% scored the maximum. Older participants reported significantly higher PEMALS scores (Spearman's r = 0.199, <i>p</i> = 0.002). <i>Conclusions:</i> The PEMALS is a valid and reliable measure for assessing patient experience in ALS care and enables systematic monitoring of person-centered quality of care.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"611-621"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438091","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}

{"title":"Tofersen treatment in SOD1 p.Leu145Phe ALS: real-world outcomes in a genetically homogeneous Croatian cohort.","authors":"Hrvoje Bilić, Marin Begović, Barbara Sitaš, Mirea Hančević, Branimir Ivan Šepec, Andrea Zemba Čilić, Vedrana Peček, Kristina Gotovac Jerčić, Josipa Mateševac, Tamara Bahčić, Laura Peček, Fran Borovečki, Niko Njirić, Jakob Nemir, Marina Petrović, Ivana Jurjević, Marijan Klarica, Iveta Merćep, Ervina Bilić","doi":"10.1080/21678421.2026.2638589","DOIUrl":"10.1080/21678421.2026.2638589","url":null,"abstract":"<p><p><i>Background</i>: Antisense oligonucleotide tofersen targets SOD1 mRNA and reduces production of misfolded SOD1 protein, with demonstrated biomarker and functional signals in clinical trials and open-label extensions. Real-world reports from genetically heterogeneous SOD1 ALS cohorts describe variable functional trajectories. Data from genetically homogeneous founder populations remain limited. We investigated clinical trajectories in a cohort carrying the same pathogenic SOD1 variant to better characterize mutation-specific patterns in a real-world setting. <i>Methods</i>: We conducted a single-center observational study at the National Referral Center for Neuromuscular Diseases and Clinical Electromyoneurography (UHC Zagreb, Croatia). Eight adults with genetically confirmed SOD1 p.Leu145Phe ALS received intrathecal tofersen according to the approved regimen. ALS Functional Rating Scale-Revised (ALSFRS-R) scores were recorded at each dosing visit, and longitudinal slopes were calculated using linear regression. Safety and tolerability were evaluated descriptively. Biomarker and formal respiratory measurements were not routinely available. <i>Results</i>: All patients exhibited lower limb-onset, predominantly lower motor neuron phenotypes consistent with a slow-progressing founder variant. Median age at symptom onset was 60 years, and median therapeutic delay was 48 months. Median on-treatment ALSFRS-R slope was -0.28 points/month (range +0.04 to -0.57). Two patients demonstrated stable trajectories, while the remainder showed gradual decline. These patterns fall within the slower range reported in heterogeneous real-world SOD1 cohorts and are consistent with the known natural history of this mutation. Tofersen was well tolerated, with no serious treatment-related adverse events. <i>Conclusions</i>: In this genetically homogeneous SOD1 p.Leu145Phe cohort, functional trajectories during tofersen therapy reflected the mutation's slow-progressing phenotype. These findings provide real-world clinical context but do not permit conclusions regarding treatment efficacy. Further mutation-specific studies incorporating prospective baseline assessment and biomarker monitoring are needed to clarify therapeutic impact.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"689-695"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147445966","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}

{"title":"Subjective sleep quality in amyotrophic lateral sclerosis: a systematic review and meta-analysis.","authors":"Juyeon Oh, Seong-Il Oh","doi":"10.1080/21678421.2026.2614597","DOIUrl":"10.1080/21678421.2026.2614597","url":null,"abstract":"<p><strong>Objective: </strong>Sleep disturbances are common and clinically significant non-motor symptoms in amyotrophic lateral sclerosis (ALS), arising from motor, respiratory, and psychological factors. This study aimed to synthesize available evidence on subjective sleep quality in ALS, estimate the prevalence of poor sleep quality, examine associated factors, and compare patients with healthy controls.</p><p><strong>Methods: </strong><b>:</b> PubMed, EMBASE, Cochrane Central, and CINAHL were searched for studies published between January 2000 and August 2025 that assessed subjective sleep quality in ALS using validated patient-reported outcome measures, such as Pittsburgh Sleep Quality Index (PSQI). Pooled analyses were performed using random-effects models. Meta-regression was applied to explore associations with demographic and clinical variables.</p><p><strong>Results: </strong>: A total of 23 studies comprising 1899 ALS patients were included, of which 20 were eligible for meta-analysis. All included studies assessed subjective sleep quality using the PSQI, and the pooled mean PSQI score was 6.94, exceeding the clinical cutoff for poor sleep quality. The pooled prevalence of poor sleepers was 56.7%. Nine studies including healthy controls showed significantly higher PSQI scores in ALS patients compared with controls (mean difference 2.69). Several factors, including functional status, depression, anxiety, fatigue, daytime sleepiness, constipation, and cognitive impairment, were associated with poorer sleep, however, meta-regression did not identify significant associations with age, sex, disease duration, or ALSFRS-R.</p><p><strong>Conclusions: </strong>: Sleep disturbances are highly prevalent and clinically significant in ALS. These findings highlight the need for systematic screening and proactive management across all stages of the disease. Future research should evaluate a wider range of interventions to improve sleep quality and patient outcomes.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"553-564"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367308","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}

{"title":"Prioritizing neuropsychological research and care in Amyotrophic Lateral Sclerosis (ALS): building an international neuropsychological framework for ALS.","authors":"Joke De Vocht, Emmet Costello, Caroline McHutchison, Ratko Radakovic, Juliette Foucher, Roisin McMackin, Colm Peelo, Leonard van den Berg, Orla Hardiman, Philip Van Damme, Niall Pender, Sharon Abrahams, Dorothée Lulé","doi":"10.1080/21678421.2025.2610290","DOIUrl":"10.1080/21678421.2025.2610290","url":null,"abstract":"","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"711-714"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913976","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}

{"title":"What can vowel acoustics reveal about the communicative participation of people living with ALS?","authors":"Abigail E Haenssler, June Okada, Marziye Eshghi, Alison Clark, Amrita Iyer, Brian D Richburg, Robert Cavanaugh, Jukka-Pekka Onnela, Katherine M Burke, James D Berry, Jordan R Green, Kathryn P Connaghan","doi":"10.1080/21678421.2025.2598433","DOIUrl":"10.1080/21678421.2025.2598433","url":null,"abstract":"<p><p><i>Objective</i>: Bulbar dysfunction often diminishes the accuracy and speed of the tongue, lip, and jaw movements necessary for speech production. Vowel acoustic features derived from speech recordings can serve as sensitive markers of articulatory accuracy and movement timing. We examined whether degraded speech caused by amyotrophic lateral sclerosis (ALS), assessed through vowel acoustic features, was associated with communicative participation restrictions. As a secondary aim, we assessed the association of two global speech characteristics, rate and intelligibility, with vowel features and communicative participation. <i>Materials & Methods:</i> Thirty-three people with ALS (plwALS) recorded a reading passage and completed surveys using a smartphone application. Speaking rate and acoustic vowel features (duration, vowel articulation index [VAI]) were extracted from the recordings. Three speech-language pathologists rated speech intelligibility. Communicative participation was assessed using the Communicative Participation Item Bank (CPIB) short form. Bivariate correlation, partial correlation, and regression analyses were used to evaluate the associations between vowel features, intelligibility, speaking rate, and CPIB scores. <i>Results:</i> Significant bivariate correlations, ranging from r_s = -0.39 to r_s = 0.64, were found between speech variables and CPIB scores. A combined regression model including VAI, vowel duration, and sex explained 52% of the variance in CPIB scores. Including speaking rate or intelligibility in the partial correlation analysis attenuated the associations between vowel acoustics and CPIB. <i>Conclusions:</i> Vowel features and global dysarthria characteristics are linked to communicative participation in ALS. Clinical practices designed to target vowel production, speaking rate, and intelligibility may help to maintain daily communication in ALS.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"632-640"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13068153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764038","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}

{"title":"A national survey of pseudobulbar affect and symptomatic treatment in Amyotrophic Lateral Sclerosis.","authors":"Christian H Steenkjaer, Jesper H Storgaard, Lotte Levison, Jakob U Blicher","doi":"10.1080/21678421.2026.2620448","DOIUrl":"10.1080/21678421.2026.2620448","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to determine diagnostic prevalence and symptom burden of pseudobulbar affect (PBA) in patients with Amyotrophic Lateral Sclerosis (ALS) in Denmark and differences in ongoing symptomatic treatment.</p><p><strong>Methods: </strong>In this national cross-sectional survey study, participants with ALS completed an online survey regarding PBA and PBA symptoms, which were quantified through the Center for Neurologic Study Lability Scale (CNS-LS). A CNS-LS score ≥ 13 served as a threshold indicative of PBA.</p><p><strong>Results: </strong>157 participants with ALS were recruited. 12.1% were diagnosed with PBA and were more likely to receive antidepressant medication compared to those not diagnosed with PBA (47.4% compared to 15.2%, p = 0.002). 30.6% scored ≥13 in the CNS-LS; however, the proportion of participants treated with antidepressants was similar compared to those scoring below the ≥13 threshold (25% compared to 16.5%, p = 0.27). Of those not diagnosed with PBA, 23.2% scored ≥13 in the CNS-LS. This PBA symptomatic, but undiagnosed group was less likely to receive symptomatic treatment compared to patients with diagnosed PBA (12.5% compared to 47.4%, p = 0.009). No differences were seen in CNS-LS score between these groups.</p><p><strong>Conclusions: </strong>The proportion of diagnosed PBA among the study population was low compared to previous studies; however, the proportion of patients with symptoms of possible PBA was markedly higher. Patients with known PBA were more likely to receive recommended symptomatic treatment compared to patients not diagnosed with PBA, despite symptoms indicative of PBA. These findings highlight the potential underrecognition of PBA in ALS and concurrent absence of symptomatic treatment.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"565-571"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095024","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}

{"title":"Bridging the gap: understanding participation barriers in ALS clinical trials through on-the-ground insights.","authors":"Erica Scirocco, Allison Pogemiller Bulat, Judith R Carey, Elisa Giacomelli, Danielle Boyce, Sabrina Paganoni, James D Berry","doi":"10.1080/21678421.2026.2640126","DOIUrl":"10.1080/21678421.2026.2640126","url":null,"abstract":"<p><strong>Objective: </strong>This study explores the experiences and perceptions of people living with amyotrophic lateral sclerosis (pALS), their caregivers, and healthcare providers regarding participation in clinical trials. The study tested the hypothesis, based on existing literature, that geographic distance from multidisciplinary ALS clinics is the primary barrier to awareness and participation in clinical trials.</p><p><strong>Methods: </strong>A road trip was conducted to engage individuals, particularly those residing more than 90 miles from specialized clinics. Qualitative and semi-quantitative methods were used to collect data from in-person interviews conducted with pALS, their caregivers, and healthcare providers in urban (high population density), suburban (residential areas on the outskirts of urban centers), and rural (sparsely populated) settings across the East Coast of the US. Thematic analysis was employed to interpret the data.</p><p><strong>Results: </strong>Based on the interviews, a trusted, supportive, and knowledgeable medical team knowledgeable about ALS research emerged as a critical factor influencing patient participation decisions. Geographic distance alone did not meaningfully impact research interest or awareness. Healthcare providers faced challenges, including time constraints and limited access to updated information about studies, which hindered their ability to promote participation. Healthcare providers cited informal partnerships with advocacy organizations and research centers as crucial for facilitating research participation.</p><p><strong>Conclusions: </strong>Tailored communication strategies that leverage established relationships between pALS and their trusted healthcare providers may enhance research participation. As decentralized research models evolve, improving trial education and access and fostering knowledge and trust could significantly boost enrollment in ALS clinical research.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"696-703"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367383","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}

{"title":"Gadolinium enhancement of the cauda equina in a case of familial ALS with p.S135G <i>SOD1</i> mutation.","authors":"Sumika Nomizo, Junji Komatsu, Ayano Shima, Daiki Muramatsu, Keitaro Matsubara, Ichiro Nozaki, Moeko Noguchi-Shinohara, Ayumi Nishiyama, Naoki Suzuki, Masashi Aoki, Kenjiro Ono","doi":"10.1080/21678421.2026.2638591","DOIUrl":"10.1080/21678421.2026.2638591","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron degeneration. Gadolinium enhancement of the cauda equina is typically associated with inflammatory diseases. We report a case of familial ALS with a Cu/Zn superoxide dismutase (SOD1) gene mutation showing marked gadolinium enhancement of the lumbar nerve roots. To date, only a few cases of ALS with gadolinium enhancement of the nerve roots have been reported. To our knowledge, this is the first reported case of ALS with an p.S135G <i>SOD1</i> mutation exhibiting gadolinium enhancement in the cauda equina.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"708-710"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367377","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}

{"title":"The World Federation of Neurology Specialty Group in ALS/MND: toward strategic partnership and new frontiers.","authors":"Matthew C Kiernan, Angela Genge, Julian Grosskreutz, Satoshi Kuwabara, Patricia Lillo, Jeffrey Rosenfeld, Cathy Cummings","doi":"10.1080/21678421.2026.2663915","DOIUrl":"10.1080/21678421.2026.2663915","url":null,"abstract":"<p><p>A memorandum of understanding was recently established between the World Federation of Neurology Specialty Group and the International Alliance of ALS/MND Associations. This new strategic partnership brings together leading clinicians and researchers with national and regional organizations dedicated to supporting ALS patients, their families, and caregivers. The purpose of partnership is to strengthen global coordination in research, education, advocacy, and clinical care for people living with MND. The agreement outlines shared priorities, including promoting equitable access to diagnosis and treatment, supporting capacity building in low- and middle-income regions, and facilitating the exchange of scientific knowledge and best practice. Both parties commit to joint initiatives such as international meetings, guideline development, clinical trials and data-sharing efforts that advance understanding of disease mechanisms and therapeutic approaches. Together, these organizations represent the scientific and human dimensions of the ALS challenge. Through partnership, the WFN Specialty Group and the International Alliance aim to accelerate progress toward improved outcomes and, ultimately, effective treatments for MND worldwide.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"501-503"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147823820","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}

{"title":"Utility of patient subgrouping in ALS clinical trials: a World Federation of Neurology white paper.","authors":"Jeffrey Rosenfeld, Sharon Abrahams, Caroline McHutchinson, Senda Ajroud-Driss, Markus Weber, Sabrina Paganoni, Hiroshi Mitsumoto, Angela Genge, Julian Grosskreutz, Leonard Van Den Berg, Jinsy Andrews, Matthew C Kiernan","doi":"10.1080/21678421.2025.2593308","DOIUrl":"10.1080/21678421.2025.2593308","url":null,"abstract":"<p><p>The heterogeneity among the amyotrophic lateral sclerosis (ALS)/MND patient population is well recognized but not well understood. Such heterogeneity may represent a significant confound in our current and prior clinical trials as certain subgroups of patients might have a selective response (or resistance) to a novel therapeutic. The basis on which to segregate the patient population is, however, unclear. The ALS/MND Committee of the World Federation of Neurology (WFN) convened a symposium to discuss various strategies that might be considered for separating (stratifying) the population to further study. The results of that conference are presented here as a white paper, reflecting current understanding of several of the various criteria that could be implemented to divide the patient population as presented and discussed at that meeting. Consideration of grouping patients based on phenotype, cognitive involvement, imaging, or electrophysiology is presented here.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"493-500"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710396","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}