Amyotrophic lateral sclerosis & frontotemporal degeneration最新文献

{"title":"Examining IGFBP7 as a potential therapeutic target in people with ALS.","authors":"Andrew Brown, Colin Stubberfield, Fernando Vieira, Richard Bedlack","doi":"10.1080/21678421.2025.2559441","DOIUrl":"10.1080/21678421.2025.2559441","url":null,"abstract":"<p><p>A single nucleotide variant in an insulin-like growth factor (IGFBP7) promotor, which reduces IGFBP7 levels in brain, was previously associated with an ALS \"reversal\" phenotype. This raises the question of whether IGFBP7 might be a therapeutic target in ALS. Here, we use a combinatorial analysis to show that IGFBP7-Antisense (AS1) is associated with resistance to ALS. In ALS patients' blood, we demonstrate increased IGFPB7 protein relative to healthy controls. In ALS patients' spinal cords and iPS-derived motor neurons, we demonstrate increased IGFBP7 mRNA levels relative to healthy controls. These four new analyses support IGFBP7 as a possible therapeutic target in ALS.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"477-480"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145055387","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":"Novel in-frame duplication variant of <i>SOD1</i> in a Japanese family with familial amyotrophic lateral sclerosis.","authors":"Masanori Nakajima, Hiroya Naruse, Yuichi Riku, Kunihiro Ueda, Takashi Matsukawa, Jun Mitsui, Yoshitsugu Nakamura, Shimon Ishida, Takashi Yamada, Naoki Moro, Naoki Kotsuki, Kentaro Nagai, Shin-Ichi Tokushige, Ayumi Uchibori, Chizuko Oishi, Hiroyuki Yabata, Makoto Urushitani, Yasushi Iwasaki, Hiroyuki Ishiura, Tatsushi Toda, Shoji Tsuji, Yaeko Ichikawa","doi":"10.1080/21678421.2025.2593302","DOIUrl":"10.1080/21678421.2025.2593302","url":null,"abstract":"<p><strong>Objectives: </strong>To analyze the cases of a family with a novel in-frame duplication variant (NM_000454.5:c.357_357 + 2dup, p.Val120dup) of <i>SOD1</i> and a structural model of the mutated SOD1 protein.</p><p><strong>Methods: </strong>The clinical profiles of three patients in the family were analyzed, including the neuropathological findings of the proband's mother. Genetic analyses were conducted for three patients. cDNA and <i>in silico</i> structural analyses were performed to evaluate the effects of duplication variants on the structure of SOD1.</p><p><strong>Results: </strong>The clinical features of the patients included predominant involvement of the lower motor neurons, asymmetric onset of motor symptoms in the lower limbs, and a relatively rapid progression of muscular weakness and respiratory insufficiency. Neuropathological findings revealed severe loss of spinal cord motor neurons, and immunohistochemistry using an anti-misfolded SOD1 antibody revealed aggregates in the spinal cord. Genetic analyses revealed a c.357_357 + 2dup at the exon 4-intron 4 boundary of <i>SOD1</i> in three patients. cDNA analysis of the proband suggested the presence of a valine (p.Val120dup) duplication in the heterozygous state, and the <i>SOD1</i> transcript level showed no significant differences from those of healthy controls. <i>In silico</i> structural analyses predicted that p.Val120dup could affect the structure of the β-barrels and copper ion binding site of SOD1, suggesting an abnormal conformation of SOD1 that is predicted to interfere with the binding of copper ions.</p><p><strong>Conclusion: </strong>We identified a novel in-frame duplication variant in the C-terminus of β7 of SOD1. This genotype-structure-phenotype study of SOD1 provides valuable insights into disease-causing mechanisms.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"352-362"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145671090","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":"Prodromal symptoms in amyotrophic lateral sclerosis from the perspective of the patient and of the caregiver.","authors":"Iris F van Wijk, Lisa Kraneburg, Ruben P A van Eijk, Jan H Veldink, Michael A van Es, Henk-Jan Westeneng, Leonard H van den Berg","doi":"10.1080/21678421.2025.2574687","DOIUrl":"10.1080/21678421.2025.2574687","url":null,"abstract":"<p><strong>Objective: </strong>Clinically manifest ALS is preceded by a prodromal phase in gene mutation carriers, characterized by mild motor impairment. A well-defined prodromal phase could enable earlier diagnosis and treatment. We investigated the presence of a prodromal phase in sporadic ALS, from the perspective of patients and caregivers.</p><p><strong>Methods: </strong>A survey was conducted of symptom onset in 279 ALS patients from a population-based registry and 150 caregivers. 244 patients and 123 caregivers were included in the primary qualitative analysis, followed by quantitative analysis of identified themes. A prodromal phase was defined as symptoms, in response to open-ended questions, before onset of recorded weakness, bulbar complaints or shortness of breath. Mild motor symptoms were defined as fasciculations, cramps, stiffness, atrophy, reduced sports performance, or mobility issues.</p><p><strong>Results: </strong>26.6% of patients and 17.5% of caregivers reported a prodromal phase, primarily with mild motor symptoms (patients 23.0%; caregivers 11.4%). Prodromal symptoms occurred a median of 6.0 months (IQR 2.8-11.8 months) before recorded disease onset. In closed-ended questions, 19.2% of patients and 22.2% of caregivers reported cognitive or behavioral symptoms before weakness onset, compared to only 0.6% and 1.8% in open-ended questions.</p><p><strong>Conclusions: </strong>In sporadic ALS, approximately a quarter of patients report a prodromal phase characterized primarily by mild motor symptoms. However, mild motor symptoms alone are unlikely to contribute to earlier disease recognition. Cognitive or behavioral symptoms are often not recognized as part of the clinical spectrum. These findings emphasize the need for reliable biomarkers to detect ALS pathology at an early stage.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"263-273"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145368958","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":"Unraveling the genetic landscape of ALS in Greece: identification of known and novel causative variants in a 353-patient cohort.","authors":"Chrisoula Kartanou, Zoi Kontogeorgiou, Theodoros Loupis, Dimitrios M Vrachnos, Nikolaos Ragazos, Ifigenia Spyropoulou, Maria Petraki, Chrysoula Koniari, Stavroula Aristeidou, Eleftheria Koropouli, Ariadne Daponte, Michail Rentzos, Elisabeth Kapaki, Marios Panas, Periklis Makrythanasis, Leonidas Stefanis, Georgios Koutsis, Georgia Karadima","doi":"10.1080/21678421.2025.2582828","DOIUrl":"10.1080/21678421.2025.2582828","url":null,"abstract":"<p><strong>Background: </strong>Amyotrophic lateral sclerosis (ALS) is an adult-onset, progressive, fatal neurodegenerative disorder characterized by progressive loss of motor neurons. Approximately 15% of individuals diagnosed with ALS have a known genetic variant that contributes to disease. Herein, we present clinical and genetic data of a large Greek ALS cohort.</p><p><strong>Patients and methods: </strong>The cohort consisted of 353 Greek consecutive index patients with ALS, including 16 patients with related motor neuron disease (MND) subtypes (nine with PLS, four with PBP, and three with PMA). Next generation sequencing raw data (obtained from the NYGC ALS Consortium) were further analyzed and used to screen for causative variants in known implicated genes. Repeat expansions in <i>C9ORF72</i> and <i>ATXN2</i> were investigated using ExpansionHunter software, repeat-primed PCR and fragment analysis.</p><p><strong>Results: </strong>Pathogenic repeat expansions in <i>C9ORF72</i> were detected in 41 patients (11.6%). In addition, 30 patients (8.5%) carried a causative variant in one of the genes studied. Known causative variants were identified in 27 cases (nine in <i>SQSTM1</i>, seven in <i>TARDBP</i>, five in <i>SOD1</i>, three in <i>NEK1</i> and one each in <i>SETX</i>, <i>VCP</i>, <i>FUS</i>), whereas novel causative variants were identified in three cases (<i>SOD1</i>, <i>FIG4</i>, <i>TBK1</i>). In total, 71 cases received a molecular genetic diagnosis (20.1%). Additionally, seven cases (2.0%) carried an intermediate repeat expansion (30-33 CAG) in <i>ATXN2</i>.</p><p><strong>Conclusion: </strong>Our results reveal the distinct genetic profile of Greek ALS patients. These findings will have an impact on genetic counseling, the design of diagnostic gene panels for the Greek population and on genotype-specific therapeutic interventions. Understanding the genetic causes of ALS in different populations is becoming increasingly important, especially with the advent of personalized medicine.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"318-327"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454178","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":"Patient-based evidence for amyotrophic lateral sclerosis prognostic health communication: \"the clock is ticking…how long do I have?\"","authors":"Shelagh K Genuis, Westerly Luth, Brianna Adams, Wendy S Johnston","doi":"10.1080/21678421.2025.2589782","DOIUrl":"10.1080/21678421.2025.2589782","url":null,"abstract":"<p><p><i>Objectives:</i> Prognostic health communication is a critical challenge for amyotrophic lateral sclerosis (ALS) health-care professions, however patient-based evidence for best practice remains limited. We investigated how the experiences of ALS patients and caregivers can inform prognostic communication and whether patient-based evidence supports clinical use of predictive tools. <i>Methods:</i> Data were drawn from ALS Talk, an asynchronous, online focus group study. Patients and family caregivers were recruited from across Canada. Seven groups interacted in a threaded web-forum structure. Sixty-four participants shared experiences and perspectives on prognostic communication. Data were qualitatively analyzed using conventional content analysis and the constant-comparative approach. <i>Results:</i> Primary themes were prognostic communication as an ongoing, evolving conversation; prognostic heterogeneity; progression as an embodiment of prognosis; and functional prognosis. The theme, information needs/wants, contributed to the primary themes. Participants highlighted the importance of stepwise discussions of general and personalized prognosis; prognostic heterogeneity as a source of hope and a potential communication barrier; and how progression facilitates material understanding of prognosis, adaptation, and future planning. Further, participants wanted more information about functional prognosis and the impact of interventions/therapies on function and survival. <i>Conclusions:</i> We discuss participants' central questions: \"how long\" and \"how well,\" and provide recommendations for patient-centred ALS prognostic communication. Participants' embodied understanding of prognosis and desire for information that anticipates functional change, informs disease management, and facilitates timely planning suggests that clinical application of ALS staging systems may meet patient and caregiver need. Testing in real-world clinical settings is needed to ensure the development of patient-centred predictive tools.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"301-311"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566540","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 is the influence of fatigue, ALSFRS-R scores, cognitive status, and pain in individuals with Amyotrophic Lateral Sclerosis? A cross-sectional study.","authors":"Stephano Silva, Diogo Aires, Aline Souza, João Macedo, Luciana Melo, Saionara Câmara, Ricardo Valentim, Ana Raquel Lindquist, Giane Samora, Tatiana Ribeiro","doi":"10.1080/21678421.2025.2557971","DOIUrl":"10.1080/21678421.2025.2557971","url":null,"abstract":"<p><p><i>Introduction:</i> Fatigue remains a poorly understood symptom in individuals with ALS, and little is known about its associtation with other symptoms, including functional impairment, cognition, and pain. <i>Objective:</i> To identify the levels of fatigue, pain, ALSFRS-R, and cognition of a Brazilian group of individuals with ALS, in order to verify possible influences between these symptoms and fatigue. <i>Methods:</i> This is a cross-sectional study conducted with individuals with ALS who were recruited intentionally, using a non-probabilistic sampling method. After agreeing to participate, they were assessed using a standardized assessment form, and data regarding fatigue level, ALSFRS-R scores, cognition, and pain were collected. Data were analyzed by categorizing fatigue (with and without fatigue) and considering sociodemographic and clinical covariates, followed by comparisons, bivariate analyses, and multiple linear regression analyses. <i>Results:</i> Data were collected from 72 individuals with ALS. Inferential statistics indicated differences between fatigue categories concerning ALSFRS-R scores, cognition, and pain. After multiple linear regression analyses, an association between fatigue and the dependent variables was identified. <i>Conclusion:</i> Fatigue is associated with lower ALSFRS-R scores, poorer cognitive status, and higher levels of pain in a Brazilian cohort of ALS. Additionally, age, sex, education, and length of illness were identified as potential factors for fatigue occurrence, observed more frequently in females than in males with the condition.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"469-476"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031223","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":"Patient experience and clinical outcome assessment validity in amyotrophic lateral sclerosis: a targeted literature review.","authors":"Sarah E Curtis, Sophi Tatlock, Louise O'Hara, Ekin Seçinti, Nicole F Mehdiyoun, Lara Ayala-Nunes, Jessica Flynn, Katherine Fernelius, Nicola Hodson, Laure Delbecque","doi":"10.1080/21678421.2025.2604233","DOIUrl":"10.1080/21678421.2025.2604233","url":null,"abstract":"<p><strong>Objective: </strong>To identify relevant concepts of measurement for people with amyotrophic lateral sclerosis (ALS) and to evaluate the face and content validity of clinical outcome assessments (COAs) that can be used to measure treatment benefits in ALS clinical trials.</p><p><strong>Methods: </strong>A targeted literature review was conducted to explore patient experience (stage 1) and COAs used in ALS research (stage 2). Abstracts were screened against predefined eligibility criteria; full-text articles were reviewed for eligible abstracts and relevant data were extracted. Face and content validity of the identified COAs were assessed.</p><p><strong>Results: </strong>Stage 1 searches identified 3,527 abstracts, of which 12 full-text articles, two summary reports, and one conference poster were included in this review. Twenty-five symptoms and 35 health-related quality of life (HRQoL) impacts were identified. Frequently reported symptoms included breathing and speech difficulties and muscle/limb weakness, each associated with a diverse range of impacts, including those related to emotional wellbeing, physical function, social and leisure activities, and activities of daily living. Stage 2 searches identified 119 COAs, of which 28 were reviewed. Many had acceptable face (13/28) and content validity (15/28), but 13 had not involved patients during development; only 10 were clearly worded and seven were lengthy, increasing patient burden risk.</p><p><strong>Conclusions: </strong>This review identified wide-ranging symptoms and HRQoL impacts experienced by people with ALS, but detailed qualitative evidence is sparse. Multiple COAs were identified as potential measures in ALS clinical trials.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"285-300"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145812411","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":"<i>MAPT</i> p.V363I mutation in a patient with presenile dementia and late amyotrophic lateral sclerosis.","authors":"Estrella Gómez-Tortosa, Pablo Agüero-Rabes, Javier Roa-Escobar, María José Sainz, Jesús Viñas, Raquel Téllez, Pedro Martínez-Ulloa, Julián Pérez-Pérez","doi":"10.1080/21678421.2025.2604238","DOIUrl":"10.1080/21678421.2025.2604238","url":null,"abstract":"<p><p>There are limited reports of motor neuron disease associated with <i>MAPT</i> mutations. We present a woman, carrier of the pathogenic <i>MAPT</i> V363I mutation, who developed a presenile dementia and, after 7 years, amyotrophic lateral sclerosis affecting both bulbar and spinal segments. This mutation has been reported in ten previous cases with various cognitive phenotypes and corticobasal syndrome, but not motor neuron disease. We also review the handful of <i>MAPT</i> mutations associated with motor neuron disease.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"481-484"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846909","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":"Examining the impact and role of lipid classes on the risk of amyotrophic lateral sclerosis (ALS) onset: a systematic review and GRADE analysis of the evidence.","authors":"Amber R Sewell-Green, Merle Kuiper, Cory J Holdom, Anita Beelen, Shyuan T Ngo, Frederik J Steyn, Kylie L Matthews-Rensch","doi":"10.1080/21678421.2025.2574685","DOIUrl":"10.1080/21678421.2025.2574685","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to synthesize existing research on pre-diagnostic blood lipid levels and the risk of amyotrophic lateral sclerosis (ALS) onset in adults, and the quality of this evidence.</p><p><strong>Methods: </strong>A systematic review was conducted (8 March 2024, updated 19 June 2025) across six databases (PubMed, Embase, CINAHL, Scopus, Cochrane Library, and Web of Science) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, identifying adult clinical studies of blood lipids measured prior to ALS onset. Studies with high risk of bias, assessed using the Quality in Prognostic Studies tool, were excluded. Standardized mean difference and 95% confidence intervals were calculated. Study outcomes were categorized by lipid class as indicating reduced, no effect, or increased ALS risk. Certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.</p><p><strong>Results: </strong>Of 7222 studies identified, eight (<i>n</i> = 7 sterol lipids, <i>n</i> = 1 fatty acids) met inclusion. No significant differences in sterol lipids were observed between ALS cases and controls (<i>I</i>² = 69.9-77.3%). Most studies reported no association or increased risk between ALS onset and higher total cholesterol, triglycerides, LDL-C, HDL-C, or LDL/HDL ratio. For HDL-C, two studies showed protective associations. A single fatty acid study reported increased disease risk with higher arachidonic acid and reduced risk with higher alpha-linoleic acid. Certainty of evidence was low to very low.</p><p><strong>Conclusion: </strong>Circulating sterol lipid levels were inconsistently associated with ALS risk. The overall low certainty of evidence, and variability of findings across studies call for research using standardized designs, high-resolution lipid profiling, and robust causal inference approaches to clarify the role of lipids in ALS risk.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"370-382"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423568","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":"Spanish adaptation of the Primary Lateral Sclerosis Functional Rating Scale (PLSFRS).","authors":"Alejandro Caravaca Puchades, Mònica Povedano Panadés, María Bea Sintes, Raúl Domínguez Rubio, Andrés Paipa","doi":"10.1080/21678421.2025.2574678","DOIUrl":"10.1080/21678421.2025.2574678","url":null,"abstract":"<p><p><i>Objective:</i> Primary Lateral Sclerosis (PLS) is a progressive neurodegenerative disease with no current therapy. So far, the lack of a specific evaluation instrument has been a barrier for clinical trials. The Primary Lateral Sclerosis Functional Rating Scale (PLSFRS) is a novel tool designed to specifically assess disease progression and functional impairment in patients with PLS. We sought to translate and validate the PLSFRS to the Spanish language. <i>Methods:</i> We back-translated the PLSFRS scale to Spanish and assessed a cohort of 10 PLS patients by two independent raters. Both inter- and intrarater reliability were evaluated, with assessments conducted through both in-person and over-the-phone interviews. <i>Results:</i> The PLSFRS demonstrated excellent inter- and intrarater reliability for the total score (ICC = 0.90-1.00) and for most subdomains (ICC > 0.90). Agreement between in-clinic and over-the-phone assessments was similarly strong. Squared weighted kappa coefficients for individual items indicated substantial to almost perfect agreement. Bland-Altman analysis revealed no significant systematic bias, with mean differences close to zero and acceptable limits of agreement. <i>Conclusion:</i> This study demonstrates high reliability for the Spanish version of the PLSFRS scale.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"312-317"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423565","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}