Amyotrophic lateral sclerosis & frontotemporal degeneration最新文献

{"title":"Sleep disturbances and respiratory dysfunction in amyotrophic lateral sclerosis.","authors":"Kato Bracaval, Joke De Vocht, Fouke Ombelet, Laura Van Den Bulcke, Anne-Marie Peeters, Boris Deleu, Bart Vrijsen, Alexandros Kalkanis, Bertien Buyse, Dries Testelmans, Maarten Van Den Bossche, Philip Van Damme","doi":"10.1080/21678421.2026.2671162","DOIUrl":"10.1080/21678421.2026.2671162","url":null,"abstract":"<p><strong>Objective: </strong>To investigate how respiratory dysfunction and site of onset influences changes in sleep architecture in people with ALS (pwALS).</p><p><strong>Methods: </strong>We conducted a retrospective observational study, analyzing demographic data, lung function tests, and polysomnography (PSG) measures. Descriptive statistics, correlation analyses, and survival analyses were performed.</p><p><strong>Results: </strong>Our cohort had 240 pwALS, 63% male, median age at onset 59.3 (IQR 16.5) years. Median time from onset to PSG was 27.5 (IQR 25) months. Most pwALS had spinal onset (79%). Spirometry at time of PSG showed a reduced Forced Vital Capacity (FVC) (58; (IQR 26) %). We saw a significant FVC decline (3.9; (IQR 4) % per month) in the months before PSG. The sleep quality assessment in pwALS revealed a reduced total sleep time (339; (IQR 144.7) minutes), diminished sleep efficiency (62.8; (IQR 26.5)%) and increased wake after sleep onset (172; (IQR 130.2) minutes) when compared to normal values of healthy age-matched adults. The spinal onset group had a higher number of arousals. In the multivariate linear regression model adjusted for age and sex, FVC is a significant predictor for sleep efficiency (β = 3.359, <i>p</i> = 0.0059). Spinal onset, a slower rate of FVC decline in the months preceding PSG and a preserved FVC (≥ 70%) at the time of PSG were associated with improved survival.</p><p><strong>Conclusion: </strong>We observed substantial sleep disturbances in our cohort overall with substantially increased arousals in the spinal group. FVC is a significant predictor for sleep efficiency and the decline in FVC is linked to survival.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"877-883"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148058504","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":"Innate immune signaling as a potential pathomechanistic biomarker for distinct subtypes in amyotrophic lateral sclerosis.","authors":"Marcel Naumann, Stefanie Kretschmer, Johannes Dorst, Hanna Lapp, Kevin Peikert, Susanne Petri, Burkhard Gess, Christine Wolf, Annekathrin Rödiger, Uta Smesny, Francisco Pan-Montojo, Philippe Kerschen, Torsten Grehl, Johannes Prudlo, Martin Regensburger, Albert Ludolph, René Günther, David Brenner, Min Ae Lee-Kirsch, Andreas Hermann","doi":"10.1080/21678421.2026.2663910","DOIUrl":"10.1080/21678421.2026.2663910","url":null,"abstract":"<p><p>Stimulation of the innate immune system has been implicated in ALS and particularly in distinct monogenic forms of ALS. To address whether this is of diagnostic value, we performed a proof-of concept study using qPCR to assess the Interferon score in blood samples of genetic ALS.</p><p><p>56.5% of genetic ALS patients showed significant IFN activation, highest in C9orf72HRE patients (77.3%). About half of FUS-ALS (52.2%), but none of SOD1-ALS patients demonstrated pathological IFN scores. The IFN score significantly correlated with the ALSFRS-R slope and inversely with the time to severe event as a survival surrogate in this genetic ALS cohort. IFN + patients were more likely to be male, showed more rapid disease progression and higher neurofilament levels.</p><p><p>The IFN score might have the potential as a stratification and readout tool for biomarker-guided individualized therapy in ALS.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"938-945"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148260654","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":"Clinical parameters affecting the course of amyotrophic lateral sclerosis: a longitudinal analysis of the Greek registry for amyotrophic lateral sclerosis (ALS-GR).","authors":"Ioannis Liampas, Vasilios K Kimiskidis, Vasiliki Zouvelou, Dimitra Veltsista, Afroditi Moscholouri, Eleftherios Triantafyllou, Ariadni Daponte, Sofia Xirou, Angeliki-Erato Sterpi, Stavroula Salakou, Vasiliki Poulidou, Marianthi Arnaoutoglou, Zisis Tsouris, Styliani Ralli, Efthimios Dardiotis, Sotirios Papagiannopoulos, Alexandros Zampetakis, Ιoannis Zaganas, Panayiotis Mitsias, Alexandros Giannakis, Spyridon Konitsiotis, Fotios Kefalas, Eleni Alexiou, Panagiotis Stoiloudis, Dimitrios Parissis, Stratis Kiamelidis, Aikaterini Terzoudi, Georgios Tsivgoulis, Michail Rentzos, Elisabeth Chroni","doi":"10.1080/21678421.2026.2648293","DOIUrl":"10.1080/21678421.2026.2648293","url":null,"abstract":"<p><strong>Background: </strong>Reliable prognostic factors are essential for both clinical and research purposes in amyotrophic lateral sclerosis (ALS). The current study aimed to investigate the prognostic properties of clinical parameters regarding the course of ALS.</p><p><strong>Methods: </strong>A mixed retrospective-prospective cohort study was conducted in 11 specialized centers in Greece. Participants with ALS were assessed on the ALS functional rating scale-revised (ALSFRS-R) at baseline and follow-up (on 6-9-12-18-24 months). In case of dropouts, we elucidated whether death had occurred. Adjusted survival analyses were used to explore associations with mortality; adjusted generalized estimating equations were used to examine associations with the rate of functional decline.</p><p><strong>Results: </strong>A total of 165 individuals with an average follow-up of 12.6 ± 6.3 months were included in the current longitudinal analysis. Baseline ALSFRS-R was the strongest determinant of survival [Hazard-ratio; HR = 0.949 (0.921-0.977)], followed by age at diagnosis [HR = 1.043 (1.011-1.075)] and restrictive respiratory pattern [HR = 2.321(1.193-4.515)], while cramps [HR = 0.485 (0.249-0.946)] and pain [HR = 2.007 (1.041-3.868)] were the least influential. Regarding functional decline rates, the strongest predictor was dysphagia [<i>β</i>= -0.633 (-0.992, -0.274)], followed by pseudobulbar syndrome [<i>β</i>= -0.460 (-0.832, -0.088)], depression [<i>β</i>= -0.375 (-0.688, -0.062)], pain [β=-0.362 (-0.627, -0.096)]. fatigue [<i>β</i>= -0.338 (-0.644, -0.033)], spasticity [<i>β</i>= -0.362 (-0.644, -0.081)] and the interval between diagnosis and baseline visit to a specialized unit in months [<i>β</i> = 0.031 (0.013, 0.048)].</p><p><strong>Conclusions: </strong>Lower baseline ALSFRS-R scores, older age at diagnosis, restrictive respiratory pattern, pain and absence of cramps were linked to shorter survival in ALS. Dysphagia, pseudobulbar syndrome, depression, pain, fatigue, spasticity and shorter intervals between diagnosis and baseline visit to specialized units were related to steeper functional decline.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"910-919"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147596582","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":"Air pollutants and amyotrophic lateral sclerosis in a population-based registry: investigating disease susceptibility, progression and survival.","authors":"Elisabetta Pupillo, Elisa Bianchi, Luca Diamanti, Roberto Bergamaschi, Enrico Pisoni, Nilo Riva, Christian Lunetta, Massimiliano Filosto, Alessandro Padovani, Lucio Tremolizzo, Maria Luisa De Lodovici, Maurizio Angelo Leone","doi":"10.1080/21678421.2026.2677537","DOIUrl":"10.1080/21678421.2026.2677537","url":null,"abstract":"<p><p><i>Objective:</i> to investigate the association between long-term exposure to fine particulate matter (PM2.5) and nitrogen oxides (NOx) with ALS risk, progression, and survival. <i>Methods:</i> We conducted a population-based study in Lombardy, Italy. A case-control analysis included 161 incident ALS cases (2011-2014) and 161 age-, sex-, and province-matched controls. Average residential exposures to PM2.5 and NOx over the 20 years before diagnosis were estimated using European Monitoring and Evaluation Programme data and analysed with conditional logistic regression. A retrospective cohort of 135 ALS cases was used to assess associations with disease progression (ΔFS) and mortality using logistic and Cox regression models, adjusting for demographic and lifestyle factors. <i>Results:</i> Higher PM2.5 exposure in the 20 years preceding diagnosis was associated with increased ALS risk (adjusted OR per 5 µg/m³ increase 1.19; 95% CI 1.01-1.40), with consistent findings across sensitivity analyses. NOx was not associated with ALS incidence. In contrast, NOx exposure in the 5 years before diagnosis was marginally associated with increased mortality (adjusted HR 1.12; 95% CI 1.00-1.26), whereas PM2.5 was not. Neither pollutant was significantly associated with disease progression rate. <i>Conclusions:</i> Long-term PM2.5 exposure was associated with higher ALS risk, while NOx showed a modest association with mortality. These findings support a role of air pollution in ALS susceptibility and highlight the need for integrated environmental prevention strategies to mitigate the burden of neurodegenerative diseases.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"847-855"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148044646","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":"Speech and swallow outcome measures for ALS and perspectives on remote monitoring: an international survey of speech & language therapists.","authors":"Lesley Doyle, Miriam Galvin, Avril Mc Tague, Dara Meldrum, David Murphy, Orla Hardiman, Deirdre Murray","doi":"10.1080/21678421.2026.2655735","DOIUrl":"10.1080/21678421.2026.2655735","url":null,"abstract":"<p><strong>Objective: </strong>Dysarthria and dysphagia occur frequently in Amyotrophic Lateral Sclerosis (ALS). To manage these symptoms, speech & language therapists (SLTs) must identify relevant speech and swallow outcomes and select suitable outcome measurement instruments. Remote monitoring is an evolving mode of health status tracking. This survey aimed to establish SLT perspectives on ALS assessment regarding 1) the clinical meaningfulness of existing outcome measurement instruments 2) remote monitoring 3) usefulness of assessment devices for patient care and 4) bulbar function outcomes and measurement instruments useful for research studies.</p><p><strong>Methods: </strong>An online English-language survey was distributed internationally through gatekeepers and social media.</p><p><strong>Results: </strong>Sixty-six SLTs responded from 13 countries. Current outcome measurement instruments were regarded as clinically meaningful in ALS by 35% for speech and 41% for swallow. Only 12% had access to remote monitoring, but 77% would like to avail of it, with 58% perceiving its potential to enhance care. Eighty-two percent deemed remote monitoring using digital patient-reported outcome measures (PROMs) useful. Speech intelligibility measurement was selected as the most useful communication outcome for remote monitoring (92%) and research (94%). SLTs agreed that speech intelligibility test software (72%), smart device apps (70%) and tongue pressure measurement devices (54%) are useful assessment equipment.</p><p><strong>Conclusions: </strong>SLTs want better measurement instruments for speech and swallow in ALS. They regarded technologies including remote monitoring incorporating digital PROMs as useful. Outcomes reflecting communication and swallow functional success level were deemed most useful. These survey findings can inform the selection of digital speech and swallow outcomes for ALS.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"808-820"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147730781","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":"Strengthening care and research in ALS in Southeast Asia: a call for action.","authors":"Wai Yee Fung, Sheila Agustini, Jakkrit Amornvit, Josiah Chai, Ludwig F Damian, Nurul Fadli, Dk Hjh Norazieda Pg Hj Mohd Yassin, Southanalinh Keovilayhong, Dhayalen Krishnan, Kongkiat Kulkantrakorn, Minh Duc Nguyen Tran, Kay Ng, Hoang T T Nghia, Ohnmar Ohnmar, Dayangku Siti Nur Ashikin Pengiran Tengah, Mario Prado, Rabani Remli, Arada Rojana-Udomsart, Tu Quoc Le Tuan, Ahmad Yanuar, Nortina Shahrizaila","doi":"10.1080/21678421.2026.2671159","DOIUrl":"10.1080/21678421.2026.2671159","url":null,"abstract":"<p><p>In Southeast Asia (SEA), healthcare resources, infrastructure, and access to therapies in amyotrophic lateral sclerosis (ALS) remain limited compared to other parts of the Asia-Pacific region. Many SEA countries continue to face delays in diagnosis, fragmented care pathways, and limited representation in international research. Beyond health system challenges, ALS in SEA may also differ biologically. Emerging studies suggest that genetic variants and clinical phenotypes in Asian populations are not fully mirrored in Western cohorts. In this report, the authors summarize their country-specific background and status of care in ALS as well as their consensus on future strategies and actions. Key short- and long-term strategies are proposed, highlighting the critical need for regional collaboration and patient engagement to advance ALS care and research in the region.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"723-728"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990184","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":"Dysphagia in behavioural variant of frontotemporal dementia- a systematic review.","authors":"Elishka S Bailey, Alayna Rowell, Rachel Mulheren","doi":"10.1080/21678421.2026.2652328","DOIUrl":"10.1080/21678421.2026.2652328","url":null,"abstract":"<p><strong>Objective: </strong>Dementia is associated with changes in feeding and swallowing that pose a significant risk to health. This systematic review aimed to examine the diagnosis of dysphagia in behavioral variant of frontotemporal dementia (bvFTD).</p><p><strong>Methods: </strong>Four research databases were systematically searched for studies reporting dysphagia in bvFTD. Selection criteria included human participants with bvFTD, documentation of swallowing function, report of original data, availability in English, and full-text access. Included reports were assessed for quality and risk of bias.</p><p><strong>Results: </strong>Twenty-two studies met the inclusion criteria. Studies were analyzed and categorized by symptom presence/absence (<i>n</i> = 9), symptom description (<i>n</i> = 12) and swallowing physiology (<i>n</i> = 1). Participants with bvFTD and dysphagia were noted to have a wide range of disease severity and associated symptoms, including motor, cognitive-emotional, and perceptual changes. When specified, assessment methods typically included caregiver questionnaires and brief screening tools. The most frequently reported signs and symptoms of dysphagia were choking, coughing, and chewing difficulties. Hyperphagia and oral packing were noted in 13 studies. Only one study used imaging to assess swallowing, and noted an incongruence between caregiver report and imaging results. The quality of included studies was limited by sampling and sample size.</p><p><strong>Conclusion: </strong>Although dysphagia has been reported in bvFTD, diagnosis is often through unreported, nonstandardized, observational measures. Limitations to current evidence include small sample sizes, reliance on caregiver reports, and lack of imaging. Further research is warranted to develop standards for assessment of swallowing and dysphagia intervention in bvFTD.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"884-895"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700671","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":"Evolving 10-year epidemiological landscape of amyotrophic lateral sclerosis (ALS) in Ceará, Brazil.","authors":"José Marcelino Aragão Fernandes, Avelino Missialdes Dutra Junior, Florian P Thomas, Francisco De Assis Aquino Gondim","doi":"10.1080/21678421.2026.2663916","DOIUrl":"10.1080/21678421.2026.2663916","url":null,"abstract":"<p><p><i>Objective</i>: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that affects upper and lower motor neurons with variable cognitive impairment. Despite its rarity, ALS has a major social and economic impact and increasing incidence worldwide. There are few population-based studies of ALS in Brazil. <i>Methods</i>: We present a descriptive and quantitative study, with a retrospective and prospective design, of patients with ALS followed at the Walter Cantídio University Hospital (HUWC) from January 2013 to December 2023, with the aim of describing the clinical, epidemiological, and genetic aspects of ALS in this population, as well as the ALS epidemiology within the state of Ceará, Brazil. <i>Results</i>: Two hundred and forty patients had their medical records analyzed. One hundred and thirty-four (55.8%) cases were male, with a male to female ratio of 1.3:1. The mean age of symptom onset was 56.39 ± 13.05 years. 92.1% (221) of cases were sporadic, 7.9% (19) were familial. Spinal onset was most common (72.1%). Genetic mutations were found in 10 patients, with SOD1 mutations (variant: c.358G > C; p.Val120Leu) being the most common. Using riluzole prescription data, the prevalence and incidence of ALS in 2022 were estimated at 2.32 and 0.8/100.000/inhabitants, respectively. <i>Conclusion</i>: The epidemiology of ALS in the state of Ceará is similar to what has been reported in prior studies from Brazil and other developing countries; SOD1 mutations were the most prevalent genetic subtype.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"821-827"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790525","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":"Brain activity in an end-stage ALS patient suggests the presence of an unresponsive wakefulness syndrome.","authors":"Sandra Frycz, Wiktor Więcławski, Marcin Skotniczny, Marek Binder","doi":"10.1080/21678421.2026.2688249","DOIUrl":"10.1080/21678421.2026.2688249","url":null,"abstract":"<p><strong>Objective: </strong>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting motor neurons. It is widely assumed that cortical structures beyond motor neurons are relatively preserved, and patients in the end-stage ALS are regarded as being in complete locked-in syndrome (cLIS). However, emerging evidence suggests substantial heterogeneity in cognitive functioning among ALS patients, indicating possible extra-motor cortical involvement and impaired levels of consciousness. We report a case study assessing electrophysiological markers and auditory system integrity to evaluate the presence of covert consciousness in end-stage ALS.</p><p><strong>Methods: </strong>The patient was a 42-year-old woman with bulbar-onset, end-stage ALS, a six-year disease duration, and no means of communication. She underwent several EEG-based protocols, including resting-state EEG (RS-EEG), a passive auditory oddball paradigm, and 40 Hz auditory steady-state responses (ASSR). Audiological evaluation comprised transient-evoked and distortion-product otoacoustic emissions, as well as auditory brainstem responses (ABR).</p><p><strong>Results: </strong>RS-EEG was dominated by prefrontal 1-3 Hz activity resembling frontal intermittent rhythmic delta activity. Power spectra were poorly differentiated and consistent with a 1/f profile. No event-related potentials were observed in the oddball paradigm, and no ASSR responses were detected. Audiological testing revealed absent otoacoustic emissions and ABR indicating severe to profound hearing loss.</p><p><strong>Conclusions: </strong>Our findings indicate severe cortical dysfunction and provide no electrophysiological evidence of covert consciousness. The electrophysiological profile closely resembles that observed in unresponsive wakefulness syndrome. This case supports the hypothesis that advanced ALS following cLIS onset may be more appropriately conceptualized as a disorder of consciousness rather than persistent cLIS.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"870-876"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148267159","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":"Opportunities and challenges related to participant stratification and cohort enrichment in ALS clinical trials.","authors":"Sabrina Yusuf, Matti D Allen, HyungMo Kang, Daniel E Phillips, Angela Genge","doi":"10.1080/21678421.2026.2659128","DOIUrl":"10.1080/21678421.2026.2659128","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is marked by substantial clinical heterogeneity. This heterogeneity has impacted clinical trials by obscuring treatment effects and causing inefficiency. In this review, we summarize potential approaches for addressing heterogeneity in ALS via patient stratification and cohort enrichment methods and highlight potential challenges and limitations. These categories include stratification based on genetics, clinical characteristics (e.g. pattern of weakness, ALS Functional Rating Scale rates of progression), wet biomarkers (e.g. neurofilament light chain), neuroimaging, and novel methods employing statistical modeling or machine learning. These stratification methods have yet to be fully leveraged in clinical trial design. But these strategies must be employed thoughtfully and judiciously due to potential issues stratification can introduce. Future clinical trials should explore how participant stratification and cohort enrichment strategies may improve our ability to identify treatment effects, which may ultimately aid in the quest to establish more personalized medicine for persons with ALS.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"729-738"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790497","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}