Amyotrophic lateral sclerosis & frontotemporal degeneration最新文献

{"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}

{"title":"Translation and validation of the Arabic version of the amyotrophic lateral sclerosis assessment questionnaire (ALSAQ40-AR).","authors":"Radwa Soliman, Mahmoud S Swelam, Nagia Fahmy, Hebatallah R Rashed","doi":"10.1080/21678421.2025.2603311","DOIUrl":"10.1080/21678421.2025.2603311","url":null,"abstract":"<p><strong>Aim: </strong>To validate Arabic version of the ALSAQ-40, (ALSAQ40-AR) and assess the QOL in a cohort of Egyptian patients with ALS.</p><p><strong>Methods: </strong>This is a prospective study. One hundred consecutive ALS patients were included from the Neuromuscular Unit, Ain Shams University Hospital, in the period from February 2022 to June 2024. Functional and cognitive assessments were done using the Arabic version of ALSFRS-R and ECAS-EG questionnaires, respectively. Disease stage was identified via Kings Clinical Staging. QOL was evaluated using the Arabic WHOQOL-BREF and an Arabic version of ALSAQ-40.</p><p><strong>Results: </strong>ALSAQ40-AR showed high internal consistency using Cronbach's alpha of >0.9, Inter-rater reliability was tested, values for all variables were compared, and no statistically significant differences were found (ICC = .997). Both WHOQOL-BREF and ALSAQ40-AR domains demonstrated significant correlation with each other and with ALSFRS-R (p-value < 0.0001), denoting construct validity. Moreover, ALSAQ40-AR domains correlated significantly with time since disease onset, and showed significant increase across disease stages (p-value < 0.0001). Ceiling and floor effects were analyzed in both QOL scales, but only WHOQOL-BREF showed ceiling and floor effects.</p><p><strong>Conclusion: </strong>ALSAQ40-AR and the WHOQOL-BREF were reliable and valid tools to evaluate QOL in patients with ALS; we suggest that the validated ALSAQ40-AR is more suited for ALS patients because it is a disease specific questionnaire that showed higher internal consistency with no floor or ceiling effects. QOL in ALS was correlated with time since disease onset, disease stage, functional, and cognitive disabilities.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"592-601"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145812378","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 characterization of the proximal lower-limb ALS phenotype: a retrospective cohort study.","authors":"Alexandre Montalvo, Marta Gromicho, Miguel Oliveira Santos, Mamede de Carvalho","doi":"10.1080/21678421.2026.2630882","DOIUrl":"10.1080/21678421.2026.2630882","url":null,"abstract":"<p><p>This study characterizes a rare phenotype of Amyotrophic Lateral Sclerosis (ALS) presenting with predominant proximal lower limb weakness at onset, a presentation often mimicking myopathy. We retrospectively reviewed 1980 patients, identifying 15 (0.75%) with this atypical onset. The majority were males (73%) with a median age of onset of 58.7 years. Approximately half presented with symmetric proximal lower limb weakness. Nine of the 11 tested patients had higher CK. Follow-up (median 53.7 months) revealed that 6 patients maintained isolated lower limb weakness for a median of 60.1 months, while others progressed to upper limbs or bulbar regions. NSG sequencing (in nine patients) identified mutations in three patients (SOD1, VAPB, and C9ORF72). This pattern poses a diagnostic challenge. While limitations include a small sample size and retrospective design, the findings highlight a heterogenous but often slow-spreading and benign course for this specific ALS subtype, offering valuable clinical information for differential diagnosis.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"704-707"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286256","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":"Cognitive and behavioral impairment may influence shared care planning and treatment decisions in amyotrophic lateral sclerosis.","authors":"Veria Vacchiano, Arianna Cherici, Maria Sasca Criante, Elena Mengoli, Cristina Fonti, Luigi Bonan, Silvia de Pasqua, Vincenzo Donadio, Maria Pia Giannoccaro, Giovanni Rizzo, Cecilia Celidea Quarta, Eleonora Marzocchi, Floriana Taggi, Rocco Liguori","doi":"10.1080/21678421.2025.2597937","DOIUrl":"10.1080/21678421.2025.2597937","url":null,"abstract":"<p><p><i>Background:</i> Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor neurons, often accompanied by cognitive and/or behavioral impairments. Shared Care Planning (SCP) involves a collaborative decision-making process, playing a key role in aligning medical treatments with patient values. This study aimed to investigate potential associations between neuropsychological impairment and treatment decisions in ALS patients. <i>Methods:</i> We included 118 ALS patients who had completed at least the cognitive section of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). As part of routine clinical practice, patients were invited to participate in Shared Care Planning (SCP) discussions regarding key medical interventions, namely noninvasive ventilation (NIV), artificial nutrition via PEG/RIG, and tracheostomy. <i>Results:</i> SCP discussions were initiated with 78% of patients. NIV was accepted by 96% of patients, PEG/RIG by 63.9% and tracheostomy by 17.8%. Patients who accepted PEG/RIG were more frequently female (<i>p</i> = 0.047) and had significantly lower adjusted scores on the total ECAS (<i>p</i> = 0.027), ALS-specific domains (<i>p</i> = 0.020), verbal fluency (<i>p</i> = 0.012), and semantic fluency (<i>p</i> = 0.042), compared to those who refused PEG/RIG. Acceptance of tracheostomy was more common among younger patients (<i>p</i> < 0.001) and those with cognitive or behavioral impairments (<i>p</i> = 0.014). Binary logistic regression analysis, using tracheostomy acceptance as the dependent variable and age, sex, and Strong's diagnostic categories as independent variables, revealed a significant association with age (<i>p</i> = 0.002) and with certain Strong's categories, particularly ALS with combined cognitive and behavioral impairment (ALS-CBI) (<i>p</i> = 0.031). <i>Conclusions:</i> Cognitive and behavioral impairment appeared to increase the likelihood of consenting to invasive treatments in ALS patients.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"622-631"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764870","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":"Interleukin-6 in ALS: metabolic mediator or marker of ventilatory decline?","authors":"Ana Catarina Pronto-Laborinho, Mamede De Carvalho","doi":"10.1080/21678421.2026.2667283","DOIUrl":"10.1080/21678421.2026.2667283","url":null,"abstract":"","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"715-716"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846762","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 aging brain that doesn't fail: how neural resilience masks neurodegeneration.","authors":"Andrew Eisen, Heather D Durham, Erik Pioro","doi":"10.1080/21678421.2026.2705693","DOIUrl":"https://doi.org/10.1080/21678421.2026.2705693","url":null,"abstract":"<p><p>Neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease are usually framed as consequences of aging-related pathogenic processes, including impaired proteostasis with protein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Yet, most individuals, even into advanced age, do not develop clinically significant neurodegenerative disease. This discrepancy suggests that the nervous system possesses robust and redundant protective mechanisms that maintain neural integrity despite cumulative molecular and cellular stress. In this perspective, we propose that neurodegenerative diseases arise not simply from the presence of pathogenic processes, but when integrated resilience systems fail to maintain homeostasis or when reserve mechanisms no longer compensate for accumulated pathology. We have synthesized a threshold-based model of disease emergence based on evidence across proteostasis, mitochondrial function, neuroimmune regulation, glial biology, network-level compensation, and barrier integrity, while integrating genetic, environmental, developmental, and stochastic modifiers. We distinguish biological resilience, which actively limits or repairs pathology, from reserve, which permits function despite pathology. We further propose that clinical disease emerges only when age-related cumulative stress exceeds the combined capacity of resilience and reserve. Reframing neurodegeneration as a failure of preservation systems offers new directions for prevention and therapeutic development.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-15"},"PeriodicalIF":2.8,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148594736","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":"SOD1-lowering therapy for patients with wildtype <i>SOD1</i>-ALS: a case report.","authors":"Nathan Carberry, Joanne Wuu, Michael Benatar","doi":"10.1080/21678421.2026.2705142","DOIUrl":"https://doi.org/10.1080/21678421.2026.2705142","url":null,"abstract":"<p><p><i>Background and Objectives</i>: To describe clinical and biomarker experience using an SOD1 antisense oligonucleotide (ASO) in a patient with non-<i>SOD1</i> amyotrophic lateral sclerosis (ALS). <i>Methods</i>: Case report. <i>Results</i>: In a 72-year-old male with non-SOD1 ALS, rapid decline on the ALS functional rating scale revised (ALSFRS-R) and a rise in serum neurofilament light chain (NfL) concentration were observed following 3 loading doses of an SOD1 ASO before the patient succumbed to disease. The time from symptom onset to death was 9 months. <i>Discussion</i>: While treatment was initiated relatively late (∼7 months) after symptom onset and follow-up duration was short, the observed increase (as opposed to a reduction) in serum NfL and accompanying rapid functional decline, suggest the lack of a therapeutic effect in someone with fast progressing non-<i>SOD1</i> ALS.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-3"},"PeriodicalIF":2.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551514","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":"Intermuscular coherence as a candidate biomarker for primary lateral sclerosis.","authors":"Naoum P Issa, Elena Badillo-Goicoechea, Serdar Aydin, Nathan Carberry, Sean Smith, Mark A Garret, Doreen Ho, Rachel Freedman, Kelly McCoy-Gross, Alejandra Casas, Betty Soliven, Kourosh Rezania","doi":"10.1080/21678421.2026.2699211","DOIUrl":"https://doi.org/10.1080/21678421.2026.2699211","url":null,"abstract":"<p><p><i>Objective</i>: Reliable and widely accessible neurophysiological biomarkers are needed to assess upper motor neuron (UMN) dysfunction. We investigated whether intermuscular coherence in the beta-gamma frequency range (IMCβγ) and its imaginary component (ICOHβγ) can serve as a biomarker for PLS. <i>Methods</i>: IMCβγ and ICOHβγ were evaluated in upper and lower limb muscle pairs in 21 individuals with PLS along with 42 age- and sex-matched neurotypical control participants. PLS participants underwent clinical evaluations including deep tendon reflex assessment and manual muscle strength testing. <i>Results</i>: IMCβγ and ICOHβγ were significantly lower in PLS patients in both the arms and legs. Area under the receiver-operating characteristic curve ranged between 0.71 and 0.77 for differentiating PLS from neurotypical control participants based on measurements in a single limb. Using an abnormal coherence measurement in any two limbs as a diagnostic test for PLS, test sensitivity was 0.76, specificity was 0.86, and accuracy was 0.83. <i>Conclusions</i>: Both IMCβγ in the arms and ICOHβγ in the legs distinguish PLS patients from neurotypical control participants, supporting their potential as accessible biomarkers of UMN dysfunction.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-12"},"PeriodicalIF":2.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148431626","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":"Feasibility and sensitivity of a multimodal digital endpoint panel for amyotrophic lateral sclerosis: a prospective cohort study.","authors":"Lianne C M Botman, Jordi W J van Unnik, Anita Beelen, Jaap N E Bakers, Nina D van der Schoot, Manon A P Gremmen, Sybel van Helm, Leonard H van den Berg, Ruben P A van Eijk","doi":"10.1080/21678421.2026.2696382","DOIUrl":"https://doi.org/10.1080/21678421.2026.2696382","url":null,"abstract":"<p><p><i>Background</i>: The use of digital technology may improve monitoring of amyotrophic lateral sclerosis (ALS) but a multimodal approach is likely required to capture the full disease phenotype. We evaluated the feasibility of a multimodal home monitoring protocol in ALS. <i>Methods</i>: We conducted a 3-month prospective cohort study at the University Medical Center Utrecht, Netherlands, with monthly home assessments of spirometry, accelerometry, speech, and questionnaires on functioning. The primary outcome was protocol adherence, defined as percentage of completed assessments. Secondary outcomes included acceptability ((totally) agree, neutral, (totally) disagree), and perceived burden, ranging from 0 (no burden) to 10 (extremely burdensome). Exploratory analyses were performed to evaluate changes in digital endpoints using linear mixed-effects models. <i>Findings</i>: Fifty patients with ALS were included (January 2023 - June 2025), of whom 47 (94%) completed the 3-month follow-up. Overall adherence was 83.2% (95% CI 76.9-88.6) and did not differ across modalities (<i>p</i> = 0.75<i>)</i>. Adherers did not differ from non-adherers in either demographic or disease characteristics. In month 3, 93.0% to 95.3% of patients considered monthly remote assessments as acceptable, with a mean burden score of 2.0 (95% CI 1.7 to 2.3); burden was highest for speech (2.5) and the lowest for questionnaires (1.5). Digital endpoints showed significant change over 3 months (all <i>p</i> < 0.05). <i>Interpretation</i>: This study demonstrates good adherence and acceptability of a multimodal remote monitoring protocol. Digital endpoints offer an innovative approach to capturing disease progression. Future research should assess its long-term feasibility, added value, and integration alongside established clinical outcomes.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-10"},"PeriodicalIF":2.8,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148392646","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":"Reduced penetrance in genetic ALS/FTD spectrum disorders: implications for genetic counseling, predictive testing and treatment.","authors":"Elizabeth A Harrington, Laynie Dratch, Tara A Jones, Jamie C Fong, Daniel D Kinnamon, Jill Goldman, Wendy R Uhlmann, Jennifer Roggenbuck","doi":"10.1080/21678421.2026.2696378","DOIUrl":"https://doi.org/10.1080/21678421.2026.2696378","url":null,"abstract":"<p><p>As the offer of genetic testing for people with ALS/FTD becomes standard of care, clinicians and affected individuals should have accurate and balanced information regarding the clinical and familial implications of test results, including the penetrance of identified variants. Published estimates of the penetrance of specific ALS/FTD variants, including the <i>C9orf72</i> repeat expansion, have varied widely. However, it is now apparent that most pathogenic variants identified in clinical testing exhibit reduced penetrance. Although data on the disease risk of many variants is limited and likely to evolve in the coming years, the challenges of estimating penetrance should not preclude transparent discussion of these issues with affected individuals and their families. Here, we review published penetrance data and highlight genetic counseling considerations to support the clinician in discussing disease risk and facilitating decision-making in genetic testing and patient care.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-12"},"PeriodicalIF":2.8,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148388415","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}