Amyotrophic lateral sclerosis & frontotemporal degeneration最新文献

{"title":"Identifying diagnostic markers in the health records of prediagnostic amyotrophic lateral sclerosis patients.","authors":"Dor Simoni, Marc Gotkine, Iddo Z Ben-Dov, Boaz Lerner","doi":"10.1080/21678421.2025.2539898","DOIUrl":"https://doi.org/10.1080/21678421.2025.2539898","url":null,"abstract":"<p><p><i>Objective</i>: Amyotrophic lateral sclerosis (ALS) has a poorly understood preclinical phase, particularly concerning diagnostic blood markers. Our objective was to determine whether distinct patterns in routinely collected clinical and laboratory markers exist during the preclinical phase and could be incorporated to facilitate early diagnosis. <i>Methods</i>: We conducted a longitudinal, retrospective, case-control study with health records of prediagnostic ALS patients (PDALS) from health maintenance organizations covering approximately 40% of the Israeli population. We included PDALS with at least 10 clinical visits and a minimal observation period of 36 months prior to the diagnosis date to measure differences between PDALS and controls and analyzed data from 1,810 adult individuals; 362 PDALS and 1,448 age- and sex-matched controls. <i>Results</i>: Significant differences were found in PDALS many months before the diagnosis date. These included biochemical parameters such as urea, creatinine, CK, calcium, iron, and liver enzymes, hematological values, and BMI. Some differences were detectable over 10 years prior to the diagnosis date. <i>Conclusions</i>: This study highlights the potential for early detection of ALS based on blood markers in the years preceding clinical diagnosis. These findings could significantly expedite diagnosis, identify individuals at risk for ALS, and uncover unrecognized disease mechanisms.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-11"},"PeriodicalIF":2.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002027","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":"A <i>VAPB</i> (P56S) mutation in a Dutch patient with familial motor neuron disease: a case report.","authors":"Sean W Willemse, Koen C Demaegd, Ruben P A Van Eijk, Philippe Van Damme, Elizabeth Harrington, Matthew B Harms, Neil A Shneider, Wouter Van Rheenen, Jan H Veldink, Leonard H Van Den Berg, Michael A Van Es","doi":"10.1080/21678421.2025.2555218","DOIUrl":"10.1080/21678421.2025.2555218","url":null,"abstract":"<p><p>The c.166C > T p.(Pro56Ser) or P56S mutation in the <i>VAPB</i> gene was initially identified as a cause of motor neuron disease in Brazil in a large extended pedigree comprising >1,500 individuals including more than 200 cases. This <i>VAPB</i> mutation gives rise to three phenotypes: late-onset spinal muscular atrophy, classical ALS with bulbar involvement, pyramidal signs and rapid disease progression, and atypical ALS with slow progression. Nearly all known cases originate from a single founder, with most cases outside of Brazil being related to this pedigree. However, there is one report of an independent German family with the same mutation on a different haplotype, indicating a second founder event. Here, we report the first Dutch patient with a P56S mutation in <i>VAPB</i> and motor neuron disease. Documenting rare genetic causes of MND and their natural history are of increasing importance in light of emerging gene-specific therapies.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-3"},"PeriodicalIF":2.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994539","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":"Epidemiology, clinical features, and management of amyotrophic lateral sclerosis in the neurology department of the Bogodogo University Hospital in Ouagadougou, Burkina Faso.","authors":"Bademain Jean Fabrice Ido, Alfred Anselme Dabilgou, Abdou Salam Doulgou, Emeline Agathe Carama, Mazongue Kanlanfe Lamine Ganame, Christian Napon","doi":"10.1080/21678421.2025.2549323","DOIUrl":"https://doi.org/10.1080/21678421.2025.2549323","url":null,"abstract":"<p><p><i>Objective</i>: To describe the epidemiology, the clinical features, and the management of amyotrophic lateral sclerosis (ALS) in the neurology department of the Bogodogo University Hospital. <i>Methods</i>: This was a retrospective study including patients followed in the neurology department of the Bogodogo University Hospital between April 15, 2017 and December 31, 2024 for ALS. The socio-demographic, clinical and follow-up data of these patients were studied. <i>Results</i>: During our study period, 14 patients were followed for ALS, an average of 2 cases per year. The mean age of patients at symptom onset was 38.50 ± 14.23 years. The mean time to diagnosis was 19.71 ± 5.27 months. Four patients underwent no spinal cord magnetic resonance imaging (MRI). Riluzole was prescribed in 02 patients (14.29%). No patient benefited from noninvasive ventilation or gastrostomy. Six patients (42.85%) were discharged against medical advice. On December 31, 2024, there were 2 patients alive (14.29%), 5 patients who died (14.29%) and 7 patients (50%) who were lost to follow-up. <i>Conclusion</i>: Our cohort is characterized by a low hospital incidence, a young age of patients and difficulties in the care and follow-up of patients.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-3"},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980660","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":"Automatically measured speech intelligibility models bulbar-specific disease severity and progression in Amyotrophic Lateral Sclerosis.","authors":"Johannes Tröger, Andreas Rouvalis, Felix Dörr, Louisa Schwed, Nicklas Linz, Alexandra König, Judith Machts, Stefan Vielhaber, Tabea Thies, Johannes Prudlo, Andreas Hermann, Elisabeth Kasper","doi":"10.1080/21678421.2025.2549317","DOIUrl":"https://doi.org/10.1080/21678421.2025.2549317","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to widespread motor deterioration, including significant motor speech impairments. Speech intelligibility is a crucial component of communication affected in ALS, requiring objective, scalable assessment methods as an indicator of disease progression and treatment efficacy. <b><i>Objective:</i></b> This study investigates whether speech and bulbar function in ALS could be evaluated and monitored utilizing an automated digital measure of speech intelligibility derived from naturalistic picture descriptions. <b><i>Methods:</i></b> Speech recordings from 44 patients living with ALS (plwALS) and 49 matched healthy controls (HC) were analyzed and processed utilizing an automated speech analysis pipeline to extract an intelligibility score. These were part of a cross-sectional and longitudinal study involving two assessments. <b><i>Results</i>:</b> The findings confirmed that speech intelligibility is significantly reduced in plwALS compared to HC. Those with bulbar-onset ALS have lower intelligibility than those with spinal-onset ALS, and the intelligibility of individuals with bulbar symptoms-regardless of the onset type-is lower than in plwALS without bulbar symptoms. Declining ALS-related speech scores correspond with worsening intelligibility in longitudinal assessments. Intelligibility correlates strongly with bulbar-specific clinical measures but not with global scores, highlighting its role in tracking bulbar progression. In some plwALS, we were able to demonstrate that automated speech analyses are more effective in detecting worsening in intelligibility earlier than standard clinical scoring. <b><i>Conclusion</i>:</b> Our findings highlight that automated speech intelligibility assessments can be a valuable marker to improve clinical monitoring and facilitate earlier intervention in ALS as a supplement to standard assessments.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-9"},"PeriodicalIF":2.8,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980666","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 phenotype of frontotemporal dementia associated with the Pro392Leu <i>SQSTM1</i> mutation.","authors":"Javier Roa-Escobar, Pablo Agüero-Rabes, Pedro Martínez-Ulloa, María José Sainz, Julián Pérez-Pérez, Estrella Gómez-Tortosa","doi":"10.1080/21678421.2025.2549308","DOIUrl":"https://doi.org/10.1080/21678421.2025.2549308","url":null,"abstract":"<p><p><i>Objective</i><b>:</b> To characterize the phenotypic spectrum of patients with frontotemporal dementia (FTD) carrying the P392L <i>SQSTM1</i> mutation. <i>Methods:</i> We describe the clinical phenotype of three well-characterized probands carrying the P392L mutation, and review ten previously published FTD cases with the mutation. <i>Results:</i> All three cases were male with a presenile age of onset (52 or 64 years). Case 1 developed an amnestic-anomic syndrome followed by a behavioral variant of FTD (bvFTD). Case 2, with an autosomal dominant family history of dementia, developed a bvFTD associated with parkinsonism. Both cases had Paget's disease of the bone (PDB). Case 3 presented with a semantic aphasia and, years later, developed a hemilateral upper motor neuron disease (MND) (Mills syndrome). Among the ten previously reported cases (four from the same family), bvFTD was the cognitive phenotype in five, but semantic, nonfluent and logopenic aphasic variants, as well as a pure hippocampal amnestic syndrome were also documented. PDB was observed in six cases, two exhibited parkinsonism, and one MND. Neuroimaging findings showed a tendency toward asymmetric temporal/frontal atrophy, sometimes with periventricular white matter signal abnormalities. Only one third of the cases reported a family history of dementia. <i>Conclusions:</i> The P392L mutation exhibits a pleiotropic effect, giving rise to a broad phenotypic spectrum that includes PDB, FTD, amnestic syndrome, parkinsonism, and MND. Penetrance for the different phenotypes is variable and may be influenced by additional factors. The outlined features may encourage healthcare professionals to screen for this gene, even in cases without a clear family history.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-9"},"PeriodicalIF":2.8,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980655","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":"Perceptions of healthcare professionals on optimal delivery of noninvasive ventilation care to people living with motor neuron disease.","authors":"Lucy S Musson, Susan K Baxter, Paul Norman, David O'Brien, Mark Elliott, Stephen Bianchi, Georgios Kaltsakas, Christopher J Mcdermott, Esther V Hobson, Theocharis Stavroulakis","doi":"10.1080/21678421.2025.2539896","DOIUrl":"https://doi.org/10.1080/21678421.2025.2539896","url":null,"abstract":"<p><p><i>Background:</i> Patients with motor neuron disease (MND) often do not experience the full survival and quality of life benefits of noninvasive ventilation (NIV). Successful delivery of NIV is challenging to multiple healthcare professionals involved in the respiratory care patient journey and considering their perspectives is crucial in order to understand how to deliver optimal care. <i>Objective:</i> To identify the factors that influence NIV delivery in MND from a healthcare professional perspective and understand how obstacles can be overcome to optimize care. <i>Methods:</i> Qualitative focus group discussions with healthcare professionals delivering respiratory care and support to MND patients in the UK and charity representatives. <i>Results:</i> Thirty healthcare professionals and three charity representatives participated in five focus groups. A range of factors that influence the delivery of NIV across the entire respiratory care pathway were identified. These were grouped under four main themes: multidisciplinary working; NIV service structure; professional further education and training; and good use of NIV and effective ventilation. <i>Conclusions:</i> There is a need for specific resources to support service delivery; frequent, funded, and structured training to support healthcare professionals to deliver good care; as well as ways to encourage optimal staff practice so patients get the best care.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-8"},"PeriodicalIF":2.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980745","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":"Neurofilament light chain dynamics in the pre-symptomatic phase of amyotrophic lateral sclerosis: a case report.","authors":"Pilar H García-Casanova, Francisco Gascón-Giménez, Jéssica Castillo-Villalba, Michael Benatar, Juan F Vázquez-Costa","doi":"10.1080/21678421.2025.2542918","DOIUrl":"10.1080/21678421.2025.2542918","url":null,"abstract":"<p><p>This case report aims to describe the presymptomatic and prodromal phases of the disease in a sporadic patient with amyotrophic lateral sclerosis (ALS). A 41-year-old woman presented with acute hypesthesia due to transverse myelitis, with normal serum NfL levels. After six months, an increase in serum NfL, without clinical correlate, was found. One year after the myelitis, while serum NfL continued to increase, she experienced mild motor symptoms in the right hand, without definite signs of ALS. Disease progression over the following months finally lead to an ALS diagnosis, just as the NfL reached its peak. The emergence of both mild motor impairment as a prodromal stage of disease, and the sustained increase in NfL presymptomatically in a patient with sporadic ALS, highlights the expected similarities between genetic and non-genetic forms of disease. This case suggests the utility of NfL as a risk/susceptibility biomarker for predicting phenoconversion also in sporadic ALS patients.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-5"},"PeriodicalIF":2.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876926","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 use of genetic testing in amyotrophic lateral sclerosis (ALS): a practical approach.","authors":"Amina Chaouch, Ashley Crook, Andrew G L Douglas, Christopher J McDermott, Ammar Al-Chalabi, Alisdair McNeill, Jennifer Bedford, Jade Howard, Rhona MacLeod","doi":"10.1080/21678421.2025.2539895","DOIUrl":"https://doi.org/10.1080/21678421.2025.2539895","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disease thought to be precipitated by genetic, environment and lifestyle factors. In the UK, whole genome sequencing has become available to all people living with ALS, regardless of their family history or age of onset of disease. However, there is currently no formal guidance on how to deliver genetic counseling and testing in busy mainstream clinics. This article offers practical suggestions to clinicians who may wish or need to discuss genomic testing. As more clinical trials and targeted gene therapies develop, it is likely that conversations will evolve, reflecting the dynamic nature of this important and complex field.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-7"},"PeriodicalIF":2.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805398","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":"Challenging the boundaries: c9orf72 mutation presenting as Alzheimer's disease.","authors":"Federico Garrou, Fabiola De Marchi, Lucia Corrado, Gian Mauro Sacchetti, Sandra D'alfonso, Silvia Daniela Morbelli, Daniela Perani, Letizia Mazzini, Giacomo Tondo","doi":"10.1080/21678421.2025.2541761","DOIUrl":"https://doi.org/10.1080/21678421.2025.2541761","url":null,"abstract":"<p><p>C9orf72 hexanucleotide repeat expansion is a major cause of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD), while its link with Alzheimer's disease (AD) is still unclear. We describe the case of a 53-year-old man with progressive memory and language deficits, mood disturbances, and a positive family history for ALS-FTD. Cerebrospinal fluid showed amyloid positivity, confirmed by amyloid-PET, with normal tau levels; [¹⁸F]FDG-PET revealed an AD-like temporoparietal hypometabolism. Genetic testing detected a pathogenic C9orf72 expansion, also present in his mother. This case suggests phenotypic heterogeneity of C9orf72-related disorders and a possible interplay with amyloid pathology.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-4"},"PeriodicalIF":2.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790862","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":"ALS patients and PAD: description and comparison of patients from a neuromuscular clinic in Canada.","authors":"Pierre Trudel, Marie-Hélène Quesnel-Olivo, Mathieu Blais, Usha Ramanathan, Nicolas Dupré","doi":"10.1080/21678421.2025.2539894","DOIUrl":"https://doi.org/10.1080/21678421.2025.2539894","url":null,"abstract":"<p><strong>Objectives: </strong>In Canada, patients with ALS (PALS) who meet specific criteria can request Medical Assistance in Dying (MAiD), also known as Physician-Assisted Death (PAD). However, little is known about the characteristics of those patients. This study describes PALS who died of MAiD and compares them with patients who died from natural disease complications.</p><p><strong>Methods: </strong>A retrospective study of 209 consecutive PALS' electronic medical records was performed. Patients selected had follow-up at the CHU de Québec-Université Laval and died between January 2014 and April 2023. Sociodemographic and disease evolution data were collected. Fisher's exact test and Kolmogorov-Smirnov tests were used.</p><p><strong>Results: </strong>The analysis included 174 patients. MAiD PALS (<i>N</i> = 64) were mainly males (54.7%), of median age 67 years, in a relationship (68.7%), and parents of adult children (71.9%). Both cohorts had similar past medical histories of depressive disorders (15%, <i>p</i> > 0.999). MAiD PALS elected to use percutaneous endoscopic gastrostomy (PEG) feeding in 18.7% of cases compared to 28.2% of PALS who died of complications of ALS (<i>p</i> = 0.203). Palliative care teams were significantly more likely to be involved with PALS elected to request MAiD (86.6%, <i>p</i> = 0.023).</p><p><strong>Discussion: </strong>PALS who request MAiD share similar demographic and clinical characteristics with those who died from natural disease progression in our cohort. Trends toward differences were observed, namely, in the rate of disease progression, with PALS who requested MAiD more likely to be fast progressors than their counterparts, and in PEG feeding use with ALS MAiD patients less likely to request it. Palliative care involvement was more prevalent with MAiD PALS.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-7"},"PeriodicalIF":2.8,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769424","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}