BMJ Neurology Open最新文献

{"title":"Whole Exome Sequencing Identifies Novel Homozygous LGI1 Variant Mimicking ADAM22-Related Pathologies in a Moroccan Family.","authors":"Hinde El Mouhi, Badreddine Elmakhzen, Amina Bouyahyaoui, Mustapha Hida, Karim Ouldim, Laila Bouguenouch, Sana Chaouki","doi":"10.1136/bmjno-2025-001267","DOIUrl":"10.1136/bmjno-2025-001267","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy-related ligand-receptor complex, leucine-rich glioma-inactivated 1 (<i>LGI1</i>)<i>-</i>a disintegrin and metalloproteinase 22 (<i>ADAM22</i>), regulates neuronal excitability and synaptic transmission and has emerged as a determinant of brain excitability. Epilepsy-related variants have been described in both <i>LGI1</i> and <i>ADAM 22</i> genes. A partial epilepsy, autosomal dominant lateral temporal epilepsy (ADLTE) is caused by an <i>LGI1</i> heterozygous variant. A recessive developmental and epileptic encephalopathy with infantile onset is due to homozygous inactivating <i>ADAM22</i> variants.</p><p><strong>Objective: </strong>We present the case of Moroccan siblings with epileptic encephalopathy due to a homozygous variant within the <i>LGI1</i> gene previously unreported in the homozygous state.</p><p><strong>Methods: </strong>We performed whole-exome sequencing and family segregation analysis to identify and confirm the genetic cause of the condition in the affected siblings.</p><p><strong>Results: </strong>The clinical features mimic <i>ADAM22-</i>related developmental and epileptic encephalopathy rather than the typical <i>LGI1</i>-associated autosomal dominant lateral temporal epilepsy. Family segregation analysis demonstrated variable expressivity, with asymptomatic carrier parents and a cousin with focal temporal epilepsy carrying the variant in the heterozygous state.</p><p><strong>Conclusion: </strong>This case highlights a homozygous <i>LGI1</i> variant previously unreported in the homozygous state, leading to a clinical presentation more reminiscent of <i>ADAM22</i>-related pathology rather than the classical ADLTE, expanding our understanding of <i>LGI1</i>-associated conditions.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 2","pages":"e001267"},"PeriodicalIF":2.4,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated UPper limb and Language Impairment and Functional Training (UPLIFT) after stroke: study protocol for an umbrella Bayesian Optimal Phase IIa clinical trial.","authors":"Kathryn S Hayward, Geoffrey Donnan, Erin Godecke, Anna Balabanski, Ruth Barker, Julie Bernhardt, Sandra Brauer, Amy Brodtmann, Emily Brogan, Sonia Brownsett, Paul Chapman, David Copland, Elise Cowley, Emily Dalton, Fiona Ellery, Paul Fink, Carlos Garcia Esperon, Annie J Hill, Heidi Janssen, Siobhan Kavanagh, Timothy Kleinig, Liudmyla Olenko, Joanne Je Quek, Trevor Russell, Moira Smith, Lillian Taylor, Vincent Thijs, Claire Tucak, John Turner, Declan Wode, Andrew Wong, Bronwyn Williams, Bruce C V Campbell, Leonid Churilov","doi":"10.1136/bmjno-2025-001212","DOIUrl":"10.1136/bmjno-2025-001212","url":null,"abstract":"<p><strong>Introduction: </strong>One in six stroke survivors continue to experience arm and language disability at 3 months post-stroke. This study aims to identify which model(s) of integrated UPper limb and Language Impairment and Functional Training (UPLIFT) show promise for people 3 months to 24 months post-stroke. We hypothesise that at least one promising UPLIFT model of rehabilitation will be identified.</p><p><strong>Methods and analysis: </strong>This is an adaptive Phase IIa master protocol umbrella design that includes four simultaneous Bayesian Optimal Phase II studies to evaluate individual UPLIFT interventions against prespecified objective performance criteria. The intervention is upper limb and language training at 2 or 4 hours/day, 5 days/week for 4 weeks, delivered either in person (severe stratum) or via telerehabilitation (mild-moderate stratum). Up to 160 adult participants will be recruited across six metropolitan/regional university or healthcare hubs spanning five Australian states. Baseline and post-intervention assessments are blinded. A promising response is defined as a composite binary outcome combining indicators of promise of efficacy, safety and feasibility. For each UPLIFT intervention, the proportion of participants with a promising response will be monitored at three equally spaced, predefined interim stopping points and one final analysis point (n=40 participants/study). An intervention will be stopped if too few promising responses are observed.</p><p><strong>Ethics and dissemination: </strong>Ethical approval was obtained from The Royal Melbourne Human Research Ethics Committee. All participating sites obtained local governance approval. All recruited participants will provide informed consent. Trial results will be disseminated through peer-reviewed publications and presented at major stroke and rehabilitation conferences.</p><p><strong>Trial registration number: </strong>ACTRN12622000373774.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 2","pages":"e001212"},"PeriodicalIF":2.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of deep brain stimulation on patients with Parkinson's disease with excessive daytime sleepiness.","authors":"Sunny Vansdadia, Pooja Dhupati, Priya Ramaiah, Robert W Bina","doi":"10.1136/bmjno-2025-001125","DOIUrl":"10.1136/bmjno-2025-001125","url":null,"abstract":"<p><strong>Background: </strong>Excessive daytime sleepiness (EDS) is a prevalent non-motor symptom in Parkinson's disease (PD), significantly impairing quality of life. While deep brain stimulation (DBS) effectively improves motor symptoms, its impact on EDS remains unclear.</p><p><strong>Objective: </strong>This systematic review aims to evaluate the effects of DBS on EDS in patients with PD.</p><p><strong>Methods: </strong>Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search of PubMed, Scopus, Embase and PsycInfo databases published by 2024) was conducted using terms related to DBS, EDS and PD. 20 studies met the inclusion criteria. Data on demographic characteristics, DBS parameters, sleep assessment scales and Levodopa-equivalent daily dose (LEDD) changes were extracted and analysed.</p><p><strong>Results: </strong>Among the 20 studies, 9 reported improvements in EDS post-DBS, with a mean Epworth Sleep Scale (ESS) reduction of 26.8%. However, 11 studies found no significant change. All studies reported LEDD reductions (mean 47.7%), but only two demonstrated a significant correlation between LEDD reduction and ESS improvement. Notably, some studies revealed discrepancies between subjective improvements in sleep quality and objective measures.</p><p><strong>Conclusion: </strong>The effect of DBS on EDS in PD remains inconclusive, with mixed findings across studies. While DBS consistently reduces LEDD and improves overall sleep quality, its direct impact on EDS varies. Further research with larger cohorts, objective sleep assessments and focus on confounders is necessary to elucidate DBS's role in managing EDS in patients with PD.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 2","pages":"e001125"},"PeriodicalIF":2.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burden of Duchenne muscular dystrophy in Australia: a scoping review.","authors":"Eugene Lee, Seulki Choi, Hansoo Kim","doi":"10.1136/bmjno-2025-001230","DOIUrl":"10.1136/bmjno-2025-001230","url":null,"abstract":"<p><strong>Background: </strong>Duchenne muscular dystrophy (DMD) is a rare X-linked recessive disorder characterised by progressive muscle degeneration leading to severe disability and early mortality, with no cure. This disease process affects nearly every aspect of daily functioning, from basic movements to respiratory and cardiac functions, and consequently imposes a significant burden on patients, caregivers and families. We aimed to review the available literature examining the epidemiological, health-related quality of life (HRQoL) and economic burden of DMD in Australia from a societal perspective.</p><p><strong>Methods: </strong>This scoping review was conducted by searching Embase and PubMed databases up until 22 August 2024. Two independent reviewers screened titles, abstracts and full texts. Studies that evaluated the epidemiological, HRQoL-related or economic burden of DMD in an Australian-specific context were included.</p><p><strong>Results: </strong>We identified 169 articles and assessed the full text of 32, of which nine were included in the review. Eight studies were observational with one theoretical/computational study. Four studies addressed the epidemiological burden, estimating a birth prevalence of 18.6 to 22.7 DMD cases per 100 000 male live births. Another four studies examined the HRQoL-related burden with three generic patient-reported outcome measures (PROMs) used to assess HRQoL. Two PROMs indicated lower self-reported and parent proxy HRQoL scores in boys with DMD compared with the general population, and the other PROM evaluated parental/caregiver HRQoL. One study detailed the economic burden in 104 households, reporting significant annual socioeconomic burden of DMD associated with high levels of healthcare costs, non-medical resource use and caregiving burden to households.</p><p><strong>Conclusions: </strong>Although the data estimating the epidemiological, HRQoL-related and economic burden of DMD in Australia is limited, existing evidence demonstrates a considerable societal burden of DMD. In the context of emerging disease-modifying therapies for DMD, it provides a summary of existing local evidence and research gaps, highlighting a need for further research.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 2","pages":"e001230"},"PeriodicalIF":2.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the progression of Parkinson's disease: a review.","authors":"Peter A Kempster","doi":"10.1136/bmjno-2025-001215","DOIUrl":"10.1136/bmjno-2025-001215","url":null,"abstract":"<p><p>Over the long term, Parkinson's disease (PD) appears to progress, in a linear fashion, at an annual rate of about 2% of the maximum motor disability score. This figure aligns quite well with pathological research on the rate that substantia nigra dopaminergic neurons are lost. An unexpected finding from cohort studies and clinical trials is that progression is twice as fast in prodromal PD, leading up to clinical diagnosis, and in recently diagnosed PD prior to the commencement of dopaminergic therapy. Levodopa initiation reduces motor disability by 40% of the pretreatment level. This benefit is composed of the short duration response, which is easily measured as the difference between <i>on</i> and <i>off</i> states, and the long duration response, which is comparable in size though not directly observable. Despite clinical impressions to the contrary, there is little evidence that the response to levodopa wanes over time or that axial motor deficits affecting speech, gait and balance become increasingly resistant to treatment. While not revealed by prospective longitudinal studies, the advanced PD phase, accompanied by visual hallucinations and cognitive decline, may show an exponential rate of change. Serial motor scale assessment, informed by a knowledge of symptomatic dopaminergic treatment effects, is probably still the best way to measure the underlying rate of progression of PD in clinical trials.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 2","pages":"e001215"},"PeriodicalIF":2.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of outcomes for patients with nitrous oxide-related myeloneuropathy treated with self-injection of hydroxocobalamin versus nurse-led injections on an ambulatory care pathway.","authors":"Mohamoud Hashi, Laura Smith, Marta Patyjewicz, Barbara Onen, Katrina Mamigo, Eunice Adu-Poku, Gillian Fox, Alastair J Noyce","doi":"10.1136/bmjno-2025-001234","DOIUrl":"10.1136/bmjno-2025-001234","url":null,"abstract":"<p><strong>Background: </strong>Nitrous oxide (N₂O)-related neurotoxicity is a significant public health concern among young people in the UK. Recognition necessitates timely diagnosis, abstinence from N₂O consumption and replacement of vitamin B12, usually via intramuscular (IM) hydroxocobalamin. This service development project evaluated a self-injection programme (SIP) compared with a nurse-led approach, within an established ambulatory care pathway, with the aim of improving treatment adherence and completion.</p><p><strong>Methods: </strong>Between June and December 2024, a total of 46 patients presenting with N₂O-induced neurological symptoms were included in the evaluation. Patients were given the choice of self-injecting (SIP, n=25) or attending the hospital for nurse-led administration (non-SIP, n=21). Clinical outcomes, adherence and functional improvement (including the 10 metre walk test (10MWT)) were assessed.</p><p><strong>Results: </strong>Most patients were young (median age of 23), male (n=29, 63%), of Asian or Asian British ethnicity (n=29, 63%), and regularly using N₂O (n=32, 70%). SIP patients had higher adherence, missing fewer IM B12 doses compared with non-SIP (79.7% vs 20.3%, p<0.001). Clinical recovery rates were comparable, with 74% achieving full or substantial improvement across both groups. Walking speed (10MWT) improved across both groups following treatment and did not differ between groups.</p><p><strong>Conclusion: </strong>Self-injection of IM hydroxocobalamin is a feasible and likely cost-effective alternative to nurse-led administration while maintaining clinical efficacy.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 2","pages":"e001234"},"PeriodicalIF":2.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in functional Neurological disorder.","authors":"Wendy Phillips, Mark Edwards","doi":"10.1136/bmjno-2025-001285","DOIUrl":"10.1136/bmjno-2025-001285","url":null,"abstract":"","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 2","pages":"e001285"},"PeriodicalIF":2.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transplacental transfer of ravulizumab in a pregnant woman with neuromyelitis optica: a case report.","authors":"Anu Jacob, Azza Mahmoud, Luai Eldweik, Asia Mubashir","doi":"10.1136/bmjno-2025-001286","DOIUrl":"10.1136/bmjno-2025-001286","url":null,"abstract":"<p><p><b>Background</b> Neuromyelitis optica spectrum disorder (NMOSD) is a rare relapsing autoimmune disease of the central nervous system (CNS). Management during pregnancy is challenging due to limited safety data for disease-modifying therapies. <b>Case presentation</b> We report a case of a 41-year-old woman with aquaporin-4 (AQP4) IgG positive NMOSD who was switched from rituximab to ravulizumab during pregnancy. Ravulizumab was initiated shortly after conception and continued throughout pregnancy. Pregnancy was uneventful and she delivered a healthy term infant. At birth, umbilical cord blood testing revealed detectable ravulizumab levels and low C5 activity, confirming transplacental transfer of ravulizumab. The infant, now 4 months old, remains well. <b>Conclusions</b> This is the first reported case of ravulizumab use during pregnancy, with documentation of transplacental drug transfer and neonatal complement inhibition. Despite laboratory evidence of pharmacologic exposure, the neonate remained clinically well. These findings suggest that ravulizumab may be a viable treatment option for NMOSD during pregnancy when traditional agents are contraindicated or ineffective. However, further studies and longitudinal monitoring of exposed infants are essential to establish safety and clinical guidelines.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 2","pages":"e001286"},"PeriodicalIF":2.4,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered amyloid plasma profile in patients with disabling headaches after SARS-CoV-2 infection and vaccination.","authors":"Anne Hege Aamodt, Thor Ueland, Marion Boldingh, Burcu Ella Bezgal, Maria Bengtson Argren, Cecilia Adele Dunne, Kari Otterdal, Ida Gregersen, Vigdis Bjerkeli, Annika Elisabet Michelsen, Andreas Husøy, Åse Hagen Morsund, Kristina Devik, Anne Christine Poole, Kristine Bodding Gjendemsjø, Katrin Schlüter, Sara Maria Mathisen, Mari Aalstad-Johansen, Thor Håkon Skattør, Julie Sønnervik, Turid Birgitte Boye, Trine Haug Popperud, Einar August Høgestøl, Hanne Flinstad Harbo, Fridtjof Lund-Johansen, Pål Aukrust, Erling Tronvik, Tuva Børresdatter Dahl, Bente Evy Halvorsen","doi":"10.1136/bmjno-2024-001013","DOIUrl":"10.1136/bmjno-2024-001013","url":null,"abstract":"<p><strong>Background and objectives: </strong>Persistent headache has emerged as a symptom following acute COVID-19 and, to a lesser extent, after SARS-CoV-2 vaccination. However, the underlying mechanisms remain poorly understood. This study aimed to evaluate plasma levels of amyloid-related biomarkers in patients experiencing persistent headaches after COVID-19 or SARS-CoV-2 vaccination.</p><p><strong>Methods: </strong>In this prospective observational cohort, patients presenting with severe headache as the dominating symptom after COVID-19 (n=29) or SARS-CoV-2 vaccination (n=31) had neurological assessments with reassessments after 6 months. Plasma levels of amyloid precursor protein (APP), pregnancy zone protein (PZP), cathepsin L1 (CTSL) and serum Amyloid A (SAA1) were measured using ELISA and compared with levels in healthy controls (n=16).</p><p><strong>Results: </strong>We found a strong and persistent upregulation of APP in patients with headache after COVID-19 as compared with the two other groups. Notably, APP levels remained elevated at both inclusion and after 6 months in individuals with accompanying cognitive symptoms. In contrast, PZP levels were increased in patients with headache after SARS-CoV-2 vaccination at both time points relative to healthy controls. CTSL was only elevated in the post-COVID-19 at baseline, whereas SAA1 showed levels comparable across all groups.</p><p><strong>Conclusion: </strong>Altered plasma levels of soluble markers, potentially reflecting changes in amyloid processing, were found in patients with persistent headache following SARS-CoV-2 vaccine, particularly in those with persistent headache after COVID-19. In the latter group, we also found some association with cognitive symptoms.</p><p><strong>Trial registration numbers: </strong>NCT04576351 and NCT05235776.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 2","pages":"e001013"},"PeriodicalIF":2.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144978261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urinary P75: a promising biomarker for amyotrophic lateral sclerosis.","authors":"Laura R Chapman, Stephanie Shepheard, Nick Verber, Martin R Turner, Andrea Malaspina, Mary-Louise Rogers, Pamela J Shaw","doi":"10.1136/bmjno-2025-001088","DOIUrl":"10.1136/bmjno-2025-001088","url":null,"abstract":"<p><strong>Abstract: </strong></p><p><strong>Background: </strong>Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease. The urinary neurotrophin receptor p75 extracellular domain (p75^ECD) has previously been reported as a potential disease biomarker for diagnosis, severity assessment and monitoring therapeutic response.</p><p><strong>Methods: </strong>This study measured urinary p75^ECD using an enzyme-linked immunoassay and normalised the results against urinary creatinine. Participants were recruited via A Multicentre Biomarker Resource Strategy in ALS (AMBroSIA) programme. Study participants included 97 ALS patients, 24 of whom were studied longitudinally, and 27 healthy controls. The study focused on urinary p75^ECD and its potential association with different subtypes of ALS, change over time, disease progression, severity of symptoms and survival from symptom onset.</p><p><strong>Results: </strong>Confirming previous findings, urinary p75^ECD levels were significantly higher in patients with ALS (median 6.78 ng/mg, 95% CI (5.12 to 9.23)) compared with controls (4.57 ng/mg, 95% CI (3.35 to 5.89)) at first study visit. There was a significant negative correlation between absolute change in the Revised ALS Functional Rating Scale score and p75^ECD levels (Spearman's rho=-0.371, p≤0.0004, 95% CI (-0.543 to -0.169)), indicating that an increase in the severity of motor neuron injury correlated with an increase in p75^ECD levels. There was a significant increase in p75^ECD between first and second samples in the same participants, indicating an increase in the level of this biomarker longitudinally during the disease course (moderate effect size of -0.3).</p><p><strong>Conclusions: </strong>Urinary p75^ECD is a promising candidate as a biomarker, which increases with disease progression and has the potential to serve as a pharmacodynamic biomarker.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"7 2","pages":"e001088"},"PeriodicalIF":2.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144978298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}