{"title":"Clinical utility and methodological implementation of smartphone-based mobility analysis: a scoping review.","authors":"Edwin H Y Lui, Ralph Jasper Mobbs","doi":"10.1007/s00415-026-14131-2","DOIUrl":"10.1007/s00415-026-14131-2","url":null,"abstract":"<p><strong>Background: </strong>Mobility is an informative marker of neurological function, physiological reserve, and functional independence. Laboratory gait analysis requires costly specialized equipment, while research wearables can impose sustained-use burdens. Smartphone inertial measurement units (IMUs) offer a widely available platform for longitudinal assessment within a patient's natural environment.</p><p><strong>Methods: </strong>Following PRISMA-ScR guidelines, PubMed, Embase, and Scopus were searched for peer-reviewed studies using internal smartphone sensors to map reported clinical applications, methodological implementation, validation approaches, and translational barriers.</p><p><strong>Results: </strong>Eighty-four studies met the inclusion criteria. Neurology was the most frequently represented clinical domain (36.9%), with additional applications in geriatrics (14.3%) and orthopedics (13.1%). 10.7% (n=9) were classified as validation-focused; the remainder had diagnostic (36.9%), prognostic (38.1%), or longitudinal monitoring (14.3%) aims. Most assessments remained controlled (54.8%), supervised (67.9%), and dependent on active testing protocol (73.8%), whereas only 23.8% captured passive, free-living mobility. Implementation was heterogeneous: 71.4% of protocols required fixed device placements, 82.1% used custom software, and 7.1% integrated with native platforms. The extracted measures included activity volume, gait-quality metrics, and machine-learning features derived from raw inertial data.</p><p><strong>Conclusion: </strong>Smartphones provide a widely available platform for multidimensional mobility sensing, but the mapped evidence largely concerns feasibility, technical validation, or associations with clinical status and outcomes. Routine clinical utility has not been established. Translation will require standardized acquisition and reporting, cross-device and cross-platform validation, context-aware analysis, privacy-preserving data governance, and prospective evidence that implementation improves clinical decisions or patient-relevant outcomes. Passive monitoring may complement standardized assessment by providing longitudinal measures of real-world performance.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13577997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Xie, Shaolong Wu, Yan Zhang, Chao Ju, Shun Zhang, Yi Wang, Wenzhen Zhu, Meiyun Wang
{"title":"Comparison of iron and myelin changes in U‑fiber regions of relapsing-remitting multiple sclerosis and neuromyelitis optica spectrum disorders.","authors":"Yan Xie, Shaolong Wu, Yan Zhang, Chao Ju, Shun Zhang, Yi Wang, Wenzhen Zhu, Meiyun Wang","doi":"10.1007/s00415-026-14054-y","DOIUrl":"10.1007/s00415-026-14054-y","url":null,"abstract":"<p><strong>Objective: </strong>To explore iron and myelin changes in U-fiber regions of relapsing-remitting multiple sclerosis (RRMS) and neuromyelitis optica spectrum disorders (NMOSD) by susceptibility separation imaging, and to evaluate the clinical relevance of these changes.</p><p><strong>Methods: </strong>This study included 119 RRMS patients, 47 NMOSD patients, and 93 healthy controls (HC). The U-fiber region was defined as the white matter within 4 mm beneath the gray-white matter boundary. Susceptibility separation imaging was reconstructed from 3D multi-echo gradient echo data, and total susceptibility, positive susceptibility (χ<sub>pos</sub>) and negative susceptibility (χ<sub>neg</sub>) were extracted from each U-fiber subregion. General linear models were performed to compare these metrics among the three groups. Partial correlation analyses were conducted to explore the associations between susceptibility metrics and clinical characteristics.</p><p><strong>Results: </strong>Compared with HC, RRMS patients showed significantly decreased χ<sub>pos</sub> in multiple temporal and limbic U-fiber regions, and significantly increased χ<sub>neg</sub> in widespread U-fiber subregions. However, no significant differences in susceptibility metrics were observed between NMOSD patients and HC in any U-fiber subregion. Notably, after adjusting for potential confounding effects of disease severity and lesion burden, there were no significant differences in susceptibility metrics between RRMS and NMOSD patients. In RRMS patients, χ<sub>neg</sub> in U-fiber subregions was significantly correlated with Expanded Disability Status Scale, particularly in the left superior frontal region.</p><p><strong>Conclusion: </strong>Susceptibility separation imaging provided surrogate markers suggestive of iron loss and demyelination in the U-fiber region of RRMS patients. These metrics were closely associated with lesion burden and may hold promise as imaging correlates of clinical disability.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long-term safety of CGRP pathway inhibitors in migraine patients with prior cerebrovascular or cardiovascular disease.","authors":"Alessia Bellotti, Roberta Noseda, Roberto Masciullo, Claudio Staedler, Claudio Gobbi, Chiara Zecca","doi":"10.1007/s00415-026-14099-z","DOIUrl":"10.1007/s00415-026-14099-z","url":null,"abstract":"<p><strong>Background: </strong>Calcitonin gene-related peptide (CGRP) pathway inhibitors are highly effective migraine preventives, but their long-term cerebrovascular and cardiovascular safety in patients with prior ischaemic events remains uncertain, as such individuals were largely excluded from clinical trials.</p><p><strong>Methods: </strong>We analysed data from a prospective real-world registry of migraine patients treated with CGRP pathway inhibitors at our tertiary Headache Centre. Patients with a history of ischaemic stroke, transient cerebral ischaemic attack, or ischaemic heart disease were included. Clinical characteristics, treatment response, and vascular outcomes were assessed during follow-up.</p><p><strong>Results: </strong>Among 420 consecutive migraine patients treated with CGRP pathway inhibitors in our registry, 17 (4%) had a history of cerebrovascular and/or cardiovascular disease and met the inclusion criteria. These patients (median age 54.5 years, 76% female; 82% chronic migraine) contributed a total of 31 patient-years of exposure, with follow-up up to 5 years. Median time from event to treatment initiation was 5.0 years (IQR 4.5). 13 patients (76%) achieved ≥ 50% reduction in monthly migraine days (10/14 in chronic migraine; 3/3 in episodic migraine). No recurrent cerebrovascular events or worsening of underlying cardiac disease were observed during treatment. Serial neuroimaging, available in a subset, showed no new ischaemic lesions.</p><p><strong>Conclusions: </strong>In this small real-world cohort patients with prior cerebrovascular and/or cardiovascular disease, the use of CGRP pathway inhibitors was not associated with new clinical or radiological ischaemic events over 31 patient‑years of follow‑up. These safety findings are reassuring but only exploratory and hypothesis-generating requiring further confirmation.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gretchen A McNally, Grace Ji-Eun Shin, Lise Worthen-Chaudhari, Patrick M Schnell, Laura Flora, Surith Sanjay Krishna, Tim Voorhees, Robert Baiocchi, David Bond, Beth Christian, Kami Maddocks, Yazeed Sawalha, Maryam B Lustberg
{"title":"Longitudinal plasma neurofilament light chain and patient-reported outcomes as complementary markers of vincristine-associated peripheral neuropathy in adults with lymphoma: a cohort study.","authors":"Gretchen A McNally, Grace Ji-Eun Shin, Lise Worthen-Chaudhari, Patrick M Schnell, Laura Flora, Surith Sanjay Krishna, Tim Voorhees, Robert Baiocchi, David Bond, Beth Christian, Kami Maddocks, Yazeed Sawalha, Maryam B Lustberg","doi":"10.1007/s00415-026-14096-2","DOIUrl":"10.1007/s00415-026-14096-2","url":null,"abstract":"<p><p>Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurotoxicity of cancer treatment with limited diagnostic, monitoring, and treatment options. Neurofilament light chain (NfL) is an axonal cytoskeletal protein released during neuroaxonal injury and a promising biomarker of CIPN, but prospective evidence for NfL as a marker of CIPN from vincristine-containing lymphoma chemotherapy treatment remains limited. To fill this gap, we conducted a pragmatic single-center prospective observational cohort study of adults with non-Hodgkin lymphoma (NHL) receiving first-line vincristine-containing chemotherapy to evaluate NfL dynamics across multiple pre-cycle visits and assess relationships with patient-reported and clinician-graded neuropathy measures. We followed 25 participants during 4-6 months of chemotherapy, and a small subset of those participants (n=6) for 24-42 months post-chemotherapy. Serial plasma NfL was measured and CIPN symptoms were assessed using patient- and clinician-reported measures. Longitudinal changes were analyzed using mixed-effects models. Plasma NfL increased relative to pre-cycle1 at all timepoints (all p<0.001), increasing approximately fourfold by pre-cycle4. Patient-reported CIPN scores and clinician-graded neuropathy also increased during treatment. Exploratory pooled visit-level analyses showed a modest NfL-CIPN association (repeated measures correlation=0.439, p=0.020), while timepoint-specific, lagged, and post hoc sensitivity analyses suggested potential to predict persistent CIPN symptoms from early NfL concentrations. To our knowledge, these findings extend prospective evidence supporting NfL as a biomarker of vincristine exposure in adults with NHL receiving vincristine-containing therapy and may complement patient-reported symptom assessment, clinician grading, and dose-modification context in future CIPN monitoring studies.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Helga Maria Grétarsdóttir, Janet L Cunningham, Annica Rasmusson, Joachim Burman, Kim Kultima, Martin Paucar, Per Svenningsson, Radu Constantinescu, Valter Niemelä
{"title":"Decreased cerebrospinal fluid TNFRSF8 (sCD30) confirmed as a biomarker of Huntington's disease progression.","authors":"Helga Maria Grétarsdóttir, Janet L Cunningham, Annica Rasmusson, Joachim Burman, Kim Kultima, Martin Paucar, Per Svenningsson, Radu Constantinescu, Valter Niemelä","doi":"10.1007/s00415-026-14112-5","DOIUrl":"10.1007/s00415-026-14112-5","url":null,"abstract":"<p><strong>Background: </strong>In Huntington's disease (HD), clinical heterogeneity in age at onset and disease progression poses demands on precision medicine approaches. Biofluid biomarkers are needed to monitor disease progression, but may also provide insights into pathogenic mechanisms and support the development of disease-modifying therapies (DMTs).</p><p><strong>Objective: </strong>To identify dysregulated cerebrospinal fluid (CSF) proteins in HTT gene expansion carriers (HDGECs), and to evaluate their relationship with disease progression.</p><p><strong>Method: </strong>CSF was collected from a discovery and a validation cohort, both comprising HDGECs and neurologically unaffected controls (HCs). A total of 734 proteins were quantified using a high-sensitive Proximity Extension Assay (PEA) (Olink Neuro Explore panel 1 and 2). Protein association with disease progression was evaluated using the composite Unified HD Rating Scale (cUHDRS). Disease stage was classified according to the HD Integrated Staging System (HD-ISS).</p><p><strong>Results: </strong>In total, samples included HDGECs (n=61), HCs (n=54), and longitudinal HDGEC samples (n=21). Sixteen proteins were nominally dysregulated in HDGECs vs. HCs. Most pronounced was a twofold decrease of TNFRSF8 (sCD30) in HDGECs, and longitudinally declining levels were found. TNFRSF8 correlated significantly with cUHDRS, after adjustment for age, sex, and CAG. Levels of TNFRSF8 were similarly reduced in the validation cohort, and correlated with Total Functional Capacity (TFC).</p><p><strong>Conclusion: </strong>TNFRSF8 recently emerged as a biomarker of neuroimmune dysfunction in HD. The results indicate and confirm that it is highly dysregulated in HDGECs and also tracks clinical disease progression. This pathway may be a promising potential target for DMTs.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tao Chen, Qingyu Sun, David Foxe, Manisha Narasimhan, Claris Teng, Sau Chi Cheung, James Carrick, James R Burrell, Yun Tae Hwang, Rebekah M Ahmed, Olivier Piguet, Muireann Irish
{"title":"Behavioural and psychological symptom determinants of carer burden across clinical syndromes associated with frontotemporal lobar degeneration and Alzheimer's disease: a transdiagnostic analysis.","authors":"Tao Chen, Qingyu Sun, David Foxe, Manisha Narasimhan, Claris Teng, Sau Chi Cheung, James Carrick, James R Burrell, Yun Tae Hwang, Rebekah M Ahmed, Olivier Piguet, Muireann Irish","doi":"10.1007/s00415-026-14132-1","DOIUrl":"10.1007/s00415-026-14132-1","url":null,"abstract":"<p><strong>Background: </strong>This study characterised overall transdiagnostic associations between psychological and behavioural symptoms and carer burden, and examined syndrome-specific contributions across clinically probable FTLD and AD groups.</p><p><strong>Methods: </strong>A total of 432 individuals with clinically probable FTLD and AD were included. The primary analytic cohort comprised 358 participants with complete carer burden data, including 230 and 128 individuals in the FTLD and AD diagnostic groups, respectively. Behavioural and psychological symptoms were assessed using the Cambridge Behavioural Inventory-Revised (CBI-R). Carer burden was measured with the Zarit Burden Interview (ZBI). Longitudinal CBI-R and ZBI data were analysed in 172 participants with available ZBI data at both baseline and follow-up (mean interval ≈ 1 year).</p><p><strong>Results: </strong>Behavioural rigidity (standardised β = 0.15, 95% CI [0.03, 0.28], p = 0.015) and apathy (standardised β = 0.14, 95% CI [0.02, 0.26], p = 0.020) showed the strongest associations with carer burden overall. Behavioural rigidity was salient in the FTLD group (standardised β = 0.18, 95% CI [0.02, 0.33], p = 0.024), whereas apathy (standardised β = 0.26, 95% CI [0.04, 0.47], p = 0.021) and abnormal behaviour (standardised β = 0.26, 95% CI [0.05, 0.48], p = 0.018) were salient in the AD group. Longitudinal increases in mood-related symptoms (standardised β = 0.24, 95% CI [0.001, 0.48], p = 0.048) predicted greater carer burden at follow-up.</p><p><strong>Conclusions: </strong>Our findings highlight the relevance of symptom-focussed strategies for managing carer burden across dementia syndromes. Group-specific analyses suggest prioritising behavioural rigidity in FTLD syndromes and apathy and abnormal behaviour in AD subtypes, while timely management of changes in mood symptoms may help alleviate carer burden over time.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bridget H Maher, Neven Maksemous, Heidi G Sutherland, Robert A Smith, Omar Dabash, Annette Greenhow, Fatima A Nasralla, Dale R Nyholt, Arn M J M van den Maagdenberg, Rodney A Lea, Lyn R Griffiths
{"title":"Investigating genetic susceptibility to concussion through rare variants in ion channel and neurotransmission genes.","authors":"Bridget H Maher, Neven Maksemous, Heidi G Sutherland, Robert A Smith, Omar Dabash, Annette Greenhow, Fatima A Nasralla, Dale R Nyholt, Arn M J M van den Maagdenberg, Rodney A Lea, Lyn R Griffiths","doi":"10.1007/s00415-026-14139-8","DOIUrl":"10.1007/s00415-026-14139-8","url":null,"abstract":"<p><p>Some individuals appear more susceptible to concussion or mild traumatic brain injury (mTBI) and the severity, range, and the persistence of post-concussion symptoms vary considerably between affected individuals. Genetic factors are likely to contribute to this variability. Symptomatic overlap of post-concussion syndrome with neurological conditions such as familial hemiplegic migraine (FHM) caused by rare pathogenic variants in ion channel and synapse protein genes, with high sensitivity to head trauma for some patients, suggests that variation in similar pathways may influence concussion susceptibility and recovery. To investigate this hypothesis, we performed whole exome sequencing in 93 unrelated individuals who had sustained a single or multiple concussions and examined rare protein-altering variants in FHM genes, other neuronal ion channel and transporter genes, and genes involved in neurotransmission. We identified 62 different rare missense variants across 24 genes in 59 participants (63%), with 26 individuals carrying 2 or more variants. The prevalence of specific likely damaging rare variants in the 16 ion channel-related genes that were identified was approximately fivefold higher than that observed from gnomAD population controls (Odds Ratio = 5.44, 95% CI [4.13,7.18], P < 0.0001). Notably, voltage-gated calcium and sodium channel genes, including SCN9A, together with neurotransmission-related genes such as SNCAIP, harboured multiple potentially deleterious variants. These findings suggest that rare deleterious variants in genes involved in ion homeostasis and neurotransmission may contribute to an individual's susceptibility to concussion or more severe post-concussion symptoms. This study provides a foundation for future genetic and functional investigations aimed at improving our understanding of concussion susceptibility and outcomes. Further validation in larger cohorts and mechanistic studies is warranted to determine their utility as biomarkers of concussion risk and prognosis.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stent retrievers for acute ischemic stroke: technological advances, clinical applications, and future perspectives.","authors":"Zhiyuan Xie, Zixuan Wang, Peijie Fu, ZhiXing Shi, Zixuan Zhuang, Huiqin Wang, Yuanyuan Xiang, Xiaoping Yin, Zhiying Chen","doi":"10.1007/s00415-026-14126-z","DOIUrl":"10.1007/s00415-026-14126-z","url":null,"abstract":"<p><p>Acute ischemic stroke caused by large vessel occlusion remains a leading cause of death and disability despite established reperfusion therapies. Although stent retriever-based thrombectomy has become the standard of care, outcomes are still constrained in complex occlusions and anatomically challenging cases. This review summarizes and critically appraises recent advances in stent retriever technology, thrombectomy techniques, and evidence expansion in acute ischemic stroke. Device development has progressed from first-generation retrieval systems to self-expanding stent retrievers and recent integrated retrieval-protection platforms, leading to improved clot engagement, higher first-pass reperfusion, and reduced distal embolization. Parallel refinements in procedural strategies including combined aspiration catheters, balloon guide catheters, and dual-stent techniques have enhanced recanalization efficiency and procedural control. Clinical evidence has extended thrombectomy indications beyond conventional time windows to include posterior circulation occlusion, large infarct cores, and selected medium/distal vessel occlusions under imaging-guided selection. Advances in thrombus characterization, biomaterials, surface engineering, and territory-specific devices are further enabling more tailored mechanical approaches. Nevertheless, fibrin-rich resistant thrombi, embolic complications, vascular injury, and limited high-level evidence for emerging devices remain unresolved challenges. Ongoing integration of engineering innovation and clinical data is expected to support more individualized and safer thrombectomy strategies with improved functional outcomes.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}