Journal of Neurology最新文献

{"title":"Streamlining Alzheimer's disease diagnosis: real-world validation of two-cut-off diagnostic models based on plasma p-tau/Aβ42 ratios.","authors":"Martina Poli, Chiara Giuseppina Bonomi, Martina Gaia Di Donna, Ilaria Barberis, Emanuele Luca Ginevra, Marzia Nuccetelli, Sergio Bernardini, Diego Centonze, Alessandro Martorana, Caterina Motta","doi":"10.1007/s00415-026-13833-x","DOIUrl":"https://doi.org/10.1007/s00415-026-13833-x","url":null,"abstract":"<p><strong>Introduction: </strong>Anti-amyloid monoclonal antibodies have increased the need for scalable, minimally invasive biomarkers for Alzheimer's disease (AD). In this single-center cohort study, we evaluated plasma biomarkers performance in detecting biologically defined AD, assessing diagnostic accuracy and generalizability outside dedicated laboratory settings and exploring suitability for clinical implementation.</p><p><strong>Methods: </strong>We enrolled 204 outpatients referred to the memory clinic of Policlinico \"Rome Tor Vergata\" who underwent standard work-up, lumbar puncture for cerebrospinal fluid (CSF) biomarkers and paired blood sampling. Among plasma biomarkers, phosphorylated tau (p-tau) 181, p-tau217, and their ratios adjusted for Aβ42 were measured on the Lumipulse platform. AD pathology was defined by CSF p-tau181/Aβ42 ≥ 0.069. ROC analyses estimated AUCs, and a two-cut-off approach targeting 90% sensitivity and specificity classified individuals as low, intermediate, or high AD risk. Subgroup analyses examined the impact of sex, age (< 75, ≥ 75 years), chronic kidney disease, and cognitive impairment (MMSE ≥ 26/30, < 26/30) on plasma biomarker levels.</p><p><strong>Results: </strong>Among single analytes, plasma p-tau217 showed the highest discriminative capacity (AUC 0.883). Combined ratios improved overall performance (p-tau181/Aβ42, AUC 0.928; p-tau217/Aβ42, AUC 0.894) and reduced intermediate-risk classifications to < 15%, with slightly better performance in women, patients < 75 and cognitively unimpaired. The two-cut-off model improved accuracy and rule-in ability.</p><p><strong>Discussion: </strong>Plasma p-tau/Aβ42 ratios show high and robust accuracy for detecting CSF-defined AD pathology. A two-step approach based on p-tau181/Aβ42 or p-tau217/Aβ42 could streamline diagnostic workflows in memory clinics, reserving second-line assessments to indeterminate cases and supporting selection of candidates for disease-modifying anti-amyloid therapies.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 6","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838947","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":"Refining neuropsychological assessment strategies in multiple sclerosis: insights from long-term cognitive trajectories.","authors":"Gianpaolo Maggi, Manuela Altieri, Alessandro d'Ambrosio, Mario Risi, Riccardo Maria Borgo, Valentina Rippa, Rosaria Sacco, Luigi Lavorgna, Simona Bonavita, Gabriella Santangelo, Alessandro Tessitore, Alvino Bisecco, Antonio Gallo","doi":"10.1007/s00415-026-13800-6","DOIUrl":"https://doi.org/10.1007/s00415-026-13800-6","url":null,"abstract":"<p><strong>Objective: </strong>Cognitive evolution in people with multiple sclerosis (pwMS) may follow different trajectories. This study investigated long-term cognitive evolution in pwMS while controlling for methodological factors and psychological variables, to refine neuropsychological monitoring.</p><p><strong>Methods: </strong>A cohort of pwMS (n = 148) underwent neuropsychological evaluations at three time points: baseline (BL), re-baseline (RBL; ~ 1 year later), and long-term follow-up (LTFU; ~ 6 years after BL). Annualized cognitive change scores were analyzed to compare changes during BL-RBL interval with those in RB-LTFU. Participants were classified over time as cognitively preserved (CP) or cognitively impaired (CI) and McNemar's test evaluated classification changes. Sensitivity analysis was conducted in a subgroup of recently diagnosed pwMS (n = 91). Reliable Change Indices (RCI) at the 95% confidence level were calculated for each neuropsychological test to identify significant improvements or declines between assessments, while accounting for practice effects. Exploratory analysis examined baseline demographic and clinical differences between pwMS who showed cognitive recovery and those with persistent CI.</p><p><strong>Results: </strong>After controlling for test-retest effects, cognitive improvements occurred across several domains during BL-RB, while performance remained stable in RBL-LTFU. Shifts between CP and CI were more frequent in BL-RBL. Nearly 40% of pwMS classified as CI at BL reverted to CP at RBL, and approximately 50% reverted at LTFU. CP participants remained stable, with conversion rates to CI below 1%. RCI confirmed a higher number of reliable improvements than declines in the BL-RBL interval. Cognitive status at RBL and female sex were associated with cognitive recovery at LTFU.</p><p><strong>Discussion: </strong>Cognitive trajectories in pwMS are dynamic with early improvements partly reflecting baseline measurement bias. Clinically, CI individuals at BL should undergo RBL assessment to improve long-term prognostic accuracy, whereas CP participants can be monitored avoiding unnecessary evaluations, optimizing resource allocations.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 6","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838880","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":"The practice effect of smartphone-derived cognitive processing speed assessments as a proxy of cognitive functioning in multiple sclerosis.","authors":"Daan J de Jong, Pam C G Molenaar, Vera Verhoef, Lenka Novakova, Elisa Colato, Tommy A A Broeders, Samantha Noteboom, Ka-Hoo Lam, Sonja Cloosterman, Bastiaan Moraal, Dennis Nieuwkamp, Oliver Gerlach, Jop Mostert, Eva M M Strijbis, Menno M Schoonheim, Joep Killestein, Tom A N Fuchs","doi":"10.1007/s00415-026-13835-9","DOIUrl":"https://doi.org/10.1007/s00415-026-13835-9","url":null,"abstract":"<p><strong>Background: </strong>In multiple sclerosis (MS), symbol digit modalities test (SDMT) scores are often influenced by practice effects. We evaluated the SDMT practice effect as a proxy of cognitive performance by relating it to disease severity and future performance.</p><p><strong>Methods: </strong>People with MS (pwMS) and healthy controls (HCs) were evaluated at baseline and five-year follow-up. Practice effects were modeled using two-part piecewise linear regression on daily smartphone SDMT (sSDMT) scores. Cognitive impairment (CI) and preservation (CP) were defined relative to HC baseline sSDMT z-scores (CI: z < -1.67, CP: z ≥ -1.67). Practice outcomes across HC/CP/CI were compared using ANCOVA and correlated to baseline variables. They were also assessed in relation to clinical outcomes and brain volumes in cross-sectional and baseline-follow-up models.</p><p><strong>Results: </strong>85 pwMS (CP/CI: 66/19) and 20 HCs were analyzed. 73 pwMS completed follow-up (5.39 ± 0.38y). A practice plateau occurred in 80%/82%/100% of HC/CI/CP. Higher baseline sSDMT was related to higher plateau sSDMT (ρ = 0.930, p < 0.001) and lower %-increase (ρ = -0.266, p = 0.013). %-increase was higher in CI than CP (CI/CP = 22.0%/15.5 adj.p = 0.004), but the absolute ∆-increase and breakpoint were similar across groups. Associations of disability, cognition, and brain volumes with the plateau sSDMT were stronger when compared to the baseline sSDMT. No other associations were found cross-sectionally and in the baseline-follow-up models.</p><p><strong>Conclusions: </strong>Early-phase sSDMT practice effects were related to cognitive performance but were unique to disease status or associated with disease severity in pwMS. Plateau sSDMT showed stronger associations with disability and brain volumes than baseline performance. Interpretation of SDMT performance should therefore consider practice effects.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 6","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838911","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":"A new era in neuropharmacology: assessing the efficacy and safety of novel anti-amyloid and non-amyloid drug targets for Alzheimer's disease.","authors":"Mohamed M Hafez, Haidy A Abbas, Nabil A Shoman, Ayman A Soubh, Omnia Aly, Mohamed F Sallam, Mahmoud Seliem, Fady A Malaak","doi":"10.1007/s00415-026-13829-7","DOIUrl":"https://doi.org/10.1007/s00415-026-13829-7","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer disease (AD) is the most common cause of dementia in the world with the prevalence expected to increase threefold to 152.8 million people by 2050. The current medications provide a short-term ameliorative effect, and this requires development of disease-modifying treatments, which address the biological pathogenesis.</p><p><strong>Methods: </strong>This review assesses the changing neuropharmacological environment offering a critical analysis of anti-amyloid monoclonal antibodies and investigates the so-called expanding frontier of non-amyloid targets. It also examines the approaches of clinical trials and the trend of biomarker-based patient selection and precision medicine.</p><p><strong>Results: </strong>Although β-site APP-cleaving enzyme 1 (BACE1) and secretase inhibitors did not achieve success in clinical trials because of mechanism-based toxicity and cognitive impairment, new monoclonal antibodies such as lecanemab and donanemab have shown high amyloid plaque clearance and reduced cognitive deterioration. Nevertheless, the treatments are associated with amyloid-related imaging abnormalities (ARIA). In addition to amyloid, studies are focusing on tau hyperphosphorylation, neuroinflammation through triggering receptor on myeloid cells 2 (TREM2) and NLR family pyrin domain containing 3 (NLRP3) and growth factor-mediated synaptic plasticity through brain-derived neurotrophic factor (BDNF).</p><p><strong>Conclusions: </strong>AD treatment has entered the new era that demands a paradigm shift from monotherapies to multi-target cocktails. The future lies in precision neuropharmacology, where genetic stratification and individual biomarker analysis are used to provide the correct treatment at the most appropriate biological stage.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839212","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":"Prospective gait analysis in patients from the French registry of glycogen storage disease type III: implications for clinical trials.","authors":"Jean-Yves Hogrel, Frédéric Fer, Isabelle Ledoux, François Petit, Martha Darce-Bello, Philippe Labrune, Karim Wahbi, Dalila Habes, Antoine Gardin, Marion Masingue, Pascal Laforêt, Valérie Decostre","doi":"10.1007/s00415-026-13793-2","DOIUrl":"https://doi.org/10.1007/s00415-026-13793-2","url":null,"abstract":"<p><strong>Background and objectives: </strong>Glycogen storage disease type III (GSD-III) is a genetic metabolic disorder affecting liver and muscle, frequently leading to walking difficulties in adults. This study aimed to quantify walking performance and its progression in GSD-III, identify relevant outcome measures for future clinical trials, and determine predictors of gait decline.</p><p><strong>Methods: </strong>Participants enrolled in the French GSD-III registry underwent an annual assessment of their 6-min walk distance (6MWD) combined with 3D trunk accelerometry. Muscle strength for flexion and extension of the knee and ankle, as well as Motor Function Measure (MFM) scores, were also collected.</p><p><strong>Results: </strong>Among registry participants, 93% were ambulant without assistance. The 6MWD of participants with GSD-III (n = 46, aged 10-49 years) was lower than that of controls (n = 53) (adjusted p < 0.001), due to reduced stride frequency and stride length/height ratio (adjusted p < 0.001). Accelerometry revealed no abnormalities beyond those related to slower walking speed. 6MWD correlated with muscle strength and accelerometry variables. In adults, total MFM score declined with age (adjusted p < 0.001), whereas 6MWD remained stable overall, despite a gradual decline in a few patients. Preliminary models suggest that lower baseline MFM sub-scores and specific trunk accelerometry variables may predict 6MWD deterioration.</p><p><strong>Discussion: </strong>The walking impairment remains stable in most patients. MFM sub-scores and accelerometry variables may help identify the rare individuals at risk of gait decline. Unlike 6MWD, total MFM score worsened in adulthood and appears to be the most relevant muscle outcome measure for future clinical trials in GSD-III.</p><p><strong>French gsd-iii registry registration number: </strong>NCT06616545 was retrospectively registered on 27 SEP 2024.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838899","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":"Outcome associations of CSF total tau in suspected non-Alzheimer pathophysiology.","authors":"Nils Briel, Marc Borsi, Simon J Schreiner, Thomas Schneider, Sandra V Loosli, Claudio Togni, Manfredi C Carta, Jan Loosli, Alexander Köpp, Mario Ziegler, Tommaso Nicoletti, Michael Weller, Ansgar Felbecker, Tobias Weiss, Hans H Jung","doi":"10.1007/s00415-026-13841-x","DOIUrl":"https://doi.org/10.1007/s00415-026-13841-x","url":null,"abstract":"<p><strong>Introduction: </strong>Cognitively impaired patients with negative biomarkers of amyloidosis but with neurochemical evidence of Tau pathophysiology or neurodegeneration or both are classified as \"suspected non-Alzheimer pathophysiology\" (SNAP), according to the 2018 research framework for a biological definition of Alzheimer's disease (AD). The SNAP concept remains incompletely characterized, and associations of amyloid and tau biomarkers with survival outcomes in the SNAP context remain unclear.</p><p><strong>Methods: </strong>We conducted a retrospective study in patients with a SNAP biomarker constellation, recruited from two tertiary centers between 2019 and 2024. We extracted clinical demographic variables, biomarker results, and survival times to all-cause-mortality or last seen from electronic health records. SNAP patients were defined based on normal cerebrospinal fluid (CSF) levels of amyloid-β_1-42 (Aβ₄₂) and a normal Aβ₄₂/Aβ₄₀ ratio, and abnormal levels of phospho-Tau-181 (pTau) and/or total Tau (tTau), as measured with the Lumipulse G chemiluminescence assay. We computed the Youden index to dichotomize SNAP subgroups by CSF biomarkers and demographic variables in a data-driven approach and assessed survival using Kaplan-Meier curves and multivariable Cox hazard models. Patients were categorized as having either idiopathic or secondary neurodegenerative diseases, while those with prion disease were excluded from the final analyses.</p><p><strong>Results: </strong>Compared across amyloid-tau-neurodegeneration-defined categories, patients with SNAP had a shorter median survival than those with AD (31 vs. 42 months), while the Alzheimer's pathological change with concurrent neurodegeneration (APC + N) category exhibited the shortest median survival at 16 months. Patients with SNAP (n = 99) had a median age of 72 (inter-quartile range, IQR: 64; 77) years and a median follow-up time of 12 (IQR 1;27, max. 60) months. Among selected variables, tTau performed best in predicting survival during the follow-up period (area under the curve, AUC = 0.83) in non-prion SNAP, followed by the pTau/tTau ratio (AUC = 0.82). The optimal prognostic tTau cutpoint of ≥ 600 pg/mL was higher than the age-adjusted diagnostic reference (300-500 pg/mL). Patients with SNAP exhibiting higher tTau levels or a reduced pTau-181/tTau ratio had significantly shorter median survival times. Multivariable Cox hazard modeling confirmed tTau to be independently associated with survival with a hazard ratio of 6.1-6.8 (p < 0.001).</p><p><strong>Conclusion: </strong>We have identified CSF tTau as a novel predictor of survival in patients with SNAP. Although this descriptive diagnosis encompasses primarily various idiopathic neurodegenerative causes, we also demonstrate tTau's prognostic value in the context of secondary neurodegenerative processes. This finding can enhance prognostication in clinical settings.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774295","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":"Factors influencing accelerated progression in behavioral variant frontotemporal dementia.","authors":"Molly Split, Zachary J Kunicki, Daliah Ross, Rachel Keszycki, Sarah Prieto, Masood Manoochehri, Alyssa N De Vito, Brian Appleby, Chadwick M Hales, Chiadi Onyike, Corey T McMillan, David Clark, David Irwin, David Knopman, Douglas R Galasko, Dylan Wint, Erik D Roberson, Gabriel C Léger, Ging-Yuek Robin Hsiung, Hilary W Heuer, Howard J Rosen, Ian M Grant, Ian R Mackenzie, Irene Litvan, John Kornak, Justin Kwan, Katya Rascovsky, Kimiko Domoto-Reilly, Lauren Massimo, Lawrence S Honig, Leah K Forsberg, M Carmela Tartaglia, Mario F Mendez, Neill Graff-Radford, Nupur Ghoshal, Peter Ljubenkov, R Ryan Darby, Sami Barmada, Sandra Weintraub, Suzee Lee, A Campbell Sullivan, Adam Boxer, Adam M Staffaroni, Allison Snyder, Andrea Bozoki, Belen Pascual, Bradford C Dickerson, Bradley F Boeve, Edward D Huey, Megan Barker","doi":"10.1007/s00415-026-13839-5","DOIUrl":"https://doi.org/10.1007/s00415-026-13839-5","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to identify neuropsychiatric, motor, and cognitive features associated with accelerated disease progression in behavioral variant frontotemporal dementia (bvFTD).</p><p><strong>Methods: </strong>192 participants were classified as having mild or moderate disease severity based on CDR + NACC FTLD global scores, with scores of 0.5 or 1.0 defined as mild (n = 106) and 2.0 as moderate (n = 86). Participants were further categorized as having accelerated (mild: n = 35; moderate: n = 32) or non-accelerated (mild: n = 71; moderate: n = 54) progression rates based on change in CDR + NACC FTLD-SB sum of boxes (SB) scores (≥ 3.5 points) between Visit 1 and 2. Random forest modeling and logistic regression identified features most predictive of accelerated progression within each group.</p><p><strong>Results: </strong>In mild bvFTD, episodic memory impairment and presence of frontal-behavioral neuropsychiatric symptoms were predictive of accelerated progression, whereas in moderate bvFTD, language impairments and motor signs were the strongest predictors. Identified features improved prediction of accelerated progression beyond demographic and clinical factors in mild (∆R2 = .22, p < 0.001) and moderate bvFTD (∆R2 = 0.11, p = 0.08) but did not achieve statistical significance in the moderate group.</p><p><strong>Discussion: </strong>Distinct clinical profiles predict accelerated progression in mild versus moderate bvFTD, underscoring the importance of stage-specific clinical markers for prognosis and care.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774255","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":"Identifying diagnostic biomarkers in functional motor disorders through multimodal behavioral, neurophysiological, and imaging assessment using explainable machine learning.","authors":"Marialuisa Gandolfi, Angela Sandri, Michela Russo, Elisabetta Sarasso, Andrea Gardoni, Silvia Basaia, Roberto Erro, Sofia Cuoco, Immacolata Carotenuto, Carlo Ricciardi, Francesco Amato, Claudia Vinciguerra, Annibale Botto, Marianna Amboni, Daniele Romano, Ilaria Antonella Di Vico, Mirta Fiorio, Giulia Pedrotti, Anna Paolicelli, Mauro Crestani, Anna Fratucello, Giancarlo Mansueto, Francesca Benedetta Pizzini, Marco Barillari, Matteo Francesco Lauriola, Mariachiara Tozzi, Francesca Rusciano, Christian Geroin, Melania Fasoli, Angela Marotta, Francesca Salaorni, Giovanna Maddalena Squintani, Sara Mariotto, Stefano Tamburin, Fabio Paio, Giuseppe De Biasi, Giuseppe Piscosquito, Lucia Zenere, Elisa Canu, Paolo Barone, Massimo Filippi, Federica Agosta, Maria Teresa Pellecchia, Michele Tinazzi","doi":"10.1007/s00415-026-13838-6","DOIUrl":"10.1007/s00415-026-13838-6","url":null,"abstract":"<p><strong>Background: </strong>Functional motor disorders (FMDs) represent a frequent and disabling neurological condition. The lack of reliable diagnostic biomarkers and their heterogeneity might affect diagnosis. We identified multimodal biomarkers distinguishing FMDs from healthy controls (HCs) using machine-learning approaches.</p><p><strong>Methods: </strong>In this multicenter cross-sectional study, consecutive adults with a clinically established FMDs diagnosis (n = 75, 74.7% female; mean age 44.20 ± 12.92) and age- and sex-matched HCs (n = 75; 58.6% female; 48.42 ± 11.67) were recruited. All participants underwent standardized behavioral, neurophysiological, and brain MRI assessment exploring motor, exteroceptive, and interoceptive domains. A Random Forest (RF) classifier combined with repeated stratified k-fold cross-validation was trained on the collected features. Predictive performance was evaluated using accuracy, sensitivity, specificity, precision, F1-score, and AUC-ROC. SHapley Additive exPlanations interpreted feature importance.</p><p><strong>Results: </strong>The strongest diagnostic biomarkers were lower dual-task effect scores for postural sway area under eyes-closed motor and cognitive conditions, and gait speed during the motor dual-task, followed by increased vDMN and basal ganglia networks functional connectivity, reduced baseline ipsilateral-contralateral R2 blink reflex area, and higher DNIC-to-baseline N2P2 amplitude ratios for the lower limb. The RF classifier achieved robust performance (accuracy 85.0%, sensitivity 83.9%, specificity 86.1%, F1-score 85.7%, AUC-ROC 0.921).</p><p><strong>Conclusions: </strong>Motor, functional neuroimaging, and neurophysiological markers demonstrated diagnostic value in distinguishing FMDs from healthy controls, addressing the current lack of objective tools and supporting more confident and accurate diagnosis of these heterogeneous conditions.</p><p><strong>Trial registration: </strong>Trial registration number NCT06328790. Registered on 26 March 2024.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774348","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":"\"Getting to diagnosis was an absolute nightmare\": survey insights about the lived experience of spinal CSF leak in Australia and Aotearoa New Zealand.","authors":"Lachlan S W Knight, Rachel L Smith, Alexis Ceecee Britten-Jones, Sam E John, David B Grayden, Bang V Bui, Lauren N Ayton, Bao N Nguyen","doi":"10.1007/s00415-026-13840-y","DOIUrl":"https://doi.org/10.1007/s00415-026-13840-y","url":null,"abstract":"<p><strong>Background: </strong>Spinal cerebrospinal fluid (CSF) leak is a disabling and often misdiagnosed condition characterised by CSF hypovolemia. Associated neurological symptoms are diverse and often leave individuals bed-bound due to their orthostatic nature. Prior literature describing the difficulties in diagnosis, treatment, and ongoing impact of CSF leak is, thus far, confined to Europe and North America. This study provides a novel account of lived experiences of spinal CSF leak in Australia and Aotearoa New Zealand (NZ).</p><p><strong>Methods: </strong>An online survey exploring symptoms, diagnosis, treatment, and effect on daily life of a person's \"first\" CSF leak was designed with consumer involvement. Responses were received from May to August 2025. Open-text responses were analysed using thematic analysis.</p><p><strong>Results: </strong>In total, 106 surveys were completed. Over 70 symptoms were reported; the most common were orthostatic headache (95.3%), neck pain (85.8%), and brain fog (79.2%). Most people considered their diagnosis (73.6%) and treatment (65.3%) difficult, underscored by limited clinician awareness and access to care, leaving individuals to self-advocate. Amongst symptomatic participants (73.6%), median EuroQol Visual Analogue Scale score was 40 (interquartile range 25-64; indicating low health-related quality-of-life) and mean Headache Impact Test-6 score was 69 ± 5 (indicating severe impact). Other challenges identified included navigating change to social identity and daily functioning.</p><p><strong>Conclusions: </strong>The spinal CSF leak experience in Australia and NZ is comparable to reports from other high-income countries, highlighting the global need to increase awareness of spinal CSF leak, support timely diagnostic, referral and treatment pathways, and mitigate its impact on quality of life.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816434","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":"Association between post-COVID-19 neuropsychiatric symptoms and persistent glial activation in the limbic system: a TSPO PET study.","authors":"Joel Tuomaala, Maija Saraste, Emma Smith, Matilda Kuusi, Elisabet Westerberg, Eveliina Honkonen, Rahim Kargar, Sini Laaksonen, Jussi Lehto, Amelie Luoma, Markus Matilainen, Olavi Misin, Janne Atosuo, Mari Kanerva, Helena Liira, Sini Laakso, Tatiana Posharina, Virva Saunavaara, Saara Wahlroos, Johan Rajander, Laura Airas","doi":"10.1007/s00415-026-13842-w","DOIUrl":"10.1007/s00415-026-13842-w","url":null,"abstract":"<p><strong>Background: </strong>A subset of individuals experience prolonged neurological and psychiatric symptoms following SARS-CoV-2 infection, a condition referred to as long COVID (LC). Limited evidence implicates ongoing neuroinflammatory processes as a driver of LC. This study investigates neuroinflammation in LC using translocator protein positron emission tomography (TSPO PET).</p><p><strong>Methods: </strong>14 LC, 11 healthy control (HC) and 13 multiple sclerosis (MS) participants were included in the study. They underwent [¹¹C]PK11195 TSPO PET and 3T magnetic resonance imaging (MRI) to evaluate glial activation, white matter (WM) pathology and brain volumetrics. Serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were measured as markers of neuronal and glial damage. LC participants completed neurological examinations and mental health assessments.</p><p><strong>Results: </strong>TSPO availability, measured as distribution volume ratio (DVR), was not elevated in LC compared to HCs but was significantly lower in LC compared to MS (WM DVR 1.03 vs. 1.06; p = 0.007). Individuals imaged within 16 months of SARS-CoV-2 infection showed higher WM DVR compared to those with a longer disease duration (1.05 vs. 1.02; p = 0.04). Moreover, lower quality of life was associated with higher DVRs in the hippocampus, amygdala and thalamus (ρ = - 0.83- - 0.70), and depression and anxiety correlated positively with DVRs in the hippocampus and amygdala (ρ = 0.75-0.97).</p><p><strong>Conclusions: </strong>LC TSPO availability did not differ from HCs in any studied brain area. However, lower WM TSPO availability in individuals with longer LC duration suggests COVID-19-associated neuroinflammation may subside with time, while the association between limbic TSPO availability and LC severity may imply a role for limbic activity in LC symptomology.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774178","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}