Neurological research and practice最新文献

{"title":"Heparin-calibrated anti-factor Xa activity as a surrogate marker for direct oral anticoagulant levels in acute stroke care: a large observational single-center study.","authors":"Martin Büchsel, Katharina Lisko, Hanna Gölz, Jürgen Bardutzky, Heinz Wiendl, Saúl Beltrán Felipa, Johann Lambeck","doi":"10.1186/s42466-026-00524-1","DOIUrl":"https://doi.org/10.1186/s42466-026-00524-1","url":null,"abstract":"<p><strong>Background and purpose: </strong>Direct oral anticoagulants (DOAC) complicate therapeutic decision-making, as rapid assessment of anticoagulant activity is critical in emergency patients, particularly in acute ischemic stroke (AIS). The administration of systemic thrombolysis (IVT) in anti-coagulated patients requires careful risk-benefit evaluation, given the potential for hemorrhagic complications. Substance-specific DOAC plasma level measurements are often unavailable outside tertiary centers. This study evaluated whether widely available heparin-calibrated anti-factor Xa (anti-Xa) activity can reliably estimate clinically relevant DOAC levels and support urgent clinical decision-making.</p><p><strong>Methods: </strong>This retrospective single-center study (2015-2023) analyzed 969 patients treated with apixaban, rivaroxaban, or edoxaban. All patients had parallel measurements of anti-Xa activity and specific DOAC levels. Correlations were assessed using Spearman's coefficient. Receiver operating characteristic (ROC) analyses were performed to derive anti-Xa cut-off values corresponding to DOAC concentrations of 30, 50, and 100 ng/mL.</p><p><strong>Results: </strong>Anti-Xa activity strongly correlated with DOAC plasma levels for all substances (Spearman's ρ ≈ 0.95-0.96). ROC analyses demonstrated excellent diagnostic accuracy, with areas under the curve ≥ 0.97 for all evaluated thresholds. Similar anti-Xa cut-offs were observed for apixaban and rivaroxaban, whereas these were lower for edoxaban. For all DOACs combined, anti-Xa cut-offs of approximately 0.36U/mL, 0.56U/mL, and 1.19U/mL corresponded to DOAC levels of 30, 50, and 100ng/mL, respectively, with high sensitivity and specificity.</p><p><strong>Conclusions: </strong>Heparin-calibrated anti-Xa activity is a reliable surrogate marker for clinically relevant DOAC levels. Defined anti-Xa cut-offs are highly specific and sensitive and enable rapid and standardized assessment of anticoagulant activity in this cohort.</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"8 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803945","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":"Biomarker-based assessment of cerebral small vessel disease progression after ischemic stroke - a prospective cohort study (MA-BIO).","authors":"Lachin Hasanova, Paula Klassen, Anastasia Nosanova, Malak Babayeva, Dorothée Lulé, Hayrettin Tumani, Hans-Peter Müller, Deniz Yilmazer-Hanke, Nico Sollmann, Kornelia Kreiser, Karl Georg Haeusler, Mona Laible","doi":"10.1186/s42466-026-00514-3","DOIUrl":"https://doi.org/10.1186/s42466-026-00514-3","url":null,"abstract":"<p><strong>Background: </strong>Cerebral small vessel disease (CSVD) is a leading cause of ischemic stroke and vascular cognitive impairment, yet currently lacks clinically established biomarkers for monitoring disease activity. While clinical routine magnetic resonance imaging (MRI) can provide quantitative measures of structural brain changes, it does not capture ongoing pathophysiological processes. Blood-based biomarkers offer a minimally invasive approach to detect dynamic changes in CSVD and may provide novel insights into mechanisms of progression and potential targets for intervention. This study aims to evaluate longitudinal trajectories of candidate blood biomarkers and their association with MRI-derived markers and cognitive outcomes in patients with CSVD.</p><p><strong>Methods: </strong>In this single-center, prospective observational cohort study at the University Hospital Ulm, Germany, up to 180 adults with MRI-proven evidence of CSVD will be recruited and stratified into three groups: (1) CSVD without acute ischemic stroke, (2) CSVD with acute lacunar ischemic stroke, and (3) CSVD with territorial ischemic stroke. Participants will undergo comprehensive assessments at baseline, at 3, 6, and 12 months after enrollment. The primary outcome is defined as longitudinal changes of White Matter Hyperintensities (WMH) volumes. Secondary outcomes upon one year include DTI-derived measures, changes in blood biomarkers, cognitive performance, clinical functional measures, and incidence of new cerebrovascular events. Imaging, neurovascular ultrasound, and neuropsychological assessments will be conducted using standardized protocols. Clinical primary and secondary outcomes will be correlated to post-mortem CSVD pathology in the brain in prospectively studied patients, who have consented to autopsy.</p><p><strong>Discussion: </strong>By integrating blood-based biomarkers with advanced imaging and longitudinal cognitive assessments, this study aims to advance our understanding of CSVD pathophysiology and may identify biomarkers of disease activity. Our findings hopefully inform future precision-medicine approaches and novel therapeutic strategies.</p><p><strong>Trial registration: </strong>German Clinical Trials Registry (DRKS00038936), registered February 3, 2026.</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"8 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803993","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":"Guideline of the German Society of Neurology (DGN): \"diagnosis and therapy of HIV-1-associated neurological disorders\".","authors":"Katrin Hahn, Gabriele Arendt, Christian Eggers, Cristina Granziera, Matthias Maschke","doi":"10.1186/s42466-026-00519-y","DOIUrl":"https://doi.org/10.1186/s42466-026-00519-y","url":null,"abstract":"<p><p>Epidemiology and treatment of HIV changed substantially within the last three decades. However, HIV-associated neurological disorders such as mild forms of HIV-associated neurocognitive disorder (HAND) as well as HIV-associated distal symmetrical sensory polyneuropathy are amongst the most frequent complications in patients with longstanding HIV infection. Opportunistic infections occur less frequently compared to former years, but especially in patients with late presentation of HIV progressive multifocal leukoencephalopathy (PML) (0.7 per 1,000 patient-years), toxoplasma encephalitis (0.4 per 1,000 patient-years) and cryptococcal meningitis (0.2 per 1,000 patient-years) remain the most common opportunistic infections. The guidelines for diagnosis and treatment of HIV-associated neurological disorders of the German Society of Neurology were revised addressing recent changes in treatment opportunities of HAND, HIV associated complications of the peripheral nervous system and muscles and opportunistic infections of the central nervous system (CNS).</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"8 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13474671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761121","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":"Physical activity promotes clinical benefits beyond dopaminergic preservation in Parkinson's disease: a longitudinal analysis of the PPMI cohort.","authors":"Minkyeong Kim, Kyoungjune Pak, Jae-Hyeok Lee, Myung Jun Lee","doi":"10.1186/s42466-026-00518-z","DOIUrl":"10.1186/s42466-026-00518-z","url":null,"abstract":"<p><strong>Background: </strong>Physical activity is associated with better clinical outcomes in Parkinson's disease (PD). This study aimed to investigate the effects of physical activity on longitudinal changes in dopamine transporter (DAT) availability and motor and cognitive outcomes. Additionally, it explored whether striatal dopaminergic integrity mediates these effects.</p><p><strong>Methods: </strong>Using data from the Parkinson's Progression Markers Initiative, we included patients with PD who had at least 4 years of follow-up data on the Physical Activity Scale for the Elderly and at least two assessments of DAT imaging, motor and cognitive functions, resulting in three analytical datasets (n = 141, 233, and 259, respectively). Linear mixed-effects models were used to analyse the influence of physical activity on the progression of DAT availability and clinical outcomes. Multilevel mediation analyses investigated the mediation effect of physical activity on the rate of clinical progression.</p><p><strong>Results: </strong>Higher levels of physical activity were significantly associated with a slower decline in caudate DAT availability, attenuated progression of axial symptoms, rigidity, and overall motor severity, and better preservation of Montreal Cognitive Assessment and Symbol Digit Modalities Test scores. Mediation analyses demonstrated that higher physical activity was significantly associated with slower caudate DAT decline; however, none of the clinical outcomes were significantly mediated by caudate DAT preservation, as all indirect effects were non-significant.</p><p><strong>Conclusion: </strong>These findings suggest that physical activity is associated with both dopaminergic degeneration and clinical progression in PD. However, the observed clinical benefits are likely primarily driven by mechanisms beyond striatal dopaminergic preservation.</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"8 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13463522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148715110","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":"Disease modifying treatment of hereditary transthyretin amyloidosis with polyneuropathy in Germany - expert consensus of the German society of amyloid diseases (DGAK) and the German neurological society (DGN).","authors":"Markus Weiler, Maike F Dohrn, Stefan Gingele, Thomas Skripuletz, Matthias Schilling, Tim Hagenacker, Ernst Hund, Juliane Sachau, Ralf Baron, Helena Pernice, Sebastian Spethmann, Cyrus Khandanpour, Alexander Carpinteiro, Caroline Morbach, Katrin Hahn","doi":"10.1186/s42466-026-00521-4","DOIUrl":"10.1186/s42466-026-00521-4","url":null,"abstract":"<p><p>Hereditary transthyretin (ATTRv) amyloidosis is a rare, progressive multisystem disease caused by pathogenic variants in the transthyretin (TTR) gene. ATTRv-associated Polyneuropathy (ATTRv-PN) manifests in a length-dependent sensorimotor and autonomic pattern, commonly accompanied by cardiomyopathy. In recent years, clinical trials have introduced two classes of disease modifying treatments (DMT), TTR stabilizers and gene silencers. Across populations and outcome parameters, all trials share one result disease progression was significantly slowed and patients' span and quality of life substantially improved compared to placebo, even though a function once lost would not be retrieved. This expert consensus paper provides recommendations for the treatment of ATTRv-PN in Germany and was jointly developed by experts from the German Society of Amyloid Diseases (DGAK) and the German Neurological Society (DGN). In addition to evidence from pivotal clinical trials, the recommendations incorporate benefit assessments of the German Federal Joint Committee (G-BA). For first-line treatment, the DGAK/DGN recommends one of the two second-generation TTR gene-silencing agents, vutrisiran or eplontersen, for most patients with symptomatic ATTRv-PN. For patients showing even minor signs of disease progression under a TTR stabilizer, the authors recommend immediate switch to a gene silencer. Evidence is limited for or against switching between silencers or combining different agents. Informed patient participation is crucial upon initiation and adaptation of DMT. For central nervous system (CNS) involvement, none of the approved agents sufficiently crosses the blood-brain barrier. Aligned with that, there are no observed or expected CNS side effects of any of the DMTs. In the future, next-generation RNA-interference therapies, gene-editing approaches, and amyloid-depleting antibodies are expected to further expand therapeutic options.</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"8 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13466188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148715098","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":"A mechanosensitive gene signature associated with immune landscape and survival in glioma: a multi-cohort analysis.","authors":"Tianxue Yang, Ye Yuan, Nianhong Lu, Rui Han, Ziran Xu","doi":"10.1186/s42466-026-00515-2","DOIUrl":"10.1186/s42466-026-00515-2","url":null,"abstract":"<p><strong>Background: </strong>Glioma is characterized by substantial molecular heterogeneity and poor clinical outcomes. Emerging evidence suggests that mechanotransduction-related pathways may influence tumor progression and immune remodeling. However, the prognostic relevance of mechanosensitive genes in glioma remains unclear.</p><p><strong>Methods: </strong>RNA-sequencing data and clinical information from the TCGA, CGGA-301, CGGA-325, and GSE16011 cohorts were analyzed. Mechanosensitive genes were identified from curated gene sets, and a prognostic signature was constructed using LASSO and Cox regression analyses. Immune infiltration, immune checkpoint expression, TIDE predictions, and drug sensitivity were evaluated. The risk score was consistently and positively correlated with SPP1 expression across four independent cohorts, and single‑cell analysis further suggested that SPP1‑related signaling may contribute to immune microenvironment remodeling. Selected genes were validated by qRT-PCR in glioma cell lines.</p><p><strong>Results: </strong>A nine-gene mechanosensitive signature stratified glioma patients into high- and low-risk groups with significantly different overall survival across multiple cohorts. The risk score was independently associated with established clinicopathological factors, including WHO grade, IDH mutation status, 1p/19q co-deletion status, and MGMT promoter methylation status. High-risk tumors exhibited increased macrophage and neutrophil infiltration, elevated immune checkpoint expression, and higher predicted immune evasion potential. Single-cell analysis suggested that SPP1-related signaling may contribute to immune microenvironment remodeling. Experimental validation supported differential expression of selected genes in glioma cells.</p><p><strong>Conclusions: </strong>This mechanosensitive gene signature is associated with immune landscape heterogeneity and survival in glioma. The model may provide complementary stratification information and support further investigation of mechanobiology-related tumor-microenvironment interactions.</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"8 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690628","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":"Mental health and suicidality in glioblastoma patients in germany - a multicenter cross-sectional observational study protocol (SHINE-GLIO Study).","authors":"Mareike Rutenkröger, Maximilian Scheer, Niklas Benedikt Pepper, Felix Ehret, Franziska M Ippen, Teresa Schmidt, Jana Grieger, Giorgio Cappello, Leon Jekel, Lazaros Lazaridis, Ulrich Sure, Laurèl Rauschenbach, Yahya Ahmadipour, Christoph Kleinschnitz, Lasse Dührsen, Joachim Peter Steinbach, Heidrun Golla, Corinna Seliger-Behme, Christoph Oster, Sied Kebir","doi":"10.1186/s42466-026-00520-5","DOIUrl":"10.1186/s42466-026-00520-5","url":null,"abstract":"<p><strong>Introduction: </strong>Glioblastoma is an aggressive primary brain tumor with poor survival. Depressive and anxiety symptoms and suicidality are common and impair quality of life and care. Prospective multicenter data using validated measures of suicidal ideation and behavior in German glioblastoma cohorts are scarce. We aim to quantify psychiatric symptom burden and suicidality and examine associations with demographic, clinical, and tumor-related characteristics.</p><p><strong>Methods: </strong>SHINE-GLIO is a multicenter, cross-sectional observational study at German neuro-oncology centers. Adults with newly diagnosed isocitrate dehydrogenase wild-type glioblastoma after primary radiotherapy and before first recurrence are eligible. Exclusion criteria include clinically significant aphasia, other malignancies, and known tumor predisposition syndromes. At one outpatient visit, participants undergo physical examination and complete validated self-report questionnaires assessing suicidality (SSEV), depressive symptoms (PHQ-8), anxiety (GAD-7), social support (SUCE-4), and quality of life (EORTC QLQ-C30 and QLQ-BN20). Tumor characteristics, clinical history, and concomitant medications are extracted from medical records. Prespecified regression models will examine associations with suicidality while accounting for demographic, clinical, and tumor-related factors.</p><p><strong>Perspective: </strong>This study will provide a standardized multicenter assessment of suicidality and related psychiatric symptoms in German patients with glioblastoma. The findings may inform screening and referral pathways for mental health care.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT07409584. First posted prospectively on February 12, 2026.</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"8 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687327","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":"Syphilis and cerebral stroke: a case report and systematic review.","authors":"Judith N Wagner, Matthias Klein, Susanne Dyckhoff-Shen","doi":"10.1186/s42466-026-00510-7","DOIUrl":"10.1186/s42466-026-00510-7","url":null,"abstract":"<p><strong>Background: </strong>Syphilis is a multifaceted disease caused by Treponema pallidum. It has re-emerged as a public health concern and represents a potentially treatable cause of cerebrovascular disease. Neurosyphilis (NS) can involve the central nervous system at any stage of infection, with meningovascular syphilis leading to ischemic or, less frequently, hemorrhagic stroke. Diagnosis remains challenging due to heterogeneous clinical presentations and challenging serological diagnostics.</p><p><strong>Methods: </strong>We report a case of ischemic stroke as the first manifestation of syphilis and performed a systematic review of the literature on syphilis-associated stroke. A structured search of PubMed, the COCHRANE Library, and secondary sources was conducted for studies published from 1972 onward.</p><p><strong>Results: </strong>The reported case describes a 44-year-old HIV-negative man presenting with ischemic stroke due to presumed small-vessel meningovascular syphilis, supported by CSF pleocytosis and positive treponemal serology in serum and CSF. The patient improved substantially following ceftriaxone therapy. The systematic review identified 98 relevant publications, including 73 individual cases and 36 cohort studies. Stroke frequently led to the initial diagnosis of syphilis and predominantly affected younger male patients. Ischemic stroke was the most common presentation, mainly due to large-vessel disease. Penicillin was the most frequently used therapy, with ceftriaxone as an effective alternative.</p><p><strong>Discussion: </strong>Syphilis is an important and underrecognized risk factor for stroke, particularly in younger patients. NS should be considered in cases of cryptogenic stroke, and standardized diagnostic and therapeutic approaches are needed to improve recognition and outcomes. Few data on the specific stroke treatment in syphilis exist.</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"8 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671801","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":"Ethical challenges in treatment-goal transitions in invasively ventilated ALS: a case-based topical review.","authors":"Sarah K Bublitz, Benedikt Becker, Antonia F Demleitner, Petra Dietz-Laukemann, Paul Lingor, Benno Littger, Stefan Lorenzl, Berend Feddersen","doi":"10.1186/s42466-026-00522-3","DOIUrl":"10.1186/s42466-026-00522-3","url":null,"abstract":"<p><strong>Introduction: </strong>In advanced amyotrophic lateral sclerosis (ALS), eye movements often represent the last channel for intentional communication. While oculomotor function has traditionally been considered relatively preserved, emerging evidence indicates progressive impairment in long-term survivors on tracheostomy-invasive ventilation (TIV). As a result, eye-based communication may become increasingly unreliable before complete loss, challenging clinical decision-making and advance care planning (ACP).</p><p><strong>Methods: </strong>We conducted a case-based topical review integrating clinical observation and literature to examine the trajectory of oculomotor decline, its impact on communication, and implications for treatment decisions. Three patients with ALS receiving TIV in a home-care setting illustrate key clinical and ethical challenges.</p><p><strong>Results: </strong>Across cases and literature, oculomotor decline followed a gradual trajectory from effective eye-tracking communication to a complete locked-in syndrome. We identify a transitional phase of communicative ambiguity, in which residual ocular signals persist but can no longer be reliably attributed to intentional, patient-controlled communication. This phase is characterized by increasing inconsistency of signals and a divergence between observable responses and their interpretive certainty, creating uncertainty in assessing patient preferences.</p><p><strong>Implications: </strong>Communicative ambiguity represents a clinically underrecognized but critical threshold in advanced ALS, marking the transition from direct patient autonomy to interpretative and surrogate-based decision-making. Failure to recognize this phase risks misinterpretation of patient intent and may undermine goal-concordant care. Timely and iterative ACP, initiated before communication becomes unreliable, is essential. We further propose four clinical pathways for treatment goal conversations, highlighting their differing implications for timing, symptom burden, and ethical decision-making.</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"8 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633244","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":"Impact of brain frailty on language recovery in patients with acute post-stroke aphasia: a post-hoc analysis of the LEXI randomized controlled trial.","authors":"Johannes Wischmann, Robert Forbrig, Julia Franzen, Leanna Brasch, Friederike Häfner, Katharina Feil, Lars Kellert","doi":"10.1186/s42466-026-00516-1","DOIUrl":"10.1186/s42466-026-00516-1","url":null,"abstract":"<p><strong>Background: </strong>The influence of brain frailty on post-stroke aphasia recovery in the acute phase and its interaction with Speech and Language Therapy (SLT) intensity is unclear. We investigated the association between brain frailty components and language outcome and assessed whether brain frailty modifies the dose-dependent treatment effect of SLT.</p><p><strong>Methods: </strong>This is a post-hoc analysis of the LEXI multicenter randomized controlled trial, that enrolled patients with acute post-stroke aphasia from 07/2021 to 09/2024. Patients with pre-stroke cognitive impairment or dementia were not eligible for the trial. Participants were randomized to tablet-assisted SLT (Neolexon application) or standard SLT. Brain frailty was retrospectively assessed by outcome-blinded raters on interrater-adjusted baseline non-contrast CT, using cortical and subcortical atrophy, white matter changes (Fazekas score), lacunes, and chronic infarctions to derive a composite brain frailty score (BFS; range 0-3; higher scores indicate higher brain frailty burden). Primary outcome was the 90-days Bielefelder Aphasia Screening Test percentile rank.</p><p><strong>Results: </strong>56 patients (median age 75 years; 48.2% female) were included. 43 patients (76.8%) had a BFS of 0-1 and 13 (23.2%) of 2-3. Higher BFS were independently associated with worse 90-day language outcome (β -5.3; 95%CI -10.35 to -0.21; p = 0.042), with higher Fazekas scores contributing most (β -4.0; 95%CI -7.6 to -0.5; p = 0.028). Higher SLT dose was associated with improved outcome (β 0.34; 95%CI 0.07 to 0.61; p = 0.016). There was no statistical evidence that brain frailty modified the association between SLT duration and language outcome (p_interaction = 0.507), although the interaction analysis was limited by sample size.</p><p><strong>Conclusions: </strong>Higher white matter disease burden, as a component of brain frailty, was associated with poorer post-stroke language recovery in patients without pre-stroke cognitive impairment or dementia. We found no evidence that brain frailty modified the association between SLT intensity and language outcome, although larger studies are needed to assess effect modification. Routine imaging-based assessment of white matter disease burden may improve prognostic stratification and neurorehabilitation trial design.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov Identifier: NCT04080817; Study Details. Neolexon® Aphasia-App in Acute Aphasia After Stroke.</p><p><strong>Clinicaltrials: </strong>gov. Date of Registration: September 4, 2019).</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"8 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633247","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}