Journal of Neurology最新文献

{"title":"Improving survival in Duchenne muscular dystrophy across eras: a systematic review and cumulative meta-analysis.","authors":"Lara Benning, Zoe Bousraou, Bastian Gruber, Silvia Ulrich, Esther I Schwarz","doi":"10.1007/s00415-026-14121-4","DOIUrl":"https://doi.org/10.1007/s00415-026-14121-4","url":null,"abstract":"<p><strong>Background: </strong>Duchenne muscular dystrophy (DMD) was historically associated with death in the late teens or early twenties, mainly from respiratory failure. Survival has improved substantially with home mechanical ventilation (HMV) and multidisciplinary care, although variability remains. This study evaluated temporal trends in survival in DMD and the impact of HMV.</p><p><strong>Methods: </strong>A study-level cumulative meta-analysis (PROSPERO CRD420251163011) of studies reporting survival outcomes in patients with DMD was conducted (PubMed 1977 to 13 October 2025). Pooled estimates of median survival were calculated, and random-effects meta-analyses with predefined subgroups (HMV and study period) were performed, alongside meta-regressions. Risk of bias was assessed using the Newcastle-Ottawa Scale.</p><p><strong>Results: </strong>53 studies (median follow-up 8 years), comprising more than 13,000 patients, of whom 60% received HMV, were included. Median survival differed substantially between ventilated (29 years, 95%CI 27 to 31) and non-ventilated (19 years, 95%CI 18 to 20) patients. Survival improved progressively over time in both groups. Glucocorticoid therapy was not associated with improved survival (p=0.45), whereas treatment with heart failure medications, including renin-angiotensin system inhibitors (p=0.002) and β-blockers (p=0.02), was associated with longer survival. The predominance of mortality shifted from respiratory to cardiac causes, while enhanced cardiac management was associated with a growing contribution of other causes of death.</p><p><strong>Conclusion: </strong>Survival in DMD has increased substantially over time, with median survival now approaching the third decade of life among ventilated patients. The growing contribution of cardiac and other non-respiratory causes of death highlights the importance of long-term multidisciplinary and early cardioprotective intervention.</p><p><strong>Study registration: </strong>The meta-analysis and systematic review have been registered on PROSPERO (CRD420251163011).</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897446","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":"Therapeutic coma in non-convulsive status epilepticus is associated with increased complications and mortality: a retrospective cohort study.","authors":"Eyad Altarsha, Norma J Diel, Minja Braun, Daniela Schoene, Alia Kaadan, Haidar Moustafa, Simon Winzer, Annahita Sedghi, Timo Siepmann, Martin Lesser, Hagen B Huttner, Kristian Barlinn","doi":"10.1007/s00415-026-14090-8","DOIUrl":"https://doi.org/10.1007/s00415-026-14090-8","url":null,"abstract":"<p><strong>Introduction: </strong>While therapeutic coma is an established escalation strategy in generalized convulsive status epilepticus, evidence for benefit in non-convulsive status epilepticus (NCSE) is limited and treatment-related complications may affect outcome.</p><p><strong>Methods: </strong>We performed a retrospective cohort study of patients with NCSE treated at a tertiary hospital. Patients were classified according to receipt of therapeutic coma, defined as continuous intravenous and/or inhalational anesthetic administration for seizure control. The primary outcome was the occurrence of predefined clinically relevant in-hospital medical complications, including pneumonia, sepsis, cardiac arrhythmias, acute renal failure, renal replacement therapy, venous thromboembolism and cardiopulmonary resuscitation. Secondary outcomes included in-hospital mortality, ICU length of stay and successful termination of NCSE. Confounding by indication was addressed using inverse probability of treatment weighting (IPTW) based on propensity scores.</p><p><strong>Results: </strong>Among 283 patients with NCSE, 111 (39.2%) received therapeutic coma. In IPTW-adjusted analyses, therapeutic coma was associated with higher odds of pneumonia (OR 20.40, 95% CI 8.93-46.58; p < 0.001), sepsis (OR 6.09, 95% CI 3.14-11.80; p < 0.001), cardiac arrhythmias (OR 13.96, 95% CI 4.57-42.65; p < 0.001), acute renal failure (OR 4.17, 95% CI 1.85-9.40; p = 0.001), renal replacement therapy (OR 4.97, 95% CI 1.65-14.97; p = 0.004) and cardiopulmonary resuscitation (OR 11.22, 95% CI 2.35-53.63; p = 0.002), whereas the association with venous thromboembolism did not reach statistical significance (OR 3.04, 95% CI 0.97-9.51; p = 0.057). Therapeutic coma was also associated with increased in-hospital mortality (RR 1.86, 95% CI 1.28-2.71; p=0.001) and prolonged ICU length of stay (β = 1.36, 95% CI 1.13-1.60; p < 0.001). Successful NCSE termination occurred less frequently in patients treated with therapeutic coma (70.3% vs. 84.3%; p = 0.005).</p><p><strong>Conclusion: </strong>In NCSE, therapeutic coma was associated with higher complication rates, longer ICU stay and increased in-hospital mortality, while no higher rates of short-term seizure control were observed.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897531","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":"Evaluation of the 2022 international consensus criteria for optic neuritis: the role of clinical features and visual evoked potentials.","authors":"Luca Bollo, Angela Vidal-Jordana, Breogán Rodríguez-Acevedo, Sofia Sceppacuercia, Neus Mongay-Ochoa, Valeria Zancan, Paola Ajdinaj, Nathane Braga, Sergio Cabello, Manel Alberich, Juanfra Corral, Cristina Auger, Mar Tintoré, Xavier Montalban, Deborah Pareto, Dulce Moncho, Àlex Rovira, Jaume Sastre-Garriga","doi":"10.1007/s00415-026-13972-1","DOIUrl":"https://doi.org/10.1007/s00415-026-13972-1","url":null,"abstract":"<p><strong>Background and aim: </strong>Optic neuritis (ON) diagnosis is challenging due to variable clinical presentations and the limited prospective validation of current criteria. This study evaluates the 2022 international consensus criteria for optic neuritis (ICON) criteria, and the impact of adding visual evoked potentials (VEPs) and new clinical definitions to improve diagnostic accuracy.</p><p><strong>Methods: </strong>We introduced modifications to the ICON 2022 criteria, including a less strict clinical category allowing ON diagnosis with incomplete clinical features and the incorporation of VEPs as an additional paraclinical test. We then prospectively studied 46 patients with a first episode of unilateral subacute ON. Alongside standard clinical, MRI, OCT, and laboratory assessments, diagnostic classifications were compared between the original and modified criteria.</p><p><strong>Results: </strong>Using the original ICON 2022 criteria, 20 patients (43.5%) were classified as definite ON. This number increased to 32 patients (69.6%; p < 0.001) when applying the modified clinical criteria together with two abnormal paraclinical tests (MRI, OCT, or laboratory findings). When VEPs were incorporated alongside the less stringent clinical criteria, the number of definite ON cases further increased to 39 (84.8% vs. 43.5%; p < 0.001).</p><p><strong>Conclusion: </strong>The inclusion of VEPs, together with the adoption of less stringent clinical criteria, significantly increased the proportion of patients classified as having definite ON compared with the 2022 ICON criteria. This was particularly evident in patients with incomplete clinical presentations but typical paraclinical features, thereby supporting revisions aimed at broader clinical applicability.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892073","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":"Treatment updates in myotonic disorders.","authors":"Emma Matthews, Mark J Specterman, Karlien Mul","doi":"10.1007/s00415-026-14073-9","DOIUrl":"https://doi.org/10.1007/s00415-026-14073-9","url":null,"abstract":"<p><p>Myotonia is delayed muscle relaxation after forceful contraction. It is due to hyperexcitability of the skeletal muscle membrane. It can arise from primary skeletal muscle ion channel dysfunction, involving chloride or sodium channels, but is also a prominent clinical feature in myotonic dystrophies where altered RNA splicing leads to secondary ion channel dysregulation amongst other systemic manifestations. Clinically, myotonia can range from delayed eye opening to a disabling symptom causing impaired mobility, functional difficulty and sometimes pain. It can also be a \"hidden disability\" with many patients feeling socially embarrassed by \"looking healthy\", yet being unable to do everyday physical tasks or to do them as effortlessly as their peers. It is a symptom that almost always indicates a genetic diagnosis, although it can occur in acquired conditions, including metabolic and drug-induced causes. To experience myotonia without knowing what it is can be baffling. To receive a genetic diagnosis associated with it can be life changing. Although there is no cure, there are many effective and available symptomatic treatments for myotonia and currently we are in an exciting era of clinical trials for new molecular disease-modifying therapies for myotonic dystrophy type 1. In this review, we consider recent developments in the treatment of myotonic disorders and how they may change clinical practice.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892067","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":"Insomnia symptoms and stress exposure interact in relation to Alzheimer's disease biomarkers.","authors":"Jasper Holleman, Ingemar Kåreholt, Manasa Shanta Näsholm, Charlotte Sørensen, Göran Hagman, Malin Aspö, Miia Kivipelto, Alina Solomon, Shireen Sindi","doi":"10.1007/s00415-026-14102-7","DOIUrl":"10.1007/s00415-026-14102-7","url":null,"abstract":"<p><strong>Background: </strong>Several modifiable factors affect Alzheimer's disease (AD) risk. However, evidence on how these factors interact remains scarce, limiting our understanding of their role in AD development. This study aims to assess interactions between chronic stress exposure and insomnia in relation to AD biomarkers beta-amyloid (Aβ₄₂), total tau, and phosphorylated tau.</p><p><strong>Methods: </strong>The present study included 124 memory clinic patients without dementia from the Cortisol and Stress in Alzheimer's disease (Co-STAR) cohort study. Insomnia symptoms, stressful life events (SLEs) and current perceived stress were self-reported via questionnaires, while AD biomarkers were assessed from the cerebrospinal fluid (CSF). Cross-sectional interactions between stress and insomnia in relation to AD biomarkers were examined using linear regression models.</p><p><strong>Results: </strong>Insomnia and SLEs interacted in relation to Aβ₄₂. Greater stressor exposure was associated with reduced CSF Aβ₄₂ levels, reflecting greater brain amyloid accumulation, only in those with moderate-to-high insomnia scores. No interactions were found for total or phosphorylated tau.</p><p><strong>Conclusions: </strong>This study suggests that chronic stress and sleep disturbances exhibit an interactive relationship in their associations with AD pathology, and highlights the need for further research into interactive effects of multiple modifiable risk factors in the development of AD.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886965","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":"Distinct characteristics and risk factors of symptomatic and incidental DWI lesions in cerebral amyloid angiopathy.","authors":"Yuhui Sha, Juanjuan Wu, Yaping Zhou, Ziyue Liu, Fei Han, Ming Yao, Lixin Zhou, Yicheng Zhu, Joanna M Wardlaw, Jun Ni","doi":"10.1007/s00415-026-14107-2","DOIUrl":"https://doi.org/10.1007/s00415-026-14107-2","url":null,"abstract":"<p><strong>Background and objectives: </strong>Cerebral amyloid angiopathy (CAA) has long been regarded as a hemorrhagic age-related small vessel disease (SVD). However, cerebral ischemia, indicated by symptomatic and incidental diffusion-weighted imaging (sDWI and iDWI) hyperintensities, remains controversial regarding its clinical relevance and pathological mechanisms. This study aimed to investigate the prevalence, distributing characteristics, and risk factors of sDWI and iDWI lesions in patients with CAA.</p><p><strong>Methods: </strong>Participants meeting the criteria for probable CAA (Boston criteria version 1.5) were recruited from a prospective cohort of cerebral small vessel disease at Peking Union Medical College Hospital between March 2017 and February 2026. Baseline clinical data and neuroimaging markers of SVD were collected. sDWI lesions and iDWI lesions were recorded at any MRI time point, with topography showing via lesion probability maps. Cumulative incidence was estimated using Kaplan-Meier method. The characteristics were compared between patients with sDWI lesions or iDWI lesions and those without any DWI lesion at baseline. The prospective Cox regression analyses were performed to identify risk factors for sDWI lesions and iDWI lesions, respectively.</p><p><strong>Results: </strong>We enrolled 185 patients with probable CAA, of whom 99 underwent follow-up MRI with a total of 163 scans. sDWI lesions were detected in 29 patients and iDWI lesions in 49 patients. sDWI lesions predominantly involved deep regions (72.7%), whereas iDWI lesions were mainly located in cortical-juxtacortical regions (62.5%). In the prospective analysis, the 3-year cumulative incidence was 9.45% (95% CI: 0.67%-17.46%) for sDWI lesions and 25.74% (95% CI:15.2%-34.97%) for iDWI lesions, respectively. Cox analysis of 99 patients with follow-up MRI identified that the number of traditional vascular risk factors (hypertension, diabetes mellitus, coronary artery disease, and smoking) (HR: 2.968; P = 0.013) and lacunes (HR: 1.187; P = 0.016) were independent predictors for sDWI lesions after adjusting for age, sex. The independent predictive values of iDWI lesions were lacunes (HR: 1.158; P < 0.001), disseminated cSS (HR: 2.994; P = 0.014), and lobar CMB grade (HR: 2.059; P = 0.019), after adjusting for age, sex, number of traditional vascular risk factors, and focal cSS.</p><p><strong>Conclusions: </strong>Cerebral ischemia was not uncommon in CAA. sDWI and iDWI lesions had distinct topographical distributions and risk factor profiles, suggesting potentially different underlying mechanisms. DWI-positive lesions may provide a useful imaging marker of SVD activity and injury in future longitudinal studies and clinical trials of CAA.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 9","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865465","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":"Immune-mediated necrotizing myopathies: clinico-serological features and treatment outcomes of a large Italian cohort of patients.","authors":"Silvia Bonanno, Erika Salvi, Marta Cheli, Franco Salerno, Matteo Lucchini, Alessandra Cicia, Vincenzo Carlomagno, Antonio Lauletta, Laura Tufano, Francesco Girolamo, Lucia Nicolini De Gaetano, Marco Fornaro, Elia Pancheri, Federico Zaottini, Elena Faedo, Patrizia Rovere Querini, Rebecca De Lorenzo, Marina Scarlato, Francesca Bottazzi, Pietro Riguzzi, Sara Gibertini, Barbara Risi, Alessia Pugliese, Dario Zoppi, Lucia Ruggiero, Giulia Ricci, Paolo Manganotti, Gabriele Siciliano, Carmelo Rodolico, Massimiliano Filosto, Luca Bello, Elena Pegoraro, Lorenzo Cavagna, Stefano Carlo Previtali, Chiara Fiorillo, Marina Grandis, Gaetano Vattemi, Paola Tonin, Florenzo Iannone, Giovanni Antonini, Matteo Garibaldi, Massimiliano Mirabella, Lorenzo Maggi","doi":"10.1007/s00415-026-14089-1","DOIUrl":"https://doi.org/10.1007/s00415-026-14089-1","url":null,"abstract":"<p><strong>Background: </strong>Immune-mediated necrotizing myopathy (IMNM) is a distinct entity with limited large-cohort data. We aimed to characterize clinico-serological features and treatment outcomes of anti-SRP, anti-HMGCR, and seronegative IMNM in a large Italian cohort.</p><p><strong>Methods: </strong>Retrospective multicenter study of adults diagnosed with IMNM (224th ENMC criteria) across 14 Italian neuromuscular centers between 2019 and 2022 was performed.</p><p><strong>Results: </strong>We included 159 subjects (57% female, median age 62 years): 40 SRP+, 71 HMGCR+, 41 seronegative, and 7 untested. SRP+ more frequently presented with proximal upper limb weakness and axial involvement versus HMGCR+ (OR = 3.89, padj = 0.007, OR = 3.47, padj = 0.04) and seronegative (OR = 4.00, padj = 0.014, OR = 15.2, padj = 0.005). Lung involvement was higher in SRP+ (7.5%), vs none in HMGCR+ and 2.4% in seronegative (p=0.028). Extramuscular features were more frequent in HMGCR+ (OR = 3.78, p = 0.019, padj = 0.057). SRP+ had higher odds of loss of motor independence (OR=4.22, padj =0.011) and relapse (OR = 14.4, padj = 0.010) than HMGCR+. Seronegative had better functional outcomes than SRP+ (p=0.047). Cancer associated myositis predicted worse disability (OR = 6.93, p = 0.0044). Overall, 71.7% improved with corticosteroids (OR=3.83, padj =0.01) and immunosuppressants (OR=2.296, padj =0.037), without serotype differences. CK decreased in 81.8% and normalized in 40.3% of patients; ΔCK was associated with improvement (p=0.017), clinical remission (p=0.002) and correlated with post-treatment functional scores (R=0.19, p= 0.044).</p><p><strong>Conclusion: </strong>Subtype-specific differences and prognostic factors emerge. Exploratory functional assessment and ΔCK may capture treatment response in real-world settings.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 9","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865544","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":"Clinical features of sleep disturbance in temporal lobe variants of frontotemporal dementia.","authors":"Eva K Larsen, Benjamin A Levett, Lucy B Core, Ciro Della Monica, Hana Hassanin, Giuseppe Atzori, Emma Harding, Derk-Jan Dijk, Victoria L Revell, Sofia H Eriksson, Jonathan D Rohrer, Jason D Warren, Jessica Jiang","doi":"10.1007/s00415-026-14104-5","DOIUrl":"https://doi.org/10.1007/s00415-026-14104-5","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 9","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865552","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":"APOE in subjective cognitive decline: a systematic review and meta-analysis.","authors":"Paolo Alonge, Ludovico Baiamonte, Giulia Gerardi, Angelo Torrente, Eloise Lo Mauro, Nicola Veronese, Angelo Labate, Roberto Monastero","doi":"10.1007/s00415-026-14077-5","DOIUrl":"10.1007/s00415-026-14077-5","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is increasingly conceptualised as a biological and clinical continuum that includes Subjective cognitive decline (SCD), mild cognitive impairment (MCI), and overt dementia. We conducted a systematic review and meta-analysis to assess the prevalence of APOE ε4 allele in individuals with SCD.</p><p><strong>Methods/aims: </strong>Main databases were searched to identify studies published up to 15 April 2026, plus citation checking. Eligible studies included participants with SCD defined according to standardized criteria, with available APOE genotype data. Application of SCD-plus criteria was also recorded.</p><p><strong>Results: </strong>Of 474 screened records, 49 studies were included in the quantitative synthesis. The pooled prevalence of APOE ε4 allele carriers was 28.3% (95% CI 25.1-31.8%) in SCD, 41.0% (95% CI 35.3-46.8%) in MCI, and 22.0% (95% CI 18.6-25.9%) in cognitively normal (CN) individuals. Multivariate analysis showed that the odds of being an APOE ε4 allele carrier were significantly higher in SCD compared to HC (OR = 1.28, 95% CI 1.12-1.46, p <0.001) and higher in MCI compared to SCD (OR = 1.48, 95% CI 1.23-1.76, p <0.0001). Meta-regression analyses indicated that age and education contributed to heterogeneity in SCD cohorts, while sex distribution did not. Sensitivity analyses restricted to SCD-plus studies confirmed the robustness of these findings.</p><p><strong>Conclusion: </strong>The prevalence of APOE ε4 allele in SCD falls between that observed in CN and MCI populations, supporting its role as an intermediate stage in the AD continuum. However, substantial heterogeneity persists, highlighting the need for more accurate stratification approaches integrating genetic and clinical markers.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 9","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860452","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":"Neuropsychiatric and multisystem toxicity following recreational inhalation of tiletamine-zolazepam (Zoletil 50): a retrospective case series with two-year prospective follow-up.","authors":"Ping Hua, Xing Wang, Jie Chen, Weiguo Liu, RuiJuan Sha, WeiWei Jiang","doi":"10.1007/s00415-026-14098-0","DOIUrl":"https://doi.org/10.1007/s00415-026-14098-0","url":null,"abstract":"<p><strong>Background: </strong>Tiletamine-zolazepam (Zoletil) is a veterinary anesthetic, which is increasingly being abused by humans. However, the chronic neurotoxicity of this compound in humans and its long-term clinical outcomes have rarely been reported.</p><p><strong>Objective: </strong>To characterize the neurological and systemic injury following recreational Zoletil 50 inhalation, including relapse behavior and persistent deficits.</p><p><strong>Methods: </strong>We performed a retrospective case series of patients presenting to our institution with Zoletil 50 toxicity. We analyzed the clinical features, laboratory results, and neuroimaging findings, and assessed long-term outcomes and relapse rates during a two-year observation period.</p><p><strong>Results: </strong>All 36 subjects (100%) demonstrated postural tremor, with 22 (61.1%) showing sustained, high-amplitude tremor early after admission. Four patients (11%) presented with bradykinesia and rigidity. Cerebellar ataxia was present in 30 (83%), visual disturbance in 20 (56%), and concomitant hallucinations in 16 (44%). Biochemical abnormalities included elevated transaminases (53%) and hypokalemia (44%). Two patients died in hospital due to cardiorespiratory failure. Of 34 discharged patients, 20 (59%) relapsed, 17 within the first month. A third death occurred during follow-up after a fifth relapse. At two years, residual deficits persisted in 11 of 33 survivors: subjective memory decline in seven, visual impairment in six, and bradykinesia requiring levodopa in two.</p><p><strong>Conclusions: </strong>Zoletil 50 inhalation is associated with a broad spectrum of neurological and systemic injury, with tremor, ataxia, and visual disturbance as the most consistent features. Relapse is common and early; one-third of long-term survivors still had neurological deficits at two years. Clinicians should consider tiletamine-zolazepam exposure when evaluating young patients with unexplained tremor, ataxia, and perceptual disturbance as standard toxicology screens do not detect this compound. Prospective controlled studies are needed to confirm causation and define the full spectrum of toxicity.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 9","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850807","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}