Neurology最新文献

{"title":"Increased Risk of Misdiagnosis and Treatment Complication in Late-Onset Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.","authors":"Romain Marignier,Yael Hacohen","doi":"10.1212/wnl.0000000000213681","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213681","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"20 1","pages":"e213681"},"PeriodicalIF":9.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Features and Factors Associated With Outcome in Late Adult-Onset Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.","authors":"Alessandro Dinoto,Laura Cacciaguerra,Nisa Vorasoot,Vyanka Redenbaugh,Sebastian A Lopez-Chiriboga,Cristina Valencia-Sanchez,Kai Guo,Smathorn Thakolwiboon,Susan E Horsman,Stephanie B Syc-Mazurek,Nanthaya Tisavipat,Jay Mandrekar,Deena Tajfirouz,Eric R Eggenberger,Misha L Pless,Kevin Chodnicki,Jan-Mendelt Tillema,Sean J Pittock,John Jing-Wei Chen,Eoin P Flanagan","doi":"10.1212/wnl.0000000000213557","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213557","url":null,"abstract":"BACKGROUND AND OBJECTIVESData regarding late adult-onset myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are scant. This study sought to assess the frequency, characteristics, and outcome of late adult-onset MOGAD and identify differences from early adult-onset MOGAD.METHODSThis retrospective, observational study included Mayo Clinic patients with MOGAD per 2023 diagnostic criteria and with onset age 50 years or older. Clinical, laboratory, radiologic, treatment, and outcome data were collected and compared between patients aged 50-59 years and those aged 60 years or older. Finally, the characteristics and outcome of patients with late adult-onset MOGAD (aged 50 or older) were compared with a reference group of patients with early adult-onset (aged 18-49) MOGAD (n = 141).RESULTSThere were 107 patients with late adult-onset MOGAD included, representing 25% of the MOGAD cohort (n = 436). The median age at onset was 59 years (range: 50-88), and 71 (66%) were female. Medical comorbidities were noted in 86 of 105 (83%). Optic neuritis was the most frequent onset attack (77/107, 72%), and the median Expanded Disability Status Scale (EDSS) score at nadir was 3 (range: 1-9). In 32 of 107 (30%), a potential trigger was noted, mostly infections. In 32 patients (30%), an alternative diagnosis was considered before MOGAD identification, most commonly giant cell arteritis (n = 15 [11 undergoing temporal artery biopsy]). By a median follow-up duration of 22 months (range: 0-306), 50 patients (47%) had a relapsing course, and preventive treatment was administered in 53 (50%). Medication side effects were common (41/107, 38%). No differences were observed in patients with MOGAD aged 50-59 years vs 60 years or older. Lastly, late adult-onset patients had more optic nerve involvement (p = 0.015; OR: 1.9; 95% CI 1.1-3.3), brainstem/cerebellar involvement (p = 0.008; OR: 3.4; 95% CI 1.1-3.3), and cognitive decline (p = 0.01; OR: 5.3; 95% CI 1.4-19.4) and less frequent myelitis (p < 0.001; OR: 0.4; 95% CI 0.2-0.7) vs those with early adult-onset MOGAD, but EDSS scores and frequency of a relapsing course were similar.DISCUSSIONLate adult-onset MOGAD accounts for one-quarter of patients with MOGAD. Optic neuritis is the dominant phenotype in this age group with MOGAD and is under-recognized and frequently misdiagnosed. Outcomes in late adult-onset MOGAD are similar to those in early adult-onset disease.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"26 1","pages":"e213557"},"PeriodicalIF":9.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teaching NeuroImage: Temporal Intermittent Rhythmic Delta Activity: An Epileptiform Equivalent.","authors":"Kaley J Marcinski Nascimento,Doyle Yuan,Adam S Greenblatt,Sándor Beniczky,Fábio A Nascimento","doi":"10.1212/wnl.0000000000213635","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213635","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"137 1","pages":"e213635"},"PeriodicalIF":9.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pearls & Oy-sters: Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Presenting as Encephalomyelitis With Leptomeningeal Enhancement.","authors":"Alex P Vu,Ronak K Kapadia,Jodie I Roberts","doi":"10.1212/wnl.0000000000213662","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213662","url":null,"abstract":"Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an uncommon diagnosis in the differential for leptomeningeal enhancement. This case highlights the presentation, imaging features, and investigations important for diagnosis of GFAP astrocytopathy to ensure timely treatment of this corticosteroid-responsive disease. A 50-year-old man from Hong Kong presented with 10 days of progressive urinary retention, dysarthria, diplopia, and gait ataxia after a viral illness. Initial nonenhanced MRI brain was negative. After he developed encephalopathy, repeat MRI with gadolinium on admission day 6 revealed diffuse basal and spinal cord leptomeningeal enhancement. This imaging pattern, in combination with CSF eosinophilia and epidemiologic risk factors, precipitated empiric treatment for tuberculosis meningitis (including dexamethasone). Extensive investigations for an alternate infectious, autoimmune, or malignant diagnosis were negative. Dexamethasone cessation after a gastrointestinal bleed led to clinical and radiologic deterioration. This prompted further CSF and serum testing, which showed positive CSF GFAP-IgG immunofluorescence assay (IFA) (1:128) solidifying the diagnosis of autoimmune GFAP astrocytopathy. Induction with high-dose corticosteroids, intravenous immunoglobulins, and rituximab produced clinical and radiologic remission. Autoimmune GFAP astrocytopathy is an autoimmune disorder with a characteristic perivascular radial enhancement imaging pattern. However, a variety of other clinical and radiologic presentations may be seen, including leptomeningeal enhancement and T2/FLAIR hyperintensities. Diagnosis is confirmed with CSF GFAP-IgG testing. We provide a differential diagnosis for leptomeningeal enhancement and highlight clinical pearls for the diagnosis and management of autoimmune GFAP astrocytopathy.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"2 1","pages":"e213662"},"PeriodicalIF":9.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Cortical Atrophy Patterns With Clinical Phenotypes and Histopathological Findings in Patients With Rasmussen Syndrome.","authors":"Tobias Bauer,Nina R Held,Lennart Walger,Christian Hoppe,Johannes Reiter,Anna Tietze,Valeri Borger,Julika Pitsch,Louisa Specht-Riemenschneider,Angela M Kaindl,Boris C Bernhardt,Hartmut Vatter,Kerstin Alexandra Klotz,Christoph Helmstaedter,Albert J Becker,Alexander Radbruch,Rainer Surges,Theodor Rüber","doi":"10.1212/wnl.0000000000213629","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213629","url":null,"abstract":"BACKGROUND AND OBJECTIVESAutomated MRI analyses have identified variable patterns of cortical atrophy in Rasmussen syndrome. In this study, we aim to identify imaging phenotypes of Rasmussen syndrome, to clinically characterize these phenotypes, and to validate this imaging-based approach through histopathologic analysis.METHODSFor this retrospective case-control study, individuals with Rasmussen syndrome diagnosed according to the European Consensus Statement and at least one 3D T1-weighted MRI scan (<20 years after onset) were identified from the University Hospital Bonn (1995-2023). Healthy controls were selected from databases at the University Hospital Bonn, Charité University Hospital Berlin, and the Human Connectome Project. Disease epicenters, describing brain regions highly connected to atrophy regions, were mapped individually using network-based atrophy modeling. Subtypes were identified through k-means clustering. Neuropsychological test results and results from neuropathologic analyses of biopsies were ascertained, and correlations between subtype-specific atrophy maps and normative maps (enhancing neuro imaging genetics through meta analysis [ENIGMA] and neuromaps toolbox) were used to characterize atrophy profiles and epicenter susceptibility.RESULTSThe study incorporated 54 individuals with Rasmussen syndrome (median age at MRI: 18 years, range 2-61, 65% female) and 270 healthy individuals (median age at MRI: 26.5 years, range 3-61, 49% female). Four distinct atrophy subtypes were identified (temporoparietal, centrotemporal, frontal, and bilateral). Individuals with the centrotemporal subtype were younger at onset (median 5.5 years) than individuals with temporoparietal (median 11.5 years, p = 0.02) and frontal (median 6 years, p = 0.02) subtypes. Most severe neuropsychological impairment was observed for the temporoparietal and frontal subtypes. In the temporoparietal and frontal subtypes, atrophy occurred preferentially in hubs (r = -0.28, p = 0.006; r = -0.30, p = 0.02). Disease epicenter susceptibility was associated with higher cortical thickness (r = -0.57, p = 0.005), lower myelin content (r = 0.47, p = 0.02), lower cerebral blood flow (r = 0.42, p = 0.03), lower blood volume (r = 0.57, p = 0.006), and lower oxygen metabolism (r = 0.47, p = 0.01). Brain biopsies showing strong inflammation were taken from likely epicenters, whereas biopsies with weaker inflammation came from less likely epicenters (p = 0.04).DISCUSSIONUsing Rasmussen syndrome as a model, we validate imaging-based mapping of individual disease epicenters with histopathologic evidence. With further validation, network-based mapping of individual disease epicenters could potentially be used in Rasmussen syndrome to guide biopsy site selection, inform treatment decisions, and improve outcome prognoses.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"8 1","pages":"e213629"},"PeriodicalIF":9.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of Accelerated Biological Aging With Dementia and the Mediation Role of Brain Structure: Findings From a Longitudinal Study.","authors":"Yacong Bo,Liuqiao Sun,Shengsheng Hou,Fenghua Zhang,Haowen Zhang,Xueyi Feng,Sisi Zhuo,Shiyu Feng,Hui Chang,Xiaoan Zhang,Zhengbin Wang,Zengli Yu,Xin Zhao","doi":"10.1212/wnl.0000000000213616","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213616","url":null,"abstract":"BACKGROUND AND OBJECTIVESThe association between biological aging and dementia, as well as the underlying mechanism, remains limited. The aim of this study was to investigate the relationships of biological age (BA) with incident dementia and examine the underlying neurobiological mechanisms.METHODSThis study used data from the UK Biobank, a prospective longitudinal study. We included participants free of diagnosed dementia at baseline. BA was evaluated from clinical traits using the Klemera-Doubal method biological age (KDM-BA) and PhenoAge algorithms. Genetic risk of dementia was assessed using the apolipoprotein E (APOE) ε4 genotype and polygenic risk scores (PRSs). Cox proportional hazard regression models were used to estimate the associations of BA and the combined effect of genetic risk and BA with dementia. In addition, the potential roles of brain structures (gray matter volume [GMV], cortical mean thickness, and cortical surface area) in the associations between BA and dementia were evaluated using mediation analysis.RESULTSA total of 280,918 participants (mean age 56.80 years, 54.59% female) were enrolled in this study. Over a median follow-up of 13.58 years, 4,770 cases of dementia were recorded. Every SD increase in KDM-BA accelerations and PhenoAge accelerations was associated with a 14% (hazard ratio [HR] = 1.14; 95% CI 1.10-1.18) and 15% (HR = 1.15; 95% CI 1.12-1.19) higher incidence of dementia, respectively. Individuals with APOE ε4 and highest PhenoAge accelerations had the highest risk of dementia (HR = 4.20, 95% CI 3.69-4.78) compared with those with non-APOE ε4 and lowest PhenoAge accelerations, with significant interaction effect (Pinteraction < 0.001). We did not find significant modification effects of PRS on the associations between BA accelerations and dementia (Pinteraction = 0.347 for KDM-BA acceleration, Pinteraction = 0.279 for PhenoAge acceleration), as well as APOE ε4 on the association between KDM-BA accelerations and dementia (Pinteraction = 0.212). Mediation analysis showed that the identified GMV, cortical mean thickness, and cortical surface area partly mediated the association between BA accelerations and incident dementia, with proportion-mediated percentage ranging from 6.64% to 17.98%.DISCUSSIONAdvanced BA may be a potential risk factor of incident dementia. The risk is possibly mediated through the widespread reduction of brain structures.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"72 1","pages":"e213616"},"PeriodicalIF":9.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Follow-Up Results of Antiseizure Medication Withdrawal in Grade 2 and 3 Glioma Patients: A Prospective Observational Study.","authors":"Pim B van der Meer,Melissa Kerkhof,Linda Dirven,Marta Fiocco,Maaike J Vos,Mathilde Kouwenhoven,Tjeerd J Postma,Jacoline E C Bromberg,Martin J Van Den Bent,Martin Taphoorn,Johan Koekkoek","doi":"10.1212/wnl.0000000000213590","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213590","url":null,"abstract":"BACKGROUND AND OBJECTIVESThe aim of this study was to evaluate the long-term results of seizure recurrence after antiseizure medication (ASM) withdrawal vs continuation in patients with diffuse glioma, grades 2 and 3.METHODSA prospective multicenter observational study was conducted, and patients were recruited from January 2014 until May 2016 from 3 neuro-oncology outpatient clinics in the Netherlands. The main inclusion criteria were as follows: history of ≥1 seizure, for which ASM was started; clinically and radiologically stable disease for ≥12 months; and seizure freedom for ≥12 months from the date of last antitumor treatment or seizure freedom for ≥24 months from the last seizure if seizures occurred after the last antitumor treatment. The primary outcome was time to recurrent seizure. A competing risk model was used to estimate cumulative incidences of recurrent seizure for ASM groups (i.e., ASM withdrawal vs ASM continuation) with death as the competing event. The proportional hazard assumption was violated for the ASM group; therefore, 2 Cox models were constructed for different time intervals (<48 months and ≥48 months since study inclusion).RESULTSA total of 71 patients were included (39 men [55%] and 58 older than 40 years [82%]); 46 patients with glioma (65%) were in the ASM withdrawal group and 25 (35%) in the ASM continuation group. The cumulative incidence of a recurrent seizure at 48 and 96 months was 48% (95% CI 33%-61%) and 66% (95% CI 48%-78%) for the ASM withdrawal group vs 28% (95% CI 12%-46%) and 52% (95% CI 31%-70%) for the ASM continuation group. The risk of a recurrent seizure differed in the 2 time intervals between the ASM continuation group (reference) and the ASM withdrawal group (cause-specific adjusted hazard ratio [aHR] 2.32 [95% CI 0.93-5.81], p = 0.071, during <48 months, and cause-specific aHR 0.73 [95% CI 0.21-2.49], p = 0.611, during ≥48 months since study inclusion).DISCUSSIONRisk of recurrent seizure when withdrawing ASM was not statistically significantly higher in patients continuing ASM. However, a clinically relevant higher percentage of patients had a recurrent seizure in the ASM withdrawal group compared with the ASM continuation group. The lack of a statistical difference may be explained by the small sample size. Larger studies are needed to confirm these findings. Our results suggest that ASM withdrawal should be initiated cautiously and only when necessary.CLASSIFICATION OF EVIDENCEThis study provides Class III evidence that withdrawal of ASM does not significantly increase the risk of recurrent seizures in patients with glioma with stable disease and no seizures for >1 year. Confidence intervals do not exclude a clinically important increased risk of seizures.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"35 1","pages":"e213590"},"PeriodicalIF":9.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pearls & Oy-sters: ADCY5-Related Dyskinesia: From a Longstanding Misdiagnosis of Drug-Resistant Epilepsy.","authors":"Ana Moreno-Estébanez,Miriam Sánchez-Horvath,Ainhoa Marinas,Claudio Catalli,Tamara Fernandez-Valle,Pablo de Ceballos,Aida Lagüela Alonso,Iñigo Garamendi Ruiz","doi":"10.1212/wnl.0000000000213661","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213661","url":null,"abstract":"ADCY5-related dyskinesia (ADCY5-RD) is a hyperkinetic movement disorder of childhood onset, resulting from pathogenic variants in the ADCY5 gene. Paroxysmal worsening of the movements and movements that occur in relation to sleep and/or awakenings are hallmarks of ADCY5-RD. ADCY5-RD is therefore often misdiagnosed as sleep-related hypermotor epilepsy, sleep disorders, paroxysmal hyperkinesias, childhood onset chorea, or psychogenic events. In this case, a 59 year-old woman with a longstanding misdiagnosis of drug-resistant epilepsy was ultimately diagnosed with ADCY5-RD following video EEG. She had been followed for paroxysmal episodes of nonvoluntary movements mostly occurring during sleep since 2 years of age. She also exhibited continuous progressive dysarthria and axial hypotonia. Episodic orofacial dystonia was present as well. For 57 years, these symptoms had been treated with various combinations of antiseizure medications. However, the diagnosis was reconsidered when prolonged video-EEG monitoring recorded sleep-onset nonepileptic events, starting during N1 and N2 stages of NREM sleep. Genetic testing of ADCY5 confirmed the diagnosis. Caffeine and progressive withdrawal of antiseizure medications except clonazepam resulted in clinical improvement in paroxysms, which became less intense and less frequent. Given that ADCY5-RD was first described in 2012, there may be more adult patients misdiagnosed in childhood. Thus, we recommend considering alternative diagnosis for adult patients with paroxysmal sleep-related events to detect ADCY5-RD in adults. Although there are still no treatment guidelines for ADCY5-RD, adenosine-2A receptor antagonists have emerged as a promising therapeutic option.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"69 1","pages":"e213661"},"PeriodicalIF":9.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teaching NeuroImage: Primary Central Nervous System Vasculitis With Thalamic Involvement.","authors":"Cansu Sarıkaya,Tolga Çetindamar,Aydın Sav,Gazanfer Ekinci,Uğur Türe,Rana Karabudak","doi":"10.1212/wnl.0000000000213665","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213665","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"44 1","pages":"e213665"},"PeriodicalIF":9.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Thrombolytics on Delayed Reperfusion After Incomplete Thrombectomy: Target Trial Emulation.","authors":"Adnan Mujanovic,Vignan Yogendrakumar,Felix C Ng,Thomas Gattringer,Bettina Lara Serrallach,Thomas R Meinel,Leonid Churilov,Oliver Nistl,Shaokai Zheng,Peter J Mitchell,Nawaf Yassi,Mark W Parsons,Gagan Jyoti Sharma,Hannes A Deutschmann,Geoffrey Alan Donnan,Marcel Arnold,Fabiano Cavalcante,Eike I Piechowiak,Timothy John Kleinig,David Julian Seiffge,Stephen M Davis,Tomas Dobrocky,Jan Gralla,Markus Kneihsl,Urs Fischer,Bruce C V Campbell,Johannes Kaesmacher","doi":"10.1212/wnl.0000000000213641","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213641","url":null,"abstract":"BACKGROUND AND OBJECTIVESMore than half of the endovascularly treated ischemic stroke patients with incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction [eTICI] <3) show delayed reperfusion (DR) on 24-hour perfusion imaging, which is associated with favorable clinical outcome. The effect of intravenous thrombolysis (IVT) on the rates of DR remains unclear. This study aimed to assess the treatment effect of IVT on the occurrence of DR.METHODSPooled data from 3 randomized controlled trials (EXTEND-IA and EXTEND-IA TNK parts 1 and 2) and 2 comprehensive stroke centers (University Hospitals Graz and Bern) were analyzed. Only patients with a final reperfusion score of eTICI 2a-2c and available perfusion imaging at follow-up of 24 ± 12 hours were included. The primary outcome was the presence of DR on 24-hour follow-up CT/MRI perfusion imaging, defined as the absence of any focal perfusion deficit on perfusion imaging, despite incomplete reperfusion on the final angiography series during thrombectomy. For the secondary analysis, we explored the association between the primary outcome (DR) and the time elapsed between start of IVT and the end of an intervention. To address confounding in observational data, we performed a target trial emulation.RESULTSOf 832 included patients with eTICI 2a-2c (median age 74 years, 49% female), 511 (61%) had DR. There was an independent treatment effect of IVT on DR (standardized risk ratio [sRR] 1.1, 95% CI 1.0-1.3; standardized risk difference [sRD] 8.2%, 95% CI 0.2%-16.1%), after adjusting for age, sex, atrial fibrillation, number of device passes, collateral score, and eTICI. Among those patients who have received IVT (n = 524/832, 63%), when adjusting for the aforementioned covariates, there was a causal effect of shorter time between administration of thrombolytics and end of the intervention on DR (sRR 0.93%, 95% CI 0.87-0.98; sRD -5.2%; 95% CI -9.1% to -1.3%, per hour increase).DISCUSSIONExposure to thrombolytics showed independent treatment effect on the occurrence of DR among patients with incomplete reperfusion after thrombectomy who undergo perfusion imaging at the 24-hour follow-up. The effect of thrombolytics on DR was observed if there was a high chance of therapeutic concentrations of thrombolytics at the time point when the proximal vessel was recanalized, but distal occlusions persisted and/or occurred.CLASSIFICATION OF EVIDENCEThis study is rated Class III because it is a nonrandomized study and there are substantial differences in baseline characteristics of the treatment groups.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"24 1","pages":"e213641"},"PeriodicalIF":9.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}