Annals of Clinical and Translational Neurology最新文献

{"title":"Safety and efficacy of intravenous thrombolytic therapy in the extended window up to 24 hours: A systematic review and meta-analysis.","authors":"Omar M Al-Janabi, Seyed Behnam Jazayeri, Michelle A Toruno, Yamama M Mahmood, Sherief Ghozy, Shadi Yaghi, Alejandro A Rabinstein, David F Kallmes","doi":"10.1002/acn3.52239","DOIUrl":"https://doi.org/10.1002/acn3.52239","url":null,"abstract":"<p><strong>Objective: </strong>About 25% of patients with acute ischemic stroke (AIS) present within the intravenous thrombolytic (IVT) therapeutic window of <4.5 h. This study is to elucidate the safety and efficacy of IVT in the extended therapeutic window (ETW) in patients with AIS.</p><p><strong>Methods: </strong>Using PRISMA guidelines, a systematic review was conducted using PubMed, Embase, and Scopus. A rigorous risk of bias assessment was conducted using the RoB2 tool. Rates of excellent and good functional outcome (mRS 0-1 and mRS 0-2) at 90 days, symptomatic intracranial hemorrhage (sICH), and mortality at 90 days were pooled using generalized linear mixed model and compared with controls. Meta-analyses were conducted employing random-effect models with risk ratio (RR) and 95% confidence intervals (CIs). Subgroup analysis was performed to assess the effect of imaging modalities used for patient selection.</p><p><strong>Results: </strong>Eight randomized controlled trials (n = 2221, 59% male) were included. At 90 days IVT showed higher rates of functional recovery: mRS 0-1: RR 1.21 95% CI 1.1-1.34, p < 0.001, and mRS 0-2: RR 1.11 95% CI 1.03-1.18, p = 0.004. Rate of mortality at 90 day was not different between groups: RR 1.17 95% CI 0.93-1.48, p = 0.17. However, the rate of sICH was higher among IVT group: RR 2.93 95% CI 1.53-5.6, p = 0.001. Subgroup analysis showed higher mRS 0-1 among patients who were selected based on perfusion imaging (p < 0.05).</p><p><strong>Interpretation: </strong>The use of IVT in AIS in ETW is beneficial especially with the use of perfusion imaging for patients' selection.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520469","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":"FDG-PET patterns associate with survival in patients with prion disease.","authors":"Nick Corriveau-Lecavalier, Yoav D Piura, Brian S Appleby, Dror Shir, Leland R Barnard, Venkatsampath Gogineni, David T Jones, Gregory S Day","doi":"10.1002/acn3.52230","DOIUrl":"10.1002/acn3.52230","url":null,"abstract":"<p><strong>Objective: </strong>Prion disease classically presents with rapidly progressive dementia, leading to death within months of diagnosis. Advances in diagnostic testing have improved recognition of patients with atypical presentations and protracted disease courses, raising key questions surrounding the relationship between patterns of neurodegeneration and survival. We assessed the contribution of fluorodeoxyglucose (FDG-PET) imaging for this purpose.</p><p><strong>Methods: </strong>FDG-PET were performed in 40 clinic patients with prion disease. FDG-PET images were projected onto latent factors generated in an external dataset to yield patient-specific eigenvalues. Eigenvalues were input into a clustering algorithm to generate data-driven clusters, which were compared by survival time.</p><p><strong>Results: </strong>Median age at FDG-PET was 65.3 years (range 23-85). Median time from FDG-PET to death was 3.7 months (range 0.3-19.0). Four data-driven clusters were generated, termed \"Neocortical\" (n = 7), \"Transitional\" (n = 12), \"Temporo-parietal\" (n = 13), and \"Deep nuclei\" (n = 6). Deep nuclei and transitional clusters had a shorter survival time than the neocortical cluster. Subsequent analyses suggested that this difference was driven by greater hypometabolism of deep nuclei relative to neocortical areas. FDG-PET-patterns were not associated with demographic (age and sex) or clinical (CSF total-tau, 14-3-3) variables.</p><p><strong>Interpretation: </strong>Greater hypometabolism within deep nuclei relative to neocortical areas associated with more rapid decline in patients with prion disease and vice versa. FDG-PET informs large-scale network physiology and may inform the relationship between spreading pathology and survival in patients with prion disease. Future studies should consider whether FDG-PET may enrich multimodal prion disease prognostication models.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520468","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":"Altered exosomal miRNA profiles in patients with paraneoplastic cerebellar degeneration.","authors":"Eirik Tveit Solheim, Liv Cecilie Vestrheim Thomsen, Line Bjørge, Shamundeeswari Anandan, Elise Peter, Virginie Desestret, Cecilie Totland, Christian A Vedeler","doi":"10.1002/acn3.52232","DOIUrl":"https://doi.org/10.1002/acn3.52232","url":null,"abstract":"<p><strong>Objective: </strong>Patients with ovarian cancer (OC) may develop anti-Yo-associated paraneoplastic cerebellar degeneration (PCD)-a cerebellar ataxia associated with tumor-induced autoimmunity against CDR2 and CDR2L proteins. Dysregulation of circulating exosomal microRNAs (miRNAs) occur in OC. Here, we investigated whether PCD is associated with changes in the exosomal miRNA profiles of OC patients.</p><p><strong>Methods: </strong>Serum exosomes were isolated from patients with OC (n = 15), patients with OC and anti-Yo-associated PCD (n = 14) and healthy controls (HC, n = 15). Small RNA sequencing was used to identify differentially expressed miRNAs. Receiver operating characteristic curves were used to evaluate biomarker sensitivity and specificity, and miRNA target prediction analysis was employed to elucidate gene targets.</p><p><strong>Results: </strong>OC patients with PCD exhibited a distinct exosomal miRNA expression profile. We detected 103 differentially expressed exosomal miRNAs in PCD patients compared to OC patients without PCD and 139 differentially expressed exosomal miRNAs compared to controls. Particularly miR-486-5p, miR-4732-5p, miR-98-5p and miR-21-5p exhibited notable sensitivity and specificity for discriminating PCD patients from both OC patients without PCD and healthy controls. miRNA target prediction showed that several of the differentially expressed miRNAs in PCD patients targeted the CDR2 and CDR2L genes.</p><p><strong>Interpretation: </strong>Our results demonstrate that OC patients with anti-Yo-associated PCD exhibit a distinct exosomal miRNA profile compared to OC patients without PCD. Several of the differentially expressed exosomal miRNAs in PCD patients showed diagnostic potential and may hold relevance for understanding the pathogenesis of PCD.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542303","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":"Blood-brain barrier profile pretreatment is associated with hemorrhagic transformation after endovascular reperfusion.","authors":"Richard Leigh, Pierre Seners, Vanessa Rousseau, Soren Christensen, Jean-François Albucher, Amel Drif, Christophe Cognard, Adrien Guenego, Alain Viguier, Agnes Sommet, Nicolas Raposo, Lionel Calviere, Anne-Christine Januel, Michael Mlynash, Fabrice Bonneville, Brice Gaudilliere, Claire Thalamas, Igor Sibon, Thomas Tourdias, Mikael Mazighi, Jeremy J Heit, Benjamin Maier, Gregory W Albers, Jean-Marc Olivot","doi":"10.1002/acn3.52236","DOIUrl":"https://doi.org/10.1002/acn3.52236","url":null,"abstract":"<p><strong>Background: </strong>While advances in endovascular thrombectomy (EVT) have led to high reperfusion rates, most patients treated with EVT do not avoid disability. Post-reperfusion hemorrhagic transformation (HT) is a potential target for improving outcomes. This study examined pretreatment blood-brain barrier (BBB) disruption in tissue that would subsequently become part of the final infarct to evaluate its role in post-EVT HT.</p><p><strong>Methods: </strong>This post hoc analysis of the FRAME study, which enrolled patients with anterior large vessel occlusion who received EVT within 6 hours of onset, included patients if they had successful pretreatment MRI perfusion weighted imaging (PWI) and underwent successful EVT. BBB disruption was measured as the percent signal change due to gadolinium leakage on the PWI source images prior to thrombectomy. Mean permeability derangement (MPD) was defined as the average of all voxels in the stroke core that are two standard deviations above normal. The primary outcome was hemorrhagic transformation with parenchymal hematoma (PH).</p><p><strong>Results: </strong>In total, 164 patients were included; mean age was 71 and 48% were female. PH occurred in 57 patients. Median MPD was 13.5% for patients with PH versus 3.6% for patients without (p < 0.0001). Elevated MPD was independently associated with PH with a 20% increased risk of PH for each 5% increase in MPD (OR 1.206; 95% CI 1.037:1.405; p = 0.0147, adjusted for NIHSS and procedure duration).</p><p><strong>Conclusions: </strong>Even in patients who are successfully recanalized in an early time window, pretreatment BBB disruption in regions that go on to infarct is associated with an increased risk of post-EVT HT.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491386","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":"Subcutaneous ocrelizumab in multiple sclerosis: Results of the Phase 1b OCARINA I study.","authors":"Scott D Newsome, Lawrence Goldstick, Derrick S Robertson, James D Bowen, Robert T Naismith, Ben Townsend, Catarina Figueiredo, Heidemarie Kletzl, Mylene Giraudon, Oscar Bortolami, Dusanka Zecevic, Caroline Giacobino, Susanne Clinch, Yun-An Shen, Gurpreet Deol-Bhullar, Robert A Bermel","doi":"10.1002/acn3.52229","DOIUrl":"https://doi.org/10.1002/acn3.52229","url":null,"abstract":"<p><strong>Objective: </strong>Subcutaneous ocrelizumab is being developed to provide treatment flexibility and additional choice to patients with multiple sclerosis. OCARINA I (NCT03972306) is an open-label, multicenter, Phase 1b, dose-finding study to investigate the pharmacokinetics, safety, tolerability, and immunogenicity of subcutaneous ocrelizumab and to select a dose for the Phase 3 OCARINA II study (NCT05232825).</p><p><strong>Methods: </strong>Patients with relapsing or primary progressive multiple sclerosis (aged 18-65 years; Expanded Disability Status Scale score 0.0-6.5) were enrolled into two groups: previously treated with intravenous ocrelizumab (Group A) or naïve to ocrelizumab (Group B). Patients received single ascending doses of subcutaneous ocrelizumab up to 1200 mg. Following dose escalation, new patients in Group A were randomized (1:1) to receive a single 600 mg intravenous ocrelizumab dose or the candidate subcutaneous dose, which was predicted to result in similar exposure as the 600 mg intravenous dose while being safe and well tolerated. The area under the concentration-time curve for both formulations was used to select the subcutaneous ocrelizumab dose. Patients in all cohorts could enter a dose-continuation phase.</p><p><strong>Results: </strong>Eighty-eight and 47 patients were enrolled into Group A and B, respectively; most patients were female (72.7%/63.0%), and mean age at baseline was 45.7 and 39.7 years, respectively. Subcutaneous ocrelizumab was well tolerated across all doses tested. The 920 mg subcutaneous ocrelizumab dose was selected for the OCARINA II study based on pharmacokinetic and safety data.</p><p><strong>Interpretation: </strong>Subcutaneous ocrelizumab may provide patients with multiple sclerosis with an additional treatment option.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491407","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":"RNA mis-splicing in children with congenital myotonic dystrophy is associated with physical function.","authors":"Julia M Hartman, Kobe Ikegami, Marina Provenzano, Kameron Bates, Amanda Butler, Aileen S Jones, Kiera N Berggren, Jeanne Dekdebrun, Marnee J McKay, Jennifer N Baldwin, Kayla M D Cornett, Joshua Burns, Michael Kiefer, Nicholas E Johnson, Melissa A Hale","doi":"10.1002/acn3.52224","DOIUrl":"10.1002/acn3.52224","url":null,"abstract":"<p><strong>Objectives: </strong>Dysregulated RNA alternative splicing is the hallmark of myotonic dystrophy type 1 (DM1). However, the association between RNA mis-splicing and physical function in children with the most severe form of disease, congenital myotonic dystrophy (CDM), is unknown.</p><p><strong>Methods: </strong>Eighty-two participants (42 adults with DM1 and 40 children with CDM) with muscle biopsies and measures of myotonia, motor function, and strength were combined from five observational studies. Data were normalized and correlated with an aggregate measure of alternative splicing dysregulation, [MBNL]_inferred, in skeletal muscle biopsies. Multiple linear regression analysis was performed to predict [MBNL]_inferred using clinical outcome measures alone. Similar analyses were performed to predict 12-month physical function using baseline metrics.</p><p><strong>Results: </strong>Myotonia (measured via vHOT) was significantly correlated with RNA mis-splicing in our cross-sectional population of all DM1 individuals; CDM participants alone displayed no myotonia despite a similar range of RNA mis-splicing. Measures of motor performance and muscle strength were significantly associated with [MBNL]_inferred in our cohort of all DM1 individuals and when assessing children with CDM independently. Multiple linear regression analyses yielded two models capable of predicting [MBNL]_inferred from select clinical outcome assessments alone in all subjects (adjusted R² = 0.6723) or exclusively in children with CDM (adjusted R² = 0.5875).</p><p><strong>Interpretation: </strong>Our findings establish significant correlations between skeletal muscle performance and a composite measure of alternative splicing dysregulation, [MBNL]_inferred, in DM1. The strength of these correlations and the development of predictive models will assist in designing efficacious clinical trials for individuals with DM1, particularly CDM.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491393","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":"Association between atherosclerotic disease and cervical artery dissection in a population-based cohort of older people.","authors":"Joshua Kahan, Cenai Zhang, Ava L Liberman, Alan Z Segal, Santosh B Murthy, Jiwon Kim, Hooman Kamel, Alexander E Merkler","doi":"10.1002/acn3.52216","DOIUrl":"https://doi.org/10.1002/acn3.52216","url":null,"abstract":"<p><strong>Objectives: </strong>Many cases of cervical artery dissection are considered \"spontaneous.\" Recent data suggest that while cervical artery dissection may proportionally explain more strokes in young patients, hospitalization for dissection increases with age, suggesting a potential role of acquired vascular disease. In this study, we hypothesized that traditional vascular risk factors and comorbidities are associated with cervical artery dissection.</p><p><strong>Methods: </strong>We performed a retrospective cohort study using administrative claims data from a 5% sample of Medicare beneficiaries. Exposures of interest included traditional vascular risk factors and comorbidities: coronary artery disease, hyperlipidemia, hypertension, diabetes mellitus, heart failure, chronic kidney disease, chronic obstructive pulmonary disease, valvular heart disease, atrial fibrillation, tobacco use, and alcohol abuse. The primary outcome was a new diagnosis of cervical artery dissection. Marginal structural Cox models were used to characterize the association between the exposures and outcomes, adjusted for time-dependent confounding.</p><p><strong>Results: </strong>Among 2,256,710 eligible Medicare beneficiaries, 730 (0.03%) developed cervical artery dissection. The following exposures were found to be significantly associated with the development of cervical artery dissection: hypertension (HR 1.84 [95% CI: 1.40-2.41]), alcohol use (HR 1.83 [1.52-2.21]), atrial fibrillation (HR 1.80 [1.53-2.11]), tobacco use (HR 1.80 [1.52-2.13]), coronary artery disease (HR 1.56 [1.33-1.82]), and valvular heart disease (HR 1.23 [1.05-1.45]).</p><p><strong>Interpretation: </strong>In a large cohort of older people, several traditional vascular risk factors and comorbidities were associated with subsequent cervical artery dissection. Further studies exploring the role of such factors in the development of cervical artery dissection are warranted.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491385","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":"Visual Snow Syndrome is unstable: A longitudinal investigation of VSS symptoms in a Naïve population.","authors":"Amy Claire Thompson, Patrick T Goodbourn, Jason D Forte","doi":"10.1002/acn3.52228","DOIUrl":"https://doi.org/10.1002/acn3.52228","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the nature of subclinical Visual Snow Syndrome (VSS). We sought to develop a means of recruiting naïve participants with subclinical VSS symptoms to participate in research; and to understand whether subclinical VSS symptoms are stable across time. VSS is a recently characterised neurological condition, whose primary symptom is visual snow (dynamic noise in the visual field). There is evidence that VSS may be common in the general population and that it is unnoticed by many who experience it. To fully characterise VSS, it is important to understand whether (and how) subclinical VSS progresses to a clinical form.</p><p><strong>Methods: </strong>Here, we present two related studies: Study 1 develops and validates the Melbourne Visual Snow Questionnaire (MVSQ), a tool for screening the general population for VSS symptoms; and Study 2 investigates the stability of subclinical VSS. We developed the MVSQ based on the results of other recent work investigating undiagnosed cases of VSS, and a validated questionnaire designed to identify people with tinnitus for research participation. We then tested the MVSQ in a population with clinical VSS, including assessing face validity (i.e., the extent to which people with clinical VSS believed the questionnaire accurately captured their symptoms). In Study 2, we deployed the MVSQ in a naïve sample of 155 participants, who completed the MVSQ twice, 6 weeks apart.</p><p><strong>Results: </strong>The results of Study 1 indicated that the MVSQ was a viable method of recruiting people who experience VSS symptoms for research participation. It was deemed to have appropriate face validity and to pose little burden to those who completed it. In Study 2, VSS symptoms changed substantially across a 6-week period. Cohen's weighted kappa for diagnosis was 0.56, 95% CI [0.43, 0.69]. However, the impact of perceptual experiences was low and did not change over time, rank ICC = 0.71, 95% CI [0.59, 0.82].</p><p><strong>Interpretation: </strong>The MVSQ is appropriate for assessing perceptual experiences in the general population. Determining the exact time scale across which symptoms fluctuate is important for understanding both clinical and subclinical cases of VSS.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491408","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":"Comparison of intraepidermal nerve fiber density and confocal corneal microscopy for neuropathy.","authors":"Evan L Reynolds, Fallon Koenig, Maya Watanabe, Alyssa Kwiatek, Melissa A Elafros, Amro Stino, Don Henderson, David N Herrmann, Eva L Feldman, Brian C Callaghan","doi":"10.1002/acn3.52218","DOIUrl":"https://doi.org/10.1002/acn3.52218","url":null,"abstract":"<p><strong>Objective: </strong>Compare the diagnostic characteristics of intraepidermal nerve fiber density (IENFD) and confocal corneal microscopy (CCM) for distal symmetric polyneuropathy (DSP) and small fiber neuropathy (SFN).</p><p><strong>Methods: </strong>Participants with obesity were recruited from bariatric surgery clinics and testing was performed prior to surgery. DSP and SFN were determined using the Toronto consensus definitions of probable neuropathy. IENFD was assessed from 3 mm punch biopsies of the distal leg and proximal thigh. CCM was performed on both eyes with manual and automated counting. The Michigan Neuropathy Screening Instrument questionnaire (MNSIq) was also completed. Diagnostic capability was determined using areas under the receiver operating characteristics curve (AUC) from logistic regression.</p><p><strong>Results: </strong>We enrolled 140 participants (mean [standard deviation [SD]] age: 50.3 years [7.1], 77.1% female, BMI: 44.4 kg/m² [6.7]). In this population, 22.9% had DSP and 14.3% had SFN. Distal leg IENFD had the largest AUC (95% confidence interval) for DSP (0.78, 0.68-0.89) and SFN (0.85, 0.75-0.96). Proximal thigh IENFD (DSP: AUC: 0.59, 0.48-0.69, SFN: AUC: 0.59, 0.46-0.73) and CCM metrics (DSP: AUC range: 0.55-0.60, SFN: AUC range: 0.45-0.62) had poorer diagnostic capability than distal leg IENFD for DSP/SFN (P < 0.05). MNSIq had similar diagnostic capability to distal leg IENFD for both DSP/SFN (DSP: AUC: 0.76, 0.68-0.85, SFN: AUC: 0.81, 0.73-0.88). More participants (52%) preferred skin biopsies to CCM.</p><p><strong>Interpretation: </strong>Distal leg IENFD was the best quantitative measure of DSP/SFN. CCM had poor diagnostic characteristics and fewer patients preferred this test to IENFD. The MNSIq had similar diagnostic characteristics to distal leg IENFD, indicating its value as a diagnostic tool in the clinical setting.</p><p><strong>Clinical trial registration: </strong>clinicaltrials.gov: NCT03617185.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453937","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":"Prediction of stroke severity: systematic evaluation of lesion representations.","authors":"Anna K Bonkhoff, Alexander L Cohen, William Drew, Michael A Ferguson, Aaliya Hussain, Christopher Lin, Frederic L W V J Schaper, Anthony Bourached, Anne-Katrin Giese, Lara C Oliveira, Robert W Regenhardt, Markus D Schirmer, Christina Jern, Arne G Lindgren, Jane Maguire, Ona Wu, Sahar Zafar, John Y Rhee, Eyal Y Kimchi, Maurizio Corbetta, Natalia S Rost, Michael D Fox","doi":"10.1002/acn3.52215","DOIUrl":"https://doi.org/10.1002/acn3.52215","url":null,"abstract":"<p><strong>Objective: </strong>To systematically evaluate which lesion-based imaging features and methods allow for the best statistical prediction of poststroke deficits across independent datasets.</p><p><strong>Methods: </strong>We utilized imaging and clinical data from three independent datasets of patients experiencing acute stroke (N₁ = 109, N₂ = 638, N₃ = 794) to statistically predict acute stroke severity (NIHSS) based on lesion volume, lesion location, and structural and functional disconnection with the lesion location using normative connectomes.</p><p><strong>Results: </strong>We found that prediction models trained on small single-center datasets could perform well using within-dataset cross-validation, but results did not generalize to independent datasets (median R² _N1 = 0.2%). Performance across independent datasets improved using large single-center training data (R² _N2 = 15.8%) and improved further using multicenter training data (R² _N3 = 24.4%). These results were consistent across lesion attributes and prediction models. Including either structural or functional disconnection in the models outperformed prediction based on volume or location alone (P < 0.001, FDR-corrected).</p><p><strong>Interpretation: </strong>We conclude that (1) prediction performance in independent datasets of patients with acute stroke cannot be inferred from cross-validated results within a dataset, as performance results obtained via these two methods differed consistently, (2) prediction performance can be improved by training on large and, importantly, multicenter datasets, and (3) structural and functional disconnection allow for improved prediction of acute stroke severity.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453941","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}