Neurology最新文献

{"title":"Longitudinal Evolution of Posterior Cortical Atrophy: Diagnostic Delays, Overlapping Phenotypes, and Clinical Outcomes.","authors":"Dror Shir, Noah Lee, Stuart J McCarter, Vijay K Ramanan, Hugo Botha, David S Knopman, Ronald C Petersen, Bradley F Boeve, Gregory Scott Day, Neill R Graff-Radford, David T Jones, Melissa E Murray, Aivi T Nguyen, R Ross Reichard, Dennis W Dickson, Deena Tajfirouz, Mary M Machulda, Jennifer L Whitwell, Keith Anthony Josephs, Jonathan Graff-Radford","doi":"10.1212/WNL.0000000000213559","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213559","url":null,"abstract":"<p><strong>Background and objectives: </strong>Although several large studies have evaluated individuals with posterior cortical atrophy (PCA) cross-sectionally, its longitudinal progression remains poorly characterized. The objectives of this study were to determine the longitudinal trajectory of PCA, encompassing the temporal aspects of diagnosis, the spectrum of clinical manifestations, and patient outcomes.</p><p><strong>Methods: </strong>This retrospective study included participants evaluated and diagnosed with PCA at the Mayo Clinic, between 1995 and 2023. Clinical data (demographics, neurologic evaluations, and cognitive tests at initial presentation and late stage) were extracted from medical records. Initial clinical diagnoses during previous medical evaluations, including ophthalmologic assessments after onset of neurologic symptoms, were documented. Participants were retrospectively classified as PCA-pure if they solely met PCA criteria or as PCA-plus if they exhibited complex phenotypes also meeting criteria for other neurodegenerative syndromes. CSF analyses and neuropathology findings were documented.</p><p><strong>Results: </strong>The cohort of 558 participants (65% female) had a mean age at symptom onset of 61 ± 8 years, with 68% meeting early-onset criteria (younger than 65 years). The mean duration from symptom onset to diagnosis was 3.6 ± 2.5 years. Ophthalmologic/optometric evaluations (49%) and completion of ophthalmologic procedures (16%) were common before PCA diagnosis. Psychiatric diagnoses were made in 23% of participants before PCA diagnosis, particularly among younger women. Common initial symptoms included misplacement of items, difficulties with reading and driving, and concerns pertaining to basic visual processing. Notable signs were constructional apraxia, dyscalculia, simultanagnosia, and space perception deficits. CSF biomarkers were consistent with Alzheimer disease in 139 of 158 individuals (88%). Superimposed features of non-PCA clinical syndromes were observed in a quarter of the participants at presentation, with frequency of PCA-plus cases increasing longitudinally. Longitudinal analysis of Short Test of Mental Status scores predicted an initial rapid decline in cognitive function, with the rate of decline gradually slowing over 0-10 years (time coefficient [SE] = -4.20 [0.29], <i>p</i> < 0.001).</p><p><strong>Discussion: </strong>This study highlights the protracted time from symptom onset and frequent misdiagnoses/misattribution of symptoms in PCA. Ophthalmologic evaluations often preceded neurologic assessments. Psychiatric diagnoses were more frequent among younger women. These observations highlight the need to improve diagnostic processes and earlier recognition of PCA, which may enhance the effectiveness of emerging disease-modifying therapies.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 9","pages":"e213559"},"PeriodicalIF":7.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811154","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":"Child Neurology: TRAPPC4-Related Neurodevelopmental Disorder.","authors":"Andreia Forno, Joana Oliveira, Marta Zegre Amorim, Carla Conceição, Paulo Rego Sousa","doi":"10.1212/WNL.0000000000213538","DOIUrl":"10.1212/WNL.0000000000213538","url":null,"abstract":"<p><p>Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy, first described in 2020, is associated with autosomal recessive inheritance of pathogenic variant in the <i>TRAPPC4</i> gene. Given a relatively high carrier frequency, it is crucial to recognize and consider this diagnosis. We report 2 sisters with pathogenic homozygous variants (c.454+3A>G) in the <i>TRAPPC4</i> gene, diagnosed after an extensive and time-consuming clinical investigation. This report reviews the phenotypic spectrum of TRAPPC4-related neurodevelopmental disorder, particularly homozygous pathogenic variant c.454+3A>G in <i>TRAPPC4</i>, to raise awareness of this diagnosis.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 9","pages":"e213538"},"PeriodicalIF":7.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772768","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":"Prehospital Large-Vessel Occlusion Stroke Detection Scales: A Pooled Individual Patient Data Analysis of 2 Prospective Cohorts.","authors":"Luuk Dekker, Jasper D Daems, Mariam Ali, Martijne H C Duvekot, Truc My T Nguyen, Esmee Venema, Marcel D J Durieux, Erik W van Zwet, Walid Moudrous, Ido R van den Wijngaard, Henk Kerkhoff, Hester F Lingsma, Diederik W J Dippel, Marieke J H Wermer, Bob Roozenbeek, Nyika D Kruyt","doi":"10.1212/WNL.0000000000213570","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213570","url":null,"abstract":"<p><strong>Background and objectives: </strong>Various prehospital scales have been developed to detect patients with anterior-circulation large-vessel occlusion (aLVO) ischemic stroke to enable direct transportation to a thrombectomy-capable stroke center. To guide implementation, a head-to-head comparison of aLVO stroke detection scales is needed to determine which scale is most useful for prehospital triage in different regional contexts. We aimed to systematically identify and compare these scales.</p><p><strong>Methods: </strong>Published prehospital aLVO stroke scales were identified with a systematic literature search. Scales were reconstructed from individual patient data of 2 large prospective observational cohort studies conducted between 2018 and 2019, the Leiden Prehospital Stroke Study and PREhospital triage of patients with suspected STrOke symptoms study. Both studies included consecutive adult patients suspected by paramedics of having a stroke within 6 hours of symptom onset, from 4 Dutch ambulance regions, encompassing 15 stroke centers and serving 3.7 million people. All data used for the reconstruction of scales were acquired by paramedics in the field before hospital arrival. Scales' diagnostic performance to detect aLVO stroke was compared with the area under the receiver operating characteristic curve (AUROC) of the full scale and sensitivity and specificity at the scales' original cut-point. Decision curve analysis was used to evaluate harm-benefit trade-offs between delaying IV thrombolysis and expediting endovascular thrombectomy with direct transportation of patients to a thrombectomy-capable center.</p><p><strong>Results: </strong>We identified 63 aLVO scales, of which 14 could be reconstructed. Of 2,358 included patients (mean age 70 years; 47% female), 231 (9.8%) had aLVO stroke. The AUROC was highest for Rapid Arterial oCclusion Evaluation (RACE) (0.81, 95% CI 0.78-0.84), Los Angeles Motor Scale (LAMS) (0.80, 95% CI 0.77-0.83), Gaze-Face-Arm-Speech-Time (G-FAST) (0.80, 95% CI 0.77-0.83), and modified Gaze-Face-Arm-Speech-Time (mG-FAST) (0.79, 95% CI 0.76-0.82). The Emergency Medical Stroke Assessment had highest sensitivity (85%, 95% CI 80%-90%) but lowest specificity (58%, 95% CI 56%-61%) while Cincinnati Prehospital Stroke Scale with an adjusted cut-point of 3 + gaze had highest specificity (94%, 95% CI 93%-95%) but lowest sensitivity (35%, 95% CI 29%-41%). In decision curve analysis, RACE had the highest benefit across a clinically reasonable range of harm-benefit trade-offs.</p><p><strong>Discussion: </strong>RACE, LAMS, G-FAST, and mG-FAST are the best-performing scales, with RACE being preferred in most triage settings. Our findings may support policymakers with implementing a scale suitable for their region.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 9","pages":"e213570"},"PeriodicalIF":7.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811785","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":"Incidence of Amyloid-Related Imaging Abnormalities in Phase III Clinical Trials of Anti-Amyloid-β Immunotherapy: An Updated Meta-Analysis.","authors":"So Yeong Jeong, Chong Hyun Suh, Jae-Sung Lim, Woo Hyun Shim, Hwon Heo, Yangsean Choi, Ho Sung Kim, Sang Joon Kim, Jae-Hong Lee","doi":"10.1212/WNL.0000000000213483","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213483","url":null,"abstract":"<p><strong>Background and objectives: </strong>Amyloid-related imaging abnormalities (ARIA) are key safety considerations in anti-amyloid-β (Aβ) immunotherapy. ARIA can be categorized into 2 types: ARIA characterized by edema and effusion (ARIA-E) or microhemorrhages and superficial siderosis (ARIA-H). In this study, we assessed the incidence of ARIA in phase 3 randomized controlled trials (RCTs) of anti-Aβ immunotherapy and compared the incidence among different agents and <i>APOE</i> ε4 carrier status.</p><p><strong>Methods: </strong>PubMed and Embase databases were searched for phase 3 RCTs of anti-Aβ immunotherapy published on or before May 23, 2024. The inclusion criteria were phase 3 trials of anti-Aβ immunotherapy for mild cognitive impairment due to Alzheimer disease (AD) or mild AD dementia, with sufficient data on ARIA-E/H. The pooled incidences of ARIA and subgroup analyses according to various agents and <i>APOE</i> ε4 carrier status were calculated. A sensitivity analysis excluding outliers was performed. The pooled odds ratio (OR) of ARIA-E according to the <i>APOE</i> ε4 carrier status was also calculated.</p><p><strong>Results: </strong>Nine phase 3 RCT cohorts from 8 eligible studies were identified, analyzing data from 6,315 patients. The pooled incidence of ARIA-E was 9.5% (95% CI 2.8%-27.3%), and the adjusted pooled incidence of ARIA-E was 25.5% (95% CI 20.4%-31.8%) in the sensitivity analysis. The pooled incidence of symptomatic ARIA-E was 6.7% (95% CI 3.5%-12.5%) and that of severe ARIA-E was 3.5% (95% CI 13.8%-8.4%). The pooled incidence of ARIA-H was 17.8% (95% CI 11.0%-27.5%), with the incidence of superficial siderosis was 9.3% (95% CI 6.1%-13.9%). The pooled incidence of isolated ARIA-H was 8.7% (95% CI 7.6%-10.1%). Subgroup analysis showed that homozygous <i>APOE</i> ε4 carriers had significantly higher odds of developing ARIA-E (OR 5.6, 95% CI 3.8-8.2, <i>p</i> < 0.001) than noncarriers. Heterozygous <i>APOE</i> ε4 carriers also had significantly higher odds of developing ARIA-E (OR 1.9, 95% CI 1.5-2.4, <i>p</i> < 0.001) than noncarriers.</p><p><strong>Discussion: </strong>Although limited by small sample size and cohort-level data, our meta-analysis shows the adjusted pooled incidence of ARIA-E was 25.5% and the pooled incidence of ARIA-H was 17.8% in the recent phase 3 RCTs of anti-Aβ immunotherapy. Homozygous <i>APOE</i> ε4 carriers have a 5.6-fold higher risk of developing ARIA-E than noncarriers.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e213483"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670427","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":"Racial and Ethnic Differences in Advance Care Planning and End-of-Life Care in Older Adults With Stroke: A Cohort Study.","authors":"Susan Enguidanos, Yujun Zhu, Claire J Creutzfeldt","doi":"10.1212/WNL.0000000000213486","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213486","url":null,"abstract":"<p><strong>Background and objectives: </strong>Stroke is a leading cause of death and disability in the United States and may result in cognitive impairment and the inability to participate in treatment decisions, attesting to the importance of advance care planning (ACP). Although racial and ethnic differences have been shown for ACP in the general population, little is known about these differences specific to patients with stroke. The aim of this study was to examine the presence of ACP and receipt of life-prolonging care by race and ethnicity among decedents who had suffered a stroke.</p><p><strong>Methods: </strong>We used the Health and Retirement Study, a nationally representative longitudinal survey. We conducted a cohort study of decedents who died between 2000 and 2018 using multivariable logistic regression models to explore the association between self-reported ethnicity and race and completion of ACP (including a living will [LW] and durable power of attorney for healthcare [DPOAH]) and receipt of life-prolonging care at end of life, controlling for covariates. Stratified models for each race and ethnicity also were conducted.</p><p><strong>Results: </strong>This study included 3,491 decedents with a reported history of stroke; 57.4% were women, and the mean age was 81.5 years (SD = 10.2). Decedents who identified as non-Hispanic White had the highest end-of-life planning rates (LW: 57%, DPOAH: 72%, and ACP conversation: 63%) compared with those identifying as non-Hispanic Black (LW: 20%, DPOAH 40%, and ACP conversation: 41%) and Hispanic (LW: 20%, DPOAH: 36%, and ACP conversation: 42%; <i>p</i> < 0.001). The presence of ACP discussions, LW, and DPOAH was associated with lower odds of receiving life-prolonging care at end-of-life among non-Hispanic White decedents (OR = .64, CI = .447-0.904; OR = .30, CI = .206-0.445; OR = .61, CI = .386-0.948) but not among those who identified as Hispanic or non-Hispanic Black.</p><p><strong>Conclusions: </strong>Hispanic or non-Hispanic Black decedents with stroke had significantly lower rates of ACP discussions, LWs, and naming a DPOAH compared with those who identified as non-Hispanic White. In addition, ACP activities were inversely associated with receipt of life-prolonging care among non-Hispanic White decedents, but not among those who identified as non-Hispanic Black and Hispanic. Small ethnic/racial subgroup sizes limit the generalizability of this study.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e213486"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670432","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":"Grief and Economic Stressors by Sex, Gender, and Education: Associations With Alzheimer Disease-Related Outcomes.","authors":"Eleni Palpatzis, Muge Akinci, Marina Garcia-Prat, Kaj Blennow, Henrik Zetterberg, Clara Quijano-Rubio, Gwendlyn Kollmorgen, Norbert Wild, Juan Domingo Gispert, Marc Suárez-Calvet, Oriol Grau-Rivera, Karine Fauria, Anna Brugulat-Serrat, Gonzalo Sanchez-Benavides, Eider M Arenaza-Urquijo","doi":"10.1212/WNL.0000000000213377","DOIUrl":"10.1212/WNL.0000000000213377","url":null,"abstract":"<p><strong>Background and objectives: </strong>The prevalence and impact of stressful life events (SLEs) on age-related and Alzheimer disease (AD)-related pathways may depend on social determinants including gender and education. We investigated whether specific SLEs are associated with AD pathology and neurodegeneration and how these associations differ by gender and education.</p><p><strong>Methods: </strong>This cross-sectional study included cognitively unimpaired participants, most with a family history of sporadic AD, from the ALzheimer's and FAmilies (ALFA) cohort, based in Barcelona, Spain. Participants had available assessments on occurrence and type of lifetime SLEs and lumbar puncture and/or structural MRI. We performed multiple regression analyses to examine the associations of specific SLE type with (1) AD pathologies (CSF phosphorylated tau 181 [p-tau181] and β-amyloid [Aβ] 42/40) and (2) neurodegeneration markers (CSF neurogranin and GM volumes voxel-wise) including interaction and stratification analyses by gender (women/men) and education.</p><p><strong>Results: </strong>In total, 1,290 cognitively unimpaired participants (mean age = 59.4 years, range: 48-77 years, 99% White participants, 61% women) were included (393 with lumbar puncture and 1,234 with spectroscopic MRI assessments). Less educated participants and women reported more grief-related and economic-related SLEs. Furthermore, women reported more abuse and reproductive SLEs. Grief-related SLEs were associated with AD and neurodegeneration CSF outcomes while economic SLEs were associated with MRI-based GM outcomes, both in an age-independent manner. Specifically, partner's death was associated with lower Aβ42/40 (B = -5.19; 95% CI -9.61 to -0.76; <i>p</i> = 0.022) and higher p-tau181 (B = 0.18; 95% CI 0.05-0.32; <i>p</i> = 0.007) and neurogranin (B = 0.19; 95% CI 0.05-0.32; <i>p</i> = 0.007). The associations with Aβ42/40 were driven by less educated participants and men and associations with p-tau181 and neurogranin driven by women. Unemployment and economic loss were associated with lower GM volumes in limbic and frontal areas, driven by more educated participants and men and by women, respectively.</p><p><strong>Discussion: </strong>Older adults at risk of cognitive decline with less education and women may be more susceptible to experience more SLEs. Men who have experienced widowhood and unemployment and women who have experienced financial difficulties may benefit from interventions.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e213377"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Subacute Mild Traumatic Brain Injury Symptoms With Long-Term Persistent Symptoms, Functional Limitations, and Quality of Life.","authors":"Shawn R Eagle, Nancy Temkin, Jason K Barber, Michael McCrea, Joseph T Giacino, David Okonkwo, Geoffrey T Manley, Lindsay Nelson","doi":"10.1212/WNL.0000000000213427","DOIUrl":"10.1212/WNL.0000000000213427","url":null,"abstract":"<p><strong>Background and objectives: </strong>The objective was to evaluate the association of subacute postconcussion symptoms (with the total Rivermead Post-Concussion Questionnaire [RPQ] score) with persistent symptoms, functional limitations, and quality of life at 6 months in patients with mild traumatic brain injury (mTBI).</p><p><strong>Methods: </strong>This was a secondary analysis of the Transforming Research and Clinical Knowledge of Traumatic Brain Injury, which was a prospective cohort study of patients with TBI and admission Glasgow Coma Scale score between 13 and 15 at 18 US Level 1 trauma centers through 2014-2018. Participants were included in the study if presenting within 24 hours of external force trauma to the head and met the American Congress of Rehabilitation Medicine's criteria for TBI. Participants completed the RPQ, Glasgow Outcome Scale-Extended (GOSE), and Quality of Life after Brain Injury Overall Scale (QOLIBRI-OS). Primary outcomes were persistent symptoms (≥3 individual RPQ symptoms higher than preinjury level), incomplete recovery (GOSE score <8), and lower quality of life (QOLIBRI-OS score ≤51) at 6 months. Multivariable regression models were developed including RPQ clinical cutoffs at 2 weeks and 3 months and risk factors. Adjusted odds ratios (aORs) and 95% CI are reported for multivariable models. Receiver operating characteristic curves were built to identify discriminative ability of the cutoffs with area under the curve (AUC).</p><p><strong>Results: </strong>The age of the study cohort (n = 2,000) was 41.1 ± 17.3 years; 33% were female (n = 669), 67% male, 57% White (n = 1,141), and 20% Hispanic (n = 408). RPQ total score ≥14 was associated with higher odds of persistent symptoms (aOR 7.25, 95% CI 5.51-9.54), incomplete recovery (aOR 4.85, 95% CI 3.69-6.39), and lower quality of life (aOR 5.31, 95% CI 3.82-7.40) at 6 months compared with patients below the cutoff. AUC for RPQ total score ≥14 at 2 weeks was 0.76-0.81 across outcomes. RPQ total score ≥12 at 3 months was associated with higher odds of persistent symptoms (aOR 18.22, 95% CI 13.09-25.35), incomplete recovery (aOR 8.44, 95% CI 6.18-11.51), and lower quality of life (aOR 7.45, 95% CI 5.40-10.26) at 6 months compared with patients below the cutoff, with AUCs of 0.80-0.88 across outcomes.</p><p><strong>Discussion: </strong>Clinical cutoffs for a commonly used TBI symptom questionnaire had acceptable-to-excellent discrimination for 6-month outcomes and can be used by clinicians at 2 weeks after injury to identify patients at risk of chronic impairments and refer for targeted rehabilitation.</p><p><strong>Classification of evidence: </strong>This study provides Class III evidence that overall TBI symptoms at 2 weeks are predictive of 6-month clinical outcomes.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e213427"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain Network Functional Connectivity in Children With a Concussion.","authors":"Adrian Onicas, Stephanie Deighton, Keith O Yeates, Signe Bray, Kirk Graff, Nishard Abdeen, Miriam H Beauchamp, Christian Beaulieu, Bruce H Bjornson, William Craig, Mathieu Dehaes, Sylvain Deschenes, Emily L Dennis, Quynh Doan, Stephen B Freedman, Bradley G Goodyear, Jocelyn Gravel, Catherine Lebel, Andrée-Anne Ledoux, Roger Zemek, Ashley L Ware","doi":"10.1212/WNL.0000000000213502","DOIUrl":"10.1212/WNL.0000000000213502","url":null,"abstract":"<p><strong>Background and objectives: </strong>Pediatric concussion can disrupt functional brain network connectivity, but prospective longitudinal research is needed to clarify recovery and identify moderators of change. This study investigated network functional connectivity (FC) up to 6 months after pediatric concussion.</p><p><strong>Methods: </strong>This prospective longitudinal concurrent cohort observational study consecutively recruited children (aged 8 to 17 years) at 5 Canadian pediatric hospital emergency departments within 48 hours of sustaining a concussion or mild orthopaedic injury (OI). Children completed 3T MRI scanning postacutely (2 to 33 days) and at either 3 or 6 months after injury (randomly assigned at the postacute visit). Reliable change between retrospective preinjury (based on parent report) and 1-month postinjury symptom ratings based on parent and child report was used to classify concussion with or without persisting symptoms. Within-network and between-network FC was computed for 8 brain networks from resting-state fMRI scans and analyzed using linear mixed-effects models, with multiple comparison correction.</p><p><strong>Results: </strong>Groups (385 with concussion/198 with OI; 59% male; 69% White; age 12.42 ± 2.29 years) did not differ in within-network FC. Relative to OI, connectivity between the visual and ventral attention networks was lower after concussion, <i>d</i> (95% CI) = -0.46 (-0.79 to -0.14), across time. Connectivity between the visual and default mode networks was lower at 6 months after concussion, -0.60 (-0.92 to -0.27). At 3 months after concussion, connectivity between the frontoparietal and ventral attention networks was lower in younger children, -0.98 (-1.58 to -0.37), but higher in older children, 0.81 (0.20 to 1.42). For symptom groups based on parent report, connectivity between the dorsal and ventral attention networks was higher in female children at 3 months after concussion without persisting symptoms relative to concussion with persisting symptoms, 1.25 (2.05 to 0.46), and OI, 0.87 (0.25 to 1.49).</p><p><strong>Discussion: </strong>Time after injury, age at injury, biological sex, and persistent symptom status are important moderators of FC after pediatric concussion for children seen in emergency department settings. Postacute FC may not enhance clinical diagnosis. Although within-network connectivity is preserved, between-network connectivity differences emerge after most children clinically recover and persist up to 6 months after pediatric concussion, providing a potential objective biomarker for lasting changes in brain function.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e213502"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social Science Meets Neuroscience: The Next Frontier in Defining Structural Racism.","authors":"Karlon Johnson, Gillian L Gordon Perue","doi":"10.1212/WNL.0000000000213549","DOIUrl":"10.1212/WNL.0000000000213549","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e213549"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Imaging Markers of Cardiac Function and Brain Health: A Meta-Analysis of Community-Based Studies.","authors":"Amber Yaqub, Joshua C Bis, Stefan Frenzel, Marisa Koini, Djass Mbangdadji, Gina M Peloso, Rajesh Talluri, Alvaro Alonso, Martin Bahls, Robin Bülow, Marcus Dörr, Stephan Felix, Alison Fohner, Nele Friedrich, Edith Hofer, Maryam Kavousi, Lenore J Launer, Tran Le, Will Longstreth, Thomas H Mosley, Meike W Vernooij, Henry Völzke, Katharina Wittfeld, Alexa S Beiser, Hans J Grabe, Vilmundur Gudnason, Mohammad Arfan Ikram, Bruce M Psaty, Reinhold Schmidt, Jeannette Simino, Sudha Seshadri, Frank J Wolters","doi":"10.1212/WNL.0000000000213421","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213421","url":null,"abstract":"<p><strong>Background and objectives: </strong>Cardiac dysfunction and heart failure are linked to cognitive impairment, but the underlying brain pathology remains undetermined. We investigated associations between cardiac function (measured by echocardiography or cardiac MRI), clinical heart failure, and structural markers on brain MRI, including volumes of gray and white matter (WM), the hippocampus, and white matter hyperintensities (WMHs).</p><p><strong>Methods: </strong>We leverage data from 7 prospective, community-based cohorts across Europe and the United States, all part of the Cross-Cohort Collaboration. The included cohorts were the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in Communities study, Austrian Stroke Prevention Study, Cardiovascular Health Study, Framingham Heart Study, Rotterdam Study, and Study of Health in Pomerania (SHIP-START and SHIP-TREND). Each cohort performed cross-sectional multivariable linear regression analyses, after which estimates were pooled through random-effects meta-analysis. Heterogeneity was assessed by the <i>I</i>² index (%).</p><p><strong>Results: </strong>Among 10,889 participants (mean age: 66.8 years, range 52.0-76.0; 56.7% women), markers of systolic dysfunction were consistently associated with smaller total brain volume (TBV) (e.g., adjusted standardized mean difference for moderate to severe dysfunction -0.19, 95% CI -0.31 to -0.07, <i>I</i>² = 20%). Impaired relaxation and restrictive diastolic dysfunction were also associated with smaller TBV (e.g., for impaired relaxation -0.08, 95% CI -0.15 to -0.01, <i>I</i>² = 32%) and hippocampal volume (-0.18, 95% CI -0.33 to -0.03, <i>I</i>² = 0%), with similar results for the E/A-ratio. Systolic and diastolic dysfunction was not consistently associated with volume of WMHs. Among 5 cohorts with available data, 302 (3.4%) participants had clinical heart failure, which was associated with smaller brain volumes, particularly in the hippocampus (-0.13, 95% CI -0.23 to -0.02, <i>I</i>² = 1%).</p><p><strong>Discussion: </strong>In this large study among community-dwelling adults, subclinical cardiac dysfunction was associated with brain imaging markers of neurodegeneration. These findings encourage longitudinal investigations on the effect of maintaining cardiac function on brain health.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e213421"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730826","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}