ImportanceProgressive multifocal leukoencephalopathy (PML) is a life-threatening demyelinating disease caused by reactivation of the JC virus (JCV) in immunocompromised patients. While immune checkpoint inhibitors (ICIs) show therapeutic potential, responses vary and predictive biomarkers are lacking.ObjectiveTo determine whether pretreatment JCV- and/or BK virus-specific T cells in the blood are associated with treatment efficacy.Design, Setting, and ParticipantsThis retrospective cohort study included 111 patients with PML who were treated with ICIs stratified by peripheral virus-specific T cell presence (ELISpot/flow cytometry) between August 2021 and May 2024, with a median (IQR) follow-up of 7 (1-13) months. Of 112 patients with definite PML across 39 centers, 1 patient refused participation; 111 patients were included.ExposurePatients received pembrolizumab (n = 81), nivolumab (n = 28), or atezolizumab (n = 2) per availability and prescribing practices at participating centers.Main Outcome and MeasuresClinical outcomes, diagnostic parameters, and immune-related adverse events were compared; association of virus-specific T-cell responses with survival was analyzed using the Kaplan-Meier method.ResultsThe study cohort consisted of 111 patients (median [IQR] age, 61 [50-70] years; 74 male [66.6%]). Twenty-one patients had detectable virus-specific T cells prior to therapy, 22 were T cell-negative and 68 had an unknown T-cell status. T cell-positive patients showed significantly higher response rates and improved survival compared to both T cell-negative patients (18/21 [86%] vs 5/22 [23%]; P < .001; median survival time, none [95% CI, undefined] vs 136.5 days [95% CI, 19 to ∞]; P = .002) and those with unknown T-cell status (18/21 [86%] vs 29/68 [43%]; P = .001; median survival time, none vs 162 days [95% CI, 66 to ∞]; P = .004). They achieved better functional outcomes (median [IQR] modified Rankin Scale score, 3 [2-4] vs 4 [3-6]; P = .009) and lower JC viral load in cerebrospinal fluid (median [IQR], 0 copies/mL [0-502.5] vs 2500 copies/mL [0-6900]; P = .01) during follow-up compared to T cell-negative patients. Immune-related adverse events were most frequent in T cell-negative patients (10/20 [50%]), including the most severe events, and least frequent in T cell-positive patients (2/20 [10%]) (P = .02).Conclusions and RelevancePreexisting functional virus-specific T cells were associated with better clinical response, longer survival, and lower toxicity in PML. These findings suggest the likely importance of preexisting antiviral immunity for successful ICI therapy.
进行性多灶性脑白质病（PML）是一种危及生命的脱髓鞘疾病，由免疫功能低下患者的JC病毒（JCV）再激活引起。虽然免疫检查点抑制剂（ICIs）显示出治疗潜力，但反应各不相同，缺乏预测性生物标志物。目的探讨预处理血液中JCV和/或BK病毒特异性T细胞是否与治疗效果相关。设计、环境和参与者这项回顾性队列研究纳入了111例PML患者，这些患者在2021年8月至2024年5月期间接受了外周病毒特异性T细胞存在（ELISpot/流式细胞术）分层的ICIs治疗，中位（IQR）随访时间为7（1-13）个月。在39个中心的112名确诊PML患者中，1名患者拒绝参与；纳入111例患者。根据参与中心的可用性和处方实践，患者接受了派姆单抗（n = 81）、尼武单抗（n = 28）或阿特唑单抗（n = 2）。主要结局和测量：比较临床结局、诊断参数和免疫相关不良事件；使用Kaplan-Meier方法分析病毒特异性t细胞反应与存活的关系。结果研究队列包括111例患者（中位[IQR]年龄61[50-70]岁，男性74例[66.6%]）。21名患者在治疗前检测到病毒特异性T细胞，22名患者T细胞阴性，68名患者T细胞状态未知。与T细胞阴性患者相比，T细胞阳性患者的有效率和生存率均显著提高(18/21 [86%]vs 5/22 [23%]; P < .001；中位生存时间，无[95% CI，未定义]vs 136.5天[95% CI， 19至∞]；P =。002)和t细胞状态未知的患者（18/21 [86%]vs 29/68 [43%]; P = .001；中位生存时间，无vs 162天[95% CI， 66至∞]；P = .004）。他们获得了更好的功能结局(修正Rankin量表中位数[IQR]， 3 [2-4] vs 4 [3-6]；009)和脑脊液JC病毒载量较低(中位数[IQR]， 0拷贝/mL [0-502.5] vs 2500拷贝/mL [0-6900]； P =。与T细胞阴性患者相比，p < 0.01)。免疫相关不良事件在T细胞阴性患者中发生率最高（10/20[50%]），其中T细胞阳性患者发生率最低（2/20 [10%]）（P = .02）。先前存在的功能性病毒特异性T细胞与PML患者更好的临床反应、更长的生存期和更低的毒性相关。这些发现表明，预先存在的抗病毒免疫对成功的ICI治疗可能很重要。
{"title":"Virus-Specific T Cells and Response to Checkpoint Inhibitors in Progressive Multifocal Leukoencephalopathy.","authors":"Nora Möhn,Lea Grote-Levi,Agnes Bonifacius,Sabine Tischer-Zimmermann,Sandra Nay,Konstantin Fritz Jendretzky,Mieke Luise Sassmann,Kevin Karacondi,Melanie Zent,Franz Felix Konen,Kurt-Wolfram Sühs,Sven G Meuth,Marc Pawlitzki,Clemens Warnke,Ilya Ayzenberg,Ruth Schneider,Christoph Helmchen,Norbert Brüggemann,Stephan Klebe,Marcel Hildner,Christian Grefkes,Louisa Nitsch,Petra Hühnchen,Sebastian Böltz,Laura Alt,Hayrettin Tumani,Christoph Kleinschnitz,Refik Pul,Oliver Grauer,David Clifford,Sharmilee Gnanapavan,Rebecca Wicklein,Thomas Perpoint,Martijn Beudel,Arnaud Del Bello,Sebastian Rauer,Heinz Wiendl,Ilijas Jelcic,Jacques Gasnault,Eleonora Cimini,Andrea Antinori,Carmela Pinnetti,Valérie Pourcher,Nicolas Weiss,Nicolas Lambert,Britta Maecker-Kolhoff,Günter U Höglinger,Sara Zahraeifard,Irene Cortese,Britta Eiz-Vesper,Guillaume Martin-Blondel,Thomas Skripuletz, ","doi":"10.1001/jamaneurol.2025.5318","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.5318","url":null,"abstract":"ImportanceProgressive multifocal leukoencephalopathy (PML) is a life-threatening demyelinating disease caused by reactivation of the JC virus (JCV) in immunocompromised patients. While immune checkpoint inhibitors (ICIs) show therapeutic potential, responses vary and predictive biomarkers are lacking.ObjectiveTo determine whether pretreatment JCV- and/or BK virus-specific T cells in the blood are associated with treatment efficacy.Design, Setting, and ParticipantsThis retrospective cohort study included 111 patients with PML who were treated with ICIs stratified by peripheral virus-specific T cell presence (ELISpot/flow cytometry) between August 2021 and May 2024, with a median (IQR) follow-up of 7 (1-13) months. Of 112 patients with definite PML across 39 centers, 1 patient refused participation; 111 patients were included.ExposurePatients received pembrolizumab (n = 81), nivolumab (n = 28), or atezolizumab (n = 2) per availability and prescribing practices at participating centers.Main Outcome and MeasuresClinical outcomes, diagnostic parameters, and immune-related adverse events were compared; association of virus-specific T-cell responses with survival was analyzed using the Kaplan-Meier method.ResultsThe study cohort consisted of 111 patients (median [IQR] age, 61 [50-70] years; 74 male [66.6%]). Twenty-one patients had detectable virus-specific T cells prior to therapy, 22 were T cell-negative and 68 had an unknown T-cell status. T cell-positive patients showed significantly higher response rates and improved survival compared to both T cell-negative patients (18/21 [86%] vs 5/22 [23%]; P < .001; median survival time, none [95% CI, undefined] vs 136.5 days [95% CI, 19 to ∞]; P = .002) and those with unknown T-cell status (18/21 [86%] vs 29/68 [43%]; P = .001; median survival time, none vs 162 days [95% CI, 66 to ∞]; P = .004). They achieved better functional outcomes (median [IQR] modified Rankin Scale score, 3 [2-4] vs 4 [3-6]; P = .009) and lower JC viral load in cerebrospinal fluid (median [IQR], 0 copies/mL [0-502.5] vs 2500 copies/mL [0-6900]; P = .01) during follow-up compared to T cell-negative patients. Immune-related adverse events were most frequent in T cell-negative patients (10/20 [50%]), including the most severe events, and least frequent in T cell-positive patients (2/20 [10%]) (P = .02).Conclusions and RelevancePreexisting functional virus-specific T cells were associated with better clinical response, longer survival, and lower toxicity in PML. These findings suggest the likely importance of preexisting antiviral immunity for successful ICI therapy.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"275 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005018","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}
Pub Date : 2026-01-12DOI: 10.1001/jamaneurol.2025.5261
Jason K Russell,Zinayida Schlachetzki,Beau M Ances,Michael S Rafii,
{"title":"Concordance of Biological and Clinical Staging of Alzheimer Disease Pathology in Down Syndrome.","authors":"Jason K Russell,Zinayida Schlachetzki,Beau M Ances,Michael S Rafii, ","doi":"10.1001/jamaneurol.2025.5261","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.5261","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"29 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949572","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}
Pub Date : 2026-01-12DOI: 10.1001/jamaneurol.2025.5255
Katrin Wolfova,Bo Lars Engdahl,Julie Horn,Claire S Riley,Natalie A Bello,Eliza C Miller,Sarah E Tom
ImportanceAlthough concordance rates for multiple sclerosis (MS) are higher among dizygotic twins than among nontwin siblings-suggesting a potential influence of prenatal and perinatal factors-few large-scale studies have systematically investigated the role of maternal adverse pregnancy outcomes in risk of MS in offspring.ObjectiveTo explore whether preterm birth, being born small or large for gestational age (SGA and LGA, respectively), maternal hypertensive disorders of pregnancy (HDP), placental abruption, and maternal diabetes are associated with the risk of adult-onset MS in offspring.Design, Setting, and ParticipantsA closed cohort study with a follow-up beginning in January 2009 and continuing until the first event, death, emigration, or end of follow-up (December 2019). Data were derived from Norwegian national registers. All live births (N = 1 303 802) in the Medical Birth Registry of Norway from 1967 to 1989 were identified. MS cases were identified through the National Patient Register. Cox models were used to estimate the association between adverse pregnancy outcomes and MS among participants aged 18 years and older at the beginning of the follow-up and MS-free during the previous year. Data were analyzed from February to October 2025.ExposuresPrimary exposures included preterm birth (before gestational age of 37 completed weeks), SGA (birth weight <10th percentile), LGA (birth weight >90th percentile), HDP (preeclampsia, eclampsia, gestational hypertension, and chronic hypertension), placental abruption, and maternal diabetes (type 2, unspecified pregestational diabetes, gestational diabetes, and use of antidiabetic medication during pregnancy).Main Outcomes and MeasuresMS diagnosis defined by International Classification of Diseases and Related Health Problems, Tenth Revision, code G35.ResultsAmong 1 166 731 infants (597 330 [51.2%] male), 4295 MS cases were identified in 2009 and onwards. Adjusting for confounders, the hazard ratio [HR] for LGA was 1.13 (95% CI, 1.03-1.25), while the HR for SGA was 0.88 (95% CI, 0.78-0.98). The HR for maternal diabetes was 2.15 (95% CI, 1.37-3.37). Preterm birth, placental abruption, and HDP were not associated with MS.Conclusions and RelevanceIn this cohort study, being born LGA and being exposed to maternal diabetes were associated with a higher risk of adult-onset MS, whereas begin born SGA was associated with a lower risk. While high childhood body mass index and diabetes are known MS risk factors, these findings suggest susceptibility may begin as early as the prenatal period.
{"title":"Maternal Pregnancy Outcomes and Offspring Risk of Adult-Onset Multiple Sclerosis.","authors":"Katrin Wolfova,Bo Lars Engdahl,Julie Horn,Claire S Riley,Natalie A Bello,Eliza C Miller,Sarah E Tom","doi":"10.1001/jamaneurol.2025.5255","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.5255","url":null,"abstract":"ImportanceAlthough concordance rates for multiple sclerosis (MS) are higher among dizygotic twins than among nontwin siblings-suggesting a potential influence of prenatal and perinatal factors-few large-scale studies have systematically investigated the role of maternal adverse pregnancy outcomes in risk of MS in offspring.ObjectiveTo explore whether preterm birth, being born small or large for gestational age (SGA and LGA, respectively), maternal hypertensive disorders of pregnancy (HDP), placental abruption, and maternal diabetes are associated with the risk of adult-onset MS in offspring.Design, Setting, and ParticipantsA closed cohort study with a follow-up beginning in January 2009 and continuing until the first event, death, emigration, or end of follow-up (December 2019). Data were derived from Norwegian national registers. All live births (N = 1 303 802) in the Medical Birth Registry of Norway from 1967 to 1989 were identified. MS cases were identified through the National Patient Register. Cox models were used to estimate the association between adverse pregnancy outcomes and MS among participants aged 18 years and older at the beginning of the follow-up and MS-free during the previous year. Data were analyzed from February to October 2025.ExposuresPrimary exposures included preterm birth (before gestational age of 37 completed weeks), SGA (birth weight <10th percentile), LGA (birth weight >90th percentile), HDP (preeclampsia, eclampsia, gestational hypertension, and chronic hypertension), placental abruption, and maternal diabetes (type 2, unspecified pregestational diabetes, gestational diabetes, and use of antidiabetic medication during pregnancy).Main Outcomes and MeasuresMS diagnosis defined by International Classification of Diseases and Related Health Problems, Tenth Revision, code G35.ResultsAmong 1 166 731 infants (597 330 [51.2%] male), 4295 MS cases were identified in 2009 and onwards. Adjusting for confounders, the hazard ratio [HR] for LGA was 1.13 (95% CI, 1.03-1.25), while the HR for SGA was 0.88 (95% CI, 0.78-0.98). The HR for maternal diabetes was 2.15 (95% CI, 1.37-3.37). Preterm birth, placental abruption, and HDP were not associated with MS.Conclusions and RelevanceIn this cohort study, being born LGA and being exposed to maternal diabetes were associated with a higher risk of adult-onset MS, whereas begin born SGA was associated with a lower risk. While high childhood body mass index and diabetes are known MS risk factors, these findings suggest susceptibility may begin as early as the prenatal period.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"48 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949614","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}
Pub Date : 2026-01-05DOI: 10.1001/jamaneurol.2025.5174
Jianyuan Zhang,Yuying Zhao,Cuiping Zhao
{"title":"Generalized Dystonia and Defects in Dopaminergic System With Methylmalonic Acidemia.","authors":"Jianyuan Zhang,Yuying Zhao,Cuiping Zhao","doi":"10.1001/jamaneurol.2025.5174","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.5174","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"42 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903697","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}
Pub Date : 2026-01-05DOI: 10.1001/jamaneurol.2025.5196
James V. Nguyen, Phillippe A. Bilodeau, João Vitor Mahler, Natalia Drosu, Natasha Bobrowski-Khoury, Carson Quinn, Takahisa Mikami, Monique Anderson, Michael Levy
This cohort study examines the incidence of primary central nervous system vasculitis relapse and whether the cerebrospinal fluid profile is associated with recurrence.
本队列研究探讨原发性中枢神经系统血管炎复发的发生率，以及脑脊液特征是否与复发相关。
{"title":"Early Relapse Risk in Biopsy-Confirmed Primary Central Nervous System Vasculitis","authors":"James V. Nguyen, Phillippe A. Bilodeau, João Vitor Mahler, Natalia Drosu, Natasha Bobrowski-Khoury, Carson Quinn, Takahisa Mikami, Monique Anderson, Michael Levy","doi":"10.1001/jamaneurol.2025.5196","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.5196","url":null,"abstract":"This cohort study examines the incidence of primary central nervous system vasculitis relapse and whether the cerebrospinal fluid profile is associated with recurrence.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"24 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145897756","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}
Pub Date : 2026-01-05DOI: 10.1001/jamaneurol.2025.5145
Winok Lapidaire, Jamie Kitt, Samuel Krasner, Paul A. Bateman, Hannah R. Cutler, Logan Barr, Annabelle Frost, Katherine Tucker, Katie Suriano, Yvonne Kenworthy, George Milner, Miriam Lacharie, Rebecca Mills, Cristian Roman, Lucy Mackillop, Christina Aye, Alexandra Cairns, Basky Thilaganathan, Lucy C. Chappell, Adam J. Lewandowski, Richard J. McManus, Paul Leeson
Importance Hypertensive pregnancy increases risk of cognitive decline, stroke, and dementia, especially after preeclampsia. Women with prior hypertensive pregnancy show lower brain volumes, but it was unknown whether early postpartum blood pressure optimization could alter these outcomes. Objective To evaluate whether an intervention designed to achieve better postpartum blood pressure control after a hypertensive pregnancy is associated with differences in brain volumes around 9 months post partum compared with usual care. Design, Setting, and Participants This randomized clinical trial, the Physician Optimized Postpartum blood pressure self-management trial (POP-HT), was a prospective, open-label, blinded end-point study conducted at a single tertiary center in the UK. Participants were older than 18 years and had preeclampsia or gestational hypertension requiring antihypertensive treatment at hospital discharge. Enrollment began February 21, 2020; the last follow-up was on November 2, 2021; and the mean follow-up time was approximately 9 months. Secondary outcome analyses (primary results published 2022) were conducted May 2025. Interventions Telemonitored self-management with research physician-guided titration or usual postnatal care. Main Outcomes and Measures This substudy analyzed the secondary outcomes T1-weighted magnetic resonance imaging (MRI) brain volumes (gray matter, white matter, cerebrospinal fluid, subcortical structures) acquired approximately 9 months post partum. Analyses used linear regression models adjusted for total intracranial volume. Results Of 252 eligible participants, 32 declined, and 220 were randomized (mean [SD] age, 33.4 [5.1] years). The T1 brain MRI of 157 participants was available for analysis; 96 participants (63%) had preeclampsia, and 56 (37%) had gestational hypertension. The intervention group (n = 81) had larger total white matter volumes (adjusted mean difference, 11.50 cm <jats:sup>3</jats:sup> ; 95% CI, 2.04 to 20.96; <jats:italic>P</jats:italic> = .02) compared with the usual care group (n = 71). In usual care, participants with preeclampsia had smaller putamen (adjusted mean difference, −0.83 cm <jats:sup>3</jats:sup> ; 95% CI, −1.20 to −0.46; <jats:italic>P</jats:italic> &lt; .001), accumbens (adjusted mean difference, −0.15 cm <jats:sup>3</jats:sup> ; 95% CI, −0.24 to −0.05; <jats:italic>P</jats:italic> = .003), and pallidum (adjusted mean difference, −0.13 cm <jats:sup>3</jats:sup> ; 95% CI, −0.26 to −0.01; <jats:italic>P</jats:italic> = .04) volumes compared with those with gestational hypertension. These differences were not observed in the intervention group. Conclusions and Relevance This study found that short-term postpartum optimization of blood pressure control after hypertensive pregnancy was associated with larger brain volumes during the first year post partum. Because brain volume is a surrogate of brain health linked to tissue preservation and cognitive outcomes, these fin
高血压妊娠增加认知能力下降、中风和痴呆的风险，尤其是子痫前期。有高血压妊娠史的女性表现出较低的脑容量，但尚不清楚产后早期血压优化是否会改变这些结果。目的评价高血压妊娠后更好的产后血压控制干预是否与产后9个月左右脑容量的差异有关。这项随机临床试验，即医生优化产后血压自我管理试验（POP-HT），是一项在英国单一三级中心进行的前瞻性、开放标签、盲法终点研究。参与者年龄大于18岁，患有先兆子痫或妊娠期高血压，出院时需要抗高血压治疗。2020年2月21日开始招生；最后一次后续行动是在2021年11月2日；平均随访时间约为9个月。次要结果分析（主要结果于2022年发表）于2025年5月进行。干预措施远程监测自我管理与研究医生指导的滴定或通常的产后护理。本亚研究分析了产后约9个月获得的t1加权磁共振成像（MRI）脑体积（灰质、白质、脑脊液、皮质下结构）的次要结果。分析采用线性回归模型调整总颅内容积。结果在252名符合条件的参与者中，32人下降，220人随机分组（平均[SD]年龄33.4[5.1]岁）。157名参与者的T1脑MRI可用于分析；96名参与者（63%）有先兆子痫，56名参与者（37%）有妊娠高血压。干预组（n = 81）与常规护理组（n = 71）相比，总白质体积更大（调整后平均差值为11.50 cm 3; 95% CI, 2.04 ~ 20.96; P = 0.02）。在常规护理中，先兆子痫患者的壳核较小（调整后的平均差异为- 0.83 cm 3; 95% CI, - 1.20至- 0.46;P & lt;）。与妊娠期高血压患者相比，伏隔核（校正平均差值，- 0.15 cm 3; 95% CI, - 0.24至- 0.05;P = 0.003）和白脑（校正平均差值，- 0.13 cm 3; 95% CI, - 0.26至- 0.01;P = 0.04）体积。在干预组中没有观察到这些差异。结论与意义本研究发现，高血压妊娠后短期优化血压控制与产后第一年脑容量增大有关。由于脑容量是与组织保存和认知结果相关的脑健康的替代指标，这些发现表明，潜在的神经血管益处在子痫前期女性中最为明显。临床试验注册ClinicalTrials.gov标识符：NCT04273854
{"title":"Brain Volumes After Hypertensive Pregnancy and Postpartum Blood Pressure Management","authors":"Winok Lapidaire, Jamie Kitt, Samuel Krasner, Paul A. Bateman, Hannah R. Cutler, Logan Barr, Annabelle Frost, Katherine Tucker, Katie Suriano, Yvonne Kenworthy, George Milner, Miriam Lacharie, Rebecca Mills, Cristian Roman, Lucy Mackillop, Christina Aye, Alexandra Cairns, Basky Thilaganathan, Lucy C. Chappell, Adam J. Lewandowski, Richard J. McManus, Paul Leeson","doi":"10.1001/jamaneurol.2025.5145","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.5145","url":null,"abstract":"Importance Hypertensive pregnancy increases risk of cognitive decline, stroke, and dementia, especially after preeclampsia. Women with prior hypertensive pregnancy show lower brain volumes, but it was unknown whether early postpartum blood pressure optimization could alter these outcomes. Objective To evaluate whether an intervention designed to achieve better postpartum blood pressure control after a hypertensive pregnancy is associated with differences in brain volumes around 9 months post partum compared with usual care. Design, Setting, and Participants This randomized clinical trial, the Physician Optimized Postpartum blood pressure self-management trial (POP-HT), was a prospective, open-label, blinded end-point study conducted at a single tertiary center in the UK. Participants were older than 18 years and had preeclampsia or gestational hypertension requiring antihypertensive treatment at hospital discharge. Enrollment began February 21, 2020; the last follow-up was on November 2, 2021; and the mean follow-up time was approximately 9 months. Secondary outcome analyses (primary results published 2022) were conducted May 2025. Interventions Telemonitored self-management with research physician-guided titration or usual postnatal care. Main Outcomes and Measures This substudy analyzed the secondary outcomes T1-weighted magnetic resonance imaging (MRI) brain volumes (gray matter, white matter, cerebrospinal fluid, subcortical structures) acquired approximately 9 months post partum. Analyses used linear regression models adjusted for total intracranial volume. Results Of 252 eligible participants, 32 declined, and 220 were randomized (mean [SD] age, 33.4 [5.1] years). The T1 brain MRI of 157 participants was available for analysis; 96 participants (63%) had preeclampsia, and 56 (37%) had gestational hypertension. The intervention group (n = 81) had larger total white matter volumes (adjusted mean difference, 11.50 cm <jats:sup>3</jats:sup> ; 95% CI, 2.04 to 20.96; <jats:italic>P</jats:italic> = .02) compared with the usual care group (n = 71). In usual care, participants with preeclampsia had smaller putamen (adjusted mean difference, −0.83 cm <jats:sup>3</jats:sup> ; 95% CI, −1.20 to −0.46; <jats:italic>P</jats:italic> &amp;lt; .001), accumbens (adjusted mean difference, −0.15 cm <jats:sup>3</jats:sup> ; 95% CI, −0.24 to −0.05; <jats:italic>P</jats:italic> = .003), and pallidum (adjusted mean difference, −0.13 cm <jats:sup>3</jats:sup> ; 95% CI, −0.26 to −0.01; <jats:italic>P</jats:italic> = .04) volumes compared with those with gestational hypertension. These differences were not observed in the intervention group. Conclusions and Relevance This study found that short-term postpartum optimization of blood pressure control after hypertensive pregnancy was associated with larger brain volumes during the first year post partum. Because brain volume is a surrogate of brain health linked to tissue preservation and cognitive outcomes, these fin","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"27 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145897821","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}
Pub Date : 2026-01-01DOI: 10.1001/jamaneurol.2025.3408
Jo-Hsuan Wu
{"title":"More Than a Quick Look.","authors":"Jo-Hsuan Wu","doi":"10.1001/jamaneurol.2025.3408","DOIUrl":"10.1001/jamaneurol.2025.3408","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"9-10"},"PeriodicalIF":21.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112962","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：