小儿创伤性脑损伤中的白质破坏：ENIGMA小儿中重度创伤性脑损伤研究结果
White Matter Disruption in Pediatric Traumatic Brain Injury: Results From ENIGMA Pediatric Moderate to Severe Traumatic Brain Injury.
作者信息
Dennis Emily L, Caeyenberghs Karen, Hoskinson Kristen R, Merkley Tricia L, Suskauer Stacy J, Asarnow Robert F, Babikian Talin, Bartnik-Olson Brenda, Bickart Kevin, Bigler Erin D, Ewing-Cobbs Linda, Figaji Anthony, Giza Christopher C, Goodrich-Hunsaker Naomi J, Hodges Cooper B, Hovenden Elizabeth S, Irimia Andrei, Königs Marsh, Levin Harvey S, Lindsey Hannah M, Max Jeffrey E, Newsome Mary R, Olsen Alexander, Ryan Nicholas P, Schmidt Adam T, Spruiell Matthew S, Wade Benjamin S C, Ware Ashley L, Watson Christopher G, Wheeler Anne L, Yeates Keith Owen, Zielinski Brandon A, Kochunov Peter, Jahanshad Neda, Thompson Paul M, Tate David F, Wilde Elisabeth A
机构信息
From the Department of Neurology (E.L.D., T.L.M., E.D.B., N.J.G.-H., E.S.H., H.M.L., B.S.C.W., B.A.Z., D.F.T., E.A.W.), University of Utah School of Medicine; George E. Wahlen Veterans Affairs Medical Center (E.L.D., N.J.G.-H., H.M.L., D.F.T., E.A.W.), Salt Lake City, UT; Cognitive Neuroscience Unit (K.C., N.P.R.), School of Psychology, Deakin University, Geelong, Australia; Center for Biobehavioral Health (K.R.H.), The Abigail Wexner Research Institute at Nationwide Children's Hospital; Department of Pediatrics (K.R.H.), The Ohio State University College of Medicine, Columbus; Department of Psychology (T.L.M., E.D.B., N.J.G.-H., C.B.H., H.M.L.) and Neuroscience Center (T.L.M., E.D.B.), Brigham Young University, Provo, UT; Kennedy Krieger Institute (S.J.S.); Departments of Physical Medicine & Rehabilitation and Pediatrics (S.J.S.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Psychiatry and Biobehavioral Sciences (R.F.A., T.B.), Semel Institute for Neuroscience and Human Behavior, Brain Research Institute (R.F.A.), and Department of Psychology (R.F.A.), UCLA; UCLA Steve Tisch BrainSPORT Program (T.B., K.B., C.C.G.), Los Angeles; Department of Radiology (B.B.-O.), Loma Linda University Medical Center; Departments of Neurology (K.B.) and Neurosurgery (C.C.G.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Pediatrics (L.E.-C., C.G.W.), Children's Learning Institute, University of Texas Health Science Center at Houston; Division of Neurosurgery (A.F.) and Neuroscience Institute (A.F.), University of Cape Town, South Africa; Department of Pediatrics (C.C.G.), Division of Neurology, UCLA Mattel Children's Hospital, Los Angeles, CA; Department of Physical Medicine and Rehabilitation (C.B.H.), Virginia Commonwealth University, Richmond; Ethel Percy Andrus Gerontology Center (A.I.), Leonard Davis School of Gerontology, and Department of Biomedical Engineering (A.I.), Viterbi School of Engineering, University of Southern California, Los Angeles; Emma Children's Hospital (M.K.), Amsterdam UMC, University of Amsterdam, Emma Neuroscience Group, the Netherlands; H. Ben Taub Department of Physical Medicine and Rehabilitation (H.S.L., M.R.N., M.S.S., E.A.W.), Baylor College of Medicine; Michael E. DeBakey Veterans Affairs Medical Center (H.S.L., M.R.N.), Houston, TX; Department of Psychiatry (J.E.M.), University of California, San Diego, La Jolla; Department of Psychiatry (J.E.M.), Rady Children's Hospital, San Diego, CA; Department of Psychology (A.O.), Norwegian University of Science and Technology, Trondheim; Department of Physical Medicine and Rehabilitation (A.O.), St. Olavs Hospital, Trondheim University Hospital, Norway; Department of Clinical Sciences (N.P.R.), Murdoch Children's Research Institute; Department of Paediatrics (N.P.R.), University of Melbourne, Australia; Department of Psychological Sciences (A.T.S.), Texas Tech University, Lubbock; Ahmanson-Lovelace Brain Mapping Center (B.S.C.W.), Department of Neurology, University of California, Los Angeles; Department of Psychology (A.L. Ware, K.O.Y.), University of Calgary, Alberta; Hospital for Sick Children (A.L. Wheeler), Neuroscience and Mental Health Program; Physiology Department (A.L. Wheeler), University of Toronto, Ontario; Alberta Children's Hospital Research Institute and Hotchkiss Brain Institute (K.O.Y.) and Departments of Pediatrics and Clinical Neurosciences (K.O.Y.), University of Calgary, Alberta, Canada; Department of Pediatrics (B.A.Z.), University of Utah School of Medicine, Salt Lake City; Maryland Psychiatric Research Center (P.K.), University of Maryland School of Medicine, Baltimore; Imaging Genetics Center (N.J., P.M.T.), Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina Del Rey; and Departments of Neurology, Pediatrics, Psychiatry, Radiology, Engineering, and Ophthalmology (P.M.T.), USC, Los Angeles, CA.
出版信息
Neurology. 2021 Jul 19;97(3):e298-e309. doi: 10.1212/WNL.0000000000012222.
OBJECTIVE
Our study addressed aims (1) to test the hypothesis that moderate-severe traumatic brain injury (TBI) in pediatric patients is associated with widespread white matter (WM) disruption, (2) to test the hypothesis that age and sex affect WM organization after injury, and (3) to examine associations between WM organization and neurobehavioral outcomes.
METHODS
Data from 10 previously enrolled, existing cohorts recruited from local hospitals and clinics were shared with the Enhancing NeuroImaging Genetics Through Meta-Analysis (ENIGMA) Pediatric Moderate/Severe TBI (msTBI) working group. We conducted a coordinated analysis of diffusion MRI (dMRI) data using the ENIGMA dMRI processing pipeline.
RESULTS
Five hundred seven children and adolescents (244 with complicated msTBI and 263 controls) were included. Patients were clustered into 3 postinjury intervals: acute/subacute, <2 months; postacute, 2 to 6 months; and chronic, ≥6 months. Outcomes were dMRI metrics and postinjury behavioral problems as indexed by the Child Behavior Checklist. Our analyses revealed altered WM diffusion metrics across multiple tracts and all postinjury intervals (effect sizes range d = -0.5 to -1.3). Injury severity is a significant contributor to the extent of WM alterations but explained less variance in dMRI measures with increasing time after injury. We observed a sex-by-group interaction: female patients with TBI had significantly lower fractional anisotropy in the uncinate fasciculus than controls (β = 0.043), which coincided with more parent-reported behavioral problems (β = -0.0027).
CONCLUSIONS
WM disruption after msTBI is widespread, persistent, and influenced by demographic and clinical variables. Future work will test techniques for harmonizing neurocognitive data, enabling more advanced analyses to identify symptom clusters and clinically meaningful patient subtypes.
目的
我们的研究旨在实现以下目标：（1）检验小儿中重度创伤性脑损伤（TBI）与广泛的白质（WM）破坏相关这一假设；（2）检验年龄和性别对损伤后WM组织有影响这一假设；（3）研究WM组织与神经行为结果之间的关联。
方法
来自之前在当地医院和诊所招募的10个现有队列的数据与通过荟萃分析增强神经影像遗传学（ENIGMA）小儿中重度TBI（msTBI）工作组共享。我们使用ENIGMA扩散磁共振成像（dMRI）处理流程对dMRI数据进行了协同分析。
结果
纳入了507名儿童和青少年（244名患有复杂msTBI，263名作为对照）。患者被分为3个损伤后时间段：急性/亚急性，<2个月；亚急性，2至6个月；慢性，≥6个月。结果指标为dMRI测量值以及以儿童行为量表为指标的损伤后行为问题。我们的分析显示，在多个脑区以及所有损伤后时间段，WM扩散测量值均发生了改变（效应大小范围d = -0.5至-1.3）。损伤严重程度是WM改变程度的一个重要影响因素，但随着损伤后时间的增加，其在dMRI测量中所解释的方差较少。我们观察到了性别与分组的交互作用：患有TBI的女性患者钩束的分数各向异性显著低于对照组（β = 0.043），这与家长报告的更多行为问题相一致（β = -0.0027）。
结论
msTBI后的WM破坏广泛且持续，并受人口统计学和临床变量的影响。未来的工作将测试用于协调神经认知数据的技术，以便能够进行更高级的分析来识别症状集群和具有临床意义的患者亚型。
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