PMID- 33734414
OWN - NLM
STAT- MEDLINE
DCOM- 20210617
LR  - 20231115
IS  - 2574-3805 (Electronic)
IS  - 2574-3805 (Linking)
VI  - 4
IP  - 3
DP  - 2021 Mar 1
TI  - Neuroanatomical Substrates and Symptoms Associated With Magnetic Resonance 
      Imaging of Patients With Mild Traumatic Brain Injury.
PG  - e210994
LID - 10.1001/jamanetworkopen.2021.0994 [doi]
LID - e210994
AB  - IMPORTANCE: Persistent symptoms after mild traumatic brain injury (mTBI) 
      represent a major public health problem. OBJECTIVE: To identify neuroanatomical 
      substrates of mTBI and the optimal timing for magnetic resonance imaging (MRI). 
      DESIGN, SETTING, AND PARTICIPANTS: This prospective multicenter cohort study 
      encompassed all eligible patients from the Collaborative European NeuroTrauma 
      Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study (December 19, 
      2014, to December 17, 2017) and a local cohort (November 20, 2012, to December 
      19, 2013). Patients presented to the hospital within 24 hours of an mTBI (Glasgow 
      Coma Score, 13-15), satisfied local criteria for computed tomographic scanning, 
      and underwent MRI scanning less than 72 hours (MR1) and 2 to 3 weeks (MR2) after 
      injury. In addition, 104 control participants were enrolled across all sites. 
      Data were analyzed from January 1, 2019, to December 31, 2020. EXPOSURE: Mild 
      TBI. MAIN OUTCOMES AND MEASURES: Volumes and diffusion parameters were extracted 
      via automated bespoke pipelines. Symptoms were measured using the Rivermead Post 
      Concussion Symptoms Questionnaire in the short term and the extended Glasgow 
      Outcome Scale at 3 months. RESULTS: Among the 81 patients included in the 
      analysis (73 CENTER-TBI and 8 local), the median age was 45 (interquartile range 
      [IQR], 24-59; range, 14-85) years, and 57 (70.4%) were male. Structural sequences 
      were available for all scans; diffusion data, for 73 MR1 and 79 MR2 scans. After 
      adjustment for multiple comparisons between scans, visible lesions did not differ 
      significantly, but cerebral white matter volume decreased (MR2:MR1 ratio, 0.98; 
      95% CI, 0.96-0.99) and ventricular volume increased (MR2:MR1 ratio, 1.06; 95% CI, 
      1.02-1.10). White matter volume was within reference limits on MR1 scans (patient 
      to control ratio, 0.99; 95% CI, 0.97-1.01) and reduced on MR2 scans (patient to 
      control ratio, 0.97; 95% CI, 0.95-0.99). Diffusion parameters changed 
      significantly between scans in 13 tracts, following 1 of 3 trajectories. Symptoms 
      measured by Rivermead Post Concussion Symptoms Questionnaire scores worsened in 
      the progressive injury phenotype (median, +5.00; IQR, +2.00 to +5.00]), improved 
      in the minimal change phenotype (median, -4.50; IQR, -9.25 to +1.75), and were 
      variable in the pseudonormalization phenotype (median, 0.00; IQR, -6.25 to +9.00) 
      (P = .02). Recovery was favorable for 33 of 65 patients (51%) and was more 
      closely associated with MR1 than MR2 (area under the curve, 0.87 [95% CI, 
      0.78-0.96] vs 0.75 [95% CI, 0.62-0.87]; P = .009). CONCLUSIONS AND RELEVANCE: 
      These findings suggest that advanced MRI reveals potential neuroanatomical 
      substrates of mTBI in white matter and is most strongly associated with odds of 
      recovery if performed within 72 hours, although future validation is required.
FAU - Richter, Sophie
AU  - Richter S
AD  - University Division of Anaesthesia, Department of Medicine, University of 
      Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
FAU - Winzeck, Stefan
AU  - Winzeck S
AD  - University Division of Anaesthesia, Department of Medicine, University of 
      Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
AD  - BioMedIA, Department of Computing, Imperial College London, London, United 
      Kingdom.
FAU - Kornaropoulos, Evgenios N
AU  - Kornaropoulos EN
AD  - University Division of Anaesthesia, Department of Medicine, University of 
      Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
FAU - Das, Tilak
AU  - Das T
AD  - Department of Radiology, Addenbrooke's Hospital, Cambridge, United Kingdom.
FAU - Vande Vyvere, Thijs
AU  - Vande Vyvere T
AD  - Department of Radiology, University Hospital and University of Antwerp, Antwerp, 
      Belgium.
AD  - Research and Development, icometrix, Leuven, Belgium.
FAU - Verheyden, Jan
AU  - Verheyden J
AD  - Research and Development, icometrix, Leuven, Belgium.
FAU - Williams, Guy B
AU  - Williams GB
AD  - Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of 
      Cambridge, Cambridge, United Kingdom.
FAU - Correia, Marta M
AU  - Correia MM
AD  - MRC (Medical Research Council) Cognition and Brain Sciences Unit, University of 
      Cambridge, Cambridge, United Kingdom.
FAU - Menon, David K
AU  - Menon DK
AD  - University Division of Anaesthesia, Department of Medicine, University of 
      Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
FAU - Newcombe, Virginia F J
AU  - Newcombe VFJ
AD  - University Division of Anaesthesia, Department of Medicine, University of 
      Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
CN  - Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain 
      Injury Magnetic Resonance Imaging (CENTER-TBI MRI) Substudy Participants and 
      Investigators
LA  - eng
GR  - MR/M009041/1/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20210301
PL  - United States
TA  - JAMA Netw Open
JT  - JAMA network open
JID - 101729235
SB  - IM
CIN - JAMA Netw Open. 2021 Mar 1;4(3):e211824. PMID: 33734409
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Brain Injuries, Traumatic/*diagnostic imaging
MH  - Female
MH  - Humans
MH  - Injury Severity Score
MH  - *Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Time Factors
MH  - White Matter/*diagnostic imaging
MH  - Young Adult
PMC - PMC7974642
COIS- Conflict of Interest Disclosures: Dr Richter reported receiving personal fees 
      from the Wellcome Trust (PhD Fellowship) during the conduct of the study. Mr 
      Verheyden reported receiving grants from the FP7 Framework (NCT02210221) during 
      the conduct of the study. Dr Menon reported receiving grants from the National 
      Institute for Health Research (NIHR) UK and European Union Framework Program 7 
      during the conduct of the study; personal fees from Lantmannen AB, 
      GlaxoSmithKline plc, Calico Life Sciences LLC, PresSura Neuro, Integra 
      Neurosciences, and NeuroTrauma Sciences, LLC; grants from GlaxoSmithKline plc; 
      and a shared National Institutes of Health grant from Gryphon Collaborators on a 
      grant application outside the submitted work. Dr Newcombe reported receiving 
      grants from F. Hoffman-La Roche Ltd and personal fees from Neurodiem Honorarium 
      for a talk put into the University of Cambridge research fund outside the 
      submitted work. No other disclosures were reported.
EDAT- 2021/03/19 06:00
MHDA- 2021/06/22 06:00
PMCR- 2021/03/18
CRDT- 2021/03/18 12:48
PHST- 2021/03/18 12:48 [entrez]
PHST- 2021/03/19 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2021/03/18 00:00 [pmc-release]
AID - 2777632 [pii]
AID - zoi210051 [pii]
AID - 10.1001/jamanetworkopen.2021.0994 [doi]
PST - epublish
SO  - JAMA Netw Open. 2021 Mar 1;4(3):e210994. doi: 10.1001/jamanetworkopen.2021.0994.