Neuropsychological Outcome and Diffusion Tensor Imaging in Complicated versus Uncomplicated Mild Traumatic Brain Injury

PLOS ONE, Apr 2015

This study examined whether intracranial neuroimaging abnormalities in those with mild traumatic brain injury (MTBI) (i.e., “complicated” MTBIs) are associated with worse subacute outcomes as measured by cognitive testing, symptom ratings, and/or diffusion tensor imaging (DTI). We hypothesized that (i) as a group, participants with complicated MTBIs would report greater symptoms and have worse neurocognitive outcomes than those with uncomplicated MTBI, and (ii) as a group, participants with complicated MTBIs would show more Diffusion Tensor Imaging (DTI) abnormalities. Participants were 62 adults with MTBIs (31 complicated and 31 uncomplicated) who completed neurocognitive testing, symptom ratings, and DTI on a 3T MRI scanner approximately 6-8 weeks post injury. There were no statistically significant differences between groups on symptom ratings or on a broad range of neuropsychological tests. When comparing the groups using tract-based spatial statistics for DTI, no significant difference was found for axial diffusivity or mean diffusivity. However, several brain regions demonstrated increased radial diffusivity (purported to measure myelin integrity), and decreased fractional anisotropy in the complicated group compared with the uncomplicated group. Finally, when we extended the DTI analysis, using a multivariate atlas based approach, to 32 orthopedic trauma controls (TC), the findings did not reveal significantly more areas of abnormal DTI signal in the complicated vs. uncomplicated groups, although both MTBI groups had a greater number of areas with increased radial diffusivity compared with the trauma controls. This study illustrates that macrostructural neuroimaging changes following MTBI are associated with measurable changes in DTI signal. Of note, however, the division of MTBI into complicated and uncomplicated subtypes did not predict worse clinical outcome at 6-8 weeks post injury.

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Neuropsychological Outcome and Diffusion Tensor Imaging in Complicated versus Uncomplicated Mild Traumatic Brain Injury

April Neuropsychological Outcome and Diffusion Tensor Imaging in Complicated versus Uncomplicated Mild Traumatic Brain Injury William J. Panenka 0 1 2 Rael T. Lange 0 1 2 Sylvain Bouix 0 1 2 Jason R. Shewchuk 0 1 2 Manraj K. S. Heran 0 1 2 Jeffrey R. Brubacher 0 1 2 Ryan Eckbo 0 1 2 Martha E. Shenton 0 1 2 Grant L. Iverson 0 1 2 0 1 Department of Psychiatry, University of British Columbia , Vancouver , Canada , 2 Defense and Veterans Brain Injury Center, Walter Reed National Military Medical Center , Bethesda , Maryland, United States of America, 3 Psychiatry Neuroimaging Laboratory, Brigham Women's Hospital, Harvard Medical School , Boston , Massachusetts, United States of America, 4 Department of Radiology, University of British Columbia , Vancouver , Canada , 5 Department of Emergency Medicine, University of British Columbia , Vancouver , Canada , 6 VA Boston Healthcare System, Brockton, Massachusetts, United States of America, 7 Department of Physical Medicine and Rehabilitation, Harvard Medical School, Spaulding Rehabilitation Hospital, & Red Sox Foundation and Massachusetts General Hospital Home Base Program , Boston, Massachusetts , United States of America 1 Data Availability Statement: All relevant data are within the paper 2 Academic Editor: Jan Kassubek, University of Ulm , GERMANY This study examined whether intracranial neuroimaging abnormalities in those with mild traumatic brain injury (MTBI) (i.e., complicated MTBIs) are associated with worse subacute outcomes as measured by cognitive testing, symptom ratings, and/or diffusion tensor imaging (DTI). We hypothesized that (i) as a group, participants with complicated MTBIs would report greater symptoms and have worse neurocognitive outcomes than those with uncomplicated MTBI, and (ii) as a group, participants with complicated MTBIs would show more Diffusion Tensor Imaging (DTI) abnormalities. Participants were 62 adults with MTBIs (31 complicated and 31 uncomplicated) who completed neurocognitive testing, symptom ratings, and DTI on a 3T MRI scanner approximately 6-8 weeks post injury. There were no statistically significant differences between groups on symptom ratings or on a broad range of neuropsychological tests. When comparing the groups using tract-based spatial statistics for DTI, no significant difference was found for axial diffusivity or mean diffusivity. However, several brain regions demonstrated increased radial diffusivity (purported to measure myelin integrity), and decreased fractional anisotropy in the complicated group compared with the uncomplicated group. Finally, when we extended the DTI analysis, using a multivariate atlas based approach, to 32 orthopedic trauma controls (TC), the findings did not reveal significantly more areas of abnormal DTI signal in the complicated vs. uncomplicated groups, although both MTBI groups had a greater number of areas with increased radial diffusivity compared with the trauma controls. This study illustrates that macrostructural neuroimaging changes following MTBI are associated with measurable changes in DTI signal. Of note, however, the division of MTBI into complicated and uncomplicated subtypes did not predict worse clinical outcome at 6-8 weeks post injury. - Funding: Primary funding for this study was provided by the Canadian Institute of Health Research (200903MOP-200377-BSB-CAAA-161276); provided to RTL as PI). MES and GLI note that this work was supported in part by the INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium funded by the Department of Defense Psychological Health/Traumatic Brain Injury Research Program (X81XWH-07-CC-CSDoD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: WJP No competing financial interests exists. RTL - No competing financial interests exists. SB - No competing financial interests exists. JRS - No competing financial interests exists. MKSH - No competing financial interests exists. JRB - No competing financial interests exists. RE - No competing financial interests exists. MES - No competing financial interests exists. GLI- Has been reimbursed and/or received honorariums from the government, professional scientific bodies, and commercial organizations for lectures relating to mild TBI and sport-related concussion at meetings, scientific conferences, and symposiums. He has a private consulting practice in forensic neuropsychology involving individuals who have sustained mild TBIs. He has received research funding from several test publishing companies, including ImPACT Applications, Inc., CNS Vital Signs, and Psychological Assessment Resources (PAR, Inc.), but not in the past 3 years. He receives royalties for two edited books in neuropsychology and one neuropsychological test (WCST-64). This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. Introduction n177 ts ltaa1 ts keew xS <on1 and6 ysda aem sop ,ry itnoa .r om i1n jryu dan iltua ,k2 ,tsh .tsh 04 P ya ju c a Pith ifn P va ee on on <P N d in vo ye N w o N e w m m N C o g m m v rea rpo AN oC on icn a h n n P x e P it m ae P m o o N S y N w 1 y N 3 m m A T a A C M (N e ju A C M (N B B [3 D d N e e w op irv iv e litcedap ittehm naem itrneam xaeitseop rsedue a rsnehpe ry iffrcnee m bo e d C a o ipm ind com eam fr c b N m m tt o t n o o a o n o in b x d < o A A U w m su an an (d N N N e o iv n ltbaadap iitonngrcene litcpaed ltrengh rsoeow -andFE litcpaed eonGO t,sonhm trcenea tsonh iffrceene E c fe m ge ,y S m rs e m d S AN loG fun ifd o o t3 iff 2 o O A oC lon tsa GO C w a d 1 N G N s e m s s to s tcou rseu tsh oem rsue rhag d em itao nda tsh th th p th n n ym on ,P ae no tcu ae ics xan tcou lvua ,,6 no om om S m N m m O m d S o e 3 m 3 3 ed in M 4 M 8 3T 3 M s no rep itmfirs ew AN 3T 2 AN C M (N Materials and Methods Research Ethics This study was approved by the Clinical Research Ethics Board at the University of British Columbia, Vancouver, Canada. All participants gave written informed consent prior to participation. Participants Neuroimaging Uncomplicated MTBI Complicated MTBI other sixteen participants in the complicated group had trauma-related abnormalities on follow-up MRI, but not on their day-of-injury CT scan. The traumatic abnormalities identified on MRI were as follows: greater than five susceptibility foci in sixteen subjects, two to five susceptibility foci in severn subjects, and one susceptibility focus in four subjects. Traumatic abnormalities identified on CT included parenchymal contusions in six subjects, subarachnoid hemorrhage in nine subjects, subdural hemorrhage in four subjects, and diffuse axonal injury in two subjects. By group definition, no patient in the uncomplicated group had abnormalities that could be attributed to the trauma on either day-of-injury CT scan (ordered for 30 of the 31 uncomplicated MTBIs), or subsequent MRI. Subgroup analyses between those with CT and MRI abnormalities, versus those with only MRI abnormalities, were not undertaken, however, due to the small sample sizes. Neurocognition and Symptom Reporting Note: N = 62 (Uncomplicated MTBI, n = 31; Complicated MTBI); Abbreviations: CT = computed tomography; GCS = Glasgow Coma Scale; PTA = post-traumatic amnesia; LOC = loss of consciousness; MTBI = mild traumatic brain injury; MVA = motor vehicle accident; BAL = blood alcohol level. Footnotes: 1 Defined based on criteria for heavy drinking established by the National Institute on Alcohol Abuse and Alcoholism: (a) Females: 8 or more drinks per week or 4 or more drinks on a single occasion more than 52 times per year; (b) Males: 15 or more drinks per week or 5 or more drinks on a single occasion more than 52 times per year. non-significantly better scores on Word Generation (d = .35) compared to the complicated MTBI group (p = .083 to p = .181). The neurocognitive measures were further examined by calculating the number of low scores across the entire battery of tests. Low scores were defined as demographically-adjusted T-scores less than 40 (below the 16th percentile) or less than 37 (below the 10th percentile). The frequency distributions of individuals, based on number of low scores are presented in Table 6. For example, using the 16th percentile cutoff, 9.7% of subjects (3 individuals) in the Self-Report Measures Postconcussion (BC-PSI) Anxiety [57] Depression (BDI-II) Neurocognitive Indexes NAB Total Index NAB Attention Index NAB Memory Index NAB Language Index* NAB Spatial Index* NAB Executive Index* Effect Size Note: N = 62 (Uncomplicated MTBI, n = 31; Complicated MTBI, n = 31); *Cohens [74] effect size (d): small (.20), medium (.50), large (.80). *Prorated Index scores. Diffusion Tensor Imaging Complicated MTBI Note: N = 62 (Uncomplicated MTBI, n = 31; Complicated MTBI, n = 31) *Cohens [74] effect size (d): small (.20), medium (.50), large (.80). <16th percentile <10th percentile Comparison of MTBI Groups to Trauma Controls Uncomplicated MTBI Complicated MTBI Effect Size Note: N = 62 (Uncomplicated MTBI, n = 31; Complicated MTBI, n = 31); *Cohens [74] effect size (d): small (.20), medium (.50), large (.80). IQR = Interquartile Range. M = Mean number of ROIs per subject (out of 48 ROIs) with abnormal score T C - - - - - - - - C M - - - - - - - - - 3 3 3 3 3 6 2 6 9 8 0 m 1 1 2 4 0 o 1 C T C - - - - - - - - - Discussion Clinical Outcome: Cognition, Post-Concussion Symptoms, and Mental Health Limitations Conclusions Acknowledgments References 16. Hiekkanen H, Kurki T, Brandstack N, Kairisto V, Tenovuo O.Association of injury severity, MRI-results and ApoE genotype with 1-year outcome in mainly mild TBI: a preliminary study. 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William J. Panenka, Rael T. Lange, Sylvain Bouix, Jason R. Shewchuk, Manraj K. S. Heran, Jeffrey R. Brubacher, Ryan Eckbo, Martha E. Shenton, Grant L. Iverson. Neuropsychological Outcome and Diffusion Tensor Imaging in Complicated versus Uncomplicated Mild Traumatic Brain Injury, PLOS ONE, 2015, DOI: 10.1371/journal.pone.0122746