Mild Traumatic Brain Injury Across the Lifespan

Transcription

1 Mild Traumatic Brain Injury Across the Lifespan Grant L. Iverson, Ph.D. Professor, Department of Physical Medicine and Rehabilitation, Harvard Medical School; Director, MassGeneral Hospital for Children Sport Concussion Program; & Associate Director of the Traumatic Brain Injury Program, Home Base, Red Sox Foundation and Massachusetts General Hospital 1 st Nordic Neurotrauma Conference Lund, Sweden November 13, 2017

2 Funding Disclosure US Department of Defense (grants) Canadian Institute of Health Research (grants) Lundbeck Canada (grant) AstraZeneca Canada (grant) ImPACT Applications, Inc. (unrestricted philanthropic support) CNS Vital Signs Psychological Assessment Resources, Inc. Tampere University Hospital Alcohol Beverage Medical Research Council Rehabilitation Research and Development (RR&D) Service of the US Department of Veterans Affairs Defense and Veterans Brain Injury Center (former independent contractor; HJF/GD) Mooney-Reed Charitable Foundation (unrestricted philanthropic support) Heinz Family Foundation (unrestricted philanthropic support) 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) Football Players Health Study, Harvard University (NFLPA Funding)

3 Other Disclosures Speaker honorariums and travel expenses for conferences and meetings Independent practice in forensic neuropsychology, including athletes

4 Mild Traumatic Brain Injuries are Not Created Equally

5 Spectrum of MTBI Extremely Mild (Transient) Structural Damage (Permanent)

6 Continuum of Pathophysiology Minor Neurometabolic Major Neurometablic & Pathoanatomical (e.g., Contusion)

7 Rate of Day-of-Injury CT Abnormalities Incidence of intracranial abnormalities in MTBI in Emergency Department studies 5% to 40% across studies It increases with lowering of GCS: 15, 14, 13 MRI reveals a greater rate

8 First Author Year Number Scanned GCS Scores % Abnormal Livingston Stein , Jeret Moran Borczuk , Iverson Thiruppathy Stiell , Stiell , Ono , Saboori

9 Emergency Department Cohort Tampere University Hospital, Tampere, Finland August 2010-July ,023 patients presenting to ED and underwent head CT 2,766 mild head trauma Average Age: 56.4, 50% are between 34 and 77 Isokuortti et al. (in press)

10 Tampere ED Mild Head Trauma Cohort Rates of Complicated MTBI Isokuortti et al. (in press) Percentage Abnormal Stratified by GCS GCS=15 GCS=14 GCS=13

11 Acute (red) and Pre-Existing Lesions (black) Stratified by Age Group in Suspected or Confirmed MTBI (N=2,766) 90% 80% 70% 60% 50% 48.7 % 56.9 % 66.0 % 78.9 % 40% 30% 20% 10% 0% 4.9% 1.2 % 4.2 % 3.0% 11.5 % 9.9% 29.3 % 32.2 % 23.5 % 7.3% 12.2% 11.4% 22.2% 20.1% 18.6% 17.7% Acute intracranial lesion Pre-existing intracranial abnormality

12 Are intracranial abnormalities related to clinical outcomes? See Panenka et al. (2015) for a Review (Table 1)

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14 Cognitive Outcomes Those with intracranial abnormalities performed more poorly on neuropsychological testing (Table 1, 11 of 19 studies 58%) In several of these studies the relationship is modest (small to medium effect sizes) Usually on a small number of the cognitive tests

15 Functional Outcomes In 4 of 13 studies, complicated MTBI patients had greater problems as measured by the Glasgow Outcome Scale, Functional Independence Measure, Global Adaptive Functioning Scale, Return to work. Most studies, however, have not found a significant difference in functional outcomes.

16 Symptom Reporting Paradoxically some studies in the literature suggest that complicated MTBI patients report fewer symptoms. The most consistent finding is that these two groups are not different on symptom reporting (9 of the 13 studies).

17 To date, macroscopic structural injuries are not strongly related to clinical outcomes in MTBI studies More refined imaging studies might show stronger associations Personality and psychosocial factors can be vey important

18 Continuum of Biological & Psychological Vulnerability Extremely Hardy/Resilient Extremely Vulnerable

19 Patients with mtbi and moderate-to-high resilience reported significantly fewer post-concussion symptoms, less fatigue, insomnia, traumatic stress, and depressive symptoms, and better quality of life, than the patients with low resilience.

20 Pre-Existing Health Problems Possible Vulnerability Factor

21 Emergency Department Cohort Tampere University Hospital, Tampere, Finland August 2010-July ,023 patients presenting to ED and underwent head CT Average Age: 56.4, 50% are between 34 and 77 Isokuortti et al. (in press)

22 Pre-Injury Health Problems 3,023 Patients Undergoing Head CT in the ED Isokuortti et al. (in press) Cardiovascular Diseases: 39.4% Mental and Behavioral Disorders: 25.8% Chronic Detrimental Alcohol Use: 18.4% Affective Disorder: 10.3% Diseases of the Nervous System: 23.7% Stroke of Transient Ischemic Attack: 10.0% Cerebral Atrophy and/or Extensive WMHIs: 6.8% Neurodegenerative Disease: 8.3% Prior Brain Injury: 10.3% Mental Disorders OR Diseases of the Nervous System: 43.8%

23 There is no simple, reasonably explanatory model for good or poor outcome

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25 Biopsychosocial Model Pre-Injury Genetics Personality Resilience/hardiness Vulnerability Mental Health Prior brain injuries Post-Injury Traumatic axonal injury Neurophysiological / neurometabolic disturbance Social psychological factors (expectations, good-old-days bias) Depression, anxiety, traumatic stress Chronic bodily pain and/or headaches

26 Biopsychosocial Model for Poor Outcome Traumatic Axonal Injury Cognitive Diminishment Pre-Injury Factors Altered Neurotransmitter Systems Expectations Diagnosis Threat Nocebo Effect Lifestyle & Family Dynamics Changes Anger/Bitterness Justification/Entitlement Litigation Stress Mental Health Problems Social Psychological Factors Insomnia Chronic Headaches or Bodily Pain Depression Anxiety/Stress/Worry Post- Concussion -Like Symptoms Personality Characteristics or Disorders Biopsychosocial Resilience/Hardiness Biopsychosocial Vulnerability Pre-Existing Mental Health Problems Previous Brain Injuries Narcissistic Dependent Histrionic Passive- Aggressive ADHD Learning Disability Genetics Relating to Injury Vulnerability Depression Anxiety Genetic Vulnerability PTSD Copyright 2010, Grant Iverson, Ph.D.

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29 Recovery from Concussion in Sports

30 By definition, a sport-related concussion is a mild traumatic brain injury. By consensus, sport-related concussions are characterized by normal structural neuroimaging.

31 Is sport-related concussion a benign injury? Results from meta-analyses

32 Adverse Effects of Sport Concussion on Cognition

33 Pathophysiology Complex interwoven cellular and vascular changes Multilayered Neurometabolic Cascade Under certain circumstances, cells degenerate and die

34 Primary Mechanisms Ionic shifts Abnormal energy metabolism Diminished cerebral blood flow Impaired neurotransmission

35 Fortunately, the brain undergoes dynamic restoration

36 Assessment Timeline Sideline Post- Game 24 Hours First Week Second Week Third Week At Risk!

37 Recovery Time in Athletes Some evidence that biological recovery might take longer than clinical recovery in some athletes.

38 Pennsylvania High School Football Cohort 2,141 players 3-year prospective cohort study 134 concussions Players followed until recovered Collins, Lovell, Iverson, Ide, Maroon (2006)

39 Recovery Curve (N = 134) 91% 46% Days Post Injury

40 Recovery Curves (N = 134) 94% 84% Days Post Injury

41 Studies over the past decade illustrate that the large majority of athletes appear to recover clinically within one month. Some have persistent symptoms beyond a month. There might be multiple underlying causes and contributors to those persistent symptoms.

42 Possible Predictors or Effect Modifiers of Clinical Outcome Pre-injury differences Sex Age Genetics Neurodevelopmental conditions (e.g., ADHD, LD) Migraine history (personal or family) Mental Health history (personal or family) Concussion History Initial injury severity/acute symptoms (e.g., LOC, PTA, retrograde amnesia) Post-injury clinical differences Severity of cognitive deficits Development of headaches, migraines, depression Dizziness and/or oculomotor functioning

43 Predictors of Clinical Recovery and Persistent Symptoms in Children and Adolescents Multi-Center Canadian Study

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45 5P Sites

46 Derivation Study Design Multicenter, prospective cohort study 10 AM 10 PM daily, 7 days/week Real-time data collection: ipads into Enrollment: August 2013 September 2014 Follow up survey (web or phone): 1, 2, 4, 8, and 12 weeks Neuropsychological testing 1 month and 3 months

47 Patient Population Inclusion Criteria years old Have a concussion Had initial injury in previous 48 hours GCS 14+ English or French Exclusion Criteria CT(+) brain injuries Multi-system injuries Previous CNS disease Intoxication No clear trauma history as primary event (e.g., seizure, syncope or migraine) Previously enrolled

48 Primary Outcome Proportion of children with PCS at one month PCS definition based-on ICD-10 Increase in pre-concussion baseline in 3+ symptoms Post-Concussion Symptom Inventory (PCSI) Developmentally specific versions (5-7, 8-12, 13-18)

49 Results 3,063 patients were enrolled (n=2,006 in the derivation cohort; n=1,057 in the validation cohort) 2,584 completed follow-up at 28 days after the injury

50 Total Sample (Derivation and 30-33% Validation Cohorts) Demographic Variables Mechanism of Injury Ages Sports or Recreational Injury 30.3 Ages ** Non-Sports-Related Injury or Fall 28.2 Ages ** Motor Vehicle Collision (only 34 subjects) 47.1 Boys 23.1 Assault (only 19 subjects) 26.3 Girls 41.1** Injury Severity Characteristics and Clinical Features Health History GCS= No Prior Concussions 28.4 GCS=14 (only 19 subjects) or More Prior Concussions 35.1* Loss of Consciousness 36.2* Prior Concussion with 46.1** Appears Dazed and Confused 33.5* Symptoms 1 week Physician Diagnosed 42.6** Appears Confused About Events 34.2* Migraine History Learning Disability 37.9* Answers Questions Slowly 36.6** ADHD 34.2 Repeats Questions 37.1* Prior History of Anxiety 37.4* Forgetful of Recent Information 37.1* Prior History of Depression 52.8* BESS Tandem Stance 4 points or unable 54.3** *Significant predictors. Headache 31.9** **Multivariate predictors Sensitivity to Noise 40.7** Fatigue 33.5**

51 Results 45 candidate variables with univariate association with primary outcome Acceptable inter-rater agreement (K>0.6) Forward stepwise, binary logistic regression P in =0.05, P out =0.10

52 Age group Sex Longest symptom duration Personal history of migraine Answers questions slowly Tandem stance 5P Prediction Model 5P Prediction Model or <1 week 95% CI Covariate aor Lower Upper P Value 5 to to to Male Female No prior concussion week No Yes No Yes or unable Headache Sensitivity to noise Fatigue No Yes No Yes No Yes

53 Risk Factor Categories Points Age Group 5 to 7 8 to to 18 Sex Longest Symptom Duration Personal History of Migraine Answers Questions Slowly Male Female No Prior or <1 week 1+ week No Yes No Yes Tandem Stance , or unable to do test Headache Sensitivity to Noise Fatigue No Yes No Yes No Yes

54 5P Points: Risk Point total Estimate of Risk Lower 95% CI Upper 95% CI Observed % with PCS-4 Weeks /6 (0%) /37 (16%) /98 (11%) /156 (10%) /239 (17%) /289 (25%) /299 (30%) /243 (40%) /172 (47%) /103 (56%) /43 (70%) /13 (69%) /3 (100%)

55 Predictors of clinical recovery from concussion: a systematic review

56 Objective Review the factors that might be associated with, or influence, clinical recovery from concussion. Clinical Recovery a return to normal activities, including school and sports, following injury. Encompasses resolution of symptoms and return to normal balance and cognitive functioning.

57 Methodological Differences in the Literature Methodological differences in: Outcomes (e.g., symptom resolution, cognition, balance, return to sports, return to school) Time between injury and outcome (e.g., days to several months) Settings (e.g., high school, college, specialty clinic, emergency department) Number of modifiers examined in each study (e.g., 1-47) Univariate Multivariate

58 Considerations: Greater Pre-Injury/Baseline Symptom Reporting Females (Brown et al., 2015; Iverson et al., 2015) Athletes with a history of ADHD (Iverson et al., 2015; Nelson et al, 2015), learning disability (Zuckerman et al., 2013; Elbin et al., 2013), mental health treatment (Iverson, 2015), substance use treatment (Iverson et al., 2015), migraine treatment (Iverson et al., 2015), headache treatment (Brooks et al., 2016). Individuals with multiple prior concussions (Iverson et al., 2015; Brooks et al., 2016). Some athletes without any of these prior conditions report concussion-like symptoms in their daily lives (Iverson et al., 2015), potentially related to stress (Edman et al., 2012), depression (Covassin et al., 2012), or insufficient sleep (McClure et al., 2014).

59 PRISMA 7,648 initially identified 4,777 after duplicate removals 101 full-text articles and 13 conference abstracts ultimately included Study Inclusion Criteria 1. Published by June Examined clinical recovery from concussion

60 Caveats for Interpreting Results Results of all predictors were mixed. Many older studies examined outcome during the first 2 weeks post injury, while more recent studies examined those who are slow to recover (e.g., > 1 month).

61 Mixed Evidence For All Potential Predictors Predictor of Clinical Recovery Studies supporting it as a predictor of recovery Studies not supporting it as a predictor of recovery Age (younger age) 7 24 Sex (female sex) History of Concussions Prior Psychiatric History 7 1 Personal Migraine History 1 9 Family Migraine History 1 2 ADHD 1 10 Learning Disability 1 7 Loss of Consciousness 9 22 Post-Traumatic Amnesia 9 16 Retrograde Amnesia 5 5 Greater Acute/Subacute Symptoms 21 3

62 Younger Age Yes Chermann (2014) ; Field (2003) ; Terwilliger (2016) ; Covassin (2012) ; Majerske (2008) ; Pellman (2006) ; Zuckerman (2012) No Lau (2012) ; Hang (2015) ; McDevett (2015) ; Nelson (2016) ; Asplund (2004) ; Chrisman (2013) ; Vargas (2015) ; Nelson (2016) ; Morgan ; Meehan ; Meehan (2013), ; McCrea 2013, ; Lee (2013) ; Baker (2015) ; Greenhill (2016) ; Nelson (2016) ; Corwin (2014) ; Preiss-Farzenagan (2009) ; Heyer (2016) ; Kontos (2012) ; Kriz (2016) ; Miller (2016) ; Ellis

63 Age There is some, but not definitive, support for a gradient age and level of play effect with clinical recovery being fastest in professional athletes, followed by college athletes, followed by high school athletes. No age effects in several studies, including some large scale studies (Nelson, Guskiewicz, et al., 2016; Nelson, Tarima, et al., 2016). In the large multicenter Canadian study (Zemek et al., 2016), children presenting to the ED following injury, the rates of those having persistent symptoms > 4 weeks: Ages 5-7=17.9%, ages 8-12=26.3%, ages 13-17=39.9%.

64 Female Sex Yes Baker (2016) ; Berz ; Henry ; Kostyun ; Bock 2015; ; Zuckerman ; Covassin ; Covassin ; Covassin ; Majerske ; Colvin ; Eisenberg ; Ellis ; Miller ; Preiss- Farzenagan (2009) (in adults); Heyer (2016) No Chermann ; Moor ; Hang ; Nelson ; Mayers ; Asplund ; Black ; Chrisman ; Zuckerman ; Zuckerman ; Vargas ; Terwilliger ; Morgan ; Frommer ; Baker ; McDevett ; Nelson (2016) ; Lax (2015) ; Ono (2016) ; Preiss-Farzenagan (2009) (in children/adolescents); Covassin (2007) ; Kontos (2012) ; Wasserman (2015) ; Yang (2015)

65 Sex Comparable number of studies show positive and negative findings that worse outcomes are associated with female sex. Some large-scale and epidemiological studies indicate that girls and young women are at greater risk for having symptoms that persist for more than a month (e.g., Wasserman et al., 2016; Zemek,et al., 2016; Kostyun et al., 2016). The extent to which recovery is slower/outcomes are worse for females is still unclear.

66 Prior Concussions Yes Hang (2015) ; Nelson (2016) ; Guskiewicz (2003) ; Castile (2011) ; Chrisman (2013) (football only); Zuckerman (2016) ; Morgan (2015) ; Covassin (2013) ; Kerr (2014) ; Colvin (2009) ; Iverson (2006) ; Miller (2016) ; Wasserman (2015) ; Slobounov (2007) ; Benson (2011) ; Corwin (2014) No Asken (2016) ; Barlow (2011) ; Moor (2015) ; Brown (2014) ; Lau (2012) ; Mautner (2015) ; McDevett (2015) ; Vargas (2015) ; Terwilliger (2016) ; McCrea (2013) ; Erlanger (2003) ; Majerske (2008) ; Baker (2015) ; Ellis (2015) ; Field (2003) ; Makdissi (2013) ; Pellman (2006) ; Gibson (2013) ; Heyer (2016) ; Miller (2016) ; Chrisman (2013) (non-football only)

67 Prior Concussions Many studies find an association between prior concussions and worse clinical outcomes. A greater number of studies have not found that prior concussions are associated with worse outcomes. Still likely a significant modifier because: Prior history of concussion is a risk factor for future concussions (Abrahams et al., 2012) Prior concussions are associated with greater pre-injury symptom reporting in some athletes (Abrahams et al., 2012; Iverson et al., 2015) Some large-scale studies show an association between concussion history and increased risk for symptoms lasting more than four weeks (e.g., Castile et al., 2012; Miller et al., 2016; Wasserman et al., 2016)

68 Health History Mental Health History Almost all studies suggest worse outcome. ADHD History Almost all studies do not suggest worse outcome. Learning Disability History Almost all studies do not suggest worse outcome. Personal Migraine History Almost all studies do not suggest worse outcome. One large well-designed study reported that a personal history of migraine is associated with risk for symptoms lasting more than four weeks (Zemek et al., 2016).

69 Injury Severity Loss of consciousness Some studies report positive findings that LOC is associated with worse outcomes, but most do not find an association with LOC. Post-traumatic amnesia/ amnesia Mixed, but more studies do not find association with worse outcomes. Retrograde amnesia Less frequently studied. Consistently associated with worse outcome in the first 10 days following injury.

70 Greater Acute Symptoms Yes Chermann (2014) ; Brown (2014) ; Hang (2015) ; Resch (2015) ; Castile (2011) ; Chrisman (2013) ; Zuckerman (2016) ; Meehan (2014) ; Meehan (2013) ; McCrea (2013) ; Benson (2011) ; Greenhill (2016) ; Makdissi (2013) ; Nelson (2016) ; Merritt (2015) ; Prichep (2013) ; Heyer (2016) ; Iverson (2007) No Barlow (2011) ; Moor (2015) ; Morgan (2015)

71 Acute Clinical Findings Acute/sub-acute symptom burden Associated with worse outcome Of all possible predictors, it was the most consistently associated with worse outcome. Acute/Subacute Post-injury Headaches Almost all studies suggest worse outcome.

72 Conclusions Strongest/most consistent predictor of slow recovery: more severe acute/subacute symptoms after injury. Those with preinjury mental health problems or migraines seem to be at a slightly increased risk for persistent symptoms. Those with ADHD/learning disabilities do not seem to be at an increased risk for persistent symptoms. Teenagers may be at the highest risk for persistent symptoms. Girls have a higher likelihood of prolonged recovery.

73 Recovery from Mild Traumatic Brain Injury in Civilians

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75 Subjects Tampere University Hospital, ED, Finland 49 patients with MTBIs No history of medical, mental health, or substance abuse problems All underwent MRI for clinical or research purposes: 24.5% Abnormal First Research Visit, SCAT2; M = 30.4 hours (SD = 27.3) and all within 5 days

76 One Month Outcome ICD-10 Postconcussional Syndrome, Mild in Severity = 23% of the MTBI sample 12% of the Community Control sample with remote ankle injuries

77 Acute Predictors of One-Month Post-Concussion Syndrome Loss of Consciousness: No Retrograde Amnesia: No Post-Traumatic Amnesia: No Abnormal MRI: No High Symptom Reporting in first few days: Yes Acute Psychological Distress: Yes (strongest predictor)

78 Most people recover functionally within 3 months following injury.

79 Examples of Neuropsychology Meta-Analyses

80 Most people return to work within 3 months. Return to work rates are highly variable across studies and are likely influenced by many factors separate from the injury to the brain.

81 Are there Microstructural White Matter Abnormalities? Cannot see on standard CT or MRI If present, are these abnormalities associated with persistent symptoms?

82 Why is White Matter Vulnerable? 1. Anatomy 2. Physics & Forces

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85 Traumatic Axonal Injury In general, unless exposed to very serious forces, axons do not shear at the point of injury. Stretch causes a temporary deformation of an axon that gradually returns to the original orientation and morphology even though internal damage might have been sustained

86 Traumatic Axonal Injury In summary, a single acceleration/deceleration event might result in: (a) no apparent change in structure or function, (b) functional or metabolic change, (c) eventual structural change in the axon, or (d) frank separation of the axon into proximal and distal segments. These outcomes are dependent on the force applied to the brain.

87 Diffusion Tensor Imaging (DTI) DTI measures both the directionality and the magnitude of water diffusion in white matter. Often considered proxy measures for the microstructural integrity of white matter in the human brain.

88 Region of Interest Common Analyses Tract-Based Spatial Statistics Tractography Emerging: Multivariate ROIs (Atlas-Based Approach)

89 Review of 50 DTI Studies in MTBI (Wäljas et al., 2014) Findings Yes No Not Reported Abnormal White Matter 88% 12% --- Correlated with: Return to Work 0% 2% 98% Post-Concussion Symptoms 12% 6% 82% Cognitive Functioning 54% 8% 38% Mental Health Problems 6% 8% 86%

90 DTI is interesting and has advanced knowledge in TBI. Remember, however, white matter abnormalities are present in many conditions even in healthy adults. And many of these conditions are present before injury or sometimes in the years after injury.

91 ADHD

92 Learning Disability/Dyslexia

93 Depression

94 Hypertension

95 Non-Traumatic TMJ Disorder

96 Migraine

97 Marijuana & Alcohol Abuse in Adolescents

98 More Bad News for Smokers These data suggest that smoking affects the microstructural integrity of cerebral white matter and support previous data that smoking is associated with impaired cognition.

99 CONCLUSIONS: We document lower cognitive performance and reductions in brain structural integrity among adolescents with Metabolic Syndrome, thus suggesting that even relatively short-term impairments in metabolism, in the absence of clinically manifest vascular disease, may give rise to brain complications.

100 Isolated White Matter Hyperintensities in Healthy Adults

101 Examining DTI in a Civilian Biopsychosocial Outcome from MTBI Study

102 Prospective Study of One Year Outcome from Civilian MTBI Tampere, Finland Recruited from the Emergency Department Imaging and Clinical Assessment at 3-4 Weeks Clinical Assessment at 1 Year Wäljas M, Iverson GL, Lange RT, Hakulinen U, Dastidar P, Huhtala H, Liimatainen S, Hartikainen K, Öhman J. A prospective biopsychosocial study of the persistent postconcussion symptoms following mild traumatic brain injury. J Neurotrauma Apr 15;32(8):

103 Prospective Outcome Study on MTBI (N = 126 at one month and 103 at one year) Wäljas et al. (2015) ICD-10 Mild Post-Concussion Syndrome MTBI One Month: 59% MTBI One Year: 38% Healthy Controls: 31%

104 Abnormal Structural MRI and/or DTI Variable from days to weeks post injury (Average = 1 month) Abnormal structural MRI = 12.1% Diffusion Tensor Imaging (DTI): Multifocal areas of unusual white matter MTBI Group = 50.7% Healthy Controls =12.4%

105 Predictors of the Post-Concussion Syndrome One Month: pre-injury mental health problems and bodily injuries. Being symptomatic at one month was a significant predictor of being symptomatic at one year. Depression was significantly related to PCS at both one month and one year.

106 Structural MRI abnormalities and microstructural white matter findings (DTI) were not significantly associated with greater post-concussion symptom reporting, and they were not significant predictors of PCS at onemonth or one-year following injury.

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108 Participants and Procedures 62 adults with MTBIs 31 complicated and 31 uncomplicated Neurocognitive testing (many tests) Symptom Ratings British Columbia Postconcussion Symptom Inventory Beck Depression Inventory-Second Edition Beck Anxiety Inventory DTI on a 3T MRI scanner approximately 6-8 weeks post injury.

109 Reduced FA in body and genu of the corpus callosum and the left frontal corona radiata and Increased radial diffusivity in genu of the corpus callosum and left frontal corona radiata

110 No Significant Differences Symptoms Broad range of neuropsychological tests

111 Biopsychosocial Model Continued: Persistent Symptoms Depression, Anxiety, Traumatic Stress, Chronic Pain, and the Post-Concussion Syndrome

112 Many clinical conditions are associated with symptoms. Vestibular Injury Depression Post-Traumatic Stress Pre-injury health and mental health is important. Brain Injury Cognitive Difficulty & PCS Symptoms Anxiety/ Cognitive Hypochondriasis Personality characteristics and socialenvironmental factors can be important. Chronic Headaches Chronic Bodily Pain Insomnia/ Sleep Disturbance Life Stress A biopsychosocial model is most appropriate.

113 Civilians who sustain an MTBI are at substantially increased risk for experiencing depression in the first year following injury. The etiology of depression is likely individualized and multifactorial.

114 Post-concussion-like symptoms can be mimicked or magnified by traumatic stress, anxiety, pain, depression, sleep disturbance, and social psychological factors at any point in the recovery trajectory.

115 Mild TBI Chronic Pain Depression Symptoms Insomnia Anxiety Life stressors Traumatic stress 115

116 Individuals who are symptomatic at 3-6 months are at considerable risk for being symptomatic at 1-2 years post injury.

117 Factors Affecting Recovery Time General health Previous concussions / neurological problems Pre-injury mental health problems Mechanism of Injury: MVA vs. Sports Acute Psychological Distress in the first few days Severity of concussion symptoms in the first week Post-Acute co-occurring conditions (depression, PTSD, chronic pain) Personality Characteristics Motivation Litigation

118 Conclusions Mild TBIs are heterogeneous. Most athletes appear to recover within one month and most civilians appear to recover within three months. Macroscopic intracranial lesions are not strongly related to outcome. Microstructural differences as measured by DTI are not strongly related to outcome. A biopsychosocial model helps conceptualize good and poor outcome in individual cases.

119 Careful and Comprehensive Assessment = Targets for Treatment and Rehabilitation

120 Reduce Symptoms; Improve Function Sleep Disturbance Stress & Anxiety Depression Headaches Deconditioning Bodily Pain

121 Treat what you can treat. Vestibular Injury Depression Post-Traumatic Stress Success begets success. Brain Injury Cognitive Difficulty & PCS Symptoms Anxiety/ Cognitive Hypochondriasis Chronic Headaches Life Stress Reduce symptoms. Chronic Bodily Pain Insomnia/ Sleep Disturbance Improve functioning.

122 Thank You