mild traumatic brain injury across the lifespan · 2017. 11. 20. · demographic variables...
TRANSCRIPT
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
1st Nordic Neurotrauma Conference
Lund, Sweden
November 13, 2017
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)
Other Disclosures
• Speaker honorariums and travel expenses for
conferences and meetings
• Independent practice in forensic
neuropsychology, including athletes
Mild Traumatic Brain Injuries
are Not Created Equally
Spectrum of MTBI
Extremely Mild Structural Damage
(Transient) (Permanent)
Continuum of Pathophysiology
Minor Major Neurometablic & Neurometabolic Pathoanatomical
(e.g., Contusion)
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
First
Author
Year
Number
Scanned
GCS
Scores
%
Abnormal
Livingston 1991 111 14-15 14
Stein 1992 1,538 13-15 17.2
Jeret 1993 702 15 9.4
Moran 1994 96 13-15 8.3
Borczuk 1995 1,448 13-15 8.2
Iverson 2000 912 13-15 15.8 Thiruppathy 2000 912 13-15 15.8
Stiell 2005 2,171 13-15 12.1
Stiell 2005 1,822 15 8.0
Ono 2007 1,064 14-15 4.7
Saboori 2007 682 15 6.7
Emergency Department Cohort
• Tampere University Hospital, Tampere, Finland
• August 2010-July 2012
• 3,023 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)
Tampere ED Mild Head Trauma Cohort
Rates of Complicated MTBI Isokuortti et al. (in press)
10.1
40.7
52
0
10
20
30
40
50
60
GCS=15 GCS=14 GCS=13
Percentage Abnormal Stratified by GCS
Acute (red) and Pre-Existing Lesions (black) Stratified by
Age Group in Suspected or Confirmed MTBI (N=2,766)
4.9%
3.0% 9.9%
7.3% 12.2% 11.4% 22.2%
20.1% 18.6% 17.7%
1.2 %
4.2 %
11.5 %
23.5 %
29.3 % 32.2 %
48.7 %
56.9 %
66.0 %
78.9 %
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
20-29 30-39 40-49 50-54 55-59 60-64 65-69 70-74 75-79 80+
Acute intracranial lesion Pre-existing intracranial abnormality
Are intracranial abnormalities
related to clinical outcomes?
See Panenka et al. (2015) for a
Review (Table 1)
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
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.
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).
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
Continuum of
Biological & Psychological
Vulnerability
Extremely Hardy/Resilient Extremely Vulnerable
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.
Pre-Existing Health Problems
Possible Vulnerability Factor
Emergency Department Cohort
• Tampere University Hospital, Tampere, Finland
• August 2010-July 2012
• 3,023 patients presenting to ED and underwent
head CT
• Average Age: 56.4, 50% are between 34 and 77
• Isokuortti et al. (in press)
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%
There is no simple, reasonably
explanatory model for good or poor
outcome
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
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
Cognitive
Diminishment
Mental Health Problems
Social
Psychological
Factors
Insomnia
Chronic Headaches
or Bodily Pain
Depression
Traumatic
Axonal Injury
Altered
Neurotransmitter
Systems
Expectations
Diagnosis Threat
Nocebo Effect
Lifestyle & Family
Dynamics Changes
Anger/Bitterness
Justification/Entitlement
Litigation Stress
Anxiety/Stress/Worry
PTSD
Biopsychosocial Model for Poor Outcome
Copyright © 2010, Grant Iverson, Ph.D.
Pre-Injury Factors
Recovery from Concussion in
Sports
By definition, a sport-related
concussion is a mild traumatic brain
injury.
By consensus, sport-related
concussions are characterized by
normal structural neuroimaging.
Is sport-related concussion a benign
injury?
Results from meta-analyses
Adverse Effects of Sport Concussion on Cognition
Pathophysiology
• Complex interwoven cellular and vascular changes
• Multilayered Neurometabolic Cascade
• Under certain circumstances, cells degenerate and die
Primary Mechanisms
• Ionic shifts
• Abnormal energy metabolism
• Diminished cerebral blood flow
• Impaired neurotransmission
Fortunately, the brain undergoes
dynamic restoration
Assessment Timeline
Sideline Post-
Game
24 Hours
First Week
Second Week
Third Week
At Risk!
Recovery Time in Athletes
Some evidence that biological recovery
might take longer than clinical recovery
in some athletes.
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)
Recovery Curve (N = 134)
91%
46%
Days Post Injury
Recovery Curves (N = 134)
Days Post Injury
94%
84%
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.
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
Predictors of Clinical Recovery and Persistent
Symptoms in Children and Adolescents
Multi-Center Canadian Study
5P Sites
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
Patient Population
Inclusion Criteria
• 5 - 17.9 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
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)
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
Total Sample (Derivation and
Validation Cohorts) 30-33%
Demographic Variables Mechanism of Injury Ages 5-7 17.9 Sports or Recreational Injury 30.3 Ages 8-12 26.3** Non-Sports-Related Injury or Fall 28.2
Ages 13-17 39.9** 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=15 29.7 No Prior Concussions 28.4 GCS=14 (only 19 subjects) 36.8 1 or More Prior Concussions 35.1* Loss of Consciousness 36.2*
Prior Concussion with
Symptoms ≥ 1 week 46.1** Appears Dazed and Confused 33.5*
Physician Diagnosed
Migraine History 42.6** Appears Confused About Events 34.2*
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**
Results
• 45 candidate variables with univariate
association with primary outcome
– Acceptable inter-rater agreement (K>0.6)
• Forward stepwise, binary logistic regression
– Pin=0.05, Pout=0.10
5P Prediction Model
Covariate
aOR
95% CI P Value
Lower Upper
Age group
5 to 7 0.000
8 to 12 1.54 1.09 2.19
13 to 18 2.31 1.62 3.32
Sex Male 0.000
Female 2.24 1.78 2.82
Longest symptom
duration
No prior concussion
or <1 week 0.011
1+ week 1.53 1.10 2.13
Personal history of
migraine
No 0.001
Yes 1.73 1.24 2.43
Answers questions
slowly
No 0.008
Yes 1.37 1.08 1.74
Tandem stance
0-3 0.022
4+ or unable 1.31 1.04 1.66
Headache No 0.013
Yes 1.66 1.11 2.48
Sensitivity to noise No 0.002
Yes 1.47 1.15 1.87
Fatigue No 0.000
Yes 1.84 1.37 2.46
5P Prediction Model
Risk Factor Categories Points
Age Group 5 to 7
8 to 12
13 to 18
0
1
2
Sex Male
Female
0
2
Longest Symptom Duration No Prior or <1 week
1+ week
0
1
Personal History of Migraine No
Yes
0
1
Answers Questions Slowly No
Yes
0
1
Tandem Stance 0-3
4+, or unable to do test
0
1
Headache No
Yes
0
1
Sensitivity to Noise No
Yes
0
1
Fatigue No
Yes
0
2
5P Points: Risk
Point total
Estimate
of Risk
Lower
95% CI
Upper
95% CI
Observed %
with PCS-4 Weeks
0 0.04 0.02 0.07 0/6 (0%)
1 0.06 0.04 0.09 6/37 (16%)
2 0.08 0.06 0.13 11/98 (11%)
3 0.12 0.08 0.18 15/156 (10%)
4 0.16 0.12 0.22 41/239 (17%)
5 0.22 0.17 0.30 71/289 (25%)
6 0.30 0.23 0.38 90/299 (30%)
7 0.38 0.30 0.47 96/243 (40%)
8 0.48 0.39 0.57 80/172 (47%)
9 0.57 0.48 0.66 58/103 (56%)
10 0.66 0.57 0.74 30/43 (70%)
11 0.74 0.66 0.82 9/13 (69%)
12 0.81 0.75 0.88 3/3 (100%)
Predictors of clinical recovery from
concussion: a systematic review
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.
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
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).
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 2016
2. Examined clinical recovery
from concussion
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).
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) 17 27
History of Concussions 20 21
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
Younger Age
Yes Chermann (2014) 25741414; Field (2003) 12756388; Terwilliger (2016) 26421452; Covassin (2012) 22539534; Majerske (2008) 18523563; Pellman (2006) 16462480; Zuckerman (2012) 23227435
No Lau (2012) 21841522; Hang (2015) 26430968; McDevett (2015) 26502998; Nelson (2016) 26974186; Asplund (2004) 15523205; Chrisman (2013) 23252433; Vargas (2015) 25643158; Nelson (2016) 26974186; Morgan 2015 25745949; Meehan 2010 20716683; Meehan (2013), 23628374; McCrea 2013, 23058235; Lee (2013) 24063601; Baker (2015) 26084537; Greenhill (2016) 27005467; Nelson (2016) 27164666; Corwin (2014) 25262302; Preiss-Farzenagan (2009) 19627902; Heyer (2016) 27056449; Kontos (2012) 22503738; Kriz (2016) 26781190; Miller (2016) 26684762; Ellis 2015 26359916
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%.
Female Sex
Yes Baker (2016) 26378093; Berz 2013 23703518; Henry 2016 26445375; Kostyun 2015 25553213; Bock 2015; 26243160; Zuckerman 2014 24206343; Covassin 2012 22539534; Covassin 2013 24197616; Covassin 2016 26950073; Majerske 2008 18523563; Colvin 2009 19460813; Eisenberg 2013 23753087; Ellis 2015 26359916; Miller 2016 26684762; Preiss-Farzenagan (2009) 19627902 (in adults); Heyer (2016) 27056449
No Chermann 2014 25741414; Moor 2015 25883871; Hang 2015 26430968; Nelson 2016 26974186; Mayers 2013 23686028; Asplund 2004 15523205; Black 2016 26862834; Chrisman 2013 23252433; Zuckerman 2016 27032916; Zuckerman 2012 23030348; Vargas 2015 25643158; Terwilliger 2016 26421452; Morgan 2015 25745949; Frommer 2011 21214354; Baker 2015 26084537; McDevett 2015 26502998; Nelson (2016) 27164666; Lax (2015) 26362811; Ono (2016) 26672026; Preiss-Farzenagan (2009) 19627902 (in children/adolescents); Covassin (2007) 17762747; Kontos (2012) 22503738; Wasserman (2015) 26546304; Yang (2015) 25649775
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.
Prior Concussions
Yes Hang (2015) 26430968; Nelson (2016) 26974186; Guskiewicz (2003) 14625331; Castile (2011) 22144000; Chrisman (2013) 23252433 (football only); Zuckerman (2016) 27032916; Morgan (2015) 25745949; Covassin (2013) 23959963; Kerr (2014) 26535354; Colvin (2009) 19460813; Iverson (2006) 16537266; Miller (2016) 26684762; Wasserman (2015) 26546304; Slobounov (2007) 17762746; Benson (2011) 21502355; Corwin (2014) 25262302
No Asken (2016) 27111584; Barlow (2011) 21904694; Moor (2015) 25883871; Brown (2014) 24394679; Lau (2012) 21841522; Mautner (2015) 25353721; McDevett (2015) 26502998; Vargas (2015) 25643158; Terwilliger (2016) 26421452; McCrea (2013) 23058235; Erlanger (2003) 12650417; Majerske (2008) 18523563; Baker (2015) 26084537; Ellis (2015) 26359916; Field (2003) 12756388; Makdissi (2013) 23479491; Pellman (2006) 16462480; Gibson (2013) 23758286; Heyer (2016) 27056449; Miller (2016) 26684762; Chrisman (2013) 23252433 (non-football only)
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)
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).
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.
Greater Acute Symptoms
Yes Chermann (2014) 25741414; Brown (2014) 24394679; Hang (2015) 26430968; Resch (2015) 26565424; Castile (2011) 22144000; Chrisman (2013) 23252433; Zuckerman (2016) 27032916; Meehan (2014) 25381296; Meehan (2013) 23628374; McCrea (2013) 23058235; Benson (2011) 21502355; Greenhill (2016) 27005467; Makdissi (2013) 23479491; Nelson (2016) 27164666; Merritt (2015) 25685959; Prichep (2013) 22588360; Heyer (2016) 27056449; Iverson (2007) 17304003
No Barlow (2011) 21904694; Moor (2015) 25883871; Morgan (2015) 25745949
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.
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.
Recovery from Mild Traumatic Brain Injury
in Civilians
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
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
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)
Most people recover functionally within 3 months
following injury.
Examples of Neuropsychology Meta-Analyses
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.
Are there Microstructural White Matter
Abnormalities?
Cannot see on standard CT or MRI
If present, are these abnormalities associated with
persistent symptoms?
Why is White Matter
Vulnerable?
1. Anatomy
2. Physics & Forces
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
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.
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.
Common Analyses
• Region of Interest
• Tract-Based Spatial Statistics
• Tractography
• Emerging: Multivariate ROIs (Atlas-Based Approach)
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%
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.
ADHD
Learning Disability/Dyslexia
Depression
Hypertension
Non-Traumatic TMJ Disorder
Migraine
Marijuana & Alcohol Abuse in
Adolescents
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.
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.
Isolated White Matter Hyperintensities
in Healthy Adults
Examining DTI in a Civilian
Biopsychosocial Outcome from
MTBI Study
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 post-concussion symptoms following mild traumatic brain injury. J Neurotrauma. 2015 Apr 15;32(8):534-47.
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%
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%
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.
• 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 one-
month or one-year following injury.
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.
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
No Significant Differences
• Symptoms
• Broad range of neuropsychological tests
Biopsychosocial Model Continued:
Persistent Symptoms
Depression, Anxiety, Traumatic Stress,
Chronic Pain, and the Post-Concussion Syndrome
Vestibular
Injury
Brain
Injury
Chronic
Headaches
Chronic
Bodily
Pain
Insomnia/
Sleep
Disturbance
Life Stress
Anxiety/
Cognitive
Hypochondriasis
Post-Traumatic
Stress
Depression
Cognitive
Difficulty
& PCS
Symptoms
Many clinical
conditions are
associated with
symptoms.
Pre-injury
health and
mental
health is
important.
Personality
characteristics
and social-
environmental
factors can be
important.
A
biopsychosocial
model is most
appropriate.
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.
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
Symptoms
Mild TBI
Depression
Anxiety
Traumatic stress
Life stressors
Insomnia
Chronic
Pain
Individuals who are symptomatic at 3-6 months are
at considerable risk for being symptomatic at 1-2
years post injury.
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
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.
Careful and Comprehensive Assessment
= Targets for Treatment and
Rehabilitation
Reduce Symptoms; Improve Function
• Sleep Disturbance
• Stress & Anxiety
• Depression
• Deconditioning
• Headaches
• Bodily Pain
Vestibular
Injury
Brain
Injury
Chronic
Headaches
Chronic
Bodily
Pain
Insomnia/
Sleep
Disturbance
Life Stress
Anxiety/
Cognitive
Hypochondriasis
Post-Traumatic
Stress
Depression
Cognitive
Difficulty
& PCS
Symptoms
Treat
what you
can treat.
Success
begets
success.
Reduce
symptoms.
Improve
functioning.
Thank You