Download The Mild Traumatic Brain Injury Disability Debate

Issues in MTBI
Ford Vox, MD
Staff Physician, Shepherd Center, Brain Injury Rehabilitation Program
Adjunct Assistant Professor, Emory University School of Medicine
Today's Topics

The debate: mTBI/Concussion as a major
cause of disability

Pro / Con
Traumatically induced physiological
disruption of brain function, as
manifested by at least one of the
Following:
1) Any period of loss of consciousness.
2) Any loss of memory for events
immediately before or after the
Accident.
3) Any alteration in mental state
at the time of the accident
(eg, feeling dazed, disoriented,
or confused).
4) Focal neurological deficit(s) that
may or may not be transient.
AND
*Loss of consciousness of
approximately 30minutes or less.
*After 30minutes, an initial Glasgow
Coma Scale (GCS) score of 13–15.
* and posttraumatic amnesia (PTA)
not greater than 24 hours.
ACRM Definition
of MTBI
1) Direct blow to the head, face, neck, or
elsewhere on the body with an "impulsive" force
transmitted to the head
2) Rapid onset of short-lived impairment of
neurological function that resolves
spontaneously.
3) Acute clinical symptoms primarily reflecting
functional disturbance versus structural injury.
4) Graded set of clinical syndromes that may or
may not involve loss of consciousness (LOC),
with resolution of clinical and cognitive symptoms
generally following a sequential course.
5) Typically grossly normal structural
neuroimaging studies.
International
Conference
on Concussion
in Sport
MTBI Pathophysiology: DAI
Axonal stretching
Pathological excitatory neurotransmitter release.
Disruption of ion gradients
Metabolic mismatch / vulnerability
Increased glucose demand to feed Na/K pump
No change in CBF
Normalization: days to weeks.
Giza & Hovda 2001
Postconcussive Syndrome
Cara Camiolo Reddy's organization of PCS symptoms
Cognition
Balance
Symptoms
Impairment on any
neurocognitive
domain (such as
Neuropsych exam
or computer-based
testing)
Impairment on any
balance measure,
such as BESS,
Balance tests on
SCAT2, Biodex
Any subjective
symptoms
experienced by the
athelete (can
include
cognition/balance/
psychological, etc)
Common grouping of PCS symptoms in sports medicine
Somatic
Neurological
Psychological
Headaches, neck
pain, dizziness,
sleep disorders,
sensory sensitivies
Cognitive
symptoms:
impaired
concentration,
poor memory,
distractability
Depression,
anxiety, PTSD
Michael Alexander's grouping of PCS symptoms
Proposition:
MTBI Disability is Overblown
Proposition:
MTBI is a
Major Cause
of Disability
The media has
gone overboard.
An Ordinary Football Game, Then a Player Dies
October 19, 2011
“Concussion” mentioned 5X in the article
Subdural hematoma = Not a concussion
An Ordinary Football Game, Then a Player Dies
October 19, 2011
“As those who play and coach football learn new ways to
improve safety — through training, medical response and
equipment — sometimes they are left to contemplate this:
brains remain vulnerable, and even the most ordinary
collisions on the field can kill.”
The media is
right to alarm us
Point: Media right to alarm
Alarming numbers:
1.7 Million/year (CDC ER data)
1.4 - 3.8 Million/year
(Comprehensive)
Need for public ed: belief LOC required
still widely held.
Point: Media right to alarm
Catastrophic injury: Second Impact Syndrome
Teenagers
Malignant brain swelling
Second hit during symptomatic period
94 Cases from 1989-2002
Boden AJSM 2007
- 75 SDH, 10 SDH with diffuse swelling, 5 diffuse swelling,
4 AVM or aneurysm
- 92 cases high school (2 college)
- 59% previous concussion(s).
- 71% same season as death.
- 39% evidence of residual symptoms from prior
concussion.
PCS treatment
suggests
a heterogeneous
condition
Point: MTBI treatment suggests
a heterogeneous condition



Just as there is no unique PCS symptom,
there is no unique treatment.
We tackle headaches, dizziness, sleep,
etc, in their own treatment algorithms
Powerful treatment: Education: natural
history, sleep hygiene, coping strategies,
stress management, avoidance
ETOH/drugs.
Ponsford. Impact of early intervention on outcome following mild head injury in adults.
J Neurol Neurosurg Psychiatry. 2002 Sep;73(3):330-2.
PCS treatment
must be patientcentered
Point: PCS treatment should be
patient-centered
Symptoms complexes appear tied together.
Require interdisciplinary treatment.
Holistic approach.
CASE: A 34-year-old male MTBI patient complained of
problems with attention and concentration. The medical
records included documentation of cervical pain. When asked
about his neck pain, the patient explained that turning his
head during the night resulted in sharp pain that woke him up
multiple times each night. At the time of the evaluation, this
sleep disturbance had persisted for 4 months. His reduced
mental stamina resulted in significant problems at work and
he was placed on sick leave 3 weeks earlier. The combination
of pain and reduced concentration resulted in an elevated
stress level that further compounded the disordered sleep
and pain cycle. Jogging was too painful, and thus his
premorbid coping strategy for stress management was
unavailable. The unrelenting high levels of stress resulted in
tension headaches that originated in the back of his head and
exacerbated his neck pain. This dysfunctional loop was selfreinforcing and not responsive to various medications that
were prescribed.
Ruff 2005
Even the experts
can't agree
Point: Even the experts can't agree

Clinical Practice Guidelines are of poor quality
 Rigor of development
 Editorial independence
Little guidance for cases that do not remit
spontaneously

Quality of clinical practice guidelines for persons who have sustained mild traumatic brain injury.
Brain Injury, July 2011; 25(7–8): 742–751
Need to study
the right signal
Point: Need to study right signal
Can't lump together normals and the “Miserable
Minority”
One group says little about the other.
Studies should focus on PCS population, not
MTBI in general.
Prediction of PCS should be the goal.
Current factors crude, inflexible (age, gender, previous
concussions, psych history, migraine history)
Postconcussion
syndrome is
meaningless
Point: PCS is meaningless
The acute symptoms and chronic symptoms are
reflective of two distinct disorders
 Early symptoms have specific treatments
(neurologic or psychologic). Early symptoms
resolve.
 For patients that experience chronic symptoms,
psychological factors dominate.
 The symptoms of chronic PCS can be seen
after any trauma. There is no need for a TBI.

Point: PCS is meaningless
PCS prevalence after MTBI ranges from 10
to 64% depending on criteria used (ICD-10,
DSM-IV, Rivermead)
 Studies of incidence rarely account for
preinjury factors or include a proper
comparison group
 Once numbers of everyone “dazed and
confused” included, and “complicated” MTBI
excluded, incidence drops to around 5%.

Point: PCS is meaningless

PCS symptoms overlap with:
 Chronic pain
 Depression
 PTSD
 Healthy people
PCS is a label that serves mask other conditions
the clinician might diagnose and treat.

Symptom checklist given to 1,116 Kaiser Permanente patients.
Fox DD, Lees-Haley PR, Earnest K, Dolezal-Wood S.
Base rates of postconcussive symptoms in health maintenance organization patients and controls.
Neuropsychology 1995;9:606-611.
104 healthy volunteers in Vancouver.
All had no history of psychological disorder, neurological disorder, or substance abuse.
All given the British Columbia Postconcussion Symptom Inventory-Short Form
Symptoms rated on Likert scale of intensity
79.6% met DSM-IV criteria, 72.1% met ICD-10 criteria
Iverson GL, Lange RT. Examination of "postconcussion-like" symptoms in a healthy sample.
Appl Neuropsychol 10:137–144, 2003
Memory Impairment: A Symptom of Life
Things We Normally Forget
"Symptom"
of People
Forgets telephone numbers
Forgets people's names
Forgets where car was parked
Loses car keys
Forgets groceries
Forgets why they entered a room
Forgets directions
Forgets appointment dales
Forgets store location in shopping center 20%
Loses items around the house
Loses wallet or pocketbook
Forgets content of daily conversations
Percent
58%
48%
32%
31%
28%
27%
24%
20%
17%
17%
17%
At least this part of
Rick Perry is normal.
Athletic MTBI
story casts
doubt on general
population's
experience
Point: Too much variance with
athletic MTBI

80% of athletes have no symptoms at 3 weeks.
Up to 80% of general population reports
symptoms at 3 MONTHS.

Can an athlete's physiology really be so
different?

Collins M, Lovell MR, Iverson GL, Ide T, Maroon J. Examining concussion
rates and return to play in high school football players wearing
newer helmet technology: A three-year prospective cohort study. Neurosurgery
2006;58:275-286.
Sigurdardottir S, Andelic N, Roe C, et al. Post-concussion symptoms
after traumatic brain injury at 3 and 12 months post-injury: A prospective
study. Brain Inj 2009;23:489-497.
Point: Too much variance with
athletic MTBI
No similar dichotomy in pain/disability/recovery
rates with musculoskeletal injuries.
 Torn ACL recovery similar in sports and general
population


Massive fudge factor – non-biological
Athletes with long recovery times have early
fogginess, memory deficit, or dizziness.
 General population: early anxiety predictive.

Dischinger PC, Rybe GE, Kufera JA, Auman KM. Early predictors of postconcussive
syndrome in a population of trauma patients with mild traumatic brain injury. J Trauma
2009;66:289-296.
Athletes have
major
advantages in
recovery from
MTBI
Point: Athletic Advantage
Sports concussions:
Population is more homogeneous: younger,
healthier, more motivated.
Circumstances:
Acute stress reaction.
Role of anticipation of the hit, mental
readiness
Non-athletic MTBI's: assaults, accidents,
traumatic situations.
Expectation
becomes
etiology
Point: Expectation becomes etiology
Control: 223 volunteers, no history of head
injury, and didn't know anyone with head injury.

Comparison: 100 MTBI patients 1 to 7 years out
referred to neuropsychology.

Both groups asked to estimate the presence of
30 symptoms before and after an imaginary
(control) or real (comparison) head injury.

Mittenberg W, DiGiulio DV, Perrin S, Bass AE. Symptoms following
mild head injury: Expectation as aetiology. J Neurol Neurosurg Psychiatry
1992;55:200-204.
Little difference between what we expect to experience, and what we do
 When symptoms rank ordered, correlation is 0.82.
 Anticipated symptoms explain 67% of the variance in incidence.

MTBI patients underestimate normal rate of symptoms
 Pattern suggests misattribution of symptoms to the MTBI.

Point: Expectation becomes etiology
Mittenberg Pathway:
1) Activation of typical symptom expectancies when mild head
injury occurs. The concussion is inherently stressful and
also normally induces autonomic/emotional arousal
2) Symptom expectancies bias selective attention to internal
state
3) Attentional bias and arousal augment symptom perception
4) which then elicits additional autonomic/emotional
response, reinforcing expectations.
Medical Student's Disease
70% of medical students express concern about their own symptoms
and sensations matching diseases they have learned about.
On spectrum of hypochondriasis
Point: Expectation becomes etiology
Prospective cohort study of 73 subjects
interviewed at week 1-3 post MTBI and again at
month 3.
 At first assessment, given Illness Perception
Questionnaire-R:

aetiology of
it will
social
Identity: Beliefs concerning the illness label or diagnosis and associated
symptoms.
Cause: Beliefs concerning the factors or conditions implicated in the
the illness.
Timeline: Beliefs concerning the expected duration of the illness—whether
be acute (such as influenza) or chronic (such as diabetes)
Consequences: Beliefs concerning the effects an illness has on physical,
and psychological well-being.
Control/cure: Beliefs concerning the extent to which the illness can be
controlled or cured.
Whittaker R, Kemp S, House A: Illness perceptions and outcome in mild head injury:
a longitudinal study. J Neurol Neurosurg Psychiatry 78:644–646, 2007
Point: Expectation becomes etiology
All were symptomatic at beginning.
 18 (25%) diagnosed with PCS at followup.
 Severity of injury (LOC, PTA, GCS) not
associated with outcome.
 Psychological distress at baseline not
predictive of outcome.
 Severity of PCS symptoms at baseline not
predictive of outcome.
 Worse Illness perception at baseline (Timeline,
Consequences) allowed prediction of 80% of
the cases of PCS.

Whittaker R, Kemp S, House A: Illness perceptions and outcome in mild head injury:
a longitudinal study. J Neurol Neurosurg Psychiatry 78:644–646, 2007
Psychology is
biology
Point: Psychology is biology
Stress:
Causes dendritic hypertrophy
 Increases sensitivity to input in the
amygdala
 Remodels dendrites of CA3
pyramidal neurons
 Reduces the numbers of
synapses on neurons in
hippocampus
 Inhibits neurogenesis in the
dentate gyrus
 Modulates expression of genes
involved in neuronal differentiation
and/or structural remodeling

Point: Psychology is biology
An adult “second impact” syndrome?
First hit: cognitive reserve, social stressors, personality,
somaticization, genetics.
Second hit: The MTBI
Point: Psychology is biology



135 complicated mild to severe TBI patients
completed Sickness Impact Profile
Early depression not predictive of more injuryrelated impairment
Rather more perceived impairment = more late
depression.
Pagulayan et. al. Functional limitations and depression after traumatic brain injury:
examination of the temporal relationship. Arch Phys Med Rehabil. 2008 Oct;89(10):1887-92.
Point: Psychology is biology

Expectation as etiology:


Suggestion is powerful but...
Remember, just because you expect your thumb to
hurt after you hit it with a hammer, doesn't mean
your thumb would have felt fine had you not
expected pain.
Litigation has a
massive
influence on
PCS
Point: Litigation's massive influence
Hindsight bias, compared to general medical
population, even worse.
Personal injury litigants rate their premorbid work
or school status, marriage, and relationships with
their children as better than controls.
Litigation is
stressful
Point: Litigation is stressful
Patients in litigation consistently report more
symptoms.
Association does not equal causation.
Litigation is stressful, activating hypothalamicpituitary-adrenal axis.
Patients with more symptoms may be more prone
to litigate.
Neuropsychological tests can help tease out
malingerers (About 30% with noncredible test
results, and 25% with poor effort).
Much of PCS is a
manifestation of
PTSD
Point: Too Much PTSD Overlap
PTSD Includes:
1) Cognitive: impaired concentration, learning, and
decision making, memory impairment, forgetfulness,
confusion, and slower processing speed
2) Behavioral: irritability, increased relational conflict,
social withdrawal, alienation, reduced relational intimacy,
and impaired work and school performance
3) Somatic: exhaustion, insomnia, headaches, startle
response, hyperarousal, and cardiovascular,
gastrointestinal, and musculoskeletal disorders
Point: Too Much PTSD Overlap
DSM-IV: One intrusion symptom. Three avoidance
symptoms. Two hyperarousal symptoms.
The 4 Major Criteria for diagnosis of PTSD: Overlap as well
Point: Too Much PTSD Overlap
2,525 soldiers surveyed. Screened for MTBI, PTSD, Depression.
Multivariate analyses performed:
15% had a MTBI. This population had much higher rates of physical and mental
health problems.
>40% of soldiers with LOC had PTSD.
PTSD and Depression (not MTBI) were the major variables influencing all
physical health symptoms (except for headache and heart pounding).
Odds of high PHQ-15 fell from 2.60 to 0.92 after adjustment for PTSD and depression.
Odds ratio for a high PHQ-15 with PTSD was 7.86. Odds ratio for major depression was 7.47.
PTSD is a
symptom of PCS
Point: PTSD a flavor of PCS
MTBI may “set up” for PTSD.
Damage to medial prefrontal cortex: region
needed to dampen overactivated amygdala.
MTBI = fewer cognitive resources to manage
PTSD fears.
LOC? Intrusive memories generated from
before/after event.
Much of MTBI
disability due to
other injuries
Point: Other injuries a major factor
299 MTBI patients seen in a Level 1 trauma center
completed surveys 6 months after injury.
1/3 had additional injuries. Most not back to work,
more physical impairments.
Patients with isolated MTBI reported more PCS
symptoms than those with MTBI and other injuries.
On average, those with additional injuries had
suffered more severe MTBI as well.
Stulemeijer et al. Impact of Additional Extracranial Injuries on Outcome
after Mild Traumatic Brain Injury. J Neurotrauma. Volume 23, Number 10, 2006.
Repetitive injury
increases
disability
Point: Repetitive injury increases
disability
Repeated concussions linked to:
Chronic traumatic encephalopathy
 Cognitive impairments
 Early dementia
 Movement disorders
 Psychological disorders
 ALS-like disease

PCS more common with repeat injuries.
3 or more athletic concussions increase risk PCS.
Biomarkers
point to
reversibility of
MTBI pathology
Point: Biomarkers point to
reversibility of MTBI neuropathology
N-acetylaspartate (NAA)
Neuron-specific enolase (NSE)
Cleaved tau protein (CTP)
S-100beta
Point: Biomarkers point to
reversibility of MTBI neuropathology
N-acetylaspartate (NAA)
Prominently seen in MRS

Produced in neuronal mitochondria at high
energy cost.

Periods of low ATP = low NAA

NAA a marker of metabolic status

NAA levels decrease roughly in proportion to
severity of TBI

Normalize after MTBI – typically by one
month.

Controls: 30 healthy volunteers
Subjects: 40 Athletes with concussion
Symptoms resolved by day 15
NAA ratios normalized by day 30
Vagnozzi R et al. Assessment of metabolic brain damage and recovery following mild traumatic brain injury:
A multicentre, proton magnetic resonance spectroscopic study in concussed patients. Brain 2010;133:3232-3242.
Point: Biomarkers point to
reversibility of MTBI neuropathology
Neuron-Specific Enolase (NSE)
Protein in neuron cytoplasm, helps increase
Cl during excitation

Sensitivity to MTBI poor. Ranges 40-85%

High levels = no correlation with PCS

Point: Biomarkers point to
reversibility of MTBI neuropathology
Cleaved-Tau Protein (CTP)
Tau is a component of axonal microtubules

Tau degraded after TBI, producing CTP

No difference in CTP levels after MTBI,
though after mod to severe TBI, elevated CTP is
64%
sensitive, and 82% specific for significant
disability.

No relation to PCS.

Point: Biomarkers point to
reversibility of MTBI neuropathology
Serum S-100 beta (S-100b)





S-100b is an astrocytic protein involved in
neuronal cell cycle.
Elevation post MTBI about 61% sensitive and
77% specific.
Plenty of elevated levels occur in sport without
concussion (S-100b also in cartilage, skin)
No correlation with PCS
If level below 0.10ug/L, 90-100% chance of
normal CT scan.
Look with the
right biomarkers
Point: Look with the right biomarkers
PCS is linked to:






PET: Hypoperfusion frontal/parietal lobes
Magnetisation Transfer Imaging: Global MTR
decrease
Eye movements: Impaired saccades
DTI: Disruption of long white matter tracts
ERP: Event related potential delays
fMRI: Impaired activation dorsolateral prefrontal
cortex
Point: Look with the right biomarkers
DTI of PCS:
20 patients one month post MTBI
PCS rated by Rivermead questionnaire
12 healthy controls
Only one patient had a macrostructural injury
(petechial hemorrhage).
Reduced FA with more severe PCS in the splenium of
the corpus callosum, the internal capsule, and the
uncinate fasciculus and IFO, as well as in the parietal
and frontal subcortical white matter fibers.
Smits et al. Microstructural brain injury in post-concussion syndrome
after minor head injury. Neuroradiology. 2011 Aug;53(8):553-63.
fMRI during working memory task
Chen et al. Recovery from mild head injury in sports: Evidence from
serial functional magnetic resonance imaging studies in male athletes.
Clin J Sport Med 2008;18:241-247.
This is the end.