Issues in MTBI

Ford Vox, MDStaff 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 physiologicaldisruption of brain function, asmanifested by at least one of theFollowing:

1) Any period of loss of consciousness.2) Any loss of memory for eventsimmediately before or after theAccident.3) Any alteration in mental stateat the time of the accident(eg, feeling dazed, disoriented,or confused).4) Focal neurological deficit(s) thatmay or may not be transient.

AND

*Loss of consciousness ofapproximately 30minutes or less.*After 30minutes, an initial GlasgowComa Scale (GCS) score of 13–15.* and posttraumatic amnesia (PTA)not greater than 24 hours.

ACRM Definitionof MTBI

International Conference

on Concussion in Sport

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.

MTBI Pathophysiology: DAI

Giza & Hovda 2001

Axonal stretchingPathological excitatory neurotransmitter release.Disruption of ion gradientsMetabolic mismatch / vulnerabilityIncreased glucose demand to feed Na/K pumpNo change in CBF

Normalization: days to weeks.

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 DiesOctober 19, 2011

“Concussion” mentioned 5X in the article

Subdural hematoma = Not a concussion

An Ordinary Football Game, Then a Player DiesOctober 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 SyndromeTeenagersMalignant brain swellingSecond hit during symptomatic period

94 Cases from 1989-2002- 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.

Boden AJSM 2007

PCS treatment suggests

a heterogeneous condition

Point: MTBI treatment suggestsa 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 patient-

centered

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 self-reinforcing and not responsive to various medications that were prescribed.

Ruff 2005

Even the experts can't agree

Clinical Practice Guidelines are of poor qualityRigor of developmentEditorial independence

Little guidance for cases that do not remit spontaneously

Point: Even the experts can't agree

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.

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.

Symptom checklist given to 1,116 Kaiser Permanente patients.

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 FormSymptoms 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" Percent of People

Forgets telephone numbers 58%Forgets people's names 48%Forgets where car was parked 32%Loses car keys 31%Forgets groceries 28%Forgets why they entered a room 27%Forgets directions 24%Forgets appointment dales 20%Forgets store location in shopping center 20%Loses items around the house 17%Loses wallet or pocketbook 17%Forgets content of daily conversations 17%

At least this part ofRick 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 concussionrates and return to play in high school football players wearingnewer helmet technology: A three-year prospective cohort study. Neurosurgery2006;58:275-286.

Sigurdardottir S, Andelic N, Roe C, et al. Post-concussion symptomsafter traumatic brain injury at 3 and 12 months post-injury: A prospectivestudy. 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 followingmild head injury: Expectation as aetiology. J Neurol Neurosurg Psychiatry1992;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:

Identity: Beliefs concerning the illness label or diagnosis and associated symptoms.

Cause: Beliefs concerning the factors or conditions implicated in the aetiology of the illness.

Timeline: Beliefs concerning the expected duration of the illness—whether it will be acute (such as influenza) or chronic (such as diabetes)

Consequences: Beliefs concerning the effects an illness has on physical, social 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 biologyStress:

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 injury-related 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 influenceHindsight 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 stressfulPatients in litigation consistently report more symptoms.

Association does not equal causation.

Litigation is stressful, activating hypothalamic-pituitary-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 speed2) Behavioral: irritability, increased relational conflict, social withdrawal, alienation, reduced relational intimacy, and impaired work and school performance3) Somatic: exhaustion, insomnia, headaches, startle response, hyperarousal, and cardiovascular, gastrointestinal, and musculoskeletal disorders

Point: Too Much PTSD Overlap

The 4 Major Criteria for diagnosis of PTSD: Overlap as well

DSM-IV: One intrusion symptom. Three avoidance symptoms. Two hyperarousal symptoms.

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 mentalhealth problems.

>40% of soldiers with LOC had PTSD.

PTSD and Depression (not MTBI) were the major variables influencing allphysical 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 neuropathologyN-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.

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.

Controls: 30 healthy volunteersSubjects: 40 Athletes with concussion

Symptoms resolved by day 15NAA ratios normalized by day 30

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 questionnaire12 healthy controlsOnly 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.

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.

fMRI during working memory task

This is the end.