Traumatic Brain Injuries: Pathophysiology, Treatment and Prevention

Disclaimer

The views expressed in this presentation are those of the author and do not reflect the official policy of the Department of the Army, Department of Defense, or U.S. Government.

Defense and Veterans Brain Injury Center (DVBIC)

DVBIC, founded in 1991 as the Defense and Veterans Head Injury Program (DVHIP), a congressionally funded DoD-VA Disease Management Program.

The DVBIC mission:

conduct clinical research

ensure optimal clinical care

education for military, veterans, and their families.

Military Sites: WRAMC, NMCSD, WH-BAMC

VAMC’s – Richmond, Minn, Palo Alto, Tampa

civilian community reentry programs – Virginia Neurocare and Laurel Highlands (Western Penna)

Mechanisms of Injury Traumatic Brain Injury Blunt(Closed) Penetrating Explosion Fall GSW Stab Blast Fragment Motor vehicle crashes (MVC)

Traumatic Brain Injury Description GCS = Glasgow Coma Scale LOC = Loss of consciousness PTA = Posttraumatic amnesia >7 days >24 hrs. 3 – 8 Severe > 24 hrs. - <7days 1 – 24 hrs. 9 – 12 Moderate <24 hr <20 min-1 hr 13 – 15 Mild PTA LOC GCS Severity

American Congress of Rehabilitation Medicine: Mild Traumatic Brain Injury (MTBI) Definition

A traumatically induced physiological disruption of brain function manifested by at least one of these symptoms:

Loss of consciousness < 30 minutes

Loss of memory for events immediately before (retrograde amnesia) or after the accident (Post Traumatic Amnesia < 24 hours)

Any alteration in mental state at the time of the injury (dazed, disoriented, confused)

Presence of focal neurological deficits

If given, GCS score > 13

Kay, et al., 1993

Relative Proportion of Levels of Care for TBI Source: CDC: Traumatic Brain Injury in the United States, October 2004 50,000 Deaths 235,000 Hospitalizations 1,111,000 Emergency Department Visits ??? Other Medical Care or No Care

Head Injury in the U.S. Military Ommaya AK, Ommaya AK, Dannenberg AL, Salazar AM. Causation, incidence, and costs of traumatic brain injury in the U.S. Military Medical System. J Trauma . 1996

Traumatic Brain Injury (TBI) Epidemiology: Incidence From D. Hovda, UCLA BIRC Program (modified from Kraus JF, et. al. 1996 and Durkin MS, et. al. 1998) Age (years) Incidence (cases/100,000)

Incidence of TBI-Related Hospitalizations Among Active Duty US Army Personnel ( Ivins, et al, Neuroepidemiology, 2006)

Mechanisms of Injury Diffuse Axonal Contra coup Penetrating Gun Shot Wound From the Centre for Neuro Skills

Pathophysiology of Injury

Primary Injury: Function of energy transmitted to brain

Very little can be done by health care providers to influence

Command enforcement of personal protection

Helmets, Seatbelts

Secondary Injury: Function of damage to brain from systemic physiology

Systemic

Hypotension: Acute and easily treatable

Hypoxia: Acute and easily treatable

Fever and Electrolyte Imbalances

Seizures

Intracranial Pressure  Can Lead to Herniation

Neuropathology of Closed TBI

Primary Injury:

Contusions/Hemorrhages

Diffuse Axonal Injury (DAI)

Secondary Injury (Intracranial):

Blood Flow and Metabolic Changes

Traumatic Hematomas

Cerebral Edema

Hydrocephalus

Increased Intracranial Pressure

Severe and Penetrating Brain Injury: Clinical Challenges

Craniectomy

Vascular Complications

47.4% had traumatic cerebral vasospasm. Majority were blast related injury ( Armonda, R., Bell, R., Vo,A., et al 2006. Wartime traumatic cerebral vasospasm: Recent review of combat casualties. Neurosurgery, 59(6), 1215 -1225.)

Autonomic Instability/Sympathetic Storms

Infectious Complications

Archives of Physical Medicine and Rehab (Invited Manuscript) R. Riechers, et al.

Brain-Behavior Relationships and Regional Cortical Vulnerability to TBI Figure adapted from Arciniegas and Beresford 2001) Dorsolateral prefrontal cortex (executive function, including sustained and complex attention, memory retrieval, abstraction, judgement, insight, problem solving) Amygdala (emotional learning and conditioning, including fear/anxiety) Anterior temporal cortex (memory retrieval, sensory-limbic integration) Ventral brainstem (arousal, ascending activation of diencephalic, subcortical, and cortical structures) Hippocampal-Entorhinal Complex (declarative memory) Viewed on coronal MRI Orbitofrontal cortex (emotional and social responding) (

Postconcussion Symptoms (PCS)

SOMATIC

Headache

Dizziness

Fatigue – for physical and mental

Visual Disturbances

Sensitivity to Noise

and Light

COGNITIVE

Decreased Concentration

Memory Problems

NEUROPSYCHIATRIC

Anxiety

Depression

Irritability

Mood Swings

Sleep Disturbances

Post Concussive Symptoms in Mild TBI

Natural history is recovery within weeks/months (Levin 1987)

A small percentage will have persistent symptoms (Alexander, Neurology 1995)

Repeat concussions – more morbidity (Collins, et al, Neurosurgery 2002)

Educational interventions effective in reducing symptoms ( Ponsford, et al. 2002 )

Cognitive Changes

Attention/Concentration

Speed of Mental Processing

Learning/Information Retrieval

Executive Functions (e. g., Planning, Problem Solving, Self Monitoring) May see judgment problems, apathy, inappropriate behaviors

fMRI study of MTBI and Memory (McAllister, et al, 2000)

Neurometabolic Changes and Concussion (Hovda et al, 1998)

Simple Reaction Time Warden D, Bleiberg J, Cameron K, et al, Neurology , 2001 Baseline 1 hour post 4 days post p < 0.05

Concussion:Time to Recovery Bleiberg J., et al. Neurosurgery, 2004.

Post Deployment TBI Questions

Did you have any injury(ies) during your deployment from any of the following? (check all that apply):

1. Fragment

2. Bullet

3. Vehicular (any type of vehicle, including airplane)

4. Fall

5. Blast (Improvised Explosive Device, RPG, Land mine, Grenade, etc.)

6. Other specify:

Did any injury received while you were deployed result in any of the following? (check

all that apply):

1. Being dazed, confused or “seeing stars”

2. Not remembering the injury

3. Losing consciousness (knocked out) for less than a minute

4. Losing consciousness for 1-20 minutes

5. Losing consciousness for longer than 20 minutes

6. Having any symptoms of concussion afterward (such as headache, dizziness, irritability, etc.)

7. Head Injury

8. None of the above (any of 1-5 suggest a MTBI diagnosis)

Post-Deployment TBI Screening

DVBIC has worked with multiple sites screening returning war fighters

Approximately 10-20% war fighters had a TBI while in theater (Army Times-Sept 5, 2005)

Virtually all were mild TBI

Most are now asymptomatic

WRAMC TBI Screening Flow Chart Involved in/exposed to/experienced: Blast, vehicular crash, fall, GSW to head/face and/or neck, (including superficial wounds): Yes TBI Symptom Screening/Interview: Any LOC, AOC, PTA and symptoms endorsed on the Post Concussive Symptom Checklist Cognitive, physical, and/or emotional symptoms or findings thought to be due to TBI Cognitive, physical, and/or emotional symtoms or findings thought to be due to PTSD or other psychiatric disorder Medical Evaluation Yes Note: Both may be present at this level

Walter Reed OIF/OEF TBI Experience (1/03 to 4/05)

N=433 Hospitalized patients with TBI

68% of injuries were due to explosion/blast

88.5% were closed TBI

Post Traumatic Amnesia (PTA) < 24 hours: 43%

Warden et al., Journal of Neurotrauma 2005; 22:1178

Walter Reed OIF/OEF TBI Experience (cont.)

Complications - 14% shock; 9.5% hypoxia; 25% skull fracture; 18.7% subdural hematoma; and 1.5% epidurals

6% had seizures

19% had limb amputations; lower extremity most common

91 % reported post concussive symptoms:

headache (47%)

memory deficits (46%)

irritability/aggression (45%)

attention/concentration difficulties (41%)

Of 43% with a psychiatric symptoms noted, depression was the most

common (27%).

Warden et al., Journal of Neurotrauma 2005; 22:1178

Military Context

Blast Wave Physics Courtesy of Keith Prusaczyk, Ph.D.

Evaluation of MTBI in the field

Medic obtains history using

Military Acute Concussion Evaluation (MACE)

New Clinical Practice Guideline drawing on sports concussion and operational experts released 22 Dec 06– includes the SAC – Standard Assessment of Concussion (McCrea 2000)

Conclusions Regarding PTSD in TBI Patients

Studies suggest that PTSD following TBI does occur, but may be modified by the brain injury.

Intrusive memories are less common in individuals; when present, highly predictive of PTSD

PTSD is more likely in mild TBI than severe TBI

(Bombardier, C., et al. 2006. J Neuropsychiatry Clin Neurosci: Posttraumatic Stress Disorder Symptoms During the First Six Months After Traumatic Brain Injury: 18:4:501-508)

Treatment Areas

Education and support for the patient’s family

Rest and avoidance of another injury

Individual and group therapies

Medication including symptom mgt

Rehab (acute, sub-acute, community re-entry)

Guidelines for the Pharmacologic Treatment of Neurobehavioral Sequelae of TBI

Symptom Management

Addresses 3 topic areas

Aggression

Cognitive disorders

Affective disorder/Anxiety/Psychotic disorders

Warden D ., Gordon B., McAllister T., et al (2006). Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury. Journal of Neurotrauma , 10 (23), 1468-1501.

Guidelines for the Pharmacologic Treatment of Neurobehavioral Sequelae of TBI

Despite reviewing a significant number of studies on drug treatment of neurobehavioral sequelae after TBI, the quality of evidence did not support any treatment standards and few guidelines due to a number of recurrent methodological problems.

Guidelines were established for the use of methylphenidate in the treatment of deficits in attention and speed of information processing, as well as for the use of beta-blockers for the treatment of aggression following TBI.

Options were recommended in the treatment of depression, bipolar disorder/mania, psychosis, aggression, general cognitive functions, and deficits in attention, speed of processing, and memory after TBI.

Prevention Areas