Jonathan Lifshitz, Ph.D. jlifshitz@uky.edu



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Traumatic Brain Injury Jonathan Lifshitz, Ph.D. Spinal Cord & Brain Injury Research Center jlifshitz@uky.edu

Getting injured or the ways an injury occurs http://www.youtube.com/watch?v=rwhe3lsbjtg http://www.youtube.com/watch?v=8hb_huy3t94 http://www.youtube.com/watch?v=zyjopmk20bo http://www.youtube.com/watch?v=xlivjqv7mxo Consequences of the injury; living with the injury http://www.youtube.com/watch?v=sailqewofqk http://www.youtube.com/watch?v=fgthvbf4t E http://www.youtube.com/watch?v=4m1uls9k p// / _ 4w Expert/professional information about the mechanisms of injury. http://www.youtube.com/watch?v=amaml1 F2LE http://www.youtube.com/watch?v=856rpjxdu1m

Traumatic vs. Atraumatic Brain Damage Acquired brain injury Occurs after birth Not the result of genetic disorder, birth trauma, or degenerative disease Atraumatic: damage/forces progress over time Traumatic: Causedby an outsideforce that impacts the head hard enough to cause damage to the brain Outcome depends d on: Cause of the damage Area(s) of thebrain damaged Extent of the damage

Atraumatic Brain Damage

Willis McGahee Baltimore Ravens RB Ryan Clark Pittsburgh Steelers DB 2009 AFC Championship January 18 th, 2009

Traumatic Brain Damage

Rotational Force on the Brain Ropper & Gorson (2007) NEJM 356:166-172.

Cell body Nerve Cells neurons Comprises gray matter Axon Myelin forms white matter Dendrite Synapse http://www.giantmicrobes.com/

Nedergaard et al. (2002) Beyond the role of glutamate as a neurotransmitter. Nature Reviews Neuroscience 3:748 755.

Nedergaard et al. (2002) Beyond the role of glutamate as a neurotransmitter. Nature Reviews Neuroscience 3:748 755.

Neurovascular Unit

How does TBI cause the damage? http://www.neuroskills.com

Diffuse Injury Diffuse axonal injury Diffuse vascular injury Diffuse neuronal injury Diffuse glial injury Diffuse etcetera injury.

A. Normal connection between neurons. B. Wallerian degeneration and chromatolysis after axonal injury occurs together with retrograde and anterograde changes. C. Surviving, axotomized neurons often atrophy and form ineffective axonal sprouts. Anterograde degeneration of the distal stump denervates postsynaptic neurons.

Injury Induced Induced Circuit Changes Deafferentation

Injury Induced Induced Circuit Changes Deafferentation Neuroplasticity

Chklovskii et al. (2004) Cortical rewiring and information storage. Nature 431:782 788.

Traumatic Brain Injury Diffuse Brain Pathology Circuit it Reorganization Circuit Training Restructured Circuit Morbidity http://www.neuroskills.com

Deficits Correlate with Location of Injury Consequences of brain injury vary tremendously, depending on the type of injury and the area of brain damaged Factors prior to and at the time of injury influence the injury and recovery Left vs. Right sided deficits Intelligence, judgment, behavior memory

Mild Brain Injury Report significant Headache Fatigue Irritability Poor concentration Poor attention Memory problems Word finding difficulty Anxiety Depression Difficulty returning to routine, daily activities, including work Frontal lobe Sylvian fissure Golstein FC, Levin HS. J Clin Exp Neuropsychol. 2001;23(6):739 53. Central sulcus Temporal lobe Parietal lobe Occipital lobe Cerebellum

TBI Alters Personality

Perhaps our discussions will revolve around the importance or relevance of protective gear. See the following website, for example: http://www.headbumpa.com.au/ If you were to use the same search terms in Google, the results are more than likely personal injury lawyer webpages. Would you rely on medical information provided through a law firm?

Traumatic Brain Injury Brain injury is NOT a progressive condition. Brain injury is, however, a lifelong disability. "No head injury is too severe to despair of, nor too trivial to ignore. Hippocrates

**FUNCTIONAL CONSEQUENCES

Functional Consequences of Brain Damage Motorcontrol and perception Communication effects Cognitive i changes Personality change and affective response

Functional Consequences: Motor & Perceptual Consequences Movement, coordination or balance Visual spatial relations Perception Vision and hearing Touch, taste, smell Eating and swallowing Endurance Bowel, bladder and sexual function

Speech Functional Consequences: Communication Effects Physical inability to produce sounds Inability to position and sequence muscle movements Language H d t t th t d How words are put together to convey and understand concepts

Memory Functional Consequences: Cognitive Changes Attention and concentration Slf Self awareness Problem solving and decision making Information processing and concept formation Judgment

Types of Memory Cognitive Changes: Memory Immediate memory / working memory Short term memory Long term memory Amnesia Retrograde amnesia Anterograde amnesia Memory impairments can be the most limiting of all potential cognitive consequences of TBI, since they affect the ability to learn, store and retrieve information. Ability to profit from experience

Cognitive Changes: Self awareness Lack insight into the appropriateness of their behavior and may be unaware of the impact certain aspects of their behavior have on other people

Cognitive Changes: Information Processing Moretime may be needed to synthesize verbal or visual input cognitive delay

Functional Consequences: Personality Change & Affective Response Misinterpreted by others Laziness, disinterest, uncooperativeness Personality changes Emotionally explosive, outbursts of anger or anxiety Anger or irritability Aggressive behavior bh verbal blor physical, active or passive Decreased patience Nonconformance to social norms Disinhibition, inadequate social skills Apathy and depression Loss of self esteem

**FUNCTIONAL IMPLICATIONS

Functional Implications of Brain Damage Psychological Issues Social Issues Lifestyle Issues Vocational Issues

Functional Implications: Psychological lissues in Brain Damage Emotional reactivity, loss of emotional control, emotional lability Depression, mood swings, psychosis Impulsivity

Personality traits that were present prior to brain damage may become exaggerated after the damage has occurred, or there may be dramatic personality change, so that an individual who was quiet and passive prior to brain damage may become boisterous and aggressive after injury. Often because of changes in temperament, behavior and personality, there is a disruption in family cohesion and feelings of entrapment by family members.

Functional Implications: Social Issues in Brain Damage Family relationships are significantly altered Prolonged stress of caregiving Financial burden Neither the family nor the individual has the opportunity to prepare for the emotional and economic impact of TBI

Functional Implications: Lifestyle Issues in Brain Damage Implementation and acceptance of new accommodations and assistive devices Independence Operating motor vehicle Eating behavior Physical component Planning and maintaining diet

Functional Implications: Vocational Issues in Brain Damage Helpingthemfindalternativeways to perform tasks and to develop strategies to reduce, organize, and retrieve information can reduce the disabling effects of memory impairment. To overcome difficulty organizing gtheir day and improve performance Implementing structured routines Using written notes or lists Using audiotaped reminders Too much information may cause the individual Too much information may cause the individual to become overwhelmed and confused

**CIRCUIT REWIRING

Injury Induced Circuit Rewiring The schematic shows two neurons (green, blue), dendrites (thick lines), axons (thin lines) and synapses (red circles). In the initial wiring diagram, signaling is from the blue neuron to the green one. Synapse formation and elimination can result in weight changes alone (b) or can include a wiring change (c, d). Wiring changes can occur with (c) or without (d) axon or dendrite growth. In the new wiring diagram, signaling occurs from blue to green and from green to blue. Chklovskii et al. (2004) Cortical rewiring and information storage. Nature 431:782 788.

Potential for Circuit Rewiring Concentric cylinders surrounding the postsynaptic dendrite show the volume accessible by the spine (inner cylinder), and the volume accessible by remodelling of an axon or dendrite (outer cylinder). Among those presynaptic axons that cross through the inner cylinder (blue), only a small fraction form actual connections (red). Green denotes the population of presynaptic candidates that cross through the outer cylinder. The much larger population of inaccessible axons is shown in grey. Chklovskii et al. (2004) Cortical rewiring and information storage. Nature 431:782 788.

**TYPES OF HEAD INJURY

Brain Injury is a Mechanical Event

Types of Traumatic Brain Injury Open/penetrating injury Functional impairments localized and related to function of affected brain area Closed head injury Diffuse axonal injury (DAI) Edema swelling Hematoma blood

**INCIDENCE & FUNDING

50,000000 Deaths 235,000 Hospitalizations 1,111,000111 Emergency Department Visits??? Receiving Other Medical Care or No Care

Incidence of TBI in Europe Compared to 500 the United States 503.1 n rate 100,000) admission cases per Annual a mber of c (num 400 300 270 200 100 313 314 281 169 91 0 England Scotland France Spain Norway Italy United & Wales States Servadei, F et al, Neuroepidemiology, 2002;21:297 304. Bazarian, J et al, Brain Injury, 2004, 1 10.

Comparison of Annual Incidence 2,000,000 1,500,000 Data compiled and arranged by the Brain Injury Association of America based on data from the Centers for Disease Control and Prevention, the American Cancer Society, and the National Multiple Sclerosis Society Traumatic brain injuries 1,500,000 1,000,000 500,000 Breast cancer 176,300 100,000 10,000 Multiple sclerosis 10,400 Spinal cord injuries 11,000 HIV/AIDS 51,334

**CONSTANTLY EVOLVING DAMAGE

TBI: Constantly Evolving Damage

Where does damage occur? Tabor & Hurley (2007) J. Neuropsych & Clin Neurosci 19: iv:104.

Tabor & Hurley (2007) J. Neuropsych & Clin Neurosci 19: iv:104.

**NURSERY RHYMES

Jack and Jill went up the hill, To fetch a pail of water, Jack fell down and broke his crown, And Jill came tumbling after. Up Jack got and home he ran, As fast as he could caper. There his mother bound his head, With vinegar and brown paper.

**SECONDARY CASCADES

Willmore & Ueda (2008) Neurochem. Res.

Soma Dendrite Axon Astrocyte Microglia Oligodendrocyte Endothelial Cell Blood Brain Barrier Neurons Glia Which brain components are damaged by TBI? Blood Vessels Physical Cell Death Physiology How does TBI damage the brain? Vascular Genetic Metabolic Axotomy Membrane Perturbation Mechanosensitive Channels Apoptosis Necrosis Autophagy Spreading Depression Ionic Disturbance Excitatory Amino Acids Calcium Flux Cytotoxic Edema Blood Brain Barrier Vasogenic Edema Transcription Translation Free Radicals Energy Substrates