Traumatic Brain Injury

Question 1

What is a mild traumatic brain injury? What percentage of those with mTBI have persisting cognitive dysfunction?

Answer 1

Diffuse axonal injury or concussion. It is an injury that cannot be seen on an imaging scan. About 15-20% of mTBI patients have persisting cognitive dysfunction.

Question 2

What is the biggest risk factor for concussion?

Answer 2

Being male

Question 3

What type of injury causes diffuse axonal injury?

Answer 3

Inertial loading causes tensile elongation of axons which results in diffuse axonal injury. The rate of the injury is what is important.

Question 4

Describe the neuropathology of diffuse axonal injury.

Answer 4

Swelling throughout white matter tracts, disconnections, stretches, and bulb formation.

Question 5

Describe the cellular and molecular mechanisms behind the neuropathology of diffuse axonal injury.

Answer 5

TBI produces axonal undulations. Stretch injury breaks microtubules at the peaks of undulations. Tau binds axons together such that they can move relative to one another but too much stress still causes breakage.

As undulations relax, there is chemical dissolution of the broken microtubules and transport being sent down broken axons accumulates in swellings because of transport interruption. Partial transport interruption is responsible for the formation of axonal variscosities.

Taxol inhibits relaxation of undulations by stabilizing microtubules which prevents their breakdown and degeneration.

Question 6

Describe the ionic dysregulation that occurs in diffuse axonal injury.

Answer 6

Trauma damages the sodium inactivation gates leading to sodium influx and swelling. Calcium influx increases because the sodium-calcium exchanger gets reversed and voltage sensitive calcium channels are activated. Calcium activated proteases digest the sodium inactivation gate which makes it worse.

There may be an increase in the number of sodium channels after an injury which makes axons more susceptible to another injury. We do not know how long this period of vulnerability lasts but it leads to an exaggerated response to a second injury.

Question 7

What form of imaging can be used to visualize diffuse axonal injury?

Answer 7

Diffusion tensor imaging follows water movement through directional axons.

Question 8

Traumatic brain injury is the highest epigenetic risk factor for what disease? What pathology does TBI share with this disease?

Answer 8

TBI is the highest epigenetic risk factor for developing Alzheimer’s disease like dementia. Extracellular accumulations of amyloid beta plaques occur in both AD and acutely post TBI. Diffuse axonal injury produces a reservoir of APP chronically–there is ongoing axonal pathology.

Neurofibrillary tangles are abnormal hyperphosphorylated intraneuronal accumulations of microtubule associated protein tau. Neurofibrillary tangles begin to accumulate a year after injury.

There is also chronic microgliosis and atrophy after a single TBI–the disconnection of axons does not stop.

Question 9

Where in the skull are the blood vessels located?

Answer 9

Subarachnoid space

Question 10

What is the difference between a linear, compound, and complex fracture? Depressed and contrecoup fracture?

Answer 10

• Linear: secondary to contact with a large flat object, fracture begins along inner table and is usally not lethal
• Compound: associated with scalp lacerations
• Complex: fracture involving multiple bones
• Depressed: secondary to contact with small objects
• Contrecoup: located distant from point of injury

Question 11

What are the different types of dural hemorrhages? Describe the pathogenesis of each.

Answer 11

An epidural hemorrhage is between the skull and dura and is associated with fractures of the temporal bone and laceration of the middle meningeal artery. It presents with immediate loss of consciousness followed by the individual waking up and then lossing consciousness and falling into a coma a few hours layer. The brain is compressed laterally and midbrain may be compressed.

A subdural hemorrhage occurs below the dura and takes longer for blood accumulation to cause symptoms. They are more common than epidural hematomas and can be associated with subarachnoid hemorrhage due to tearing of subarachnoid arteries. This results from motion of the brain with respect to the skull and dura and tearing of bridging veins. Blood compresses the brain on all sides.

Question 12

Where does focal damage to the brain most commonly occur?

Answer 12

Focal damage to the brain is the most common traumatic lesion of the brain and typically is located at gyral crests. It is associated with brain swelling.

Fracture contusions/lacerations occur at the site of the fracture and tend to be severe.

Coup contusions are caused by bending/rebound of skull at the site of injury with or without fracture. Caused by a moving object striking at stationary head.

Contrecoup contusions are located opposite the point of impact and are caused by a moving head striking a fixed object.

Question 13

What may happen to old contusions?

Answer 13

They are typically associated with seizures due to scarring in patients who recover.

Question 14

What are the three principle types of diffuse brain injury?

Answer 14

Diffuse axonal injury, concussion, and brain swelling

Question 15

What are the pathophysiological effects of a severe concussion? What causes traumatic brain swelling?

Answer 15

• Elevated concentration of glutamate
• Activation of ATP dependent sodium potassium pump
• Elevated intracellular calcium leading to neuron death
• Elevated lactic acid

Traumatic brain swelling is caused by increased intracranial pressure secondary to cerebral vasodilation and/or edema.

Question 16

Trauma associated with ischemic brain damage can be caused by?

Answer 16

Concussion, hypotension-cardiac arrest, status epilepticus

Question 17

What percentage of deaths in abused infants are caused by CNS trauma? What type of hematomas and injuries are common (or uncommon) in shaken babies?

Answer 17

65% of deaths in abused infants are caused by CNS trauma, with or without external evidence of trauma or fractures of the skull or long bones.

Subdural hematomas are common in shaken babies (80-90%) but usually not lethal. Gliding contusions are often seen in shaken babies, the tissue can split without bleeding and the corpus callosum may be transected. Violent shaking can cause transection or damage to the spinal cord, ganglia, and eyes because the neck and retina are unstable.

Black brain is caused by total brain necrosis secondary to shock or severe concussion in abused infants.

Question 18

Describe the prevalence and gender bias seen in traumatic brain injury.

Answer 18

There are about 50,000 deaths per year and 230,000 hospitalizations each year due to TBI. They occur twice as often in men–younger men engage in more risks (often caused by firearms and vehicles) and older men are more likely to fall (often secondary to drinking).

Question 19

What are the three components of the Glasgow coma scale? How is TBI graded on this scale?

Answer 19

Eye score:

• 4: open spontaneously
• 3: open to verbal command
• 2: open to pain
• 1: no response

Motor score (most important):

• 6: obeys verbal command
• 5: localizes pain to stimulus
• 4: flexion-withdrawal response
• 3: flexion-abnormal response (decorticate)
• 2: extensor response (decerebrate)
• 1: no response

Verbal score:

• 5: oriented and converses
• 4: disoriented and converses
• 3: inappropriate words
• 2: incomprehensible sounds
• 1: no response

Severe: GCS < 9

Moderate: GCS 9-12

Minor: GCS > 12

Question 20

What is the Glasgow outcome scale?

Answer 20

• 1: good recovery
• 2: moderate disability
• 3: severe disability
• 4: vegetative
• 5: death

Question 21

Describe CT grading in TBI.

Answer 21

Diffuse injury

• I: no swelling
• II: minimal swelling
• III: cisterns absent
• IV: swelling and shift

Evacuated mass lesion

Non-evacuated mass lesion

Question 22

Describe the relationship between CT diagnosis and outcome.

Answer 22

Good outcomes correlate with diffuse injuries with minimal to no swelling

Question 23

Describe the complications that can occur in TBI before arriving to the hospital and the implications that this has for TBI management.

Answer 23

Complications: hypoxia, hypotension, anemia

Pre-hospital complications occur in 50% of TBI

Goals: resuscitation, maintain adequate perfusion to preent secondary injury

Question 24

What is the difference between contact loading and inertial loading?

Answer 24

Contact loading involves getting hit in the head while inertial loading involves movement that causes the brain to move in the skull. Contact loading can result in contusions and hematomas (focal injury) as well as inertial loading (diffuse axonal injury).

Question 25

What kind of imaging is useful for visualizing diffuse axonal injury?

Answer 25

Diffusion tract imaging can show where axons have been damaged. It does not show up on MRI and CT so it would be a diagnosis of exclusion otherwise.

Question 26

What are the molecular and morphologic events that occur after TBI?

Answer 26

• Necrosis and apoptosis
• Inflammation
• Atrophy (occurs progressively over a year)

Question 27

What are the stages of recovery after TBI?

Answer 27

• Plasticity: synapses can repair and a different neuron can take over if one is lost
• Neurogenesis: the brain does produce new neurons in some areas (hippocampus and olfactory bulb)
• Physiological recovery
• Behavioral response

Plasticity can be aberrant–seizures can occur after TBI, phantom limb pain, etc.

Question 28

Describe the sprouting that occurs in the hippocampus.

Answer 28

The outer molecular layer (granule cell layer) of the dentate gyrus is innervated by septal fibers and fibers from the entorhinal cortex. If one set of fibers is eliminated, the other set will sprout and reinnervate the outer molecular layer.

The uncus contains the entorhinal cortex which is ablated by herniation and if the cells are visualized later there is proliferation and sprouting of septal fibers.