Traumatic Brain Injury

Question 1

What is a traumatic brain injury

Answer 1

traumatically induced structural injury/physiologic disruption of brain function
result of external force
indicated by onset or worsening of at least one clinical sign

Question 2

What are the clinical signs o TBI

Answer 2

loss in consciousness/memory
alteration in mental state at time of injury
neurological deficit
intracranial lesion

Question 3

what are the causes of TBI

Answer 3

falls, vehicle accidents, assault

Question 4

Describe mild TBI

Answer 4

GCS 13-15
<30 mins of unconsciousness
post-traumatic amnesia <24hrs

Question 5

Describe moderate TBI

Answer 5

GCS 9-12
30min-24hrs unconsciousness
post traumatic amnesia 1-7 days

Question 6

Describe severe TBI

Answer 6

> 24hrs unconscious
post traumatic amnesia >7 days
GCS <8

Question 7

Why is TBI considered a chronic disease process

Answer 7

permanent 
non-reversible pathological alterations 
special rehab 
inc long-term mortality 
dec life expectancy 
inc seizures, sleep disorders neurodegenerative diseases etc

Question 8

What is the mechanism of TBI

Answer 8

rotational/linear acceleration forces

blunt trauma w/impact deceleration

Question 9

Describe the primary injury of TBI

Answer 9

focal contusions + intracranial bleeds
diffuse axonal + vascular injury
penetrating
blast

Question 10

Describe the secondary TBI injury

Answer 10

neuroinlammation
cerebral oedema
oxidative stress
excitotoxicity 
diffuse axonal injury

Question 11

Describe what primary focal injury means

Answer 11

require object to strike head/physical contact between brain + skull
coup injury = acceleration force
countercoup injury = deceleration force
pathology = skull fracture, intracranial haemorrhage, contusion

Question 12

describe primary injury of contusions

Answer 12

where focal injuies occur where brain tisue contacts protuberances of skull base (likely inferior aspect frontal lobes/poles + inferior temporal lobes) damage to bv + parenchyma => haem perpendicular to cortical surface

Question 13

Describe Intracranial haem

Answer 13

can be extradural 
or intradural (subdural, subarachnoid, intracerebral haematoma)

Question 14

Describe primary diffuse

Answer 14

doesnt require contact
brian moves in cranical cavity bc accel/decel
pathology = traumatic axonal injjury, diffuse vascular in jury

Question 15

describe traumatic axonal injury

Answer 15

rotational forces generate intracranial pressure gradients as brain inertia lags
gradients => shearing + strain forces => stretch + damage axons
prone to damage from rotational + linear accel/decel bc: large size, weight relative to body, gyrencephalic, high ration whiteto grey matter

Question 16

What is the largest driver of functional deficits

Answer 16

injury to axons

Question 17

why are the specific gravities of white and grey matter relevant

Answer 17

shearing has a predilection for axons at the grey-white matter junction

Question 18

What is the result of primary traumatic axonal injury

Answer 18

pure mechanical stretch => tears axonal fibres => retract +retraction bulbs
primary axotomy = rare

Question 19

Describe secondary injury neuroinflammation

Answer 19

glial cell activation
leuk recruitment
upreg inlflam mediators
chemokines, cytokines, ROS
activated following TBI bc mechanostim + release damaged activated molecular patterns
macs + T cells -> brain => inflam spread from injury to surrounding tissue

Question 20

how do microglia respond during neuroinflammation

Answer 20

help clear debris from dead cells through phagocytosis

Question 21

how is inflammation characterised and waht does this define

Answer 21

early secretion of cytokines, chemokines, cell adhesion, anti-finalm cytokines + neutrophic actors
expression profile ictates temporal course of cerebral inflam + termination
failure to resolve => dysfunction, astroglial scar form, neuronal death + axonal patho

Question 22

whats an acute problem with neuroinflammation

Answer 22

breakdown BBB -> vasogenic oedema -> inc ICP

Question 23

describe excitotoxicity as a secondary injury

Answer 23

mvm brain => release ntsm like glutamate

acc Ca+ act Ca2+ dependent enzymes + degrade cellular structures (neuronal degeneration)

Question 24

Describe oxidative stress as a secondary injury

Answer 24

free radicals => autocatalytic reactions damaging lipids, proteins + DNA
=> oxidative stress

Question 25

Describe axonal injury as a secondary injury

Answer 25

forces cause partial damange to axon => trigger molecular pathway => secondary axotomy
inflammatory + apoptotic => potential therapuetic treatment?

Question 26

describe the axon cytoskeleton

Answer 26

microtubulues - highways for transportation to soma
microfilaments (actin) organising plasma membrane + cortical scaffold
neurofilaments - strucutral protein

Question 27

Describe axonal injury patho

Answer 27

microtubules break -> disruption axonal transport of moleculs
Ca2+ accumulates through mechanical opening of chans + mito disruption -> act calpain => breakdown neuroilamnets -> axonal collapse

Question 28

what can injured axons produce

Answer 28

amyloi beta plaques (brown)
Tau
TP-43 (diseae-associated protein in ALS)

Question 29

risk o developing other conditions after the acute period?

Answer 29

2x risk dementia, 4x risk severe TBI

inc parkinsons, MN (linked to alpha synuclein & TDP-43 accumulation)

Question 30

how can we treat moderate-severe TBI

Answer 30

surgery to control brain bleed
monitoring + controlling ICP
adequate blood flow to brain
treating body for other injuries + infection

Question 31

what are the outcomes following moderate-severe TBI

Answer 31

1/3 death
1/3 back to work
1/3 moderate mental/physical disability (cognitive decline, dec memory, ptheadache, ptdepression, insomnia)

Question 32

why have potential TBI treatments faile

Answer 32

difd treatments or focal vs difuse?
need classification from biomarkers?
therapies targeting one secondary injury factor tend to exacerbate others (eg block excitotixicity induces oxidative stress)
consider unerlying patient characteristics? gender? age?