Traumatic Brain Injury Flashcards
What is a traumatic brain injury
traumatically induced structural injury/physiologic disruption of brain function
result of external force
indicated by onset or worsening of at least one clinical sign
What are the clinical signs o TBI
loss in consciousness/memory
alteration in mental state at time of injury
neurological deficit
intracranial lesion
what are the causes of TBI
falls, vehicle accidents, assault
Describe mild TBI
GCS 13-15
<30 mins of unconsciousness
post-traumatic amnesia <24hrs
Describe moderate TBI
GCS 9-12
30min-24hrs unconsciousness
post traumatic amnesia 1-7 days
Describe severe TBI
> 24hrs unconscious
post traumatic amnesia >7 days
GCS <8
Why is TBI considered a chronic disease process
permanent non-reversible pathological alterations special rehab inc long-term mortality dec life expectancy inc seizures, sleep disorders neurodegenerative diseases etc
What is the mechanism of TBI
rotational/linear acceleration forces
blunt trauma w/impact deceleration
Describe the primary injury of TBI
focal contusions + intracranial bleeds
diffuse axonal + vascular injury
penetrating
blast
Describe the secondary TBI injury
neuroinlammation cerebral oedema oxidative stress excitotoxicity diffuse axonal injury
Describe what primary focal injury means
require object to strike head/physical contact between brain + skull
coup injury = acceleration force
countercoup injury = deceleration force
pathology = skull fracture, intracranial haemorrhage, contusion
describe primary injury of contusions
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
Describe Intracranial haem
can be extradural or intradural (subdural, subarachnoid, intracerebral haematoma)
Describe primary diffuse
doesnt require contact
brian moves in cranical cavity bc accel/decel
pathology = traumatic axonal injjury, diffuse vascular in jury
describe traumatic axonal injury
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
What is the largest driver of functional deficits
injury to axons
why are the specific gravities of white and grey matter relevant
shearing has a predilection for axons at the grey-white matter junction
What is the result of primary traumatic axonal injury
pure mechanical stretch => tears axonal fibres => retract +retraction bulbs
primary axotomy = rare
Describe secondary injury neuroinflammation
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
how do microglia respond during neuroinflammation
help clear debris from dead cells through phagocytosis
how is inflammation characterised and waht does this define
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
whats an acute problem with neuroinflammation
breakdown BBB -> vasogenic oedema -> inc ICP
describe excitotoxicity as a secondary injury
mvm brain => release ntsm like glutamate
acc Ca+ act Ca2+ dependent enzymes + degrade cellular structures (neuronal degeneration)
Describe oxidative stress as a secondary injury
free radicals => autocatalytic reactions damaging lipids, proteins + DNA
=> oxidative stress
Describe axonal injury as a secondary injury
forces cause partial damange to axon => trigger molecular pathway => secondary axotomy
inflammatory + apoptotic => potential therapuetic treatment?
describe the axon cytoskeleton
microtubulues - highways for transportation to soma
microfilaments (actin) organising plasma membrane + cortical scaffold
neurofilaments - strucutral protein
Describe axonal injury patho
microtubules break -> disruption axonal transport of moleculs
Ca2+ accumulates through mechanical opening of chans + mito disruption -> act calpain => breakdown neuroilamnets -> axonal collapse
what can injured axons produce
amyloi beta plaques (brown)
Tau
TP-43 (diseae-associated protein in ALS)
risk o developing other conditions after the acute period?
2x risk dementia, 4x risk severe TBI
inc parkinsons, MN (linked to alpha synuclein & TDP-43 accumulation)
how can we treat moderate-severe TBI
surgery to control brain bleed
monitoring + controlling ICP
adequate blood flow to brain
treating body for other injuries + infection
what are the outcomes following moderate-severe TBI
1/3 death
1/3 back to work
1/3 moderate mental/physical disability (cognitive decline, dec memory, ptheadache, ptdepression, insomnia)
why have potential TBI treatments faile
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?
