TBI Flashcards
describe the two broad types of traumatic brain injury.
Focal TBI-This are related to damage to specific regions.
- Bleeding (epidural/ extradural hemotoma) sub arrachnoid hamerhage)
- Hematoma can cause the squashing of the brain and the shifting of the midline.
- Fractures- intracranial contusions aslo confer with the sights of fractures.
- There is some commonality to to these hitting the back of the head is commonaly asasociated with frontal contusions as the brain rebound into the front of th skul.
Diffuse axonal injury- This involved ciuirty damge as a result of the shearing of white matter tracts. They are particular vulnerable to the rapid decceleration associated with hitting the head and are commonly seen in sites of thin long tracts like the brain stem and corpus callosum.
What are TBIs? what are often the outcomes and how do we measure them (just names)? What are the spread of symtoms?
Traumatic brain injuries are damge related to impacts on the brain.
- They are the biggest cause of death in people under 40 largely stemming from falls, vehicular accident, violence and sports related injiuries.
- The can b related to focal damge including, fraccturs, intracerebral contusions and bleeding or diffuse axonal lesions which relaibly track otcomes.
Symptoms
- These can vary between severity and mild cases.
- We can assess severity often through the mayo classification method taking into account, imaging, GCS, LOC, Death, and PTA length.
- symptoms:
- Headache
- Dizzyness
- Cognitive defects
- Behavioural changes, increase crimnality and breakdown of realtionships, Issues with attention and working memory, Issdues with executive function often being impulsive.
- sleep disturbance
- fatigue
- irritability
- anxiety
- depression
Outcome.
- Outcomes tend to be poor. We can assess outcomes using Glagow outcome scale or the Glasgow coma scale to assess progression.
- Examples of outcomes can bee seen looking at the use of craniectomy in cases of increased cranial presure (ICP) thus this release pressure and prevent brain compression onto brain stem.
- Although this is effective at saving lifes the outcomes are bleak as they have a Low GCS with severe dissabiltiy.
- Also sen in the attempt to use acute neuroprotective treament, like glutamate anatagonists to stop excitotoxicity and counter seizure, and steroids to counter neuroinflamation.
- Fairly useless in trial for countering negative impact.
Why is the demographic slowly shifting to the older generation in TBI?
The demographic is slowly shifting to the older generation due their increased age and use of blood thinners and thus increasing their risk of haemorrhage following a fall.
What are the current and emerging treatments (issues) for TBI?
Craniectomy -in cases of increased cranial presure (ICP) thus this release pressure and prevent brain compression onto brain stem.
* Although this is effective at saving lifes the outcomes are bleak as they have a Low GCS with severe dissabiltiy.
Acute neuroprotective treament- glutamate anatagonists to stop excitotoxicity and counter seizure, and steroids to counter neuroinflamation.
- Fairly useless in trial for countering negative impact.
Scott eat al 2018
Attempts to counter neuro infalmations by using minocyclidine which turns of glial cells, and thus stops the action of enhnace microglia.
- They found this was innefeciv and actually increase neruodegenration in individuals (shown by increase light neurofilaments in blood plasma- sign of neurodegen)
- Also showed continued inflamation years kater with increased microglail actvation.
- Would appear then that micro glia have an important repair role in the chronic stages of TBI.
What are the current methods of assessing the severity and damage (diagnosis included) in TBIs? What can advnaced MRI offer that is an improvement?
Diagnosis- commonl achieved by imaging to see what damage has occured.
- Computer tomography
- Using an array of x-ray imaging to produce a collective image of the brain
- Primarily useful in focal TBI
- Blood and bone senstiive and so can image hematomas and skull fractures
- MRI:
- 2 forms used the basic FLAIR sequence for focal damge
- more so use the SWI (selctively weighted imaging) which is sensitve to blood. This can be used to identify small issues like DAI represnted as micro bleed.
More effective advanced MRI
Difusion tensor imaging-
- This assesses the diffusion of molecules in the brain in aprticualr water.
- This means things like white matter tracks act as obstacles obstructing diffusion. This is shown by increased uneven ANISOTROPIC diffusion.
- Hence, in damage the fraction of anisotropic diffusion around white matter is reduced. increased diffusion.
(in a dmonstarted case of a car crash, the CT was normal and SWI MRI also nromal at the time. Persistenmt cognitive issue later on culd be attributed to DAI shown by DTI.)
Resting state fMRI
- The is a suggestion that the correlatio of activation in the resting brain is altered in TBI.
- using this imaging has identified a loss o corewaltion in the frontoparietal networks.
Single positron emmision computed tomography
- SPECT can be used to trac particualr proteins like the dopamine trransporter in the brain to track dopamine activity.
- dopmainergic activity is reduced and correlates with cognitive issues (JENKINS et al)
- Deficts would explain the hypo-motor behvaiour and slow motor processing in TBI patients.
Symptoms-
Cognitive symptoms are often assessed using tests along side input from close family as often the patients has little insight and often issues like inteligence, mood and medicine can alter findings. ( also capped score can mask very severe cases to be just bad)
- they test whether they have functional planning or inhibibtions,
* stroop test- test of congruence- read colour when name doesnt match colour
* trail making test- draw line between set of number and letter like 1>A>2>B>3>C
*Wisconsin Card sorting test.- given a set of cards and asked to match them but not told how. This could be done by symbol shape, number of symbols, or symbol colour) they are simply told if they ar right or worng and have to work it out.
Porgress and Outcome
Glagow coma scale: this is used to assess progress of patients in ITU
- There is a score of of 15 and used to assess the patients conciousness. 15 is normal and 3 indicates severely effceted concious ness.
- Tested on 3 aspects eye response (4 scores), verbal response (5 scores), Motor response (6 scores), movement after asome pain.
- 1 in all cases is complete lack of repsonse often attributed to heavy sedation.
- 2 is often very bad as it confers a unconcious repsonse. e.g in motor this is ‘extending’ unconcious reflex no idea of where pain is or where it is.
Glagow outcome scale : asseses outcome
- seen in hte cases of cerebral trauma: 5 scores
1 * Death- related to serious injury or detah with no recovery
2 * vegetative state- constant lack of higher mental function.
3* severe disability- require constant supervision and help
4* moderate dissability- no need for assistance but requires special eqiptment to function
5* Mild- limmitied issues and minor neurological and psychological deficits.
Assesing sevrity
- Ofte done using the Mayo classification which is able to distinguish between possible and probable TBI and moderate and severe TBI with a specificity of 99% and sensitivity of 89% (means its criteria is very specific bu does not always succesfully diagnose TBI, thi sis becaus eif you have this criteria you likely have a TBI if you dont have all of them you still could have a TBI.
- Death
- Loss of conciousness for more than 30 mins
- Pos traumatic amnesia for 24 hours or more ( this is limmitted memory of anything after the incident and innability to form new memories (anterograde). if This lasts longer than 2 weeks they will likely never return to work)
- GCS score ( scores should have returned to 13 within a day if safe
- evidemce od injury like bleeding or fracture from scans.
Predictive
- Argument for PTA- Length of PTA correlates with cance of going back to work and exent of cognitive deficits.
- But this is highly variable between patients
- DAI is a much better predictor of outcome.
At the celullar level what dysfUnction can be seen follwing TBI?
This often involves a cascade of activity related to ion dysregulation
- Calcium depolarisation of neurons is seen overloading mitochondria depolarising them and disrupting the MRC and ATP production, thus disrupting pumps regulating ion channel levels.
- This leads to further issues such as execssive glutamate release asscoiate with excitiotoxicity and seixure activity.
- Disruption of MRC drives ROS release that can cause DNA, protein and lipid damage.
- Also can be linked to caclium activation of the capsase apoptotic pathway and NOS with pottentiates NO release and this further disrupts the MRC competing with 02 at complex IV and binds ROS to form toxic Peroxynitrite.
- Axoinal amge is common wihth sweeling of axons observable whic dirsurpts signalling.
- Breakdown of the exoskeleton and leaage f protein like tau out int the periphery has been asscoiated with the progressive build up of patholog in Chronic trauma Encephalopathy, like dementia pugilistica.
What cognitive deficits can be associated with network dysfucntion in TBI?
- issues with working memory and attention
- executive function, often impulsive.
- behvaioural issues- breakdwon of relationships, increased criminality like drug use, likely linke dto impulsivity.
- social cognition deficits
Whats the difference between concussion and brain injury?
Concussion unlike TBI is not seen with damage although it odes share the symptoms of concussion.
- This is why concussion is commnaly refered t as the symtpms followwing TBI
- it is improtant to recognise and its own condition without injury and thus below the mild end of the TBI spectrum.
Discuss investigaations of neurodegenration in TBI
attempts to stop te effcets of exictotoxity and sieyure with glutamate anatgonists and prevent neuroinflamation with steroids were innefective at improving outcome.
Scott eat al 2018
Attempts to counter neuro inflamations by using minocyclidine which turns of glial cells, and thus stops the action of enhnace microglia.
- They found this was innefeciv and actually increase neruodegenration in individuals (shown by increase light neurofilaments in blood plasma- sign of neurodegen)
- Also showed continued inflamation years kater with increased microglail actvation.
- Would appear then that micro glia have an important repair role in the chronic stages of TBI.
Cole et al 2018, showed progressie degenrstion in MRI wih time follwoimg original assesment.
- Is this more than 1% a year, the nromal rate, need more longitudinal tests.
Discuss investigations into sport related TBI and degenerative disroder
CTE
- macroscopic changes include a reduction in brain weight, gray and white matter atrophy (typically most severe in the frontal and anterior temporal lobes), enlargement of the lateral and third ventricles,
- atrophy of the thalamus, hypothalamus and mammillary bodies
related to re-ocurring mild TBI that prmiarly leads t the build up of Phos-TAU in early stages (route unknown)
stages
1- largely charcterised by focal perivascular tau
2-mild enlargement of the ventricles and wider occurnece of p-tau in NFTS
3-reduction in brain weight, can see the rise of TDP-43 INCLUSIONS IN THE MAJORITY OF CASES.
4-can be substantial weight change in brain is possible generlaised by atrophy throughtout the cerrbellum and the frontal, temporal lobes. clear large spread of the of NFT throughot this same for TDP-43.
- observe markeloss of myelinated fibres.
NFL patients that have died young and had behvioural disroder, autopsies have presented with tau pathology , tauopathies.
- The is a growing idea that braintrauma leads to a build of of oxic pathology fromaing Chronic traumatic Encephalopathies.
- This is releated to the release of proteins like tau follwoing head injury.
-A WELL DOCUMENTED FROM IN IN boxers which is DEMENTIA PUGILISTICA, or punch-drunk syndrome. this confers a progressive decline cognitive ablity
* issues with STM
* dysarthria
* physical tremors
* loss of physical condition
* changes in emotional control- jealousy
This has been linked with amyloid depostion with an underrlying pathology of tau.
Studies by Mckee et al at the reported 47 cases of CTE were 85% boxers and 10% NFL, comapring there brain slices shows that th tau satining patterns are very simmilar
- recent boston institute reports are fom 111 cases 99% are NFL.
- issue is they have an ascertainment bias, given that majority of peopl giving brains are NFL.
Issues of co-morbidity
Lack of bioimarkers are an issue here.
- PET imaging shows some promise of distinguishing CTE in the ealry stages. Most recently in a retired NFL patient showing signs of AD. they found marking for AB showed negative but using T-807 was positive marking for Tau.
Corsallis- of the individuals he reviewd other issues is of many cases originaly diagnosed as CTE can turn out to be other neuropathological disroders and only 33% were CTE
-10% of CTE cases devlope MND
There ae also large issues with the lack of explanation of how TBI causes this and the theory is general
-Tau pathology is seen alongside sevral others like TDP-43 and amyloid. (although amyloid plaques are rare)
-mpatholoical definition and theory is still under developement
This is seen in the large overlap of symptoms with other psychological conditions.
- in many cases the symptoms do not align with the sport related injury and in others where symptoms can be releated to sports there is no brain injury.
- No pattern of degen.
0 issue is diagnosis cannot be confrimed until after death as there are limitted biomarkeds
Discuss 2 exmples of alternative oucomes of TBI besides concussion?
Case of an australien cricketer. He wa shit in the tempal by a fast moving ball but claimed to be fine until the next day he colapse.
- His issue was associated with severe disturbance to his vestibular system reuslting in severe vertigo from inner ear damage.
A rugby player found himself unable to shout or swallow. later in the show he felt cold on one side and had a assymetical drrop in his face. He had suffered a stroke in his brain stem.
What network dysfunction can explain Post-traumatic amnesia is TBI?
This has been related to tthe hippocampla circuits in the limbic structure of the tempral lobe. in particualar the precentral gryus projections to the cingulatevia the cingulum. the prehippocmapal gyrus has the EC which is the primary nput into the HPC.
DI simoni et 2016
- Took people with definite brain injury and split them into thos ewithou and without PTA.
- PTA struggled with learning tasks in particular in the use of spatial memory associated with the HPC.
- Using DTI he was able to discover widespread DAI partcularly in the connectons in the cingulum from the cigulate cortex and the Prehipocoapal gyrus.
- hence it is dyfunction here that causes PTA, hippocampal disocnnection from the limbic system.
Whats the next plans fro TBI?
Increased the use of advanced imaging.
more longterm investigation of the efects of brain trauma oer time.
improving biomarkers for CTEs to track them
- example is csf marker CCL11 which seems to track tau pathology. (being looked at)
