Traumatic brain injury (TBI) results from external mechanical forces causing temporary or permanent brain dysfunction. The document discusses the definition, types, risk factors, biomechanics, pathology and pathophysiology of TBI. It notes that TBI causes around 200 injuries per 100,000 people annually and is a major cause of disability. Common pathological findings include contusions, diffuse axonal injury, vascular lesions and cerebral edema. The pathophysiology involves neuronal death through necrosis and apoptosis, as well as effects on cerebral metabolism and circulation.

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2. Pathology and pathophysiology of
Traumatic Brain Injury- TBI
PRESENTER: DR. JITHIN T JOSEPH
CHAIR : DR.JAYAPRAKSH P
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3. Overview
• Definition
• Problem statement
• Types of head injury
• Risk factors
• Biomechanics of head injury
• Pathological changes
• Pathophysiology
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5. What Is TBI?
• Traumatic brain injury (TBI) is a non degenerative, non
congenital insult to the brain,from an external mechanical
force, possibly leading to permanent or temporary
impairment of cognitive, physical, and psychosocial
functions, with an associated diminished or altered state of
consciousness.
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6. Problem statement ?
• About 200 per 100 000 population per year suffer a head injury.
• In the majority of these the head injury is classified as mild yet as
many as 100 per 100 000 per year go on to suffer significant disability
at 1 year.
• In 1991 the economic cost in the USA was put at more than $48
billion per year
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7. Problem statement ?
• In the developed world, head injuries may be declining, probably
reflecting better road safety.
• But in the developing countries the picture is not so, may be due to
increased use of two wheelers, poor roads
• The vast majority of head injuries in civilian life are closed injuries and
result from acceleration/deceleration forces.
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8. INDIAN SCENARIO
• Nearly 1.5 to 2 million persons are injured and 1 million succumb to death
every year in India(1)
• Road traffic injuries are the leading cause (60%) of TBIs followed by falls
(20%-25%) and violence (10%)
• Alcohol involvement is known to be present among 15%-20% of TBIs at the
time of injury
• Most of the time the prehospital care and the golden hour care is delayed ,
adding on to mortality and morbidity.
1. http://www.ijciis.org/article.asp?issn=2229-5151;year=2012;volume=2;issue=3;spage=167;epage=171;aulast=Agrawal
2. http://www.nature.com/sc/journal/v45/n9/full/3102005a.html
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9. INDIAN SCENARIO
• Mortality is 6.4% with the majority of deaths occurring among
persons in the most productive age groups(20-40 years).(2)
• Recovery with minimal disability was observed in only approximately
60% of cases
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1. http://www.ijciis.org/article.asp?issn=2229-5151;year=2012;volume=2;issue=3;spage=167;epage=171;aulast=Agrawal
2. http://www.nature.com/sc/journal/v45/n9/full/3102005a.html

10. TBI TYPES
• OPEN VS CLOSED
• DIFFUSE VS LOCAL
• MILD/MODERATE/SEVERE
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11. TBI SEVERITY CLASSIFICATION
Parameters MILD MODERATE SEVERE
Duration of LOC 0-30 mnts 30mnts -24 hours >24 hours
PTA(post traumatic
amnesia)
<1 day 1-7 days >7 days
GCS SCORE 13-15 9-12 <9
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12. GLASGOW COMA SCALE
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13. Risk factors for sustaining TBI
1. Male sex
2. Younger age (peak at 15–24 years with a smaller peak in the elderly)
3. Alcohol
4. Lower socioeconomic status
5. Individuals with a history of substance abuse
6. Individuals who have suffered a previous TBI
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14. Biomechanics of concussion and
traumatic brain injury
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15. What is a concussion?
• Concussion may be defied as an immediate and transient alteration
or loss of consciousness, or other disturbance of neurological
function, when sudden mechanical forces are applied to the head.
• Loss of consciousness is particularly likely to follow
acceleration/deceleration injuries where there is a rotational
component.
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16. • Rotation around coronal axis(side to side) are more likely to produce
concussion comparing to rotation around sagittal axis(nodding
movement)
• Impacts to the temporo parietal area are most likely to produce
concussion
• Also side impacts in car accidents are possibly more likely to be
associated with severe head injury.
• According to this concept injuries sustaining to face should have less
head injury , but in real life situation its not true.
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17. • Static closed head injuries, in which there is no
acceleration/deceleration of the brain, are relatively unlikely to
produce loss of consciousness (Russell & Schiller 1949).
• This was confirmed in a series of bitemporal crush injuries (Gonzalez
Tortosa et al. 2004); less than half had loss of consciousness.
• In open head injuries the dura is breached and laceration of brain
tissue is present at the site of impact but countercoup is slight or
even absent.
• The extent of the damage in open head injuries depends on the
velocity of the object.
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18. • Penetrating injury from a knife or spike (low velocity) causes localised
damage around the track.
• However, bullet wounds, particularly from modern high-velocity rifles,
produce massive shock waves throughout the brain causing
widespread damage and usually death.
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19. Pathology of head injury
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20. • The pathological changes in TBI are usually noted during autopsy,
variety of findings may be seen and this can be due to
1. Result of direct physical damage to the brain parenchyma.
2. Complicating factors such as vascular disturbances, cerebral
oedema and anoxia.
3. Infections – in penetrating injuries
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21. Contusions
• Most common finding in TBI
• Severe contusions comprise a mixture of haemorrhage and necrosis,
typically near the surface of the brain, due to severe localised forces.
• In most injuries there may be contusions at different parts of brain so
locating area of impact using site of contusion may be difficult
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22. Contusions..
• There are certain areas of brain with increased predilection for head
injury
1. The orbital surface of the frontal lobes, particularly medially
2. The underside and tips of the temporal lobe
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23. • When the head is at rest at the time of injury, as in assault, the lesion
will be maximal at the site of impact.
• When in motion, as in falls or traffic accidents, the countercoup
effect is likely to be most pronounced.
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26. Diffuse axonal injury
• The diffuse interruption and degeneration of nerve fibres, with breakdown
and resorption of myelin and the formation of retraction balls, is called
diffuse axonal injury.
• First reported in patients dying after very severe brain injuries.
• Acceleration /deceleration injuries produce swirling movements
throughout the brain. The resulting rotational and linear stresses tear and
damage nerve fibres throughout the brain.
• It may be seen in mild closed head injuries also
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27. Diffuse axonal injury..
Katz and Alexander defined patients with diffuse axonal injury as those
with
1. Acceleration /deceleration injury
2. Immediate loss of consciousness
3. Computed tomography (CT) and magnetic resonance imaging
(MRI) findings of petechial white matter haemorrhages, isolated
intraventricular or subarachnoid haemorrhage, diffuse swelling or
normal scan.
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28. • Changes in the following areas can be seen in the brain
1. Parasagittal central white matter and the grey–white matter
interface of hemispheres
2. The corpus callosum
3. The long tracts in the brainstem.
4. With more severe injuries small haemorrhages are seen,
particularly in the corpus callosum and the parasagittal white
matter.
5. In the longer term, severe diffuse axonal injury produces
ventriculomegaly with thinning of the corpus callosum.
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29. • Clinically, it may present with
1. Prolonged loss of consciousness in the absence of intracerebral
contusions.
2. Later results in neurological sequelae related to damage to white
matter tracts in the brainstem, particularly the superior cerebellar
peduncle- slurring of speech and ataxia.
3. Diffuse axonal injury is now sometimes used to describe a clinical
syndrome of diffuse injury where loss of consciousness is not
explained by focal lesions.
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31. Vascular lesions
This can be
• Scattered punctate haemorrhages throughout the brain, along with
large and small infarcts.
• Sometimes the whole or part of the territory of a major cerebral
artery may become necrotic.
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32. This can be due to combination of factors such as
1. Reduced cerebral blood flow immediately after the injury
2. Hypotension , embolism, pre-existing atheroma
3. Rise of intracranial pressure sufficient to occlude the arteries
4. Spasm of vessels due to mechanical strain at the junction of brain
and vessel
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33. • Posterior cerebral artery strokes occur in tentorial herniation, due to
brain compressing the vertebro-basilar sysytem
• Dissection of the major cerebral arteries, both carotid and
vertebrobasilar, can occur after head injury.
• Extensive bleeding may occur into the subarachnoid space, with the
appearance of blood in the cerebrospinal fluid(CSF)
• Subdural hematomas , intracranial bleeds can occur
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T1 T2

35. Cerebral oedema
• Its an acute finding
• It is more common to occur in the region of contusions, lacerations,
infarcts and haematomas.
• Cellular mechanisms are responsible , and its more common in
children
• Diffuse oedema causes increased ICT, which can cause herniation of
brain through tentorium, which can be fatal.
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• In less severe cases there may be focal necrosis and
haemorrhage in the medial temporal lobe structures and
brainstem , around the aqueduct and fourth ventricle
(Duret’s haemorrhages).

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Effaced sulcus
Widened gyri
Obliterated
ventricles

38. Cerebral anoxia
• CAUSES:
• Cerebral oedema and other local changes
• Hypotension , blood loss.
• Disturbances in regulation of the cerebral circulation
• Respiratory insufficiency
• Maintenance of arterial oxygenation and blood pressure are crucial to
management in the GOLDEN HOUR to prevent anoxic damage.
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• Diffuse brain oedema
• Loss of grey and white matter
differentiation( reversal sign)
• White cerebellum sign
• Linear hyper density outlining
cortex-cortico laminar necrosis
Normal CT brain

40. • Anoxia can cause various neuronal lesion in brain and it is aggravated
by increased metabolic demand.
• Cortical necrosis in the depths of the cortical sulci
• Lesions in Ammon’s horn and the basal ganglia
• Disappearance of Purkinje cells from the cerebellum
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41. • In children with non traumatic brain injury(shaken baby syndrome) ,
the possible mechanism of brain injury is hypoxia than diffuse axonal
injury
• The hypoxia is as a result of apnoea following damage to the cranio-
cervical junction
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42. Open head injuries
• In open head injuries the skull and dural coverings are perforated.
• Extensive local laceration may lead to large cystic cavities and
ventricular dilatations, haemorrhage may occur locally,
• Infection is an ever-present risk.
• Small fractures in the neighbourhood of the nasal sinuses may pave
the way for meningitis or local abscess formation.
• Following gunshot wounds, cerebral artery spasm (associated with
subarachnoid bleeding) may be seen.
• The fibro-glial scar that follows open head injury increases the risk of
epilepsy.
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45. Pathophysiology of COMA/CONCUSSION
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46. • The possible mechanisms of coma following head injury is still poorly
understood
1. Brain stem involvement
• Loss of consciousness , respiratory arrest, generalised vasoconstriction, loss of
corneal reflexes and paralysis of deglutition are seen in coma which are usually
brainstem functions.
• The non epileptic seizures that can follow head injury also points to brainstem
involvement .
• Experimental studies in monkeys also showed that it’s the medial RAS EEG
changes are more prominent than cortical EEG changes.
• Some studies suggested the role of cholinergic system, which also point to
brainstem .
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47. 2. It has been proposed that the forces and resulting injury usually
spread centripetally, from the cortex to the brainstem in which case
only more severe head injuries affect the brainstem. (Ommaya &
Gennarelli 1974),
3. Mechanically induced cellular depolarisation
• Trauma results in massive and rapid release of potassium into the extracellular
space
• This is associated with excessive glutamate release and produces depolarisation
of neurones and unconsciousness
• Followed by a hypermetabolic state as Na+/K+ pumps are activated to restore
extracellular potassium levels to normal.
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48. 4. Histological studies can provide only indirect evidence of
the mechanism of loss of consciousness, especially since mild
concussion may represent loss of function without structural alteration.
• Neuronal changes have been shown in the brainstem of animals in proportion to
the strength of the blows inflicted.
5. Neuroimaging in head injury suggests that hemisphere damage may
be associated with loss of consciousness, with brainstem mechanisms
suffering secondarily.
6. Raised intracranial pressure early after injury predicts poor
prognosis and is likely to be one factor contributing to coma (Signorini
et al. 1999a)
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49. Pathophysiology of diffuse axonal injury
• It takes hours to develop.
• At the moment of impact there is little evidence of axons being torn
apart, but their axolemma is damaged by the stretching and
compression forces.
• Calcium enters cell, activate proteases and it damages intracellular
transport proteins( neuro filaments and micro tubules), and thus
axonal transport is inhibited.
• Transport products accumulate, resulting in axonal swelling,
lobulation, and ultimately transection with formation of the classic
retraction ball in 1-2 days. 49

50. • Over the ensuing weeks and months attempts at regrowth and
regeneration can be observed, with sprouting from the proximal
segment
• The β-amyloid precursor protein (βAPP)
• Is a protein transported along axons and becomes detectable by
immuno-cytochemical staining when the axonal transport systems are
disrupted and it accumulates.
• It is used as a sensitive marker of diffuse axonal injury which become
evident in first few hours when there is no histological changes.
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51. • High levels are found following closed head injury.
• Not specific, seen in hypoxic brain injury( different staining pattern),
and in opioid overdose.
• New concept is to differentiate traumatic vs non traumatic DAI
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53. Neuronal death
• Both necrotic and apoptotic mechanisms are involved
• There is overlap of both mechanisms
• Both are characterised by an increased intracellular calcium
• Both neurones and glial cells are affected
• Both necrotic and apoptotic cell death are seen in focal injury
• Necrotic cell death being predominant in the core of the damaged
area, and apoptotic cell death being observed in the pericontusional
zone.
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54. • Necrotic cell death
• Necrotic cell death is produced by cellular disruption, either from the destructive
forces of the trauma on the cell membrane or due to ischaemia
• Necrotic cell death is rapid and relatively passive, with swelling of cytoplasm and
mitochondria.
• Mechanisms
1. Toxic effects of excitatory neurotransmitters, particularly glutamate
2. Mitochondrial dysfunction
3. Calcium activation of proteases and phospholipases
4. Formation of toxic free radicals and low intracellular magnesium.
5. Immunological processes -activation of interleukins
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55. • Apoptotic cell death
• Is an active process involving receptor activation and enzymatic processes
• Tissue studies had shown that there is alteration in the pro and anti apoptotic
factors(Bcl2)
• There is upregulation of pro apoptotic proteins like bax and caspases and down
regulation of BCL2 family
• Its also found that there is increased FAS ligand mediated cell death
• Mechanisms
• Caspases, which cleave proteins, are central to the pathways causing cell death
• Activation of endonucleases that attack the cell’s DNA, producing DNA fragments
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56. Effects on cerebral metabolism
• There is increased metabolic demand following head injury.
• Alcoholics are at an increased risk ,because of the chance of
withdrawal states which in turn increases metabolic demand.
• The blood flow is reduced in the first 24 hours followed by
hyperaemia (luxury perfusion)
• Glucose uptake is also increased in the first 3-4 days followed by
reduced uptake lasting for weeks in severe head injury.
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57. • Global reductions in blood flow after head injury are associated with
worse outcome
• Disordered autoregulation may contribute to a mismatch between
cerebral blood flow and metabolism.
• Patients with very severe injury show reduced oxygen and glucose
utilisation in grey matter.
• Those with lower cerebral metabolic rates have worse outcomes, and
reductions in deep structures relate to prolonged coma.
• In white matter, a mismatch between increased glucose metabolism
but without increased oxygen consumption may be seen.
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58. Aβ peptide deposition
• Aβ peptides, which are produced by cleavage of βAPP protein, have been found to
accumulate in about 30% of patients after TBI and may form plaques similar to those
seen in Alzheimer’s disease.
• This lead to the proposal that head injury may be a risk factor for Alzheimer’s disease.
• The ε4 allele of apolipoprotein E (ApoE) is known to be a risk factor for Alzheimer’s and
other neurological diseases, perhaps related to effects on Aβ metabolism.
• The relationship between ApoE ε4 status and head injury outcome had been studied.
• This have found that ε4-positive status (whether homozygous or heterozygous) is
associated with worse outcome.
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59. Neurotransmitters
• Studies had shown that there is reduced activity of dopaminergic
system in the CNS than nor adrenaline after head injury particularly in
frontal lobes.
• This is evident from a study where dopamine agonists were used to
treat loss of executive function.
• In patients with very severe brain injury it has been suggested that
lesions around the substantia nigra may cause parkinsonism.
• Single photon emission computed tomography (SPECT) has found
evidence of dopamine transporter loss in striatum after TBI, indicating
presynaptic dopamine loss. 59

60. • Elevated acetyl choline levels are found in CSF after head injury.
• In the long term, reductions in choline acetyltransferase, the presynaptic
marker of cholinergic neurones, are found in cortex without changes in
postsynaptic nicotinic or muscarinic receptors. (Murdoch et al. 1998) .
• There is histological evidence of damage to nucleus basalis of Meynert
• MRI findings of reduced grey matter density of basal forebrain ,being the
location of the nucleus basalis of Meynert and the septal nuclei, the main
cholinergic nuclei and source of presynaptic neurones also give evidence
for this theory.
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62. Thank you….
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