describes the pathophysiology and epidemiology of TBI based on Indian scenario...

2. We will go through…
1 EPIDEMIOLOGY OF TBI BASED ON INDIAN SCENARIO
2 PATHOPHYSIOLOGY OF TBI
3 CEREBRAL VASCULAR PHYSIOLOGY IN TBI

3. Definition
Traumatic brain injury 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

4. Severity based on GCS
severe= 3-8
Moderate = 9-12
Mild = 13-15

5. We know all about others ;
nothing about ourselves….!
At the global level, the annual incidence and
mortality from Traumatic Brain Injuries (TBIs) is 200
and 20 per 1,00,000 per year, respectively
National level data in India is not available for
traumatic brain injuries as in many developed
countries.
• The only epidemiological study was undertaken in
Bangalore by Dr Gururaj et al at NIMHANS during
the period March 2000 to March 2003, over a

6. What it revealed about TBI IN
INDIA….
the incidence, mortality and case fatality rates were
150/100000, 20/100000 and 10%, respectively
At the national level, nearly two million people
sustain brain injuries, 0.2 million loose their lives
and nearly one million need rehabilitation services
every year.

7. What it revealed about TBI IN
INDIA….
.

8. What it revealed about TBI IN
INDIA….
Nearly 10,000 people sustain brain injury every
year in the city of Bangalore with more than 1,000
deaths.
20 - 25 patients are registered every day with a
head injury at NIMHANS and TBIs constituted 39%
of total registration during 2000

9. How they worked it out?
7,164 persons were enrolled into a Neurotrauma
Registry during the year 2000 at NIMHANS.
While Phase–1 study focused on identifying and
measuring all epidemiological correlates in a hospital
setting,
phases–II and III focused on identifying disability
patterns, extent of socio-economic burden &
measuring quality of life

10. Various Traumas leading to Brain Injur
RTIs
Falls
(25%) (59%)
1 2
3 4
Violenc
e (10%) .

11. The social picture
• majority of these individuals are males, in their
early years (5 - 44 years) [male to female ratio of
4:1]
Individuals in the age group of 21 - 35 years were
represented to the extent of 40%
The majority of those injured were with less than
collegiate levels of education

12. Education affects our road
culture also…
• ,

13. Road Traffic Injuries
RTIs occurred predominantly in the age group of 15
- 40 years, among men and during evenings and
nights (66%).
Pedestrians (26%), two-wheeler riders (31%) and
pillions (12%) and bicyclists (8%) were represented
in higher numbers
The majority of the RTIs took place in midblocks of
roads (70%).

14. Should I walk or go by a
vehicle?
• .

15. Injury mechanism among two
wheelers
• .

16. Pedestrian TBI- „Hit By‟
• .

17. Our genome always shows
perfect inheritance of
disobedience!
Not wearing helmets
driving under influence of alcohol
over speeding and overtaking
crossing in the middle of the road
……………………
were the major behavioural factors.

18. Remain indoor for a prosperous
life!
Poor visibility of vehicles and or roads
mechanical problems of vehicles
……………….……
were responsible for one-third of injuries
Road design and structural issues
……………………..
were responsible for another 30% of TBIs.

19. I am fit…. So unfit for driving
• .

20. A fools‟ adventures in a dirty road….

21. ROLE OF THE CONDITION
OF ROADS
• ,

22. Other causes
Falls were the second-leading cause (25%), with the
majority occurring in children and elderly.
Amongst them domestic falls (57%) were the leading
cause followed by falls in public places (15%).
Violence/assault (10%) were the third-leading cause,
more frequent among men and associated with use
of blunt physical objects.

23. Prehospital and emergency care
was poor in these areas:
availability of First Aid Services
high referrals from local hospitals
safer transportation
longer interval between injury and reaching
definitive hospital (only 13% within one hour and
40% in one to three hours)

24. Severity and patterns
In total, 71% of TBIs were mild, 15% moderate and
13% severe in nature based on Glasgow Coma
Scale.
Concussions (36%), contusion (32%), skull
fractures (12%) and brain haemorrhages (13%)
were the injury patterns.

25. Hospital stay
• .

26. We are just observers in many
situations…
Severe polytrauma was noticed in 22% of total
injuries.
5.5% died in hospital and 4% were discharged in a
persistent vegetative state.
Severe and moderate disabilities were observed in
15% and 37%, respectively.
Various types of disabilities affecting activities of
daily living, memory, communication, social
interaction and ability to work were seen in 52% of
the patients at hospital discharge time.

27. Disabilities…
• .

28. Quality of life @ 1 year
• .

29. In 1 sec, life is turned upside
down…
35% had problems in health, social, economic
dimensions of life at 1-year follow-up
more than 50% of them continued to have
problems in similar areas at second year follow up
The quality of life was poor in nearly 30% of brain-
injured persons at two years post discharge.

30. Income wise….
• .

31. When we treat him/her for umpty
no: of days, we should be aware
of….
major economic burden on individuals and families
to meet costs of hospitalization and rehabilitation
affected families had to spend resources [ their own
or borrowed ] to reach definitive hospitals, to take
care of injured person during hospital stay and after
discharge.
The indirect costs due to loss of work and income
are substantial

32. Foundation for gathering all
these data is a……
a neurotrauma register
provides
detailed description of all individuals sustaining a
TBI
during a given period (beginning with a date)
in a defined population,
the major demographic features of which are

33. CRITERIA
• The criteria of a neurotrauma registry are:-
.
1) Uniform definition
2) Inclusion of all subjects with a TBI in a defined area
3) Case identification from multiple sources
4) Case evaluation by a trained team
5) Consistency in diagnosis
6) Established classification methods.

34. HOW IT IS VITAL IN
EPIDEMIOLOGY OF TBI
The registry can identify major causes, pattern and
mode of injury occurrence in subcategories of
injured persons, thus identifying "Population at risk”
It improves diagnostic accuracy as all subjects are
weighed in comparison with gold standard.
Registry helps in in establishing cause-effect
associations over a period of time (e.g.: Epilepsy
and TBI's).

35. HOW IT IS VITAL IN
EPIDEMIOLOGY OF TBI
The registry reveal vital data on morbidity, mortality
and disability rates (Incidence,fatality and disability
rates)
will reveal temporal changes in occurrence and
pattern of neurotrauma
it can serve as a basic ground tool for clinical and
intervention trials. It would highlight how much
change has been brought about by an intervention

36. HOW IT IS VITAL IN
EPIDEMIOLOGY OF TBI
helps in developing and understanding prognosis in
neurotrauma management and in anticipating
future risks.
reveal the socioeconomic burden and health needs
of a community
this will help in creating awareness among policy
makers and public to place neurotrauma prevention
high on the public health agenda

37. .
PATHOPHYSIOLOG
Y PRIMARY
INJURY

38. TBI
Traumatic brain injury (TBI) is the result of an
external mechanical force applied to the cranium
and the intracranial contents, leading to temporary
or permanent impairments, functional disability, or
psychosocial maladjustment

39. Injuries are divided into 2
subcategories
(1) primary injury, which occurs at the moment of
trauma, and
(2) secondary injury, which occurs immediately
after trauma and produces effects that may
continue for a long time.

40. Primary injury-
Physical mechanisms
Impact loading - Collision of the head with a solid
object at a tangible speed [through a combination
of contact forces and inertial forces]
Impulsive loading - Sudden motion without
significant physical contact
Static or quasistatic loading :occurs when a slowly
moving object traps the head against a fixed rigid
structure and gradually squeezes the skull, causing
many comminuted fractures and deforms the brain

41. 3 basic types of tissue
deformation
Compressive - Tissue compression
Tensile - Tissue stretching
Shear - Tissue distortion produced when tissue
slides over other tissue

42. Types of Primary Injuries
focal injuries (eg, skull fractures, intracranial
hematomas, lacerations, contusions, penetrating
wounds)
diffuse (as in diffuse axonal injury).

43. Skull fractures
vault fractures or basilar fractures.
stellate, closed, or open fractures
depressed or nondepressed
simple fracture and compound fracture
Vault fractures may extend into the sinuses
Basal skull fractures may be associated with injuries
to the cranial nerves and discharges from the ear,

44. Auditory/vestibular dysfunction
conductive or sensorineural hearing loss.
Benign paroxysmal positional vertigo

45. Intracranial hemorrhages
Epidural hematoma
Subdural hematoma
Intracerebral hemorrhages
Intraventricular hemorrhage
Subarachnoid hemorrhage

46. Intracranial hemorrhages
Epidural hematoma
Subdural hematoma
Intracerebral hemorrhages
Intraventricular hemorrhage
Subarachnoid hemorrhage

47. Epidural hematoma
laceration of the dural arteries or veins, or by diploic
veins in the skull's marrow
a tear in the middle meningeal artery
when hematoma occurs from laceration of an artery,
blood collection can cause rapid neurologic
deterioration.

48. Intracerebral hemorrhages
Due to injury to larger, deeper cerebral vessels
occurring with extensive cortical contusion.
Intraventricular hemorrhage tends to occur in the
presence of very severe TBI and is, therefore,
associated with an unfavorable prognosis.

49. Subarachnoid hemorrhage
by lacerations of the superficial microvessels in the
subarachnoid space.
If not associated with another brain pathology, this
type of hemorrhage could be benign.
may lead to a communicating / noncommunicating
hydrocephalus if blood products obstruct the
arachnoid villi / the third or fourth ventricle.

50. Coup and contrecoup
contusions
Coup contusions occur at the area of direct impact to
the skull
and occur because of the creation of negative
pressure
when the skull, distorted at the site of impact, returns
to its normal shape.

51. Coup and contrecoup
contusions
Contrecoup contusions are are located opposite the
site of direct impact.
Cavitation in the brain, from negative pressure due to
translational acceleration impacts
as the skull and dura matter start to accelerate before
the brain on initial impact.

52. contusion is coup or
contrecoup type?
impact from a small, hard object tends to dissipate at
the impact site, leading to a coup contusion.
In contrast, impact from a larger object causes less
injury at the impact site, because energy is dissipated
at the beginning or end of the head motion, leading to
a contrecoup contusion

53. Concussions
caused by deformity of the deep structures of the
brain
leading to widespread neurologic dysfunction
that can result in impaired consciousness or coma
Concussion is considered a mild form of diffuse
axonal injury.

54. Diffuse axonal injury
characterized by extensive, generalized damage to
the white matter of the brain.
Strains of the tentorium and falx during high-speed
acceleration/deceleration produced by lateral motions
of the head may cause the injuries.
also could occur as a result of ischemia

55. Neuropathologic findings in
patients with diffuse axonal
injury
Grade 1 - Axonal injury mainly in parasagittal white
matter of the cerebral hemispheres
Grade 2 - As in Grade 1, plus lesions in the corpus
callosum
Grade 3 - As in Grade 2, plus a focal lesion in the
cerebral peduncle
...........Gennarelli and colleagues

56. .
PATHOPHYSIOLOG
Y
SECONDARY

57. Secondary injuries
Due to further cellular damage from the effects of
primary injuries.
develop over a period of hours or days following the
initial traumatic assault.
mediated through the following neurochemical
mediators..

58. Excitatory amino acids
glutamate and aspartate
influx of Cl,Na and Ca, leading to acute neuronal
swelling., vacuolization, and neuronal death
↓high-energy phosphate stores or ↑ free radical
production...
cause astrocytic swellings via volume-activated anion
channels (VRACs). Tamoxifen is a potent inhibitor of

59. Endogenous opioid peptides
modulating the presynaptic release of EAA
neurotransmitters.
Heightened metabolism in the injured brain is
stimulated by
an increase in the circulating levels of
catecholamines
from TBI-induced stimulation of the

60. First stage..
.

61. Second stage..
.

62. Oxidative stress
excessive production of reactive oxygen species due
to excitotoxicity and exhaustion of the endogenous
antioxidant system induces peroxidation of cellular
and vascular structures.These mechanisms can
cause....
immediate cell death
inflammatory processes and

63. Endogenous opioid peptides
.

64. Increased intracranial
pressure
The severity increase due to heightened ICP [esp if
the pressure exceeds 40 mm Hg.]
also can lead to cerebral hypoxia, cerebral ischemia,
cerebral edema, hydrocephalus, and brain herniation

65. Hydrocephalus
communicating type of hydrocephalus is more
common
The noncommunicating type of hydrocephalus is
often caused by blood clot obstruction of blood flow
at the interventricular foramen, third ventricle,
cerebral aqueduct, or fourth ventricle.

66. Cerebral edema-contributors
neurochemical transmitters
increased ICP.
Disruption of the blood-brain barrier
impairment of vasomotor autoregulation leading to
dilatation of cerebral blood vessels

67. Brain herniation
Supratentorial herniation is attributable to direct
mechanical compression by an accumulating mass or
to increased intracranial pressure.
Types :

68. Subfalcine herniation
The cingulate gyrus of the frontal lobe is pushed
beneath the falx cerebri when an expanding mass
lesion causes a medial shift of the ipsilateral
hemisphere.
This is the most common type of herniation.

69. Central transtentorial
herniation
characterized by the displacement of the basal nuclei
and cerebral hemispheres downward while the
diencephalon and adjacent midbrain are pushed
through the tentorial notch.

70. Cerebellar herniation
involves the displacement of the medial edge of the
uncus and the hippocampal gyrus medially and over
the ipsilateral edge of the tentorium cerebelli
foramen, causing compression of the midbrain; the
ipsilateral or contralateral third nerve may be
stretched or compressed.

71. Cerebellar herniation
This injury is marked by an infratentorial herniation in
which the tonsil of the cerebellum is pushed through
the foramen magnum and compresses the medulla,
leading to bradycardia and respiratory arrest.

72. Cerebellar herniation
.

73. .
CEREBROVASCULAR
PHYSIOLOGY AFTER
TBI

74. Altered Cerebral Blood Flow
and Metabolism
can cause flow-metabolism uncoupling, resulting in
cerebral ischemia or cerebral hyperemia;
Hyperemia is as bad as ischemia
[vasoparalysis↑CBV ↑ICP]
show 3 phases
FIRST[6-12 HRS]: brain may suffer poor perfusion and
cerebral ischemia
SECOND phase of hyperemia[CBF>55ml/100g/min]: With
luxury perfusion & ↑ ICP
THIRD: vasospasm and poor perfusion

75. Altered Cerebral Blood Flow
and Metabolism
Focal/global ischemia occurs frequently & is a a
major causative factor for poor outcome
the critical threshold of CBF for the development of
irreversible tissue damage is 15 ml 100 g21 min21 in
patients with TBI

76. How TBI causes ischemia?
Morphological injury (e.g. vessel distortion)
hypotension in the presence of autoregulatory failure
inadequate availability of nitric oxide or cholinergic
neurotransmitters
potentiation of prostaglandin-induced
vasoconstriction

77. Altered CO2 Vasoreactivity
During the early period, CO2 vasoreactivity can be
transiently impaired, but generally recovers after 4 to
7 days
may be associated with cerebral hyperemia, cerebral
ischemia, or intracranial hypertension
CO2 vasoreactivity is less in patients with lower
baseline CBF

78. Altered CO2 Vasoreactivity
Cerebrovascular CO2-reactivity seems to be a more
robust phenomenon.
It is in patients with severe brain injury and poor
outcome, where CO2-reactivity is found to be
impaired in the early stages ; it was intact in most
other patients with lesser insults

79. Altered CO2 Vasoreactivity
hyperventilation to induce cerebral vasoconstriction
and reduce CBF, ICP and cerebral blood volume may
unintentionally lead to secondary ischemic damage
after TBI
hyperventilation may not be effective in TBI if CO2
vasoreactivity is decreased.

80. Altered CO2 Vasoreactivity
hyperventilation to induce cerebral vasoconstriction
and reduce CBF, ICP and cerebral blood volume may
unintentionally lead to secondary ischemic damage
after TBI
hyperventilation may not be effective in TBI if CO2
vasoreactivity is decreased.

81. Impaired Cerebral Pressure
Autoregulation
incidence is 28% after moderate and 67% after
severe TBI
a recent study of severe pediatric TBI reported that
cerebral autoregulation often changed and worsened
during the first 9 days after injury

82. The vicious cycle “vasodilator
cascade”
.
↓CPP ↓MAP
cerebral
vasodilatio ↓CPP&C
n, BF
↑in CBV

83. Impaired Cerebral Pressure
Autoregulation
autoregulatory vasoconstriction seems to be more
resistant compared with autoregulatory vasodilation
indicates that patients are more sensitive to damage
from low rather than high CPPs.16

84. Secondary Insults and Injuries
Secondary insults, include systemic causes such as
hypotension, hypocarbia, hypercarbia, hypoxia,
hyperthermia, and hyperglycemia
result in secondary injuries

85. Cerebral vasospasm
occurs in more than one-third of patients with TBI and
indicates severe damage to the brain.
• onset varies from post-traumatic day 2 to 15 and
hypoperfusion
• (haemodynamically significant vasospasm) occurs
• in 50% of all patients developing vasospasm

86. The mechanisms behind
Cerebral vasospasm
chronic depolarization of vascular smooth muscle
due to reduced potassium channel activity
release of endothelin along with reduced availability
of nitric oxide
cyclic GMP depletion of vascular smooth muscle
potentiation of prostaglandin-induced
vasoconstriction

87. Cerebral metabolic
dysfunction
Cerebral metabolism and cerebral energy state are
frequently
reduced after TBI
outcome is worse in patients with lower metabolic
rates compared with those with minor or no metabolic
dysfunction.

88. Mechanisms-metabolic
dysfunction
mitochondrial dysfunction with
reduced respiratory rates and ATP-production
a reduced availability of the nicotinic co-enzyme pool
intramitochondrial Ca2-overload ……
may not be associated with matching decreases in
CBF.
reflects uncoupling of CBF and metabolism, probably

89. Cerebral oxygenation
imbalance between cerebral oxygen delivery and
cerebral oxygen consumption leading to brain tissue
hypoxia.
have identified the critical threshold of brain tissue
oxygen pressure in patients suffering from TBI 15–
10 mm Hg PtO2 below which infarction of neuronal
tissue occurs.
oxygen deprivation of the brain with consecutive

90. Oedema - vasogenic
caused by breakdown of the endothelial cell layer of
brain vessels
allows for uncontrolled ion and protein transfer from
the intravascular to the extracellular (interstitial) brain
compartments
Anatomically, this pathology increases the volume of
the
extracellular space

91. Oedema - vasogenic
caused by breakdown of the endothelial cell layer of
brain vessels
allows for uncontrolled ion and protein transfer from
the intravascular to the extracellular (interstitial) brain
compartments
Anatomically, this pathology increases the volume of
the
extracellular space

92. Oedema - Cytotoxic
• Caused by intracellular water accumulation due to an
increased cell membrane permeability for ions, ionic
pump failure due to energy depletion, and cellular
reabsorption of osmotically active solutes
• irrespective of the integrity of the vascular endothelial
wall.
• more frequent than vasogenic oedema in TBI

93. Inflammation
Both primary and secondary insults activate the
release of cellular mediators including
proinflammatory cytokines, prostaglandins, free
radicals, and complement  induce chemokines and
adhesion molecules and in turn mobilize immune and
glial cells
injured and adjacent tissue is replaced astrocytes
produce microfilaments and neutropines ultimately to

94. Inflammation
The additional release of vasoconstrictors
(prostaglandins and leucotrienes)
• the obliteration of microvasculature through adhesion
of leucocytes and platelets,
• the blood–brain barrier lesion,
• and the oedema formation
• further reduce tissue perfusion and consequently
aggravate secondary brain damage

95. Necrosis vs apoptosis
Two different types of cell death may occur after TBI
Necrosis occurs in response to severe mechanical or
ischaemic/hypoxic tissue damage
neurons undergoing apoptosis are morphologically
intact
The clinical relevance of apoptosis relates to the
delayed onset of cellular deterioration, potentially
offering a more realistic window of opportunity for

96. Outcome of the last hour should
be…..
Understanding the multidimensional cascade of
injury offers therapeutic options including the
management
of CPP, mechanical (hyper-) ventilation, kinetic therapy
to improve oxygenation and to reduce ICP, and
pharmacological intervention to reduce excitotoxicity
and ICP

97. THANK YOU