Pathophysiology and Epidemiology of Traumatic Brain Injury

Epidemiology &

Pathophysiology of

Head injuriesDr

Unnikrishnan P

1 EPIDEMIOLOGY OF TBI BASED ON INDIAN SCENARIO

PATHOPHYSIOLOGY OF TBI

CEREBRAL VASCULAR PHYSIOLOGY IN TBI

2

3

We will go through…

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

Severity based on GCS

severe= 3-8

Moderate = 9-12

Mild = 13-15

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 period of three years

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.


.


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

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

The scenario is likely to be similar for other Indian cities and in some of the other developing countries.

1

Falls (25%

)2

RTIs (59%)

3

Violence

(10%)

4

.

Various Traumas leading to Brain Injury

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

Education affects our road culture also…• ,

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%).

Should I walk or go by a vehicle?• .

Injury mechanism among two wheelers• .

Pedestrian TBI- ‘Hit By’• .

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.

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.

I am fit…. So unfit for driving• .

A fools’ adventures in a dirty road….

ROLE OF THE CONDITION OF ROADS• ,

Other causesFalls 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.

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)

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.

Hospital stay

• .

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.

Disabilities…• .

Quality of life @ 1 year• .

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.

Income wise….• .

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

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

known and representative of the selected

population.

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.

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).


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


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

brings out problems in diagnostic classification

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PATHOPHYSIOLO

GY PRIMARY

INJURY

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

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.

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

3 basic types of tissue deformation

Compressive - Tissue compression

Tensile - Tissue stretching

Shear - Tissue distortion produced when

tissue slides over other tissue

Types of Primary Injuries

focal injuries (eg, skull fractures, intracranial

hematomas, lacerations, contusions,

penetrating wounds)

diffuse (as in diffuse axonal injury).

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, nose, and throat.

Auditory/vestibular

dysfunctionconductive or sensorineural hearing loss.

Benign paroxysmal positional vertigo

Intracranial hemorrhages

Epidural hematoma

Subdural hematoma

Intracerebral hemorrhages

Intraventricular hemorrhage

Subarachnoid hemorrhage

Intracranial hemorrhages

Epidural hematoma

Subdural hematoma


Intraventricular hemorrhage


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.


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.


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.

Coup and contrecoup

contusionsCoup 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.

Coup and contrecoup

contusionsContrecoup 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.

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

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.

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

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

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PATHOPHYSIOLO

GY

SECONDARY INJURY

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..

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 VRACs and potentially

could be of therapeutic value.

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

sympathoadrenomedullary axis and

serotonergic system

with associated depression in glucose

utilization, contributing to further brain injury.

First stage..

.Ischemiaanaerobic metabolismLA formation

Inadequate energy supplyATP depletionfailure of pumps

↑membrane permeability oedema

Second stage..

. Terminal membrane depolarizationexcitatory AAs

Catabolic intracellular processes

Membrane degradation of vascular and cellular structuresapoptosis

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

induction of early or late apoptotic

programmes

Endogenous opioid peptides

.

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

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.

Cerebral edema-contributors

neurochemical transmitters

increased ICP.

Disruption of the blood-brain barrier

impairment of vasomotor autoregulation

leading to dilatation of cerebral blood vessels

Brain herniation

Supratentorial herniation is attributable to

direct mechanical compression by an

accumulating mass or to increased intracranial

pressure.

Types :

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.

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.

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.


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.


.

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CEREBROVASCULAR

PHYSIOLOGY AFTER

TBI

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

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

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

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


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


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.


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.

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

The vicious cycle “vasodilator cascade”

.

↓MAP

↓CPP&CBF

cerebral vasodilati

on, ↑in CBV

↓CPP

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

Secondary Insults and Injuries

Secondary insults, include systemic causes

such as hypotension, hypocarbia, hypercarbia,

hypoxia, hyperthermia, and hyperglycemia

result in secondary injuries

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

The mechanisms behindCerebral 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

free radical formation.

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.

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 due to increased adenosine availability

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 secondary brain damage may

occur even in the presence of normal CPP or

ICP

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

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

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

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 synthesize scar

tissue

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

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 therapeutic (anti-apoptotic)

interventions

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

THANK YOU

Health & Medicine

Pathophysiology and Epidemiology of Traumatic Brain Injury