ANAT2012 - Module 8 Brain Injury

2 types of dura mater

periosteal and meningeal

3 purposes of dural folds

1. partially separate intracranial compartments

2. hold them together

3. restrict movement

describe falx cerebri

- fold of dura mater that dips into the longitudinal fissure and divides cerebral hemispheres

- acts as a seatbelt -> if left hemisphere moves, falx cerebri reduces movement of right hemisphere

describe tentorium cerebelli

separates cerebral cortex (supratentorial) from cerebellum (infratentorial)

what is tentorial notch

- anterior free edge of tentorium cerebella

- encircles midbrain

- allows cerebellum and midbrain to communicate

purpose of CSF for brain

provides buoyancy and cushioning of mechanical forces. Brain would be distorted by its own weight if not suspended in CSF

describe brain's storage mechanisms for glucose

is not effective - requires continuous and copious blood supply

where can fluid leak throughout brain interstitial space

1. fluid leaks across BBB and enters interstitial space

2. fluid flows into choroid plexus which creates CSF, then flows into ventricles

3. CSF from ventricle flows across ependymal lining into interstitial space

4. CSF flows into spinal cord through subarachnoid space

describe texture of brain tissue (4 points)

1. inhomogeneous

2. cells include neurons, glia, grey/white matter

3. ECM composed of 70% interstitial fluid and various fibres/cells

4. fibre direction and length is inhomogeneous as well

describe the 2 ways external loading to head may affect intracranial contents

1. direct contact - displacing or deforming skull, has high focal connective energy and low cranial momentum (e.g. fixed head + blow)

2. differential motion - motion between skull/dura and intracranial contents. Has low kinetic energy and large momentum (rotation, tensile, and shear forces)

describe linear impact to head

- in line with centre of gravity of brain

- doesn't cause rotation of brain inside skull

- skull absorbs more stress, more likely to fracture, less likely to damage brain

describe oblique impact to head

- more common

- produces both linear and rotational kinematics

- causes diffuse axonal injury where axons snap by shear impacts

what is poroelastic

brain is poroelastic - it is a porous, fluid-saturated solid

what is the resistance to fluid flowing throughout brain and why

high resistance - very low permeability of fluid vessels

what is a bulk modulus - does the brain have high or low bulk modulus

if object is equally pressured on all sides, how much pressure is required to change the volume.

brain has high bulk modulus = doesn't change volume easily

does brain have high or low compression modulus

very low = extremely soft/compliant (<5 kPa)

does brain have high or low shear modulus

very very low shear modulus (<1kPa), extremely sensitive to shear. When different layers of tissue move differentially to each other, fine connections (axons) between them break easily

is brain viscoelastic

yes , except for infants who are insensitive to the strain rate

is white matter or grey matter stiffer (in general)

white matter (in general) but it depends on direction of force because white matter fibres run in many different ways.

is grey matter anisotropic

no

do smaller or larger brains tolerate greater acceleration/deceleration forces better

smaller brains

what is an acquired brain injury

any brain injury that occurs after birth (not congenital) - can be trauma, stroke, tumour, poison, infection, anoxic episodes

definition of traumatic brain injury (TBI)

traumatically induced structural and/or physiologic disruption of brain functions a result of external force

4 clinical signs of traumatic brain injury (TBI)

1. consciousness - loss or decreased level

2. memory - any loss of memory for events immediately before or after injury

3. mental state - altered (e.g. confusion, slowed thinking)

4. neurological deficits - weakness, balance, visual, speech, sensory

2 main categories of traumatic brain injuries

diffuse and focal

4 types of diffuse traumatic brain injuries

1. concussion

2. diffuse axonal injury

3. blast (e.g. explosion)

4. abuse head trauma/shaken baby syndrome

3 main types of focal traumatic brain injuries

1. contusion

2. haematoma

3. penetrating (e.g. knife through skull)

5 types of haematoma

1. epidural

2. subdural

3. subarachnoid

4. intracerebral

5. intraventricular

5 classification schemes for TBI

1. primary or secondary injury

2. focal, multifocal, or diffuse

3. physical mechanism

4. symptoms/severity

5. pathoanatomy - relate where lesion of brain is to symptoms

likely injuries from linear impact

skull fracture, contusion, epidural haematoma (force is absorbed by skull)

likely injuries from oblique impact

DAI, contusion, subdural/intracerebral hematoma (force absorbed by brain and rotation)

what are primary vs secondary TBIs

primary = what immediately happens to skull or brain

secondary = consequences caused by primary injuries that can occur minutes to weeks after injury.

what are examples of primary TBIs

skull fracture, cerebral laceration, contusion, haemorrhage, BBB compromise, DAI, necrotic cell death

what are examples of secondary TBIs

- cerebral blood flow deregulation

- increased intracranial pressure + oedema

- hypoxic ischaemia

- neuroinflammation

- excitotoxicity / Ca2+ influx

- neuronal death

what can occur after secondary traumatic brain injuries

neurobehavioral deficits e.g. cognitive disfunction, sleep disorder, seizure, psychosis

what is diffuse axonal injury (4 points)

1. leading cause of morbidity from TBI

2. axons are vulnerable: viscoelastic (rapid deformation = brittle), being highly aligned in tracts (anisotropic), and can only strain 6-7%

3. under highly tensile stress, axons can snap (axotomy) which damages connections/communication in brain

4. occurs more with unrestricted head because it allows rotational acceleration which increases tissue deformation and axonal tension

how does vascular haemorrhage occur

tearing of blood vessels, expanding and filling potential or true spaces. Potential spaces = epidural and subdural spaces. True spaces = subarachnoid space

haemorrhage vs haematoma

haemorrhage = active bleed that is currently bleeding

haematoma = pool of blood, usually clotted, sitting within brain

describe an epidural haematoma (common MOI, imaging results, treatment)

- occurs with skull fracture which slices and ruptures the L/R middle meningeal artery - pressure from bleed separates dura from bone

- shows biconvex haemorrhage on x-ray because expansion of blood is contained by tight adherence of dura mater to skull

- treated with prompt surgical evacuation

describe a subdural haematoma (common MOI, imaging results, treatment)

- occurs with violent shaking of head which snaps bridging veins between dura mater and subarachnoid space, haematoma causes mass effect midline shift of brain

- classified with crescent-shaped haematoma not contained by dura, but is contained by falx cerebri and tentorium cerebelli

describe a subarachnoid haematoma (common MOI, diagnosis, treatment)

- various trauma or stroke causes damage to cerebral arteries, which bleed into subarachnoid space

- most likely caused by rotational acceleration and breakage of vessels

- vasospasm can occur in attempt to reduce blood flow to bleeding vessels, may cause focal areas of ischaemia

- blood mixes with CSF, so can be diagnosed with blood in spinal tap

describe intracerebral haemorrhage and MOI

haemorrhage of small arterioles and capillaries in brain tissue (parenchymal vessels)

- commonly acceleration/deceleration trauma

- disrupts BBB and lets in harmful molecules

what is an inter-ventricular haemorrhage

bleed directly into ventricles of brain

what is a brain contusion

focal surface bruises - cell death, bleeding, oedema of surface brain tissue

which part of brain is most susceptible to contusions

crests of gyri

what other injury is associated with brain contusions

subarachnoid haemorrhage

what is a coup and contrecoup

coup = site underneath impact due to compression

contrecoup = site on opposite side of brain where it impacts the skull. Can be used to show direction of impact

what is the preferred imaging modality for acute traumatic brain injuries

unenhanced brain CT scan

advantages and disadvantages of unenhanced brain CT scan

advantages

- CT scans are available, fast

- accurate for detecting intracranial haemorrhage.

- can display mass effect, distinguish brain contusions from haematomas. Excellent for detecting depressed facial and skull fractures

disadvantages

- low resolution - patient with significant deficit could show 'normal' scan

- T2 MRI superior for subacute or chronic contusions

what are the score descriptions for 'eye opening' category on Glasgow coma scale

4 = spontaneous

3 = to speech

2 = to pain

1 = none

what are the score descriptions for 'best verbal response' category on Glasgow coma scale

5 = oriented

4 = confused

3 = inappropriate words

2 = incomprehensible sounds

1 = none

what are the score descriptions for 'best motor response' category on Glasgow coma scale

6 = obeys commands

5 = localises to pain

4 = withdraws from pain

3 = abnormal flexion to pain

2 = extension to pain

1 = none

what GCS score means mild, moderate, and severe

mild = 15-13

moderate = 12-9

severe = <9

what factors affects mortality rate of TBIs

time to regain consciousness. Once >6 hours, chance of survival is much worse

describe a mild GCS TBI

- most common

- lost consciousness <30min

- post-traumatic amnesia <24 hours

- no macroscopic damage

- physical = fatigue, nausea, and altered balance, vision, hearing

- cognitive = attention, concentration, memory, etc

- behaviour = insomnia, irritable, anxious, depressed

what happens if blood flow to brain is reduced from 55mL/min to 20mL/min and even further to 10mL/min

20mL/min = neurons stop generating electrical signals

10mL/min = necrosis and infarct

what is a stroke and what are the two categories

stroke = abrupt vascular insufficiency

categories = ischaemic and haemorrhagic

describe an ischaemic stroke - how does it occur

- sudden blockage of blood flow to brain and an area is deprived of blood

- most common form of stroke

- occlusion of artery occurs via a thrombus (blood clot) or embolus (plaque or thrombus breaks off and blocks artery downstream)

what is a transient ischaemic attack (TIA)

thrombus/embolus blocks vessel temporarily, then is moved away due to building pressure of blood. Causes temporary symptoms as neurons stopped electrical activity but didn't die.

general pattern of infarction in ischaemic stroke

- occurs in one half of brain because an artery only supplies one side.

- territory depends on size and location of occlusion because each artery supplies different areas.

what happends when ischaemic stroke affects branches of basilar arteries

supplies brain stem => cranial nerve defects

describe a haemorrhagic stroke

ruptured vessel leaks blood into brain.

MOI of haemorrhagic stroke

- hypertension (weakens walls)

- rupture of an aneurysm

- vascular malformation

- complication of anticoagulation medication

incidence, mortality, MOI of spontaneous intracerebral haemorrhage

- 10-15% of strokes

- high morbidity and mortality

- main MOI is hypertension

common places for intracerebral haemorrhages

most common = basal ganglia and thalamus

middle = lobes

least common = pons (highest mortality)

3 consequences of intracerebral haemorrhage

1. haematoma expansion

2. cell death due to pressure or chemical toxicity

3. peri-haematomal oedema which increases intracranial pressure and herniation

incidence, mortality rate, and MOI of subarachnoid haemorrhage

- 5% of strokes

- incredibly high mortality

- MOI = rupture of intracranial aneurysm in 85% of cases

timeline of subarachnoid haemorrhage (3 stages)

1. early brain injury - ischaemia and toxic effects of blood in subarachnoid space

2. delayed cerebral ischemia in 1/3 of patients

3. systemic response - increases SNS activity, angiotensin system activation, inflammatory cytokines activated

symptoms of subarachnoid haemorrhage

- sudden onset of most severe headache ever, peaks within 1 minute

- neck pain/stiffness combined with headache

- CT +/- lumbar punture to diagnose

what is a saccular/berry aneurysm

when arteries branch, blood hitting fork point causes it to balloon out and distend with blood. Common in circle of Willis. Causes gradual degeneration of internal elastic lamina and tunica media which eventually ruptures. Can grow to 6-7mm

what is a fusiform aneurysm

all sides of blood vessel balloon out uniformly

what is an arteriovenous malformation

- generally congenital

- tangled mass of thin dilated blood vessels creating abnormal channels between arteries and veins that rupture

- blood bypasses the typical capillary network which means poor nutrient and gas exchange and less regulation of BP

incidence and mortality of ischaemic stroke vs intracranial haemorrhage vs subarachnoid haemorrhage

incidence: ischaemic > ICH > SAH

mortality: SAH > ICH > Ischaemic

stroke risk factors modifiable and non-modifiable

non-modifiable = older age (weakened vessels), female, family history, previous incidence

modifiable = smoking, alcohol, high BP

what are the FAST signs of stroke

F - facial drooping (generally one side)

A - arm can't be raised

S - slurred speech

T - time is critical

how can BBB breakdown cause secondary injuries

can allow infiltration of immune cells (different to brain's immune cells) that secrete IL-6 and TNF-∂ which activate Caspase which triggers apoptosis of neurons

what is necrosis and apoptosis, how do they differ

- have different MOI - necrosis generally primary injury while apoptosis is secondary injury in response to dysfunctional cells

- necrosis = cell swells and bursts, releasing cellular contents WITHOUT membrane to bind them up

- apoptosis = cell breaks up and shrinks rather than ruptures, apoptotic bodies are membrane bound and eaten by phagocytes

6 axonal impairments of diffuse axonal injury

rapid tensile stretch of axons causes:

1. myelin degeneration

2. impaired axonal transport

3. axonal swelling and accumulation of protein

4. damaged axonal cytoskeleton

5. influx of Ca2+ and Na+

6. secondary axotomy (axotomy of non-severed axons due to secondary injuries)

which all lead to cell death

consequence of excitotoxicity

influx of excitatory NTs like glutamate causes influx of Ca2+ and Na+ which eventually causes apoptosis

what is neuroinflammation

infiltration of immune cells passing through broken BBB which secrete their immune factors which cause inflammation and damage to CNS

what are consequences of reactive oxygen species (free radicals) in brain e.g. H2O2, O2-, OH

1. activates Caspase within cells which is a major trigger for apoptosis

2. cause DNA damage to cells - can cause fragmentation, micro deletions, damage telomeres etc

5 categories of treatment for acquired brain injuries

1. prevention

2. prediction

3. manage secondary injury

4. repair consequences of injury

5. treat ongoing symptoms

describe 2 prevention measures of acquired brain injuries

1. avoid the trauma which is generally a MVA - don't drink and drive

2. exercise and diet to lower smoking, hypertension, cholesterol, BP

describe a prediction strategy for acquired brain injury

develop biomarkers/diagnostic tools to predict outcome/personalise treatment e.g. concussion protocols for sports trainers

3 types of drugs to manage secondary brain injuries

1. anti-oxidants - oppose action of reactive oxygen species

2. calcium channel blocker - reduce excitotoxicity

3. competitive inhibitor - binding to excitatory amino acid receptors instead of excitatory NTs like glutamate

what are the 4 ways to repair consequences of an acquired brain injury

1. stem cell therapy (pluripotent -> neuron)

2. regrow damaged axonal connections

3. encourage brain plasticity

4. surgical intervention of haematoma

describe stem cell therapy for treatment of acquired brain injury

- pluripotent stem cell planted in brain to replace dysfunctioning neurons

- can use embryonic cells, adult donor cells, other tissue stem cells

- risk of cancer

how can you encourage brain plasticity

- cognitive exercises

- exercise, diet, and sleep are great for neuroplasticity

- aim is to recruit healthy neurons to take over job of lost neurons

- exercise can prompt endogenous stem cells to build neural cells

4 ways to treat ongoing symptoms of acquired brain injuries

1. rehabilitation and retraining for motor deficits

2. pharmaceutical or therapy for cognitive deficits

3. rearrange life + plan routines so they can cope with lost planning skills, attention, memory etc

4. callosotomy - stop seizures spreading across hemisphere but changes lateralisation of function