CNS Trauma: Neuropathology

Question 1

Types of head trauma

Answer 1

• non missile (acceleration/deceleration, rotation, RTA, falls, assaults)
• missile (conflict-related)
• focal (fractures, intracerebral contusions, bleeding (SAH, extradural/subdural, intracerebral)
• diffuse (Diffuse axonal injury (DAH): damage to connections between regions)

Question 2

How to determine the extend of damage from head trauma without imaging?

Answer 2

GCS]- learn fully

13+: mild brain injury
9-12: moderate brain injury
8 or less: severe injury

Question 3

What is ischaemia?

Answer 3

Lack of oxygen AND nutrients (i.e. lack of blood supply providing these)

Question 4

Define scalp laceration

Answer 4

Breach of the scalp

Question 5

Define cerebral contusion

Answer 5

Bruise on the surface of the brain

Question 6

Define cerebral laceration

Answer 6

Breaching of the pia and meninges- extends to parenchyma (disturbance of the actual brain substance)

Question 7

Difference between diffuse axonal injury and (diffuse) traumatic axonal injury?

Answer 7

• Diffuse axonal injury- interpreting radiology in terms of likely outcome
• (Diffuse) Traumatic injury- a pathological phenomenon (can physically be seen in the tissue)

Question 8

Where do fissure fractures often extend to?

Answer 8

Base of the skull
(may pass through middle ear/anterior cranial fossa and cause CSF leakage)

-> otorrhea/rhinorrhea (+infection risk)

Question 9

Signs of skull base fractures?

Answer 9

• Battle’s sign (just behind the ear)

- Racoon eyes (peri-orbital haemorrhage)

Question 10

What causes a contusion?

Answer 10

Collision of brain with the skull (causing surface bruising)

Question 11

Difference between “coup” and “contrecoup”

Answer 11

• Coup: damage on site of impact

- Contrecoup: damage on opposite side of impact

Question 12

[When looking at pathology specimen]- You can’t see any midline structures?

Answer 12

You are looking at an end piece of brain

Question 13

Most common CNS trauma that causes coma?

Answer 13

Diffuse axonal injury

Question 14

Diffuse axonal injury affects which particular structures?

Answer 14

Midline structures:

• corpus callosum
• rostral brainstem
• septum pellucidum

Question 15

How to grade diffuse axonal injury (DAI)?

Answer 15

Grade 1: parasagittal frontal (white matter from longitudinal fissure), internal capsule, cerebellum

Grade 2: As Grade 1 plus corpus callosum

Grade 3: As Grade 2 plus dorsal brainstem

Question 16

Molecular pathogenesis of DAI?

Answer 16

[calcium influx at the site of tear] -> activation of calcium dependent proteases (e.g. calpain) -> membrane sealing + cytoskel disruption -> swelling

Primary axotomy: immediate disconnect

Secondary axotomy: stabilising -> secondary insult -> late disconnection

Question 17

How to detect traumatic axonal injury?

Answer 17

Immunostaining for amyloid precursor protein (APP)

[NB: this is not always detectable using silver staining methods]

Question 18

What does a midline shift indicate?

Answer 18

Space-occupying lesion (could be blood though)

Question 19

Describe the causes of brain swelling

Answer 19

• vasodilatation and increased cerebral blood volume -> congestion
• blood vessel damage (vasogenic oedema)
• increased water content of cells -> cytotoxic cerebral oedema

Question 20

3 main sites of herniation within cranial cavity?

Answer 20

• Subfalcine herniation (cingulate cortex pushed under falx)]- rarest, due to SOL above tentorium
• Transtentorial herniation (medial temporal lobe pushed into posterior cranial fossa)(Supratentorial raised ICP)
• Tonsillar herniation (inferior cerebellum pushed through foramen magnum)]- Base of skull (global raised ICP/supratentorial raised ICP) —-also seen in coning when an LP is done at a raised ICP

Question 21

Difference between necrosis and apoptosis

Answer 21

• Necrosis = passive cell death

- Apoptosis = programmed cell death that requires an energy supply

Question 22

Role of inflammation in CNS trauma?

Answer 22

(initially seen as protective response)- but goes on for too long in brain

Involved in chronic, long term, degenerative conditions

BBB breakage -> immune cell infiltration -> activation of microglial cells

Cytokines

• Proinflammatory
• Neuroprotective -> regeneration

Microglial cells- balance of inflammatory M1 and neuroprotective M2

Question 23

Relationship between acute head injury and Alzheimer’s

Answer 23

Acute head injury has been shown to have Aβ and tau pathology, just like Alzheimer’s

Question 24

Relationship between chronic traumatic encephalopathy (CTE) and Alzheimer’s

Answer 24

Both involve astrocytic tau

Question 25

Key cytological features of CTE pathology

Answer 25

Perivascular distribution of tau pathology in astrocytes- found at the base of the sulci

Question 26

Major clinical presentations of CTE?

Answer 26

• behaviour/mood variants (generally younger onset)

- cognitive impairment (generally older onset)

Question 27

Available methods to treat CNS trauma?

Answer 27

• Treat/prevent secondary damage: (neuroprotection, anti-inflammatories, protease inhibitors)
• Hypothermia- minimise metabolic + breakdown activity
• Hyperbaric treatment