Neuro Pathology

Question 1

Describe PNS regeneration

Answer 1

1-2 days: Wallerian degeneration starts to occur
2 weeks post injury: nucleus peripherally displaced, loss of Nissl bodies (chromatolysis)
3 weeks post injury: Schwann cells remain in the space previously occupied by the axon -> proliferate, provide cord for new axons
New axons sprout -> growth cones use Schwann cells as a guide to reach target
Schwann cells also provide trophic support

Question 2

Describe CNS regeneration

Answer 2

Oligodendrocytes don’t remain viable following axonal injury and so can’t provide trophic support and axon guidance
CNS neurons and support cells undergo apoptosis -> sometimes liquefactive necrosis and cavitation
Microglia phagocytose axonal/myelin debris, but very slowly
Damaging injury environment: gliosis/astrocytes form a glial scar faster than regeneration can occur -> physical barrier inhibiting axonal growth
Presence of myelin inhibitors eg Nogo, MAG, OMgp and inhibitory axon guidance molecules (EphA4, semaphorins) prevent growth of regenerating axons via activn of Rho signalling pathway.

Question 3

In PNS regeneration, is a crush injury or axon severance more likely to have a repair well? Why?

Answer 3

Crush injury.
Growth cones of sprouting axons use the Schwann cell cord to help reach target. In axon severance, the cord may be displaced.

Question 4

What are the 3 main forms of cerebral/cerebellar herniation?

Answer 4

subfalcine/cingulate
transtentorial/uncinate
tonsillar/cerebellar

Question 5

Consequences of transtentorial/uncinate herniation?

Answer 5

CN III compression -> ipsi pupil dilation, ocular palsies
Distortion of adjacent brainstem (midbrain/pons) -> compression of RAS -> LOC
PCA compression -> ischemia/infarction of visual cortex
Compression of ipsi/contr cerebral peduncles against free edge of tentorium -> contra/ipsi hemiparesis (Kernohan’s notch)
Duret haemorrhages in pons/midbrain 2o to downward compression -> stretching of perforating branches -> ischaemia and haemorrhage (usually fatal)

Question 6

Consequences of tonsillar/cerebellar herniation?

Answer 6

Compression and compromise of respiratory centres in the medulla (almost always fatal)

Question 7

Consequences of a subfalcine/cingulate herniation?

Answer 7

Can compress pericallosal arteries -> infarct in their distribution (esp corpus callosum)

Question 8

Main types of intracranial bleeds?

Answer 8

Extradural haematoma
Subdural haematoma
Subarachnoid haemorrhage
Intracerebral haemorrhage

Question 9

What is an intracerebral haemorrhage?

Answer 9

bleeding into the cerebral parenchyma

traumatic or non-traumatic causes

Question 10

What is a sub arachnoid haemorrhage?

Answer 10

bleeding into the subarachnoid space in the meninges
Important cause: rupture of a Berry aneurysm in the Circle of Willis
Presents as a ‘thunderclap’ headache - worst ever

Question 11

Complications of SAH?

Answer 11

Incr ICP and sequelae thereof
irritative vasospasm -> cerebral infarction
hydrocephalus

Question 12

Main features of extradural haematoma?

Answer 12

Main cause is trauma, skull fracture at pterion -> MMA rupture
head trauma -> LOC -> lucid period -> rapid deterioration

Question 13

Main features of subdural haematoma?

Answer 13

Main cause is trauma

rupture of bridging veins bn cerebral veins and venous sinuses

Question 14

Most important causes of non-traumatic intracranial haemorrhage?

Answer 14

HTN (hyaline arteriolosclerosis -> stiff brittle walls). Commonly in putamen, thalamus, pons
Amyloid angiopathy eg in a pt w Alzheimer’s
Berry/saccular aneurysm rupture - congenital wall defect, at branch points esp CoW
Coagulopathies - genetic and iatrogenic

Question 15

What is a lacunar infarct?

Answer 15

dt small occlusion in a single deep penetrating artery eg lenticulostriate arteries
small ischaemic subcortical infarcts, but large effect b/c they occur in BG and internal capsule
infarction occurs in end arteries w no collateral supply
commonly caused by arteriolosclerosis dt HTN

Question 16

What is a watershed infarct?

Answer 16

occurs when there is global cerebral hypoperfusion (eg low CO state)
areas of tissue at the border zone of vascular supply (which have poor collateral supply) will become ischaemic and at risk of infarction

Question 17

Main pathological features of Alzheimer’s disease? (intra and extracellular)

Answer 17

Amyloid plaques:

• extracellular
• beta-amyloid cleaved from APP

Neurofibrillary tangles:

• intracellular
• made of hyperphosphorylated Tau

Question 18

In AD, does the tangle burden or plaque burden more closely correlate w the degree of dementia?

Answer 18

Tangle burden

Question 19

What are Lewy bodies?

Answer 19

spherical, intraneuronal, cytoplasmic, eosinophilic inclusions composed mainly of alpha-synuclein

Question 20

What are the 3 Lewy body diseases?

Answer 20

Dementia with Lewy Bodies (DLB)
Parkinson’s Disease (PD)
Parkinson’s Disease Dementia (PDD)

Question 21

Briefly, what is the pathophysiology of Parkinson’s?

Answer 21

Lewy bodies in the substantia nigra -> death of dopaminergic neurons -> motor symptoms

Question 22

Briefly, what is the pathophysiology of Dementia w Lewy bodies?

Answer 22

Lewy bodies prominent in the cortex -> death of cholinergic neurons -> cognitive deficits

Question 23

Why do embolic events usually result in haemorrhagic infarcts?

Answer 23

due to reperfusion thru collaterals and/or after dissolution of embolic material

Question 24

Do embolic events usually result in haemorrhagic or non-haemorrhagic infarcts?
What about thrombotic events?

Answer 24

Embolic events -> haemorrhagic infarcts

Thrombotic events -> non-haemorrhagic infarcts?

Question 25

Where do berry aneurysms occur?

Answer 25

In large cerebral arteries, esp. in the CoW, which lie in the sub-arachnoid space -> rupture causes bleeding into this space

Question 26

Blunt head trauma is most likely to cause which type(s) of intracranial bleed(s)?

Answer 26

Extradural and subdural haematomas

Can also cause contusions and petechiae.

Question 27

Where does haemorrhage tend to occur in CAA?

Answer 27

Peripherally, because CAA generally affects the leptomeningeal and superficial cortical vessels first.

Question 28

In a haemorrhagic cerebral infarct, what causes the dark discolouration in the patient’s brain?

Answer 28

Bleeding from necrosed vessels following reperfusion

Question 29

In a haemorrhagic infarct, what would you see macroscopically at 1 hr, 6-8 hrs, 2 days, 3 weeks and 12 weeks

Answer 29

1 hr: no changes visible
6-8 hrs: swelling + pallor
2 days: necrosis has developed. Visible swelling, and bleeding from necrosed vessels
3 weeks: necrotic tissue is beginning to be removed -> loss of architecture
12 weeks: cavitation

Question 30

What occurs in transtentorial/uncinate herniation?

Answer 30

Medial temporal lobe is displaced under the tentorium cerebelli -> compression of ipsilateral CN III -> dilated pupil, oculomotor palsy
If the displaced temporal lobe compresses the RAS -> decr level of conciousness
Duret haemorrhages may also occur

Question 31

What causes Duret haemorrhages?

Answer 31

Haemorrhagic disruption to the vascular supply of the midbrain/pons

Question 32

What occurs in subfalcine herniation?

Answer 32

Displacement of the cingulate gyrus under the falx cerebri -> compression of the ACA -> infarction in this territory

Question 33

What occurs in tonsillar herniation?

Answer 33

Displacement of the cerebellar tonsils through the foramen magnum (coning)

• > compression of cardiac and resp. centres in the medulla
• > usually rapidly fatal

Question 34

How does vasospasm after a SAH lead to ischemic change?

*vasospasm is not an acute complication, occurs days later

Answer 34

The breakdown of blood from SAH acts directly on the vessels to cause vasospasm
Prolonged vasospasm can cause ischaemia

Question 35

Briefly, what is the pathophysiology of CAA?

Answer 35

deposition of beta-amyloid in the media and adventitia of small-mid-sized arteries of the cerebral cortex

• present in AD in 80% of cases
• progressive deterioration of cortical function (disorientation, memory loss, aphasia…)
• incr risk of lobar haemorrhage

Question 36

How does CAA predispose to intracerebral/lobar haemorrhage?

Answer 36

amyloid damage -> thickening of BM, vessel lumen stenosis, fragmentation of the internal elastic lamina = weak vessel walls

Question 37

What is an arteriovenous malformation (AVM)?

Answer 37

congenital lesions composed of a complex tangle of arteries and veins connected by one or more fistulae

• clinically silent
• occurs in young people