Pathology of Stroke Flashcards
What is the typical presentation of a cerebrovascular isease:
- Patients present clinically as “stroke”
: Sudden loss of brain function
:+/- loss of consciousness - Suddenness suggests a vascular cause
Vascular disease in the CNS includes 3 pathologies
Occlusion -> infarction
Narrowing -> decreased flow -> infarction
Ruptured vessel- > haemorrhage
2 processes occur in cerebrovascular disease- whatare these?
- Hypoxia, ischemia, and infarction resulting from IMPAIRED BLOOD SUPPLY & oxygenation of the CNS tissue
- HAEMORRHAGE resulting from the rupture of a CNS vessel
Cerebrovascular disease includes:
Thrombosis
Embolism
Haemorrhage
Narrowing/occlusion
Cerebrovascular Infarction due to VASCULAR OCCLUSION- causes?
Thrombosis or Embolism
Cerebrovascular Infarction due to VASCULAR OCCLUSION-
Arterial Thrombosis - what are the most common sites?
Carotid bifurcation
Origin of middle cerebral artery
End of basilar aa
Vascular Occlusion causing CC infarct:
ARTERIAL THROMBOSIS
What are the changes you would see pathologically?
Changes in the :
Lumen- changes in blood composition
Wall- mural disease
External compression - very rare
Vascular Occlusion causing CC infarct:
ARTERIAL THROMBOSIS
What disorders could cause a luminal change?
• Haematological disorders → leading to increased thrombotic tendency o Sickle cell disease o Polycythemia rubra vera o Thombocythaemia o Waldenstrom’s o PNH o TTP o Multiple myeloma o Circulating lupus anticoagulant
Vascular Occlusion causing CC infarct:
ARTERIAL THROMBOSIS
What disorders could cause a change in the wall?
Atheroma (large vessels) – most common! - Diabetes, basilar artery thrombosis, ruptured plaque, pontine infarction
Lipohyalinosis – (small vessels at centre of brain)
Vasculitis - in wall alters endothelium -> atherosclerosis
Arterial dissection
Arterial Vasospasm- Uncommon cause of infarction .Causes:
• Surgical interference
• IV contrast
• Severe head injury
• Ruptured berry aneurysm (occurs day 3 & becomes maximal after 7 days – caused by breakdown products causing the muscle to spasm)
Cerebrovascular Infarction due to EMBOLISM causes?
Atrial mural thrombus (most common - MI, valvular disease, afib)
Atheroma carotid
Paradoxical embolus (DVT in legs or pelvis + patent foramen ovale/atrial-septal defect?
Mitral valve vegetations
Ventricular mural thrombus (IE, myocarditis?)
AV vegetations
Atheroma aorta
Pulmonary vein thrombus (uncommon)
Embolic infarctions are clinically what?
- Are often haemorrhagic
- i.e. embolis comes into artery, extends into smaller vessel & embolus impacts and fragments into smaller pieces → blood flow restored → damaged vessels, endothelial cells leaky → blood goes into neuropil.
YOU CAN have occlusion without infarction; where?
- If there is a collateral blood supply
- So only (in the brain) if it involves the circle of willis
o i.e. thrombosis in the circle of willis will not cause infarct (generally – anatomical variation) - eg: occlusion in right anterior cerebral artery → no infarct because the anterior communicating artery is a source of collateral blood from the other side
What areas are likely to be occluded?
Large vessels- causing infarct- deep vessels.
*there are partical collateralls for distal branches of A.M/P cerebral arteries. No collaterals for deep vessels
Infarct of large vessels
Travel in the SUBARACHNOID SPACE- branch and have penetrating vessels that go into the brain.
Anterior, posterior and middle cerebral arteries- > cause a large infarct, surface based which is a wedge
Describe an acute cerebral infact
- Wedge shaped
- Pale
- Cerebral swelling - bigger, has pushed the brain over to the other side: septum pellucidum has moved to other side etc
- Subfalcine & midline shift
- Deformed ventricles
Section of acute cerebral infarct - histological features
- Neurons show evidence of infarct: Nucleus is dissolving
- Neutrophil margination
- Neutrophil emigration
- Oedema (white spaces)
- Red cell diapedesis – leaking out through spaces in endothelial cells
- Neuronal ischaemia (hyperchromasia of nucleus)
- Occasional macrophages (must be 3 days old to see this)
What are the effects of an acute cerebral infarct?
- The whole cerebral hemisphere swells
- No longer have subarachnoid space
- Cerebral swelling → TENTORIAL HERNIATION
- lateral compression of midbrain (by expanding brain & tentorial free edge) →
- CST signs & decreased consciousness
- Elongated brainstem (in AP direction) →
- Capillaries become stretched & they tear →
- secondary brainstem haemorrhage → respiratory/cardiac arrest
If they do not die- > infarct organisation- what happens:
Neutrophils: enter periphery of infarct, degenerate & release enzymes →
Dead tissue gradually disintegrates →
Day 3: macrophages enter →
Ingest & remove necrotic debris → cystic spaces
Peripheral surviving astrocytes transform to gemistocytic & fibrous astrocytes → scarring (wall off the area)
Organising infarct – 2 weeks
Lipid in the myelin is breaking down & being consumed by macs – hence yellow appearance
Still wedge shaped
Can see a gelatinous area = early gliosis (astrocytes proliferating to wall off infarct)
Micro:
Macrophages ingesting lipid (necrotic material)
Neuronal necrosis (neurons that have lost their nuclei)
Periphery in gelatinous areas: infarct margin, pink cells with long processes = gemistocytic astrocytes & neuropil oedema
What would you see in an old cerebral infarct?
- Dead tissue has been completely resorbed
- Collapsed cystic space
- Surface meningeal thickening
- Middle cerebral artery territory – smaller than represented on diagrams due to collateral circulation from ACA & PCA
What are the secondary changes you would see on an old cerebral infarct?
- Wallerian degeneration: entire neuron eventually disappears
- Leads to fiber tract atrophy
- Dead tissue resorbed
- Collapsed cystic space – loss of all the neurons that usually sit in this areas
- Surface meningeal thickening
- Sub-pial astrocyte sparing (some astrocytes survive due to Pia blood supply)
- Hydrocephalus “ex vacuo” – ventricle becomes bigger
- Thinner corpus callosum (less axons tracking across to other side)
- Midbain
o Corticospinal tracts on injured sign, pons etc all atrophied
Occlussion of Small Blood Vessels:
Penetrating vessels, mainly end arteries
What is an occlussion due to thrombosis in a small area called?
LACUNAR INFARCT
Describe
HOW, WHERE and the importance of Lacunar Infarct
How?
- Increased luminal px (hypertension) →
- Degenerative changes within walls (liohyalinosis) →
- Luminal thrombosis →
- Tiny lacunar infarcts (old)
- Where are they? o Central white matter (centrum semiovale) o Basal ganglia o Pons o Cerebellum
- Importance of Lacunar Infarction o Tiny infarcts but important due to location o Profound clinical effects (CST) o No mass effect (no brain swelling) o Patient survives o Seen at post-mortem as old infarcts
- What do you see
o Cystic space with a few BVs crossing it, a few glial fibers going across
How does a cerebral haemorrhage occur?
Due to rupture of a BV
- in subarachnoid space = subarachnoid haemorrhage and is usually due to trauma
Intracerebral- intracerebral haemorrhage and usually due to underlying vascular disease
Describe intracerebral haemorrhage
- where does it occur?
- What % of stroke make up ICH?
Central white matter, basal ganglia, cerebellum, pons
About 10% of “strokes”
Lesion of vessel → rapidly forming intracerebral haematoma → pressure on brain stem
Space-occupying lesion
Death due to acute brainstem compression
WHat are the macrosopic features of ICH?
- Intracerebral haematoma
- Compression of surrounding structures
- No central structure
- Brain shift
- May rupture through brain into →
o Subarachnoid space or ventricular system
What are the Microcsopic features of ICH?
- Expanding hematoma
- Neutrophils around edge
- 3 days: macs come in & ingest blood clot
- Weeks/months: Organised cyst with pigmented lining due to haemociderin
o Blood breakdown → haemotoidin or haemociderin
o Eventually all blood disappears → pigmented lining
Inctracerebral haemorrhages are caused by two things-
Primary (hypertensive) ICH
Secondary ICH
PRIMARY INTRACEREBRAL HAEMORRHAGE
HTN causes a number of abnormaities of the vessel wal; accellerated atherosclerosis in large aas, hyaline arteriosclerosis in smaller aa and in severe instances -> proliferative change and necrosis. Arteirolar walls are affected by hyaline change and are pressumabily weaker than normal vessels AND threfore more vulnerable to rupture
- older people, benign HTN and diabetes mellitus
- Cause infarct in: central white matter, pons and the cerebellum
Secondary INTRACEREBRAL HAEMORRHAGE
who?
Causes?
Consider if: person is young, no history of HTN, sit is somewhere other than the white matter in brain, pons or cerebellum.
- Coagulation disorders
o Anticoagulant therapy; haemopoieitic disorders; coagulation factor deficiencies
- Weakening of vessel wall (mural weakening) → o Vessel wall damage • BERRY ANEURYSM • Infective aneurysm - Complicate 3% cases of IE; Small; 20% multiple; 65% rupture within several weeks; ICH, SAH • Congophilic angiopathy • Arteritis • Cerebral metastases • Systemic amyloidosis
o Vascular malformation • Aterial-venous malformation • Microscopic o Numerous vessels embedded within brain tissue o Marked variation in wall thickness o Gliosis +/- haemosiderin o Arteries, veins & hybrid vessels • Cavernous angioma • GBM
SUBARACHNOID HAEMORRHAGE - aetiology
Due to extension of intracerebral haemorrhage
Direct bleeding into subarachnoid space
o Abnormal vascular structure: AVM: Cavernous angioma: Infective aneurysm: Arteritis
o Coagulation disorders: Anticoagulant therapy: Haemopoietic disorders: Coagulation factor deficiencies
- Ruptured berry aneurysm (most common)- anterior circulation - near major branch points- most common at branch of ACA and anterior communicating artery
Describe a BERRY ANEURYSM
o Vessels in circle of Willis arise as separate vessels & then unite: but in some people they don’t properly unite & there is a defect which bulges & forms an aneurysm
BERRY ANEURYSM- gradually enlarges
o Present ~40y.o with rupture→ ruptured aneurysms often associated with atheroma & HTN)
o May present earlier then 40 if there is a:
• AVM
• Coartcation of aorta → HTN
• Adult polycystic kidney disease → HTN
• Connective tissue disorder (EDS, MS, PXE) → weak vessel wall
• Fibromuscular dysplasia ipsilateral internal carotid artery
What are MICRO ft
- Microscopic
o Aneurysmal wall has fibrous tissue, myxoid change & atheroma - Most aneurysms bulge into subarachnoid space & hence give a subarachnoid haemorrhage; burrowing aneurysms can burrow into the brain causing intracerebral haemorrrhage
o Rarely berry aneurysm becomes attached to arachnoid → subdural haemorrhage
o SAH : 10-15% are multiple aneurysms - Burrowing berry aneurysm
o 14-40% burrow into brain & rupture
o Intracerebral haemorrhage (ICH) or IVH +/- SAH
What is the order for treatment of STROKE
→ Imaging
→ SAH or ICH or Infarct
→ SAH → berry aneurysm or vascular malformation or bleeding disorder
→ ICH→ primary or secondary (vascular malformation, tumour – angiography)
→ Infarct → lacunar or large vessel
