Cerebrovascular Injury & Stroke Flashcards
What are the two types of damage that can occur to nerve cells?
Rapid necrosis - acute functional failure
Slow atrophy - gradual dysfunction
What is another name for acute neuronal injury?
Red neuron
Describe what is meant by the term red neuron
Occurs in the context of hypoxia/ischaemia, 12-24 hours after an irreversible insult to the cell
Cell shrinks, angulation of nuclei, loss of nucleolus, intensity of red cytoplasm due to eosinophilia
How do cells respond to axonal injury?
- increased protein synthesis, leads to cell body swelling and enlarged nucleolus
- chromatolysis, margination and loss of Nissi granules
- degeneration of axon and myelin sheath distal to injury
What is simple neuronal atrophy?
Process that affects functionally related sets of neurons, shrunken angulated and loss of neurons. Small dark nuceli with reactive gliosis and lipofuscin pigment - chronic degeneration
What are inclusions?
Variety of structural abnormalities that appear to accumulate with age or in viral infections
How do oligodendrocytes react to injury?
Have low anti-oxidant reserves and high intracellular iron which makes them sensitive to oxidative injury
What does damage to oligodendrocytes result in?
Reduced conduction and exposure of axons to injury
State the role of astrocytes
- ionic, metabolic and nutritional homeostasis
- conjunction with endothelium to maintain BBB
- main cells involved in repair and scar formation in CNS
Describe gliosis
Astrocytes undergo hyperplasia and hypertrophy - nucleus enlarges, becomes vesicular with a prominent nucleolus and the cytoplasm expands
What do old lesions in the CNS look like?
Nuclei are small and dark and lie in a dense network of glial fibrils. Translucent, firm and circumscribed.
Why are the ependymal cells associated with infection?
As bacteria can pass from one cell to another via CSF and local proliferation can produce ependymal granulations
How do microglia respond to injury?
Proliferate, recruit inflammatory mediators and aggregates - around damaged tissue
Name the two types of microglia
M2 - actue anti-inflammatory
M1 - chronic pro-inflammatory
State some causes of cerebrovascular injury
Hypoxia Trauma Toxic insult Metabolic abnormalities Nutritional deficiencies Infections Genetic abnormalities Ageing
How much can cerebral blow flow increase?
two fold
What percentage of body resting oxygen consumption goes to the brain?
20%
If the brain is deprived of oxygen what can happen?
Mitochondrial inhibition of ATP synthesis so ATP reserves are consumed within a few mins
What is excitotoxicity?
Process by which neurons are damaged due to the overactivation of excitatory pathways
If energy fails, describe the exitotoxicity pathway
Neuronal depolarisation - glutamate release
Inhibition of astrocyte reuptake - failure of glutamate uptake
Both of which cause a glutamate storm and subsequent calcium release
1. Mitochondrial dysfunction
2. Oxidative stress
3. Protease activation
Name three types of oedema
- cytotoxic
- ionic
- vasogenic
Describe cytotoxic oedema
Osmotically active sodium and chloride ions move into cells and take water, no swelling occurs e.g. intoxication
Describe ionic oedema
Dysfunction of blood brain barrier extracellular space is devoid of sodium ion sand so sodium, chloride and water moves across BBB e.g SIADH
Describe vasogenic oedema
Deterioration and breakdown of BBB due to disruption of tight junctions allowing albumin and other proteins to cross therefore water follows e.g trauma, tumour
What is haemorrhagic conversion?
BBB is so damaged the red blood cells can pass
Name the three main arteries that supply the brain
Anterior, middle and posterior cerebral artery
Where does the anterior cerebral artery supply?
Midline portions of the frontal lobe and superior medial parietal lobes
Where does the middle cerebral artery supply?
Lateral cerebral cortex, it arises from the ICA and continues into the lateral sulcus where it branches - anterior temporal lobes and insular cortices
Where does the posterior cerebral artery supply?
Occipital lobe
Define cerebrovascular injury
Any abnormality of the brain caused by pathological process of blood vessels
Name four pathological processes of blood vessels
- brain ischaemia and infarction
- haemorrhage
- vascular malformations
- aneurysms
Name two types of ischaemia
Global and focal
What is global ischaemia?
Systemic compromise to the circulation, cannot be compensated for by auto-regulation e.g cardiac arrest
What is focal ischaemia?
Restriction of blood flow to a localised area of the brain typically due to a vascular obstruction
What must MAP fall to for auto-regulatory mechanisms to no longer compensate?
15mmHg
What areas of the brain are most sensitive to ischaemia?
Watershed areas at the periphery that are least well supplied
Where in the brain are neurons most sensitive?
Neocortex, hypocampus, purkinje cells
Define stroke
Sudden disturbance of cerebral function of vascular origin that causes death or lasts over 24 hours
What percentage of strokes are infarcts/haemorrhagic?
84% infarction
16% haemorrhage
Describe a thrombotic stroke?
Thrombosis in atherosclerotic segment most commonly the middle cerebral artery
Describe an embolic stroke
Atheroma in ICA and aortic arch usually from the heart or more proximal atherosclerotic segments
Name some rarer causes of infarction
- osteophytes
- vasculitis
- septal defects
State the risk factors for cerebral infarction
Atheroma, hypertension, high cholesterol, heart disease, drugs, smoking, structural defects
In the first 12 hours after a stroke what pathology is seen?
Little visible
12-24 hours after infarction what is seen?
Macro - Pale soft swollen ill defined margins
Mirco - red neuron, oedema and swelling
24-48 hours after infarction what is seen?
Increasing neutrophils, extravasation of RBC, activation of astrocytes and microglia
2-14 days after an infarction what can be seen?
Macro - Brain becomes gelatinous and friable, reduction in surrounding tissue, oedema demarcates the lesion
Micro - predominantly microglial cells, gliosis and myelin breakdown
What can be seen several months after an infarction?
Liquification, cavity formation lined by dark grey tissue
Phagocytosis and increasing cavitation and gliotic scar formation
What can cause a haemorrhagic infarct?
Disruption to BBB
Deterioration of tissue due to infarction
Intentional reperfusion through damaged vessels
Depending on the affected artery what is the clincial presentation of haemorrhagic infarct
Carotid Artery - contralateral weakness/sensory loss
Middle cerebral artery - contralateral face and arm
Anterior cerebral artery - weakness/sensory loss in contralateral leg
Vertebro-basilar artery - vertigo, atoxia, dysarthria, dysphagia
What is the pathological consequence of hypertension?
Lacunar infarcts, multi-infarct dementia, aneurysm formation and rupture, intracerebral haemorrhage, hypertensive encephalopathy
What are lacunar infarcts?
Small lake like infarcts that vary in size, occur with occlusion of small penetrating vessels e.g lenticular striate branches - basal ganglia
What can accumulation of lacunar infarcts lead to?
Mulit-infarct dementia
Describe hypertensive encephalopathy
Severe hypertension, overlap of symptoms with raised ICP, headache, vomiting, altered balance, confusion, seizures, coma
What are the pathological findings of hypertensive encephalopathy?
Global cerebral oedema
Tentorial and tonsilar herniation
Arteriolar fibrinoid necrosis
Petechiae (extravastation of RBC)
What intracranial haemorrhages can occur spontaneously?
Intracerebral
Sub-arachnoid
Haemorrhagic infarct
What intracranial haemorrhages can occur due to trauma?
Extra-dural/sub-dural Haematoma Contusion Intracerebral haemorrhage Sub-arachnoid haemorrhage
What causes an intracerebral haemorrhage?
Aneurysms Vascular Malformations Systemic coagulation disorders/iatrogenic coagulation Open heart surgery Neoplasm
Where do intracerebral haemorrhages due to neoplasm most commonly occur?
Basal ganglia including the thalamus
Cerebral white matter and cerebellum
What does a intracerebral haematoma due to neoplasm look like?
Well demarcated SOL, formed by an area of parenchyma haematoma, softening of adjacent tissue with surrounding oedema - herniation and shifts are common
Which condition is commonly associated with amyloid angiopathy?
Alzheimers
Describe amyloid angiopathy
Beta amyloid sheets are deposited in the cerebral and meningeal vessels - reduces compliance and ability to cope with pressure
When do vascular malformations usually occur?
During angiogenesis
Name some vascular malformations
Arteriovenous - MCA teritory
Cavernous angiomas
Venous angiomas
Capillary telangectases
Describe arteriovenous malformations
Smooth muscle hypertrophy, reduced compliance and shunting from artery to vein
How do vascular malformations present?
Bleeding, headaches, seizures, focal neurological deficits
What vascular malformations are at most risk of bleeding?
Ateriovenous
Cavernous angiomas
Where do 90% of sub-arachnoid haemorrhages occur?
Territory of ICA - bifurcation at circle of Willis
Name the risk factors for sub-arachnoid haemorrhage
- Acquired degenerative lesion
- PCKD
- Collagen gene abnormality
Describe the morphology of a sub-arachnoid haemorrhage
Blood in sub-arachnoid space, presence of aneurysm, infarction of brain parenchyma due to arterial spasm, mass effect due to haematoma, increased ICP, hydrocephalus
Describe the clinical presentation of a sub-arachnoid haemorrhage
Abrupt onset, headache, vomiting, loss of consciousness, high mortality, blood in CSF, midline shifts, herniation and hydrocephalus
Name some stroke mimics
Seizure, sepsis, toxic/metabolic, SOL, pre/syncope, confusion/delirium, dementia
Describe a CT of a stroke
Blood is white, only useful straight after haemorrhage
Describe a MRI of a stroke
Diffusion weighted will show infarct - little differentiation between grey/white matter, blood will appear white and static in a blocked artery
Define penumbra
Cells that are still alive but at risk of death
What is the management for acute cerebrovascular syndrome?
Thrombolysis
Endovascular therapy
Anti-platelets
Describe thrombolysis
IV tissue plasminogen activator, systemic treatment acts to break down clots - dose based on weight needs to be given less than 4.5 hours after onset - high risk of bleeding
Describe endovascular therapy
Interventional radiology - catheter passed through groin to the brain to pull out the clot, only used for proximal vessels - no risk of bleeding
What antiplatelet therapy is given after a stroke?
Aspirin ASAP
CT to exclude a bleed
Mild - aspirin + clopidogrel for up to 3 weeks
What reduces risk of DVT?
Intermittent pneumatic compression
What must be given to a patient after a TIA?
Statin and anti-platelet
How is hypertension treated after a haemorrhage?
IV GTN
What can reverse anti-coagulation?
Vitamin K - warfarin
DOACs have no licensed reversible drug but prothrombin complex is advised
What are the four key types of stroke depending on location of damage?
Total Anterior Circulation Syndrome
Partial Anterior Circulation Syndrome
Lacunar Syndrome
Posterior Circulation Syndrome
What makes up the anterior circulation?
Internal carotid
Middle cerebral
Anterior cerebral
How will TACS present?
Hemiplegia
Homonymous hemianopia
Cortical signs - neglect, dysphagia
What is partial anterior circulation syndrome?
2/3 features of TACS
- isolated cortical dysfunction
Pure motor/sensory signs
Where do lacunar infarcts occur?
Deeper parts of the brain - basal ganglia/thalamus
Small perforating arteries
What arteries are affected in posterior circulation syndrome?
Vertebral and basilar
What are the symptoms of PCS?
Ipsilateral cranial nerve palsy with contralateral motor and/or sensory deficit
Bilateral motor and/or sensory deficit
Cerebellar dysfunction
Isolated homonymous visual field defect
When does a syndrome become more specific?
When ischaemia/haemorrhage is determined
What can happen if a stroke occurs on the right?
Neglect
Spatial awareness
