Neuro Blood Supply & Cerebrovascular Disease

Question 1

Brain and SC blood supply

Answer 1

• anterior flow (~70% of CBF)-internal carotid artery
• posterior flow (~30% of CBF)-vertebral arteries
• two systems are connected by PCA (R and L) and ACA-form circle of Willis at base of the brain
  
  • CoW=get enough blood to infected area even if there are some abnormalities

Question 2

General brain requirements

Answer 2

• Brain energy source = aerobic metabolism
  
  • 20% cardiac output
  • 15% of 02 consumption
• No 02 reserve in the brain-need CONSTANT O2
• After cerebral ischemia
  
  • Normal brain function - 8‑10 seconds
  • Irreversible damage after 6‑8 minutes
• Cessation of blood flow
  
  • Reduction in the perfusion pressure = hypotension
  • Small or large vessel occlusion
• Clinical and pathologic findings depend on:
  
  • Collateral circulation
  • Duration of ischemia
  • Degree and rapidity of reduction of blood flow
• Two degrees of brain damage in ischemia:
  
  • 1. selectively affect neurons only (most sensitive cells)
  • 2. affect all cells in cerebral parenchyma=PAN-necrosis=infarct
• Cells most sensitive to ischemia:
  
  • neurons > oligodendrocytes > endothelial cells > astrocytes.
• Variable neuronal susceptibility to ischemia:
  
  • Pyramidal neurons in CA1 region of hippocampus
  • Purkinje cells of cerebellum

Question 3

Overview of injury

Answer 3

• Stroke: “abrupt onset of focal or global neurological symptoms caused by ischemia or hemorrhage”
  
  • must continue for at least 24hrs and result in permanent brain damage for stroke diagnossis
  • <24 hrs=TIA; no tissue damage on imaging, no residual neuro deficits
• Cerebrovascular disease:
  
  • due to Cerebral ischemia (lack of blood flow to brain= 85%):
    
    • Global cerebral ischemia (entire brain)
    • Focal cerebral ischemia (specific brain region)
  • Intracranial hemorrhage (bleeding into the brain = 15%):
    
    • Intraparenchymal hemorrhage (HTN, amyloid)
    • Subarachnoid hemorrhage (saccular aneurysms, AVM)

Question 4

Global Cerebral Ischemia

Answer 4

• Major etiologies:
  
  • Low perfusion (e.g. atherosclerosis-near complete or complete occlusion by atherosclerotic plaque)
  • Acute decrease in blood flow (e.g. cardiogenic shock)
  • Chronic hypoxia (e.g. anemia-brain less sensitive to hypoxia than it is to ischemia)
  • Repeated episodes of hypoglycemia (e.g. insulinoma)
• Duration and magnitude of insult:
  
  • Mild global ischemia – no permanent damage
  • Severe global ischemia – diffuse damage – vegetative state
  • Moderate global ischemia (water in the mods) – watershed infarcts and selectively vulnerable regions
• Histologic changes appear 6-12 hours after insult
• Pathology: “red dead” neurons (neuronal necrosis)
  
  • Cytoplasmic eosinophilia
    
    • any cellular or tissue death induces more affinity towards acidic tides, so neuronal cytoplasm will appear more brightly eos or red
  • Loss of Nissl substance
  • Dark (and shrunken) pyknotic nuclei
• Selective vulnerability/susceptible
  
  • Pyramidal neurons in cerebral cortex (layers 3 and 5) – leads to LAMINAR NECROSIS (if the patient survives longer than 3 days)
  • Pyramidal neurons of hippocampus-CA1! (long term memory)
  • Purkinje cells of cerebellum (due to extreme sensitivity to excitatory chemicals in the brain)

Question 5

Global ischemia: neuronal vulnerability; adults vs. infants

Answer 5

• Cerebrum
  
  • adults: “big neurons”; cerebral cortex; cortical layers 3&5, CA1 of hippocampus
  • infant: subiculum (in hippocampus)
• Diencephalon
  
  • infant: thalamus
• Midbrain:
  
  • Infant: pontine nuclei
• Cerebellum:
  
  • Adult: purkinje cells

Question 6

Laminar cortical necrosis

Answer 6

• bandlike (all layers of cortex affected); more likely to happen in watershed area (especially triple shed-between ant, med, and post circulation in occipital lobe, also inthe ant and middle watershed zone)...lenticulostriate arteries
  
  • Gross of mdial temporal lobe: selective vulnerbility (CA1 area of hippocampus-Sommer’s sector)
    
    • brown discoloration and pitting visible, microscopically would see red neurons
• severe or prolonged HTN, cortex of entire brain may show this
• Gross:
  
  • brown discoloration and pitting of the cortex in a bandlike fashion
  • microscopically: all the layers of cortex will show neuronal loss and vacuolation
• there is preserved superficial cortex on top, laminar necrosis below

Question 7

Watershed or BorderZone Infarcts

Answer 7

• The areas between the arterial territories undergoing necrosis because of low perfusion pressures.
• Middle frontal gyrus and parietal cortex and superior temporal gyrus: MCA
• Occipital cortex: PCA, watershed between ant and med
• AC: parasagittal cortex
• Gross: bilat zone infarcts
  
  • wedge-shaped areas of hyperemia and softening in ACA-MCA watershed zones

Question 8

Focal Ischemia

Answer 8

• ISCHEMIC STROKE
  
  • Regional ischemia resulting in focal neurologic deficits lasting >24 h (<24 h – TIA)
  • two main causes are:
  • 1. Thrombotic
       * In situ thrombosis
       * Atherosclerotic plaque (75%) – at bifurcation of internal carotid and MCA
       
       • ​usually more extensive in the peripheral vessels outside of the CNS, sometimes CoW guys affected
       • yellow discoloration of normally translucent vessel wall and the lumina of the internal caroti artery are open because the wall is rigid from athero; also probably Ca deposition (wont be pliable to touch, will feel rigid, with grnaular Ca deposits)
  • 2. Embolic (10%)
       * can effect multiple territories and can form after an MI due to demobility of the myocardium and the slowing down of blood flow
       * Cardioembolic (A fib – most common); goes to the MCA because its an extension of the internal carotid
       * Thrombi: Atheroembolic (carotid, vertebral sources)
  • Small vessel disease (hypertension, diabetes, vasculitis)
    
    • where perforating vessels are the main bloo supply; affect BG, caudate nucleus, pons, putamen, internal capsule (structurs with very important jobs)
    • Lacunar stroke – lenticulostriate vessels – cystic infarct <1.5 cm
    • Internal capsule – pure motor stroke
    • Thalamus – pure sensory stroke
  • MRI brain:
    
    • ischemic hemispheric infarct in MCA territory
    • midline shift and slight compression of ventricle on right side
  • Symptoms:
    
    • contralateral hemiparesis affecting the lower face and upper extremity more than the leg
    • similar distribution contralateral hemisensory loss
    • contralateral visual field deficits; dominant hemisphere infarct is often associated expressive aphasia where as non-dominant infart is associated with neglect syndrome

Question 9

Ischemic Infarction

Answer 9

• Gross and microscopic findings – differ with:
• Time after insult
  
  • Acute vs. subacute vs. remote
• Embolic (red) versus thrombotic (pale) insult
  
  • embolic: undergo reperfusion may be secondarily hemorrhagic

Question 10

Cerebral ischemia-Age of Infarct

Answer 10

• Acute
  
  • 6-48 h
  • Gross: pale, soft, swollen, indistinct border, blurred grey-white junction=only hint of smthg going on; midline shift and compressio nof lateral ventricle
  • Micro:
    
    • 6-12 h - neuronal ischemia (dead reds), general pallor (edema)
    • 1-3 days – infiltration by neutrophils–first around the arterials and then further into the parenchyma
• Subacute
  
  • 2d-3wks
  • Gross: gelatinous (due to tissue necrosis), friable, distinct border due to tissue liquefaction
    
    • less midline tissue, not as much mass affect as acute
  • Micro:
    
    • neutrophils; PMN cells (early)
    • macrophages (4-7 days)
    • vascular proliferation (2-3 weeks)
• Chronic
  
  • >3wks
  • large stroke, cant replace lost tissue, once macrophages clear necrotic debris will have cystic cavity
  • Gross: cystic, +/-hemosiderin staining, secondary degeneration
  • Micro: astrocytic gliosis, residual macrophages and some strands of remaining glial tissue

Question 11

Embolic Infarct

Answer 11

• usually smaller, centered at gray-white jxn
• Can be single or multiple
• May involve more than one vascular territory
• MCA most common
• Lacunar infarct
  
  • ​Small, usually cystic, up to 1.5 cm
  • Basal ganglia, thalamus, pons and subcortical white matter
  • Hypertension causes small vessel disease and Lipohalinosis
    
    • Lipo: wal of vessel undergoes necrosis, lumen gets narrower and eventually completely occluded…small vessel infected-usually end arteries
    • entire area supplied will undergo infarction and areas infected: BG, thalamus, pons, and sometimes subcortical white matter
  • Arterial hyalinosis (uncontrolled longstanding HTN) will lead to fibrinoid necrosis of small arteries with occlusion of the lumen

Question 12

Hemorrhagic Infarction

Answer 12

• usually emobilic and 50-70% lead to secondary hemorrhagic
  
  • reperfusion
• grossly hemorrhagic
• when emboli broken down by fibrinolytic enzymes and causes reperfusion of blood (naturally or thromboembolic therapy)
• Gross: compression of lateral ventricle and midline shift

Question 13

Intracranial hemorrhage

Answer 13

• A. Above the arachnoid
  
  • Traumatic in nature
    
    • Epidural and subdural hematomas
• B. Below the arachnoid
  
  • Underlying cerebrovascular disease
    
    • Subarachnoid hemorrhages (SAH)
      
      • Aneurysms
    • Parenchymal
      
      • Hypertension

Question 14

Intraparenchymal hemorrhage (IPH)

Answer 14

most common causes:

• HYPERTENSIVE HEMORRHAGES
  
  • Common locations (similar to lcunar infarct locations):
    
    • PUTAMEN
    • THALAMUS
    • PONS
    • CEREBELLUM
    • (hemorrhage may extend into the subarachnoid space or to the ventricles; circumscribed hematoma surrounded by brain tissue)
  • Secondary to rupture of pseudoaneurysms (Charcot‑Bouchard)
    
    • [CB aneurysms are associated with chronic HTN which causes damage to the vascular wall usually at the bifurcation of vessels)
    • (perforating end arteries) Lenticulostriate arteries, paramedial pontine vessels and short circumferential vessels of the cerebellum and in the central white matter
    • Clinical outcome depends on site and size of hemorrhage
    • Similar distribution as lacunar infarcts
• Less common causes:
  
  • cerebral vascular amyloid angiopathy
  • anti-coagulative therapy
• some rare:
  
  • tumors, illicit drug users, aneurysms, arterial venous malformation
• Microscopic:
  
  • Recent hemorrhage surrounded by cerebral edema
  • Minimal tissue necrosis
  • Resolution leaves behind cystic space with macrophages containing hemosiderin
    
    • rusty=discoloration

Question 15

Subarachnoid hemorrhage

Answer 15

• Bleeding into subarachnoid space
  
  • “Berry” aneurysm
    
    • Common cause of non-traumatic spontaneous subarachnoid hemorrhage (85%)
  • Less common: AVM and Anticoagulated state
• CSF shows xanthochromia (yellow hue due to bilirubin)
• PATHOLOGY:
  
  • Gross ‑ “berry-like” (sack-like) thin-walled (no media) outpouchings from arterial branching points
  • Site of rupture is at the dome (prone to rupture)
  • Associated vascular spasm produces global cerebral ischemia

Question 16

Saccular (Berry) Aneurysms

Answer 16

• 1.8% of autopsies
• increase in size with time; size=only predictor of rupture…critical size=1cm
• Etiology unclear
  
  • Congenital defect in media hypothesized
  • Genetic component
    
    • Associated with: autosomal dominant polycystic kidney disease, Ehlers-Danlos IV, NF I, Marfan’s
  • Female predominance (2:1)
  • Most are asymptomatic until rupture
  • Fatal in 50% of patients in first 24 hours
• Most in anterior circle of Willis (anterior communicating artery)

Question 17

Intraventricular Hemorrhage

Answer 17

• Primary
  
  • Very rare in adults
  • Common in premature infants, especially one with some hypertensive episodes or on mechanical ventilation
• Site of hemorrhage is in germinal matrix located beneath the ependyma which easily ruptures and extends into the ventricles-contains large vessles with very thin walls-vessels easily damaged
• Massive intraventricular hemorrhages are instantaneously fatal
• can also have intraparenchymal hemorrhage

Question 18

Duret hemorrhages

Answer 18

• Pons with so-called Duret hemorrhages
• Secondary to compression from herniation of the medial temporal lobe that leads to stretching and ischemia of perforating arterioles
• Compression can result from a variety of mass lesions producing herniation:
  
  • hemorrhages, inflammation, neoplasms

Question 19

Epidural hematoma (arterial bleed)

Answer 19

• Blood between dura and the skull
• Classic due to fracture of temporal bone with rupture of middle meningeal artery
• CT: lens – shaped lesion (lentiform or convex shaped collection of blood above the dura)
• Lucid interval may precede neurologic signs
• (transtentorial) Herniation is lethal complication

Question 20

Subdural Hematoma=slow venous bleed

Answer 20

• Blood underneath the dura covering brain surface
• Secondary to tearing of bridging veins between dura and arachnoid (due to venous bleeding)
• Usually due to trauma
• CT: crescent – shaped lesion (conforms to the shape of the brain)
• comression of brain surface and mild sub… herniation of the cingulate gyrus and compression of the ventricle
• Progressive neurologic signs
• ↑ in elderly due to age-related cerebral atrophy, which stretches bridging veins
• Herniation is lethal complication

Question 21

Herniation

Answer 21

• downward Displacement of the brain (cerebellar tonsils into foramen magnum) due to mass effect or increased intracranial pressure
• secondary subarachnoid hemorrhage
• Tonsillar herniation
  
  • Displacement of cerebellar tonsils into foramen magnum
  • Causes compression of brain stem and cardiopulmonary arrest
• Subfalcine herniation
  
  • Displacement of the cingulate gyrus under falx cerebri
  • may cause Compression of ACA leads to infarction
• Uncal (transtentorial) herniation
  
  • Displacement of uncus (medial temporal lobe) under tentorium cerebelli
  • Compression of CN III (oculomotor) – eye “down and out” + dilated pupil
  • Compression of PCA – occipital lobe infarct (contralateral homonymous hemianopsia)
  • Rupture of paramedian artery – Duret hemorrhages in pons

Question 22

What are the byproducts of cerebrovascular disease and how do they manifest?

Answer 22

• Ischemia or hemorrhage are the byproducts of cerebrovascular disease
• manifest as sudden, focal neurological deficits related to specific vascular territories of the central nervous system.

Question 23

TIA (transient ischemic attacks)

Answer 23

• sudden, focal neurological deficits which completely resolve within 24 hours.
• most TIAs only last minutes, but are a serious warning of high stroke risk.

Question 24

Stroke

Answer 24

• sudden, focal neurological deficit which does not completely resolve within 24 hours, but may variably improve over several weeks to months.
• Most of the time, a stroke is caused by ischemic infarction.

Question 25

Pathogenesis of ischemic cerebrovascular disease

Answer 25

• Most pts with cerebrovascular disease have significant atherosclerosis
  
  • predisposed by 1 or more RF: HTN, heart disease, DM, smoking, hyperlipidemia, + FHx of vascular disease.
    
    • Minor RF: obesity, lack of exercise, excessive alcohol consumption.
  • Atherosclerotic vascular changes more common even in older pts who lack major RF.
• Atherosclerotic changes predominate at bifurcation pts of large, major cervical and intracranial arteries
  
  • ​more turbulent blood flow at these sites
  • over months to yrs, intravascular atheromas or arterial plaques develop from:
    
    • subintimal lipid deposition
    • smooth muscle proliferation
    • fibrosis.
  • Enlarging atheromas or plaques may narrow/occlude an artery, or may ulcerate, or both.
  • As ulceration disrupts the intima, coagulation process is initiated, leads to local occlusion (thrombosis) or distal propagation (embolization) of blood clot, platelets, fibrin, cholesterol, or calcified elements (emboli) which then occlude smaller caliber arteries downstream.
• **Two basic mechanisms of ischemic infarction: local arterial thrombosis of an atheroma or embolic arterial occlusions from proximal sources.
• valuable collateral blood flow is enhanced by a congenitally “complete” circle of Willis at the base of the brain.
• neurological deficit produced by an ischemic infarction, may improve within hours to days if partially ischemic areas of brain recover (or over the subsequent weeks or months as different areas of the brain compensate for the impairment.)
• Gross: soft and swollen, less distinction of the gray-white matter junction, and some spotty hyperemia from extravasated blood. Atrophy of this area subsequently occurs.
• Microscopically
  
  • 12 to 36 hours: ischemic neurons shrink, appear eosinophilic (“pink neurons”).
  • Days later: macrophages scavenge necrotic debris, cyst formation occurs with astrocytes at the periphery of the infarction.
• Several important smaller arteries arise abruptly from the basilar artery and proximal anterior and middle cerebral arteries=perforator or lenticulostriate arteries
  
  • supply deeper structures with significant functions: BG, internal capsule, thalamus, and corona radiata.
  • lesions= lacunar infarcts, caused by Thrombosis
    
    • ​Thrombosis: ulceration disrupts the intima, coag process starts, get local occlusion/thrombosis

Question 26

Diagnosis of TIA and ischemic infarction

Answer 26

• Amaurosis fugax (monocular blindness) is one type of carotid territory TIA involving the ophthalmic artery (or its retinal branches).
  
  • Path: cholesterol emboli in retinal arterioles with occlusion of superior temporal arteriole
  • CP: “lowered dark shade” in one eye which gradually lightens up.
  • Other carotid TIAs may cause hemispheral ischemia leading to hemiparesis or aphasia.
• Vertebrobasilar territory TIAs cause ischemia of brain stem, cerebellum, or visual (occipital) cortex
  
  • symptoms: ataxia, homonymous hemianopsia, or hemiparesis associated with “crossed” brain stem syndromes.
• Certain stroke syndromes suggest occlusion of larger arteries or branches:
  
  • hemiparesis w/ greater weakness of face + upper limb= PREcentral mCA
  • hemiparesis w/ greater weakness of lower limb= infarct of PREcentral aCA.
  • Sensory deficits limited to the face and upper limb=infarct in the POSTcentral mCA
  • sensory deficits limited to the lower limb=infarct in the POSTcentral aCA.
  • Infarctions involving other MCA branches may produce aphasia or homonymous visual field deficits.
  • Cerebellar hemispheral syndromes or “crossed” brainstem syndromes (Weber syndrome, Wallenberg syndrome) occur with occlusion of large vertebrobasilar arterial branches.
  • Infarcts f/m small artery occlusions may cause one of the “classic” lacunar syndromes (or no symptoms at all)
    
    • Pure motor hemiplegia, ataxic-hemiparesis, and clumsy hand-dysarthria=lacunar syndromes from tiny infarcts in the internal capsule, corona radiata, or basilar pons.
    • pure sensory stroke= lacunar syndrome from a small vessel occlusion involving the thalamus.
• All ischemic events=problems with “plumbing system” of the “pump” (heart), “pipes” (blood vessels), or “fluid” (blood).
  
  • The heart can be a source of emboli causing TIAs or ischemic infarction in large artery territories.
  • Emboli can arise from:
    
    • endocardial clot associated with an acute MI
    • poorly contracting LV
    • LA clot created d/r afib.
    • Infected or septic emboli from endocarditis (infxn of heart valves).
    • Venous clots in adults with a patent foramen-ovale can pass from the RA->LA, and then into the cerebral circulation.
    • Arterial lesions usually consist of atherosclerotic plaques or stenoses which locally thrombose or embolize distally.
      
      • Lacunar infarctions from small vessel atherosclerotic occlusions are thrombotic in nature, and a diagnostic search for a cardiac or large artery source of emboli is not critical.
      • Hypercoagulable states (hereditary or acquired) can cause occlusions of large + small arteries, and cortical veins
        
        • Ex: sickle cell anemia, polycythemia vera, and the antiphospholipid antibody syndrome.

Question 27

Tx of TIA

Answer 27

• pt with TIAs typically has nml neuro exam, BUT should eval+tx urgently due to increased risk of future stroke.
• younger pts or those lacking stroke RF: work-up for coagulopathy or non- atherosclerotic causes of ischemia
• more typical stroke-prone pt: echo helps determine cardiac sources of emboli.
  
  • Carotid TIAs can be evaluated with ultrasound of the cervical internal carotid artery.
    
    • Other arterial imaging techniques: magnetic resonance angiography (MRA), computed tomography angiography (CTA) or more invasive catheter angiography methods.
• Pts with symptomatic atheromatous lesions of 70-99 % stenosis at origin of internal carotid artery, benefit from carotid endarterectomy (surgical removal of lesion)
  
  • A smaller risk reduction in future stroke exists when endarterectomy is done for symptomatic lesions of 50-69% stenosis, and even for asymptomatic lesions of 60-99% stenosis.
  • A complete or 100% stenotic lesion precludes any sx since its thombotic occlusion extends from neck to the base of the skull.
  • Other neuro-interventional procedures: arterial stenting and angioplasty (intravascular catheters).
• Warfarin therapy helps reduce stroke risk in pts w/ chronic afib (target INR 2.5)
  
  • In all other TIA patients, stroke reduction achieved w/ antiplatelet drugs:
    
    • aspirin 50 to 325 mg daily
    • clopidogrel 75 mg daily
    • aspirin 25 mg/dipyridamole 200 mg twice daily.
• Statin drugs reduce the risk of stroke even in the absence of hyperlipidemia.
• Medical control of BP and DM, cessation of smoking indicated in all patients.