Case 12 Learning Objectives

1. Describe cerebral circulation and common variants.

Cerebral circulation is carried by the two internal carotid arteries (ICA) and the two vertebral arteries that anastomose at the base of the
brain to form the circle of Willis. Carotid arteries and their branches (referred to as the anterior circulation) supply the anterior portion of
the brain while the vertebrobasilar system (referred to as posterior circulation) supplies the posterior portion of the brain.
Direction of blood flow: Vertebral arteries to PCA. If posterior communicating is stenosed, vessels above will be getting
majority of blood supply from internal carotids

One of the ant. comm is larger than the other, so one can be fed by the internal carotid vs. both
Can have reversal of flow if there is an obstruction
Subclavian feeds the vertebral a.
o
If there is a narrowing of subclavian (Subclavian steal syndrome), can take away blood from the
vertebral a. (brain)
o
When pts do activities that require increases blood flow in subclavian a., can cause cerebral sxs

3. Describe the mechanisms of ischemic stroke.

Vascular occlusion usually induces a territory of ischemia with the most severe deficits in blood flow at the core of this territory.
Surrounding this core is tissue with varying degrees of ischemia, depending on the availability of collateral perfusion. This region,
called the ischemic penumbra, may be salvageable if adequate perfusion is restored before cell death occurs. TIA: mildest end of
the spectrum in which no cell death results. This time-sensitive potential to rescue ischemic penumbra from infarction drives all
acute stroke therapies
Cerebral occlusion may result from local atherosclerosis, thrombosis, or embolism of a remote thrombus to the brain deprive local
brain tissue of O2 and nutrients required for normal metabolic function stroke can be viewed as the final product of diverse factors
that ultimately lead to vascular occlusion.

All ischemic stroke can be categorized into one of 5 underlying mechanisms of stroke:
I.
Embolism
a. causes ischemic stroke in one third or more of cases
b. typically cause large (>1 cm) infarcts involving the cortical surface, basal ganglia, or cerebellum
c. potential sources:
i. heart (atrial fibrillation, sick sinus syndrome, myocardial infarction with mural thrombus, dysfunctional or
artificial valves, dilated cardiomyopathy, and infective endocarditis); PFO is increasingly recognized as a
conduit for paradoxical embolism
ii. proximal internal carotid and vertebral arteries
iii. Ao arch d/t irregular surface of atherosclerotic lesions
iv. deep venous system
d. Hypercoagulable states: pregnancy, OCT, antiphospholipid syndrome may likelihood of embolization by promoting
thrombus formation
II.

large vessel disease

a. atherosclerosis and stenosis of large feeding arteries, both extracranial (internal carotids and vertebrals) and
intracranial (Circle of Willis vessels)
b. Ischemia may result from atherosclerotic occlusion or tight stenosis of a large artery that limits cerebral perfusion
distally
c. infarction may be visible in the cortex or deep white matter watershed areas (boundaries between main vascular
territories)
d. may result in local thrombosis from slow flow and endothelial factors that promote thrombosis or plaque rupture,
occluding the artery and/or allowing distal embolization of the thrombus or plaque cortical and wedge shaped,
reflecting the entire territory of the occluded artery
e. other large vessel sources typically seen in younger patients include arterial dissection, vasospasm due to migraine,
and cerebral vasculitis

III.

small vessel occlusion / lacunar stroke

a. 20% of ischemic strokes
b. small (<1 cm) infarct, located typically in the basal ganglia, internal capsule, thalamus, or pons
c. disease of the small penetrating end-arterioles, which have no collateral sources of flow
d. Occlusion arises gradually following hypertension-induced necrosis, atherosclerosis, and lipid deposition

IV.

cryptogenic: unknown causes after an appropriate evaluation is unrevealing

V.

other defined but unusual causes: dissection, arteritis, venous infarction, or infection.

5. Describe the evaluation and management of TIA.

The mainstay of treatment following acute recovery from a TIA should be to diagnose and treat the underlying cause. It is not always
immediately possible to tell the difference between a stroke and a TIA. Most patients who are diagnosed at a hospital's emergency
department as having suffered from a TIA will be discharged home and advised to contact their primary physician to organize further
investigations. TIA can be considered as the last warning. The reason for the condition should be immediately examined by imaging of
the brain. The initial treatment is aspirin, second line is clopidogrel, and third line is ticlopidine. If TIA is recurrent after aspirin treatment,
the combination of aspirin and dipyridamole is needed (Aggrenox).

An ECG may show atrial fibrillation, a common cause of TIAs, or other arrhythmias that may cause embolization to the brain. An
echocardiogram is useful in detecting thrombus within the heart chambers. Such patients benefit from anticoagulation.
If the TIA affects an area supplied by the carotid arteries, an ultrasound (TCD) scan may demonstrate carotid stenosis. For people with a
greater than 70% stenosis within the carotid artery, removal of atherosclerotic plaque by surgery, specifically a carotid endarterectomy,
may be recommended. Some patients may also be given modified release dipyridamole or clopidogrel. To reduce recurrence of an attack
ACE Inhibitors are used. The aim is not to lower blood pressure in a hurry as too low too fast may increase ischemic injury due to low
perfusion pressure.
Prevention: The use of anti-coagulant medications, heparin and warfarin; or anti-platelet medications such as aspirin.

6. List risk factors for stroke. ~CVD risks!!! (HTN, DM, smoking, dyslipidemia)

HTN
o
promotes the formation of atherosclerotic lesions, is the single most important treatable risk factor for stroke!!!
o
risk of both stroke and CAD as BP > 110/75. Not causal, since BP could be a marker for other risk factors eg. body
weight, which is associated with dyslipidemia, glucose intolerance, metabolic syndrome.
o
Should be on hypertensive therapy and those who have had a stroke should consider hypertensive therapy for the next 5yr

SMOKING Cigarette smoking is associated with an increased risk for all stroke subtypes and has a strong, dose-response
relationship for both ischemic stroke and subarachnoid hemorrhage. Observational studies have shown that the elevated risk of
stroke due to smoking declines after quitting and is eliminated by five-years later. Therefore, national guidelines recommend
smoking cessation for patients with stroke or transient ischemic attack (TIA) who have smoked in the year prior to the event and
suggest avoidance of environmental tobacco smoke.

DM Patients with diabetes mellitus have approximately twice the risk of ischemic stroke compared with those without diabetes.
Dyslipidemia, endothelial dysfunction, and platelet and coagulation abnormalities are among the risk factors that may promote the
development of carotid atherosclerosis in diabetics. Strict glycemic control reduces the risk of microvascular complications (eg,
retinopathy, nephropathy, and neuropathy) in patients with diabetes.

DYSLIPIDEMIA Hyperlipidemia is a major risk factor for coronary heart disease. However, the relationship between the serum
cholesterol concentration and stroke incidence appears to be more complex, in that cholesterol is an established risk factor for
atherosclerosis, but appears to be only a weak risk factor for ischemic stroke. Both low levels of high density lipoprotein (HDL)
cholesterol and a high total cholesterol to HDL ratio are risk factors for the development of carotid atherosclerosis. The relationship
however has found to be weak in many studies and may prove to be more important of a risk factor in those under 45. A main point
of conflict is that there has been limited relation to hyperlipidemia increasing risk of a stroke, however, statins have proved to reduce
risk of stroke.

Metabolic syndrome: presence of 3 components that include high fasting glucose, HTN, low HDL, abdominal obesity indicates a
pre-diabetic condition linked to insulin resistance. Unclear if an independent risk factor for ischemic stroke beyond the sum of its
individual components; available evidence is conflicting.

Atrial Fib - risk of developing an embolism in the cerebral vascular architechure.

Alcohol intake affects the risk of stroke in contradictory directions depending upon level of consumption, type of stroke, and
possibly ethnicity. Light drinking (1-2 drinks/day) appears to reduce risk, while heavy drinking risk.
Apolipoprotein E unsure; ligand for hepatic chylomicron and VLDL remnant receptors, leading to clearance of these. APOE e4 allele
has been reported to be a stroke risk factor in some but not other studies.
Hyperhomocysteinemia risk of CAD and cerebrovascular disease, especially of the large artery subtype of ischemic stroke,
possibly to the small artery subtype; it does not appear to be associated with cardioembolic or other stroke subtypes.
Inflammatory markers Increasing evidence suggests that inflammation plays a role in atherosclerosis and contributes to stroke
risk.
C-reactive protein long-term risk of CV events including ischemic stroke in men, although the evidence in women is less clear.
Studies found that increasing levels of both high sensitivity CRP and the acute phase reactant serum amyloid A (SAA) were
significantly associated with the short-term progression of carotid atherosclerotic lesions.
Fibrinogen associated with the risk of stroke and CVD; may act by several possible mechanisms, including promotion of
atherogenesis and inflammation, elevation of blood and plasma viscosity, increased platelet aggregability, increased tendency to
form fibrin within thrombus.
Leukocytes Leukocyte counts and neutrophil counts were associated with ischemic events including stroke, myocardial infarction,
and vascular death in a high-risk population. In the week before the recurrent event, the leukocyte count was significantly increased
over baseline levels.

8. List pharmacological therapy for stroke prevention.

Reduction of BPACE inhibitors ACE inhibitors are first-line therapy in all patients who have HF or asymptomatic LV dysfunction, in all patients who have
had an ST elevation MI, in patients with a non-ST elevation MI who have had an anterior infarct, diabetes, or systolic dysfunction, and in
patients with proteinuric chronic kidney disease.
Angiotensin II receptor blockers The specific indications for and efficacy of angiotensin II receptor blockers (ARBs) are similar to those
with ACE inhibitors.
Thiazides Diuretics should also be given for volume control in patients with heart failure or chronic kidney disease, with or without
nephrotic syndrome; these settings usually require loop diuretics. In addition, an aldosterone antagonist (spironolactone or eplerenone) is
indicated in selected patients with advanced HF who have relatively preserved renal function and, in patients with less severe disease,
for the prevention or treatment of hypokalemia.

Calcium channel blockers There are no absolute indications for calcium channel blockers in hypertensive patients. Long-acting
dihydropyridines are most commonly used. Like beta blockers, the non-dihydropyridine calcium channel blockers (verapamil, diltiazem)
can be given for rate control in patients with atrial fibrillation or for control of angina. Calcium channel blockers also may be preferred in
patients with obstructive airways disease.
Beta blockers A beta blocker without intrinsic sympathomimetic activity should be given after an acute myocardial infarction and to
stable patients with heart failure or asymptomatic left ventricular dysfunction (beginning with very low doses to minimize the risk and
degree of initial worsening of myocardial function). The use of beta blockers in these settings is in addition to the recommendations for
ACE inhibitors in these disorders.
Smoking- Quitting
DiabetesMetformin - Decreases hepatic glucose production, decreasing intestinal absorption of glucose and improves insulin sensitivity (increases
peripheral glucose uptake and utilization)
Thiazolidinediones - PPAR-gamma agonist
HyperlipidemiaStatin therapy In patients with hyperlipidemia, treatment with HMG CoA reductase inhibitors (statins) decreases the risk of stroke,
while lipid lowering by other means (eg, fibrates, resins, diet) has no significant impact on stroke incidence.
Antiplatelet therapyASPIRIN the most commonly used antiplatelet agent, inhibits the enzyme cyclooxygenase, reducing production of thromboxane A2, a
stimulator of platelet aggregation. This interferes with the formation of thrombi, thereby reducing the risk of stroke.
CLOPIDOGREL is a thienopyridine that inhibits ADP-dependent platelet aggregation.
DIPYRIDAMOLE impairs platelet function by inhibiting the activity of adenosine deaminase and phosphodiesterase, which causes an
accumulation of adenosine, adenine nucleotides, and cyclic AMP. Dipyridamole may also cause vasodilation.

9. List diagnostic evaluation for suspected stroke.

Acute stroke is still largely a clinical diagnosis, with imaging serving to exclude other stroke mimics and to contribute to the
mechanism evaluation. A stroke diagnosis rests primarily on an appropriate history and neurologic exam. The initial history must focus on
the exact time of symptom onset, a description of deficits, and the exclusion of facts that indicate a stroke mimic. An accurate history of
time of symptom onset often requires interview of witnesses and first responders in addition to the patient. Stroke mimics include
migraine aura, focal seizure, brain tumor (unusually), hypoglycemia, and nonorganic deficits such as conversion or factitious disorder.
Migraine and seizure are indicated by a history of deficits evolving over minutes to hours, often gradually progressing, reaching a
plateau, and gradually remitting in reverse order. Stroke, by contrast, presents with acute and immediate deficits without a graduated
time course. Brain tumor most often presents with subacute onset over days or weeks, but can sometimes present with acute deficits,
requiring imaging to distinguish from stroke. Nonorganic or psychiatric strokelike presentation can be diagnosed by a careful examination
to disclose nonphysiologic and effort-dependent patterns of neurological deficit.
Once the clinical history and examination suggest stroke and exclude any likelihood of stroke mimics, urgent brain imaging is
required mainly to distinguish hemorrhagic from ischemic stroke and to more definitively exclude mass lesions. The current standard of
care is emergency noncontrast head computed tomography (CT) scan. This test is highly sensitive to brain hemorrhage, but very
insensitive to acute brain ischemia. Thus, the diagnosis of ischemic stroke remains clinical based on history and exam, as the initial brain
CT merely excludes hemorrhage or mass. However, magnetic resonance imaging (MRI) is gradually replacing CT as the initial imaging
test in suspected stroke because of increasing availability and certain advantages over CT. MRI can now sensitively screen for acute
blood using gradient echo sequences, and has the advantage of exquisite delineation of acute ischemia. Diffusion-weighted MRI can
reveal ischemic brain tissue within minutes of onset. Furthermore, newer MRI and CT techniques being studied can help distinguish
reversibly ischemic brain (penumbra) from infarcted brain, allowing for more careful selection of candidates for hyperacute therapies.
Nevertheless, MRI takes longer to perform, requires a still patient, and is contraindicated or not tolerated in a variety of conditions, so CT
will remain a necessary first imaging study for some.
Transesophageal ECHO is superior for detecting PFO and for visualizing the left atrium, atrial appendage, and aortic arch. It
should be performed in patients with suspected embolism in whom the transthoracic ECHO is not revealing. All patients should undergo
12-lead electrocardiogram and cardiac telemetry monitoring to detect myocardial ischemia and rhythm disturbances, particularly atrial
fibrillation. All patients should be evaluated for hypertension, diabetes, hypercholesterolemia, smoking, and heart disease. Other
commonly ordered laboratory evaluations include complete blood count, serum creatinine, and C-reactive protein. In young patients (<50
years) and older patients with no clear cause for stroke, a workup for occult hematologic abnormalities is recommended; this includes
prothrombin time, partial thromboplastin time, antinuclear antibodies, serum protein electrophoresis, serological tests for syphilis,
erythrocyte sedimentation rate, lupus anticoagulant, anticardiolipin antibody, factor V Leiden, homocysteine, prothrombin gene mutation,
and activity of protein C, protein S, and antithrombin III. Ultimately, the risk-factor profile, vascular pathology and specific pattern of brain
infarction (usually clarified with MRI) will determine which type of stroke has occurred: large vessel, small vessel, embolic, other, or
cryptogenic.
10. List indications for carotid artery surgery/ angioplasty. There are 2 ways to treat a carotid artery that has plaque buildup in it. One is
surgery called endarterectomy. The other is a procedure called angioplasty with stent placement.
Carotid angioplasty and stenting (CAS) is a less-invasive way to repair the blockage in your carotid artery:
Your surgeon will make an incision in your groin after using some numbing medicine. You will also be given medicine to relax you.
Your surgeon will insert a catheter (a flexible tube) through the incision into an artery. The doctor will carefully guide the catheter up
to your neck to the blockage in your carotid artery.
Your surgeon will use live x-ray pictures to see your artery. This kind of x-ray is called fluoroscopy.
Next your surgeon will pass a guide wire through the catheter to the blockage. Another catheter with a very small balloon on the end
will be pushed over the guide wire and into the blockage. Then the balloon will be blown up. The balloon then presses against
the inside wall of your artery. This opens the artery and restores proper blood flow to your brain.
A stent (a wire mesh tube) may also be placed in the blocked area. The stent is inserted at the same time as the balloon catheter. It
expands when the balloon is blown up. The stent is left in place to help keep the artery open. The surgeon then removes the

balloon.