Cerebral Circulation and Brain Infarcts

=Definitions=
 * atherthrombotic stroke
 * ischemia of the brain with neurological deficits lasting more than 24 hours caused by a thrombus originating from atherosclerotic vessel like the internal carotid artery


 * cardioembolic stroke
 * ischemia of the brain with neurological deficits lasting more than 24 hours caused by an emboli from the heart, typically in a patient with endocarditis or atrial fibrilation


 * lacunar stroke
 * a stroke of small vessels, typically of the deep structures perfused by the lenticularstriate arteries. associated with better prognosis


 * NMDA receptor
 * a voltage-gated ionotropic receptor in neurons. activated by glutamate and nerve depolarization.  significance here is the association with excitotoxicity under ischemic conditions.


 * leukocyte infiltration
 * white cells produce swelling and edema following a stroke


 * free radicals
 * major pathogenic process that damages protein and mitochondria under ischemic conditions in a stroke.

=Objectives=

Explain how strokes are important in society
Strokes are the leading cause of adult disabilities, the second leading cause of dementia, and the third leading cause of death in the United States. Half of the neurological disorders in the hospital are stroke related. They are extremely expensive. Ischemic strokes are most common and occur in the elderly, but infants (ischemia, heart disease), younger life (pregnancy, vascular malformations, sickle cell, vasculitis, etc).

What are the three principle causes of ischemic stroke

 * 1) Large vessel occlusive: a clot breaks off from artery perfusing an area of brain. Also includes vasculitis, and arterial dissection.
 * 2) Small vessel occlusive: infarction following atherothrombotic or lipohyalinotic occlusion of a small artery
 * 3) Cardioembolic: embolism of thrombotic material forming on the atrial or ventricular wall or the left heart valves

What are the risk factors for these conditions

 * Large vessel occlusive
 * smoking
 * atherosclerotic disease / elevated cholesterol
 * drugs
 * prior TIA (transient ischemic attack)
 * hypercoagulable disorder
 * small vessel occlusive
 * hypertension
 * diabetes
 * cardioembolic stroke
 * atrial fibrillation
 * recent myocardial infarction
 * paradoxical emolus (eg PFO)
 * dilated cardiomyopathy
 * mechanical valve
 * endocarditis

Why are hypotension and hyperglycemia associated with bad outcomes in acute strokes?

 * Moderate hypertension (< 185 systolic) can help perfuse the penumbra of the stoke in the acute setting. Hypotension can cause ischemia in the "watershed" areas of the brain even without occlusion.
 * High glucose is associated with increased necrosis, possibly by generating excess lactate by anaerobic respiration. Glucose should be maintained under 110 with an insulin infusion (Adam & Victor's).

Define penumbra

 * The penumbra is the marginally perfused zone around the core of irreversibly necrotic/dead neurons of an infarct. It contains at-risk but viable neurons.  The goal of treatment is to preserve cells in the penumbra--the center of the infarct will die regardless of treatment.

Describe how free radicals are detrimental during a stroke

 * Free radicals are produced in the ischemic environment when an a neuron is under stress. Free radicals are also generated from during reperfusion.
 * Promote necrosis and apoptosis
 * Free radicals damage proteins and disrupt normal cellular functions

Describe areas of therapeutic research

 * 1) clot busting: researchers are pursuing new methods to remove clots and improve protocols (ie <3hrs for TPA). For example, mechanical clot retrieval is tested against TPA, the Penumbra vibrating rota-rooter device, removable stents, etc.
 * 2) Neuroprotection: many therapeutic strategies aim to reduce neuron death by modulating excitotoxicity. Mechanisms include hypothermia, ion channel modulation, antixodiants, glutamate receptor modulation, etc.

What are the indications for carotid endarterectomy

 * carotid endarterctomy (CEA)
 * surgical procedure where carotid atherosclerosis can be removed. atherosclerotic disease is associated with TIAs and high rates of stroke.  surgery is associated with ~ 6% 30 day mortality

=Links=
 * CEA is recommended for patients with > 70% stenosis with any symptoms
 * CEA is recommended for patients with >50% stenosis with non-retinal symptoms
 * CEA is slightly better than aspirin for patients with > 60% stenosis; should be considered in younger patients.
 * Harrison's Internal Medicine - Ischemic Stroke
 * Adam's and Victor's Neurology: Cerebrovascular Disease