Stroke PDF

Stroke Neurovascular System • Normal neuronal-vascular relationship is critical for normal brain functioning • Vascular reduction decreases energy transport and nutrients across the BBB • Reduced clearance of neurotoxins from the brain Brain Micro-Vessel • Endothelium contains 3 structures: o Tight...

Stroke Neurovascular System • Normal neuronal-vascular relationship is critical for normal brain functioning • Vascular reduction decreases energy transport and nutrients across the BBB • Reduced clearance of neurotoxins from the brain Brain Micro-Vessel • Endothelium contains 3 structures: o Tight intercellular junctions without fenestrations o Limited pinocytic intracellular vesicles that lack vesicular transport o Mitochondria in abundance • Basement Membrane: Surrounds endothelium 40-50nm thick • BBB is made of: o Pericytes with smooth muscle o Astrocyte envelope abluminal vessel surface What is the Brain Blood Barrier (BBB)? • Highly specialized brain endothelial structure of the fully differentiated neurovascular system • Brain is privileged • Sheltered from systemic circulation Barrier and Carrier Function • Barrier has 4 functions: o Paracellular Barrier § restricts the free movement of H2O soluble compounds o Transcellular Barrier § low level of endocytosis and transcytosis → inhibits transport of substances to the cytoplasm o Enzymatic Barrier § acetylcholinesterase, alkaline phosphatase, gamma-glutamyl transpeptidase, monoamine oxidases and other drug metabolizing enzymes capable of degrading different compounds o Cerebral Endothelium § expresses a large number of efflux transporters (ABC, ATP binding cassette transporters like ABCB1 (pglycoprotein) etc. • Carrier function o Takes nutrients to brain (glucose and AAs have special transporters thru BBB) o Removes metabolites BBB Breakdown Contributors • Metrix Metalloproteinases (MMPs): degrade the tight junctions proteins • Integrins: Interact w constituents of the basement membrane • Tight Junction Protein Complexes cause disruption What is a Stroke? #1 cause of disability • 2 types: Ischemic and Hemorrhagic o Decreases oxygen rich blood to portion of brain (ischemic) o Sudden bleeding in brain leading to brain cell damage (hemorrhagic) • Symptoms occur in parts of body that those brain cells were controlling o Sudden weakness o Paralysis/numbness of face, arm, legs o Trouble speaking/understanding speech o Trouble seeing Stroke Risk Factors • Nonmodifiable o Age, gender: Older, males, birth control pills o Race, ethnicity: African Americans, Alaska natives, American indians o History of stroke: After initial stroke, repeated stroke risk is high • Modifiable o Medical Conditions § HTN § Hyperlipidemia § Diabetes § Carotid stenosis o Behaviors § Cigarette smoking § Alcohol § Physical inactivity Ischemic Stroke • Oxygenated blood to brain is blocked o Thrombotic: blood clot o Embolic: clot or plaque • Symptoms: o Hemiparesis: paralysis of one side o Aphasia: trouble understanding speech o Dysarthria: difficulty speaking o Vision loss o Hemisensory deficits o Ataxia/vertigo o Decreased consciousness Ischemia Stroke Timeline • Right after Ischemia o Increased Na/K cotransporters o Dysregulation of homeostasis causes ischemia induced edema formation • Infiltration and Accumulation of Peripheral Immune cells o Microglial cells cause increase in IL-1 and IL-6 o Leukocyte adherence, accumulation and transmigration across the endothelium o Mediate inflammatory cascades, further exaggerating infarction • Hemorrhagic Event o BBB dysfunction leads to hemorrhagic causing mortality after tissue plasminogen activator (tPA) treatment in stroke, esp following delayed tPA tx Disruption of BBB integrity in setting of Ischemic stroke • In 4-6 hrs: o Alterations of tight junction protein complexes o Increase in paracellular permeability at cerebral microvasculature o Modulation of transport proteins and endocytic transport mechanisms o Inflammatory damage o Cognitive and motor impairment • At 24-48 hrs: Highest risk of hemorrhagic transformation Stroke vs TIA (transient ischemic attack) • Transient episode of neurological dysfunction • No persistent neurologic deficit • Caused by either: o focal brain ischemia o spinal cord ischemia o retinal ischemia o WITHOUT acute infarction. Clinical Manifestations of Cerebral Ischemia • ACA (anterior cerebral artery) o Contralateral hemiparesis o Sensory loss (worst in leg) • MCA o Contralateral hemiparesis o sensory loss (arm, face worst) o Expressive aphasia (dominant) or hemineglect and spatial disorientation (nondominant) • PCA (posterior cerebral artery) o Contralateral homonymous hemianopia or o superior quadrantanopia • SCA (superior cerebellar artery): o Gait ataxia, nausea, dizziness o Headache progressing to ipsilateral hemiataxia o Dysarthria, gaze paresis, o Contralateral hemiparesis o Somnolence • PICA (posterior inferior cerebellar artery) o Ipsilateral loss of facial sensation o Ataxia o Contralateral hemiparesis o Sensory loss Ischemic Core vs Ischemia Penumbra • Ischemic core: irreversible cell death • Ischemic Penumbra o Reversible ischemic changes o Expansion based on severity of deficit in cerebral blood flow and existence of collateral blood supply Atrial Fibrillation and Stroke • Ineffective function of LA • Clot in left atrial appendage pushed into the carotid arteries and brain Primary Prevention of Stroke • Most strokes are FIRST time event • Control blood pressure • Smoking cessation • Adequate anticoagulation • Aspirin and statin therapy • Carotid endarterectomy • Mediterranean diet • Weight reduction • Screen for sleep apnea Hemorrhagic Stroke • Occurs if any artery in brain leaks blood or ruptures • 2 types: o Intracerebral: vessel inside the brain leaks o Subarachnoid: vessel on surface of brain leaks • Leaked blood causes: o swelling on brain o Increased skull pressure • Swelling and pressure damage cells and tissues in the brain • MRI detects leaks Presentation of Hemorrhagic Stroke • Focal neurologic deficits similar to ischemic stroke • Headache (worst headache of your life) • Nausea • Vomiting • Seizures • Altered mental status • Cross neurologic signs (ipsilateral face, contralateral body) Risk Factors for Hemorrhagic Stroke • HTN • Smoking • Alcohol abuse • Sympathomimetic drugs (cocaine, meth) • Anticoagulant therapy/coagulopathy • thrombolytics Aneurysm in Subarachnoid Hemorrhage (SAH) • Mostly Berry aneurysms (inherited) • Thin walled outpouchings that protrude from Circle of Willis • Assc conditions: o Polycystic Kidney Disease o Marfan and Ehlers-Danlos syndromes o Fibromuscular dysplasia o SLE o Sickle Cell Anemia • Complications of Subarachnoid Hemorrhage o Rebleeding (most common, 30% in 1st month) o Non neurologic complications: § Cardiac ischemia § Hyponatremia (electrolyte abnormality after SAH) o Cerebral Vasospasm o Seizure o Hydrocephalus Arteriovenous Malformation (AVM) • Congenital lesion • Tangled arteries and veins connected by one or more fistulae