29 Pathophysiology and Evaluation of Cerebrovascular Disease.docx

Pathophysiology and Evaluation of Cerebrovascular Disease Objectives Identify risk factors for ischemic stroke and hemorrhagic stroke Classify cerebrovascular disease based on mechanism and brain territory Explain the pathophysiology of ischemic stroke and hemorrhagic stroke Differentiate ischemic...

Pathophysiology and Evaluation of Cerebrovascular Disease Objectives Identify risk factors for ischemic stroke and hemorrhagic stroke Classify cerebrovascular disease based on mechanism and brain territory Explain the pathophysiology of ischemic stroke and hemorrhagic stroke Differentiate ischemic stroke and hemorrhagic stroke Describe the clinical evaluation of acute ischemic stroke and hemorrhagic stroke What is “Stroke”? Heterogeneous group of disorders characterized by neurologic deficits attributed to an acute, focal injury of the central nervous system by a vascular cause AKA: cerebrovascular accident (CVA) Epidemiology Epidemiology in the U.S. Currently 7.2 million stroke survivors in the U.S. Likely underestimated: ~20% of adults > 45 report experiencing ≥ 1 stoke symptom 1st leading cause of adult disability 5th leading cause of death Annual incidence: ≈795,000 (new or recurrent) 87% ischemic strokes, 13% hemorrhagic strokes Annual cost: $40.1 billion Expensive post-hospitalization rehabilitation and nursing home care Classification Classification by Mechanism Classification by Brain Territory Territory suggested by symptoms, further delineated on neurologic exam, and confirmed on imaging Anterior Cerebral Artery (ACA) Contralateral hemiplegia (legs and feet) Contralateral sensory loss (legs and feet) Aphasia Middle Cerebral Artery (MCA) Contralateral hemiplegia (lower face, arm, hand) Contralateral sensory loss (lower face, arm, hand) Aphasia Homonymous hemianopia Hemineglect Posterior Cerebral Artery (PCA) Vertigo Double vision Contralateral homonymous hemianopia Visual hallucinations Contralateral hemiparesis Hemisensory loss Memory defect Symptom Terminology Review Term Meaning Aphasia Loss of ability to understand or express speech Contralateral Relating to or denoting the side of the body opposite to that on which a particular structure or condition occurs Dysarthria Weakness in the muscles used for speech, which often causes slowed or slurred speech Hemineglect Condition in which patients fail to be aware of items to one side of space Hemiparesis Slight paralysis or weakness on one side of the body Hemiplegia Paralysis of one side of the body Homonymous Hemianopia Condition in which a person sees only one side―right or left―of the visual field of each eye Monoparesis Weakness limited to one limb without sensory disturbance Vertigo A sudden internal or external spinning sensation Ischemic Stroke Risk Factors Previous Transient Ischemic Attacks (TIAs) Non-modifiable Age, race/ethnicity, sex, low birth weight, genetic factors Age: risk of stroke doubles for each decade > 55 years Race/ethnicity: African Americans, Asian-Pacific Islanders, and Hispanic individuals have higher rates of death from ischemic stroke compared to Caucasians African Americans have 1.5 – 2x higher stroke risk compared to Caucasians Sex: men have higher risk at younger age; women have a higher mortality and higher lifetime risk of ischemic stroke Modifiable Cigarette smoking, HTN, DM, asymptomatic carotid stenosis, DLD, AF, sickle cell disease, other cardiac diseases (CHD, HF, PAD), poor diet, obesity, physical inactivity Hypertension (HTN) is the most common risk factor: ~1 in 3 U.S. adults Atrial fibrillation (AF) increases risk of ischemic stroke 5-20% per year Diabetes (DM), dyslipidemia (DLD), smoking, and HTN contribute to atherogenesis Ischemic Stroke Caused by occlusion of a cerebral artery Atherosclerosis of large intracranial or extracranial arteries Small artery damage Cardiogenic emboli (atrial fibrillation, valvular heart disease, other prothrombogenic heart problems) Pathophysiology Cerebral autoregulation Cerebral blood vessels dilate and constrict in response to changes in blood pressure to maintain an average rate of cerebral blood flow of 50 mL/100g per minute Impaired by atherosclerosis, chronic hypertension, acute injury, embolus Ischemic penumbra: tissue surrounding a core infarction that is ischemic but may maintain membrane integrity Potentially salvageable with urgent intervention Stepwise: Insufficient oxygen supply ATP depletion Accumulation of lactate and intracellular Na+ cytotoxic edema and cell lysis Influx of intracellular Ca2+ activation of lipases and proteases protein degradation Release of excitatory amino acids (glutamate and aspartate) production of damaging prostaglandins, leukotrienes, and reactive oxygen species Cellular apoptosis and necrosis Pathophysiology Summary Cerebral artery occlusion Hypoperfusion Excitotoxicity Oxidative stress Cellular necrosis Cerebral injury Neurologic dysfunction Brain damage, disability, death Large Vessel Thrombotic Stroke Primarily due to atherosclerosis Intracranial (major cerebral arteries)- most cases Extracranial (carotid artery) Small Vessel Thrombotic Stroke AKA “Lacunar Stroke” or “Lacunar Infarction” Atherothrombotic or lipid occlusion of a small artery in the brain Stereotyped clinical syndromes Pure motor hemiparesis Pure sensory stroke Ataxic hemiparesis Dysarthria and a clumsy hand or arm Cardioembolic Stroke ~50% of ischemic strokes Presumed in patients with chronic atrial fibrillation (AF) Stroke risk = 6x higher Other sources of cerebral embolism: Valvular heart disease Prosthetic heart valves Endocarditis VERY important to distinguish this cause from others primary and secondary prevention strategies Cryptogenic Stroke Cerebral ischemia of obscure or unknown origin Unable to determine cause because: Event is transitory or reversible Investigations did not look for all possible causes Some causes truly remain unknown Deemed cryptogenic in absence of atherogenic medical history (DM, DLD, smoking, etc.) AND absence of thombogenic heart disease (AF, valvular heart disease, etc.) Recently referred to as ESUS (embolic stroke of undetermined source) Transient Ischemic Attack Arterial ischemia with transient symptoms without evidence of infarction AKA “mini stroke” Temporary blockage of cerebral blood flow Frequently result from small clots breaking away from larger, distant clots/plaques Transient neurological dysfunction Lasting < 24 hours Usually < 30 minutes – 1 hour ~50% of ischemic strokes are preceded by minor neurologic signs or ≥ 1 TIA TIAs are a strong and important risk factor for ischemic stroke! Hemorrhagic Stroke Risk Factors Non-modifiable Age, race/ethnicity, sex Modifiable Hypertension, anticoagulation, thrombolytic therapy, heavy alcohol consumption, illicit drug use (cocaine, methamphetamine) Hemorrhagic Stroke Bleeding that directly causes damage to the brain tissue Leaking blood causes displacement and compression of nearby tissue dissects into ventricles and subarachnoid space May result from injury, acute severe elevations in blood pressure, or from a variety of disorders that weaken vessels Pattern of neurologic deficits less predictable than ischemic stroke Location of bleed and factors affecting function of brain regions distant from hemorrhage (increased intracranial pressure, cerebral edema, etc.) Pathophysiology Neuronal damage occurs by a variety of mechanisms Direct irritant effect Mass effect Pathophysiology Summary Hemorrhage Neuronal damage Increased intracranial pressure Toxic effects of blood on brain tissue Neurologic dysfunction Severe brain damage, prolonged coma, death Subarachnoid Hemorrhage (SAH) Occurs when blood enters the subarachnoid space Due to trauma, rupture of an intracerebral aneurysm, or rupture of an arteriovenous malformation (AVM) Sudden onset of severe headache +/- vomiting Non-focal neurological signs Loss of consciousness, neck stiffness Intracerebral Hemorrhage (ICH) Occurs when bleeding occurs in the brain parenchyma itself Associated with uncontrolled hypertension (most common cause), anticoagulation, thrombolytic therapy, or illicit drug use Significantly higher mortality than ischemic stroke (50% vs. 25%) Evaluation of Cerebrovascular Disease Evaluation of Cerebrovascular Disease Sudden Onset Focal involvement of the central nervous system Lack of rapid resolution Vascular cause Stroke Screening Time Is Brain! There are ~130 billion neurons in human brain For every minute 1.9 million neurons are destroyed Evaluation of Cerebrovascular Disease Patient History Determine abrupt onset and duration of symptoms Patient may not be reliable due to cognitive or language deficits May need to rely on family member or other witness Neurologic Exam Signs Imaging CT +/- MRI Patient History: Symptoms Focal Symptoms Weakness, numbness, paralysis on one side of the body (arm, leg, face) Inability to speak or difficulty understanding speech Loss of vision Vertigo, loss of balance/coordination, falling Maybe headache (severe headache common in hemorrhagic stroke) Non-Focal Symptoms Generalized weakness and/or sensory disturbance Light-headedness or faintness Tinnitus (ringing in the ears) Brief loss of consciousness Confusion Incontinence of urine or feces Not a stroke in absence of focal symptoms! Differential Dx: hypoglycemia, brain tumor, epilepsy, migraine (complicated), syncope, infection Neurologic Exam: Signs Deficits Hemiparesis or monoparesis Hemiplegia Hemisensory deficit Vertigo Double vision Visual field deficits Aphasia Dysathria Altered levels of consciousness Duration of deficits Stroke: > 24 hours TIA: usually < 1 hour Imaging: CT and/or MRI To determine the presence of stroke Other Diagnostic Tests: Not in the acute setting! To determine the cause of stroke Carotid doppler (CD): carotid stenosis Electrocardiogram (ECG or EKG): atrial fibrillation Transthoracic echocardiography (TTE): valvular heart disease Transesophageal echocardiography (TEE): cardiogenic emboli Transcranial Doppler (TCD): intracranial stenosis Summary Stroke can be either ischemic or hemorrhagic Stroke is a medical emergency! Requires prompt medical attention and urgent diagnosis Must distinguish between the two main types of stroke If ischemic, distinguish thrombotic vs cardioemolic Establish a clear history of sudden onset with focal neurological deficit Signs and symptoms related to a vascular territory