Ischemic Stroke

Overview

Definition

An ischemic stroke is an acute neurologic injury that occurs as a result of brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage; this condition may be due to cerebral blood vessel occlusion by thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus or embolism or, rarely, due to systemic hypoperfusion.

Epidemiology

• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 800,000 cases per year in the US
• 2nd leading cause of death worldwide
• 2nd most common cause of disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment in adults
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency increases with age.
• Approximately 80%–85% of all strokes are ischemic (15%–20% are hemorrhagic).
• Of the ischemic strokes, approximately 80% are thrombotic (20% are embolic).
• The most common embolic cause is atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation with thromboembolism Thromboembolism Obstruction of a blood vessel (embolism) by a blood clot (thrombus) in the blood stream. Systemic Lupus Erythematosus.

Etiology/classification

Thrombotic stroke:

• Large-vessel occlusion: middle cerebral artery Middle cerebral artery The largest of the cerebral arteries. It trifurcates into temporal, frontal, and parietal branches supplying blood to most of the parenchyma of these lobes in the cerebral cortex. These are the areas involved in motor, sensory, and speech activities. Cerebrovascular System: Anatomy (MCA), posterior cerebral artery Posterior cerebral artery Artery formed by the bifurcation of the basilar artery. Branches of the posterior cerebral artery supply portions of the occipital lobe; parietal lobe; inferior temporal gyrus, brainstem, and choroid plexus. Cerebrovascular System: Anatomy, anterior cerebral artery Anterior cerebral artery Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus; internal capsule; putamen; septal nuclei; gyrus cinguli; and surfaces of the frontal lobe and parietal lobe. Cerebrovascular System: Anatomy
  • Causes:
    • Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis (most common cause) → large-vessel thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus due to a clot on an established plaque Plaque Primary Skin Lesions
    • Arteritis/ vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus
    • Arterial dissection Arterial dissection Arterial dissection is a violation of the structural integrity of the arterial wall that results in blood accumulating between the layers. Dissection of the Carotid and Vertebral Arteries
    • Moyamoya disease (spontaneous occlusion of the arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology around the circle of Willis Circle of Willis A polygonal anastomosis at the base of the brain formed by the internal carotid, proximal parts of the anterior, middle, and posterior cerebral arteries, the anterior communicating artery and the posterior communicating arteries. Subarachnoid Hemorrhage (rare))
  • Most common locations:
    • Bifurcation of the common carotid artery Common carotid artery The two principal arteries supplying the structures of the head and neck. They ascend in the neck, one on each side, and at the level of the upper border of the thyroid cartilage, each divides into two branches, the external and internal carotid arteries. Carotid Arterial System: Anatomy
    • MCA
    • Intracranial vertebral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology proximal to the middle basilar artery
    • Origin of the vertebral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology
  • Less common locations:
    • Origin of the common carotid artery Common carotid artery The two principal arteries supplying the structures of the head and neck. They ascend in the neck, one on each side, and at the level of the upper border of the thyroid cartilage, each divides into two branches, the external and internal carotid arteries. Carotid Arterial System: Anatomy
    • Posterior cerebral artery Posterior cerebral artery Artery formed by the bifurcation of the basilar artery. Branches of the posterior cerebral artery supply portions of the occipital lobe; parietal lobe; inferior temporal gyrus, brainstem, and choroid plexus. Cerebrovascular System: Anatomy
    • Origin of the major branches of the vertebral basilar arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology
    • Origin of the branches of the anterior, middle, and posterior cerebral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology
• Small vessel occlusion = lacunar infarcts:
  • Causes:
    • Lipohyalinosis due to hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
    • Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis at the origin of the small vessel or large parent artery
  • Least likely to have embolic occlusion
  • Location:
    • Small penetrating arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology that arise from the distal vertebral artery Vertebral artery The first branch of the subclavian artery with distribution to muscles of the neck; vertebrae; spinal cord; cerebellum; and interior of the cerebrum. Lateral Medullary Syndrome (Wallenberg Syndrome), basilar artery, stem of the MCA, or the circle of Willis Circle of Willis A polygonal anastomosis at the base of the brain formed by the internal carotid, proximal parts of the anterior, middle, and posterior cerebral arteries, the anterior communicating artery and the posterior communicating arteries. Subarachnoid Hemorrhage
    • Most often in the deep penetrating vessels that reach the white matter White Matter The region of central nervous system that appears lighter in color than the other type, gray matter. It mainly consists of myelinated nerve fibers and contains few neuronal cell bodies or dendrites. Brown-Séquard Syndrome and deep gray matter Gray matter Region of central nervous system that appears darker in color than the other type, white matter. It is composed of neuronal cell bodies; neuropil; glial cells and capillaries but few myelinated nerve fibers. Cerebral Cortex: Anatomy in the thalamus Thalamus The thalamus is a large, ovoid structure in the dorsal part of the diencephalon that is located between the cerebral cortex and midbrain. It consists of several interconnected nuclei of grey matter separated by the laminae of white matter. The thalamus is the main conductor of information that passes between the cerebral cortex and the periphery, spinal cord, or brain stem. Thalamus: Anatomy, basal ganglia Basal Ganglia Basal ganglia are a group of subcortical nuclear agglomerations involved in movement, and are located deep to the cerebral hemispheres. Basal ganglia include the striatum (caudate nucleus and putamen), globus pallidus, substantia nigra, and subthalamic nucleus. Basal Ganglia: Anatomy, or pons Pons The front part of the hindbrain (rhombencephalon) that lies between the medulla and the midbrain (mesencephalon) ventral to the cerebellum. It is composed of two parts, the dorsal and the ventral. The pons serves as a relay station for neural pathways between the cerebellum to the cerebrum. Brain Stem: Anatomy

Embolic stroke:

• Cardiac sources:
  • Left atrial thrombi Left Atrial Thrombi Transient Ischemic Attack (TIA)/ atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation (most frequent isolated cause)
  • Left ventricular thrombus
  • Atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation
  • Recent MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction (< 1 month)
  • Rheumatic mitral or aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy disease
  • Bioprosthetic and mechanical heart valve emboli
  • Carotid atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis 
  • Bacterial endocarditis Bacterial endocarditis Inflammation of the endocardium caused by bacteria that entered the bloodstream. The strains of bacteria vary with predisposing factors, such as congenital heart defects; heart valve diseases; heart valve prosthesis implantation; or intravenous drug use. Endocarditis (septic emboli)
  • Patent foramen ovale Foramen ovale An opening in the wall between the right and the left upper chambers (heart atria) of a fetal heart. Oval foramen normally closes soon after birth; when it fails to close the condition is called patent oval foramen. Patent Foramen Ovale
  • Arterial dissection Arterial dissection Arterial dissection is a violation of the structural integrity of the arterial wall that results in blood accumulating between the layers. Dissection of the Carotid and Vertebral Arteries (rupture of an arterial wall followed by thrombus formation and embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding)
• Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis may also be embolic (in addition to thrombotic).
  • Iatrogenic embolization Iatrogenic Embolization Transient Ischemic Attack (TIA) after an angiogram or other vascular procedures
  • Emboli released during carotid artery surgery

Systemic hypoperfusion:

• Usually global/bilateral and does not affect isolated regions
• Watershed regions between major cerebral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology are the most vulnerable.
• Causes:
  • Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) with severely reduced cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics
  • Cardiac arrest Cardiac arrest Cardiac arrest is the sudden, complete cessation of cardiac output with hemodynamic collapse. Patients present as pulseless, unresponsive, and apneic. Rhythms associated with cardiac arrest are ventricular fibrillation/tachycardia, asystole, or pulseless electrical activity. Cardiac Arrest or serious arrhythmia

Risk factors

• Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension (most important)
• Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus
• Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
• Hyperlipidemia
• Carotid stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS)
• Previous history of stroke or transient ischemic attack Transient ischemic attack Transient ischemic attack (TIA) is a temporary episode of neurologic dysfunction caused by ischemia without infarction that resolves completely when blood supply is restored. Transient ischemic attack is a neurologic emergency that warrants urgent medical attention. Transient Ischemic Attack (TIA) ( TIA TIA Transient ischemic attack (TIA) is a temporary episode of neurologic dysfunction caused by ischemia without infarction that resolves completely when blood supply is restored. Transient ischemic attack is a neurologic emergency that warrants urgent medical attention. Transient Ischemic Attack (TIA))
• Heart disease:
  • Atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation
  • Valvular heart disease
  • Cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Cardiomyopathy: Overview and Types
• Older age
• Migraine with aura Migraine with Aura A subtype of migraine disorder, characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision; hallucinations; vertigo; numbness; and difficulty in concentrating and speaking. Aura is usually followed by features of the common migraine, such as photophobia; phonophobia; and nausea. Migraine Headache
• Hypercoagulable Hypercoagulable Hypercoagulable states (also referred to as thrombophilias) are a group of hematologic diseases defined by an increased risk of clot formation (i.e., thrombosis) due to either an increase in procoagulants, a decrease in anticoagulants, or a decrease in fibrinolysis. Hypercoagulable States states:
  • Antiphospholipid syndrome Antiphospholipid syndrome Antiphospholipid syndrome (APLS) is an acquired autoimmune disorder characterized by the persistent presence of antiphospholipid antibodies, which create a hypercoagulable state. These antibodies are most commonly discovered during a workup for a thrombotic event or recurrent pregnancy loss, which are the 2 most common clinical manifestations. Antiphospholipid Syndrome
  • Cancer/ malignancy Malignancy Hemothorax
  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  • Oral contraceptive Oral contraceptive Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both. Benign Liver Tumors use (especially in women > 35 years who smoke)
• Genetic conditions: cerebral autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
• Blood disorders:
  • Sickle cell disease Sickle cell disease Sickle cell disease (SCD) is a group of genetic disorders in which an abnormal Hb molecule (HbS) transforms RBCs into sickle-shaped cells, resulting in chronic anemia, vasoocclusive episodes, pain, and organ damage. Sickle Cell Disease
  • Protein C or protein S deficiency Protein S deficiency An autosomal dominant disorder showing decreased levels of plasma protein S antigen or activity, associated with venous thrombosis and pulmonary embolism. Protein s is a vitamin k-dependent plasma protein that inhibits blood clotting by serving as a cofactor for activated protein C (also a vitamin K-dependent protein), and the clinical manifestations of its deficiency are virtually identical to those of protein C deficiency. Treatment with heparin for acute thrombotic processes is usually followed by maintenance administration of coumarin drugs for the prevention of recurrent thrombosis. Hypercoagulable States (usually congenital Congenital Chorioretinitis; can also be acquired)
  • Factor V Leiden Factor V Leiden Hypercoagulable States ( resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing to activated protein C)
  • Essential thrombocytosis
  • Polycythemia Polycythemia An increase in the total red cell mass of the blood. Renal Cell Carcinoma vera

Pathophysiology

A complete reduction in cerebral blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure results in the death of brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification tissue within 4–10 minutes:

1. Occlusion of intracranial artery
2. Reduction in blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure to the region supplied by the vessel
3. Cerebral tissue starts to undergo ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage as neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology are deprived of glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance and oxygen → failure of mitochondria Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive ribosomes, transfer RNAs; amino Acyl tRNA synthetases; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs. Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. The Cell: Organelles to produce ATP
4. Membrane ion pumps stop functioning due to lack of ATP, and neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology depolarize → intracellular calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes increases and glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids is released from the presynaptic terminals
5. Excess extracellular glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids induces greater uptake of calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes by neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology → neurotoxicity
6. Free radicals Free radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Ischemic Cell Damage are produced and accumulate within neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology → catalytic destruction of membranes
7. Infarction or necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage of brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification tissue will occur if blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure is not restored within a few minutes.
8. An area of ischemic penumbra is produced around the area of infarction, where injury and corresponding neurological dysfunction are still reversible.
9. Restoration of blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure can induce the formation of more free radicals Free radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Ischemic Cell Damage and reperfusion injury Reperfusion injury Adverse functional, metabolic, or structural changes in ischemic tissues resulting from the restoration of blood flow to the tissue (reperfusion), including swelling; hemorrhage; necrosis; and damage from free radicals. The most common instance is myocardial reperfusion injury. Ischemic Cell Damage.
10. Clinical neurological symptoms become apparent.

Clinical Presentation

History

• The affected individual may or may not recall the time of onset of neurological symptoms.
• Family members or caregivers may notice a sudden onset of a focal neurological deficit and call for transport to the ED.
• Important to establish:
  • Amount of time passed since symptom onset (the last time seen as “normal”):
    • If the individual woke up with neurologic symptoms, the last time point considered “normal” is the night before.
    • Treatment decisions for reperfusion therapy are based on the time the affected individual was last seen without stroke symptoms.
  • Precise account of the event
• Cardiovascular disease and other risk factors
• Past episodes of TIAs
• Medications

Physical examination

• Neurological exam findings represent ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage in different vascular territories:
  • Anterior cerebral artery Anterior cerebral artery Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus; internal capsule; putamen; septal nuclei; gyrus cinguli; and surfaces of the frontal lobe and parietal lobe. Cerebrovascular System: Anatomy:
    • Contralateral hemiparesis Hemiparesis The term hemiparesis refers to mild to moderate weakness involving one side of the body. Epidural Hemorrhage and sensory deficit Sensory Deficit Anterior Cord Syndrome
    • Lower extremity weakness and sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology loss
    • Limb apraxia Apraxia A group of cognitive disorders characterized by the inability to perform previously learned skills that cannot be attributed to deficits of motor or sensory function. The two major subtypes of this condition are ideomotor and ideational apraxia, which refers to loss of the ability to mentally formulate the processes involved with performing an action. For example, dressing apraxia may result from an inability to mentally formulate the act of placing clothes on the body. Apraxias are generally associated with lesions of the dominant parietal lobe and supramarginal gyrus. Cranial Nerve Palsies
    • Incontinence
  • MCA:
    • Contralateral hemiparesis Hemiparesis The term hemiparesis refers to mild to moderate weakness involving one side of the body. Epidural Hemorrhage and sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology deficits
    • The face and upper limb are more profoundly affected than the leg Leg The lower leg, or just “leg” in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg: Anatomy.
    • Contralateral visual field Visual Field The Visual Pathway and Related Disorders reduction/hemianopsia
    • Aphasia: inability to understand and utilize language (dominant hemisphere)
    • Ataxic hemiparesis Hemiparesis The term hemiparesis refers to mild to moderate weakness involving one side of the body. Epidural Hemorrhage and dysarthria Dysarthria Disorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from cranial nerve diseases; neuromuscular diseases; cerebellar diseases; basal ganglia diseases; brain stem diseases; or diseases of the corticobulbar tracts. The cortical language centers are intact in this condition. Wilson Disease (also seen with lacunar stroke)
    • Hemianopsia
  • Posterior cerebral artery Posterior cerebral artery Artery formed by the bifurcation of the basilar artery. Branches of the posterior cerebral artery supply portions of the occipital lobe; parietal lobe; inferior temporal gyrus, brainstem, and choroid plexus. Cerebrovascular System: Anatomy:
    • Contralateral homonymous hemianopia Hemianopia Transient Ischemic Attack (TIA)
    • Sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology loss
  • Posterior inferior cerebellar artery Posterior inferior cerebellar artery Cerebrovascular System: Anatomy ( PICA Pica Pica is an eating disorder characterized by a desire or recurrent compulsion to eat substances that are nonnutritive and not food. These compulsions and ingested substances are inappropriate for age or culture. Pica) = Wallenberg’s syndrome
    • Dysphonia Dysphonia Difficulty and/or pain in phonation or speaking. Epiglottitis (difficulty in phonating speech) and dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia (from cranial nerves Cranial nerves There are 12 pairs of cranial nerves (CNs), which run from the brain to various parts of the head, neck, and trunk. The CNs can be sensory or motor or both. The CNs are named and numbered in Roman numerals according to their location, from the front to the back of the brain. The 12 Cranial Nerves: Overview and Functions IX and X being affected)
    • Ipsilateral ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia with a tendency to fall to the affected side (inferior cerebellar hemisphere, spinocerebellar fibers, and cerebellar peduncle)
    • Horner syndrome Horner syndrome Horner syndrome is a condition resulting from an interruption of the sympathetic innervation of the eyes. The syndrome is usually idiopathic but can be directly caused by head and neck trauma, cerebrovascular disease, or a tumor of the CNS. Horner Syndrome: miosis Miosis Pupil: Physiology and Abnormalities, ptosis Ptosis Cranial Nerve Palsies, and anhidrosis (sympathetic fibers)
    • Ipsilateral pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and numbness on the face (loss of facial sensation)
    • Contralateral numbness on the body
    • Dysarthria Dysarthria Disorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from cranial nerve diseases; neuromuscular diseases; cerebellar diseases; basal ganglia diseases; brain stem diseases; or diseases of the corticobulbar tracts. The cortical language centers are intact in this condition. Wilson Disease (difficulty in articulating speech)
    • Vertigo Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo with nystagmus Nystagmus Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. Albinism
    • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia associated with vertigo Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo; sometimes intractable hiccups
  • Small-vessel infarcts (lacunar infarcts): pure motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology or sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology strokes
    • Pure motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology hemiplegia: contralateral pons Pons The front part of the hindbrain (rhombencephalon) that lies between the medulla and the midbrain (mesencephalon) ventral to the cerebellum. It is composed of two parts, the dorsal and the ventral. The pons serves as a relay station for neural pathways between the cerebellum to the cerebrum. Brain Stem: Anatomy or internal capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides
    • Pure sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology stroke: lacunar infarct Infarct Area of necrotic cells in an organ, arising mainly from hypoxia and ischemia Ischemic Cell Damage in the contralateral thalamus Thalamus The thalamus is a large, ovoid structure in the dorsal part of the diencephalon that is located between the cerebral cortex and midbrain. It consists of several interconnected nuclei of grey matter separated by the laminae of white matter. The thalamus is the main conductor of information that passes between the cerebral cortex and the periphery, spinal cord, or brain stem. Thalamus: Anatomy
• Cardiovascular examination Cardiovascular examination Examination of the cardiovascular system (CVS) is a critical component of a thorough physical examination. As with all components of a complete physical examination, the CVS examination consists of inspection, palpation, and auscultation. The evaluation of the CVS focuses on the heart, but also includes an assessment of the arterial system throughout the body. Cardiovascular Examination:
  • Cardiac arrhythmia (e.g., atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation) 
  • Cardiac murmurs
  • Carotid bruits 
• Ophthalmologic examination: fundoscopic signs of hypertensive or diabetic retinopathy Diabetic retinopathy Disease of the retina as a complication of diabetes mellitus. It is characterized by the progressive microvascular complications, such as aneurysm, intraretinal edema, and intraocular pathologic neovascularization. Chronic Diabetic Complications

Diagnosis

Diagnosis is made with a suggestive history and clinical examination findings and confirmed by neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant.

Standardized neurologic testing with the NIH stroke scale Scale Dermatologic Examination (NIHSS)

• 0–42 points, > 25 is a severe stroke
• Note the time interval when the test is performed:
  • Baseline
  • 2 hours post-treatment
  • 24 hours post-onset of symptoms
  • 7–10 days
• Administer in the order listed and record the performance in each category:
  • Level of consciousness
  • Best gaze-testing of horizontal eye movements
  • Visual fields
  • Facial palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies
  • Motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology evaluation in arms and legs
  • Limb ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia
  • Sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology exam
  • Evaluation of language comprehension
  • Evaluation of dysarthria Dysarthria Disorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from cranial nerve diseases; neuromuscular diseases; cerebellar diseases; basal ganglia diseases; brain stem diseases; or diseases of the corticobulbar tracts. The cortical language centers are intact in this condition. Wilson Disease

Labs

• CBC including platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology
• Urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children
• Chemistries: electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes, glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance, BUN, and creatinine
• Serum lipid profile Lipid profile Lipid Disorders: provides a baseline, but may not be accurate in acute emergencies
• PT and PTT
• Cardiac enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
• Direct factor Xa activity assay, if the individual is taking direct thrombin inhibitor Direct Thrombin Inhibitor Anticoagulants or direct factor Xa inhibitor Direct Factor Xa Inhibitor Anticoagulants and is a candidate for thrombolytic therapy

Other tests

• Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests
• ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG)

Neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant

• Noncontrast head CT scan:
  • Only for differentiation between ischemic and hemorrhagic strokes
  • Acute ischemic zones are not visualized (can be mistaken for a normal scan).
  • Preferred emergency image modality
• MRI brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification:
  • Allows visualization of acute ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage and ischemic penumbra = greater sensitivity
  • Greater resolution but longer time for imaging
  • Less availability

Management

The goal of stroke management is to ensure prompt intervention and optimal outcomes. If possible, restoration of adequate blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure to the injured regions and saving the ischemic penumbra from permanent injury should be attempted.

Initial management

• Assess airway Airway ABCDE Assessment, breathing, and circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment (ABC).
• Treat hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia or hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus accordingly (may masquerade as stroke).
• IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids
• Assess for reperfusion therapy: ideally administered within 60 minutes of arrival to the ED
• Criteria for thrombolysis with the recombinant tissue plasminogen activator Recombinant tissue plasminogen activator A proteolytic enzyme in the serine protease family found in many tissues which converts plasminogen to fibrinolysin. It has fibrin-binding activity and is immunologically different from urokinase-type plasminogen activator. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. Thrombolytics (tPA) alteplase Alteplase Thrombolytics or other agents:
  • Diagnosis of ischemic stroke causing neurologic deficits Neurologic Deficits High-Risk Headaches (and not improving)
  • < 4.5 hours after the onset of symptoms
  • ≥ 18 years of age
  • Absolute contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation to thrombolytic therapy:
    • Intracranial hemorrhage Intracranial hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most sahs originate from a saccular aneurysm in the circle of willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage on CT
    • Clinical presentation suggestive of subarachnoid hemorrhage Subarachnoid Hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most SAHs originate from a saccular aneurysm in the circle of Willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage
    • Neurosurgery Neurosurgery Neurosurgery is a specialized field focused on the surgical management of pathologies of the brain, spine, spinal cord, and peripheral nerves. General neurosurgery includes cases of trauma and emergencies. There are a number of specialized neurosurgical practices, including oncologic neurosurgery, spinal neurosurgery, and pediatric neurosurgery. Neurosurgery, head trauma Head trauma Head trauma occurs when external forces are directed to the skull and brain structures, resulting in damage to the skull, brain, and intracranial structures. Head injuries can be classified as open (penetrating) or closed (blunt), and primary (from the initial trauma) or secondary (indirect brain injury), and range from mild to severe and life-threatening. Head Trauma, or stroke in the previous 3 months
    • Uncontrolled hypertension Uncontrolled hypertension Although hypertension is defined as a blood pressure of > 130/80 mm Hg, individuals can present with comorbidities of severe asymptomatic or “uncontrolled” hypertension (≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic) that carries with it a significant risk of morbidity and mortality. Uncontrolled Hypertension (systolic blood pressure > 185 mm Hg or diastolic blood pressure > 110 mm Hg)
    • History of intracranial hemorrhage Intracranial hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most sahs originate from a saccular aneurysm in the circle of willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage
    • Known intracranial arteriovenous malformation Arteriovenous malformation Abnormal formation of blood vessels that shunt arterial blood directly into veins without passing through the capillaries. They usually are crooked, dilated, and with thick vessel walls. A common type is the congenital arteriovenous fistula. The lack of blood flow and oxygen in the capillaries can lead to tissue damage in the affected areas. Erysipelas, neoplasm, or intracranial aneurysm Intracranial aneurysm Abnormal outpouching in the wall of intracranial blood vessels. Most common are the saccular (berry) aneurysms located at branch points in circle of willis at the base of the brain. Vessel rupture results in subarachnoid hemorrhage or intracranial hemorrhages. Giant aneurysms (>2. 5 cm in diameter) may compress adjacent structures, including the oculomotor nerve. Brain Aneurysms
    • Active internal bleeding
    • Suspected or confirmed endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis
    • Known bleeding diathesis Bleeding diathesis Wiskott-Aldrich Syndrome with platelet count < 100,000/μL
    • Elevated PTT with heparin administered in the last 48 hours or with the use of oral anticoagulants Anticoagulants Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants
    • Glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance < 50 mg/dL
  • Relative contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation:
    • Recent GI or urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy bleeding (past 21 days)
    • Minor or rapidly improving stroke symptoms
    • Major surgery or serious nonhead trauma in the past 14 days
    • Seizure at stroke onset
    • Recent arterial puncture at a noncompressible site
    • Recent lumbar puncture Lumbar Puncture Febrile Infant
    • Post-MI pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis
    • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  • Other additional cautions:
    • Age > 80 years
    • History of prior stroke and diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
    • Use of any active anticoagulants Anticoagulants Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants (even with INR < 1.7)
    • NIHSS score > 25 (severe stroke)
    • CT with multilobar infarction (hypodensity > ⅓ of a cerebral hemisphere)
• Continuous blood pressure monitoring:
  • < 180/105 mm Hg for the 1st 24 hours
  • If necessary, reduction of blood pressure with IV labetalol Labetalol A salicylamide derivative that is a non-cardioselective blocker of beta-adrenergic receptors and alpha-1 adrenergic receptors. Subarachnoid Hemorrhage or other agents
• Endovascular therapy:
  • Mechanical embolectomy or angioplasty Angioplasty Reconstruction or repair of a blood vessel, which includes the widening of a pathological narrowing of an artery or vein by the removal of atheromatous plaque material and/or the endothelial lining as well, or by dilatation (balloon angioplasty) to compress an atheroma. Except for endarterectomy, usually these procedures are performed via catheterization as minimally invasive endovascular procedures. Cardiac Surgery using catheters
  • Indicated in occlusion of larger vessels (e.g., MCA) regardless of previous tPA administration
  • Indications for procedure initiation:
    • Must be within 6 hours of symptom onset (new literature supports initiation within 24 hours, particularly for occlusions in the anterior circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment)
    • High baseline level of function prior to the stroke
    • NIHSS > 6 and minimal tissue damage on CT
• Antithrombotic therapy if reperfusion is not feasible: Aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) or other antiplatelet agents Antiplatelet agents Antiplatelet agents are medications that inhibit platelet aggregation, a critical step in the formation of the initial platelet plug. Abnormal, or inappropriate, platelet aggregation is a key step in the pathophysiology of arterial ischemic events. The primary categories of antiplatelet agents include aspirin, ADP inhibitors, phosphodiesterase/adenosine uptake inhibitors, and glycoprotein IIb/IIIa inhibitors. Antiplatelet Drugs are given within 24–48 hours after symptom onset.
• Compression Compression Blunt Chest Trauma socks to prevent deep vein thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus ( DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis) and pulmonary embolism Pulmonary Embolism Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Pulmonary Embolism 
• Urgent neurologic consultation
• Neurosurgical consultation if evidence of brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema or herniation Herniation Omphalocele

Rehabilitation

• PT to improve neurologic function and reduce the risk of contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing
• Occupational therapy Occupational Therapy Skilled treatment that helps individuals achieve independence in all facets of their lives. It assists in the development of skills needed for independent living. Fetal Alcohol Spectrum Disorder:
  • Improves the quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life
  • May need splinting of hands to prevent contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing
• Swallowing Swallowing The act of taking solids and liquids into the gastrointestinal tract through the mouth and throat. Gastrointestinal Motility assessment to prevent aspiration
• Speech therapy Speech Therapy Treatment for individuals with speech defects and disorders that involves counseling and use of various exercises and AIDS to help the development of new speech habits. Myotonic Dystrophies
• Careful attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment to prevent complications due to immobility:
  • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Pressure ulcers
  • Limb contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing
• Careful assessment of the ability to drive safely
• Family and patient education:
  • Continuation of preventive measures at home
  • The FAST mnemonic is helpful for lay individuals to identify recurrence:
    • Facial droop
    • Arm weakness
    • Speech abnormality
    • Time

Prevention of recurrence

• Lifestyle changes:
  • Healthy diet (e.g., Mediterranean diet)
  • Exercise as tolerated; weight loss Weight loss Decrease in existing body weight. Bariatric Surgery if obese
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation counseling if applicable
• Risk-factor management with improved control of:
  • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Hyperlipidemia
• Medications:
  • Dual antiplatelet therapy unless contraindicated
    • Aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
    • Clopidogrel Clopidogrel A ticlopidine analog and platelet purinergic p2y receptor antagonist that inhibits adenosine diphosphate-mediated platelet aggregation. It is used to prevent thromboembolism in patients with arterial occlusive diseases; myocardial infarction; stroke; or atrial fibrillation. Antiplatelet Drugs or extended-release dipyridamole Dipyridamole A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. Phosphodiesterase Inhibitors
  • Statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins (e.g., atorvastatin Atorvastatin A pyrrole and heptanoic acid derivative, hydroxymethylglutaryl-CoA reductase inhibitor (statin), and anticholesteremic agent that is used to reduce serum levels of ldl-cholesterol; apolipoprotein b; and triglycerides. It is used to increase serum levels of hdl-cholesterol in the treatment of hyperlipidemias, and for the prevention of cardiovascular diseases in patients with multiple risk factors. Statins) in clinically important atherosclerotic disease
• Treatment of underlying causes (e.g., atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation) and anticoagulation Anticoagulation Pulmonary Hypertension Drugs as indicated

Complications and prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

Complications:

• Cerebral edema Cerebral edema Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries. An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive hydrocephalus). Increased Intracranial Pressure (ICP):
  • Accumulation of water in the cerebral parenchyma if ischemic injury goes without management for the 1st few days
  • May lead to obstructing hydrocephalus Hydrocephalus Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial. Subarachnoid Hemorrhage or brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification herniation Herniation Omphalocele
• Adverse reactions to tPA thrombolysis:
  • Bleeding complications
  • Decline in neurologic status

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas depends on these predictors of outcomes:

• Stroke severity/extent of infarction
• Age
• Time elapsed from symptom onset to diagnosis and management
• Length and intensity of therapy
• Level of functioning before the event

Differential Diagnosis

• TIA TIA Transient ischemic attack (TIA) is a temporary episode of neurologic dysfunction caused by ischemia without infarction that resolves completely when blood supply is restored. Transient ischemic attack is a neurologic emergency that warrants urgent medical attention. Transient Ischemic Attack (TIA): a temporary episode of neurologic dysfunction caused by ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage without evidence of infarction that resolves completely when blood supply is restored. No time limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation is defined as was used previously. Causes may be small clots or thromboemboli imposed on blood vessels compromised by atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis, inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation, or amyloid, or due to inadequate cerebral blood flow Inadequate Cerebral Blood Flow Syncope due to vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure or severe hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension. Clinical presentation is with transient neurologic deficits Neurologic Deficits High-Risk Headaches that resolve spontaneously. Management includes risk-factor reduction to reduce the risk of a future stroke.
• Hemorrhagic stroke Hemorrhagic stroke Stroke due to rupture of a weakened blood vessel in the brain (e.g., cerebral hemispheres; cerebellum; subarachnoid space). Subarachnoid Hemorrhage: a stroke with resulting neurologic dysfunction caused by rupture and bleeding of an intracranial vessel. Hemorrhagic stroke Hemorrhagic stroke Stroke due to rupture of a weakened blood vessel in the brain (e.g., cerebral hemispheres; cerebellum; subarachnoid space). Subarachnoid Hemorrhage is subdivided into intracerebral hemorrhage Intracerebral Hemorrhage Intracerebral hemorrhage (ICH) refers to a spontaneous or traumatic bleed into the brain parenchyma and is the 2nd-most common cause of cerebrovascular accidents (CVAs), commonly known as stroke, after ischemic CVAs. Intracerebral Hemorrhage and subarachnoid (intracranial) hemorrhage. Clinically, hemorrhages are indistinguishable from ischemic stroke and require imaging for definitive diagnosis. Management may include mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing, blood pressure control, reversal of anticoagulation Anticoagulation Pulmonary Hypertension Drugs, and risk-factor reduction for subsequent strokes.
• Migraine Migraine Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache: a common primary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess disorder characterized by episodic, moderate-to-severe headaches that may be associated with increased sensitivity to light and sound, and nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and/or vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia. Migraines may present as a “stroke mimic” with vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure, causing ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage and neurologic deficits Neurologic Deficits High-Risk Headaches similar to those seen in an ischemic stroke, including hemiplegia. Diagnosis is by clinical history, physical exam, and imaging. Management includes medications to treat migraines and by avoiding triggers.
• Intracranial tumor Tumor Inflammation: can be a primary neoplasm derived from intracranial tissues ( astrocytoma Astrocytoma Astrocytomas are neuroepithelial tumors that arise from astrocytes, which are star-shaped glial cells (supporting tissues of the CNS). Astrocytomas are a type of glioma. There are 4 grades of astrocytomas. Astrocytoma, oligodendroglioma Oligodendroglioma Oligodendrogliomas are malignant CNS tumors arising from neural glial cell precursors. Oligodendrogliomas often arise in the frontal lobes of the brain and have a generally favorable prognosis when compared to other gliomas. Oligodendrogliomas are the 3rd most common CNS tumor. The most frequent presenting symptom is a seizure. Oligodendroglioma, meningioma Meningioma Meningiomas are slow-growing tumors that arise from the meninges of the brain and spinal cord. The vast majority are benign. These tumors commonly occur in individuals with a history of high doses of skull radiation, head trauma, and neurofibromatosis 2. Meningioma) or a metastatic process from other malignancies such as lung or breast cancer Breast cancer Breast cancer is a disease characterized by malignant transformation of the epithelial cells of the breast. Breast cancer is the most common form of cancer and 2nd most common cause of cancer-related death among women. Breast Cancer. As the mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast grows, neurological presentations similar to those seen in ischemic stroke may develop. Diagnosis is by imaging, and management includes addressing the underlying cause.
• Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease: a life-threatening condition that involves the collection of pus in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification parenchyma due to an infection or as a complication of trauma or surgery. The most common presentations include headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, fever with chills Fever With Chills Brain Abscess, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures, and neurological deficits. Diagnosis is by MRI imaging and/or CT-guided aspiration of the contents for culture. Management requires surgical drainage and antibiotics.