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Stroke In The Young Adult Victoria E. Judd MD, MBA.

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1 Stroke In The Young Adult Victoria E. Judd MD, MBA

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3 What Is A Stroke ? A stroke occurs when blood flow to the brain is interrupted by a blocked or a ruptured blood vessel. A stroke occurs when blood flow to the brain is interrupted by a blocked or a ruptured blood vessel. A brain attack. A brain attack.

4 Stroke Acute stroke is typically characterized by the sudden onset of a focal neurologic deficit, though some patients have a stepwise or gradual progression of symptoms. Acute stroke is typically characterized by the sudden onset of a focal neurologic deficit, though some patients have a stepwise or gradual progression of symptoms.

5 Stroke Common deficits include: Dysphasia (difficulty swallowing) Dysphasia (difficulty swallowing) Dysarthria (difficulty speaking) Dysarthria (difficulty speaking) Hemianopia (difficulty with sight) Hemianopia (difficulty with sight) Weakness Weakness

6 Stroke Common Deficits Ataxia Ataxia Sensory loss Sensory loss Neglect Neglect Consciousness is generally normal but maybe impaired Consciousness is generally normal but maybe impaired

7 Stroke Warning Signs Sudden weakness or numbness of the face, arm or leg, especially on one side of the body Sudden weakness or numbness of the face, arm or leg, especially on one side of the body Sudden confusion, trouble speaking or understanding Sudden confusion, trouble speaking or understanding Sudden trouble seeing in one or both eyes Sudden trouble seeing in one or both eyes

8 Stroke Warning Signs Sudden trouble walking, dizziness, loss of balance or coordination Sudden trouble walking, dizziness, loss of balance or coordination Sudden, severe headaches with no known cause (for hemorrhagic stroke) Sudden, severe headaches with no known cause (for hemorrhagic stroke)

9 Stroke Warning Signs Acute loss of focal cerebral function Acute loss of focal cerebral function Abrupt onsetAbrupt onset Symptoms occur in all affected areas at the same timeSymptoms occur in all affected areas at the same time Symptoms resolve graduallySymptoms resolve gradually Symptoms are “negative”Symptoms are “negative”

10 Nature of Symptoms Positive symptoms indicate active discharge from central nervous system neurons. Typical positive symptoms can be visual (e.g., bright lines, shapes, objects), auditory (e.g., tinnitus, noises, music), somatosensory (e.g., burning, pain, paresthesias), or motor (e.g., jerking or repetitive rhythmic movements). Positive symptoms indicate active discharge from central nervous system neurons. Typical positive symptoms can be visual (e.g., bright lines, shapes, objects), auditory (e.g., tinnitus, noises, music), somatosensory (e.g., burning, pain, paresthesias), or motor (e.g., jerking or repetitive rhythmic movements). Negative symptoms indicate an absence or loss of function, such as loss of vision, hearing, feeling, or ability to move a part of the body. Negative symptoms indicate an absence or loss of function, such as loss of vision, hearing, feeling, or ability to move a part of the body.

11 Annual Incidence of Ischemic Stroke In young adults (15–45 years) has been estimated at approximately 2–11 per 100,000 in Caucasians, 22.8 per 100,000 in African Americans In young adults (15–45 years) has been estimated at approximately 2–11 per 100,000 in Caucasians, 22.8 per 100,000 in African Americans 10/100,000 in a Mayo Clinic study of women ages 15 to 29 10/100,000 in a Mayo Clinic study of women ages 15 to 29 About 2–12% of cerebral infarcts occur in young adult patients, with a higher frequency between 31 and 45 years About 2–12% of cerebral infarcts occur in young adult patients, with a higher frequency between 31 and 45 years

12 Annual Incidence of Ischemic Stroke Stroke ranks second after ischemic heart disease as a cause of lost disability-adjusted life-years in high- income countries Stroke ranks second after ischemic heart disease as a cause of lost disability-adjusted life-years in high- income countries

13 Mortality of Strokes Mortality in the first month after stroke has been reported to range from 2.5% in patients with lacunar infarcts to 78% in patients with space-occupying hemispheric infarction. Mortality in the first month after stroke has been reported to range from 2.5% in patients with lacunar infarcts to 78% in patients with space-occupying hemispheric infarction. Lacunar stroke or lacunar infarct (LACI) is a type of stroke that results from occlusion of one of the penetrating arteries that provides blood to the brain's deep structures. Lacunar stroke or lacunar infarct (LACI) is a type of stroke that results from occlusion of one of the penetrating arteries that provides blood to the brain's deep structures.

14 Stroke Stroke in young adults is surprisingly common. Stroke in young adults is surprisingly common. The differential diagnosis for potential etiologies is broader than that for older adults. The differential diagnosis for potential etiologies is broader than that for older adults.

15 Stroke In children and young adults; Congenital and acquired heart problems, Congenital and acquired heart problems, Hematologic conditions, Hematologic conditions, Vasculopathies, Vasculopathies, Metabolic disorders, Metabolic disorders, Drug ingestion Drug ingestion are more common.

16 Causes of Stroke The largest series studies of young adults with ischemic stroke cite undetermined as the most frequent etiology (up to 35% of patients) The largest series studies of young adults with ischemic stroke cite undetermined as the most frequent etiology (up to 35% of patients) Ischemic stroke is much more common than hemorrhagic Ischemic stroke is much more common than hemorrhagic

17 Causes of Stroke Up to 45% of strokes in young adults are due to spontaneous intracerebral hemorrhage. Up to 45% of strokes in young adults are due to spontaneous intracerebral hemorrhage. Vascular malformations, aneurysms, hypertension, and illicit drug use are the main causes. Vascular malformations, aneurysms, hypertension, and illicit drug use are the main causes.

18 Causes of Ischemic Stroke in Young Adults Eur Neurol 2007;57:212–218

19 Cardiovascular Risk Factors in 272 Young Patients % (n) Major cardiovascular risk factors 35 (96) Arterial hypertension 22 (59) Arterial hypertension 22 (59) Diabetes mellitus 8 (21) Diabetes mellitus 8 (21) Hypercholesterolemia 17 (46) Hypercholesterolemia 17 (46) Atherosclerosis 5 (14) Atherosclerosis 5 (14) Causes of Ischemic Stroke in Young Adults Eur Neurol 2007;57:212–218 Causes of Ischemic Stroke in Young Adults Eur Neurol 2007;57:212–218

20 Cardiovascular Risk Factors in 272 Young Patients % (n) Minor cardiovascular risk factors 63 (172) Cigarette smoking 49 (133) Cigarette smoking 49 (133) Oral contraceptives 18 (17) Oral contraceptives 18 (17) High alcohol intake 31 (84) High alcohol intake 31 (84) Causes of Ischemic Stroke in Young Adults Eur Neurol 2007;57:212–218 Causes of Ischemic Stroke in Young Adults Eur Neurol 2007;57:212–218

21 Prevention of Stroke Control high blood pressure Control high blood pressure Prevent heart disease Prevent heart disease Stop cigarette smoking Stop cigarette smoking Recognize signs of TIA Recognize signs of TIA Reduce blood cholesterol levels Reduce blood cholesterol levels

22 Stroke Risk Factors That Can Be Treated Hypertension/High Blood Pressure Hypertension/High Blood Pressure Heart Disease Heart Disease Cigarette Smoking Cigarette Smoking Transient Ischemic Attacks Transient Ischemic Attacks

23 Stroke Risk Factors That Can Be Treated Diabetes Diabetes Elevated Blood Cholesterol/Lipids Elevated Blood Cholesterol/Lipids Asymptomatic Carotid Bruits Asymptomatic Carotid Bruits

24 Stroke Risk Factors That Cannot Be Treated Age Age Gender Gender Race Race Prior stroke Prior stroke Family history Family history

25 Stroke Risk Factors Less Well- Documented Geographical Location Geographical Location Socioeconomic Factors Socioeconomic Factors Excessive Alcohol Intake Excessive Alcohol Intake Certain Kinds of Drug Abuse Certain Kinds of Drug Abuse

26 What Are the Types of Stroke ? Ischemic Stroke (Blockage) Caused by a blockage in blood vessels in brain Caused by a blockage in blood vessels in brain Hemorrhagic Stroke (Bleeding) Caused by ruptured or leaking blood vessels in brain Caused by ruptured or leaking blood vessels in brain

27 Stroke Background Inadequate blood flowInadequate blood flow Ischemic stroke Ischemic stroke Focal – thrombotic or embolic occlusion of major arteryFocal – thrombotic or embolic occlusion of major artery Global – inadequate cerebral perfusionGlobal – inadequate cerebral perfusion HemorrhageHemorrhage Parenchymal – into brain tissue Parenchymal – into brain tissue Subarachnoid – surrounding subarachnoid space Subarachnoid – surrounding subarachnoid space

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29 Causes of Stroke Some of the most common causes of ischemia in the young Cardioembolism (20–35%), Cardioembolism (20–35%), Dissection of extracranial arteries (6– 25%), Dissection of extracranial arteries (6– 25%), Migraine with aura (1–20%) Migraine with aura (1–20%) Drugs (10%) Drugs (10%) Hypercoagulable states (5–10%) Hypercoagulable states (5–10%) Premature atherosclerosis (20-25%) Premature atherosclerosis (20-25%)

30 Ischemic Stroke In patients younger than 55 years, only about 10% of strokes are caused by large-vessel atherosclerotic disease. In patients younger than 55 years, only about 10% of strokes are caused by large-vessel atherosclerotic disease.

31 What Are the Causes of Ischemic Stroke? Large vessel disease Premature atherosclerosis Premature atherosclerosis Dissection (spontaneous or traumatic) Dissection (spontaneous or traumatic) Inherited metabolic diseases (homocystinuria, Fabry’s, pseudoxanthoma elasticum, MELAS syndrome) Inherited metabolic diseases (homocystinuria, Fabry’s, pseudoxanthoma elasticum, MELAS syndrome) Fibromuscular dysplasia Fibromuscular dysplasia Infection (bacterial, fungal, tuberculosis, syphilis, Lyme) Infection (bacterial, fungal, tuberculosis, syphilis, Lyme) Vasculitis (collagen vascular diseases — systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, polyarteritis nodosa; Takayasu’s disease, Wegener’s syndrome, cryoglobulinemia, sarcoidosis, inflammatory bowel disease, isolated central nervous system angiitis) Vasculitis (collagen vascular diseases — systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, polyarteritis nodosa; Takayasu’s disease, Wegener’s syndrome, cryoglobulinemia, sarcoidosis, inflammatory bowel disease, isolated central nervous system angiitis) Moyamoya disease: (Japanese, "puff of cigar smoke") is an inherited disease in which certain arteries in the brain are constricted Moyamoya disease: (Japanese, "puff of cigar smoke") is an inherited disease in which certain arteries in the brain are constricted Radiation Radiation Toxic (illicit drugs — cocaine, heroin, phencyclidine; therapeutic drugs — L-asparaginase, cytosine arabinoside, ephedra, phenylephrine) Toxic (illicit drugs — cocaine, heroin, phencyclidine; therapeutic drugs — L-asparaginase, cytosine arabinoside, ephedra, phenylephrine)

32 What Are the Causes of Ischemic Stroke? Cardiac disease (including congenital, rheumatic valve disease, mitral valve prolapse, patent foramen ovale, endocarditis, atrial myxoma, arrhythmias, cardiac surgery) Cardiac disease (including congenital, rheumatic valve disease, mitral valve prolapse, patent foramen ovale, endocarditis, atrial myxoma, arrhythmias, cardiac surgery)

33 What Are the Causes of Ischemic Stroke? Small vessel disease Vasculopathy (infectious, noninfectious, microangiopathy) Vasculopathy (infectious, noninfectious, microangiopathy) Independent predictors of arteriopathy are sickle cell disease and recent upper respiratory infection. Independent predictors of arteriopathy are sickle cell disease and recent upper respiratory infection.

34 What Are the Causes of Ischemic Stroke? Hematologic disease Sickle-cell disease Sickle-cell disease Leukemia Leukemia Hypercoagulable states (antiphospholipid antibody syndrome, deficiency of antithrombin III or protein S or C, resistance to activated protein C, increased factor VIII) Hypercoagulable states (antiphospholipid antibody syndrome, deficiency of antithrombin III or protein S or C, resistance to activated protein C, increased factor VIII) Disseminated intravascular coagulation Disseminated intravascular coagulation Thrombocytosis Thrombocytosis Polycythemia vera Polycythemia vera Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura Venous occlusion (dehydration, parameningeal infection, meningitis, neoplasm, polycythemia, leukemia, inflammatory bowel disease) Venous occlusion (dehydration, parameningeal infection, meningitis, neoplasm, polycythemia, leukemia, inflammatory bowel disease)

35 Hematologic Disorders Many hematologic disorders are associated with ischemic stroke. Many hematologic disorders are associated with ischemic stroke. The disorders most likely to cause ischemic stroke in patients younger than 45 years are: The disorders most likely to cause ischemic stroke in patients younger than 45 years are: Antiphospholipid antibody syndrome Antiphospholipid antibody syndrome Sickle cell anemia Sickle cell anemia Heparin induced thrombocytopenia Heparin induced thrombocytopenia

36 APS Antiphospholipid syndrome (APS or APLS) or antiphospholipid antibody syndrome is a disorder of coagulation that causes blood clots (thrombosis) in both arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, or severe preeclampsia. The syndrome occurs due to the autoimmune production of antibodies against phospholipid (aPL), a cell membrane substance. In particular, the disease is characterized by antibodies against cardiolipin (anti-cardiolipin antibodies) and β2 glycoprotein. Antiphospholipid syndrome (APS or APLS) or antiphospholipid antibody syndrome is a disorder of coagulation that causes blood clots (thrombosis) in both arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, or severe preeclampsia. The syndrome occurs due to the autoimmune production of antibodies against phospholipid (aPL), a cell membrane substance. In particular, the disease is characterized by antibodies against cardiolipin (anti-cardiolipin antibodies) and β2 glycoprotein.

37 Hematologic disorders Most of the common hereditary hypercoagulable disorders, such as factor V Leiden/activated protein C resistance, the prothrombin gene mutation (G20210A), antithrombin III deficiency, protein C deficiency, and protein S deficiency, typically cause venous thrombosis much more often than they cause arterial thrombosis. Most of the common hereditary hypercoagulable disorders, such as factor V Leiden/activated protein C resistance, the prothrombin gene mutation (G20210A), antithrombin III deficiency, protein C deficiency, and protein S deficiency, typically cause venous thrombosis much more often than they cause arterial thrombosis.

38 What Are the Causes of Ischemic Stroke? Migraine: especially with aura

39 Embolism: Cardiogenic (atrial fibrillation, mural thrombus, myxoma, valvular vegetations) Artery-to-artery Fat Air Paradoxical (emboli of venous origin passing through a patent foramen ovale)

40 Cardiogenic Embolism Major risk factors: Anticoagulation Indicated Major risk factors: Anticoagulation Indicated Atrial fibrillationAtrial fibrillation Mitral stenosisMitral stenosis Prosthetic cardiac valveProsthetic cardiac valve Recent MIRecent MI Thrombus in LV or LA appendageThrombus in LV or LA appendage Atrial myxomaAtrial myxoma Infective endocarditis (No anticoagulation)Infective endocarditis (No anticoagulation) Dilated cardiomyopathyDilated cardiomyopathy

41 Cardiogenic Embolism Minor risk factors: Best treatment unclear Minor risk factors: Best treatment unclear Pathologic Mitral valve prolapse (2% of population)Pathologic Mitral valve prolapse (2% of population) Mitral annular calcificationMitral annular calcification Patent foramen ovale (25% 0f population)Patent foramen ovale (25% 0f population) Atrial septal aneurysmAtrial septal aneurysm Calcific aortic stenosisCalcific aortic stenosis LV regional wall motion abnormalityLV regional wall motion abnormality Aortic arch atheromatous plaquesAortic arch atheromatous plaques Spontaneous echocardiographic contrastSpontaneous echocardiographic contrast

42 Cardiogenic Embolism One-fifth to one-third of strokes in the young may be caused by cardioembolic phenomena. One-fifth to one-third of strokes in the young may be caused by cardioembolic phenomena.

43 Cardiogenic Embolism Paradoxical embolization from the right heart to the left is believed to occur via a patent foramen ovale or atrial septal defect (which can be found on autopsy in up to one fourth of all people. Paradoxical embolization from the right heart to the left is believed to occur via a patent foramen ovale or atrial septal defect (which can be found on autopsy in up to one fourth of all people. Atherosclerosis of the aorta or carotid arteries can be a source of both atheroemboli and thromboemboli Atherosclerosis of the aorta or carotid arteries can be a source of both atheroemboli and thromboemboli

44 Cardiogenic Embolism Left atrial thrombi account for nearly half of cardiac thromboemboli. The most common cause is atrial fibrillation; other causes are dilated cardiomyoapthy, mitral valve stenosis, and some hypercoagulable states. Left atrial thrombi account for nearly half of cardiac thromboemboli. The most common cause is atrial fibrillation; other causes are dilated cardiomyoapthy, mitral valve stenosis, and some hypercoagulable states.

45 Right atrium Left atrium Valsalva Right atrium Left atrium Figure 1. Transesophageal Echocardiograms of a Patent Foramen Ovale. In Panel A, a transesophageal echocardiogram in the longitudinal plane shows a separation between the primum septum (arrowhead) and the secundum septum — a finding consistent with the presence of patent foramen ovale. Panel B shows a transesophageal echocardiogram, also in the longitudinal plane, obtained during the injection of agitated-saline contrast material through an antecubital vein with use of the Valsalva maneuver. There is complete opacification of the right atrium, and passage of a cloud of bubbles between the primum and secundum septa into the left atrium is visible.

46 RA LA Figure 2. Transesophageal echocardiogram showing a thrombus (arrows) passing from right atrium (RA) to left atrium (LA) through a patent foramen ovale.

47 Right atrium Left atrium Right ventricle Left ventricle Right atrium Left atrium Figure 2. Transesophageal Echocardiograms of an Atrial Septal Aneurysm. In Panel A, a transesophageal echocardiogram (in the horizontal plane) shows an atrial septal aneurysm protruding into the right atrium (arrow). Atrial septal aneurysm is defined as either sustained bowing of a 15-mm segment of interatrial septal membrane in the fossa ovalis of at least 11 mm (or at least 15 mm by a more conservative definition) beyond the plane of the interatrial septum or as phasic excursion to either side totaling the same distance. Panel B shows a transesophageal echocardiogram showing the same atrial septal aneurysm (arrow) viewed in the longitudinal plane.

48 PFO Figure 3. Percutaneous Closure of a Patent Foramen Ovale. Figure 3. Percutaneous Closure of a Patent Foramen Ovale. With use of a femoral approach, a transvenous sheath is advanced across the foramen into the left atrium, where a folded disk is expanded and pulled back, apposing the primum and secundum septa closed. This step is followed by deployment of a right-sided disk, at which time the two- disk device is released. Clopidogrel and aspirin are recommended for a period of three months to prevent thrombus formation on the device, with aspirin therapy continued for an additional three months, when endothelialization is complete. Antibiotic prophylaxis for six months is recommended. Complete late closure of the foramen has been reported in 80 to 95 percent of patients. With use of a femoral approach, a transvenous sheath is advanced across the foramen into the left atrium, where a folded disk is expanded and pulled back, apposing the primum and secundum septa closed. This step is followed by deployment of a right-sided disk, at which time the two- disk device is released. Clopidogrel and aspirin are recommended for a period of three months to prevent thrombus formation on the device, with aspirin therapy continued for an additional three months, when endothelialization is complete. Antibiotic prophylaxis for six months is recommended. Complete late closure of the foramen has been reported in 80 to 95 percent of patients.

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51 Cocaine Abuse Another important cause of ischemic stroke is the use of sympathomimetic drugs such as cocaine amphetamines, ephedra, or phenylephrine. The strongest association is with cocaine, which has been seen in case series to cause cerebral vasoconstriction in a dose-dependent manner. Vasoconstriction is also related to a longer duration of cocaine use. Several case-control studies have found that the risk of stroke is 4.5 to 6.5 times higher in drug abusers than in controls, and that use of catecholamines or cocaine alone was associated with a significantly increased risk of stroke. Another important cause of ischemic stroke is the use of sympathomimetic drugs such as cocaine amphetamines, ephedra, or phenylephrine. The strongest association is with cocaine, which has been seen in case series to cause cerebral vasoconstriction in a dose-dependent manner. Vasoconstriction is also related to a longer duration of cocaine use. Several case-control studies have found that the risk of stroke is 4.5 to 6.5 times higher in drug abusers than in controls, and that use of catecholamines or cocaine alone was associated with a significantly increased risk of stroke.

52 What Are the Causes of Hemorrhagic Stroke? Occurs when a weakened blood vessel ruptures Aneurysms: Ballooning of a weakened region of a blood vessel Aneurysms: Ballooning of a weakened region of a blood vessel Arteriovenous Malformations (AVMs): Cluster of abnormal blood vessels Arteriovenous Malformations (AVMs): Cluster of abnormal blood vessels

53 Arteriovenous Malformations Cerebral AVMs are most commonly discovered in young adults aged 20-40 years. Cerebral AVMs are most commonly discovered in young adults aged 20-40 years. These lesions are usually detected in patients as the result of a seizure or hemorrhage. These lesions are usually detected in patients as the result of a seizure or hemorrhage. AVMs hemorrhage at a rate of 4% per year. AVMs hemorrhage at a rate of 4% per year. Approximately half of these hemorrhages will carry significant morbidity or mortality. Approximately half of these hemorrhages will carry significant morbidity or mortality.

54 HEMORRHAGIC Arteriovenous malformation Arteriovenous malformation Neoplasm (primary central nervous system, metastatic, leukemia) Neoplasm (primary central nervous system, metastatic, leukemia) Hematologic (sickle-cell disease, neoplasm, thrombocytopenia) Hematologic (sickle-cell disease, neoplasm, thrombocytopenia) Moyamoya disease Moyamoya disease Drug use (warfarin, amphetamines, cocaine, phenypropanolamine) Drug use (warfarin, amphetamines, cocaine, phenypropanolamine) Iatrogenic (peri-procedural) Iatrogenic (peri-procedural)

55 Moyamoya Moyamoya syndrome is characterized by progressive stenosis of the internal carotid arteries and formation of collateral vessels that give a "puff of smoke" appearance on angiography. Moyamoya syndrome is characterized by progressive stenosis of the internal carotid arteries and formation of collateral vessels that give a "puff of smoke" appearance on angiography. Moyamoya disease occurs mainly in Japanese and other Asian populations and may have a genetic basis. Moyamoya disease occurs mainly in Japanese and other Asian populations and may have a genetic basis. Secondary moyamoya syndrome is seen in association with neurofibromatosis, Down syndrome, Williams syndrome, sickle cell disease, and as a sequela of cranial irradiation. Intracranial hemorrhage is common in young adults. Secondary moyamoya syndrome is seen in association with neurofibromatosis, Down syndrome, Williams syndrome, sickle cell disease, and as a sequela of cranial irradiation. Intracranial hemorrhage is common in young adults. Dissection — Arterial dissection is the most common vascular abnormality in some young adult series Dissection — Arterial dissection is the most common vascular abnormality in some young adult series

56 Intracerebral Hemorrhage Diffuse – subarachnoid hemorrhage Diffuse – subarachnoid hemorrhage Focal – intraparenchymal Focal – intraparenchymal Accounts for 20% of all strokes Accounts for 20% of all strokes Acute rise in intracranial pressure from arterial rupture frequently results in loss of consciousness at outset Acute rise in intracranial pressure from arterial rupture frequently results in loss of consciousness at outset Some patients die from herniation Some patients die from herniation

57 Causes of Spontaneous Intracerebral Hemorrhage (ICH) Intraparenchymal hemorrhage Intraparenchymal hemorrhage TraumaTrauma HypertensionHypertension Amyloid angiopathyAmyloid angiopathy Arteriovenous malformationArteriovenous malformation Bleeding diathesis (anticoagulants, thrombolytics)Bleeding diathesis (anticoagulants, thrombolytics) Drugs (amphetamines, cocaine)Drugs (amphetamines, cocaine)

58 Causes of Spontaneous Intracerebral Hemorrhage (ICH) Cervical arterial dissection causes up to 20% of strokes in patients younger than 45 years. Cervical arterial dissection causes up to 20% of strokes in patients younger than 45 years. Dissections usually involve the extracranial portion of the vessel, and involve the internal carotid arteries at least three times as often as the vertebral arteries. Dissections usually involve the extracranial portion of the vessel, and involve the internal carotid arteries at least three times as often as the vertebral arteries.

59 Causes of Spontaneous Intracerebral Hemorrhage (ICH) In many cases the dissection is preceded by mild neck trauma, which may be as minor as a vigorous cough or turning of the head. In many cases the dissection is preceded by mild neck trauma, which may be as minor as a vigorous cough or turning of the head. Typical features of dissection include: Neck pain, headache, and Horner syndrome, followed minutes to hours later by symptoms of ocular or cerebral ischemia, usually a transient ischemic attack rather than a stroke. Typical features of dissection include: Neck pain, headache, and Horner syndrome, followed minutes to hours later by symptoms of ocular or cerebral ischemia, usually a transient ischemic attack rather than a stroke.

60 Causes of Spontaneous Intracerebral Hemorrhage (ICH) Inherited disorders that are associated with increased risk of cervical arterial dissection include: Ehlers-Danlos syndrome type IV Ehlers-Danlos syndrome type IV Marfan syndrome Marfan syndrome Autosomal dominant polycystic kidney disease Autosomal dominant polycystic kidney disease Osteogenesis imperfecta type I Osteogenesis imperfecta type I Fibromuscular dysplasia Fibromuscular dysplasia

61 Diagnosis, Management, and Prognosis of ICH CT diagnostic test of choice CT diagnostic test of choice Hyperintense area with mass effect and later hypointense surrounding edemaHyperintense area with mass effect and later hypointense surrounding edema MRI less sensitive in early stages MRI less sensitive in early stages

62 Diagnosis, Management, and Prognosis of ICH Management depends on size and location Management depends on size and location In acute phase, mass effect far greater than in large cerebral infarction, so greater risk of herniation and deathIn acute phase, mass effect far greater than in large cerebral infarction, so greater risk of herniation and death In chronic phase, prognosis for surviving patients much better than with ischemic strokeIn chronic phase, prognosis for surviving patients much better than with ischemic stroke

63 Subarachnoid Hemorrhage Aneurysms can rupture any time but more common during strenuous activity Aneurysms can rupture any time but more common during strenuous activity Most common manifestation is headache Most common manifestation is headache “worst headache of my life”“worst headache of my life” Neck pain and rigidity Neck pain and rigidity Loss of consciousness and vomiting common Loss of consciousness and vomiting common Seen on CT in 95% of cases – location may suggest site of rupture Seen on CT in 95% of cases – location may suggest site of rupture Normal CT does not rule out so do lumbar puncture – xanthochromia (develops after 6 hours) Normal CT does not rule out so do lumbar puncture – xanthochromia (develops after 6 hours)

64 Causes of Spontaneous Intracerebral Hemorrhage (ICH) Subarachnoid hemorrhage Subarachnoid hemorrhage Congenital saccular aneurysm (85%)Congenital saccular aneurysm (85%) Unknown (15%)Unknown (15%)

65 What Parts of the Brain Are Affected by Stroke?

66 Right (Non-dominant) Hemisphere Stroke: Common Pattern Neglect of left visual field Neglect of left visual field Extinction of left-sided stimuli Extinction of left-sided stimuli Left hemiparesis Left hemiparesis Left-sided sensory loss Left-sided sensory loss Left visual field defect Left visual field defect Poor left conjugate gaze Poor left conjugate gaze Dysarthria Dysarthria Spatial disorientation Spatial disorientation

67 Left (Dominant) Hemisphere Stroke: Common Pattern Aphasia Aphasia Right hemiparesis Right hemiparesis Right-sided sensory loss Right-sided sensory loss Right visual field defect Right visual field defect Poor right conjugate gaze Poor right conjugate gaze Dysarthria Dysarthria Difficulty reading, writing, or calculating Difficulty reading, writing, or calculating

68 Brain Stem / Cerebellum / Posterior Hemisphere Stroke: Common Pattern Motor or sensory loss in all four limbs Motor or sensory loss in all four limbs Crossed signs Crossed signs Limb or gait ataxia Limb or gait ataxia Dysarthria Dysarthria Dysconjugate gaze Dysconjugate gaze Nystagmus Nystagmus Amnesia Amnesia Bilateral visual field defects Bilateral visual field defects

69 Small Subcortical Hemisphere or Brain Stem Stroke: Common Pattern Pure Motor Pure Motor Weakness of face and limbs on one side of the body without abnormalities of higher brain function, sensation, or visionWeakness of face and limbs on one side of the body without abnormalities of higher brain function, sensation, or vision Pure Sensory Pure Sensory Decreased sensation of face and limbs on one side of the body without abnormalities of higher brain function, motor function, or visionDecreased sensation of face and limbs on one side of the body without abnormalities of higher brain function, motor function, or vision

70 Neurologic ExamNeurologic Exam Carotid BruitsCarotid Bruits Cardiac ExamCardiac Exam Peripheral PulsesPeripheral Pulses DermatologicDermatologic OphthalmologicOphthalmologic Physical Exam

71 Dermatologic Splinter hemorrhages and needle tracks (endocarditis) Splinter hemorrhages and needle tracks (endocarditis) Xanthoma (hyperlipidemia) Xanthoma (hyperlipidemia) Café-au-lait spots Café-au-lait spots Neurofibromas (neurofibromatosis) Neurofibromas (neurofibromatosis) Purpura (coagulopathy) Purpura (coagulopathy) Capillary angiomata (cavernous malformation) Capillary angiomata (cavernous malformation)

72 CAFÉ AU LAIT spots Xanthoma, eruptive Neurofibromas splinter hemorrhages

73 Opthalmlogic Corneal arcus (hypercholesterolemia) Corneal arcus (hypercholesterolemia) Corneal opacity (Fabry’s disease) Corneal opacity (Fabry’s disease) Lisch nodules Lisch nodules Optic atrophy (neurofibromatosis) Optic atrophy (neurofibromatosis) Lens subluxation (Marfan’s syndrome, homocystinuria) Lens subluxation (Marfan’s syndrome, homocystinuria) Retinal perivasculitis (sickle-cell disease, syphilis, connective tissue diseases, inflammatory bowel disease) Retinal perivasculitis (sickle-cell disease, syphilis, connective tissue diseases, inflammatory bowel disease) Occlusions (emboli) Occlusions (emboli) Angioma (cavernous malformation) Angioma (cavernous malformation) Hamartoma (tuberous sclerosis). Hamartoma (tuberous sclerosis).

74 optic atrophy in tuberous sclerosis lens dislocation in marfan syndrome Corneal arcus

75 Diagnostic Testing for Patients With Stroke Basic stroke evaluation Cranial computed tomography (CT) Cranial computed tomography (CT) Carotid ultrasonography ± transcranial Doppler Carotid ultrasonography ± transcranial Doppler Transthoracic echocardiography Transthoracic echocardiography EKG monitoring EKG monitoring Routine blood studies (complete blood count with differential and platelet count, prothrombin time (international normalized ratio), activated partial thromboplastin time, glucose, chemistries, serology for syphilis, and an erythrocyte sedimentation rate) Routine blood studies (complete blood count with differential and platelet count, prothrombin time (international normalized ratio), activated partial thromboplastin time, glucose, chemistries, serology for syphilis, and an erythrocyte sedimentation rate)

76 Diagnostic Testing for Patients With Stroke Comprehensive stroke evaluation Cranial magnetic resonance imaging (MRI) Cranial magnetic resonance imaging (MRI) Imaging of the intracranial arteries (MR, CT, or catheter angiography Imaging of the intracranial arteries (MR, CT, or catheter angiography of the brain) of the brain) Imaging of the extracranial arteries (MR, CT, or catheter angiography Imaging of the extracranial arteries (MR, CT, or catheter angiography of the neck) of the neck) Transesophageal echocardiography (TEE) Transesophageal echocardiography (TEE) Prolonged EKG monitoring with Holter or event loop recorder Prolonged EKG monitoring with Holter or event loop recorder Urine toxicology screen (often productive) Urine toxicology screen (often productive) Urine pregnancy test Urine pregnancy test Blood testing for a hypercoagulable state anticardiolipin antibodies, lupus anticoagulants, protein S, protein C, activated protein C resistance, antithrombin III) is requested in patients without a firmly identified cause of stroke or if the patient or family members have a history of thromboses. It is advantageous to send such a profile prior to initiating anticoagulation, as heparin can alter interpretation of some of those assays. Blood testing for a hypercoagulable state anticardiolipin antibodies, lupus anticoagulants, protein S, protein C, activated protein C resistance, antithrombin III) is requested in patients without a firmly identified cause of stroke or if the patient or family members have a history of thromboses. It is advantageous to send such a profile prior to initiating anticoagulation, as heparin can alter interpretation of some of those assays. In select cases, blood testing for rare genetic causes of stroke (CADASIL, Fabry disease, MELAS) In select cases, blood testing for rare genetic causes of stroke (CADASIL, Fabry disease, MELAS)

77 How Are Strokes Treated? Ischemic Stroke Ischemic Stroke Clot-busters e.g., t-PA Clot-busters e.g., t-PA Anticoagulants – warfarin, aspirin Anticoagulants – warfarin, aspirin Carotid Endarterectomy Carotid Endarterectomy Angioplasty/Stents Angioplasty/Stents

78 Treatment of Strokes Antiplatelet therapy remains treatment of choice to prevent recurrent thromboembolism in majority of patientsAntiplatelet therapy remains treatment of choice to prevent recurrent thromboembolism in majority of patients Anticoagulation may be appropriateAnticoagulation may be appropriate Atrial fibrillation Atrial fibrillation Recent MI Recent MI Suspected propagation of thrombus or stroke in evolution Suspected propagation of thrombus or stroke in evolution

79 Treatment of Strokes CT or MRI of the brain should be performed promptly; MRI is more sensitive for early ischemic changes, but either method can fully rule out hemorrhage. CT or MRI of the brain should be performed promptly; MRI is more sensitive for early ischemic changes, but either method can fully rule out hemorrhage. Treatment of TPA was associated with an increase of about 1.2 with minimal or no disability for every 10 patients treated. Treatment of TPA was associated with an increase of about 1.2 with minimal or no disability for every 10 patients treated.

80 Limitations of Imaging CT will miss a minority of acute bleeds CT will miss a minority of acute bleeds MRI with DWI (diffusion weighted imaging), quite sensitive for acute stroke, has an occasional false negative result (17 out of 782 patients in a recent study) MRI with DWI (diffusion weighted imaging), quite sensitive for acute stroke, has an occasional false negative result (17 out of 782 patients in a recent study) MRA’s resolution is not yet on par with conventional angiography. MRA’s resolution is not yet on par with conventional angiography.

81 Thrombolysis t-PA Guidelines for treatment:Guidelines for treatment: Present within 3 hours of onset of clearly defined stroke – frequency of symptomatic hemorrhage most likely increases after this time Present within 3 hours of onset of clearly defined stroke – frequency of symptomatic hemorrhage most likely increases after this time CT scan shows no evidence of intracranial hemorrhage CT scan shows no evidence of intracranial hemorrhage No anticoagulants or antiplatelet agents given for 24 hoursNo anticoagulants or antiplatelet agents given for 24 hours Avoid BP values > 185/110Avoid BP values > 185/110

82 Guidelines Not to Treat Previous stroke or serious head trauma in preceding 3 months Previous stroke or serious head trauma in preceding 3 months History of intracranial hemorrhage History of intracranial hemorrhage Repeated systolic BP’s > 185 mm Hg or diastolic BP’s > 110 mm Hg Repeated systolic BP’s > 185 mm Hg or diastolic BP’s > 110 mm Hg

83 Guidelines Not to Treat Requires aggressive treatment to reduce BP to specified limits Requires aggressive treatment to reduce BP to specified limits Taking anticoagulants or propensity to hemorrhage Taking anticoagulants or propensity to hemorrhage Recent invasive surgical procedure Recent invasive surgical procedure Rapidly improving neurological deficit or minor symptoms Rapidly improving neurological deficit or minor symptoms

84 How Are Strokes Treated Hemorrhagic Stroke Surgical Intervention Surgical Intervention Endovascular Procedures, e.g., “coils” Endovascular Procedures, e.g., “coils”

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86 What Is the Impact of Stroke? Stroke is the third leading cause of death in the United States On average, someone suffers a stroke every 40 seconds On average, someone suffers a stroke every 40 seconds About 795,000 Americans suffer a stroke each year About 795,000 Americans suffer a stroke each year About every 4 minutes, someone dies of a stroke About every 4 minutes, someone dies of a stroke

87 What Is the Impact of Stroke? Stroke is a leading cause of serious, long term disability Stroke is a leading cause of serious, long term disability About 6.4 million Americans are stroke survivors About 6.4 million Americans are stroke survivors Americans will pay about $73.7 billion in 2010 for stroke-related medical costs and lost productivity long-term Americans will pay about $73.7 billion in 2010 for stroke-related medical costs and lost productivity long-term

88 Rehabilitation After suffering a stroke, it’s important to begin a rehabilitation program as soon as possible. Types of rehabilitation programs: Hospital programs Hospital programs Extended care facilities Extended care facilities Outpatient programs Outpatient programs Home-based programs Home-based programs

89 Rehabilitation Specialists Provider Provider Rehabilitation specialist Rehabilitation specialist Physical therapist Physical therapist Speech therapist Speech therapist Occupational therapist Occupational therapist Physiatrist Physiatrist Psychiatrist Psychiatrist

90 Family Relationships Overall, 13 studies reported consequences of stroke for family relationships and in those studies, 5% to 54% of the samples experienced family problems. Overall, 13 studies reported consequences of stroke for family relationships and in those studies, 5% to 54% of the samples experienced family problems. Nine studies reported marital problems after stroke, including separation or divorce. Nine studies reported marital problems after stroke, including separation or divorce. Six of these reported that marital problems were a direct consequence of the stroke. Six of these reported that marital problems were a direct consequence of the stroke. One study reported that 5% of the sample had experienced deterioration in the spousal relationship, whereas another found that 38% of couples had experienced conflict since the stroke. One study reported that 5% of the sample had experienced deterioration in the spousal relationship, whereas another found that 38% of couples had experienced conflict since the stroke.

91 Sexual Relationships Ten studies investigated the impact of stroke on sexual relationships, reporting problems in participants’ sexual relationships or frequency of sexual activities. Ten studies investigated the impact of stroke on sexual relationships, reporting problems in participants’ sexual relationships or frequency of sexual activities. Prevalence of deterioration in sexual relationships reported in 8 studies ranged from 5% to 76%. Prevalence of deterioration in sexual relationships reported in 8 studies ranged from 5% to 76%.

92 Social Activities Nine studies reported consequences of stroke on social or leisure activities with 4 of these reporting deterioration or decrease in these activities. Nine studies reported consequences of stroke on social or leisure activities with 4 of these reporting deterioration or decrease in these activities. Five studies quantified reported decrease in leisure activities ranging from 15% to 79%. Five studies quantified reported decrease in leisure activities ranging from 15% to 79%.

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104 Prognosis The outcome of stroke in young adults is better than that for older adults. In a recent study of 330 patients with first stroke or transient ischemic attack, followed for an average of 96 months, 8% died, 3% had another stroke, and 3% had a myocardial infarction. Approximately 16% were dependent, but 56% had returned to work. Unfortunately, only a minority of those who smoked at the time of their stroke subsequently stopped using tobacco. The overall annual recurrence rate is less than 1%. The outcome of stroke in young adults is better than that for older adults. In a recent study of 330 patients with first stroke or transient ischemic attack, followed for an average of 96 months, 8% died, 3% had another stroke, and 3% had a myocardial infarction. Approximately 16% were dependent, but 56% had returned to work. Unfortunately, only a minority of those who smoked at the time of their stroke subsequently stopped using tobacco. The overall annual recurrence rate is less than 1%. Prognosis is often closely associated with the underlying cause. Prognosis is often closely associated with the underlying cause. A relatively good outcome may be found after many cases of arterial dissection. A relatively good outcome may be found after many cases of arterial dissection. Risk of stroke recurrence is low (2% over 5 years) in women whose first stroke occurred in pregnancy. Risk of stroke recurrence is low (2% over 5 years) in women whose first stroke occurred in pregnancy.

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107 Stroke Chameleons Strokes with atypical presentations that take on the appearance of other disease process may be termed stroke chameleons, for like the chameleon, these disguised strokes may change and evolve with time. Strokes with atypical presentations that take on the appearance of other disease process may be termed stroke chameleons, for like the chameleon, these disguised strokes may change and evolve with time. The provider is left with the daunting problem of discovering the unusual manifestation of an uncommon clinical process. The provider is left with the daunting problem of discovering the unusual manifestation of an uncommon clinical process. The presence of historical risk factors for cerebrovascular disease and the abrupt onset of symptoms may be the best clues available to the provider to detect these unusual stroke syndromes. The presence of historical risk factors for cerebrovascular disease and the abrupt onset of symptoms may be the best clues available to the provider to detect these unusual stroke syndromes.

108 Stroke Chameleons In the majority of cases of stroke, making the diagnosis is straightforward. In the majority of cases of stroke, making the diagnosis is straightforward. Especially in patients with unusual features (e.g., Gradual onset, Gradual onset, Seizure at the onset of symptoms Seizure at the onset of symptoms Impaired consciousness Impaired consciousness The differential diagnosis should include migraine, postictal paresis, hypoglycemia, conversion disorder, subdural hematoma, and brain tumors. The differential diagnosis should include migraine, postictal paresis, hypoglycemia, conversion disorder, subdural hematoma, and brain tumors.

109 Stroke Chameleons Atherosclerosis (leading to thromboembolism or local occlusion) and cardioembolism are the leading causes of brain ischemia. Atherosclerosis (leading to thromboembolism or local occlusion) and cardioembolism are the leading causes of brain ischemia. Unusual causes should be considered, especially if patients are younger (e.g., below 50 years of age) and have no apparent cardiovascular risk factors. Unusual causes should be considered, especially if patients are younger (e.g., below 50 years of age) and have no apparent cardiovascular risk factors. Some clinical clues that suggest alternative diagnoses are ptosis and miosis contralateral to the deficit (carotid-artery dissection), fever and a cardiac murmur (infective endocarditis), and headache and an elevated erythrocyte sedimentation rate. Some clinical clues that suggest alternative diagnoses are ptosis and miosis contralateral to the deficit (carotid-artery dissection), fever and a cardiac murmur (infective endocarditis), and headache and an elevated erythrocyte sedimentation rate.

110 Differential Diagnosis Seizures and migraine auras characteristically (but not always) begin with positive symptoms, while TIAs invariably are characterized by negative symptoms. Seizures and migraine auras characteristically (but not always) begin with positive symptoms, while TIAs invariably are characterized by negative symptoms. Seizures occasionally cause paralytic attacks but, on close observation, there are usually features of the history and physical examination that suggest the presence of a seizure disorder such as minor twitching of a finger or toe or a tingling sensation in the affected limb. Seizures occasionally cause paralytic attacks but, on close observation, there are usually features of the history and physical examination that suggest the presence of a seizure disorder such as minor twitching of a finger or toe or a tingling sensation in the affected limb.

111 Differential Diagnosis of Stroke Intracranial mass: Tumor, Subdural hematoma Intracranial mass: Tumor, Subdural hematoma Seizure with persistent neurological signs Seizure with persistent neurological signs Migraine with persistent neurological signs Migraine with persistent neurological signs Metabolic Metabolic

112 Differential Diagnosis of Stroke Hyperglycemia (nonketotic hyperosmolar coma) Hyperglycemia (nonketotic hyperosmolar coma) Hypoglycemia Hypoglycemia Post-cardiac arrest ischemia Post-cardiac arrest ischemia Drug/narcotic overdose Drug/narcotic overdose

113 Focal symptom s Nonfocal symptoms Common disorders Seizures++++ TIAs++++occasionally Migraine++++++++ Syncope00 Less common disorders Vestibulopathy++++ Metabolic++++ "Tumor attacks" ++++ Multiple sclerosis ++++0 Psychiatric++++ Nerves and nerve root ++++0 Transient global amnesia ++++0

114 Differential Diagnosis of Transient Neurological Diseases TIA TIA Seizure Seizure Migraine with aura Migraine with aura Syncope Syncope Hypoglycemia Hypoglycemia

115 Hypoglycemia That transient hypoglycemia may produce a stroke like picture with hemiplegia and aphasia has been known for years. That transient hypoglycemia may produce a stroke like picture with hemiplegia and aphasia has been known for years. These patients may be drowsy but are often alert and do not show the more common response to hypoglycemia of confusion, diminished level of consciousness, or coma. These patients may be drowsy but are often alert and do not show the more common response to hypoglycemia of confusion, diminished level of consciousness, or coma. Aphasia may make the history of diabetes more difficult to discover. Aphasia may make the history of diabetes more difficult to discover. Syndrome has also been reported in alcoholics with hypoglycemia. Syndrome has also been reported in alcoholics with hypoglycemia. The pathogenesis of this focal CNS dysfunction is unclear. The pathogenesis of this focal CNS dysfunction is unclear. Hypoglycemia is generally defined as a blood glucose level of less than 45 mg/dl in these studies. Hypoglycemia is generally defined as a blood glucose level of less than 45 mg/dl in these studies. The wide use of bedside rapid laboratory testing for glucose now makes this easily detectable and treatable. The wide use of bedside rapid laboratory testing for glucose now makes this easily detectable and treatable. The hemiplegia may resolve immediately with the administration of intravenous glucose but resolution over a hours is also reported. The hemiplegia may resolve immediately with the administration of intravenous glucose but resolution over a hours is also reported.

116 Mass Lesions Subdural hematoma, cerebral abscess, primary CNS tumors, and metastatic tumors are among the clinical conditions simulating stroke in the studies cited above. Subdural hematoma, cerebral abscess, primary CNS tumors, and metastatic tumors are among the clinical conditions simulating stroke in the studies cited above. The typical clinical presentation of a slowly increasing mass is a progressive syndrome; an abrupt onset of symptoms of these masses seems counter-intuitive. The typical clinical presentation of a slowly increasing mass is a progressive syndrome; an abrupt onset of symptoms of these masses seems counter-intuitive. A review of patients with brain tumors presenting to an ED showed that 6% of patients had symptoms that were of less than one day’s duration; it was thought that these patients with brief symptom duration might reflect a sub- population who suffer acute deterioration from hemorrhage into the tumor or who develop obstructive hydrocephalus. A review of patients with brain tumors presenting to an ED showed that 6% of patients had symptoms that were of less than one day’s duration; it was thought that these patients with brief symptom duration might reflect a sub- population who suffer acute deterioration from hemorrhage into the tumor or who develop obstructive hydrocephalus. Secondary effects of mass or edema on cerebral vasculature have been identified as possible causes of abrupt onset of seizures as well. Secondary effects of mass or edema on cerebral vasculature have been identified as possible causes of abrupt onset of seizures as well. Chronic subdural hematoma has been frequently reported as a cause of stroke and TIA-like symptoms. Chronic subdural hematoma has been frequently reported as a cause of stroke and TIA-like symptoms.

117 Functional Hemiparesis Little is written about a factitious or feigned stroke yet several studies discover rare patients initially thought to have cerebrovascular disease but later determined to have a functional cause of the hemiparesis or other stroke syndrome. Little is written about a factitious or feigned stroke yet several studies discover rare patients initially thought to have cerebrovascular disease but later determined to have a functional cause of the hemiparesis or other stroke syndrome. Conversion disorder is the most commonly assigned psychiatric disorder. Conversion disorder is the most commonly assigned psychiatric disorder. One study of emergency department presentations of conversion disorder noted that symptoms of paresis, paralysis, or movement disorders were common and were a presentation in almost 30% of patients. One study of emergency department presentations of conversion disorder noted that symptoms of paresis, paralysis, or movement disorders were common and were a presentation in almost 30% of patients. They noted significant comorbidity in this population, often other psychiatric disorders, and emphasized that conversion disorder is a diagnosis of exclusion. They noted significant comorbidity in this population, often other psychiatric disorders, and emphasized that conversion disorder is a diagnosis of exclusion. Patients often undergo multiple diagnostic tests before the diagnosis is assigned. Patients often undergo multiple diagnostic tests before the diagnosis is assigned.

118 Seizures Demographics Any age, often younger Any age, often younger

119 Seizures CNS Symptoms Light-headed, dim vision, noises distant, decreased alertness Light-headed, dim vision, noises distant, decreased alertness Transient loss of consciousness Transient loss of consciousness

120 Seizures CNS Symptoms Positive symptoms: limb jerking, head turning, loss of consciousness Positive symptoms: limb jerking, head turning, loss of consciousness Negative symptoms may develop, remain postictally, and persist Negative symptoms may develop, remain postictally, and persist

121 Seizures Timing 20 to 80 seconds 20 to 80 seconds Absence, atonic seizures and myoclonic jerks are shorter Absence, atonic seizures and myoclonic jerks are shorter Postictal depression Postictal depression Spells occur over years Spells occur over years

122 Seizures Associated Symptoms Tongue biting, incontinence, sore muscles, headache after attack Tongue biting, incontinence, sore muscles, headache after attack

123 Focal Seizure Partial (focal) seizure Partial (focal) seizure Positive sensory or motor symptomsPositive sensory or motor symptoms Spread quickly (60 seconds)Spread quickly (60 seconds) Negative symptoms afterward (Todd’s paresis)Negative symptoms afterward (Todd’s paresis) Multiple attacksMultiple attacks

124 What is a TIA Acute loss of focal cerebral functionAcute loss of focal cerebral function Symptoms last less than 24 hoursSymptoms last less than 24 hours Due to inadequate blood supplyDue to inadequate blood supply Thrombosis Thrombosis Embolism Embolism

125 Transient Ischemic Attacks (TIAs) Warning strokes” that can happen before a major stroke Warning strokes” that can happen before a major stroke Occur when blood flow through a brain artery is blocked or reduced for a short time Occur when blood flow through a brain artery is blocked or reduced for a short time Symptoms are temporary (<24 hours) but similar to those of a full fledged stroke Symptoms are temporary (<24 hours) but similar to those of a full fledged stroke A person who has a TIA is 9.5 times more likely to have a stroke A person who has a TIA is 9.5 times more likely to have a stroke

126 TIA Risk Factors/Epidemiology 300,000 TIAs per year in US 300,000 TIAs per year in US 5-year stroke risk after TIA 29% 5-year stroke risk after TIA 29% 43.5% in 2 years with >70% carotid stenosis treated medically43.5% in 2 years with >70% carotid stenosis treated medically Many stroke patients have had a TIA Many stroke patients have had a TIA 25% - 50% in large artery atherothrombotic strokes25% - 50% in large artery atherothrombotic strokes 11% - 30% in cardioembolic strokes11% - 30% in cardioembolic strokes 11% to 14% in lacunar strokes11% to 14% in lacunar strokes

127 Risk Factors for a TIA Risk factors are the same as stroke Risk factors are the same as stroke Increasing ageIncreasing age SexSex Family history / RaceFamily history / Race Prior stroke / TIAPrior stroke / TIA HypertensionHypertension DiabetesDiabetes Heart diseaseHeart disease Carotid artery / Peripheral artery diseaseCarotid artery / Peripheral artery disease ObesityObesity High cholesterolHigh cholesterol Physical inactivityPhysical inactivity

128 TIA Symptoms Symptoms last less than 24 hours Symptoms last less than 24 hours Most last less than one hourMost last less than one hour Less than 10 percent > 6 hoursLess than 10 percent > 6 hours Amaurosis fugax up to five minutes (Amaurosis fugax is loss of vision in one eye due to a temporary lack of blood flow to the retina. Symptoms include the sudden loss of vision in one eye.)Amaurosis fugax up to five minutes (Amaurosis fugax is loss of vision in one eye due to a temporary lack of blood flow to the retina. Symptoms include the sudden loss of vision in one eye.)

129 TIA Demography Older patients Older patients Stroke risk factors present Stroke risk factors present Men>women Men>women

130 TIA Presentation Acute loss of focal cerebral function Acute loss of focal cerebral function Abrupt onsetAbrupt onset Symptoms occur in all affected areas at the same timeSymptoms occur in all affected areas at the same time Symptoms resolve graduallySymptoms resolve gradually Symptoms are “negative”Symptoms are “negative”

131 TIA Presentation Acute loss of focal cerebral function Acute loss of focal cerebral function Motor symptomsMotor symptoms Weakness or clumsiness on one side Weakness or clumsiness on one side Difficulty swallowing Difficulty swallowing Speech disturbancesSpeech disturbances Understanding or expressing spoken language Understanding or expressing spoken language Reading or writing Reading or writing Slurred speech Slurred speech Calculations Calculations

132 TIA Presentation Acute loss of focal cerebral function Acute loss of focal cerebral function Sensory symptomsSensory symptoms Altered feeling on one side Altered feeling on one side Loss of vision on one side Loss of vision on one side Loss of vision in left or right visual field Loss of vision in left or right visual field Bilateral blindness Bilateral blindness Double vision Double vision Vertigo Vertigo

133 TIA Presentation Non-focal Symptoms (Not TIA) Non-focal Symptoms (Not TIA) Generalized weakness or numbnessGeneralized weakness or numbness Faintness or syncopeFaintness or syncope IncontinenceIncontinence Isolated symptoms (symptoms occurring alone)Isolated symptoms (symptoms occurring alone) Vertigo or loss of balance Vertigo or loss of balance Slurred speech or difficulty swallowing Slurred speech or difficulty swallowing Double vision Double vision

134 TIA Presentation Non-focal Symptoms (Not TIA) Non-focal Symptoms (Not TIA) ConfusionConfusion Disorientation Disorientation Impaired attention/concentration Impaired attention/concentration Diminution of all mental activity Diminution of all mental activity Distinguish from Distinguish from Isolated language or visual-spatial perception problems (may be TIA)Isolated language or visual-spatial perception problems (may be TIA) Isolated memory problems (transient global amnesia)Isolated memory problems (transient global amnesia)

135 TIA Significant risk factor for recurrent stroke, with average 5% risk per yearSignificant risk factor for recurrent stroke, with average 5% risk per year Prophylactic antiplatelet therapy shown to prevent secondary effectsProphylactic antiplatelet therapy shown to prevent secondary effects Aspirin Aspirin Ticlopidine: thrombotic stroke reduction Ticlopidine: thrombotic stroke reduction Clopidogrel: reduce events associated with atherosclerosis that include strokes, MI, PVD Clopidogrel: reduce events associated with atherosclerosis that include strokes, MI, PVD

136 TIA Treat with warfarin if significant risk for cardiogenic thromboembolismTreat with warfarin if significant risk for cardiogenic thromboembolism Hospital admission for new-onset and recurrent TIA’s unless confident in diagnosis of etiologyHospital admission for new-onset and recurrent TIA’s unless confident in diagnosis of etiology Angiography – treat medically or surgicallyAngiography – treat medically or surgically

137 TIA Usually minutes, mostly <1 hour Usually minutes, mostly <1 hour Spells during days, weeks, months; not usually years Spells during days, weeks, months; not usually years

138 TIA Associated Symptoms Headaches may occur during time period of a TIA Headaches may occur during time period of a TIA

139 Migraine Demography Younger age Younger age Women>men (4:1) Women>men (4:1) 10-20% of the population 10-20% of the population The risk of migraine with aura and transient ischemic attacks (TIA’s) is greater than 2 fold. The risk of migraine with aura and transient ischemic attacks (TIA’s) is greater than 2 fold. 1/3 have migraine with aura 1/3 have migraine with aura

140 Migraine with Aura Migraine with aura Migraine with aura Positive symptomsPositive symptoms Spread over minutesSpread over minutes Visual disturbancesVisual disturbances Somatosensory or motor disturbanceSomatosensory or motor disturbance Headache within 1 hourHeadache within 1 hour Migraine with aura is associated with a twofold risk of ischemic stroke. This risk is higher in women, age < 45, smokers, and women who used oral contraceptives. Migraine with aura is associated with a twofold risk of ischemic stroke. This risk is higher in women, age < 45, smokers, and women who used oral contraceptives. BMJ2009;339:b3914, Migraine and cardiovascular disease BMJ2009;339:b3914, Migraine and cardiovascular disease

141 Migraine with Aura Aura without Headache Aura without Headache 98% Visual symptoms98% Visual symptoms 30% with other symptoms30% with other symptoms 26% sensory 26% sensory 16% aphasia 16% aphasia 6% dysarthria 6% dysarthria 10% weakness 10% weakness Mean age 48.7 (vs. 62.1)Mean age 48.7 (vs. 62.1) Fewer cardiovascular risk factorsFewer cardiovascular risk factors

142 Migraine CNS Timing Usually 20 to 30 minutes Usually 20 to 30 minutes Sporadic attacks during years Sporadic attacks during years

143 Migraine with Aura

144 Migraine Associated Symptoms Headache after attack, nausea, vomiting, photophobia, phonophobia (usually GI or autonomic nervous system) Headache after attack, nausea, vomiting, photophobia, phonophobia (usually GI or autonomic nervous system)

145 Migraine Auras typically occur before the onset of migraine headache, and the headache usually begins simultaneously with or just after the end of the aura phase. However, headache onset can rarely occur an hour or more after the end of the aura phase. Although atypical, an aura can develop during or after the onset of headache, and many patients have migraine aura with only a minimal or no headache. Auras typically occur before the onset of migraine headache, and the headache usually begins simultaneously with or just after the end of the aura phase. However, headache onset can rarely occur an hour or more after the end of the aura phase. Although atypical, an aura can develop during or after the onset of headache, and many patients have migraine aura with only a minimal or no headache.

146 Migraine Most migraine auras resolve in 20 to 30 minutes and seldom last more than one hour. Typical auras may involve any of the following manifestations: Visual disturbances ( the most common type of aura) Visual disturbances ( the most common type of aura) Sensory symptoms Sensory symptoms Motor weakness Motor weakness Speech disturbances Speech disturbances

147 Migraine vs. TIA Positive visual symptoms Positive visual symptoms Gradual onset / evolution Gradual onset / evolution Sequential progression Sequential progression Repetitive attacks of identical nature Repetitive attacks of identical nature Flurry of attacks mid-life Flurry of attacks mid-life Duration up to 60 minutes Duration up to 60 minutes Headache follows ~ 50% Headache follows ~ 50% Visual loss Visual loss Abrupt Abrupt Simultaneous occurrence Simultaneous occurrence Duration <15 minutes Duration <15 minutes Headache uncommon accompaniment Headache uncommon accompaniment

148 Syncope Demography Any age, often younger Any age, often younger Women>men Women>men

149 Syncope Timing Usually a few seconds Usually a few seconds Sporadic attacks during years Sporadic attacks during years

150 Syncope Associated Symptoms Sweating, pallor, nausea Sweating, pallor, nausea

151 Most Common Types of Syncope Neurocardiogenic (vasovagal) syncope Neurocardiogenic (vasovagal) syncope Situational syncope (during or immediately after urination, defecation, cough, or swallowing) Situational syncope (during or immediately after urination, defecation, cough, or swallowing) Orthostatic syncope (associated with orthostatic hypotension) Orthostatic syncope (associated with orthostatic hypotension) Syncope related to cardiac ischemia or cardiac arrhythmia Syncope related to cardiac ischemia or cardiac arrhythmia

152 Differential diagnosis of transient neurologic symptoms SeizuresTIAsMigraineSyncope Demography Any age, often younger Older patients Younger age Any age, often younger Stroke risk factors present Women>menWomen>men Men>women Central nervous system symptoms Positive symptoms: limb jerking, head turning, loss of consciousness Negative symptoms: numbness, visual loss, paralysis, ataxia First positive symptoms, then negative in same modality: scintillating scotomas and parasthesias most common; second sensory modality is involved after first clears Light-headed, dim vision, noises distant, decreased alertness Negative symptoms may develop, remain postictally, and persist All sensory modalities affected simultaneously Transient loss of consciousness Timing 20 to 80 seconds Usually minutes, mostly <1 hour Usually 20 to 30 minutes Usually a few seconds Absence, atonic seizures and myoclonic jerks are shorter Spells during days, weeks, months; not usually years Sporadic attacks during years Postictal depression Spells occur during years Associated symptoms Tongue biting, incontinence, sore muscles, headache after attack Headaches may occur during time period of TIAs Headache after attack, nausea, vomiting, photophobia, phonophobia Sweating, pallor, nausea

153 Transient Global Amnesia Sudden disorder of memorySudden disorder of memory Antegrade and often retrogradeAntegrade and often retrograde Recurrence 3% per yearRecurrence 3% per year Etiology unclearEtiology unclear Migraine Migraine Epilepsy (7% within 1 year) Epilepsy (7% within 1 year) Unknown Unknown

154 Transient Global Amnesia No difference in vascular risk factors compared with general populationNo difference in vascular risk factors compared with general population Fewer risk factors when compared with TIA patientsFewer risk factors when compared with TIA patients Prognosis significantly better than TIAPrognosis significantly better than TIA

155 Structural intracranial lesion TumorTumor Partial seizures Partial seizures Vascular steal Vascular steal Hemorrhage Hemorrhage Vessel compression by tumor Vessel compression by tumor

156 Intracranial hemorrhage ICH rare to confuse with TIAICH rare to confuse with TIA Subdural hematomaSubdural hematoma Headache Headache Fluctuation of symptoms Fluctuation of symptoms Mental status changes Mental status changes

157 Multiple sclerosis Usually subacute but can be acuteUsually subacute but can be acute Optic neuritis Optic neuritis Limb ataxia Limb ataxia Age and risk factorsAge and risk factors Signs more pronounced than symptomsSigns more pronounced than symptoms

158 Labyrinthine Disorders Central vs. Peripheral vertigoCentral vs. Peripheral vertigo Ménière's diseaseMénière's disease Benign positional vertigoBenign positional vertigo Acute vestibular neuronitisAcute vestibular neuronitis

159 Others in the Differential Diagnosis Metabolic perturbations, such as hypoglycemia, can be associated with focal neurologic deficits. Metabolic perturbations, such as hypoglycemia, can be associated with focal neurologic deficits. Multiple sclerosis occasionally can cause paroxysmal attacks, particularly of ataxia and dysarthria. Multiple sclerosis occasionally can cause paroxysmal attacks, particularly of ataxia and dysarthria. Brain tumors can occasionally result in transient neurologic symptoms; the mechanism in these cases is thought to involve mechanical changes that result in pressure on structures adjacent to the tumor. Brain tumors can occasionally result in transient neurologic symptoms; the mechanism in these cases is thought to involve mechanical changes that result in pressure on structures adjacent to the tumor.

160 Others in the Differential Diagnosis Subdural hematomas may cause attacks of transient neurologic dysfunction, again due to mechanical changes that result in pressure on structures adjacent to the hematoma. Subdural hematomas may cause attacks of transient neurologic dysfunction, again due to mechanical changes that result in pressure on structures adjacent to the hematoma. Cerebral amyloid angiopathy, better known as a cause of intracerebral hemorrhage, may also cause transient neurologic symptoms. Affected patients complain of recurrent, brief (minutes), often stereotyped spells of weakness, numbness, paresthesias, or other cortical symptoms that can spread smoothly over contiguous body parts. Cerebral amyloid angiopathy, better known as a cause of intracerebral hemorrhage, may also cause transient neurologic symptoms. Affected patients complain of recurrent, brief (minutes), often stereotyped spells of weakness, numbness, paresthesias, or other cortical symptoms that can spread smoothly over contiguous body parts.

161 Others in the Differential Diagnosis Hepatic, renal, and pulmonary encephalopathies can produce temporary aberrations in alertness, behavior and movement. Hepatic, renal, and pulmonary encephalopathies can produce temporary aberrations in alertness, behavior and movement. Compressive myelopathy may rarely cause sudden transient sensory changes and motor deficits. Compressive myelopathy may rarely cause sudden transient sensory changes and motor deficits. Pressure- or position-related peripheral nerve or nerve root compression can cause transient paresthesias and numbness. Pressure- or position-related peripheral nerve or nerve root compression can cause transient paresthesias and numbness.

162 Others in the Differential Diagnosis Peripheral vestibulopathies can cause transient episodic dizziness. Peripheral vestibulopathies can cause transient episodic dizziness. Hysteria and other psychiatric disorders may underlie attacks that include swoons, falls, and episodic blindness, deafness, and paralysis, which can be confused with organic loss of function. Hysteria and other psychiatric disorders may underlie attacks that include swoons, falls, and episodic blindness, deafness, and paralysis, which can be confused with organic loss of function.

163 Case 1 A 19 year old man had a history of a murmur since birth and intermittent episodes of hemiparesis that he ignored. He presented with collapse while playing handball. A 19 year old man had a history of a murmur since birth and intermittent episodes of hemiparesis that he ignored. He presented with collapse while playing handball.

164 Case 1 He fell and had tonic clonic movement of his extremities. He was in distress at presentation He fell and had tonic clonic movement of his extremities. He was in distress at presentation His BP was 110/70, HR 76, RR 18. He had a persistently split S2 with a systolic ejection murmur in the upper left second intercostal area. His neurological exam was consistent with a right middle cerebral infarction with a left hemiplegia and left hemisensory defect. His BP was 110/70, HR 76, RR 18. He had a persistently split S2 with a systolic ejection murmur in the upper left second intercostal area. His neurological exam was consistent with a right middle cerebral infarction with a left hemiplegia and left hemisensory defect.

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166 Case 2 When 22-year-old Ms. KS began experiencing left arm weakness, she went to a clinic only to be told that nothing was seriously wrong. But when her symptoms persisted, so did she. She was finally referred to the Medical Center, where neurologists confirmed that her symptoms were the result of a stroke.

167 Case 2 Further testing in the Coagulation Laboratory revealed activated protein C resistance, the result of a heterozygous mutation in factor V Leiden, as well as a homozygous mutation in the methylene tetrahydrofolate reductase gene, responsible for elevated homocystine Further testing in the Coagulation Laboratory revealed activated protein C resistance, the result of a heterozygous mutation in factor V Leiden, as well as a homozygous mutation in the methylene tetrahydrofolate reductase gene, responsible for elevated homocystine

168 Case 2 Although she had had only one clinical stroke, multiple other strokes were evident by imaging studies. Factors contributing to her hypercoagulable state included: 1. the methylene tetrahydrofolate reductase deficiency, which elevated her homocystine level, 2. the heterozygous state for factor V Leiden, causing activated protein C resistance, 3. oral contraceptives, 4. smoking, and 5. hypertension. She is doing well, without recurrence, on aspirin, and antihypertensive medicines, having stopped smoking and birth control pills. Although she had had only one clinical stroke, multiple other strokes were evident by imaging studies. Factors contributing to her hypercoagulable state included: 1. the methylene tetrahydrofolate reductase deficiency, which elevated her homocystine level, 2. the heterozygous state for factor V Leiden, causing activated protein C resistance, 3. oral contraceptives, 4. smoking, and 5. hypertension. She is doing well, without recurrence, on aspirin, and antihypertensive medicines, having stopped smoking and birth control pills.

169 Case 3 In another case, a 20-year-old female college student was sent to the Medical Center after a brain scan showed what her physicians thought to be a brain tumor. Neurosurgeons quickly realized there was no tumor, and that the young woman had suffered a stroke. After thrombosis of intracranial venous sinuses was diagnosed she was treated with heparin, and then Warfarin. Repeat imaging revealed recanalization of the previously thrombosed sinuses. In another case, a 20-year-old female college student was sent to the Medical Center after a brain scan showed what her physicians thought to be a brain tumor. Neurosurgeons quickly realized there was no tumor, and that the young woman had suffered a stroke. After thrombosis of intracranial venous sinuses was diagnosed she was treated with heparin, and then Warfarin. Repeat imaging revealed recanalization of the previously thrombosed sinuses.

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171 Case 3 Investigation in the Special Coagulation Laboratory revealed deficiency of antithrombin III, on two separate occasions, several weeks apart. This patient suffered a venous infarction secondary to a hypercoagulable state induced by inherited antithrombin III deficiency, probably exacerbated by use of oral contraceptives. With anticoagulation and careful monitoring, her prognosis is good. Investigation in the Special Coagulation Laboratory revealed deficiency of antithrombin III, on two separate occasions, several weeks apart. This patient suffered a venous infarction secondary to a hypercoagulable state induced by inherited antithrombin III deficiency, probably exacerbated by use of oral contraceptives. With anticoagulation and careful monitoring, her prognosis is good.

172 Case 4 A 28-year-old man has sudden weakness of the left arm and leg and slurred speech. A 28-year-old man has sudden weakness of the left arm and leg and slurred speech. Except for untreated hypertension, his medical history is unremarkable. Except for untreated hypertension, his medical history is unremarkable. He is a current smoker. He is a current smoker. On arrival at the emergency department 1 hour 15 minutes after the onset of symptoms, he reports no headache or vomiting. On arrival at the emergency department 1 hour 15 minutes after the onset of symptoms, he reports no headache or vomiting. His blood pressure is 180/100 mm Hg, and his pulse is 76 beats per minute and is regular. His blood pressure is 180/100 mm Hg, and his pulse is 76 beats per minute and is regular. Neurologic examination shows dysarthria, a left homonymous hemianopia, severe left-sided weakness, and a failure to register light touch on the left side of the body when both sides are touched simultaneously (left tactile extinction). Neurologic examination shows dysarthria, a left homonymous hemianopia, severe left-sided weakness, and a failure to register light touch on the left side of the body when both sides are touched simultaneously (left tactile extinction).

173 Case 4 He had sudden left-sided hemiparesis, strongly suggestive of a right hemisphere stroke. He had sudden left-sided hemiparesis, strongly suggestive of a right hemisphere stroke.

174 Summary These are not isolated cases. Frequently young patients, even teenagers, who have suffered stroke are misdiagnosed. Though they may have presented with classic symptoms - dizziness, severe headache, weakness in a limb, or unilateral loss of sensation, for example - they often have been misdiagnosed by their provider, most likely because they do not fit the profile of the "typical" stroke patient. These are not isolated cases. Frequently young patients, even teenagers, who have suffered stroke are misdiagnosed. Though they may have presented with classic symptoms - dizziness, severe headache, weakness in a limb, or unilateral loss of sensation, for example - they often have been misdiagnosed by their provider, most likely because they do not fit the profile of the "typical" stroke patient.

175 Summary Misdiagnosis has included patients being told they had vertigo, migraine, alcohol intoxication or other conditions. They were discharged from clinic and later discovered to have suffered a stroke. Misdiagnosis has included patients being told they had vertigo, migraine, alcohol intoxication or other conditions. They were discharged from clinic and later discovered to have suffered a stroke.

176 Summary The second important point is that the causes of stroke in young people are much more diverse, and less likely to be the ones that commonly cause stroke in older people, such as atherosclerosis of brain-supplying vessels and emboli from cardiac disorders related to coronary artery disease. Without the right resources, providers may be at a loss to pinpoint the cause in order to treat it and prevent further damage. The second important point is that the causes of stroke in young people are much more diverse, and less likely to be the ones that commonly cause stroke in older people, such as atherosclerosis of brain-supplying vessels and emboli from cardiac disorders related to coronary artery disease. Without the right resources, providers may be at a loss to pinpoint the cause in order to treat it and prevent further damage.

177 Summary Abuse of amphetamine-like drugs ("speed" and cocaine, for example) can lead to stroke in teenagers and young adults. These drugs are popular in rural and urban areas alike. Abuse of amphetamine-like drugs ("speed" and cocaine, for example) can lead to stroke in teenagers and young adults. These drugs are popular in rural and urban areas alike.

178 Summary However, one of the increasingly recognized causes of stroke in a young person is a blood disorder that predisposes to blood clotting.This allows clots to form too readily, often in the veins, leading to stroke. Once such a disorder has been identified, treatment can help prevent future damage. Diagnosis of a hereditary disorder can also lead to identification of other family members who may be at high risk. However, one of the increasingly recognized causes of stroke in a young person is a blood disorder that predisposes to blood clotting.This allows clots to form too readily, often in the veins, leading to stroke. Once such a disorder has been identified, treatment can help prevent future damage. Diagnosis of a hereditary disorder can also lead to identification of other family members who may be at high risk.

179 Summary The long term outcome of cerebral infarction is better in young adults than in older patients, morbidity and mortality are still significant. The long term outcome of cerebral infarction is better in young adults than in older patients, morbidity and mortality are still significant. Despite a good functional and motor outcome young adult patients usually encounter difficulties in social and work caused by cognitive impairment. Despite a good functional and motor outcome young adult patients usually encounter difficulties in social and work caused by cognitive impairment.

180 Summary The bottom line: for young stroke patients, extensive testing and careful evaluation may be necessary to determine the underlying cause. The bottom line: for young stroke patients, extensive testing and careful evaluation may be necessary to determine the underlying cause.

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