What is the most likely diagnosis?A 60-year-old man is brought to the emergency room by ambulance because of slurred speech and left-side weakness. His wife states the patient went to bed at approximately 11 PM the night before and was well. At 5 AM, the time they usually get up, she noticed that he had some difficulties talking and moving his left arm and leg. They arrived at the emergency department (ED) at 6 AM. He has history of long-standing hypertension (HTN), a heart attack 10 years before, and high cholesterol. He is taking baby aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin on a daily basis. He heavily consumed alcohol in the past, but stopped after the heart attack. He still smokes a half pack of cigarettes daily. His wife remembers that about 3 months ago he complained of mild bilateral leg pain during their morning walk and had to stop after 15 minutes. Also, she remembers that 1 month ago he had “slight right eye blackout” for 5 minutes. On presentation to the ED his blood pressure is 195/118 mm Hg, his pulse is 106 beats/min, his respiratory rate is 18 breaths/min, his temperature is 99.8°F (37.6°C), and his oxygen saturation is 97% on room air. Although his pupils are equal and reactive and the ocular movements are intact, he is unable to turn his eyes voluntarily toward the left side. The neck is supple, there is no jugular venous distension, and there are no bruits. The lungs are clear, the heart sounds regular without murmurs, and the abdomen is normal. The limbs are not well-perfused distally. The neurologic examination reveals that he is alert and oriented, although he does not recognize he is sick. He is right-handed. He shows loss of awareness and attention with respect to objects or stimuli on his left side. He has mild dysarthria, but his speech is fluent and he understands and follows commands very well. There is mild weakness on the left side of the face and left-sided homonymous hemianopsia, but there is no nystagmus or ptosis, and no tongue or uvula deviation. He is not able to move his left arm and leg, has hyperreflexia, and the left great toe is upgoing.
What is the most likely diagnosis?
What is your next diagnostic step?
What is your next step in therapy?
Summary: The patient is a 60-year-old, right-handed man with history of coronary artery disease, hypertension, and hypercholesterolemia, who presents to the emergency room with a 5-hour history of slurred speech and an inability to move his left arm and leg. He had an episode of amaurosis fugax (blindness) in his right eye 1 month before admission. On physical examination, although he is alert and oriented, he has no awareness of his disability (anosognosia) and exhibits left-sided neglect. He has hypertension, dysarthria, and left hemiparesis. He also has left-sided homonymous hemianopsia, conjugate rightward gaze deviation, left hemifacial weakness, and left hyperreflexia.
• Most likely diagnosis: Cerebrovascular accident (CVA).
• Next diagnostic step: Obtain a brain computed tomography (CT) scan without contrast.
• Next step in therapy: Determine advisability for acute treatment with thrombolytic agents.
1. Recognize the significance of a correct diagnosis and evaluation of transient ischemic attacks (TIAs) and cerebrovascular accidents.
2. Recognize the conditions that can mimic a stroke.
3. Understand that the clinical evaluation gives the most important clues about diagnosis of stroke.
4. Be familiar with the accepted approach for the early management of patients with ischemic stroke.
5. Be familiar with the current strategies for prevention of ischemic stroke and TIA.
This 60-year-old patient has developed focal neurologic deficits, which is the usual presentation of patients with strokes. Considering that he has a history of hypertension, hypercholesterolemia, and vascular manifestations of atherosclerosis, such as coronary artery disease and peripheral vascular disease (lower extremity claudication), ischemic stroke is the most probable diagnosis. Furthermore, he had a TIA (amaurosis fugax) 30 days before admission, which put him at even greater risk for an ischemic stroke. His neurologic deficits are compatible with an ischemic stroke in the territory of the right middle cerebral artery, which is his nondominant hemisphere and the reason he is not aphasic.
Of immediate importance, the clinician should confirm that the neurologic impairments are secondary to ischemic stroke and not other conditions, especially intracranial hemorrhage. A brain CT without contrast should be obtained as soon as possible to exclude hemorrhage, tumor, and abscess. Blood sugar, drug screen, coagulation studies, serum electrolytes, renal function tests, lipid profile, and a complete blood count are also indicated. A cardiac monitor should be attached and a 12-lead ECG obtained so as to exclude acute myocardial infarction or atrial fibrillation.
Because it has been more than 3 hours from the onset of symptoms, this patient is not a candidate for thrombolytic therapy. The initial ABC (airway, breathing, and circulation) survey should guide treatment if the vital signs are compromised. Although his blood pressure is elevated, in the setting of an acute CVA, blood pressure management should be cautious. The patient should be admitted to the hospital for further evaluation and management, preferably to a dedicated stroke unit if available. Aspirin should be given within 48 hours of the stroke, and deep venous thrombosis prophylaxis should be used. However, anticoagulation with heparin or warfarin for the infarction itself has a poor risk-benefit ratio and is not indicated. An evaluation of his swallowing function and an early physiotherapy consultation should be obtained. Further imaging with brain magnetic resonance imaging (MRI), magnetic resonance angiography, or CT angiography can help to clarify the etiology of the stroke and guide treatment. In this patient, carotid Doppler studies are indicated as he had an episode of amaurosis fugax, which is caused by a blockage of the opthalmic artery which branches from the internal carotid.
Management of his chronic medical conditions, to try to reduce his risk of subsequent strokes, is critical. In this patient, these measures include tight control of his hypertension and hypercholesterolemia, along with smoking cessation. Because this patient had a stroke while taking aspirin, an alternative antiplatelet agent should be considered.
TRANSIENT ISCHEMIC ATTACK (TIA): A transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. There is no time cutoff that reliably distinguishes whether a symptomatic ischemic event will result in ischemic infarction.
TRANSIENT SYMPTOMS WITH INFARCTION (TSI): A transient episode of neurologic dysfunction associated with irreversible ischemic brain injury.
ISCHEMIC STROKE: An infarction of central nervous system tissue.
There are 700,000 people that suffer from stroke in the United States each year, and the incidence of TIA is approximately 200,000 to 500,000 per year. Strokes remain the third leading cause of death in North America and are a major cause of disability. TIA is defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. Most TIAs last for less than 1 hour. A stroke is presumed to have occurred if the symptoms persist for more than 24 hours. However, there is an unreliable correlation of symptom duration with actual infarction. Patients with a TIA are at increased risk of a subsequent stroke. The reported occurrence of a stroke after a TIA is as high as 5.3% within 2 days and 10.5% within 90 days. Patients with a TIA often require hospital admission, further evaluation, and the same long-term management as stroke patients. An assessment called the ABCD2 score (Age, Blood pressure, Clinical features, Duration of symptoms, and Diabetes) can be used to identify patients at high risk of ischemic stroke in the first 7 days after TIA. The ABCD2 score is as follows:
Age (≥60 years = 1 point)
Blood pressure elevation when first assessed after TIA (systolic ≥140 mm Hg or diastolic ≥90 mm Hg = 1 point)
Clinical features (unilateral weakness = 2 points; isolated speech disturbance = 1 point; other = 0 points)
Duration of neurologic symptoms (≥60 minutes = 2 points; 10 to 59 minutes = 1 point; <10 minutes = 0 points)
Diabetes (present = 1 point)
Estimated 2-day stroke risk determined by the ABCD2 score are as follows: Score 0 to 3: Low stroke risk (1 percent)
Score 4 to 5: Moderate risk (4 percent)
Score 6 to 7: High risk (8 percent)
Hypertension is the single most important risk factor for stroke, and the incidence of stroke in the United States has decreased partly as a result of better efforts to control hypertension in the past few decades. Other risk factors include diabetes mellitus, older age, male sex, family history, dyslipidemia, and smoking. Many cardiovascular conditions also predispose people to stroke, usually through an embolic clot. These conditions include atrial fibrillation, myocardial infarction, endocarditis, carotid stenosis, rheumatic heart disease, presence of mechanical valve, advanced dilated cardiomyopathy, and a patent foramen ovale or atrial septal defect which can expose the systemic arterial system to a paradoxical embolus from a venous source. Sickle cell disease is also a risk factor for stroke. Patients with sickle cell commonly experience their strokes as children.
Strokes are generally classified as being of thrombotic or embolic origin. Strokes that affect the small branches of the main arteries of brain are termed lacunar infarcts or small-vessel strokes. These strokes often forewarn a larger, more debilitating stroke. The causes of the emboli are usually of cardiovascular origin and include the previously mentioned conditions as well as dissection of various vessels. Most emboli are clots. However, emboli in rare occasions can be vegetations from infective endocarditis, sterile vegetations from Libman-Sacks endocarditis (which occurs in systemic lupus erythematosus), and marantic endocarditis (which occurs with cancer).
Sudden onset of focal neurologic deficit is the usual presentation of stroke patients, although some patients can have a gradual worsening of symptoms. Unless there is a hemispheric infarct, basilar artery occlusion, or cerebellar stroke with edema, nearly all of the patients are alert. If the middle cerebral artery territory is affected, the patient would experience aphasia (when dominant hemisphere is involved), contralateral hemiparesis, sensory loss, spatial neglect, and contralateral impaired conjugate gaze. When the territory of the anterior cerebral artery is affected, foot and leg deficits are more frequent than arm deficits. These patients often have associated cognitive and personality changes. Vertebrobasilar stroke symptoms and signs include motor or sensory loss in all four limbs, crossed signs, disconjugate gaze, nystagmus, dysarthria, and dysphagia. There can be ipsilateral limb ataxia and gait ataxia if the cerebellum is affected.
What risk factors for stroke can’t be changed?
• Age
• Heredity (family history) and race
• Sex (gender)
• Prior stroke, TIA, or heart attack
What stroke risk factors can be changed, treated, or controlled?
• High blood pressure
• Cigarette smoking
• Diabetes mellitus
• Carotid or other artery disease
• Peripheral artery disease
• Atrial fibrillation
• Coronary heart disease or heart failure
• Sickle cell disease
• High blood cholesterol
• Poor diet
• Physical inactivity and obesity
Assessment of the vital signs is important in the initial examination. Severe high blood pressure can be suggestive of hypertensive encephalopathy or intracranial hemorrhage. A fever may lead to consideration of an infectious cause. A rapid or irregularly irregular pulse may imply atrial fibrillation as a potential cause of the stroke. A timely general physical examination and comprehensive neurologic examination should follow.
The differential diagnosis of acute neurologic symptoms and signs is broad. Along with CVAs, these symptoms can be caused by seizures, acute confusional states, delirium, syncope, metabolic and toxic encephalopathy (hypoglycemia), brain tumors, CNS infections, migraines, multiple sclerosis, and subdural hematoma. Migraines with neurologic symptoms can be especially difficult to differentiate from stroke since migraines do not have to be accompanied by a headache. However, the symptoms of stroke are usually of a much more rapid onset than those of a migraine. Stroke victims are also usually alert and aware of what is happening to them, unlike people suffering from delirium or various types of encephalopathies. When it is determined that a stroke is the cause of the presentation, it is crucial to differentiate between ischemic and hemorrhagic stroke because of the implications on further treatment.
The initial assessment should establish if the patient is eligible for thrombolytic treatment. Establishing the time of symptom onset is the most important factor. The onset of symptoms is assumed to be the time that the patient was last known to be free of symptoms such as when they went to bed.
A CT scan of the brain without contrast is the initial imaging test of choice. CT of the brain may not show an ischemic stroke for up to 72 hours, but can exclude most cases of intracranial hemorrhage, tumors, or abscesses quickly. It is also more readily available, cost effective, and takes less time than MRI. CT scan can also be used to detect a hemorrhagic transformation of an infarct in a patient with an ischemic stroke whose symptoms deteriorate. If neurologic symptoms have resolved, MRI (if available) within 24 hours is the preferred imaging study due to its increased sensitivity for differentiating between a TIA and a TSI stroke.
Further imaging studies may be indicated to clarify the etiology of the stroke and to detect intracranial or extracranial arterial occlusions, which may affect treatment decisions. Evaluation of the cerebrovascular system can be accomplished with magnetic resonance angiography (MRA), CT angiography, catheter angiography, or transcranial Doppler ultrasonography.
A 12-lead ECG should be done in all stroke patients in order to detect acute myocardial infarctions, which can both cause strokes or result from a stroke. An ECG will also aid in the diagnosis of atrial fibrillation. Echocardiography may also be necessary to adequately assess the heart. Transesophageal echocardiography is particularly useful in detecting cardiac sources of embolism, such as thrombus caused by myocardial infarction, endocarditis, rheumatic heart disease, valvular prostheses, and atrial septal defects. A carotid Doppler study is often advisable as well in order to evaluate for carotid plaques or stenosis.
Blood glucose, electrolytes, renal function tests, and drug screening are important to exclude hypoglycemia and metabolic and toxic encephalopathy. If the patient is on anticoagulant therapy, the prothrombin time, partial thromboplastin time, and platelet count should be measured and are required before considering thrombolytic therapy. A lipid panel, erythrocyte sedimentation rate, anti-nuclear antibodies (ANA), complete blood count, and serologic tests for syphilis are also oftentimes indicated. In young patients with no identifiable cause for a stroke, a workup for coagulation disorders or antiphospholipid syndrome may be indicated. A lumbar puncture is indicated if subarachnoid hemorrhage is considered and the CT is not diagnostic or if a CNS infection is possible.
As in every critical patient, the initial survey should assess the ABCs. If hypoxia is detected, supplemental oxygen should be administered to maintain oxygen saturation above 92% and the cause of the hypoxia investigated (partial airway obstruction, aspiration pneumonia, atelectasis). An endotracheal tube should be placed if the airway is threatened. A cardiac monitor should be placed to detect atrial fibrillation or any other arrhythmias.
Unless a hypertensive encephalopathy, aortic dissection, acute renal failure, or pulmonary edema is present, the treatment of arterial hypertension should be cautious. Antihypertensive medication is recommended when the systolic blood pressure is greater than 220 mm Hg or the diastolic blood pressure is greater than 120 mm Hg. If the patient is suitable for thrombolytic treatment, medication should be initiated to decrease the systolic blood pressure to less than 185 mm Hg and the diastolic blood pressure less than 110 mm Hg. The agents most frequently used are IV labetalol, nicardipine, and sodium nitroprusside.
Fever and high blood sugar after a stroke are often associated with poorer outcomes and should be controlled during the poststroke period. An infectious source for the fever should be investigated.
Except when thrombolytic therapy is given, most patients with a nonhemorrhagic stroke should receive aspirin within the first 48 hours. Urgent anticoagulation is not recommended.
Judiciously selected patients can benefit from intravenous administration of recombinant tissue-type plasminogen activator (rtPA) if they can be treated within 3 hours of the onset of ischemic stroke. The risk of hemorrhage associated with rtPA treatment is approximately 5% and there are numerous contraindications to the use of thrombolytic therapy, including recent surgery, trauma, gastrointestinal bleeding, myocardial infarction, use of certain anticoagulant medications, and uncontrolled hypertension. Depending on availability, some hospitals have the capability of direct intra-arterial thrombolysis in which the thrombolytic agent is delivered directly to the clot via canalization or even mechanical retrieval of thrombus. These modes of treatment may be considered in centers with experimental protocols or extensive experience.
Poststroke cerebral edema can be a very serious complication and can lead to herniation of brain stem resulting in death. This edema can be treated with mannitol or decompression surgery, although there is insufficient evidence to show significant benefit for these treatments at this time.
Studies have shown that treatment in a dedicated stroke unit results in better outcomes and less mortality. Early posttreatment care includes mobilization once the patient is stable and evaluations of the patient’s ability to swallow. After a stroke, the patient is often immobile and needs intensive medical care in order to avoid malnutrition, skin breakdown, and other complications. The patient’s neural deficits usually improve after the stroke and can keep improving up to 6 months to a year. Prior strokes also predispose patients to seizures, and some patients may initially present with a seizure as the first symptom of stroke. When thrombolytic therapy is not used, deep vein thrombosis prophylaxis should be provided. Family support and treatment of depression should also be initiated when appropriate.
A history of a previous TIA or CVA confers a high risk for future events. Aggressive risk factor control should be undertaken in these patients. All patients should be counseled to quit smoking and to reduce alcohol intake. Hypertensive patients should be treated per JNC-7 (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, 7th report) guidelines (see Case 30). High cholesterol should be treated with a goal of low-density lipoprotein (LDL) less than 100 mg/dL. Tight diabetic control should be sought. Antiplatelet agents such as aspirin (50-325 mg/d), the combination of aspirin and extended-release dipyridamole (Aggrenox), or clopidogrel (Plavix) should be started in patients with a history of noncardioembolic ischemic stroke or TIA.
Carotid endarterectomy (CEA) can reduce the risk of stroke in someone with a history of previous TIA/CVA and carotid artery stenosis. It is indicated for symptomatic patients with carotid stenosis greater than 70% when it can be performed by an experienced surgeon with a low rate of perioperative complications. CEA can be considered for symptomatic patients with a 50% to 70% stenosis, but is not indicated when there is less than 50% stenosis. Noninvasive carotid balloon angioplasty and stenting is now also being done and is an alternative to CEA.
Anticoagulation with warfarin reduces the risk of stroke and stroke recurrence in certain circumstances. It is indicated to reduce the risk of embolic strokes for patients with persistent or paroxysmal atrial fibrillation or very advanced heart failure. It is also indicated for patients with an ischemic stroke caused by a myocardial infarction and existence of left ventricular thrombus, as well as for patients with rheumatic heart disease or a mechanical heart valve.
44.1 A 72-year-old man is brought into the emergency department because of weakness and numbness of the right arm. The medical student on the case asks the attending doctor about the diagnosis and management of transient ischemic attacks. Which of the following could be expected in patients with a TIA?
A. Resolution of symptoms within 1 hour
B. Stroke within 90 days in less than 1% of patients
C. CT evidence of infarction
D. MRI evidence of infarction
44.2 An 84-year-old African-American woman was found by her daughter-in-law walking down the street a few blocks from her house. The daughter-in-law noticed that she did not appear to know where she was and did not recognize her. Upon prompting she seemed confused and would not speak. The patient experienced a CVA 1 year previously and had mild residual deficits on her left side. She takes medication for hypertension, hyperlipidemia, constipation, and gout. In the emergency room the patient has a blood pressure of 145/76 mm Hg, pulse of 86 beats/min, respiratory rate of 18 breaths/min, and temperature of 97.9°F (36.6°C). She does not follow commands and is oriented to person. She complains of headache. A CT of the brain does not show evidence of a bleed. The physician suspects subarachnoid hemorrhage. Which of the following is the most appropriate next step in management?
A. Lumbar puncture
B. Chest x-ray
C. Brain CT with contrast
D. MRI of the brain
44.3 An 82-year-old man with suspected stroke is transferred to a major medical trauma center from an outside rural hospital. Four hours have elapsed since first presentation. Which of the following should be considered in the management of this patient?
A. Avoidance of acetaminophen
B. Aggressive blood pressure management
C. Thrombolysis
D. Early mobilization
44.4 A 65-year-old man was hospitalized due to weakness of the right arm, which was diagnosed as an ischemic stroke. Which of the following is the best step regarding prevention of future strokes in this patient?
A. He would likely benefit from oral anticoagulation.
B. If he has 60% right carotid occlusion, then he is likely to benefit from carotid endarterectomy.
C. Aspirin is an acceptable option for initial therapy.
D. LDL cholesterol should be treated with a goal of less than 130 mg/dL.
44.5 A man is brought to the emergency room by ambulance. Coworkers at his office stated that he was acting normally until approximately 1 hour ago when he became confused and had trouble walking. One coworker thought that his right leg seemed especially weak. The vitals are: temperature 98.6°F (37°C), pulse 110 beats/min, and blood pressure 120/80 mm Hg. The patient is arousable but does not follow commands. He has a medical alert bracelet on his arm indicating that he is a diabetic and allergic to penicillin. A blood glucose taken at the bedside is 20 mg/dL. Which of the following should be your immediate next step?
A. Immediately give the patient glucose or glucagon.
B. Immediately obtain a CT scan to assess possibility for giving rtPA.
C. Immediately perform a lumbar puncture to assess for meningitis.
D. Immediately give the patient mannitol.
E. Immediately start cardiopulmonary resuscitation (CPR) with chest compressions.
44.1 A. A TIA is a brief neurologic episode, typically less than 1 hour in duration that does not cause infarction. The occurrence of stroke after TIA is as high as 5.3% within 2 days and 10.5% within 90 days. Warfarin is indicated in specific circumstances, such as the presence of atrial fibrillation, but is not routinely used following a TIA.
44.2 A. Routine chest x-rays affect the clinical management in few patients with stroke, and are not recommended as routine initial workup. CT of the brain without contrast can exclude most cases of intracranial hemorrhage, tumors, or abscesses, and is the initial test of choice in the workup of suspected stroke but it can miss up to 15% of subarachnoid hemorrhages. When a subarachnoid hemorrhage is suspected but not seen on CT, a lumbar puncture is indicated for diagnosis.
44.3 D. Mobilization of stroke patients should be started when they are considered medically stable. In the setting of an acute stroke, management of high blood pressure should be cautious. Thrombolytic therapy can be beneficial in selected patients, but carries significant risks and has numerous contraindications. Fever should be treated and a workup performed to determine its etiology, as it carries an increased risk of morbidity and mortality.
44.4 C. Patients with stroke but no detected sources of embolism benefit from anti-platelet agents, not anticoagulants. Aspirin, clopidogrel, or a combination of aspirin and dipyridamole are acceptable regimens. For patients with recent TIA or ischemic stroke and ipsilateral severe (>70%) carotid artery stenosis, carotid endarterectomy is recommended. When the degree of stenosis is less than 50%, there is no indication for CEA. Patients with a history of symptomatic cerebrovascular disease should be treated to an LDL goal of less than 100 mg/dL.
44.5 A. The patient has severe hypoglycemia and needs to be treated immediately with glucose or glucagon. If the patient does not recover with glucose or glucagon infusion, then other tests, such as a CT scan, may be warranted. But the most important first step is to treat the patient’s low blood sugar. Be aware that hypoglycemia can mimic many of the symptoms of a stroke, including focal weakness. Mannitol is used in cases of cerebral edema and not for raising blood sugar.
Hypertension is the single most important risk factor for stroke.
Although most strokes are cerebral infarcts, it is crucial to differentiate between ischemic and hemorrhagic stroke because of the implications on further treatment.
CT of the brain without contrast is the initial imaging test of choice in most suspected strokes.
Unless a hypertensive encephalopathy, aortic dissection, acute renal failure, or pulmonary edema is present, the treatment of arterial hypertension should be cautious.
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Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack. Stroke. 2009;40(6):2276.
Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007;369(9558):283.
National Heart, Lung and Blood Institute. The 7th report of the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure. December 2003. Available at: www.nhlbi.nih.gov/guidelines/hypertension/express.pdf. Accessed October 21, 2011.
Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack. Circulation. 2006;113:e409-e449.
Smit WS, English JD, Johston CS. Cerebrovascular diseases. In: Fauci AS, Braunwald E, Kasper DL, et al. Harrison’s Principles of Internal Medicine. 17th ed. New York, NY: McGraw-Hill; 2008: 2513-2536.
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