RESIDENTS’ RESIDENTS’ CLINIC CLINIC 71-Year-Old Woman With Loss of Right-Sided Vision and Cognitive Deficits KEVIN M. BARRETT, MD,* AND WILLIAM D. FREEMAN, MD† A 71-year-old right-handed woman presented to the emergency department approximately 5 hours after abrupt onset of confusion, memory difficulty, and diminished right-sided vision. She reported sudden difficulty answering simple questions while conversing with a friend and noted visual difficulty to her right side. She subsequently developed “numbness” that began in the right leg, spread to the right arm, then completely resolved after 5 minutes. The other symptoms persisted. On further questioning in the emergency department, she denied headache, loss of consciousness, involuntary limb movements, or recent trauma. The patient’s medical history was remarkable for hypertension, occasional palpitations, and recurrent urinary tract infections. She denied previous transient ischemic attack or stroke. Medications included conjugated estrogen (0.625 mg/d), sulfamethoxazole-trimethoprim (200 mg/40 mg daily), and propranolol (20 mg 3 times daily). Her blood pressure was 166/110 mm Hg, pulse was 109 beats/min, and temperature was 37.5°C. General physical and neurologic findings were remarkable for an irregularly irregular cardiac rhythm and right homonymous hemianopia, inability to read, markedly decreased short-term memory, and mild wordfinding difficulty. Verbal comprehension, repetition, naming, and writing functions were intact. The patient was awake, alert, and cooperative; no weakness or sensory disturbance was detected. While in the emergency department, she experienced 2 fleeting episodes of discomfort in the left eye and toothache. 1. On the basis of clinical history and examination, which one of the following is the most likely cause of this patient’s symptoms? a. Complex partial seizure of the left temporal lobe b. Hypoglycemia c. Ischemic infarction of the left middle cerebral artery (MCA) territory d. Ischemic infarction of the left posterior cerebral artery (PCA) territory e. Rapidly progressive dementia By definition, complex partial seizures are accompanied by alteration of consciousness. In our patient, seizure is an unlikely diagnosis because she was able to provide a clear history of events; seizure would not usually persist unchanged for several hours without postictal lethargy. Hy708 Mayo Clin Proc. • poglycemia sometimes manifests as focal neurologic dysfunction, typically after prior stroke. Because the patient had no prior stroke or autonomic symptoms (eg, pallor and diaphoresis), hypoglycemia was unlikely. Sudden onset of focal neurologic deficits always raises the possibility of cerebral ischemia. The irregularly irregular cardiac rhythm suggested atrial fibrillation and a possible cardioembolic ischemic mechanism. Although 80% of emboli originating in the heart travel to anterior circulation, the presenting clinical syndrome was not compatible with left MCA territory stroke (ie, aphasia, numbness and weakness in the face and extremities on the right side). However, the patient’s symptoms and signs, which included visual field disturbance, alexia without agraphia (impaired reading with intact writing), and short-term memory problems suggested posterior circulation ischemia (left PCA territory). The syndrome of alexia without agraphia has strong localizing value. Sudden onset of symptoms and absence of preexisting memory or cognitive symptoms made a rapidly progressive dementia unlikely. No evidence of intracranial hemorrhage was seen on initial noncontrast head computed tomography. Electrocardiography confirmed atrial fibrillation with a ventricular rate of 110 to 120 beats/min and T-wave inversion in the lateral precordial leads. The patient was given aspirin (325 mg) while in the emergency department. She denied chest pain, shortness of breath, or light-headedness. 2. Which one of the following is the most appropriate next step in management of this patient? a. Administer intravenous (IV) recombinant tissue-type plasminogen activator (r-tPA) b. Perform emergency direct-current cardioversion c. Attempt to restore sinus rhythm with IV ibutilide d. Attempt to control the ventricular response with IV digoxin e. Attempt to control the ventricular response with IV diltiazem *Fellow in Neurology, Mayo School of Graduate Medical Education, Mayo Clinic, Jacksonville, FL. †Adviser to Fellow and Consultant in Neurology, Mayo Clinic, Jacksonville, FL. See end of article for correct answers to questions. Individual reprints of this article are not available. Address correspondence to William D. Freeman, MD, Department of Neurology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224 (freeman.william1@mayo.edu). © 2008 Mayo Foundation for Medical Education and Research June 2008;83(6):708-711 • www.mayoclinicproceedings.com For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings. RESIDENTS’ CLINIC Intravenous r-tPA is the only therapy approved by the Food and Drug Administration for treatment of acute ischemic stroke; it is approved for use only within 3 hours of symptom onset in patients without intracranial hemorrhage or large areas of hypodensity (more than one-third of MCA territory) on head computed tomography. In our patient, immediate management strategies focused on atrial fibrillation because the duration of symptoms (5 hours) precluded administration of r-tPA. Urgent cardioversion is usually reserved for patients who demonstrate hemodynamic instability.1 Accepted standards of blood pressure management in treatment of acute ischemic stroke complicate the choice of rate-controlling agents. Changes in cerebral hemodynamics after acute ischemic stroke warrant a cautious appr ach o to elevated systemic blood pressure and avoidance of arterial hypotension. Ibutilide was not considered a good medication choice because of occasional hypertension associated with its use. Digoxin is not associated with systemic hypotension and was used as the treatment of choice for rate control. Calcium channel antagonists were avoided because of potential hypotension. The ventricular rate was well controlled after an IV digoxin loading dose was given. The patient remained in atrial fibrillation with systolic blood pressure ranging from 130 to 160 mm Hg, pulse rate from 80 to 90 beats/min, and oxygen saturation by pulse oximetry from 95% to 96% while breathing room air. 3. Which one of the following additional management strategies in the acute setting would most likely improve this patient’s outcome? a. Administer IV hypotonic saline at a maintenance rate of 125 mL/h b. Provide supplemental oxygen by nasal cannula c. Monitor serum glucose levels and administer insulin for hyperglycemia (≥200 mg/dL) d. Monitor serum sodium levels frequently and aggressively replace with 3% hypertonic saline to maintain normal levels e. Administer pharmacologic neuroprotective agents to prevent excitotoxicity and infarct extension The maintenance fluid of choice in patients with ischemic stroke is 0.9% saline. Hypotonic saline should not be used; it may cause osmotic shifts of free water from the extracellular to the intracellular compartment and exacerbate peri-infarct edema. Routine use of supplemental oxygen in the absence of hypoxia (pulse oximetry <92% or PaO2 <60 mm Hg) is not recommended as supportive treatment of ischemic stroke2 alone; however, it may be required in patients with preexisting cardiopulmonary conditions. Hyperglycemia in patients with acute stroke is Mayo Clin Proc. • associated with worse clinical outcomes,3 and current recommendations support use of insulin to keep serum glucose at acceptable levels.4 Serum sodium levels are not associated with morbidity or mortality in ischemic stroke, and rapid transcellular fluid shifts that occur with administration of hypertonic saline increase risk of further neurologic insult. Intense research has not shown a convincing beneficial effect of pharmacologic interventions to prevent glutamate-mediated excitotoxicity. On hospital day 2, the patient’s temperature reached 38.5°C. She was able to walk and denied cough, pleuritic chest pain, or genitourinary symptoms. General physical and neurologic findings were unchanged from those obtained at admission, including absence of murmurs on cardiac auscultation or difficulty swallowing. She was hemodynamically stable without hypoxia. Results of blood cultures and urinalysis were negative. Chest radiography showed clear lung fields. 4. Given the preceding clinical information, which one of the following is the most likely cause of this patient’s fever? a. Bacterial endocarditis b. Acute ischemic stroke c. Large-vessel vasculitis (ie, giant cell arteritis) d. Metastatic disease e. Drug fever Development of fever in a hospitalized stroke patient should always arouse suspicion of infection. Urinary tract infections and aspiration pneumonia are common causes of fever. Bacterial endocarditis is an important consideration in patients with multifocal areas of cerebral infarction, fever, positive results on blood cultures, and cardiac murmur. Our patient had no signs of peripheral embolization (eg, Janeway lesions or Osler nodes), and findings on blood cultures were negative, making endocarditis an unlikely diagnosis. Attributing fever to stroke remains a diagnosis of exclusion after thorough systemic work-up. Forty percent of patients with ischemic stroke develop fever. Of these patients, 15% become febrile within 24 hours, 49% by the second day, and the remainder at some later time.5 Fever due to stroke is also associated with increased morbidity and mortality.6 On the basis of the patient’s unremarkable systemic work-up, fever due to stroke was the most likely diagnosis. Vasculitis and metastatic disease may cause fever, but in this patient, little else suggested these diagnoses. Fever is a common form of allergic reaction to many drugs and typically develops within a few days of new drug exposure. Digoxin, the only new medication introduced during hospitalization, is not associated typically with febrile reactions. June 2008;83(6):708-711 • www.mayoclinicproceedings.com For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings. 709 RESIDENTS’ CLINIC Successive blood and urine cultures yielded negative results. No empiric antibiotics were initiated, and no fever recurred during the remainder of the hospitalization. 5. Which one of the following therapies, if initiated early in the onset of this patient’s stroke, would most effectively reduce subsequent disability and prevent early stroke recurrence? a. Full-dose IV unfractionated heparin b. Warfarin with target international normalized ratio (INR) between 2.5 and 3.5 c. Aspirin, 325 mg/d d. Aggressive cognitive rehabilitation e. Carotid endarterectomy Emergency anticoagulation is not recommended after acute ischemic stroke4 because it has not been shown to improve neurologic outcomes. Early administration of IV heparin or low-molecular-weight heparin increases risk of systemic hemorrhage and symptomatic hemorrhagic conversion, especially in patients with large territorial infarctions.7,8 Oral anticoagulation therapy with warfarin (goal INR, 2.0-3.0) is an effective long-term measure to prevent stroke in patients with nonvalvular atrial fibrillation. An INR of 2.5 to 3.5 is typically reserved for patients with prosthetic heart valves. Initiation of oral anticoagulation is typically deferred for 1 to 2 weeks after moderate or large hemispheric infarctions to reduce the risk of hemorrhagic conversion. Reassessment of underlying cardiac rhythm in the weeks after stroke is warranted. Aspirin (160 mg/d or 325 mg/d), however, results in a small but statistically significant reduction in stroke-related disability and death when given within 48 hours of stroke onset9 and reduces risk of early stroke recurrence.10 Recent guidelines suggest initiating aspirin therapy within 48 hours of symptom onset.4,8 Rehabilitation is an essential component of any comprehensive stroke treatment program but does not affect risk of early stroke recurrence. Carotid endarterectomy provides robust reduction in stroke risk for symptomatic patients with carotid stenosis of 70% or more (ie, ipsilateral ocular or hemispheric symptoms), which our patient did not have. The patient showed gradual improvement in her ability to read and was transferred to a rehabilitation facility. Warfarin was later initiated to keep the INR between 2.0 and 3.0. DISCUSSION This case exemplifies a fascinating neurologic syndrome while highlighting basic management principles applicable to patients with acute ischemic stroke. As part of a broader category of disorders termed disconnection syndromes, 710 Mayo Clin Proc. • FIGURE 1. Afferent visual system with interconnections to visual and language association cortices. Schematic is oriented with radiographic conventions to facilitate comparison to magnetic resonance image in Figure 2. After infarction of the left posterior cerebral artery territory (visual cortex and splenium), all visual information necessary for activating speech centers in the left hemisphere must come from the right visual cortex. Normal flow of information from the right visual cortex to the left hemisphere (red arrows) is interrupted, resulting in alexia. alexia without agraphia, as described by Déjerine,11 results from interruption of interhemispheric communication across the posterior portion of the corpus callosum. This patient’s symptom complex offers an elegant example of lesion localization. The PCA supplies the banks of the calcarine fissure, which form the visual cortex. A left PCA distribution lesion causes the characteristic field deficit on examination (Figure 1). Also within the vascular distribution of the PCA is the splenium of the corpus callosum, which connects the right visual cortex to language centers in the left hemisphere. Infarction of these transcortical fibers interrupts the transfer of visual information from the intact right visual cortex to the left hemispheric association areas necessary for word identification. Such an infarction accounted for our patient’s inability to read. Spontaneous writing was normal because the angular gyrus and associated expressive language centers (Broca area) were intact and connected (Figure 1). Memory difficulties ordinarily result from bilateral hippocampal lesions but have been described in unilateral June 2008;83(6):708-711 • www.mayoclinicproceedings.com For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings. RESIDENTS’ CLINIC always mandate treatment and often resolves spontaneously within a f ew days. Elevat ed blood glucose levels after acute ischemic stroke are common and should be managed as correlates to overall mortality.13 This case highlights safe and evidence-based measures that can be initiated in patients with acute stroke. Applying these measures can improve the care we deliver to patients with stroke. Drs Barrett and Freeman gratefully acknowledge their late mentor, Frank A. Rubino, MD, for his tireless teaching, inspiration, and guidance. Dr Rubino encouraged and supervised the initial compilation of this report. Like so many others before us, we are grateful for the time we were able to spend in his shadow. The authors also thank M. Alice McKinney for her artwork. FIGURE 2. Diffusion-weighted magnetic resonance image. The patient had an area of acute infarction in the left occipital lobe within the distribution of the left posterior cerebral artery. destructive lesions of the dominant hemisphere. The hippocampus demarcates the most anterior supply of the PCA in the mesial temporal lobe. Fleeting sensory symptoms described by the patient may have been due to transient ischemia to the lateral thalamus, an area supplied by penetrating vessels (thalamoperforators) arising from the PCA trunk. Of further neuroanatomic interest, branches of the PCA supply the superior border of the tentorium and trigeminal nerve, which, if compromised, could have caused the patient’s retro-orbital discomfort and toothache. Magnetic resonance imaging (Figure 2) confirmed localization precisely. This case emphasizes the importance of the link between general medical disorders and neurologic disease. Atrial fibrillation led to cardioembolic ischemic stroke, creating alexia without agraphia and visual field deficits. The importance of management of blood pressure, atrial fibrillation, ventricular rate, and blood glucose in acute stroke cannot be overemphasized. Calcium channel blockers or β-blockers, often used for ventricular rate control in atrial fibrillation, also have antihypertensive effects that must be monitored carefully to avoid deleterious effects to vulnerable ischemic brain tissue. In the normal brain, autoregulation maintains constant cerebral perfusion pressure across a wide range of systemic blood pressures. Impaired autoregulation in areas of focal cerebral ischemia may result in hypoperfusion of potentially viable brain tissue (ie, the penumbra) in the setting of arterial hypotension. In the early minutes to hours after ischemic stroke, elevated blood pressure is common12 and likely acts as a protective mechanism. 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