- Email: [email protected]
Safety and Outcomes in Stroke Mimics after Intravenous Tissue Plasminogen Activator Administration: A Single-center Experience
Safety and Outcomes in Stroke Mimics after Intravenous Tissue Plasminogen Activator Administration: A Single-center Experience Christopher Lewandowski, MD,* Kathleen Mays-Wilson, RN, BSN, CCRP,† Joseph Miller, MD,* Patricia Penstone, RN,‡ Daniel J. Miller, MD,‡ Konstandinos Bakoulas, BS,‡ and Panayiotis Mitsias, MD, PhD‡
Background: Patients with symptoms that impersonate a stroke but are later found to have an alternate diagnosis are termed stroke mimics. Stroke mimics treated with intravenous (IV) tissue plasminogen activator (t-PA) are exposed to hemorrhagic complications without benefit. The objective of this study is to describe the characteristics, safety, and outcomes of stroke mimic patients treated with t-PA within 4.5 hours. Methods: All patients hospitalized after IV t-PA treatment at a tertiary care hospital and primary stroke center from January 2008 through December 2011 were reviewed. Stroke mimics were determined by review of clinical and imaging findings. Stroke mimics are described and compared with acute ischemic stroke patients for demographics, clinical characteristics, and bleeding complications. Results: We identified 38 stroke mimic (12%) and 285 ischemic stroke (88%) t-PA– treated patients. Compared with ischemic stroke patients, mimic patients were younger, more often female, and reported a history of stroke more often. There were no differences in race, baseline stroke scale, or onset to treatment time. There were no intracerebral hemorrhages or deaths in the mimic patients but there were 2 systemic hemorrhages (5.2%). Conclusions: Treatment of mimic patients with IV t-PA appears to be safe in this cohort. Concern for intracerebral hemorrhage in mimic patients need not dissuade clinicians from administering t-PA when significant concern for ischemic etiology exists. Key Words: Stroke—stroke mimics— tissue plasminogen activator—image negative stroke. Ó 2015 by National Stroke Association
Introduction In 1996, the Food and Drug Administration approved intravenous (IV) tissue plasminogen activator (t-PA) for the treatment of acute ischemic stroke. Although thromFrom the *Department of Emergency Medicine, Henry Ford Hospital, Detroit, Michigan; †Department of Emergency Medicine, Beaumont Hospital, Royal Oak, Michigan; and ‡Department of Neurology, Henry Ford Hospital, Detroit, Michigan. Received April 3, 2014; revision received June 17, 2014; accepted July 27, 2014. Address correspondence to Joseph Miller, MD, Department of Emergency Medicine, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48198. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2015 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.07.048
48
bolysis for acute ischemic stroke has been shown to improve functional outcomes, it comes with an increased risk of intracerebral hemorrhage.1 Emergency physicians are reluctant to use t-PA for stroke because of this risk.2 However, the mortality rate with IV t-PA is not increased, indicating that stroke, left untreated, is a severe disease and carries a similar mortality with much greater morbidity.1 There is consensus among stroke experts to treat patients who present to the emergency department (ED) with signs and symptoms of stroke as a medical emergency, and national guidelines call for a door-to-needle time of less than 60 minutes.3 Emergent treatment decisions are usually made by clinicians based on history, examination, and limited neuroimaging. Occasionally, patients present to the ED with neurologic deficits that
Journal of Stroke and Cerebrovascular Diseases, Vol. 24, No. 1 (January), 2015: pp 48-52
SAFETY OF IV T-PA IN STROKE MIMICS
impersonate acute ischemic stroke but ultimately are found to have an alternative etiology. These conditions are termed stroke mimics. Additionally, patients with ischemic stroke syndromes may not demonstrate an acute ischemic stroke on advanced imaging. These patients have been termed imaging-negative acute cerebral ischemia.4 Because a rapid decision needs to be made about treatment, it is inevitable that some patients with stroke mimics will receive IV thrombolysis. The expansion of the time window for administering IV t-PA to 4.5 hours may also lead to an increase in the number of stroke mimics who inadvertently are exposed to potential hemorrhagic complications of IV t-PA without the possibility of benefit. The objective of this study is to provide safety data regarding the administration of IV t-PA to patients with suspected stroke who are ultimately diagnosed with a stroke mimic. In addition, this study compares clinical characteristics of t-PA–treated ischemic stroke patients versus stroke mimic patients.
Methods This is a single-center cohort study of patients who presented to the ED with an initial diagnosis of stroke and were treated with IV t-PA within 4.5 hours from symptom onset. The initial diagnosis of stroke was based on patient presentation, neurologic findings, and results of head computed tomography. Patients were identified from a prospectively collected stroke database from January 2008 to December 2011. Investigators reviewed the subject’s hospital course to establish a final discharge diagnosis. Patients who received t-PA and had positive imaging were considered to have had an acute ischemic stroke. Patients who received t-PA but had a discharge diagnosis other than stroke with negative neuroimaging were considered stroke mimics. Patient records were analyzed for frequency of intracerebral and systemic hemorrhagic complications. All charts and neuroimaging were reviewed by 2 board certified stroke expert physicians and 2 stroke nurses for accuracy. All t-PA associated intracerebral hemorrhages from the study period were reviewed by the study team to determine association with acute ischemic stroke or stroke mimic. All patients were treated under the supervision of an on-call acute stroke team in conjunction with treating emergency physicians. The stroke team consists of vascular neurologists and emergency physicians with expertise in stroke that cover 7 EDs with approximately 330,000 annual visits. All patients treated with t-PA were transferred to the tertiary care hospital, a 750-bed, an urban teaching institution, and a Joint Commission Certified Stroke Center. This research was approved by the institutional review board Comparisons between the acute ischemic stroke and stroke mimics groups were done using SAS 9.3 (SAS,
49
Cary, NC). Comparisons included demographic factors, stroke risk factors, admission blood pressure, National Institute of Health Stroke Scale (NIHSS) score on admission and discharge, and intracerebral and systemic hemorrhagic complications. Statistical methods included t tests for continuous variables and the Fisher exact test or chi-square analysis for categorical variables. The significance value was set at .05.
Results Over the study period, 323 patients were treated with IV t-PA for presumed acute ischemic stroke. Of the 323 patients treated, 38 (11.76%) were confirmed to be a stroke mimic, and the remainder were diagnosed with acute ischemic stroke by positive neuroimaging. All patients received a 24 hours post-treatment computed tomography scan. Magnetic resonance imaging of the brain was completed in all stroke mimic cases, and all were confirmed to be negative for evidence of acute ischemia. In the acute ischemic stroke group (n 5 285), the average age was 67 6 15 years, 49% were female, 52% were African-Americans, and median admission NIHSS score was 9 (range, 1-36). In the stroke mimic group (n 5 38), the average age was 55.1 6 19 years, 68% were female, 53% were African-Americans, and median admission NIHSS score was 8 (range, 1-25). Twelve stroke mimic cases were in the 3-4.5 hours treatment window. Presenting neurologic symptoms of the stroke mimic cohort primarily included unilateral weakness (68%) and aphasia (7.8%). Few presented with isolated numbness (5.2%). Baseline characteristics differed in that stroke mimic patients were younger, more likely female and had lower rates of atrial fibrillation (Table 1). In addition, mimic patients had higher proportions of hyperlipidemia, smoking, and prior stroke. Although mean blood glucose measurements were lower in the stroke mimic group, there were no documented episodes of hypoglycemia. Additional past medical history for the stroke mimic group included a history of migraine (n 5 7, 17.9%), seizure disorder (n 5 8, 20.5%), fibromyalgia (n 5 3, 7.7%), irritable bowel syndrome (n 5 3, 7.7%), and psychiatric conditions (n 5 10, 25.6%), which included anxiety, depression, post-traumatic stress disorder, and bipolar disorder. The 3 most common stroke mimic discharge diagnoses were conversion disorder (n 5 17, 47%), seizure (n 5 12, 32%), and migraine (n 5 3, 8%). Other mimic etiologies, each with 1 patient, included meningitis, syncope, drug withdrawal, hypertensive encephalopathy, spinal cord compression, and benign paroxysmal positional vertigo (Table 2). Of the 18 patients diagnosed with conversion disorder, 9 (50%) had a documented history of psychiatric conditions or fibromyalgia. Weakness was localized to the left arm and leg in 11 (84.6%) of the conversion disorder patients
C. LEWANDOWSKI ET AL.
50
Table 1. Demographic and clinical features of patients with ischemic stroke and mimics Characteristics
Stroke mimics, N 5 38
Confirmed stroke, N 5 285
P value
Age, mean 6 SD Female, n (%) Race, n (%) White Black Other Past medical history, n (%) Hypertension Diabetes Atrial fibrillation Coronary artery disease Prior stroke Hypercholesterolemia Tobacco use Presenting systolic BP, mean 6 SD Presenting diastolic BP, mean 6 SD Presenting glucose,* mean 6 SD Time to IV t-PA, mean 6 SD, min NIHSS score admission, mean 6 SD NIHSS score discharge, mean 6 SD Complications, n (%) None Symptomatic ICH Systemic hemorrhage
55.1 6 19.1 26 (68)
67.0 6 14.8 140 (49)
,.001 .025
15 (39) 20 (53) 3 (8)
120 (42) 148 (52) 17 (6)
24 (63) 7 (18) 2 (5) 6 (16) 17 (45) 16 (42) 14 (37) 152.5 6 31.2 85.6 6 17.0 117.4 6 36.2 163.9 6 53.3 9.5 6 6.7 1.3 6 2.5
206 (72) 81 (28) 56 (20) 65 (23) 40 (14) 74 (26) 55 (19) 159.7 6 31.5 84.9 6 21.7 139.3 6 87.2 158.9 6 59.3 10.9 6 7.4 4.6 6 5.7
.243 .193 .030 .326 ,.001 .037 .013 .188 .852 .006 .626 .257 ,.001
36 (95) 0 (0) 2 (5)
264 (93) 19 (7) 2 (1)
.75 .14 .07
.878
Abbreviations: BP, blood pressure; ICH, intracerebral hemorrhage; IV t-PA, intravenous tissue plasminogen activator; NIHSS, National Institute of Health Stroke Scale; SD, standard deviation. *No hypoglycemic events in mimic cohort.
that had unilateral weakness (n 5 13) at presentation. One of the patients with right hemiparesis was believed to have a nonphysiologic exaggeration of a minor residual deficit from a prior stroke, and the other patient had a history of right rotator cuff tendinopathy, right elbow injury, and a motor vehicle accident with fracture of the right fibula and, which was believed to be the reason for the lateralization of the patients deficits to the right. All cases of symptomatic intracerebral hemorrhage occurred in the acute ischemic stroke group at a rate of 7%. No intracerebral hemorrhages occurred in the stroke
Table 2. Diagnoses of patients with stroke mimics Stroke mimic etiologies
Percentage (n)
Conversion disorder Seizure/Todd paralysis Migraine Meningitis Syncope Drug withdrawal Hypertensive encephalopathy Spinal cord compression Benign paroxysmal positional vertigo
44.7 (17) 31.6 (12) 8 (3) 2.6 (1) 2.6 (1) 2.6 (1) 2.6 (1) 2.6 (1) 2.6 (1)
mimic group. The 95% confidence interval around the point estimate for the incidence of intracerebral hemorrhage in stroke mimic patients receiving t-PA was 0%-7.9%. Major systemic hemorrhages occurred in 2 patients in each group (5% mimics group vs. 1% confirmed stroke group, P 5 .07). In the mimic group, 1 patient was treated with IV t-PA 8 hours after cardiac catheterization and developed severe bleeding at the catheterization site requiring transfusion but no long-term sequelae. The other patient developed coffee ground emesis and was intubated for airway protection. This patient did not require transfusion and was extubated the next day. Despite the lack of significant differences in presenting blood pressure, symptom onset, time to treatment, or NIHSS scores, thrombolysis-related complications were more likely in the acute ischemic stroke group (P 5 .017). In the acute ischemic stroke group, 44.2% of patients were discharged to home, 29.5% to inpatient rehabilitation, 12.3% to a skilled nursing facility, and 12.3% expired or were enrolled in hospice. In the stroke mimic group, 84.2% of patients were discharged to home, 13.1% to inpatient rehabilitation, 2.6% to a skilled nursing facility, and none were enrolled into hospice or died. Admission NIHSS scores were not significantly different between groups (9.5 6 6.7 for mimics, 10.9 6 7.4 for
SAFETY OF IV T-PA IN STROKE MIMICS
acute ischemic stroke, P 5 .257); however, discharge NIHSS scores were significantly better in the stroke mimic group (1.3 6 2.5 vs. 4.6 6 5.7 for acute ischemic stroke, P , .001).
Discussion The time-sensitive management of acute stroke limits the diagnostic testing that can be accomplished before the initiation of treatment. These results provide additional data and reassurance to the clinician concerned with diagnostic uncertainty in the management of suspected ischemic stroke patients. Within our registry of 323 consecutive patients treated with IV t-PA for suspected acute ischemic stroke, we identified 11.8% as stroke mimics. This incidence is in the higher range relative to similar published data sets, a finding that could be accounted for by the demographics of the patient population or by the system of care.5-9 Emergency physicians made primary treatment decisions with telephone support by a member of a stroke team (consisting of stroke neurologists and emergency physicians with stroke expertise). A larger multicenter study based in Europe, in which stroke neurologists primarily evaluated patients for t-PA administration, had a stroke mimic frequency of 1.8%.9 Despite the relatively higher rate of stroke mimics in our cohort, no patients had an intracerebral hemorrhage as a complication of thrombolysis. In comparison, 7% of patients in our ischemic stroke cohort that received thrombolytics had intracerebral hemorrhage. The true incidence of intracerebral hemorrhage in mimic patients may fall near estimates from the cardiology literature, in which the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) investigators demonstrated a .72% rate of hemorrhagic stroke in its t-PA arm (10,268 subjects), albeit with small differences in the dosing of t-PA and the addition of heparin administration.10 We report systemic hemorrhage rates, which have largely been left out in prior publications of stroke mimic patients receiving t-PA. One stroke mimic patient experienced systemic hemorrhage requiring a blood transfusion, which occurred at the site of femoral artery access for cardiac catheterization and was potentially avoidable. The second patient in our data set had gastric bleeding that resulted in mechanical ventilation for airway support but no long-term adverse effects. The rate of systemic bleeding in this stroke mimic study is consistent with that reported with the administration of t-PA or streptokinase for acute myocardial infarction.9 Similar to previous reports, the most common diagnoses among our stroke mimic cohort were epilepsy, conversion disorder (psychogenic), and migraine aura. Mimics were younger and more likely to be female. Although the median presenting NIHSS score of the
51
mimic cohort in our study was comparable to that of the ischemic stroke cohort, published studies have largely shown lower presenting NIHSS scores among stroke mimics. The largest data set of stroke mimics receiving t-PA showed mimics to have a median NIHSS score of 6 on presentation versus 11 in ischemic stroke patients.9 The mimics cohort in our study had similar to higher rates of vascular risk factors than the stroke cohort. This finding is likely because of inherent selection bias of the mimic cohort. Treating physicians excluded many patients with stroke mimic syndromes from receiving t-PA, and these excluded patients likely had lower cardiovascular risk factors. There a several limitations to this single-center study. Bias could be introduced in our study as members of the on-call stroke team have performed this analysis; an independent review team may have strengthened the study. Thrombolytic administration in our study was primarily given by emergency physicians in phone consultation with a stroke team physician at an academic teaching hospital or an affiliated community hospital. Whether the results can be generalized to different treatment settings is unknown. Additionally, the diagnosis of imagenegative stroke or averted stroke can be challenging and is difficult to account for in our study. Whether some stroke mimics from the pooled data fall into this group is unknown.
Conclusions This study adds to the existing literature regarding the outcomes of stroke mimic patients receiving IV t-PA. Common etiologies of mimics include conversion disorder, seizure, and migraine. In the complex decision making process of treating acute stroke, concern for mimics is not reason enough to withhold t-PA.
References 1. NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333:1581-1587. 2. Chaturvedi S, Bertasio B, Femino L. Emergency physician attitudes toward thrombolytic therapy in acute stroke. J Stroke Cerebrovasc Dis 1998;7:442-445. 3. Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:870-947. 4. Oppenheim C, Stanescu R, Dormont D, et al. False-negative diffusion-weighted MR findings in acute ischemic stroke. Am J Neuroradiol 2000;21:1434-1440. 5. Chernyshev OY, Martin-Schild S, Albright KC, et al. Safety of tPA in stroke mimics and neuroimagingnegative cerebral ischemia. Neurology 2010;74:1340-1345. 6. Scott PA, Silbergleit R. Misdiagnosis of stroke in tissue plasminogen activator-treated patients: characteristics and outcomes. Ann Emerg Med 2003; 42:611-618.
52 7. Artto V, Putaala J, Strbian D, et al. Stroke mimics and intravenous thrombolysis. Ann Emerg Med 2012; 59:27-32. 8. Tsivgoulis G, Alexandrov AV, Chang J, et al. Safety and outcomes of intravenous thrombolysis in stroke mimics: a 6-year, single-care center study and a pooled analysis of reported series. Stroke 2011;42:1771-1774.
C. LEWANDOWSKI ET AL. 9. Zinkstok SM, Engelter ST, Gensicke H, et al. Safety of thrombolysis in stroke mimics: results from a multicenter cohort study. Stroke 2013;44:1080-1084. 10. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO Investigators. N Engl J Med 1993;329: 673-682.
Background: Patients with symptoms that impersonate a stroke but are later found to have an alternate diagnosis are termed stroke mimics. Stroke mimics treated with intravenous (IV) tissue plasminogen activator (t-PA) are exposed to hemorrhagic complications without benefit. The objective of this study is to describe the characteristics, safety, and outcomes of stroke mimic patients treated with t-PA within 4.5 hours. Methods: All patients hospitalized after IV t-PA treatment at a tertiary care hospital and primary stroke center from January 2008 through December 2011 were reviewed. Stroke mimics were determined by review of clinical and imaging findings. Stroke mimics are described and compared with acute ischemic stroke patients for demographics, clinical characteristics, and bleeding complications. Results: We identified 38 stroke mimic (12%) and 285 ischemic stroke (88%) t-PA– treated patients. Compared with ischemic stroke patients, mimic patients were younger, more often female, and reported a history of stroke more often. There were no differences in race, baseline stroke scale, or onset to treatment time. There were no intracerebral hemorrhages or deaths in the mimic patients but there were 2 systemic hemorrhages (5.2%). Conclusions: Treatment of mimic patients with IV t-PA appears to be safe in this cohort. Concern for intracerebral hemorrhage in mimic patients need not dissuade clinicians from administering t-PA when significant concern for ischemic etiology exists. Key Words: Stroke—stroke mimics— tissue plasminogen activator—image negative stroke. Ó 2015 by National Stroke Association
Introduction In 1996, the Food and Drug Administration approved intravenous (IV) tissue plasminogen activator (t-PA) for the treatment of acute ischemic stroke. Although thromFrom the *Department of Emergency Medicine, Henry Ford Hospital, Detroit, Michigan; †Department of Emergency Medicine, Beaumont Hospital, Royal Oak, Michigan; and ‡Department of Neurology, Henry Ford Hospital, Detroit, Michigan. Received April 3, 2014; revision received June 17, 2014; accepted July 27, 2014. Address correspondence to Joseph Miller, MD, Department of Emergency Medicine, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48198. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2015 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.07.048
48
bolysis for acute ischemic stroke has been shown to improve functional outcomes, it comes with an increased risk of intracerebral hemorrhage.1 Emergency physicians are reluctant to use t-PA for stroke because of this risk.2 However, the mortality rate with IV t-PA is not increased, indicating that stroke, left untreated, is a severe disease and carries a similar mortality with much greater morbidity.1 There is consensus among stroke experts to treat patients who present to the emergency department (ED) with signs and symptoms of stroke as a medical emergency, and national guidelines call for a door-to-needle time of less than 60 minutes.3 Emergent treatment decisions are usually made by clinicians based on history, examination, and limited neuroimaging. Occasionally, patients present to the ED with neurologic deficits that
Journal of Stroke and Cerebrovascular Diseases, Vol. 24, No. 1 (January), 2015: pp 48-52
SAFETY OF IV T-PA IN STROKE MIMICS
impersonate acute ischemic stroke but ultimately are found to have an alternative etiology. These conditions are termed stroke mimics. Additionally, patients with ischemic stroke syndromes may not demonstrate an acute ischemic stroke on advanced imaging. These patients have been termed imaging-negative acute cerebral ischemia.4 Because a rapid decision needs to be made about treatment, it is inevitable that some patients with stroke mimics will receive IV thrombolysis. The expansion of the time window for administering IV t-PA to 4.5 hours may also lead to an increase in the number of stroke mimics who inadvertently are exposed to potential hemorrhagic complications of IV t-PA without the possibility of benefit. The objective of this study is to provide safety data regarding the administration of IV t-PA to patients with suspected stroke who are ultimately diagnosed with a stroke mimic. In addition, this study compares clinical characteristics of t-PA–treated ischemic stroke patients versus stroke mimic patients.
Methods This is a single-center cohort study of patients who presented to the ED with an initial diagnosis of stroke and were treated with IV t-PA within 4.5 hours from symptom onset. The initial diagnosis of stroke was based on patient presentation, neurologic findings, and results of head computed tomography. Patients were identified from a prospectively collected stroke database from January 2008 to December 2011. Investigators reviewed the subject’s hospital course to establish a final discharge diagnosis. Patients who received t-PA and had positive imaging were considered to have had an acute ischemic stroke. Patients who received t-PA but had a discharge diagnosis other than stroke with negative neuroimaging were considered stroke mimics. Patient records were analyzed for frequency of intracerebral and systemic hemorrhagic complications. All charts and neuroimaging were reviewed by 2 board certified stroke expert physicians and 2 stroke nurses for accuracy. All t-PA associated intracerebral hemorrhages from the study period were reviewed by the study team to determine association with acute ischemic stroke or stroke mimic. All patients were treated under the supervision of an on-call acute stroke team in conjunction with treating emergency physicians. The stroke team consists of vascular neurologists and emergency physicians with expertise in stroke that cover 7 EDs with approximately 330,000 annual visits. All patients treated with t-PA were transferred to the tertiary care hospital, a 750-bed, an urban teaching institution, and a Joint Commission Certified Stroke Center. This research was approved by the institutional review board Comparisons between the acute ischemic stroke and stroke mimics groups were done using SAS 9.3 (SAS,
49
Cary, NC). Comparisons included demographic factors, stroke risk factors, admission blood pressure, National Institute of Health Stroke Scale (NIHSS) score on admission and discharge, and intracerebral and systemic hemorrhagic complications. Statistical methods included t tests for continuous variables and the Fisher exact test or chi-square analysis for categorical variables. The significance value was set at .05.
Results Over the study period, 323 patients were treated with IV t-PA for presumed acute ischemic stroke. Of the 323 patients treated, 38 (11.76%) were confirmed to be a stroke mimic, and the remainder were diagnosed with acute ischemic stroke by positive neuroimaging. All patients received a 24 hours post-treatment computed tomography scan. Magnetic resonance imaging of the brain was completed in all stroke mimic cases, and all were confirmed to be negative for evidence of acute ischemia. In the acute ischemic stroke group (n 5 285), the average age was 67 6 15 years, 49% were female, 52% were African-Americans, and median admission NIHSS score was 9 (range, 1-36). In the stroke mimic group (n 5 38), the average age was 55.1 6 19 years, 68% were female, 53% were African-Americans, and median admission NIHSS score was 8 (range, 1-25). Twelve stroke mimic cases were in the 3-4.5 hours treatment window. Presenting neurologic symptoms of the stroke mimic cohort primarily included unilateral weakness (68%) and aphasia (7.8%). Few presented with isolated numbness (5.2%). Baseline characteristics differed in that stroke mimic patients were younger, more likely female and had lower rates of atrial fibrillation (Table 1). In addition, mimic patients had higher proportions of hyperlipidemia, smoking, and prior stroke. Although mean blood glucose measurements were lower in the stroke mimic group, there were no documented episodes of hypoglycemia. Additional past medical history for the stroke mimic group included a history of migraine (n 5 7, 17.9%), seizure disorder (n 5 8, 20.5%), fibromyalgia (n 5 3, 7.7%), irritable bowel syndrome (n 5 3, 7.7%), and psychiatric conditions (n 5 10, 25.6%), which included anxiety, depression, post-traumatic stress disorder, and bipolar disorder. The 3 most common stroke mimic discharge diagnoses were conversion disorder (n 5 17, 47%), seizure (n 5 12, 32%), and migraine (n 5 3, 8%). Other mimic etiologies, each with 1 patient, included meningitis, syncope, drug withdrawal, hypertensive encephalopathy, spinal cord compression, and benign paroxysmal positional vertigo (Table 2). Of the 18 patients diagnosed with conversion disorder, 9 (50%) had a documented history of psychiatric conditions or fibromyalgia. Weakness was localized to the left arm and leg in 11 (84.6%) of the conversion disorder patients
C. LEWANDOWSKI ET AL.
50
Table 1. Demographic and clinical features of patients with ischemic stroke and mimics Characteristics
Stroke mimics, N 5 38
Confirmed stroke, N 5 285
P value
Age, mean 6 SD Female, n (%) Race, n (%) White Black Other Past medical history, n (%) Hypertension Diabetes Atrial fibrillation Coronary artery disease Prior stroke Hypercholesterolemia Tobacco use Presenting systolic BP, mean 6 SD Presenting diastolic BP, mean 6 SD Presenting glucose,* mean 6 SD Time to IV t-PA, mean 6 SD, min NIHSS score admission, mean 6 SD NIHSS score discharge, mean 6 SD Complications, n (%) None Symptomatic ICH Systemic hemorrhage
55.1 6 19.1 26 (68)
67.0 6 14.8 140 (49)
,.001 .025
15 (39) 20 (53) 3 (8)
120 (42) 148 (52) 17 (6)
24 (63) 7 (18) 2 (5) 6 (16) 17 (45) 16 (42) 14 (37) 152.5 6 31.2 85.6 6 17.0 117.4 6 36.2 163.9 6 53.3 9.5 6 6.7 1.3 6 2.5
206 (72) 81 (28) 56 (20) 65 (23) 40 (14) 74 (26) 55 (19) 159.7 6 31.5 84.9 6 21.7 139.3 6 87.2 158.9 6 59.3 10.9 6 7.4 4.6 6 5.7
.243 .193 .030 .326 ,.001 .037 .013 .188 .852 .006 .626 .257 ,.001
36 (95) 0 (0) 2 (5)
264 (93) 19 (7) 2 (1)
.75 .14 .07
.878
Abbreviations: BP, blood pressure; ICH, intracerebral hemorrhage; IV t-PA, intravenous tissue plasminogen activator; NIHSS, National Institute of Health Stroke Scale; SD, standard deviation. *No hypoglycemic events in mimic cohort.
that had unilateral weakness (n 5 13) at presentation. One of the patients with right hemiparesis was believed to have a nonphysiologic exaggeration of a minor residual deficit from a prior stroke, and the other patient had a history of right rotator cuff tendinopathy, right elbow injury, and a motor vehicle accident with fracture of the right fibula and, which was believed to be the reason for the lateralization of the patients deficits to the right. All cases of symptomatic intracerebral hemorrhage occurred in the acute ischemic stroke group at a rate of 7%. No intracerebral hemorrhages occurred in the stroke
Table 2. Diagnoses of patients with stroke mimics Stroke mimic etiologies
Percentage (n)
Conversion disorder Seizure/Todd paralysis Migraine Meningitis Syncope Drug withdrawal Hypertensive encephalopathy Spinal cord compression Benign paroxysmal positional vertigo
44.7 (17) 31.6 (12) 8 (3) 2.6 (1) 2.6 (1) 2.6 (1) 2.6 (1) 2.6 (1) 2.6 (1)
mimic group. The 95% confidence interval around the point estimate for the incidence of intracerebral hemorrhage in stroke mimic patients receiving t-PA was 0%-7.9%. Major systemic hemorrhages occurred in 2 patients in each group (5% mimics group vs. 1% confirmed stroke group, P 5 .07). In the mimic group, 1 patient was treated with IV t-PA 8 hours after cardiac catheterization and developed severe bleeding at the catheterization site requiring transfusion but no long-term sequelae. The other patient developed coffee ground emesis and was intubated for airway protection. This patient did not require transfusion and was extubated the next day. Despite the lack of significant differences in presenting blood pressure, symptom onset, time to treatment, or NIHSS scores, thrombolysis-related complications were more likely in the acute ischemic stroke group (P 5 .017). In the acute ischemic stroke group, 44.2% of patients were discharged to home, 29.5% to inpatient rehabilitation, 12.3% to a skilled nursing facility, and 12.3% expired or were enrolled in hospice. In the stroke mimic group, 84.2% of patients were discharged to home, 13.1% to inpatient rehabilitation, 2.6% to a skilled nursing facility, and none were enrolled into hospice or died. Admission NIHSS scores were not significantly different between groups (9.5 6 6.7 for mimics, 10.9 6 7.4 for
SAFETY OF IV T-PA IN STROKE MIMICS
acute ischemic stroke, P 5 .257); however, discharge NIHSS scores were significantly better in the stroke mimic group (1.3 6 2.5 vs. 4.6 6 5.7 for acute ischemic stroke, P , .001).
Discussion The time-sensitive management of acute stroke limits the diagnostic testing that can be accomplished before the initiation of treatment. These results provide additional data and reassurance to the clinician concerned with diagnostic uncertainty in the management of suspected ischemic stroke patients. Within our registry of 323 consecutive patients treated with IV t-PA for suspected acute ischemic stroke, we identified 11.8% as stroke mimics. This incidence is in the higher range relative to similar published data sets, a finding that could be accounted for by the demographics of the patient population or by the system of care.5-9 Emergency physicians made primary treatment decisions with telephone support by a member of a stroke team (consisting of stroke neurologists and emergency physicians with stroke expertise). A larger multicenter study based in Europe, in which stroke neurologists primarily evaluated patients for t-PA administration, had a stroke mimic frequency of 1.8%.9 Despite the relatively higher rate of stroke mimics in our cohort, no patients had an intracerebral hemorrhage as a complication of thrombolysis. In comparison, 7% of patients in our ischemic stroke cohort that received thrombolytics had intracerebral hemorrhage. The true incidence of intracerebral hemorrhage in mimic patients may fall near estimates from the cardiology literature, in which the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) investigators demonstrated a .72% rate of hemorrhagic stroke in its t-PA arm (10,268 subjects), albeit with small differences in the dosing of t-PA and the addition of heparin administration.10 We report systemic hemorrhage rates, which have largely been left out in prior publications of stroke mimic patients receiving t-PA. One stroke mimic patient experienced systemic hemorrhage requiring a blood transfusion, which occurred at the site of femoral artery access for cardiac catheterization and was potentially avoidable. The second patient in our data set had gastric bleeding that resulted in mechanical ventilation for airway support but no long-term adverse effects. The rate of systemic bleeding in this stroke mimic study is consistent with that reported with the administration of t-PA or streptokinase for acute myocardial infarction.9 Similar to previous reports, the most common diagnoses among our stroke mimic cohort were epilepsy, conversion disorder (psychogenic), and migraine aura. Mimics were younger and more likely to be female. Although the median presenting NIHSS score of the
51
mimic cohort in our study was comparable to that of the ischemic stroke cohort, published studies have largely shown lower presenting NIHSS scores among stroke mimics. The largest data set of stroke mimics receiving t-PA showed mimics to have a median NIHSS score of 6 on presentation versus 11 in ischemic stroke patients.9 The mimics cohort in our study had similar to higher rates of vascular risk factors than the stroke cohort. This finding is likely because of inherent selection bias of the mimic cohort. Treating physicians excluded many patients with stroke mimic syndromes from receiving t-PA, and these excluded patients likely had lower cardiovascular risk factors. There a several limitations to this single-center study. Bias could be introduced in our study as members of the on-call stroke team have performed this analysis; an independent review team may have strengthened the study. Thrombolytic administration in our study was primarily given by emergency physicians in phone consultation with a stroke team physician at an academic teaching hospital or an affiliated community hospital. Whether the results can be generalized to different treatment settings is unknown. Additionally, the diagnosis of imagenegative stroke or averted stroke can be challenging and is difficult to account for in our study. Whether some stroke mimics from the pooled data fall into this group is unknown.
Conclusions This study adds to the existing literature regarding the outcomes of stroke mimic patients receiving IV t-PA. Common etiologies of mimics include conversion disorder, seizure, and migraine. In the complex decision making process of treating acute stroke, concern for mimics is not reason enough to withhold t-PA.
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