- Email: [email protected]
Factors Associated With Misdiagnosis of Acute Stroke in Young Adults
Factors Associated With Misdiagnosis of Acute Stroke in Young Adults Abraham Kuruvilla, MD, Pratik Bhattacharya, MD, Kumar Rajamani, MD, and Seemant Chaturvedi, MD, FAHA, FAAN
Misdiagnosis or delayed diagnosis of acute ischemic stroke can result in neurologic worsening or a missed opportunity for thrombolysis. Because stroke in young adults is less common than stroke in the elderly, we sought to determine clinical characteristics associated with misdiagnosis of stroke in young adults. Patients from the prospectively maintained Young Stroke Registry in our comprehensive stroke center were reviewed. Demographic information, past medical history, presentation within the 3-hour time window, and outcomes were assessed. We compared patients misdiagnosed and those correctly diagnosed to identify factors associated with misdiagnosis of acute stroke. A total of 57 patients aged 16-50 were enrolled in the registry during 2001-2006. Eight patients (14%; 4 men and 4 women; mean age, 38 years) were misdiagnosed. Seven of these 8 patients were discharged from the emergency department initially. Patients age ,35 years (P 5 .05) and patients with posterior circulation stroke (P 5 .006) were more likely to be misdiagnosed. All 8 misdiagnosed patients were initially evaluated at hospitals that were not certified primary stroke centers. Patients presenting with vertebrobasilar territory ischemia have a greater rate of misdiagnosis. Our study demonstrates the increasing need for ‘‘young stroke awareness’’ among emergency department personnel. Initial misdiagnosis can potentially lead to a lost opportunity for thrombolysis in otherwise good candidates. Key Words: Cerebral infarction—diagnosis—thrombolysis. Ó 2011 by National Stroke Association
Stroke is a leading cause of disability among adults, and remains the only neurologic disorder for which physicians are potentially able to completely reverse the deficits.1 Each year, nearly 800,000 people in the United States experience a new or recurrent stroke; more than 600,000 of these are first attacks, and nearly 200,000 are From the Department of Neurology and Stroke Program, Wayne State University/Detroit Medical Center, Detroit, Michigan. Received January 6, 2010; accepted March 9, 2010. The authors have no conflict of interest. Presented at the 2009 International Stroke Conference (American Stroke Association), San Diego, 2009, Feb 18-20. Address correspondence to Seemant Chaturvedi, MD, FAHA, FAAN, Stroke Program and Department of Neurology, Wayne State University, 8C-UHC, 4201 St. Antoine, Detroit, MI 48201. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2011 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2010.03.005
recurrent stroke.2 If given early enough after onset of symptoms, thrombolytic therapy can restore neurologic function in patients with acute ischemic stroke.1,3 Because stroke is less common in young adults than in older individuals, there is considerable potential for neurologic symptoms in young adults to be attributed to other causes. Furthermore, the etiologies of stroke are different in young adults and less commonly involve the typical causes in older adults, such as atherosclerosis, embolism from atrial fibrillation, and lacunar stroke due to long-standing small vessel vasculopathy. Ischemic stroke in young adults is more often due to such conditions as arterial dissection, vasculopathies, and cardiogenic sources, such as patent foramen ovale.4 Here we highlight a series of cases in which an initial diagnosis other than stroke was made in young adults who ultimately had a final diagnosis of ischemic stroke. We also explore clinical characteristics associated with
Journal of Stroke and Cerebrovascular Diseases, Vol. 20, No. 6 (November-December), 2011: pp 523-527
523
A. KURUVILLA ET AL.
524
Table 1. Clinical characteristics
Age, years, mean (SD) Male sex, n (%) Black race, n (%) Hypertension, n (%) Diabetes, n (%) Coronary artery disease, n (%) Active smoker, n (%) Past smoker, n (%) Hyperlipidemia, n (%) Migraine, n (%)
Misdiagnosed (n 5 8)
Correctly diagnosed (n 5 49)
P value
34.3 (11.2) 4 (50%) 2 (25%) 2 (25%) 1 (12.5%) 0 (0) 0 (0) 0 (0) 3 (37.5%) 1 (12.5%)
38.7 (8.0) 19 (38.7%) 14 (28.6%) 15 (30.6%) 4 (8.2%) 5 (10.2%) 11 (22.4%) 12 (24.5%) 11 (22.4%) 7 (14.3%)
.18 .83 .73 1.00 .54 1.00 .33 .18 .39 1.00
misdiagnosis of stroke in young adults. To the best of our knowledge, an analysis of factors associated with misdiagnosis of stroke in young adults has not been reported previously.
Methods Study Design/Setting/Patient Selection The Young Stroke Registry maintained since 2001 at our comprehensive stroke center is a prospective registry of patients aged 16-50 years who were seen in the outpatient stroke clinic of a university medical center. Both patients seen at our primary hospital and patients referred to our outpatient stroke clinic from other hospitals were included in the registry. Our primary hospital is located in a metropolitan area with 4 million residents. Patients referred from other hospitals were sent by outside physicians for additional advice regarding diagnosis or treatment. Patients with stroke due to substance abuse and those with no fixed residence were excluded from the registry because of the difficulty of follow-up in these patients. Patients were confirmed as having a diagnosis of ischemic stroke by vascular neurologists using clinical and neuroimaging findings, and were included regardless of initial diagnosis in the emergency department (ED). Demographic information was obtained, past medical history was recorded, and causative factors associated with stroke in younger adults (ie, vascular dissection) were investigated. Clinical data, including presenting symptoms, ED discharge diagnosis, and subsequent stroke diagnosis, were collected from the original source documents. Whether or not the hospital where the patient initially sought medical care at the onset of stroke symptoms was certified as a primary stroke center, according to the Joint Commission criteria (as of July 2008, the time of data analysis), was noted. In terms of vascular risk factors, the specific variables recorded during history-taking were hypertension, diabetes, hyperlipidemia, smoking, and history of coronary artery bypass graft surgery/stent insertion. Hypertension was considered present if the patient was taking an
antihypertensive medication or had a systolic blood pressure .140 mm Hg or a diastolic blood pressure .90 mm measured on at least 2 occasions. Diabetes was considered present if the patient was taking medication for diabetes or had a fasting blood glucose level .126 mg/dL. Hyperlipidemia was present if the patient was taking a lipid-lowering medication and had a fasting total cholesterol level .200 mg/dL and/or a low-density lipoprotein (LDL) cholesterol level .100 mg/dL.
Primary Data Analysis Because this study focused on misdiagnosis of acute stroke in young adults, we restricted our analysis to the subset of patients who were given an initial nonstroke diagnosis. Patients were categorized as misdiagnosed if they were given a nonstroke diagnosis and either admitted to the hospital or discharged from the ED. Clinical variables and their relationship to misdiagnosis were tested as univariate factors using the c2 test and Fisher’s exact test. The study design was approved by the university’s Institutional Review Board.
Results A total of 57 patients (34 women [59.6%]; mean age, 38.1 years) were enrolled in our stroke registry. In this cohort, 29.8% had hypertension, 8.8% had diabetes, 8.8% had coronary artery disease, and 40.4% were either active or former smokers. Hyperlipidemia was present in 24.6% of patients, and 14% had a history of migraine. Table 1 summarizes demographic data and risk factor information. Eight patients (14%), including 4 men and 4 women (mean age, 38.1 years) were misdiagnosed in the ED. An illustrative case is patient 8, a 35-year-old woman who collapsed at work. On arrival at a local community hospital within 1 hour of symptom onset, she had speech difficulty and right-sided weakness. She had no history of seizures and no documented seizure activity. She was diagnosed with possible postictal state and admitted to the hospital. She was examined by a neurologist the next day, and brain magnetic resonance imaging (MRI)
MISDIAGNOSIS OF ACUTE STROKE IN YOUNG ADULTS
Figure 1. Diffusion-weighted MRI of patient 8 showing large left MCA territory stroke.
revealed a large infarction in the left middle cerebral artery (MCA) territory (Fig 1). Table 2 gives the initial presenting symptoms, ED discharge diagnosis, and subsequent stroke diagnosis of
525
the 8 patients who were misdiagnosed in the ED. Altogether, 4 patients were discharged from the ED with a diagnosis of peripheral vertigo, 1 patient was discharged with a diagnosis of alcohol intoxication, 1 patient was discharged with a diagnosis of migraine headache, and 1 patient underwent lumbar puncture to exclude subarachnoid hemorrhage. The final stroke diagnosis in 6 of the 8 patients was ischemic stroke in the vertebrobasilar territory. Seven of the 8 patients presented to the ED within 3 hours of symptom onset. We judge that 3 patients might have been candidates for thrombolysis (based on deficit severity) and that 5 might have been too mild to have been considered. Two of the 8 patients had significant disabilities at 3 months poststroke, including gait ataxia and cognitive problems in patient 4 and severe aphasia in patient 8. In terms of stroke etiology, 3 patients were diagnosed with arterial dissection. Two strokes were cryptogenic and 1 each was due to atherosclerosis, small-vessel disease, and probable Sneddon’s syndrome. All 8 patients presented to hospitals that were not certified as primary
Table 2. Diagnostic characteristics of patients with misdiagnosed acute stroke
Patient
Age, years
1
18
Male
2
48
Female
3
48
Male
4
42
Male
5
29
Male
6
24
Female
7
28
Female
8
35
Female
Sex
Presenting symptoms Left hemisensory symptoms (numbness) Acute nausea and vertigo Acute blurred vision, ‘‘off balance,’’ gait ataxia, dysarthria, left hand weakness Sudden vertigo, blurred vision, headache, nausea, gait ataxia, pain radiating down neck to back Severe acute right frontal headache, slurred speech, right facial droop with numbness, severe vertigo, clumsiness of right upper and lower extremities Acute left eye pain, right arm numbness ‘‘Seeing spots’’ while putting on facial makeup, ‘‘worst headache of life’’ with neck pain, dizziness, tendency to fall Altered sensorium
ED discharge diagnosis Alcohol intoxication Inner ear disorder Benign positional vertigo
Subsequent stroke diagnosis Right posterior cerebral artery infarction Left posterior inferior cerebellar artery infarction Left basal pontine infarction
Labyrinthitis
Right posterior inferior cerebellar artery infarction
Peripheral vertigo
Right cerebellar infarction, bilateral vertebral artery dissection L . R
Migraine
Left frontoparietal subcortical infarction; severe narrowing of left distal internal carotid artery; intracranial dissection Right cerebellar infarction, right vertebral artery dissection
Excluded subarachnoid hemorrhage with brain CT and cerebrospinal fluid exam New onset seizure with prolonged postictal state
Left MCA infarction, left internal carotid artery dissection
A. KURUVILLA ET AL.
526
Table 3. Clinical variables and rate of misdiagnosis
Female Male White Black Age .35 years Age ,35 years Anterior circulation Posterior circulation Migraine No migraine
Correct diagnosis (n 5 49)
Misdiagnosis (n 5 8)
P value
30 (88%) 19 (83%) 34 (84%) 14 (88%) 41 (91%) 8 (67%) 39 (95%) 10 (63%) 8 (89%) 41 (85%)
4 (12%) 4 (17%) 6 (15%) 2 (12%) 4 (9%) 4 (33%) 2 (5%) 6 (38%) 1 (11%) 7 (15%)
.70
stroke centers. In addition, none of the 8 misdiagnosed patients was seen by a neurologist in the ED. Clinical variables and their relationship to misdiagnosis are summarized in Table 3. The rate of misdiagnosis was 38% in patients with posterior circulation stroke (P 5 .006) and 33% in patients aged #35 years (P 5 .052). There was no difference in the rate of misdiagnosis according to sex, racial group, history of migraine, or any conventional risk factors.
Discussion Previous studies of stroke in young adults have focused on etiologies and prognosis. In contrast, the present study has characterized factors associated with misdiagnosis of stroke. Our principal findings are that 14% of patients were misdiagnosed in the ED and that posterior circulation stroke was more likely to be misdiagnosed. Data concerning the precision and accuracy of clinical diagnosis in hyperacute stroke patients are limited. The level of precision tends to be lowest for subjective findings, such as sensory examination, and highest for objective elements, such as level of sensorium and degree of motor deficit.5 Misdiagnosis of stroke can occur due to ‘‘overdiagnosis’’ (ie, attributing a nonstroke condition to stroke) or ‘‘underdiagnosis’’ (ie, attributing an actual stroke to a nonstroke condition). In a series of 821 consecutive patients with an initial diagnosis of stroke, 13% were ultimately determined to have another condition. The most frequent causes of overdiagnosis were acute confusional state or delirium, syncope, seizure, neoplasms, toxins, and subdural hematoma.6 It is important to contrast the overdiagnosis of acute stroke in the foregoing series with underdiagnosis in our study, because underdiagnosis might have precluded the administration of thrombolytic therapy in some of our patients. Goldstein and Simel identified 3 factors (acute facial paresis, arm drift, and abnormal speech) that, if present, can improve diagnostic accuracy.7 In a retrospective study evaluating the ability of emergency physicians to accurately identify patients with acute
1.0 .052 .006 1.0
stroke, Kothari et al8 found that out of 351 patients with a final discharge diagnosis of ischemic stroke or transient ischemic attack (TIA), 346 were correctly identified by the emergency physician (sensitivity, 98.6 %; positive predictive value, 94.8%). In our series, seven patients discharged from the ED were subsequently confirmed to have sustained a stroke. Our study also differs from the analysis of Kothari et al8 by including only young stroke patients and incorporating patients seen at small and medium-sized community hospitals without experienced stroke teams. In fact, all misdiagnosed patients were seen at hospitals that were not certified primary stroke centers. We found that posterior circulation infarctions were more likely to be misdiagnosed. Four of the 7 patients who were misdiagnosed and discharged from the ED were diagnosed with peripheral vertigo. Dizziness, a disturbance of balance perception, is the third most-common medical symptom reported in general medical clinics.9 The likelihood of cerebrovascular disease is the same in patients with true vertigo and those with nonvertiginous dizziness.10 ED physicians are confronted with the challenge of evaluating benign causes of vertigo and potentially serious forms of vertigo that could cause disability or death.9 A previous survey of emergency physicians found that overreliance on the qualitative nature of the symptoms was linked to potential misdiagnosis.11 None of the 8 misdiagnosed patients in our series was seen by a neurologist at the initial presentation. In a prospective study analyzing the impact of ED neurologists on patient management and outcome, Moulin et al12 concluded that dizziness was the symptom most commonly associated with a missed diagnosis of stroke. The authors compared the ED team’s tentative neurologic diagnosis with the neurology team’s final discharge diagnosis and patient outcomes in 1679 patients and found 37.3% false-positive neurologic diagnoses and 36.6% falsenegative diagnoses. Neurologic consultation might not be practical in the majority of patients presenting to the ED with dizziness, however. A population-based study evaluating the proportion of stroke in patients presenting to the ED with
MISDIAGNOSIS OF ACUTE STROKE IN YOUNG ADULTS
dizziness found that stroke or TIA was diagnosed in only 3.2% (53/1666) of all patients with dizziness symptoms, including dizziness, vertigo, and imbalance.10 Of the 46 patients with stroke/TIA evaluated in the ED, 16 were not diagnosed with stroke/TIA (35%).10 A 13-year analysis of 9472 cases of dizziness evaluated in the ED found similar results, with a cerebrovascular cause for the dizziness identified in only 4% of the patients.13 Consequences of a missed diagnosis can be serious, especially with cerebellar/brain stem infarctions. In a retrospective series comprising 15 patients over a 5-year period with misdiagnosed cerebellar infarction in the ED, the overall mortality was 40%, and among the survivors, nearly 50% had disabling deficits.14 That study emphasized that failure to rapidly diagnose cerebellar infarction may lead to serious morbidity and mortality due to hydrocephalus and brain stem infarctions. Emergency physicians should understand that hyperacute computed tomography (CT) has a low sensitivity for identifying brainstem and cerebellar infarcts, which may present with vertigo as a main symptom.15-17 Our study has several limitations. Along with the moderate sample size, because the patients were seen in a tertiary center stroke clinic, there may been referral bias. A population-based study of young adults with stroke that examines the accuracy of diagnosis and the potential for missed thrombolysis would be of interest. In addition, we do not have complete information on whether patients arrived via ambulance or whether prehospital stroke scores were obtained. Finally, because our registry included only young adult patients, we cannot comment on the rate of misdiagnosis in the entire stroke population seen in our stroke clinic. In conclusion, missed or delayed diagnosis of stroke in young adults in the ED may have serious consequences, including long-term disability. Educational programs to increase young stroke awareness in paramedics and ED physicians are vital. Larger studies should also address whether there is a difference in diagnostic accuracy between certified primary stroke centers and noncertified hospitals.
527
References 1. Lyden P. Thrombolytic therapy for acute stroke: Not a moment to lose. N Engl J Med 2008;359:1393-1394. 2. American Heart Association. Heart disease and stroke statistics: 2009 update. Circulation 2009;119:e1-e161. 3. Saver JL. Time is brain-quantified. Stroke 2006;37: 263-266. 4. Putaala J, Metso AJ, Metso TN, et al. Analysis of 1008 consecutive patients aged 15 to 49 with first-ever ischemic stroke: The Helsinki Young Stroke Registry. Stroke 2009; 40:1195-1203. 5. Goldstein LB, Matcher DB. Clinical assessment of stroke. JAMA 1994;271:1114-1120. 6. Norris JW, Hachinski VC. Misdiagnosis of stroke. Lancet 1982;319:328-331. 7. Goldstein LB, Simel DL. Is this patient having a stroke? JAMA 2005;293:2391-2402. 8. Kothari RU, Brott T, Broderick JP, et al. Emergency physicians: Accuracy in the diagnosis of stroke. Stroke 1995; 26:2238-2241. 9. Capello M, di Blasi U, di Pirazza L, et al. Dizziness and vertigo in a department of emergency medicine. Eur J Emerg Med 1995;2:201-211. 10. Kerber KA, Brown DL, Lisabeth LD, et al. Stroke among patients with dizziness, vertigo, and imbalance in the emergency department: A population-based study. Stroke 2006;37:2484-2487. 11. Stanton VA, Hsieh Y, Camargo CA Jr, et al. Overreliance on symptom quality in diagnosing dizziness: Results of a multicenter survey of emergency physicians. Mayo Clin Proc 2007;82:1319-1328. 12. Moulin T, Sablot D, Vidry E, et al. Impact of emergency room neurologists on patient management and outcome. Eur Neurol 2003;50:207-214. 13. Newman-Toker DE, Hsieh YH, Camargo CA, et al. Spectrum of dizziness visits to US emergency departments: Cross-sectional analysis from a nationally representative sample. Mayo Clin Proc 2008;83:765-775. 14. Savitz SI, Caplan LR, Edlow JA. Pitfalls in the diagnosis of cerebellar infarction. Acad Emerg Med 2007;14:63-68. 15. Long J, Liang Y. Cerebellar infarction: Analysis of 22 cases. Chin Med J 1994;107:186-188. 16. Simmons Z, Biller J, Adams HP Jr, et al. Cerebellar infarction: Comparison of computed tomography and magnetic resonance imaging. Ann Neurol 1986;19:291-293. 17. Johkura K. Central paroxysmal positional vertigo: Isolated dizziness caused by small cerebellar hemorrhage. Stroke 2007;38:e26-e27.
Misdiagnosis or delayed diagnosis of acute ischemic stroke can result in neurologic worsening or a missed opportunity for thrombolysis. Because stroke in young adults is less common than stroke in the elderly, we sought to determine clinical characteristics associated with misdiagnosis of stroke in young adults. Patients from the prospectively maintained Young Stroke Registry in our comprehensive stroke center were reviewed. Demographic information, past medical history, presentation within the 3-hour time window, and outcomes were assessed. We compared patients misdiagnosed and those correctly diagnosed to identify factors associated with misdiagnosis of acute stroke. A total of 57 patients aged 16-50 were enrolled in the registry during 2001-2006. Eight patients (14%; 4 men and 4 women; mean age, 38 years) were misdiagnosed. Seven of these 8 patients were discharged from the emergency department initially. Patients age ,35 years (P 5 .05) and patients with posterior circulation stroke (P 5 .006) were more likely to be misdiagnosed. All 8 misdiagnosed patients were initially evaluated at hospitals that were not certified primary stroke centers. Patients presenting with vertebrobasilar territory ischemia have a greater rate of misdiagnosis. Our study demonstrates the increasing need for ‘‘young stroke awareness’’ among emergency department personnel. Initial misdiagnosis can potentially lead to a lost opportunity for thrombolysis in otherwise good candidates. Key Words: Cerebral infarction—diagnosis—thrombolysis. Ó 2011 by National Stroke Association
Stroke is a leading cause of disability among adults, and remains the only neurologic disorder for which physicians are potentially able to completely reverse the deficits.1 Each year, nearly 800,000 people in the United States experience a new or recurrent stroke; more than 600,000 of these are first attacks, and nearly 200,000 are From the Department of Neurology and Stroke Program, Wayne State University/Detroit Medical Center, Detroit, Michigan. Received January 6, 2010; accepted March 9, 2010. The authors have no conflict of interest. Presented at the 2009 International Stroke Conference (American Stroke Association), San Diego, 2009, Feb 18-20. Address correspondence to Seemant Chaturvedi, MD, FAHA, FAAN, Stroke Program and Department of Neurology, Wayne State University, 8C-UHC, 4201 St. Antoine, Detroit, MI 48201. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2011 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2010.03.005
recurrent stroke.2 If given early enough after onset of symptoms, thrombolytic therapy can restore neurologic function in patients with acute ischemic stroke.1,3 Because stroke is less common in young adults than in older individuals, there is considerable potential for neurologic symptoms in young adults to be attributed to other causes. Furthermore, the etiologies of stroke are different in young adults and less commonly involve the typical causes in older adults, such as atherosclerosis, embolism from atrial fibrillation, and lacunar stroke due to long-standing small vessel vasculopathy. Ischemic stroke in young adults is more often due to such conditions as arterial dissection, vasculopathies, and cardiogenic sources, such as patent foramen ovale.4 Here we highlight a series of cases in which an initial diagnosis other than stroke was made in young adults who ultimately had a final diagnosis of ischemic stroke. We also explore clinical characteristics associated with
Journal of Stroke and Cerebrovascular Diseases, Vol. 20, No. 6 (November-December), 2011: pp 523-527
523
A. KURUVILLA ET AL.
524
Table 1. Clinical characteristics
Age, years, mean (SD) Male sex, n (%) Black race, n (%) Hypertension, n (%) Diabetes, n (%) Coronary artery disease, n (%) Active smoker, n (%) Past smoker, n (%) Hyperlipidemia, n (%) Migraine, n (%)
Misdiagnosed (n 5 8)
Correctly diagnosed (n 5 49)
P value
34.3 (11.2) 4 (50%) 2 (25%) 2 (25%) 1 (12.5%) 0 (0) 0 (0) 0 (0) 3 (37.5%) 1 (12.5%)
38.7 (8.0) 19 (38.7%) 14 (28.6%) 15 (30.6%) 4 (8.2%) 5 (10.2%) 11 (22.4%) 12 (24.5%) 11 (22.4%) 7 (14.3%)
.18 .83 .73 1.00 .54 1.00 .33 .18 .39 1.00
misdiagnosis of stroke in young adults. To the best of our knowledge, an analysis of factors associated with misdiagnosis of stroke in young adults has not been reported previously.
Methods Study Design/Setting/Patient Selection The Young Stroke Registry maintained since 2001 at our comprehensive stroke center is a prospective registry of patients aged 16-50 years who were seen in the outpatient stroke clinic of a university medical center. Both patients seen at our primary hospital and patients referred to our outpatient stroke clinic from other hospitals were included in the registry. Our primary hospital is located in a metropolitan area with 4 million residents. Patients referred from other hospitals were sent by outside physicians for additional advice regarding diagnosis or treatment. Patients with stroke due to substance abuse and those with no fixed residence were excluded from the registry because of the difficulty of follow-up in these patients. Patients were confirmed as having a diagnosis of ischemic stroke by vascular neurologists using clinical and neuroimaging findings, and were included regardless of initial diagnosis in the emergency department (ED). Demographic information was obtained, past medical history was recorded, and causative factors associated with stroke in younger adults (ie, vascular dissection) were investigated. Clinical data, including presenting symptoms, ED discharge diagnosis, and subsequent stroke diagnosis, were collected from the original source documents. Whether or not the hospital where the patient initially sought medical care at the onset of stroke symptoms was certified as a primary stroke center, according to the Joint Commission criteria (as of July 2008, the time of data analysis), was noted. In terms of vascular risk factors, the specific variables recorded during history-taking were hypertension, diabetes, hyperlipidemia, smoking, and history of coronary artery bypass graft surgery/stent insertion. Hypertension was considered present if the patient was taking an
antihypertensive medication or had a systolic blood pressure .140 mm Hg or a diastolic blood pressure .90 mm measured on at least 2 occasions. Diabetes was considered present if the patient was taking medication for diabetes or had a fasting blood glucose level .126 mg/dL. Hyperlipidemia was present if the patient was taking a lipid-lowering medication and had a fasting total cholesterol level .200 mg/dL and/or a low-density lipoprotein (LDL) cholesterol level .100 mg/dL.
Primary Data Analysis Because this study focused on misdiagnosis of acute stroke in young adults, we restricted our analysis to the subset of patients who were given an initial nonstroke diagnosis. Patients were categorized as misdiagnosed if they were given a nonstroke diagnosis and either admitted to the hospital or discharged from the ED. Clinical variables and their relationship to misdiagnosis were tested as univariate factors using the c2 test and Fisher’s exact test. The study design was approved by the university’s Institutional Review Board.
Results A total of 57 patients (34 women [59.6%]; mean age, 38.1 years) were enrolled in our stroke registry. In this cohort, 29.8% had hypertension, 8.8% had diabetes, 8.8% had coronary artery disease, and 40.4% were either active or former smokers. Hyperlipidemia was present in 24.6% of patients, and 14% had a history of migraine. Table 1 summarizes demographic data and risk factor information. Eight patients (14%), including 4 men and 4 women (mean age, 38.1 years) were misdiagnosed in the ED. An illustrative case is patient 8, a 35-year-old woman who collapsed at work. On arrival at a local community hospital within 1 hour of symptom onset, she had speech difficulty and right-sided weakness. She had no history of seizures and no documented seizure activity. She was diagnosed with possible postictal state and admitted to the hospital. She was examined by a neurologist the next day, and brain magnetic resonance imaging (MRI)
MISDIAGNOSIS OF ACUTE STROKE IN YOUNG ADULTS
Figure 1. Diffusion-weighted MRI of patient 8 showing large left MCA territory stroke.
revealed a large infarction in the left middle cerebral artery (MCA) territory (Fig 1). Table 2 gives the initial presenting symptoms, ED discharge diagnosis, and subsequent stroke diagnosis of
525
the 8 patients who were misdiagnosed in the ED. Altogether, 4 patients were discharged from the ED with a diagnosis of peripheral vertigo, 1 patient was discharged with a diagnosis of alcohol intoxication, 1 patient was discharged with a diagnosis of migraine headache, and 1 patient underwent lumbar puncture to exclude subarachnoid hemorrhage. The final stroke diagnosis in 6 of the 8 patients was ischemic stroke in the vertebrobasilar territory. Seven of the 8 patients presented to the ED within 3 hours of symptom onset. We judge that 3 patients might have been candidates for thrombolysis (based on deficit severity) and that 5 might have been too mild to have been considered. Two of the 8 patients had significant disabilities at 3 months poststroke, including gait ataxia and cognitive problems in patient 4 and severe aphasia in patient 8. In terms of stroke etiology, 3 patients were diagnosed with arterial dissection. Two strokes were cryptogenic and 1 each was due to atherosclerosis, small-vessel disease, and probable Sneddon’s syndrome. All 8 patients presented to hospitals that were not certified as primary
Table 2. Diagnostic characteristics of patients with misdiagnosed acute stroke
Patient
Age, years
1
18
Male
2
48
Female
3
48
Male
4
42
Male
5
29
Male
6
24
Female
7
28
Female
8
35
Female
Sex
Presenting symptoms Left hemisensory symptoms (numbness) Acute nausea and vertigo Acute blurred vision, ‘‘off balance,’’ gait ataxia, dysarthria, left hand weakness Sudden vertigo, blurred vision, headache, nausea, gait ataxia, pain radiating down neck to back Severe acute right frontal headache, slurred speech, right facial droop with numbness, severe vertigo, clumsiness of right upper and lower extremities Acute left eye pain, right arm numbness ‘‘Seeing spots’’ while putting on facial makeup, ‘‘worst headache of life’’ with neck pain, dizziness, tendency to fall Altered sensorium
ED discharge diagnosis Alcohol intoxication Inner ear disorder Benign positional vertigo
Subsequent stroke diagnosis Right posterior cerebral artery infarction Left posterior inferior cerebellar artery infarction Left basal pontine infarction
Labyrinthitis
Right posterior inferior cerebellar artery infarction
Peripheral vertigo
Right cerebellar infarction, bilateral vertebral artery dissection L . R
Migraine
Left frontoparietal subcortical infarction; severe narrowing of left distal internal carotid artery; intracranial dissection Right cerebellar infarction, right vertebral artery dissection
Excluded subarachnoid hemorrhage with brain CT and cerebrospinal fluid exam New onset seizure with prolonged postictal state
Left MCA infarction, left internal carotid artery dissection
A. KURUVILLA ET AL.
526
Table 3. Clinical variables and rate of misdiagnosis
Female Male White Black Age .35 years Age ,35 years Anterior circulation Posterior circulation Migraine No migraine
Correct diagnosis (n 5 49)
Misdiagnosis (n 5 8)
P value
30 (88%) 19 (83%) 34 (84%) 14 (88%) 41 (91%) 8 (67%) 39 (95%) 10 (63%) 8 (89%) 41 (85%)
4 (12%) 4 (17%) 6 (15%) 2 (12%) 4 (9%) 4 (33%) 2 (5%) 6 (38%) 1 (11%) 7 (15%)
.70
stroke centers. In addition, none of the 8 misdiagnosed patients was seen by a neurologist in the ED. Clinical variables and their relationship to misdiagnosis are summarized in Table 3. The rate of misdiagnosis was 38% in patients with posterior circulation stroke (P 5 .006) and 33% in patients aged #35 years (P 5 .052). There was no difference in the rate of misdiagnosis according to sex, racial group, history of migraine, or any conventional risk factors.
Discussion Previous studies of stroke in young adults have focused on etiologies and prognosis. In contrast, the present study has characterized factors associated with misdiagnosis of stroke. Our principal findings are that 14% of patients were misdiagnosed in the ED and that posterior circulation stroke was more likely to be misdiagnosed. Data concerning the precision and accuracy of clinical diagnosis in hyperacute stroke patients are limited. The level of precision tends to be lowest for subjective findings, such as sensory examination, and highest for objective elements, such as level of sensorium and degree of motor deficit.5 Misdiagnosis of stroke can occur due to ‘‘overdiagnosis’’ (ie, attributing a nonstroke condition to stroke) or ‘‘underdiagnosis’’ (ie, attributing an actual stroke to a nonstroke condition). In a series of 821 consecutive patients with an initial diagnosis of stroke, 13% were ultimately determined to have another condition. The most frequent causes of overdiagnosis were acute confusional state or delirium, syncope, seizure, neoplasms, toxins, and subdural hematoma.6 It is important to contrast the overdiagnosis of acute stroke in the foregoing series with underdiagnosis in our study, because underdiagnosis might have precluded the administration of thrombolytic therapy in some of our patients. Goldstein and Simel identified 3 factors (acute facial paresis, arm drift, and abnormal speech) that, if present, can improve diagnostic accuracy.7 In a retrospective study evaluating the ability of emergency physicians to accurately identify patients with acute
1.0 .052 .006 1.0
stroke, Kothari et al8 found that out of 351 patients with a final discharge diagnosis of ischemic stroke or transient ischemic attack (TIA), 346 were correctly identified by the emergency physician (sensitivity, 98.6 %; positive predictive value, 94.8%). In our series, seven patients discharged from the ED were subsequently confirmed to have sustained a stroke. Our study also differs from the analysis of Kothari et al8 by including only young stroke patients and incorporating patients seen at small and medium-sized community hospitals without experienced stroke teams. In fact, all misdiagnosed patients were seen at hospitals that were not certified primary stroke centers. We found that posterior circulation infarctions were more likely to be misdiagnosed. Four of the 7 patients who were misdiagnosed and discharged from the ED were diagnosed with peripheral vertigo. Dizziness, a disturbance of balance perception, is the third most-common medical symptom reported in general medical clinics.9 The likelihood of cerebrovascular disease is the same in patients with true vertigo and those with nonvertiginous dizziness.10 ED physicians are confronted with the challenge of evaluating benign causes of vertigo and potentially serious forms of vertigo that could cause disability or death.9 A previous survey of emergency physicians found that overreliance on the qualitative nature of the symptoms was linked to potential misdiagnosis.11 None of the 8 misdiagnosed patients in our series was seen by a neurologist at the initial presentation. In a prospective study analyzing the impact of ED neurologists on patient management and outcome, Moulin et al12 concluded that dizziness was the symptom most commonly associated with a missed diagnosis of stroke. The authors compared the ED team’s tentative neurologic diagnosis with the neurology team’s final discharge diagnosis and patient outcomes in 1679 patients and found 37.3% false-positive neurologic diagnoses and 36.6% falsenegative diagnoses. Neurologic consultation might not be practical in the majority of patients presenting to the ED with dizziness, however. A population-based study evaluating the proportion of stroke in patients presenting to the ED with
MISDIAGNOSIS OF ACUTE STROKE IN YOUNG ADULTS
dizziness found that stroke or TIA was diagnosed in only 3.2% (53/1666) of all patients with dizziness symptoms, including dizziness, vertigo, and imbalance.10 Of the 46 patients with stroke/TIA evaluated in the ED, 16 were not diagnosed with stroke/TIA (35%).10 A 13-year analysis of 9472 cases of dizziness evaluated in the ED found similar results, with a cerebrovascular cause for the dizziness identified in only 4% of the patients.13 Consequences of a missed diagnosis can be serious, especially with cerebellar/brain stem infarctions. In a retrospective series comprising 15 patients over a 5-year period with misdiagnosed cerebellar infarction in the ED, the overall mortality was 40%, and among the survivors, nearly 50% had disabling deficits.14 That study emphasized that failure to rapidly diagnose cerebellar infarction may lead to serious morbidity and mortality due to hydrocephalus and brain stem infarctions. Emergency physicians should understand that hyperacute computed tomography (CT) has a low sensitivity for identifying brainstem and cerebellar infarcts, which may present with vertigo as a main symptom.15-17 Our study has several limitations. Along with the moderate sample size, because the patients were seen in a tertiary center stroke clinic, there may been referral bias. A population-based study of young adults with stroke that examines the accuracy of diagnosis and the potential for missed thrombolysis would be of interest. In addition, we do not have complete information on whether patients arrived via ambulance or whether prehospital stroke scores were obtained. Finally, because our registry included only young adult patients, we cannot comment on the rate of misdiagnosis in the entire stroke population seen in our stroke clinic. In conclusion, missed or delayed diagnosis of stroke in young adults in the ED may have serious consequences, including long-term disability. Educational programs to increase young stroke awareness in paramedics and ED physicians are vital. Larger studies should also address whether there is a difference in diagnostic accuracy between certified primary stroke centers and noncertified hospitals.
527
References 1. Lyden P. Thrombolytic therapy for acute stroke: Not a moment to lose. N Engl J Med 2008;359:1393-1394. 2. American Heart Association. Heart disease and stroke statistics: 2009 update. Circulation 2009;119:e1-e161. 3. Saver JL. Time is brain-quantified. Stroke 2006;37: 263-266. 4. Putaala J, Metso AJ, Metso TN, et al. Analysis of 1008 consecutive patients aged 15 to 49 with first-ever ischemic stroke: The Helsinki Young Stroke Registry. Stroke 2009; 40:1195-1203. 5. Goldstein LB, Matcher DB. Clinical assessment of stroke. JAMA 1994;271:1114-1120. 6. Norris JW, Hachinski VC. Misdiagnosis of stroke. Lancet 1982;319:328-331. 7. Goldstein LB, Simel DL. Is this patient having a stroke? JAMA 2005;293:2391-2402. 8. Kothari RU, Brott T, Broderick JP, et al. Emergency physicians: Accuracy in the diagnosis of stroke. Stroke 1995; 26:2238-2241. 9. Capello M, di Blasi U, di Pirazza L, et al. Dizziness and vertigo in a department of emergency medicine. Eur J Emerg Med 1995;2:201-211. 10. Kerber KA, Brown DL, Lisabeth LD, et al. Stroke among patients with dizziness, vertigo, and imbalance in the emergency department: A population-based study. Stroke 2006;37:2484-2487. 11. Stanton VA, Hsieh Y, Camargo CA Jr, et al. Overreliance on symptom quality in diagnosing dizziness: Results of a multicenter survey of emergency physicians. Mayo Clin Proc 2007;82:1319-1328. 12. Moulin T, Sablot D, Vidry E, et al. Impact of emergency room neurologists on patient management and outcome. Eur Neurol 2003;50:207-214. 13. Newman-Toker DE, Hsieh YH, Camargo CA, et al. Spectrum of dizziness visits to US emergency departments: Cross-sectional analysis from a nationally representative sample. Mayo Clin Proc 2008;83:765-775. 14. Savitz SI, Caplan LR, Edlow JA. Pitfalls in the diagnosis of cerebellar infarction. Acad Emerg Med 2007;14:63-68. 15. Long J, Liang Y. Cerebellar infarction: Analysis of 22 cases. Chin Med J 1994;107:186-188. 16. Simmons Z, Biller J, Adams HP Jr, et al. Cerebellar infarction: Comparison of computed tomography and magnetic resonance imaging. Ann Neurol 1986;19:291-293. 17. Johkura K. Central paroxysmal positional vertigo: Isolated dizziness caused by small cerebellar hemorrhage. Stroke 2007;38:e26-e27.