ARTICLE IN PRESS

Ischemic Stroke Predictors in Patients Presenting with

Dizziness, Imbalance, and Vertigo

D1X XYongwoo Kim, D2XMD, X *,1 D3X XMohammad Faysel, D4XPhD,X †,2 D5X XClotilde Balucani, MD,
D6X X PhD,‡,3
D7X XDaohai Yu, D8XPhD,
X MS,§ D9X XNadege Gilles, MPH,
,4
D10X X ║,5 and D1X XSteven R Levine, D12XMD
X {,6

Objects: To identify predictors of acute ischemic stroke (AIS) among patients pre-
senting to the Emergency Department (ED) with dizziness, imbalance, or vertigo
(DIV) based on demographic and clinical characteristics. Methods: We identified
patients admitted to the hospital after presenting to the ED with DIV from the State-
wide Planning and Research Cooperative System database of New York from 2010
to 2014. Demographic and clinical characteristics were systematically collected.
Multivariable logistic regression was used to determine predictors of a discharge
diagnosis of AIS. Results: Among 77,993 patients with DIV, 3857 (4.9%) had a dis-
charge diagnosis of AIS. Admission presentation of imbalance, African-American
race, history of hypertension, diabetes mellitus, hypercholesterolemia, tobacco use,
atrial fibrillation, and prior AIS due to extracranial artery atherosclerosis were each
positively associated with an AIS diagnosis independently. Factors negatively asso-
ciated with an AIS discharge diagnosis included: admission presentation of vertigo,
female sex, age > 81, history of anemia, coronary artery disease, asthma, depressive
disorders, and anxiety disorders. Conclusions: Multiple potential positive and nega-
tive predictive AIS risk factors were identified. Combining with currently available
centrally-caused dizziness prediction tools, these newly identified factors could pro-
vide more accurate AIS risk stratifying method for DIV patients.
Key Words: Dizziness—vertigo—imbalance—ischemic stroke—risk factors—
emergency department—risk stratification
© 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Introduction
Dizziness, imbalance, or vertigo (DIV) are common and
challenging chief complaints by patients presenting to the
emergency department (ED). While approximately 4%-11%
of patients who presented with DIV to the ED are diagnosed
with acute ischemic stroke (AIS),1-4 concern for missing AIS
may drive physicians to hospitalize patients to acquire an
MRI and provide acute clinical monitoring.2,5,6

From the *Lewis Katz School of Medicine at Temple University, Department of Neurology, Neurovascular Division, Philadelphia, Pennsylvania;
†College of Health Related Professions at SUNY Downstate Medical Center, Medical Informatics Program, Brooklyn, New York; ‡SUNY Down-
state Medical Center, The Stroke Center and Department of Neurology, Brooklyn, New York; §Lewis Katz School of Medicine at Temple Univer-
sity, Department of Clinical Sciences, Philadelphia, Pennsylvania; ║SUNY Downstate Medical Center, The Stroke Center and Department of
Neurology, Brooklyn, New York; and {SUNY Downstate Medical Center, The Stroke Center and Department of Neurology and Kings County
Hospital Center, Department of Neurology, Brooklyn, New York.
Received June 5, 2018; accepted August 1, 2018.
Sources of Funding: None.
Address correspondence to Yongwoo Kim, MD, Lewis Katz School of Medicine at Temple University, 3401 North Broad Street, Suite C525, Phila-
delphia, PA 19104. E-mail: yongwoo.kim@tuhs.temple.edu
1
Yongwoo Kim contributed in study concept and design, acquisition of data, analysis and interpretation of data, drafting and revision of
manuscript.
2
Mohammad Faysel contributed in acquisition of data, analysis and interpretation of data, revision of manuscript.
3
Clotilde Balucani contributed in study concept and design, revision of manuscript.
4
Daohai Yu contributed in critical analysis and interpretation of data.
5
Nadege Gilles contributed in acquisition of data.
6
Steven R Levine contributed in study concept and design, analysis and interpretation of data, critical revision of manuscript, study supervision.
1052-3057/$ - see front matter
© 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.08.002

Journal of Stroke and Cerebrovascular Diseases, Vol. &&, No. && (&&), 2018: pp 16 1
 ARTICLE IN PRESS
2 Y. KIM ET AL.
More accurate predictors of AIS in patients with DIV
would improve triage and risk stratification, potentially
reducing unnecessary healthcare costs and improving
diagnostic assessments. An easy to use bedside tool that
can help physicians better predict AIS in DIV patients in
the ED would be useful. We sought to determine if there
were demographic and clinical factors predicting a dis-
charge diagnosis of AIS in patients with acute DIV who
presented to the ED.
Methods
Patient Database
After SUNY Downstate Institutional Review Board
exemption for human subjects research was obtained, we
used the deidentified discharge data from the Statewide
Planning and Research Cooperative System (SPARCS)
inpatient database, a comprehensive data reporting sys-
tem of New York State hospitals.7 The database contains
many data elements including patients’ demographic
information, admission and discharge diagnosis, second-
ary diagnoses, procedures performed during hospitaliza-
tion, length of hospital stay, and ED visit indicator.
We selected patients hospitalized through the ED
with an admission presentation of dizziness (ICD-9-CM
code 780.4), imbalance (ICD-9-CM codes 781.2, 782.3),
and vertigo (ICD-9-CM codes 386.1x, 386.2, 386.9) from
January 1st, 2010 through December 31st, 2014. Patients
younger than 18 years old were excluded. We divided
the study cohort into 2 groups: those with a discharge
diagnosis of AIS (ICD-9-CM codes 433.xx, 434.xx, and
436) and those without.
Independent Variables
Patients’ demographic information (age, sex, and race),
medical history, length of hospital stays, and performance
of head CT, brain MRI, IV thrombolysis were collected.
Secondary diagnoses were used to identify patient's
medical history. We excluded codes for the description
of symptoms or signs (ICD-9-CM codes 342.xx, 344.xx,
438.xx, 780-799.xx) and supplementary ICD-9-CM
codes (E000-E999, V01-V91). Nonchronic, transient
medical conditions such as hyperkalemia (ICD-9-CM
code 276.7) were excluded. Rare conditions with less
than 2% rates in either AIS group or non-AIS group
were excluded. The diagnosis codes that apparently
have little or no clinical correlation with AIS or DIV,
such as “osteoarthrosis, localized, secondary, forearm
(ICD-9-CM code 715.23)” were excluded.
The diagnosis codes with similar clinical features
were merged into a single variable. For example, “Iron
deficiency anemia” (ICD-9-CM code 280.x), “Anemia of
Chronic Illness” (ICD-9-CM 285.2), and “unspecified
Anemia” (ICD-9-CM code 285.9) were analyzed
together as “Anemia”.
Statistical Analysis
For univariable analysis of numerical variables, Stu-
dent's t test was used when normal distributions and
equal variances could be assumed, and the Wilcoxon test
was used otherwise. For univariable analysis of categori-
cal variables, Chi-square test was performed when no
cells had expected count of less than 5, and Fisher's exact
test was used when there was at least 1 cell with an
expected count of less than 5.
Independent variables that showed a significantly
different distribution between the 2 groups (AIS versus
non-AIS) were entered into multivariable logistic
regression with the backward variable selection method
to obtain adjusted odds ratios and 95% confidence inter-
vals. Variables with too small percentage difference
(<2%) in 2 groups were excluded from entering multi-
variable regression. Statistical analyses were performed
with SPSS (version 23, IBM).
Results
Clinical Characteristics
From January 1st, 2010 through December 31st, 2014,
77,993 patients presented to the ED in New York State
hospitals with DIV at triage. Among them, presentation
D13X X
of 1713 (2.2%) patients were vertigo, 13,425 (17.2%) were
imbalance, and 62,855 (80.6%) were nonspecific dizziness.
Mean (SD) age of all DIV patients was 68.7 (15.9) years
old. Age range was 18-113 (median 71, interquartile range
58-81) years old.
A discharge diagnosis of AIS was made in 3857 (4.9%)
patients; TIA in 2096 (2.7%); ICH in 277 (.4%); and SAH in
37 (.05%). Among the 3857 patients with a discharge diag-
nosis of AIS, 1404 (36.4%) patients had brain imaging
(MRI or CT) during hospitalization.
IV thrombolysis was administered to 139 (.2%) patients.
Among these patients, 82 had AIS, 8 had TIA, 1 was asso-
ciated with ICH, and 48 were given a non-neurological
diagnosis. The ICH may have been an adverse effect of
treatment, although the exact sequence of events was not
available in the database.
Univariable Analysis
Table 1 presents demographic and clinical characteris-
tics. We found 21 variables (listed in Table 1) with signifi-
cant differences in frequencies between the AIS and non-
AIS group. Among them, 15 variables with significant
percentage difference ( 2%) between AIS and non-AIS
group were entered to multivariable regression.
Frequency of history of Meniere's disease (ICD-9-CM
code 386.0x), labyrinthine disorders (ICD-9-CM codes
386.3x, 386.4x, 386.5x, 386.8, 386.9), benign paroxysmal
positional vertigo (ICD-9-CM code 386.11), vestibular
neuronitis (ICD-9-CM code 386.12), vertigo of central ori-
gin (ICD-9-CM code 386.2), prior AIS due to embolism
 ARTICLE IN PRESS
STROKE PREDICTORS IN DIZZINESS PATIENTS 3

Table 1. Demographic and clinical characteristics (N = 77,993)

Variable Non-AIS (n = 74,136) AIS (n = 3857) P value

Age categories <.001
1st quartile (age  58) 18,914 (25.5%) 829 (21.5%)
2nd quartile (age 58-71) 19,311 (26.0%) 1162 (30.1%)
3rd quartile (age 71-81) 17,607 (23.7%) 1019 (26.4%)
4th quartile (age > 81) 18,304 (24.7%) 847 (22.0%)
Sex <.001
Female 42,258 (58.3%) 1742 (45.1%)
Male 31,878 (41.7%) 2115 (54.9%)
Race <.001
Caucasian 39,966 (53.9%) 2158 (56.0%)
African-American 15,928 (21.5%) 880 (22.8%)
Asian 2,116 (2.9%) 111 (2.9%)
Other 16,126 (21.8%) 708 (18.4%)
Admission presentation <.001
Dizziness 59,984 (80.9%) 2871 (74.4%)
Vertigo 1,669 (2.3%) 44 (1.1%)
Imbalance 12,483 (16.8%) 942 (24.4%)
Clinical characteristics (ICD-9-CM code)
Essential hypertension (401.x) 41,468 (55.9%) 2657 (68.9%) <.001
Diabetes mellitus (250.xx) 21,746 (29.3%) 1494 (38.7%) <.001
Hypercholesterolemia (272.x) 30,842 (41.6%) 2150 (55.7%) <.001
Coronary artery disease (414.0x) 17,145 (23.1%) 968 (25.1%) .005
Atrial fibrillation (427.31) 8559 (12.5%) 590 (15.3%) <.001
Aortic valve disorders (424.1) 1503 (2.0%) 105 (2.7%) .003
Prior AIS due to extracranial artery atherosclerosis (433.xx) 1943 (2.6%) 451 (11.7%) <.001
Peripheral arterial disease (443.9) 1896 (2.6%) 159 (4.1%) <.001
Tobacco use (305.1) 6097 (8.2%) 520 (13.5%) <.001
Anemia* 10,426 (14.1%) 347 (9.0%) <.001
Heart failure (428.xx) 8149 (11.0%) 382 (9.9%) .035
Epilepsy (345.xx) 2771 (3.7%) 111 (2.9%) .006
Hypothyroidism (244.x) 9257 (12.5%) 421 (10.9%) .004
Asthma (493.xx) 6287 (8.5%) 206 (5.3%) <.001
COPD (491.xx, 492.x, 496) 4784 (6.5%) 205 (5.3%) .005
Depressive disorders* 6895 (9.3%) 255 (6.6%) <.001
Anxiety and panic disorders (300.0x) 5137 (6.9%) 169 (4.4%) <.001
Abbreviations: AIS, acute ischemic stroke; COPD, chronic obstructive pulmonary disease.
Aortic valve disorders = aortic valve stenosis, sclerosis, regurgitation, or insufficiency; Heart failure = systolic failure, diastolic failure, or
combined; Anemia = code 280.x, 285.2 and 285.9; Depressive disorders = codes 296.2x, 296.3x, and 296.82.

(ICD-9-CM code 434.11), and prior AIS due to small vessel anxiety and panic disorder, female sex, age > 81, and
disease (ICD-9-CM code 434.01) were not significantly dif- “other” race were negatively associated with the odds of
ferent between the AIS and non-AIS group. having an AIS diagnosis.

Multivariable Logistic Regression Discussion

After adjustment, there were 3 demographic and 12
clinical characteristics remaining in the regression model.
Results are shown in Table 2.
Admission presentation of imbalance, essential
hypertension, diabetes mellitus, hypercholesterolemia,
atrial fibrillation, tobacco use, prior AIS due to extracra-
nial artery atherosclerosis, and African-American race
were positively associated with the odds of having an
AIS diagnosis.
Admission presentation of vertigo, history of anemia,
coronary artery disease, asthma, depressive disorder,
In a large, state-based, retrospective database, we found
that approximately 1 in every 20 (4.9%) patients present-
ing to the ED with DIV was diagnosed with an AIS upon
discharge. Our results are consistent with prior published
studies that found a stroke range from 4% to 11%.1,4,8,9
Most of the AIS predictors we identified were well-
established vascular risk factors.10,11 In addition, we
identified factors independently associated with non-
AIS diagnoses in DIV patients. To our knowledge, this
is the first study to identify “negative” AIS predictors in
DIV patients.
 ARTICLE IN PRESS
4 Y. KIM ET AL.

Table 2. Results of multivariable logistic regression analysis on discharge diagnosis of AIS

Independent variable OR (95% CI) P value

Age categories
Age  58 Reference
Age 59-71 1.07 (.97-1.18) .17
Age 72-81 1.01 (.91-1.13) .73
Age > 81 .86 (.77-.96) .01
Sex
Male Reference
Female .64 (.60-.69) <.001
Race
Caucasian Reference
African-American 1.15 (1.05-1.25) .002
Asian 1.06 (.87-1.30) .55
Other .89 (.82-.98) .02
Admission presentation
Dizziness Reference
Imbalance 1.64 (1.51-1.77) <.001
Vertigo .56 (.41-.75) <.001
Clinical characteristics (ICD-9-CM code)
Essential hypertension (401.x) 1.60 (1.49-1.72) <.001
Diabetes mellitus (250.xx) 1.39 (1.29-1.49) <.001
Hypercholesterolemia (272.x) 1.52 (1.42-1.62) <.001
Atrial fibrillation (427.31) 1.41 (1.28-1.56) <.001
Tobacco use (305.1) 1.70 (1.53-1.88) <.001
Prior AIS due to extracranial artery atherosclerosis (433.xx) 4.47 (4.00-5.01) <.001
Coronary arterial disease (414.0x) .84 (.78-.91) <.001
Anemia .65 (.58-.73) <.001
Asthma (493.xx) .68 (.59-.76) <.001
Depressive disorders .74 (.64-.84) <.001
Anxiety and panic disorders (300.0x) .70 (.59-.82) <.001

Anemia is potential cause of nonischemic dizziness.
Coronary artery disease could cause systemic hypoperfu-
sion from decreased cardiac output and that may be why
it predicted non-AIS in DIV patients. Hyperventilation
can cause dizziness.12 This potentially explains asthma as
predictive of non-AIS causes in DIV patients. The finding
that common psychiatric disorders predicted non-AIS
cause of DIV might be the reflection of adverse effects of
psychiatric medications.
Female DIV patients were at less risk of AIS then male.
This is consistent with another study.13 African-American
DIV patients had higher rates of AIS than Caucasians,
whereas “other race” DIV patients had more non-AIS
diagnosis. Patients with “other race” could be Hispanic,
Asian-Indian, Middle Eastern, or mixed-race patients,
although exact definition of this category was not avail-
able in SPARCS database. We merged Native American
patients and Pacific Islander patients into “Other” race
group for analysis, as the number of these patients were
too small to count in each AIS and non-AIS group.
We found that not every prior AIS predicted the index
AIS in DIV patients; only prior AIS due to extracranial
artery atherosclerosis were related to significantly higher
odds of having another AIS in DIV patients. In another
study, a history of prior AIS failed to show an association
with AIS diagnosis in DIV patients.14 This could reflect
not analyzing the prior AIS by etiology.
Age did not predict AIS risk in DIV patients, despite the
fact that age  60 is generally considered as a vascular risk
factor.15 In our study, age > 81 predicted non-AIS cause of
DIV. We think this could be due to the risk of increased
non-AIS disease with age and balanced the risk of AIS
and non-AIS as a cause of DIV, eventually overcoming
the risk of AIS significantly after age 81.
We also found that when the DIV patient presented
with more specific description such as vertigo or imbal-
ance, rather than nonspecific dizziness, this information
could also help predicting AIS (imbalance) or non-AIS
(vertigo).
Being able to more reliably rule out those having AIS
among DIV patients with readily available data in the ED
would be useful. Three bedside tools are currently avail-
able for the initial evaluation of patients with dizziness—
the ABCD2 score, TriAGe+ score, and the HINTS
exam.13,14,16-18
The ABCD2 score is an AIS risk predictive score for TIA
patients that consist of age  60, blood pressure  140/90,
clinical features, clinical duration, and diabetes.19,20 Navi
 ARTICLE IN PRESS
STROKE PREDICTORS IN DIZZINESS PATIENTS
Table 3. Factors associated with AIS in patients with DIV
Positive factors
Admission presentation
Imbalancex
Age
 60 years old*,y
Race
African-Americanx
Examination
BP > 140/90*,y
Central pattern nystagmusz
Other focal neurologic findings*,y,z
Past medical history
Hypertensionx
Diabetes*,x
Hypercholesterolemiax
Tobacco usex
Atrial fibrillationx
Prior AIS due to extracranial artery atherosclerosisx
AIS, acute ischemic stroke; DIV, dizziness, imbalance, vertigo.
*Component of ABCD2 score.
†
Component of TriAGe+ score.
‡
Component of HINTS exam.
§
Findings from our study.
et al reported in a retrospective study of 907 DIV patients
presenting to the ED that the ABCD2 score predicted cere-
brovascular disease with 61.1% sensitivity and 62.3%
specificity, when the cutoff is set at 4.16 The target popula-
tion of Navi et al was similar to ours.
Kuroda et al developed the TriAge+ score to predict
AIS in patients with dizziness or vertigo.13 They found
male sex, blood pressure > 140/90, initial presentation of
nonspecific dizziness, and presence of brainstem or cere-
bellar dysfunction or focal weakness or speech
impairment predicted AIS. The presence of dizziness trig-
ger and prior episode of dizziness or vertigo predicted a
lower likelihood of AIS.
The HINTS exam consists of the head impulse test, pres-
ence of nystagmus on gaze exam, and cover-uncover test of
skew. Patients with a central pattern of nystagmus (direction
changing gaze-evoked horizontal nystagmus, pure vertical,
or torsional nystagmus), positive skew, or a direction-fixed
horizontal nystagmus with normal head impulse test are
considered to have a positive test, and therefore have a
higher likelihood of having central cause of dizziness.
HINTS exam has 97%-100% sensitivity and 84%-96% speci-
ficity in identifying a central lesion (AIS, hemorrhage, active
multiple sclerosis lesion) in acute vestibular syndrome
(AVS) with nystagmus. AVS was defined to be the acute
onset of continuous vertigo or dizziness.17,18
Kerber et al analyzed predictors of a central cause in
patients having AVS with nystagmus or new imbalance
when walking.14 Independent predictors were ABCD2 score
and other CNS feature (visual field defect, dysmetria, or sen-
sory symptom). HINTS exam did not predict central cause,
5
Negative factors
Admission presentation
Vertigoy,x
Age
> 81 years oldx
Sex
Femaley,x
History of pesent illness
Dizziness triggery
Past medical history
Coronary artery diseasex
Anemiax
Asthmax
Depressive and anxiety disordersx
but when HINTS components were separately analyzed,
central pattern nystagmus predicted central cause.
Our study adds several more potentially useful AIS pre-
dictors, such as previous AIS due to extracranial artery
atherosclerosis and admission presentation of imbalance.
More importantly, our study also adds “negative” AIS
predictors, such as age > 81, anemia, and psychiatric dis-
orders. Table 3 lists the positive and negative AIS predic-
tors for DIV patients.
Our study has several important limitations. Some clini-
cal information, including the detailed neurological exam-
ination, was not available in the SPARCS database. Only
36% of patients with discharge diagnosis of AIS had diag-
nostic brain image during the ED and hospital visit, sug-
gesting potential errors in discharge diagnosis. There is a
possibility of coding mistakes, although ICD-9-CM codes
are generally accurate in providing cerebrovascular diag-
noses.21 Our study was retrospective and can only pro-
vide hypotheses for future testing. A future prospective
study would be needed to confirm our study findings.
Disclosures
None.
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