a b s t r a c t

Background: Despite the usefulness of the Cincinnati Prehospital Stroke Scale (CPSS) for rapid recognition of acute stroke, its ability to assess Stroke severity is unclear. We investigated the usefulness of CPSS for assessment of stroke severity by comparing CPSS and National Institutes of Health Stroke Scale scores in patients who were candidates for thrombolytic therapy at hospital admission within 6 hours of symptom onset.

Methods: We conducted a retrospective analysis of a prospective registry database of consecutive patients included in the Brain Salvage through Emergency Stroke Therapy program. In the emergency department, CPSS score was determined by emergency medical technicians. A CPSS cut-off score was estimated for candidates of thrombolytic therapy by comparing CPSS and NIHSS scores of patients who actually received thrombolytic therapy. Clinical outcomes were compared among patients with scores near the cut-off. Independent predictors of outcome were evaluated by multivariate logistic regression analysis.

Results: Strong correlations were observed between CPSS and NIHSS scores within 3 hours (R = 0.778) and 6 hours (R = 0.769) of symptom onset. The optimal cut-off score was 2 for CPSS was associated with actual usage of intravenous tissue plasminogen activator (odds ratio [OR] 34.455; 95% confidence interval [CI] 7.924- 149.817, P b .0001) and actual usage of thrombolytic therapy overall (intravenous tissue plasminogen activator or intra-arterial urokinase) (OR 36.310; 95% CI 10.826-121.782, P b .0001).

Conclusion: The CPSS is an effective prehospital stroke scale for the determination of stroke severity and identification of candidates for thrombolytic therapy.

(C) 2013

Introduction

The clinical catchphrase “time is brain” reflects the time-sensitive nature of stroke. The ultimate goal of stroke care is to minimize acute brain injury and maximize patient recovery [1]. Good functional outcome after acute stroke begins with immediate recognition of the stroke as it occurs [2]. The Cincinnati Prehospital Stroke Scale (CPSS) is an effective tool to identify stroke, requiring only 30 to 60 seconds, that can be used by emergency medical service (EMS) personnel and laypersons [3]. The CPSS has shown excellent reproducibility among Prehospital care providers and can accurately identify candidates for thrombolytic therapy [4].

? Conflict of interests: None.

* Corresponding author. Department of Emergency Medicine, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Republic of Korea. Tel.: +82 2 2228-2460.

E-mail address: [email protected] (I. Park).

Intra-arterial thrombolysis and intravenous administration of intravenous tissue plasminogen activator (IV-tPA) can improve outcomes for many patients if performed shortly after onset of acute stroke [5,6]. EMS personnel should consider triage to the appropriate hospital based on its stroke care capability and distance. A rapid triage system for assessing stroke severity should be used in the emergency department (ED) to minimize delays to diagnosis and therapy [1]. Although CPSS facilitates rapid recognition of acute stroke, its ability to assess stroke severity is unclear [7].

We investigated the usefulness of the CPSS to determine stroke severity by comparing CPSS and National Institutes of Health Stroke Scale scores in patients who may be candidates for thrombol- ysis on arrival at the hospital within 6 hours of symptom onset.

Methods

We carried out a retrospective analysis of a prospective registry database of all consecutive patients included in the brain salvage

0735-6757/$ – see front matter (C) 2013 http://dx.doi.org/10.1016/j.ajem.2013.08.029

1700 J.S. You et al. / American Journal of Emergency Medicine 31 (2013) 1699–1702

through emergency stroke therapy (BEST) program in a tertiary academic hospital with an annual ED census of 65,000 visits. The institutional review board of our institute approved this study. We included patients with ischemic stroke or transient ischemic attack who at the ED within 6 hours of symptom onset between Sep 1, 2010, and Sep 30, 2011.

In our hospital, the BEST program, which is based on a computerized physician Order entry system, has been used by the stroke team since 2004. Upon arrival of patients to the ED, physicians, nurses, or emergency medical technicians in the triage area rapidly identify candidates for Thrombolytic treatment based on the five stroke warning signs developed for the general population by the American Heart Association stroke council [2,6,8]. When a patient with at least one warning sign arrives within 12 hours of symptom onset, an ED physician in the triage area activates the BEST program by selecting the activation icon on the order entry window. [6,8] The patient’s name is then highlighted orange in the patient list for easy identification. At the same time, the ED physician consults an on-call neurologist and senior ED physicians. [6,8] To reduce evaluation time, medical orders for computed tomography (CT) scan and blood tests for these patients automatically activate a beeping sound and a pop- up window on the monitors of hospital staff involved in carrying out these orders. [6,8] Despite efforts for early stroke approach by magnetic resonance imaging (MRI), MRI is not as widely available as CT in our ED. Upon arrival of patients to the ED, non-contrast CT was performed in patients within 3 hours of symptom onset, and brain CT angiography including neck vessels was performed in patients after 3 hours of symptoms’ onset or without lasting symptom. The BEST program was activated for a total of 737 patients during the study period. Exclusion criteria were (1) arrival to the ED N 6 hours after symptom onset (n = 191), (2) diagnosis of hemorrhagic stroke or brain tumor on non-contrast CT (n = 96), (3) diagnosis of other diseases such as encephalitis, seizure, hypoglycemia, or syncope after admission (n = 155), (4) inability to evaluate stroke because of life- threatening disease (n = 3), (5) transfer from another hospital after MRI or IV-tPA (n = 3), and (6) incomplete data, such as incomplete stroke scoring (n = 5). In the ED, the CPSS score was determined by one of the six EMTs included in the study, and the NIHSS score was determined by a neurologist. Diagnosis was confirmed by diffusion- weighted MRI and angiography, or brain CT angiography (including neck vessels) after non-contrast CT. Patients diagnosed with acute stroke (b 3 hours duration) received IV-tPA. Intra-arterial thrombo- lytic therapy or sequential combination thrombolytic therapy was performed in selected patients with major stroke (b 6 hours duration) by occlusion of the Middle cerebral artery, vertebral artery, or Basilar artery, who were not otherwise candidates for IV-tPA or showed no

improvement after IV-tPA.

Statistical analysis

Demographic and clinical data are presented as median (Q1, Q3) or proportion, as appropriate. Patient baseline characteristics were compared by Mann-Whitney U test and ?² test. The relationship between CPSS and NIHSS scores was analyzed using Spearman rank correlation. Patients with NIHSS scores of 5 to 22 were considered

candidates for IV-tPA if symptom onset occurred b 3 hours before hospital admission. An NIHSS score N 5 qualified patients for intra- arterial urokinase (IA-UK) infusion if symptom onset occurred b 6 hours before admission. A cutoff score for the CPSS for thrombolytic therapy was determined by comparing CPSS and NIHSS scores. Youden’s index was used to determine the optimal cut-off point in the receiver operating characteristics curve to maximize the sensi- tivity and specificity.

Independent predictors of outcome were determined using multivariate logistic regression analysis, by entering significant variables from the univariate analysis; P b .05 was considered significant. Statistical analysis was conducted using SAS version 9.2 (SAS Institute Inc, Cary, NC).

Results

The study included a total of 284 (38.5%) consecutive patients with ischemic stroke or transient ischemic attack as final diagnosis who arrived at the ED within 6 hours of symptom onset. Among the 184 (64.8%) patients admitted within 3 hours of onset, thrombolytic therapy consisted of IV-tPA (n = 41, 22.3%) or the sequential combination of t-PA and IA-UK (n = 11, 6.0%). The single therapy IA- UK was given to 14 patients (b 3 hours onset; n = 5, >=3 hours onset; n

= 9). A strong correlation was observed between CPSS and NIHSS scores for patients admitted within 3 hours of symptom onset (R = 0.778; 95% CI [0.713-0.829], P b .0001) and patients admitted within 6 hours of onset (R = 0.769; 95% CI [0.716-0.812], P b .0001).

The optimal cut-off point for CPSS was determined to be 2, based on actual usage of IV-tPA in patients admitted within 3 hours of onset (96.2% sensitivity, 62.1% specificity) and actual usage of IV-tPA or IA- UK in patients admitted within 6 hours (95.5% sensitivity, 65.6% specificity) (Table 1). The CPSS cut-off score was strongly associated with actual administration of IV-tPA (P b .0001) or IA-UK (P b .0001) (Table 2). Results of multivariate logistic regression confirmed that CPSS >=2 was associated with actual IV-tPA usage (odds ratio [OR] 34.455; 95% CI 7.924-149.817, P b .0001) and NIHSS scores of 5 to 22

and was associated actual IV-tPA or IA-UK usage (OR 36.310; 95% CI 10.826-121.782, P b .0001) and NIHSS scores 5 to 42 (Table 3).

Discussion

The NIHSS is a useful clinical tool for the assessment of stroke severity and provides important information regarding early progno- sis and Treatment decisions [5]. However, this 15-item stroke scoring scale is relatively time-consuming and cumbersome in the field. The simplified 3-item CPSS, which is based on the NIHSS, rapidly identifies acute stroke by evaluating weakness in the face and arm and difficulty with speech. The Face Arm Speech Time message based on the CPSS is being reintroduced in a public education campaign to improve knowledge of stroke signs and symptoms. One or more signs of stroke in the CPSS are present in 88% of all strokes and transient ischemic attacks [2,9]. Moreover, untrained laypersons have used the CPSS to accurately identify stroke signs in mock survivors [9]. Nevertheless, this prehospital stroke scale did not predict stroke severity in a previous study [7]. The results of our study showed that

Table 1

A cut-off CPSS score was estimated by the receiver operating characteristic curve for candidates of IV-tPA and IA-UK therapy by comparing between CPSS and NIHSS scores of patients who actually received these treatments

Youden’s index = sensitivity + specificity – 1; AUC, area under the curve.

J.S. You et al. / American Journal of Emergency Medicine 31 (2013) 1699–1702 1701

Table 2

Clinical outcomes of patients with ischemic stroke according to CPSS score

Results are expressed as n (%) or median (IQR).

the CPSS score strongly correlates with the NIHSS score and can identify candidates for thrombolytic therapy within 3 or 6 hours of acute ischemic stroke onset.

Administration of IV-tPA is recommended for selected patients within 3 hours of ischemic stroke onset. In addition, intra-arterial fibrinolysis is beneficial for carefully selected patients with major ischemic stroke (b 6 hours) caused by middle cerebral artery occlusion who are otherwise candidates for IV-tPA [2]. New 2013 guidelines state that combined intravenous and intra-arterial thrombolytic therapy may achieve rapid recanalization of major intracranial artery occlusions [2,10]. For the best outcomes, EMS personnel should consider triage to the stroke center with the highest capability for Acute stroke management [1]. Although previous studies have reported variable sensitivity and specificity of the CPSS, this tool is an effective screening tool for stroke and can also be used to identify candidates for thrombolytic therapy by assessing stroke severity. A cut-off CPSS score of 2 showed 96.2% sensitivity and 62.1% specificity for the actual administration of IV-tPA within 3 hours of stroke onset and 95.5% sensitivity and 65.6% specificity for the actual administra- tion of IV-tPA or IA-UK within 6 hours of onset. We found that IV-tPA was administered to 50 (36.2%) of the 138 patients with CPSS scores

>=2 and only 2 of the 146 patients (1.4%) with CPSS scores b 2. Transient ischemic attacks were experienced by fewer patients with CPSS scores >=2 (7.2%) than those with CPSS b 2 (41.8%). Thus, a CPSS score N 2 can identify candidates for both IV-tPA and IA-UK among patients within 3 or 6 hours of stroke onset. The CPSS can be used on scene or with the BEST program for rapid triage of stroke patients in the hospital. The effectiveness of CPSS for stroke severity can be reintroduced in public education programs.

Limitations

There were several limitations to our study. First, the study was performed using convenience samples, and although the CPSS is a prehospital stroke scale, in our study the CPSS score was determined by EMTs in the ED. Second, although the participants were trained to use the CPSS, inter-observer reliability was not evaluated. Third, assessments by CPSS and NIHSS were not performed at the same time, and possible changes in symptoms between the 2 assessments were not considered in our study. Fourth, although IV-tPA is recommended for eligible patients who can be treated 3 to 4.5 hours after stroke onset [2], our predetermined protocol specified IV-tPA administration within 3 hours of symptom onset and sequential combination treatment from 3 to 4.5 hours of onset. In the future, a prospective study with a larger number of patients will be needed to determine the effectiveness of CPSS used by EMTs on the scene.

Conclusion

The CPSS is an effective prehospital stroke scale that can assess stroke severity and identify candidates for thrombolytic therapy among patients with acute ischemic stroke within 6 hours of symptom onset.

Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2013R1A1A2009391).

Table 3

Results of multivariate logistic regression

Actual IV-tPA usage Actual IV-tPA or IA-UK usage NIHSS score (5-22) NIHSS score (>=5)

1702 J.S. You et al. / American Journal of Emergency Medicine 31 (2013) 1699–1702

References

1. Jauch EC, Cucchiara B, Adeoye O, et al. Part 11: adult stroke: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122(Suppl 3):S818-28.
2. Jauch EC, Saver JL, Adams Jr HP, 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.
3. Liferidge AT, Brice JH, Overby BA, et al. Ability of laypersons to use the Cincinnati Prehospital Stroke Scale. Prehosp Emerg Care 2004;8:384-7.
4. Kothari RU, Pancioli A, Liu T, et al. Cincinnati Prehospital Stroke Scale: reproducibility and validity. Ann Emerg Med 1999;33:373-8.
5. Adams Jr HP, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/A- merican Stroke Association Stroke Council, Clinical Cardiology Council, Cardio- vascular Radiology and Intervention Council, and the Atherosclerotic Peripheral

   Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007;38:1655-711.

   Nam HS, Han SW, Ahn SH, et al. Improved time intervals by implementation of computerized physician order entry-based stroke team approach. Cerebrovasc Dis 2007;23:289-93.

6. Iguchi Y, Kimura K, Watanabe M, et al. Utility of the Kurashiki Prehospital Stroke Scale for hyperacute stroke. Cerebrovasc Dis 2011;31:51-6.
7. Heo JH, Kim YD, Nam HS, et al. A computerized in-hospital alert system for thrombolysis in acute stroke. Stroke 2010;41:1978-83.
8. Wall HK, Beagan BM, O’Neill J, et al. Addressing stroke signs and symptoms through public education: the Stroke Heroes Act FAST campaign. Prev Chronic Dis 2008;5:A49.
9. Ogawa A, Mori E, Minematsu K, et al. Randomized trial of intraarterial infusion of urokinase within 6 hours of middle cerebral artery stroke: the middle cerebral artery embolism local fibrinolytic intervention trial (MELT) Japan. Stroke 2007;38: 2633-9.