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Clinical Selection Strategies to Identify Ischemic Stroke

Patients With Large Anterior Vessel Occlusion


Results From SITS-ISTR (Safe Implementation of Thrombolysis in Stroke
International Stroke Thrombolysis Registry)
Jan F. Scheitz, MD*; Azmil H. Abdul-Rahim, MBChB, Msc(StrokeMed)*;
Rachael L. MacIsaac, PhD; Charith Cooray, MD; Heidi Sucharew, PhD; Dawn Kleindorfer, MD;
Pooja Khatri, MD, MSc; Joseph P. Broderick, MD; Heinrich J. Audebert, MD;
Niaz Ahmed, MD, PhD; Nils Wahlgren, MD, PhD; Matthias Endres, MD;
Christian H. Nolte, MD*; Kennedy R. Lees, MD, FRCP*; on behalf of SITS Scientific Committee

Background and PurposeThe National Institutes of Health Stroke Scale (NIHSS) correlates with presence of large
anterior vessel occlusion (LAVO). However, the application of the full NIHSS in the prehospital setting to select patients
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eligible for treatment with thrombectomy is limited. Therefore, we aimed to evaluate the prognostic value of simple
clinical selection strategies.
MethodsData from the Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Registry
(January 2012May 2014) were analyzed retrospectively. Patients with complete breakdown of NIHSS scores and
documented vessel status were included. We assessed the association of prehospital stroke scales and NIHSS symptom
profiles with LAVO (internal carotid artery, carotid-terminus or M1-segment of the middle cerebral artery).
ResultsAmong 3505 patients, 23.6% (n=827) had LAVO. Pathological finding on the NIHSS item best gaze was strongly
associated with LAVO (adjusted odds ratio 4.5, 95% confidence interval 3.85.3). All 3 facearmspeechtime test (FAST)
items identified LAVO with high sensitivity. Addition of the item best gaze to the original FAST score (G-FAST) or high
scores on other simplified stroke scales increased specificity. The NIHSS symptom profiles representing total anterior
syndromes showed a 10-fold increased likelihood for LAVO compared with a nonspecific clinical profile. If compared with
an NIHSS threshold of 6, the prehospital stroke scales performed similarly or even better without losing sensitivity.
ConclusionsSimple modification of the facearmspeechtime score or evaluating the NIHSS symptom profile may
help to stratify patients risk of LAVO and to identify individuals who deserve rapid transfer to comprehensive stroke
centers. Prospective validation in the prehospital setting is required. (Stroke. 2017;48:290-297. DOI: 10.1161/
STROKEAHA.116.014431.)
Key Words: FAST stroke management thrombectomy thrombolysis vessel occlusion

T he beneficial effects of endovascular treatment (EVT) in


addition to intravenous thrombolysis have been proven in
patients with acute ischemic stroke caused by large anterior
and complex diagnostic imaging resources often have limited
availability outside of comprehensive stroke centers (CSC)
or clinical trial settings, there is a pressing need to develop
vessel occlusion (LAVO).15 Given the time-dependent effects strategies to identify patients who need bypass of a primary
of revascularization,6,7 rapid recognition of potentially eligi- stroke center and transfer to CSCs with EVT capability.
ble patients for such treatment is critical, both in the prehos- These strategies should balance well between sensitivity to
pital and in the early in-hospital triage stage. Because EVT capture the majority of LAVO and appropriate specificity to

Received July 5, 2016; final revision received August 14, 2016; accepted September 14, 2016.
From the Center for Stroke Research Berlin (J.F.S., H.J.A., M.E., C.H.N.), Klinik fr Neurologie (J.F.S., H.J.A., M.E., C.H.N.), Excellence Cluster
NeuroCure (M.E.), German Center for Cardiovascular Research (DZHK) (M.E.), and German Center for Neurodegenerative Diseases (DZNE) (M.E.),
CharitUniversittsmedizin Berlin, Campus Benjamin Franklin, Germany; Stroke Research, Institute of Cardiovascular & Medical Sciences, University
of Glasgow, United Kingdom (A.H.A.-R., R.L.M., K.R.L.); Department of Clinical Neurosciences, Karolinska Institutet and Department of Neurology,
Karolinska University Hospital, Solna, Sweden (C.C., N.A., N.W.); Division of Biostatistics and Epidemiology, Cincinnati Childrens Hospital Medical
Center, OH (H.S.); and Department of Emergency Medicine, University of Cincinnati, College of Medicine, OH (D.K., P.K., J.P.B.).
Guest Editor for the article was Michael Brainin, MD, Dr (hon), FESO.
*Drs Scheitz, Abdul-Rahim, Nolte, and Lees contributed equally.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.
116.014431/-/DC1.
Correspondence to Jan F. Scheitz, MD, Department of Neurology, CharitUniversittsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm
30, D-12200 Berlin, Germany. E-mail jan.scheitz@charite.de
2017 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.116.014431

290
Scheitz et al Prediction of Large Anterior Vessel Occlusion 291

avoid overwhelming CSCs with patients who do not require the Cincinnati Stroke Triage Assessment Tool [C-STAT], and the
EVT. Prehospital Acute Stroke Severity scale [PASS]).2427 Table I in the
online-only Data Supplement summarizes components of the prehos-
A high National Institutes of Health Stroke Scale (NIHSS)
pital stroke scales that were analyzed. Because the NIHSS item best
score is strongly associated with the presence of LAVO.810 gaze is missing in the typical FAST algorithm but strongly associated
Therefore, the NIHSS is frequently recommended to select with LAVO,21,2628 we tested the hypothesis that adding the item best
patients for EVT.11,12 Because of the complexity of a complete gaze to FAST (G-FAST) may improve its predictive value.
NIHSS examination, simple stroke recognition scores like the The NIHSS item profiles that were recently described and vali-
dated may prove useful for clinical stroke prognostication and
facearmspeechtime (FAST) test are commonly used by research studies.1315 The profiles grouped the 15 individual attributes
paramedics to evaluate patients with suspected stroke in the of NIHSS, using latent class analysis, into 6 clinical symptom pro-
field. Moreover, certain NIHSS items or symptom patterns files.1315 We applied the probabilities of profile membership gener-
may be more informative of LAVO compared with simply ated by Sucharew et al13 to our cohort. Profile A represents a total
a score reflecting the overall severity of deficits. Recently, 6 anterior circulation syndrome (TACS) of the dominant hemisphere;
Profile B, a TACS of the nondominant hemisphere; Profile C, a partial
profiles of NIHSS symptoms have been proposed and shown anterior circulation syndrome (PACS) of the dominant hemisphere
to improve the clinical value of the overall NIHSS concerning with predominant language deficits; Profile D, a PACS of dominant
prediction of functional outcome and mortality.1315 To evalu- hemisphere without predominant language deficits; Profile E, a PACS
ate different simple triage strategies beyond the total NIHSS of the nondominant hemisphere; and Profile F, a mild clinical syn-
sum score, we aimed to analyze the value of the common pre- drome with low probability of abnormal findings on all NIHSS items
(Table II in the online-only Data Supplement).
hospital stroke scales and the NIHSS item profiles to predict
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LAVO in acute stroke patients.


Statistical Methods
Continuous variables were compared using the t test or Mann
Methods Whitney U test and were presented as meanstandard deviation
(SD) or median (interquartile range), where appropriate. Categorical
Data Source, Design, Patients, and Outcomes variables were compared using the Pearson 2 test and presented as
We conducted a retrospective analysis on individual patient data percentages (n). Multivariable logistic regression analysis was per-
obtained from the SITS-ISTR (Safe Implementation of Thrombolysis formed to assess the association of single NIHSS items, the prehospi-
in Stroke International Stroke Thrombolysis Registry) between tal stroke scales, and the NIHSS profiles with LAVO. Adjustment was
January 2012 and May 2014. SITS-ISTR is a multinational open made for variables significantly associated with LAVO in the univari-
registry of acute ischemic stroke patients who received reperfusion able comparison (sex, atrial fibrillation, onset-to-treatment time). We
therapies.16,17 Patients from 132 participating centers with complete also adjusted the analysis for age, prestroke modified Rankin Scale
breakdown of NIHSS scores and status of vessel occlusion were score >2 (ie, being dependent from others in activities of daily liv-
included. Baseline characteristics included data on age, sex, stroke ing), and history of previous stroke because prestroke disability and
severity according to the NIHSS, onset-to-treatment time, prestroke residual neurological deficits from a previous stroke may affect the
modified Rankin Scale, and medical history (ie, previous stroke, cur- NIHSS. For the prehospital stroke scales, the lowest score was used
rent smoking, hypertension, diabetes mellitus, atrial fibrillation, and as the reference. For the NIHSS item profiles, profile F (stroke with
chronic heart failure). low probabilities of abnormal findings on all 15 items) was used as
Our outcome of interest was the presence of LAVO (ie, occlusion reference. Regarding single NIHSS items, we applied forward step-
within the internal carotid artery, carotid-T and M1 segment of the wise regression analysis to identify the NIHSS item that improves the
middle cerebral artery). The definition of LAVO was in accordance model most.
to the recent positive EVT trials in patients with anterior circulation We computed area under the receiver operating characteristics
stroke.18,19 Vessel imaging was usually performed before treatment curve (AUC) and the respective 95% confidence intervals (CIs) to
with thrombolysis or shortly after application of bolus dose. assess the global performance of the prehospital stroke scales and
Two sensitivity analyses were conducted. First, we added basilar NIHSS symptom profiles to predict LAVO. AUC values were com-
artery occlusion (BAO) to the definition of large vessel occlusion. pared using the method of DeLong et al.29 The receiver operating
Although currently EVT is not covered by Class I recommendation characteristics curvederived optimal cutoff for the scores was deter-
in BAO, guidelines recommend clinical evaluation of patients with mined at the maximal Youden Index.30 Finally, we calculated sensitiv-
BAO in CSCs.11 Thus, prehospital detection of patients with BAO is ity, specificity, positive predictive value (PPV), negative predictive
important. Second, we confined the analysis to patients with mod- value (NPV), and overall accuracy for the prediction of LAVO at
erate stroke severity (NIHSS score =611). This group constitutes high-sensitivity (>85%) and high-specificity (>75%) cutoffs of the
a relevant subgroup because most false-positive or false-negative common prehospital stroke scales. For consistency with the sensitiv-
identifications of LAVO occur, and the majority of patients evaluated ity of the widely accepted FAST and Cincinnati Prehospital Stroke
in the field have overall moderate stroke severity. The upper limit Scale (CPSS) scores for recognition of stroke patients in the field,
of NIHSS score of 11 was chosen for consistency with optimal cut- a sensitivity >85% was considered the high-sensitivity threshold.31,32
off for prediction of LAVO in the previous studies.9,2022 The lower The target specificity of >75% is even higher than the average speci-
threshold of NIHSS score of 6 was chosen because this cutoff showed ficity of common stroke recognition tools to discriminate strokes
at least 90% sensitivity for LAVO in the present cohort and previ- from stroke mimics and suggests rate of futile transfers of <1 out
ous reports.20,21 Stroke with NIHSS score <6 is often considered mild of 4.32,33 Data analysis was performed using SPSS (version 22, IBM,
stroke, with low probability of LAVO.23 New York) or MedCalc (Version 16.2, Ostend, Belgium).

Common Prehospital Stroke Scales Results


and NIHSS Item Profiles During the study period, 3505 patients with complete break-
We evaluated prehospital stroke recognition scales that could be down of NIHSS items and data on vessel occlusion site were
derived directly from the individual breakdown of NIHSS items
at baseline (ie, FAST test) and simplified NIHSS scores that have available for analysis. LAVO was present in 23.6% (n=827) of
been shown to be associated with LAVO (ie, 3-item Stroke Scale patients. Baseline characteristics of patients with or without
[3I-SS], the Rapid Arterial Occlusion Evaluation Scale [RACE], LAVO are shown in Table1. Baseline NIHSS was strongly
292StrokeFebruary 2017

associated with LAVO (adjusted odds ratio [OR] 1.15, 95% CI especially in patients presenting with moderate stroke sever-
1.131.16, per point). Sensitivity, specificity, PPV, and NPV at ity. When compared with the NIHSS cutoff 6, which is rec-
different NIHSS cutoffs are shown in Table III in the online- ommended by current American Heart Association/American
only Data Supplement. Stroke Association guidelines to select patients for thrombec-
As shown in Table2, there was a graded relationship tomy (AUC 0.60, 95% CI 0.580.62), AUCs of the G-FAST3
between prehospital stroke scales scores and NIHSS item pro- (AUC 0.64, 95% CI 0.620.66) and C-STAT1 (AUC 0.63,
files with presence of LAVO. Compared with a FAST score 95% CI 0.610.65) were significantly higher (P<0.001), but
of 0 or 1, patients with all 3 FAST items being positive had the cut-offs showed similar sensitivity (89%91%; Table3).
an adjusted OR of 7.9 (95% CI 5.211.9) for LAVO (sensitiv-
ity 84%, specificity 44%, PPV 32%, and NPV 90%). Forward Sensitivity Analyses
stepwise multiple regression analysis suggested best gaze Similar results were obtained after addition of 93 patients with
to be the single NIHSS item with strongest association with BAO to the large vessel occlusion definition (n=920; 26.2%),
LAVO (adjusted OR 4.5, 95% CI 3.85.3). Addition of abnor- although the overall strength of the association was slightly
mal gaze to FAST improved specificity (Table2) and resulted weaker (Table V in the online-only Data Supplement). The
in significant improvement of the AUC for LAVO compared optimal NIHSS cutoff was also 12 (sensitivity 70%, specific-
with FAST alone (P<0.001; Table IV in the online-only Data ity 70%, PPV 45%, and NPV 87%), and the cutoff showing
Supplement). at least 85% sensitivity was 7 (sensitivity 88%, specific-
The 6 NIHSS symptom profiles that represent different ity 39%, PPV 34%, and NPV 90%). The optimal cutoffs for
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clinical phenotypes were reproduced from previous analy- detection of LVO including BAO were FAST=3, G-FAST=4,
ses.1315 Patients allocated to NIHSS symptom profiles rep- C-STAT2, 3I-SS2, PASS2, and RACE5 (Table VI in the
resenting TACS (profile A and B) had a >6-fold increase of online-only Data Supplement).
LAVO compared with all other profiles combined (OR 6.2, When we focused our analysis to patients with moderate
95% CI 5.17.5). stroke severity (NIHSS 611, n=1257 patients), frequency of
Table3 shows sensitivity, specificity, PPV, and NPV for LAVO was 12.6% (19.2% of all observed LAVO within the
presence of LAVO of different cutoffs of the entire NIHSS, the cohort, 159 of 827). The common prehospital stroke scales
prehospital stroke scales, and NIHSS item profiles. High sen- performances for prediction of LAVO did not differ from the
sitivity was observed for FAST2, G-FAST3, C-STAT1, overall total NIHSS score (Table III in the online-only Data
3I-SS1, PASS1, RACE3, and clinical signs of at least a Supplement), with the highest absolute AUC value for the
PACS (NIHSS symptom profiles A to E), while high speci- C-STAT. Similar to the entire cohort, increasing integer val-
ficity was observed for G-FAST=4, C-STAT3, 3I-SS=3, ues of the common prehospital stroke scales showed disparate
PASS=3, RACE6, and clinical signs of TACS (NIHSS symp- associations with LAVO (Table VII in the online-only Data
tom profile A and B). Supplement). Profiles A and B (left and right TACS) were
The AUC of the prehospital stroke scales and NIHSS item associated with a nearly 3-fold increased risk of LAVO com-
profiles to predict LAVO was similar and nearly as good as the pared with all other profiles (CF combined; adjusted OR 2.8,
entire NIHSS (Table IV in the online-only Data Supplement), 95% CI 2.04.0).

Table 1. Baseline Characteristics of the Cohort According to Presence of LAVO


Entire Cohort, LAVO, No LAVO,
N=3505 N=827 N=2678 P Value
Age, y, mean (SD) 68.1 (13.6) 68.3 (13.5) 68.1 (13.6) 0.631
Sex, male, % (n) 56.1 (1967) 52.6 (435) 57.2 (1532) 0.020
Pre-mRS score >2, % (n), 164 missings 4.0 (134) 3.7 (29) 4.1 (105) 0.577
NIHSS sum, median (IQR) 9 (616) 16 (1120) 8 (513) <0.001
Endovascular treatment, % (n) 8.0 (282) 26.6 (220) 2.3 (62) <0.001
Atrial fibrillation, % (n), 16 missings 18.9 (661) 22.8 (188) 17.7 (473) 0.001
Chronic heart failure, % (n), 21 missings 7.7 (268) 8.6 (71) 7.4 (197) 0.255
Current smoker, % (n), 121 missings 17.5 (593) 18.2 (143) 17.3 (450) 0.560
Diabetes mellitus, % (n), 13 missings 18.5 (645) 16.9 (139) 19.0 (506) 0.187
Hyperlipidemia, % (n), 34 missings 29.6 (1028) 31.5 (257) 29.1 (771) 0.188
Hypertension, % (n), 12 missings 64.6 (2258) 64.8 (533) 64.6 (1725) 0.935
Previous stroke, % (n), 20 missings 12.0 (417) 11.1 (91) 12.2 (326) 0.358
Onset-to-needle, min, median (IQR) 150 (119195) 145 (115190) 150 (120195) 0.028
IQR indicates interquartile range; LAVO, large anterior vessel occlusion; mRS, modified Rankin Scale; and NIHSS, National
Institutes of Health Stroke Scale.
Scheitz et al Prediction of Large Anterior Vessel Occlusion 293

Table 2. Association of NIHSS Categories, NIHSS Symptom Profile, and Simplified NIHSS Scores With LAVO
Number Needed to
Score Name Score Result LAVO n/N Screen* Adjusted OR for LAVO
NIHSS categories 05 72/828 11.5 1 (Reference)
610 128/1107 8.7 1.40 (1.021.92)
1115 191/679 3.6 4.29 (3.155.83)
>15 436/891 2.1 10.72 (8.0014.37)
NIHSS symptom profile A 318/793 2.5 10.24 (6.4016.38)
B 310/775 2.5 9.95 (6.2215.92)
C 38/352 9.3 1.85 (1.053.25)
D 70/644 9.2 1.62 (0.972.72)
E 68/591 8.7 1.87 (1.123.13)
F 23/350 15.2 1 (Reference)
FAST 0 3/63 20.8 1 (Reference)
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1 25/429 17.2 1.65 (0.387.18)


2 104/806 7.8 4.19 (1.0117.45)
3 695/2207 3.1 12.29 (2.9950.57)
G-FAST 0 3/56 18.6 1 (Reference)
1 22/398 18.2 1.37 (0.316.05)
2 68/686 10.0 2.85 (0.6811.99)
3 265/1334 5.0 5.96 (1.4424.68)
4 468/1029 2.2 20.52 (4.9784.99)
C-STAT 0 92/1091 11.9 1 (Reference)
1 145/953 6.6 1.85 (1.382.48)
2 108/410 3.8 4.17 (3.045.74)
3 266/606 2.3 8.81 (6.6511.66)
4 216/445 2.1 10.58 (7.8214.32)
PASS 0 23/296 12.8 1 (Reference)
1 153/1446 9.4 1.38 (0.862.24)
2 333/1074 3.2 5.63 (3.538.97)
3 318/689 2.2 11.16 (6.9218.00)
RACE 01 55/781 14.2 1 (Reference)
2 63/587 9.3 1.75 (1.182.60)
3 55/368 6.7 2.35 (1.543.57)
4 65/327 5.0 3.42 (2.275.14)
56 153/590 3.9 4.79 (3.386.79)
79 436/852 2.0 15.18 (10.9621.02)
3I-SS 0 68/803 11.8 1 (Reference)
1 221/1419 6.4 1.90 (1.412.56)
2 367/900 2.5 7.47 (5.5610.00)
3 171/383 2.2 8.44 (6.0311.81)
3I-SS indicates 3-item stroke scale; C-STAT, Cincinnati Stroke Triage Assessment Tool; FAST, facearmspeechtime test; G-FAST,
gazefacearmspeechtime score; LAVO, large anterior vessel occlusion; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio;
PASS, Prehospital Acute Stroke Severity scale; and RACE, Rapid Arterial Occlusion Evaluation Scale.
*Number needed to screen with the respective test result to identify a LAVO, per 100 patients.
Adjusted for age, sex, atrial fibrillation, pre-mRS, prior stroke, and onset-to-treatment time.
In G-FAST, the item best gaze was added to the FAST score (G-FAST).
In contrast to the original version, only one point was assigned per pathological item.
294StrokeFebruary 2017

Table 3. Sensitivity, Specificity, PPV, and NPV for Presence of LAVO at Certain Cutoffs of the NIHSS, Simplified
NIHSS Scores, and NIHSS Symptom Profiles
n/N (%) Sensitivity Specificity PPV NPV Accuracy
Cutoffs of scores with >85% sensitivity and highest possible specificity
NIHSS8 2183/3505 (63.2) 85.6 44.9 28.2 91.3 54.5
NIHSS6* 2677/3505 (76.4) 91.3 28.2 28.2 91.3 43.1
FAST2 3013/3505 (86.0) 96.6 17.3 26.5 94.3 36.0
FAST=3 or abnormal item best
2410/3505 (68.8) 89.1 37.5 30.6 91.8 49.7
gaze
G-FAST3 2363/3505 (67.5) 88.7 39.1 31.0 91.8 50.8
C-STAT1 2414/3505 (68.9) 88.9 37.3 30.4 91.6 49.5
3I-SS1 2702/3505 (77.1) 91.8 27.5 28.1 91.5 42.7
PASS1 3209/3505 (91.6) 97.2 10.2 25.1 92.2 30.7
RACE3 2137/3505 (61.0) 85.7 46.7 33.2 91.4 55.9
NIHSS profile AE (at least PACS or
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3155/3505 (90.0) 97.2 12.2 25.5 93.4 32.3


worse) vs profile F
Cutoffs of scores with specificity >75% and highest possible sensitivity
NIHSS14 1133/3505 (32.3) 63.1 77.2 46.1 87.1 73.9
G-FAST=4 1029/3505 (29.4) 56.7 79.0 45.5 85.5 73.7
C-STAT3 1051/3505 (30.0) 58.3 78.8 45.9 85.9 73.9
3I-SS=3 383/3505 (10.9) 20.7 92.1 44.6 79.0 75.3
PASS=3 689/3505 (19.7) 38.5 86.2 46.2 81.9 74.9
RACE6 1154/3505 (32.9) 62.2 76.1 44.5 86.7 72.8
NIHSS profile A 793/3505 (22.6) 38.5 82.3 40.1 81.2 72.0
NIHSS profile B 775/3505 (22.1) 37.5 82.6 40.0 81.1 72.0
Statistically optimal cutoffs
NIHSS12 1420/3505 (40.5) 72.1 69.2 42.0 88.9 69.9
FAST=3 2207/3505 (63.0) 84.0 43.5 31.5 89.9 53.1
G-FAST3 2363/3505 (67.5) 88.7 39.1 31.0 91.8 50.8
C-STAT2 1461/3505 (41.7) 71.3 67.5 40.4 88.4 68.4
3I-SS2 1283/3505 (36.6) 65.0 72.2 41.9 87.0 70.5
PASS2 1763/3505 (50.3) 78.7 58.5 36.9 89.9 63.3
RACE5 1442/3505 (41.1) 71.2 68.2 40.8 88.5 68.9
NIHSS symptom profile A or B 1568/3505 (44.7) 75.9 64.9 40.1 89.7 67.5
3I-SS indicates 3-item Stroke Scale; AHA, American Heart Association; ASA, American Stroke Association; C-STAT, Cincinnati Stroke Triage
Assessment Tool; FAST, facearmspeechtime test; G-FAST, gazefacearmspeechtime score; LAVO, large anterior vessel occlusion;
NIHSS, National Institutes of Health Stroke Scale; NPV, negative predictive value; PACS, partial anterior circulation syndrome; PASS, Prehospital
Acute Stroke Severity scale; PPV, positive predictive value; and RACE, Rapid Arterial Occlusion Evaluation Scale.
*NIHSS6 is an inclusion criterion for endovascular treatment with stent retrievers according to current AHA/ASA Focused Update of the
2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment.12
In contrast to the original version, only one point was assigned per pathological item.

Discussion of false negatives and false positives are acceptable from the
One of the major challenges of the current stroke care is to perspective of society as a whole. Local circumstances should
translate the implications of the endovascular stroke trials into also influence the choice of selection criteria.
clinical practice. Noninvasive vessel imaging and rapid trans- In general, prehospital triage tools for detection of LAVO
fer of eligible patients to CSCs with EVT treatment option should be as simple as possible and easily performed and mem-
need to be organized effectively. Because no triage strategy orized by emergency medical services personnel. In addition,
performs perfectly, some patients with LAVO will be inevi- the ideal scores are supposed to discriminate stroke patients
tably missed, and many patients without LAVO will be trans- from stroke mimics. In our cohort, the simple prehospital
ferred to CSCs.22 It is a political issue to decide what range stroke scales performed nearly as well as the entire NIHSS in
Scheitz et al Prediction of Large Anterior Vessel Occlusion 295

identifying LAVO and at least as well as the entire NIHSS in futile transfers. This was observed for patients with abnormal
patients with moderate severity. Importantly, highly sensitive gaze and all 3 FAST items being positive (ie, G-FAST=4),
cutoffs of the prehospital scores performed as well as or even C-STAT3, 3I-SS=3, PASS=3, RACE6, and clinical signs of
better than NIHSS cutoff 6, which is recommended to select TACS (NIHSS symptom profile A and B).
patients for thrombectomy according to the current American Third, we consider a patient who arrives at a primary
Heart Association/American Stroke Association guidelines.12 stroke center and is evaluated by trained stroke physicians.
Thus, our findings emphasize the potential of simplified In this case, full examination of the NIHSS is feasible. It
NIHSS scores to detect LAVO in the prehospital setting. Our has been shown that no single variable beyond the NIHSS is
sensitivity analysis demonstrated comparable findings when able to improve prediction of LAVO in a clinically meaning-
BAO was included in the large vessel occlusion category. ful way.10 Current recommendations by the European Stroke
Several stroke recognition tools have been validated for pre- Organisation are based on the statistically optimal NIHSS cut
hospital evaluation of patients with suspected strokes.3133 The point observed in the large Bernese stroke registry (NIHSS9
FAST score is already widely used and shows the best sensi- within 3 hours, NIHSS7 within 6 hours).8,11 Our findings sug-
tivity for correct diagnosis of stroke together with the similar gest that lower NIHSS cutoffs could be used to improve sensi-
CPSS.31,32 To identify stroke patients with underlying LAVO in tivity (>90% with NIHSS6 and >95% with NIHSS5). Yet,
the field, it seems reasonable to use a 2-step screening process there are certain constellations in which application of highly
starting with the FAST score. FAST has the advantage of using specific LAVO scores or the highly specific NIHSS symptom
the item facial palsy that has been shown to be the NIHSS item profiles A or B could be helpful. Among others, these are late
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with best capability to discriminate between strokes and mim- arrival close to 6 hours, relative contraindications to computed
ics.34 In a second step, another tool is needed for the triage tomography-angiography like severely impaired kidney func-
regarding vessel imaging and facilitate transfer to EVT centers. tion or uncontrolled hyperthyroidism, and to avoid expenses
Ideally, this secondary score should be deduced from the initial of screening failures in a randomized controlled trial.
score but require addition of only a few more items with higher Although all NIHSS items contribute equally to the sum
sensitivity and specificity for presence of LAVO. In line with score, certain items and item constellations may reflect larger
previous studies,21,27,28 we found that gaze deviation was the ischemic lesions that carry a high attributable risk of an under-
most sensitive clinical sign suggestive of LAVO. Thus, a simple lying LAVO. Not surprisingly, we observed a graded associa-
expansion of the typical FAST score by the NIHSS item best tion of the NIHSS item profiles with LAVO. The 2 symptom
gaze was developed in our study (G-FAST). G-FAST would profiles with the highest risks, profiles A and B, represent left
fulfill the criteria mentioned above and has the advantage of and right total hemispheric syndrome, respectively. Thus,
mentioning all tested signs as an acronym. The C-STAT fol- our findings suggest that patterns of deficit rather than sim-
lows a similar concept and also seems promising at the second ply scores reflecting severity of deficit will be more useful in
stage as cortical signs (especially gaze) strengthen the score, triage. Although the exact concept of the NIHSS symptom
but still it maintains simplicity.18 By using the questions and profiles may be difficult to conduct by paramedics, our find-
commands from the NIHSS instead of the language and speech ings support the notion that suspected stroke patients who
items that are complex for many emergency medical services, presented with NIHSS symptom profiles A or B, at any sever-
the C-STAT makes the rating objective, rather than subjective. ity, should prompt an urgent neurovascular imaging and con-
Of note, G-FAST and C-STAT performed particularly well in sideration for transfer to a dedicated stroke center with EVT
patients with moderate stroke severity, which represents the capability. Given that right-hemispheric symptoms are under-
majority of cases seen in the field. represented in the NIHSS, patients with right LAVO might be
Importantly, the optimal prehospital triage strategy depends missed in case of mild to moderate stroke severity based on
on various time variables. Besides time from symptom onset NIHSS scoring alone.
until first evaluation by paramedics, transport time to next Our study has limitations. While the overall extent and accu-
CSC has to be considered. Our analysis adds relevant findings racy of data collected within SITS-ISTR allow for statistically
in at least 3 different clinical scenarios. robust analyses, the retrospective and observational design
First, we consider a patient with suspected stroke who is inherits potential for bias. Our cohort consists of patients who
evaluated by paramedics early after onset of symptoms or with received revascularization treatments after a clinical diagnosis
short transfer time to a CSC. In this case, a high sensitivity (ie, of acute ischemic stroke was already established and hemor-
low false-negative rate for LAVO) should be achieved, ideally rhagic stroke was ruled out by brain imaging. Consequently,
close to 90%. This was observed in different symptom com- sensitivity and specificity of the simplified NIHSS scores for
binations in our study with similar overall accuracy, namely, LAVO might differ in prehospital cohorts with suspected stroke
all 3 FAST items positive or abnormal NIHSS item best gaze, that include stroke mimics and hemorrhagic strokes. Majority
G-FAST3, C-STAT1, RACE3, and clinical signs of at of data were derived from primary stroke centers with limited
least a PACS (NIHSS symptom profiles A to E). availability of vessel imaging compared with CSCs. Moreover,
Second, we consider a patient with suspected stroke who is data on LAVO status were obtained from assessment by local
evaluated by paramedics at the end of intravenous thromboly- radiologists at the respective centers (not necessarily neuro-
sis time window or with long transfer time to the nearest CSC. radiologists). It is reassuring that 96% of patients within the
In this case, a high specificity (ie, low false-positive rate for ESCAPE trial (Endovascular Treatment for Small Core and
LAVO) is warranted, such as >75%, resulting in <1 out of 4 Anterior Circulation Proximal Occlusion With Emphasis on
296StrokeFebruary 2017

Minimizing CT to Recanalization Times) had the correct tar- 6. Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, et al;
Stroke Thrombolysis Trialists Collaborative Group. Effect of treatment
get-vessel occlusion status by using similar LAVO definition as
delay, age, and stroke severity on the effects of intravenous thrombolysis
per our analysis, after review from central adjudication labora- with alteplase for acute ischaemic stroke: a meta-analysis of individual
tory.2 In addition, it is possible that residual deficits related to patient data from randomised trials. Lancet. 2014;384:19291935. doi:
prior stroke or other reasons may affect baseline NIHSS score, 10.1016/S0140-6736(14)60584-5.
7. Sheth SA, Jahan R, Gralla J, Pereira VM, Nogueira RG, Levy EI, et al;
consequently leading to incorrect ratings. We have accounted SWIFT-STAR Trialists. Time to endovascular reperfusion and degree of
for this by adjusting the analysis for prestroke modified Rankin disability in acute stroke. Ann Neurol. 2015;78:584593. doi: 10.1002/
Scale and previous stroke. Finally, we were not able to evalu- ana.24474.
ate other established stroke recognition tools (eg, Los Angeles 8. Heldner MR, Zubler C, Mattle HP, Schroth G, Weck A, Mono ML, et al.
National Institutes of Health stroke scale score and vessel occlusion in
Motor Scale [LAMS], Los Angeles Prehospital Stroke Screen 2152 patients with acute ischemic stroke. Stroke. 2013;44:11531157.
[LAPSS], Melbourne Ambulance Stroke Screen [MASS], doi: 10.1161/STROKEAHA.111.000604.
Recognition of Stroke in the Emergency Room [ROSIER]),32,33 9. Cooray C, Fekete K, Mikulik R, Lees KR, Wahlgren N, Ahmed N.
Threshold for NIH stroke scale in predicting vessel occlusion and func-
because grip strength was not part of the NIHSS recording, tional outcome after stroke thrombolysis. Int J Stroke. 2015;10:822829.
and some scores require additional information other than the doi: 10.1111/ijs.12451.
NIHSS score (eg, history of seizures). 10. Vanacker P, Heldner MR, Amiguet M, Faouzi M, Cras P, Ntaios G, et al.
In summary, we found that the common simplified NIHSS Prediction of large vessel occlusions in acute stroke: National Institute of
Health Stroke Scale is hard to beat. Crit Care Med. 2016;44:e336e343.
scores may be useful to stratify patients risk of LAVO in the doi: 10.1097/CCM.0000000000001630.
prehospital setting. Certain cutoffs seem sufficiently accurate to 11. Wahlgren N, Moreira T, Michel P, Steiner T, Jansen O, Cognard C, et
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give guidance in clinical settings that require either high sensitiv- al; ESO-KSU, ESO, ESMINT, ESNR and EAN. Mechanical thrombec-
tomy in acute ischemic stroke: consensus statement by ESO-Karolinska
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Stroke Update 2014/2015, supported by ESO, ESMINT, ESNR and
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with additional gaze deviation (G-FAST) may be considered for 12. Powers WJ, Derdeyn CP, Biller J, Coffey CS, Hoh BL, Jauch EC, et
urgent neurovascular imaging and transfer to CSC. This subset al; American Heart Association Stroke Council. 2015 American Heart
Association/American Stroke Association Focused Update of the 2013
of patients may be readily identifiable by paramedics during the Guidelines for the Early Management of Patients With Acute Ischemic Stroke
prehospital stage. Our findings deserve prospective validation, Regarding Endovascular Treatment: A Guideline for Healthcare Professionals
ideally in the prehospital setting. The upcoming specialized From the American Heart Association/American Stroke Association. Stroke.
stroke ambulances seem to be one of the promising settings to 2015;46:30203035. doi: 10.1161/STR.0000000000000074.
13. Sucharew H, Khoury J, Moomaw CJ, Alwell K, Kissela BM, Belagaje S,
validate our findings and the feasibility of triage tools. et al. Profiles of the National Institutes of Health Stroke Scale items as a
predictor of patient outcome. Stroke. 2013;44:21822187. doi: 10.1161/
Sources of Funding STROKEAHA.113.001255.
14. Abdul-Rahim AH, Fulton RL, Sucharew H, Kleindorfer D, Khatri P,
Dr Scheitz is a participant in the Charit Clinical Scientist Program Broderick JP, et al; VISTA Collaborators. National institutes of health
funded by the CharitUniversittsmedizin Berlin and the Berlin stroke scale item profiles as predictor of patient outcome: external vali-
Institute of Health. The research was done with support from European dation on independent trial data. Stroke. 2015;46:395400. doi: 10.1161/
Academy of Neurology via a Research Fellowship grant awarded to STROKEAHA.114.006837.
Dr Scheitz. Dr Endres receives funding from the DFG (Excellence clus- 15. Abdul-Rahim AH, Fulton RL, Sucharew H, Kleindorfer D, Khatri P,
ter NeuroCure; SFB TR43, KFO 247, KFO 213), Bundesministerium Broderick JP, et al; SITS-MOST Steering Committee. National Institutes
fr Bildung und Forschung (BMBF, Center for Stroke Research of Health Stroke Scale item profiles as predictor of patient outcome:
Berlin), European Union (European Stroke Network, Wake-Up, external validation on Safe Implementation of Thrombolysis in Stroke-
Counterstroke), and Volkswagen Foundation (Lichtenberg Program). Monitoring Study data. Stroke. 2015;46:27792785. doi: 10.1161/
STROKEAHA.115.010380.
16. Mazya MV, Lees KR, Collas D, Rand VM, Mikulik R, Toni D, et al.
Disclosures IV thrombolysis in very severe and severe ischemic stroke: results from
None. the SITS-ISTR Registry. Neurology. 2015;85:20982106. doi: 10.1212/
WNL.0000000000002199.
17. Mazya MV, Ahmed N, Ford GA, Hobohm C, Mikulik R, Nunes AP, et
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Clinical Selection Strategies to Identify Ischemic Stroke Patients With Large Anterior
Vessel Occlusion: Results From SITS-ISTR (Safe Implementation of Thrombolysis in
Stroke International Stroke Thrombolysis Registry)
Jan F. Scheitz, Azmil H. Abdul-Rahim, Rachael L. MacIsaac, Charith Cooray, Heidi Sucharew,
Dawn Kleindorfer, Pooja Khatri, Joseph P. Broderick, Heinrich J. Audebert, Niaz Ahmed, Nils
Downloaded from http://stroke.ahajournals.org/ by guest on January 26, 2017

Wahlgren, Matthias Endres, Christian H. Nolte and Kennedy R. Lees


on behalf of SITS Scientific Committee

Stroke. 2017;48:290-297; originally published online January 13, 2017;


doi: 10.1161/STROKEAHA.116.014431
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SUPPLEMENTAL MATERIAL

Clinical selection strategies to identify stroke patients with large anterior vessel occlusion-Results from SITS-ISTR

Jan F Scheitz1,2*,MD, Azmil H Abdul-Rahim3*, MBChB, MSc(StrokeMed), Rachael L MacIsaac3,PhD, Charith Cooray4,MD, Heidi Sucharew5, PhD, Dawn Kleindorfer6,
MD, Pooja Khatri6, MD, MSc, Joseph P Broderick6, MD, Heinrich J. Audebert1,2, MD, Niaz Ahmed4, MD, PhD, Nils Wahlgren4,MD, PhD, Matthias Endres1,2,7,8,9,MD,
Christian H Nolte1,2*,MD, Kennedy R Lees3*, MD, FRCP

On behalf of SITS Scientific Committee


1 Center for Stroke Research Berlin, Charit - Universittsmedizin Berlin, Berlin, Germany.
2 Klinik fr Neurologie, Charit- Universittsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
3 Stroke Research, Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow G12 8QQ, UK
4 Department of Clinical Neurosciences, Karolinska Institutet and Department of Neurology, Karolinska University Hospital, Solna, Sweden
5 Division of Biostatistics and Epidemiology, Cincinnati Childrens Hospital Medical Center, Cincinnati, OH, USA
6 Department of Emergency Medicine, University of Cincinnati, College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267
7 Excellence Cluster NeuroCure, Charit Universittsmedizin Berlin, Berlin, Germany
8 German Center for Cardiovascular Research (DZHK), Charit - Universittsmedizin Berlin, Berlin, Germany.
9 German Center for Neurodegenerative Diseases (DZNE) Charit - Universittsmedizin Berlin, Berlin, Germany.
* authors contributed equally
Table I Components of the evaluated simple NIHSS scores
NIHSS Points FAST Points C-STAT Points PASS Points 3I-SS* Points RACE Points

LOC 0-3 - LOC questions AND LOC questions


commands (NIHSS>=1) Level of consciousness
LOC Questions 0-2 - - 1 1 1 - -
(NIHSS >=1 each) (NIHSS >=1)
LOC commands 0-2 -

Gaze 0-2 - - NIHSS >=1 2 NIHSS >=1 1 NIHSS >=1 1 Gaze 1

Visual field 0-3 - - - - - - - - -

Facial droop -
Facial palsy 0-3 1 - - - - Facial palsy 1-2
(NIHSS >=1)
Arm drift (NIHSS Arm weakness Arm weakness
Motor Arm 0-4 1 1 1 Hemiparesis 1 Arm motor function 1-2
>=1) (NIHSS >=2) (NIHSS >=1)
(Arm AND Leg motor
function on NIHSS >=1)
Motor Leg 0-4 - - - - - Leg motor function 1-2

Limb ataxia 0-2 - - - - - - - - -

Sensory 0-2 - - - - - - - - -

Speech problems Aphasia (if right


Best language 0-3 1 - - - - - 1-2
(dysarthria or hemiparesis)
language
Dysarthria 0-2 abnormality >=1) - - - - - - - -

Extinction and Agnosia (if left


0-2 - - - - - - - 1-2
Inattention hemiparesis)

Total 42 Total 3 Total 4 Total 3 Total 3 Total 9

Abbreviations: 3I-SS - 3-item Stroke Scale, C-STAT - Cincinnati Stroke Triage Assessment Tool, FAST face arm speech time test, LAVO large anterior vessel occlusion, LOC level of consciousness, NIHSS - National
Institutes of Health Stroke Scale, PASS prehospital acute stroke severity scale, RACE - Rapid Arterial Occlusion Evaluation Scale.
* In the original version 2 points were assignable to each of the three items depending on the overall severity
Table II - Clinical description of NIHSS symptom profiles

NIHSS symptom Profile Description


profiles

Profile A Severe Left TACS Severe stroke with decreased level of consciousness, facial palsy, abnormal
motor function on the right side, language deficit and dysarthria
Profile B Severe Right TACS Severe stroke with some decreased level of consciousness, facial palsy, abnormal
motor function on the left side and, dysarthria
Profile C Moderate Left PACS Stroke with language deficit and signs of dysarthria, mild abnormal normal motor
function on the right side possible
Profile D Moderate Left PACS Facial palsy, abnormal motor function on the right side, and
dysarthria
Profile E Moderate Right PACS Facial palsy and abnormal motor function on the left side, and dysarthria
Profile F Mild - Non-specific syndrome with low probabilities of
abnormal findings on all 15 items
Table III Sensitivity, specificity, PPV, NPV and accuracy for presence of LAVO according to different NIHSS cut-offs
n/N (%) Sensitivity Specificity PPV NPV Accuracy

NIHSS >=1 3494/3505 (99.7) 100.0 0.4 23.7 100.0 23.9

NIHSS >=2 3472/3505 (99.1) 99.6 1.1 23.7 90.9 24.3

NIHSS >=3 3389/3505 (96.7) 99.4 4.1 24.3 95.7 26.6

NIHSS >=4 3230/3505 (92.2) 97.8 9.6 25.0 93.5 30.4

NIHSS >=5 2972/3505 (84.8) 95.4 18.5 26.5 92.9 36.6

NIHSS >=6 2677/3505 (76.4) 91.3 28.2 28.2 91.3 43.1

NIHSS >=7 2395/3505 (68.3) 89.1 38.1 30.8 91.9 50.1

NIHSS >=8 2183/3505 (62.3) 85.6 44.9 32.4 91.0 54.5

NIHSS >=9 1928/3505 (55.0) 82.1 53.4 35.2 90.6 60.2

NIHSS >=10 1744/3505 (49.8) 79.4 59.4 37.7 90.3 64.1

NIHSS >=11 1570/3505 (44.8) 75.8 64.8 39.9 89.7 67.4

NIHSS >=12* 1420/3505 (40.5) 72.1 69.2 42.0 88.9 69.9

NIHSS >=13 1258/3505 (35.9) 67.4 73.2 44.3 88.0 71.8

NIHSS >=14 1133/3505 (32.3) 63.1 77.2 46.1 87.1 73.9

NIHSS >=15 1021/3505 (29.1) 58.0 80.1 47.4 86.1 74.9

NIHSS 16-20 891/3505 (25.4) 52.7 83.0 48.9 85.0 75.8

NIHSS >20 356/3505 (10.2) 23.0 93.8 53.4 79.8 77.1

Abbreviation: NIHSS - National Institutes of Health Stroke Scale


Table IV - AUC for the association between the entire NIHSS, the simplified pre-hospital scales, and NIHSS item profiles with LAVO

Score AUC (95% CI) Entire cohort* AUC (95% CI) patients with moderate stroke severity

N=3505 N= 1257

NIHSS 0.751 (0.736-0.765) 0.601 (0.573-0.628)

3I-SS 0.707 (0.692-0.722) 0.601 (0.573-0.628)

C-STAT 0.732 (0.717-0.747) 0.618 (0.590-0.645)

FAST 0.645 (0.629-0.661) 0.593 (0.566-0.621)

G-FAST 0.722 (0.707-0.737) 0.628 (0.600-0.655)

PASS 0.714 (0.699-0.729) 0.599 (0.572-0.627)

RACE 0.755 (0.740-0.769) 0.617 (0.589-0.644)

NIHSS profiles 0.709 (0.694-0.724) 0.619 (0.591-0.646)

*AUC of entire NIHSS=RACE (p=0.43). AUC of NIHSS and RACE >C-STAT (p<0.01). AUC of C-STAT=G-FAST (p=0.10). AUC of NIHSS, RACE, C-STAT, G-FAST > 3I-SS.
AUC of NIHSS, RACE, C-STAT, G-FAST > PASS (p<0.01). AUC of PASS=3I-SS (p=0.34). AUC of all scores > FAST (p<0.01).
moderate stroke severity was defined as NIHSS 6-11. AUC of G-FAST>FAST (p<0.01), all other scores not significantly different
Abbreviations: 3I-SS - 3-item Stroke Scale, AUC area under the receiver operating characteristics curve, CI confidence interval, C-STAT - Cincinnati Stroke Triage Assessment
Tool, FAST face, arm, speech and time test, G-FAST Go FAST score, LAVO large anterior vessel occlusion, NIHSS - National Institutes of Health Stroke Scale, PASS
prehospital acute stroke severity scale, RACE - Rapid Arterial Occlusion Evaluation Scale.
Table V - AUC for the association between entire NIHSS, simplified NIHSS scores and NIHSS item profiles with LVO (basilar artery or LAVO)

Score AUC (95% CI) Entire cohort* AUC (95% CI) patients with moderate stroke severity

N=3505 N= 1257

NIHSS 0.747 (0.733-0.762) 0.607 (0.564-0.650)

3I-SS 0.713 (0.698-0.728) 0.624 (0.580-0.669)

C-STAT 0.731 (0.716-0.746) 0.637 (0.594-0.681)

FAST 0.632 (0.615-0.648) 0.575 (0.533-0.617)

G-FAST 0.713 (0.698-0.728) 0.635 (0.592-0.678)

PASS 0.708 (0.693-0.723) 0.597 (0.569-0.624)

RACE 0.741 (0.726-0.755) 0.597 (0.566-0.621)

NIHSS profiles 0.698 (0.682-0.713) 0.578 (0.531-0.625)

*AUC of entire NIHSS=RACE (p=0.15). AUC of NIHSS>C-STAT (p<0.01). AUC of C-STAT=RACE (p=0.10). AUC of C-STAT, NIHSS, RACE>G-FAST (p<0.01), AUC of C-
STAT, NIHSS, RACE, G-FAST >3I-SS (p<0.01). AUC of C-STAT, NIHSS, RACE, G-FAST >PASS (p<0.01). AUC of all scores >FAST (p<0.01).

moderate stroke severity was defined as NIHSS 6-11. AUC of G-FAST, 3I-SS and C-STAT>FAST (p<0.05), AUC of C-STAT >RACE (p<0.05), all other scores not
significantly different
Abbreviations: 3I-SS - 3-item Stroke Scale, C-STAT - Cincinnati Stroke Triage Assessment Tool, FAST face, arm, speech and time test, G-FAST Go FAST score, LAVO large

anterior vessel occlusion, NIHSS - National Institutes of Health Stroke Scale, PASS prehospital acute stroke severity scale, RACE - Rapid Arterial Occlusion Evaluation Scale.
Table VI Sensitivity, specificity, PPV, and NPV for presence of large vessel occlusion (including BAO) at different cut-offs of the NIHSS, simplified

NIHSS scores and NIHSS symptom profiles.

Cut-offs of scores with >85% sensitivity and highest possible specificity.

n/N (%) Sensitivity Specificity PPV NPV Accuracy

NIHSS >=7 2395/3505 (66.3) 88.0 38.7 33.8 90.1 51.6

FAST >=2 3013/3505 (86.0) 96.0 17.6 29.3 92.5 38.1

G-FAST>=3 2363/3505 (67.5) 87.5 39.7 34.0 89.9 52.2

C-STAT>=1 2414/3505 (68.9) 88.0 40.0 33.6 89.9 55.5

3I-SS>=1 2702/3505 (77.1) 91.5 28.0 31.2 90.3 44.6

PASS >=1 3222/3505 (91.9) 96.4 10.2 27.6 88.9 32.8

RACE >=2 2724/3505 (77.7) 92.2 27.4 31.1 90.8 44.4

NIHSS profile A-E (at least PACS or 3155/3505 (90.0) 95.6 12.0 27.9 88.3 33.9
worse) vs profile F

Cut-offs of scores with specificity >75% and highest possible sensitivity

NIHSS >=14 1133/3505 (32.3) 60.7 77.8 49.2 84.7 73.3

G-FAST=4 1029/3505 (29.4) 54.3 79.5 48.5 83.0 72.9

C-STAT>=3 1051/3505 (30.0) 56.2 79.3 49.2 83.6 73.2

3I-SS =3 383/3505 (10.9) 21.4 92.8 51.4 76.8 74.1


PASS =3 565/3505 (16.1) 37.3 86.6 49.8 79.5 73.7

RACE >=6 1154/3505 (32.9) 59.9 76.7 47.7 84.3 72.3

NIHSS profile A 793/3505 (22.6) 38.3 82.9 44.3 79.1 71.2

NIHSS profile B 775/3505 (22.1) 34.9 82.4 41.4 78.1 70.0

Statistical optimal cut-offs

NIHSS >=12 1420/3505 (40.5) 69.5 69.8 45.0 86.5 69.7

FAST=3 2207/3505 (63.0) 81.2 43.5 33.8 86.7 53.4

G-FAST=4 1029/3505 (29.4) 54.3 79.5 48.5 83.0 72.9

C-STAT >=2 1461/3505 (41.7) 71.1 68.8 44.8 87.0 69.4

3I-SS >=2 1283/3505 (36.6) 64.6 73.4 46.3 85.3 71.1

PASS >=2 1802/3505 (51.4) 77.3 59.3 40.3 88.0 64.0

RACE >=5 1442/3505 (41.1) 68.9 68.8 44.0 86.1 68.9

NIHSS symptom profile A or B 1568/3505 (44.7) 73.0 65.3 44.9 87.2 67.3
Table VII Sensitivity, specificity, PPV, and NPV for presence of LAVO at different cut-offs of the NIHSS, simplified NIHSS scores and NIHSS symptom

profiles in patients with moderate stroke severity (NIHSS 6-11)

Cut-offs of scores with >85% sensitivity and highest possible specificity

n/N (%) Sensitivity Specificity PPV NPV Accuracy

NIHSS >=7 975/1257 (77.6) 88.7 24.0 14.5 93.6 32.1

FAST >=2 1115/1257 (88.7) 95.0 12.2 13.5 94.4 22.6

G-FAST>=2 1134/1257 (90.2) 96.2 10.7 13.5 95.1 21.5

3I-SS>=1 964/1257 (76.7) 85.5 24.6 14.1 92.2 32.3

PASS>=1 1228/1257 (97.7) 99.4 2.6 12.9 96.7 14.8

RACE >=2 1038/1257 (82.6) 91.8 18.8 14.1 94.1 28.0

NIHSS profile A-E (at least PACS or worse) vs profile F 1201/1257 (95.5) 98.7 4.9 13.1 96.4 16.7

Cut-offs of scores with specificity >75% and highest possible sensitivity

NIHSS >=10 324/1257 (25.8) 38.4 76.0 18.8 89.5 71.3

G-FAST=4 143/1257 (11.4) 24.5 90.0 27.4 89.2 81.7

C-STAT >=2 116/1257 (9.2) 32.7 82.1 20.9 89.4 75.9

3I-SS >=2 219/1257 (17.4) 30.8 84.5 22.4 89.4 77.7

PASS=3 52/1257 (4.1) 5.7 96.1 17.3 87.6 84.7


RACE >=5 73/1257 (5.8) 25.8 84.5 19.4 88.7 77.1

NIHSS profile A or B 316/1257 (25.1) 45.3 77.8 22.8 90.8 73.7

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