RESEARCH ARTICLE OPEN ACCESS

Prehospital Detection of Large Vessel Occlusion

Stroke With EEG
Results of the ELECTRA-STROKE Study
Maritta N. van Stigt, MSc,* Eva A. Groenendijk, MSc,* Laura C.C. van Meenen, MD, PhD, Correspondence
Anita A.G.A. van de Munckhof, MD, MSc, Monique Theunissen, BSc, Gaby Franschman, MD, PhD, Dr. Coutinho
Martin D. Smeekes, MD, MSc, Joffry A.F. van Grondelle, BSc, Geertje Geuzebroek, BSc, Arjen Siegers, MD, MSc, j.coutinho@
Marieke C. Visser, MD, PhD, Sander M. van Schaik, MD, PhD, Patricia H.A. Halkes, MD, PhD, amsterdamumc.nl
Charles B.L.M. Majoie, MD, PhD, Yvo B.W.E.M. Roos, MD, PhD, Johannes H.T.M. Koelman, MD, PhD,
Miou S. Koopman, MD, MSc, Henk A. Marquering, PhD, Wouter V. Potters, PhD,† and
Jonathan M. Coutinho, MD, PhD†

®
Neurology 2023;101:e2522-e2532. doi:10.1212/WNL.0000000000207831

Abstract RELATED ARTICLE

Background and Objectives Editorial

Endovascular thrombectomy (EVT) is standard treatment for anterior large vessel occlusion What Will the Mobile
stroke (LVO-a stroke). Prehospital diagnosis of LVO-a stroke would reduce time to EVT by Stroke Unit of the Future
Look Like, and Will EEG
allowing direct transportation to an EVT-capable hospital. We aim to evaluate the diagnostic
Have a Role?
accuracy of dry electrode EEG for the detection of LVO-a stroke in the prehospital setting.
Page 1085
Methods
MORE ONLINE
ELECTRA-STROKE was an investigator-initiated, prospective, multicenter, diagnostic study, per-
formed in the prehospital setting. Adult patients were eligible if they had suspected stroke (as assessed Class of Evidence
by the attending ambulance nurse) and symptom onset <24 hours. A single dry electrode EEG Criteria for rating
recording (8 electrodes) was performed by ambulance personnel. Primary endpoint was the di- therapeutic and diagnostic
agnostic accuracy of the theta/alpha frequency ratio for LVO-a stroke (intracranial ICA, A1, M1, or studies
proximal M2 occlusion) detection among patients with EEG data of sufficient quality, expressed as the NPub.org/coe
area under the receiver operating characteristic curve (AUC). Secondary endpoints were diagnostic
accuracies of other EEG features quantifying frequency band power and the pairwise derived Brain
Symmetry Index. Neuroimaging was assessed by a neuroradiologist blinded to EEG results.
Downloaded from https://www.neurology.org by Universiteit Utrecht on 4 March 2024

Results
Between August 2020 and September 2022, 311 patients were included. The median EEG duration
time was 151 (interquartile range [IQR] 151–152) seconds. For 212/311 (68%) patients, EEG data
were of sufficient quality for analysis. The median age was 74 (IQR 66–81) years, 90/212 (42%)
were women, and the median baseline NIH Stroke Scale was 1 (IQR 0–4). Six (3%) patients had an
LVO-a stroke, 109/212 (51%) had a non–LVO-a ischemic stroke, 32/212 (15%) had a transient
ischemic attack, 8/212 (4%) had a hemorrhagic stroke, and 57/212 (27%) had a stroke mimic. AUC
of the theta/alpha ratio was 0.80 (95% CI 0.58–1.00). Of the secondary endpoints, the pairwise
derived Brain Symmetry Index in the delta frequency band had the highest diagnostic accuracy
(AUC 0.91 [95% CI 0.73–1.00], sensitivity 80% [95% CI 38%–96%], specificity 93% [95% CI
88%–96%], positive likelihood ratio 11.0 [95% CI 5.5–21.7]).

*These author contributed equally as co-first authors.

†These author contributed equally as co-last authors.

From the Departments of Clinical Neurophysiology (M.N.v.S., E.A.G., J.H.T.M.K.), Neurology (M.N.v.S., E.A.G., L.C.C.v.M., A.A.G.A.v.d.M., M.C.V., Y.B.W.E.M.R., J.M.C.), Radiology and
Nuclear Medicine (C.B.L.M.M., M.S.K., H.A.M.), and Biomedical Engineering and Physics (H.A.M.), Amsterdam UMC location University of Amsterdam; Witte Kruis Ambulancezorg
(M.T., G.F.), Alkmaar; Ambulancezorg Nederland (M.D.S.), Zwolle; Ambulance Amsterdam (J.A.F.v.G., G.G., A.S.); Department of Neurology (S.M.v.S.), OLVG Hospital location West,
Amsterdam; Department of Neurology (P.H.A.H.), Noordwest Ziekenhuisgroep location Alkmaar; TrianecT (W.V.P.), Utrecht, the Netherlands.

Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

The Article Processing Charge was funded by the authors.

This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.

e2522 Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
 Glossary
AUC = area under the ROC curve; EVT = endovascular thrombectomy; IQR = interquartile range; LVO-a stroke = anterior
circulation large vessel occlusion stroke; ROC = receiver operating characteristic.

Discussion
The data from this study suggest that dry electrode EEG has the potential to detect LVO-a stroke among patients with suspected
stroke in the prehospital setting. Toward future implementation of EEG in prehospital stroke care, EEG data quality needs to be
improved.

Trial Registration Information

ClinicalTrials.gov identifier: NCT03699397.

Classification of Evidence
This study provides Class II evidence that prehospital dry electrode scalp EEG accurately detects LVO-a stroke among patients
with suspected acute stroke.

Introduction
Endovascular thrombectomy (EVT) is standard treatment
for patients with an anterior circulation large vessel occlu-
sion stroke (LVO-a stroke).1 EVT must be initiated as soon
as possible because patient outcome after EVT is highly
time-dependent.2-4 A large group of LVO-a stroke patients
(45%–83%) is initially transported to a non–EVT-capable
primary stroke center, necessitating interhospital transfer
to a comprehensive stroke center.5-9 On average, this so-called
drip-and-ship workflow delays the initiation of EVT by
39–114 minutes and is associated with a 7.8%–21.4% lower
chance of functional independence at 90 days.5,7,91011
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Methods
Study Design and Population
ELECTRA-STROKE was a prospective, investigator-
initiated, multicenter, diagnostic study, consisting of an in-
hospital and a prehospital phase. The results of the in-hospital
phase have been published previously.26 Here, we report the
results of the prehospital phase.
The study was performed by 2 ambulance services (Ambu-
lance Amsterdam and Witte Kruis Ambulancezorg Alkmaar)
and 3 receiving hospitals in the Dutch province of North
Holland (Amsterdam UMC, OLVG Hospital, and Noordwest
Ziekenhuisgroep). The patient recruitment took place be-

A triage instrument that can quickly and reliably identify pa-
tients with an LVO-a stroke in the prehospital setting would
allow direct transportation of these patients to a compre-
hensive stroke center, which could substantially shorten EVT
treatment initiation times. Several methods for prehospital
detection of LVO-a stroke currently exist, including clinical
stroke scales and mobile stroke units.12-18 However, none of
these methods have been implemented on a widespread scale,
and inadequate prehospital stroke triage remains an impor-
tant issue in acute care organization. EEG is a promising
technique for prehospital stroke triage because it is highly
sensitive to the reduction of the cerebral blood flow almost
immediately after onset.19-23 Previous studies have shown that
EEG can discriminate between LVO-a stroke patients and
other suspected stroke patients in an in-hospital setting,242526
but studies in the prehospital setting have not been per-
formed. The primary aim of the ELECTRA-STROKE study
was to determine the diagnostic accuracy of dry electrode
EEG for LVO-a stroke detection in the prehospital setting,
expressed as the area under the receiver operating charac-
teristic (ROC) curve (AUC) of the theta/alpha ratio.
tween August 2020 and September 2022.
We included adult patients with a clinically suspected stroke as
judged by the ambulance nurse and onset of symptoms or time
last seen well less than 24 hours before start of the EEG re-
cording. Patients with a wound or active infection of the scalp in
the dry electrode cap placement area and patients with a
(suspected) COVID-19 infection were excluded.
Standard Protocol Approvals, Registrations,
and Patient Consents
The study protocol (eSAP, links.lww.com/WNL/D121) was
approved by the institutional review board of the Amsterdam
UMC and by each participating hospital. The study protocol was
published previously.27 The study was monitored by the Clinical
Research Unit of the Amsterdam UMC. Because of the emer-
gency setting of the study, we used a deferred informed consent
procedure in line with national legislation and with approval of
the institutional review board.28 Written informed consent was
obtained from all patients or their legal representatives after EEG
data acquisition.

Neurology.org/N Neurology | Volume 101, Number 24 | December 12, 2023 e2523


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e2524
Study Procedures
A single EEG recording was performed using a dry electrode
EEG cap with 8 electrodes covering the vascular territory of
the middle cerebral artery (FC3, FC4, CP3, CP4, FT7, FT8,
TP7, and TP8; Waveguard touch, Eemagine, Berlin, Ger-
many) and a compatible EEG amplifier (eego amplifier EE-
411; Eemagine, Berlin, Germany). EEG data were acquired at
a sample frequency of 500 Hz using clinical EEG software
(NeuroCenter EEG, Clinical Science Systems, Leiden, The
Netherlands). EEG recordings were performed in the pre-
hospital setting by ambulance personnel who attended a
1-hour training in performing dry electrode EEG recordings
for the purpose of this study. A portable and lightweight
bag was used to store all equipment required for the EEG
recording (Figure 1). In December 2020 (Witte Kruis
Ambulancezorg Alkmaar) and February 2021 (Ambulance
Amsterdam), we adapted the acquisition software to provide
visual feedback on the electrode-skin impedances to guide
optimization of the electrode-skin contact. We time-limited
both the impedance optimization step (1.5 minutes) and the
EEG recording step (2.5–3.0 minutes) to minimize delay in
the prehospital workflow. As of January 2021, we collected
information on the length of the hair of the patients in whom
an EEG recording was performed by ambulance personnel of
Witte Kruis Ambulancezorg Alkmaar.
Figure 1 EEG Setup as Used in the ELECTRA-STROKE Study
Neurology | Volume 101, Number 24 | December 12, 2023
Routine stroke workup included a noncontrast CT, and, if
indicated, CT angiography and CT perfusion were performed
in the receiving hospital.
Definitions and Outcomes
The primary endpoint of the study was the diagnostic ac-
curacy of dry electrode EEG to discriminate LVO-a stroke
from all other strokes and stroke mimics, expressed as the
AUC of the theta/alpha ratio. The theta/alpha ratio was
defined as:
PðθÞ − PðαÞ
TAR = ; (1)
PðθÞ + PðαÞ
with PðθÞ the power in the theta frequency band (4–8 Hz)
and PðαÞ the power in the alpha frequency band (8–13 Hz).
The theta/alpha ratio was chosen as this EEG feature had
highest diagnostic accuracy for LVO-a stroke detection in the
first 100 patients included in the in-hospital phase of the
study.26 Besides the AUC, sensitivity, specificity, positive
predictive value, negative predictive value, and positive like-
lihood ratio were determined.
Secondary endpoints, which should be considered exploratory
only, were the diagnostic accuracies of the relative delta (1–4
Hz), theta (4–8 Hz), alpha (8–13 Hz), and beta (13–18 Hz)
(A) EEG equipment stored in a portable and lightweight bag.
(B) Dry electrode EEG cap (Waveguard touch, Eemagine,
Berlin, Germany). (C) EEG recording in the ambulance.
Neurology.org/N
 power; the delta/alpha ratio, the (delta + theta)/(alpha + beta)
ratio, and the pairwise derived Brain Symmetry Index for LVO-
a stroke detection; and the logistical and technical feasibility of
ambulance personnel performing an EEG recording with a dry
electrode cap in the prehospital setting in patients with a sus-
pected stroke. Definitions of the EEG features are included in
the eAppendix 1 (links.lww.com/WNL/D119). We quantified
the logistical and technical feasibility by calculating the per-
centage of patients with EEG data of sufficient quality for
analysis and the percentage of clean EEG data per patient.
To account for learning effects and hardware and software
improvements, we compared the percentage of clean EEG
data of the first 50 EEG recordings with the percentage of
clean EEG data of the last 50 EEG recordings performed in
this study. The principal safety outcome was the occurrence
of device-related adverse events.
We defined an LVO-a stroke as an occlusion of the intracranial
part of the internal carotid artery, the first or proximal second
segment of the middle cerebral artery (M1 and proximal M2,
respectively), or the first segment of the anterior cerebral artery
(A1). The occlusion location was determined by an adjudica-
tion committee—consisting of a neuroradiologist (M.S.K.) and
a stroke neurologist (J.M.C.)—based on CT angiography data.
The adjudication committee was blinded for EEG results. In
case a patient was not clinically suspected of having an LVO-a
stroke and therefore did not undergo CT angiography, the
patient was scored as not having an LVO-a stroke.
Data Analysis
EEG data were re-referenced to a 12-channel bipolar montage
with 6 bipolar channels located at each hemisphere and band-
pass filtered between 0.5 and 35 Hz using a third order But-
terworth filter. Artifacts were detected and rejected per 2-second
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bipolar channel segment using an automatic Convolutional
Neural Network algorithm specifically developed for the de-
tection of artifacts in dry electrode EEG data.29 The pairwise
derived Brain Symmetry Index was calculated using EEG
channels located on both hemispheres. All other EEG features
Figure 2 Patient Flowchart
Neurology.org/N
were calculated per hemisphere. For patients with a stroke, we
kept the ipsilesional EEG features, and for patients with a stroke
mimic, we averaged the EEG features over both hemispheres
(if available). Further details are provided in the eMethods
(links.lww.com/WNL/D120).
Statistical Analysis
The sample size was calculated based on an expected
specificity of dry electrode EEG for LVO-a stroke of 70%. At
the start of the study, the sample size was set at 222, based
on an expected incidence of LVO-a stroke of 7% and a
dropout rate of 20%. An interim analysis, based on 137
suspected stroke patients in whom a dry electrode EEG
recording was performed in the prehospital setting, showed
an actual incidence of LVO-a stroke of 5% and a dropout
rate of 58%. Patients were considered a dropout if EEG data
were of insufficient quality, time of symptom onset was
more than 24 hours before the start of the EEG recording, or
no informed consent was provided. A revised incidence of
LVO-a stroke of 5%, an alpha of 0.05 and a maximum
margin of error of 7% indicated that 174 patients with a
suspected stroke were required.30 As EEG data quality im-
proved over time,26 we assumed a dropout rate of 55% when
recalculating the sample size. Considering this dropout rate,
our revised estimation resulted in a sample size of 386 pa-
tients with a suspected stroke.
The diagnostic accuracies of all EEG features were evaluated
by calculating areas under the ROC curves. Two cutoff values
were determined as the highest sensitivity at a specificity of
≥70% and ≥80% for LVO-a stroke, respectively. The latter is
defined as optimal cutoff. For both cutoff values, sensitivity,
specificity, positive predictive value, negative predictive value,
and positive likelihood ratio are reported with 95% confidence
intervals. The 95% confidence intervals were estimated using
the method of Hanley and McNeil31 for the AUC; the Wilson
interval32 for the sensitivity, specificity, positive predictive
value, and negative predictive value; and the method of Simel
et al.33 for the positive likelihood ratio.
LVO-a stroke = anterior circulation
large vessel occlusion stroke.
Neurology | Volume 101, Number 24 | December 12, 2023 e2525
 Table 1 Baseline Characteristics of the Patients Included in and Excluded From the Final Analysis
Included (n = 212) Excluded (n = 99) p Value

Age, median (IQR) 74 (66–81) 76 (67–84) 0.21

Sex, male, n/N (%) 122/212 (58) 41/99 (41) 0.01

Diagnosis, n/N (%)

LVO-a stroke 6/212 (3) 9/99 (9) 0.02

Non–LVO-a ischemic stroke 109/212 (51) 55/99 (56) 0.58

Transient ischemic attack 32/212 (15) 7/99 (7) 0.07

Hemorrhagic stroke 8/212 (4) 8/99 (8) 0.18

Seizure 6/212 (3) 1/99 (1) 0.44

Other stroke mimic 51/212 (24) 19/99 (19) 0.42

Blood pressure, mean ± SD

Systolic pressure 168 ± 28a 163 ± 30b 0.20

c d
Diastolic pressure 91 ± 17 91 ± 19 0.87

Glasgow Coma Scale, n/N (%)

<9 1/212 (<1) 1/99 (1) 0.54

≥9 211/212 (>99) 98/99 (99) 0.54

NIHSS, median (IQR) 1 (0–4) 2 (1–6) 0.007

Treatment, n/N (%)

IVT 36/212 (17) 21/99 (21) 0.46

e f
EVT 9/212 (4) 8/99 (8) 0.26

g h
Symptom onset to start EEG, minutes, median (IQR) 121 (50–449) 169 (59–502) 0.23

Hair length

Short 68/80 (85)i 21/31 (68)j 0.07

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i j
Long 12/80 (15) 10/31 (32) 0.07

Abbreviations: EVT = endovascular thrombectomy; IQR = interquartile range; IVT = IV thrombolysis; LVO-a stroke = anterior circulation large vessel occlusion
stroke; NIHSS = NIH Stroke Scale.
Reasons for exclusion were insufficient data quality (n = 94), absence of EEG data (n = 4), and a corrupted European Data Format file (n = 1).
Number of patients who received IVT before EVT: e7; f4.
Number of missing values: a9; b3; c10; d3; g15; h15; i132; j68.

Baseline characteristics and EEG feature values of patients Data Availability

with an LVO-a stroke and those without an LVO-a stroke
were compared using the independent samples t test for
normally distributed continuous variables, the Mann-Whitney
U test for non-normally distributed continuous variables, and
the χ 2 test (if any of the cells had expected count ≥5) or Fisher
exact test (if any of the cells had expected count <5) for
categorical variables. Percentages of clean EEG data of the
first and last 50 EEG recordings were compared using the
Mann-Whitney U test. A p value ≤0.05 was considered sta-
tistically significant.
Data were analyzed with Python (version 3.8; Python Soft-
ware Foundation, Wilmington, DE).
Individual patient data cannot be made available under Dutch
law because we did not obtain patient approval for sharing
individual patient data, even in coded form.
Results
Ambulance personnel performed a dry electrode EEG re-
cording in 386 patients, of whom 75/386 (19%) were sub-
sequently excluded because no informed consent could be
obtained (n = 65), symptom onset was >24 hours (n = 9), or
symptoms were absent during EEG recording (n = 1;
Figure 2). Of the 311 patients included in the study, 99 (32%)
were excluded from analysis because of insufficient quality of

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 Table 2 Baseline Characteristics of All Patients Included in the Final Analysis
All patients (n = 212) LVO-a stroke (n = 6) No LVO-a stroke (n = 206) p Valuea

Age, median (IQR) 74 (66–81) 72 (69–80) 75 (65–81) 0.72

Sex, n/N (%) 122/212 (58) 5/6 (83) 117/206 (57) 0.24

Diagnosis, n/N (%)

Ischemic stroke 115/212 (54) 6/6 (100) 109/206 (53)b NA

LVO-a stroke 6/212 (3) 6/6 (100) 0/206 (0) NA

M1 3/212 (1) 3/6 (50) 0/206 (0) NA

Proximal M2 3/212 (1) 3/6 (50) 0/206 (0) NA

Transient ischemic attack 32/212 (15) 0/6 (0) 32/206 (16) NA

c
Hemorrhagic stroke 8/212 (4) 0/6 (0) 8/206 (4) NA

Seizure 6/212 (3) 0/6 (0) 6/206 (3) NA

Another stroke mimic 51/212 (24) 0/6 (0) 51/206 (25) NA

Medical history, n/N (%)

Ischemic stroke 51/212 (24) 1/6 (17) 50/206 (24) >0.99

Hemorrhagic stroke 4/212 (2) 0/6 (0) 4/206 (2) >0.99

Blood pressure, mean ± SD

Systolic pressured 168 ± 28 154 ± 27 168 ± 28 0.22

Diastolic pressuree 91 ± 17 88 ± 11 92 ± 18 0.62

Glasgow Coma Scale, n/N (%)

<9 1/212 (<1) 0/6 (0) 1/206 (<1) >0.99

≥9 211/212 (>99) 6/6 (100) 205/206 (>99) >0.99

NIHSS, median (IQR) 1 (0–4) 14 (7–17) 1 (0–3) <0.001

Treatment, n/N (%)

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IVT 36/212 (17) 4/6 (67) 32/206 (16) 0.008

EVT 9/212 (4) 5/6 (83)f,g 4/206 (2)h,i <0.001

Symptom onset to start EEGj, minutes, median (IQR) 121 (50–449) 46 (32–64) 139 (51–476) 0.05

Abbreviations: EVT = endovascular thrombectomy; IQR = interquartile range; IVT = IV thrombolysis; LVO-a stroke = anterior circulation large vessel occlusion
stroke; NA = not applicable; NIHSS = NIH Stroke Scale.
a
p value for the difference between patients with and without an LVO-a stroke.
b
Of the 109 patients with a non–LVO-a ischemic stroke, 2 had an LVO stroke of the posterior circulation, located in the first segment of the posterior cerebral
artery (n = 1) and basilar artery (n = 1). Seventy (64%) non–LVO-a ischemic strokes were located in the vascular territory of the anterior circulation.
c
All were intraparenchymal hemorrhages.
f
The patient with an LVO-a stroke who did not receive EVT had an occlusion of the extracranial internal carotid artery and proximal second segment of the
middle cerebral artery (both left). The risk of EVT was deemed to great considering the minimal neurologic deficit (NIHSS: 3).
h
The patients without an LVO-a stroke who received EVT had a distal occlusion of the second segment of the middle cerebral artery (n = 3) and an occlusion of
the third segment of the middle cerebral artery (n = 1).
Number of patients who received IVT before EVT: g3; i5.
Number of missing values: d9; e10; j15.

the EEG data (n = 94) or the absence of EEG data due to
technical failure (n = 5). The median (interquartile range
[IQR]) percentage of clean EEG data over all patients was 14%
(4%–39%). Data quality improved over time (median [IQR]
percentage of clean EEG data of the first 50 EEG recordings
vs the last 50 EEG recordings: 11% [9%–12%] vs 26%
[25%–27%], p < 0.001). The median EEG duration time was
151 (IQR 151–152) seconds. A comparison of baseline char-
acteristics between patients included and excluded in the analysis
is presented in Table 1. Excluded patients were more often
female (59% vs 42%, p = 0.01) and more often had an LVO-a
stroke (9% vs 3%, p = 0.02). Patients who were excluded from
analysis also more often had long hair (32% vs 15%, p = 0.07).
Of the 212 patients included in data analysis, 6 (3%) had an
LVO-a stroke, 109 (51%) a non–LVO-a ischemic stroke, 32
(15%) a TIA, 8 (4%) a hemorrhagic stroke, and 57 (27%) a
stroke mimic. Patients with an LVO-a stroke had a higher

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 Table 3 Diagnostic Accuracy of EEG Features for LVO-a Stroke Detection at Optimal Cutoff
AUC Sensitivity, Specificity, PPV, NPV, PLR
(95% CI) % (95% CI) % (95% CI) % (95% CI) % (95% CI) (95% CI)

Frequency band powera

Relative deltab 0.59 (0.34–0.83) 0 (0–39) 100 (98–100) NA 97 (93–99) NA

Relative thetac 0.68 (0.44–0.92) 33 (10–70) 80 (74–85) 5 (1–17) 97 (94–99) 1.7 (0.5–5.4)

Relative alphad 0.77 (0.54–0.99) 67 (30–90) 84 (78–89) 12 (5–27) 99 (96–100) 4.2 (2.2–8.0)

e
Relative beta 0.50 (0.26–0.73) 33 (10–70) 80 (74–85) 5 (1–17) 97 (94–99) 1.7 (0.5–5.4)

f
Delta/alpha ratio 0.76 (0.53–0.98) 50 (19–81) 86 (81–90) 10 (4–26) 98 (95–99) 3.6 (1.5–8.7)

Theta/alpha ratiog 0.80 (0.58–1.00) 50 (19–81) 83 (77–88) 9 (3–22) 98 (95–99) 2.9 (1.2–6.9)

h
(Delta + theta)/(alpha + beta) ratio 0.70 (0.47–0.94) 33 (10–70) 80 (74–85) 5 (1–17) 97 (94–99) 1.7 (0.5–5.4)

i
Frequency asymmetry

pdBSI

Deltaj 0.91 (0.73–1.00) 80 (38–96) 93 (88–96) 24 (10–47) 99 (97–100) 11.0 (5.5–21.7)

k
Theta 0.78 (0.54–1.00) 60 (23–88) 92 (87–95) 18 (6–41) 99 (96–100) 7.6 (3.2–18.3)

Alphal 0.47 (0.22–0.73) 20 (4–62) 97 (93–98) 14 (3–51) 98 (94–99) 5.9 (0.9–40.5)

Betam 0.78 (0.53–1.00) 20 (4–62) 96 (92–98) 12 (2–47) 98 (94–99) 5.1 (0.8–33.9)

Abbreviations: AUC = area under the receiver operating characteristic curve; LVO-a stroke = anterior circulation large vessel occlusion stroke; NA = not
available; NPV = negative predictive value; pdBSI = pairwise derived Brain Symmetry Index; PLR = positive likelihood ratio; PPV = positive predictive value.
The primary classifying metric, the AUC, is bolded.
a
194 patients, of whom 6 had an LVO-a stroke, used for analysis.
i
183 patients, of whom 5 had an LVO-a stroke, used for analysis.
The presence of an LVO-a stroke was indicated if the EEG features were: b>0.88; c>0.25; d<0.12; e<0.07; f>0.64; g>0.26; h>0.58; j>0.52; k>0.52; l>0.52; m>0.53.

median NIH Stroke Scale (15 vs 1, p < 0.001), more often with an LVO-a stroke and patients without an LVO-a stroke
received IV thrombolysis and EVT (67% vs 16%, p = 0.008 are presented in eTable 2 (links.lww.com/WNL/D123).
and 83% vs 2%, p < 0.001, respectively), and had lower onset
to EEG time (median: 46 vs 139 minutes, p = 0.05) (Table 2).
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EEG recordings were performed before initiation of any

reperfusion therapy in all patients. No device-related adverse
events were reported.
For the frequency band powers and pairwise derived Brain
Symmetry Index, 194 (6 LVO-a stroke) and 183 (5 LVO-a
stroke) patients were available for analysis, respectively.
The AUC of the theta/alpha ratio was 0.80 (95% CI
0.58–1.00; Table 3; Figure 3A). At optimal cutoff, we found a
sensitivity of 50% (95% CI 19%–81%), a specificity of 83%
(95% CI 77%–88%), a positive predictive value of 9% (95%
CI 3%–22%), and a negative predictive value of 98% (95% CI
95%–99%; Figure 3C). Of the secondary endpoints, the
pairwise derived Brain Symmetry Index in the delta frequency
band had highest diagnostic accuracy for LVO-a stroke de-
tection with an AUC of 0.91 (95% CI 0.73–1.00); at optimal
cutoff, a sensitivity of 80% (95% CI 38%–96%) and a speci-
ficity of 93% (95% CI 88%–96%) (Figure 3, B and D). The
diagnostic measures of all EEG features at maximum sensi-
tivity at a specificity of ≥70% are presented in eTable 1 (links.
lww.com/WNL/D122). The EEG feature values for patients
Discussion
In this prehospital study, dry electrode EEG detected LVO-
a stroke with a high diagnostic accuracy in a population of
suspected stroke patients. However, EEG data were of in-
sufficient quality for analysis in around one-third of
patients.
In ELECTRA-STROKE, an ambulatory LVO-a stroke de-
tection device was tested by ambulance personnel in the
prehospital setting. In line with other prehospital stroke
trials,34,35 we demonstrate that successful conduct of a pre-
hospital stroke study is feasible but has its challenges. Con-
sistent with the MR ASAP trial,35 obtaining written deferred
consent proved to be more challenging in a prehospital setting
than in stroke trials that ran in an in-hospital setting, such as
the MR CLEAN NO-IV trial.36 Lack of written informed
consent led to exclusion of 17% of the patients. Still, without a
deferred informed consent procedure, performing the study
would have been logistically more challenging and could have
resulted in substantial treatment delays.

e2528 Neurology | Volume 101, Number 24 | December 12, 2023 Neurology.org/N

 Figure 3 ROC Curves for LVO-a Stroke Detection
Prehospital detection of patients with an LVO-a stroke would
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enable direct transport of these patients to a comprehensive
stroke center while still allowing other suspected stroke pa-
tients to be transported to the closest primary stroke center.
Data from nonrandomized studies suggest that this workflow
can lead to shorter EVT treatment initiation times and better
clinical outcomes for patients with an LVO-a stroke.5,7,91011
By contrast, the RACECAT trial—performed in a nonurban
area with relatively long initial transport times—did not find a
difference in clinical outcome in suspected LVO stroke pa-
tients between a mothership and drip-and-ship model.37 This
discrepancy between studies may be attributed to geographic
differences and emphasize the need for regional solutions to
optimize stroke care.
Recent in-hospital studies have demonstrated the potential of
EEG for LVO-a stroke detection. In the first 100 patients
enrolled in the in-hospital phase of the ELECTRA-STROKE
study, the diagnostic accuracies of the frequency band powers
were comparable with this study, with the theta/alpha ratio as
the best performing EEG feature (AUC = 0.83).26 The pair-
wise derived Brain Symmetry Index, however, did not have a
good diagnostic accuracy in that study (AUC = 0.38), while in
this study, this EEG feature showed the best performance
Neurology.org/N
(A) ROC curve of the theta/alpha ratio
with, at optimal cutoff, a sensitivity of
50% and specificity of 83% for LVO-a
stroke. (B) ROC curve of the pairwise
derived Brain Symmetry Index in the
delta frequency band with, at optimal
cutoff, a sensitivity of 80% and specificity
of 93% for LVO-a stroke. (C) Contingency
table of LVO-a stroke prediction by the
theta/alpha ratio. (D) Contingency table
of LVO-a stroke prediction by the pairwise
derived Brain Symmetry Index in the delta
frequency band. LVO-a stroke = anterior
circulation large vessel occlusion stroke;
ROC = receiver operating characteristic.
(AUC = 0.91). This disparity may be due to a difference in
EEG data quality, as the pairwise derived Brain Symmetry
Index is known to be highly susceptible to artifacts and this
study included an improved, more sensitive, artifact detection
algorithm than the in-hospital study. Erani et al.24 performed
dry electrode EEG recordings in 100 suspected stroke pa-
tients and found moderately high diagnostic accuracy of EEG
for LVO-a stroke detection (AUC = 0.69) when using a
combination of the ipsilesional relative theta and alpha power.
We assume that the diagnostic accuracy is lower compared with
our study because none of the utilized EEG features contained
information on both hemispheres—as is the case for the
pairwise derived Brain Symmetry Index—and the diagnostic
accuracy was validated on unseen data. In our study, we did not
validate the results in unseen data, which may have led to an
overestimation of the diagnostic accuracy. Sergot et al.25 in-
vestigated LVO detection by means of a portable wet electrode
EEG and somatosensory-evoked potentials device. They used
data of 109 suspected stroke patients and found a sensitivity
and specificity for LVO stroke of both 80%.
The value of using prehospital stroke scales, especially the
RACE, G-FAST, and ACT-FAST, for LVO-a stroke detection
has recently been demonstrated.15,38 The best performing
Neurology | Volume 101, Number 24 | December 12, 2023 e2529
 scale, the RACE, reached an AUC of 0.83 in a group of 1,039 grants from CVON/Dutch Heart Foundation, European
suspected stroke patients. Although clinical scales have the Commission, TWIN Foundation, Stryker, and Healthcare
potential to be easily implemented in the prehospital setting Evaluation Netherlands, all outside the submitted work (paid
and can be applied to most patients, assessment remains to institution), and is shareholder of Nicolab. Y.B.W.E.M. Roos
subjective. An important aspect of progress may lie in is minor shareholder of Nicolab. J.H.T.M. Koelman and M.S.
combining EEG with clinical scales in future studies. The Koopman report no disclosures relevant to the manuscript.
improvement of diagnostic accuracy for LVO-a stroke de- H.A. Marquering is co-founder and minor shareholder of
tection, when combining EEG and clinical data, has been Nicolab and TrianecT. W.V. Potters is co-founder, employee
shown by Erani et al.24 Unfortunately, both the RACE and and shareholder of TrianecT. J.M. Coutinho received related
G-FAST scales are not routinely used by ambulance per- research support from the Dutch Heart Foundation and
sonnel in the regions where ELECTRA-STROKE was per- Medtronic and unrelated research support from Bayer and
formed; thus, we could not study the value of combining Boehringer (all fees were paid to his employer), and is co-
both techniques in this study. founder and shareholder of TrianecT. Go to Neurology.org/N
for full disclosures.
Our study has several limitations. First, EEG data quality was
insufficient in approximately one-third of patients. The fact Publication History
that ambulance personnel had to perform the measurement in Received by Neurology June 8, 2023. Accepted in final form July 31, 2023.
a limited timeframe and while under pressure of transporting Submitted and externally peer reviewed. The handling editor was
a suspected stroke patient as quickly as possible undoubtedly Editor-in-Chief José Merino, MD, MPhil, FAAN.
contributed to this. Future innovations in EEG hardware and
software should specifically address this issue, especially
among groups with higher dropout rates due to insufficient Appendix Authors
EEG data quality (women, those with longer hair and those
Name Location Contribution
with more severe neurologic deficits). Second, we only had a
limited number of LVO-a stroke patients in the study, in- Maritta N. van Departments of Clinical Drafting/revision of the
Stigt, MSc Neurophysiology and manuscript for content,
creasing the statistical uncertainty of the results. Third, we had Neurology, Amsterdam including medical writing
insufficient power to determine whether EEG can distinguish UMC location University of for content; major role in
Amsterdam, the the acquisition of data;
between LVO-a stroke and hemorrhagic stroke. This should Netherlands study concept or design;
be the focus of future studies because hemorrhagic stroke is an analysis or interpretation
of data
important mimic of LVO-a stroke and there are data that
suggest that subjecting patients with a hemorrhagic stroke Eva A. Departments of Clinical Drafting/revision of the
Groenendijk, Neurophysiology and manuscript for content,
to longer transportation times may negatively affect their MSc Neurology, Amsterdam including medical writing
outcome.37 UMC location University of for content; analysis or
Amsterdam, the interpretation of data
Netherlands
Downloaded from https://www.neurology.org by Universiteit Utrecht on 4 March 2024

In conclusion, the data from this study suggest that dry

electrode EEG has potential to detect LVO-a stroke among Laura C.C. van Department of Neurology, Drafting/revision of the
Meenen, MD, Amsterdam UMC location manuscript for content,
patients with suspected stroke in the prehospital setting. PhD University of Amsterdam, including medical writing
Toward future implementation of EEG in prehospital stroke the Netherlands for content; major role in
the acquisition of data;
care, EEG data quality needs to be improved and additional study concept or design
validation in a larger cohort of patients is necessary.
Anita A.G.A. Department of Neurology, Drafting/revision of the
van de Amsterdam UMC location manuscript for content,
Acknowledgment Munckhof, University of Amsterdam, including medical writing
MD, MSc the Netherlands for content; major role in
We thank the ambulance services for recording the EEG data the acquisition of data
in the prehospital setting and providing us with feedback on
the EEG equipment. Monique Witte Kruis Ambulancezorg, Drafting/revision of the
Theunissen, Alkmaar, the Netherlands manuscript for content,
BSc including medical writing
Study Funding for content; major role in
the acquisition of data
This study was funded by the Dutch Heart Foundation
(2018T001), Health;Holland, and by an unrestricted re- Gaby Witte Kruis Ambulancezorg, Drafting/revision of the
Franschman, Alkmaar, the Netherlands manuscript for content,
search grant from Medtronic. MD, PhD including medical writing
for content
Disclosure Martin D. Ambulancezorg Nederland, Drafting/revision of the
M.N. van Stigt, E.A. Groenendijk, L.C.C. van Meenen, Smeekes, MD, Zwolle, the Netherlands manuscript for content,
MSc including medical writing
A.A.G.A. van de Munckhof, M. Theunissen, G. Franschman, for content
M.D. Smeekes, J.A.F. van Grondelle, G. Geuzebroek, A. Sieg-
Joffry A.F. van Ambulance Amsterdam, the Major role in the
ers, M.C. Visser, S.M. van Schaik, and P.H.A. Halkes report no Grondelle, BSc Netherlands acquisition of data
disclosures relevant to the manuscript. C.B.L.M. Majoie reports

e2530 Neurology | Volume 101, Number 24 | December 12, 2023 Neurology.org/N

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