Review

Prehospital stroke management in the thrombectomy era

Klaus Fassbender, Silke Walter, Iris Q Grunwald, Fatma Merzou, Shrey Mathur, Martin Lesmeister, Yang Liu, Thomas Bertsch, James C Grotta

Acute stroke management has been revolutionised by evidence of the effectiveness of thrombectomy. Because time is Lancet Neurol 2020; 19: 601–10
brain in stroke care, the speed with which a patient with large vessel occlusion is transferred to a thrombectomy- Department of Neurology,
capable centre determines outcome. Therefore, each link in the stroke rescue chain, starting with symptom onset and Saarland University Medical
Center, Homburg, Germany
ending with recanalisation, should be streamlined. However, in contrast to inhospital delays, prehospital delays are
(Prof K Fassbender MD,
unchanged despite substantial efforts in quality improvement. Furthermore, thrombectomy is offered by only a few, Prof S Walter MD, F Merzou MD,
usually distant, specialised centres and not by the many other, usually nearer, hospitals. To take maximum advantage S Mathur MD,
of the first so-called golden hours after stroke, and because of the difficulty of on-scene triage decision making with M Lesmeister Dipl-Phys,
Y Liu MD); School of Medicine,
respect to the target hospital offering the required level of care, the focus of stroke research has shifted to the
Anglia Ruskin University,
prehospital setting. Current research focuses on the effects of public education, implementation of protocols for Chelmsford, UK
emergency medical services for streamlining clinical investigations and accurate triage, use of preclinical scales (Prof I Q Grunwald MD); School
for stroke recognition, and deployment of novel technical solutions such as smartphone applications, telemedicine, of Medicine, University of
Dundee, Dundee, UK
and mobile stroke units.
(Prof I Q Grunwald); Institute of
Clinical Chemistry, Laboratory
Introduction for non-treatment is delayed hospital presentation, often Medicine and Transfusion
Stroke is one of the most common causes of disability resulting in exclusion from treatment at thrombectomy- Medicine, Paracelsus Medical
University, Nuremberg,
and death, with severe associated socioeconomic conse­ capable centres because of loss of salvageable brain Germany (Prof T Bertsch MD);
quences.1 The occlusion of large proximal arteries supply­ tissue.2,10 Importantly, when treatment is still possible, and Department of Neurology,
ing the brain (large vessel occlusion) is associated with outcomes of thrombectomy are highly time sensitive.2,10,11 Memorial Hermann Hospital,
especially poor functional outcomes and high mortality.1 In For example, a meta-analysis of several thrombectomy Houston, TX, USA
(Prof J C Grotta MD)
2015, several trials provided compelling evidence that, trials found that chances of a good outcome decrease
Correspondence to:
for stroke due to large vessel occlus­ion, thrombectomy rapidly over time with no average benefit at 7·3 h after
Prof Klaus Fassbender,
resulted in signi­ficantly better recan­alisation and clinical symptom onset.10 Notably, most delays occur in the pre­ Department of Neurology,
outcomes than did intravenous thrombolysis alone.2 A hospital phase of acute stroke management and these Saarland University Medical
meta-analysis of pooled data from five ran­domised trials, delays, in contrast to inhospital delays, have not improved Center, 66421 Homburg,
Germany
involving 1287 patients with large vessel occlusion of the over the past two decades, despite great effort.12
klaus.fassbender@uks.eu
distal internal carotid artery or the proximal middle Thus, the aim of this Review is to address prehospital
cerebral artery, found that thrombectomy resulted in a barriers and inefficiencies in the delivery of thrombectomy
significant reduction of disability at day 90 (odds ratio and to discuss, following the consecutive steps of the
[OR] 2·26; 95% CI 1·67–3·06; p<0·0001).2 Until 2018, the stroke rescue chain, the results of research into stream­
treatment window was limited to 4·5 h for intravenous lining the delivery of this efficient but highly time-
alteplase and to 6 h for thrombectomy. New trials have sensitive advanced treatment of stroke.
expanded these windows for patients selected by imaging
and have changed the concept from a fixed to an individual Streamlining the prehospital stroke rescue chain
treatment window.3–6 Regarding intravenous thrombolysis, For the purpose of analysing the options available for
studies involving patients with salvageable brain tissue as improving the delivery of recanalising treatment, we
detected by multi­modal MRI3 or multimodal CT4 showed consider management of acute stroke to be a sequence of
that alteplase is still effective from 4·5 h to 9·0 h after the events starting with the onset of stroke symptoms and
onset of symptoms and for patients with wake-up stroke; ending with recanalisation. In such a stroke rescue chain
however, the number of patients potentially eligible for (figure 1), prehospital and inhospital phases can be
alteplase in this expanded treatment window was small in discriminated, subdivided by diagnostic and therapeutic
these studies. Regarding thrombectomy, studies have milestones.
shown that the procedure was still effective for patients
with large vessel occlusion who had imaging mismatch5 Patients’ help-seeking behaviour
and arrived within 6–16 h after they were last known to be Poor knowledge about stroke and the urgency in calling
well, or who had clinical-imaging mismatch6 and arrived for help are important reasons for prehospital delays.11
within 6–24 h after. However, although the dynamics of Although the involvement of emergency medical services
patho­physiological events can vary among patients and has been shown to be key in reducing delays to treatment,
even among brain regions (eg, depending on the viability these services are not regularly used (eg, by only 50–60%
of collateral circulation), recanalisation should always of patients in the USA).13 A Swiss cohort study14 involving
occur as soon as possible. 336 patients with an acute stroke admitted to a hospital
Although an estimated 11–20% of patients with ischae­ showed that visiting the family doctor rather than calling
mic stroke can have large vessel occlusion,7,8 fewer than 2% the emergency medical services was a strong risk factor for
receive thrombectomy in daily practice.7,9 A relevant reason prehospital delay (OR 4·19; 95% CI 1·85–9·46; p=0·001).

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 Review

Arrival of emergency
medical services
Symptom onset

Groin puncture
Recanalisation
Departure

Handover

Handover
On scene

Door out
Dispatch

Needle

Door 2
Door 1
Call

Emergency Emergency
Dispatch
Patient medical Hospital 1 medical Hospital 2
office
services services

Symptom onset-to-call Call-to-on scene On Transport Door-to-needle Interhospital Door-to-groin

scene transfer puncture
Door in-to-door out

Time

Figure 1: The stroke rescue chain

The prehospital and inhospital phases of stroke management consist of additional intervals that are defined by milestones of treatment performance, in which
various groups of health-care professionals are relevant. If large vessel occlusion is first diagnosed in a stroke centre that cannot provide thrombectomy, the patient
might be secondarily transferred to a thrombectomy-capable centre. Delays that occur at each link of the stroke rescue chain are cumulative and worsen outcome.

For more than two decades, stroke public awareness
campaigns have been investigated. Although most studies
supported that awareness of stroke signs and symp­toms
can be improved by campaigns, such know­ledge was only
retained for weeks or months.11,15 Only a few studies
analysed the effects of campaigns on clinically relevant
quality indicators, such as use of emergency medical
services or time to hospital admission.11 For example, a
2015 study16 showed that, in regions in Australia receiv­
ing multi­ media advertisements on this issue, the use
of emergency medical services for stroke increased by up
to 9·9%, an effect lasting for approximately 3 months. One
cluster randomised clinical trial17 in Germany involved an
infor­mational letter that was sent to 75 720 house­holds
about stroke symptoms and the urgency of calling emer­
gency medical services. Prehospital times were under 3 h
for 189 (34%) of 556 intervention patients, but for only
176 (28%) of 630 of control patients who did not receive
such information; however, this effect was signi­ficant only
for women.17
Despite these disappointing results, there is no alter­
native to public education.18 Future campaigns should
better target populations at high risk—ie, ethnic minor­
ities and older people.19,20 Because the symptoms of severe
stroke alone can render victims unable to call for help, it is
important that campaign messages also target individuals
in the environment of potential patients (eg, children as
witnesses or multipliers).21 Additionally, future campaigns
should use effective instruments (eg, videos, music, multi­
media, and social media) and useful platforms (eg, barber
shops, churches, and schools), as study observations
suggest.19,21 These campaigns should state concretely what
to do (eg, what number to call)20 and should be repetitive,
as is the case with commercial advertisements.11
Stroke identification in the dispatch office
The correct identification of stroke symptoms in the
phone call to the emergency medical services is not trivial.
On one hand, symptoms associated with the right
hemisphere or the posterior circulation can be difficult to
recognise; on the other hand, as many as 32% of symp­
toms are caused by stroke mimics such as seizures,
delirium, migraine, peripheral vertigo, intoxication, and
somatoform disorders.22 A review showed that the pro­
portion of dispatch officers who correctly recognised
stroke symptoms was highly variable, ranging from
13% to 83%.11 To improve stroke recognition, guidelines
for the management of acute stroke recommend the use
of tools for structured assessment.18,23 Additionally, to
better recognise the symptoms of posterior strokes, some
researchers have used modifications of the Face Arm
Speech Test, extended with indicators of leg weakness and
acutely reduced consciousness.24
First responders on scene
Apart from on-scene stabilisation and evaluation (includ­
ing glucose testing), obtaining the patient’s history of
malignant diseases, recent surgical procedures, coagu­la­
tion disorders, atrial fibrillation, anticoagulant use, and
times when last seen well is a key component of patient
assessment. A study25 involving 520 patients found that
the main causes of on-scene delays were the use of time-
consuming procedures (eg, intravenous cannulation or
electro­cardiography) and poor quality of communica­tion

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 Review

Los Angeles Rapid Arterial Cincinnati Three-item Vision, Prehospital Gaze Face Field Assessment
Motor oCclusion Stroke Triage stroke aphasia, and Acute Stroke Arm Speech Stroke Triage for
Scale36 Evaluation scale Assessment scale39 neglect40 Severity Time Test38 Emergency
(RACE)37 Tool34 Scale33 Destination35
Number of items 3 6 3 3 4 3 4 5
Cutoff point for large ≥4 ≥5 ≥2 ≥4 ≥1 ≥2 ≥3 ≥4
vessel occlusion
Items
Facial palsy 0 or 1 0, 1, or 2 ·· ·· ·· ·· 0 or 1 0 or 1
Arm weakness 0, 1, or 2 0, 1, or 2 0 or 1 0, 1, or 2 Required but 0 or 1 0 or 1 0, 1, or 2
not scored
Leg weakness ·· 0, 1, or 2 ·· Combined ·· ·· ·· ··
with arm
testing
Grip strength 0, 1, or 2 ·· ·· ·· ·· ·· ·· ··
Gaze and head ·· 0 or 1 0 or 2 0, 1, or 2 Tested as 0 or 1 0 or 1 0, 1, or 2
deviation neglect sign
Consciousness ·· ·· ·· 0/1/2 ·· ·· ·· ··
(alertness)
Consciousness ·· ·· 0 or 1 ·· ·· 0 or 1 ·· ··
(questions, commands)
Visual field deficit ·· ·· ·· ·· 0 or 1 ·· ·· ··
Aphasia ·· 0, 1, or 2 (if right ·· ·· 0 or 1 ·· ·· ··
hemiparesis)
Speech ·· ·· ·· ·· ·· ·· 0 or 1 0, 1, or 2
Neglect ·· 0, 1, or 2 (if left ·· ·· 0 or 1 ·· ·· 0, 1, or 2
hemiparesis)

Table: Different prehospital stroke scales for identification of large vessel occlusion in patients with stroke

with the hospital. An observational study26 found that
training sessions focusing on time awareness reduced
median on-scene times from 25·0 min (IQR 20·5–31·0)
for 148 patients to 22·5 min (18·0–28·5) for 141 patients
(p<0·001).
Use of scales for stroke recognition and triage on scene
As is the case in the dispatch office, identification of stroke
on scene is often difficult. A study27 done in the USA with
paramedic-based emergency medical services found only
62% accuracy in diagnosing stroke. A Swedish study28
with a physician-based emergency service reported that no
more than 52% of strokes were diagnosed. Scales have
been developed for identification of stroke, most of which
are derived from the National Institutes of Health Stroke
Scale (NIHSS). The prototypical Cincinnati Prehospital
Stroke Scale is a short, three-item neurological test that
rates the presence or absence of facial palsy, asymmetric
arm weakness, and speech disturbance (by asking the
patient to repeat “The sky is blue in Cincinnati.”). The Face
Arm Speech Time scale is similar to the Cincinnati
Prehospital Stroke Scale, but assesses language ability by
typical conversation.
A systematic review29 concluded that these two scales
and other first-generation prehospital scales, such as the
Los Angeles Prehospital Stroke Screen, the Melbourne
Ambulance Stroke Screen, and the Recognition of Stroke
in the Emergency Room tool, missed as many as 30% of
acute strokes on scene. One reason is that these scales are
not sensitive to symptoms of posterior circulation, such as
disorders of the visual field, consciousness, or coordina­
tion.30 Although guidelines for stroke management rec­
om­mend the use of such scales without favouring one
over the other,18,31 their application and documentation are
handled highly variably under emergency conditions.
Apart from these scales for identifying symptoms of
acute stroke, scales have also been developed to detect
symptoms suggesting stroke due to large vessel occlusion
(ie, second-generation prehospital scales). The rationale is
that the occlusion of large vessels supplying the brain
is usually associated with severe strokes and by estimating
stroke severity, these scales can identify large vessel
occlusion. Although use of the time-consuming NIHSS32
would not be practical on scene, this scale has been the
basis for developing simpler scales aimed at identifying
large vessel occlusion (table).33–40 Some of these scales
identify the presence of not only motor symptoms but also
cortical symptoms (eg, gaze, neglect, and aphasia), as well
as containing screening steps for excluding mimics and
treatment contraindications.41
Unfortunately, however, many large vessel occlu­
sions remain undetected by scales. For example, a study42
comparing the accuracy of 13 scales detecting large vessel
occlusion among 1004 patients with stroke showed that the
use of published cutoff points for triage decision making
left 20% of large vessel occlusions undetected. Similarly,
a meta-analysis43 of 66 studies found that large vessel
occlusion was detected with a sensitivity of 38–76% and a

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 Review
specificity of 72–87%. No threshold on any scale could
detect large vessel occlusion with both a high sensitivity
and a high specificity.43 These find­ings might be explained
by the fact that large vessel occlus­ion can initially cause
only minor symptoms; however, the symptoms frequently
worsen if left untreated. For example, one study44 involving
88 patients who had large vessel occlusion with minor
symptoms found that NIHSS scores increased by at least
1 point for 17 (41%) of 41 patients if no intervention
occurred. Additionally, scales for detecting large vessel
occlusion are not effective for strokes in the posterior
circulation or in the right hemisphere, and they discrim­
inate poorly between large vessel occlusion and intra­
cerebral haemor­rhage.24 The accuracy of scales for detecting
large vessel occlusion is related to the prevalence of symp­
toms, which depends on dispatch call identification and
local prevalence.42,43
Where and how to transport the patient with stroke
Guidelines for acute stroke management recommend
trans­ferring patients with stroke to the nearest hospital
offer­ing stroke treatment.18,23 It has been suggested that
patients with potential large vessel occlusion and evident
contra­indications to alteplase might benefit from direct
transport to a thrombectomy-capable centre, regardless of
travel times.45 Furthermore, if distance to a centre not
capable of thrombectomy is roughly equal to a centre that
is, emergency medical personnel should always transfer
patients to the facility offering the higher level of care.23,46
According to the American Heart Association and
American Stroke Association Mission: Lifeline Stroke
Committee,46 centres not capable of thrombectomy can be
bypassed for patients with suspected large vessel occlusion
if the travel time to a thrombectomy-capable centre is
no more than 15 min longer. According to a consensus
statement of the European Stroke Organisation, additional
travel times might even extend to 30–45 min for candidates
of potential thrombectomy;23 however, further research into
the acceptable amount of extra time is required. Optimal
travel times obviously depend on factors such as time
of symptom onset, likelihood of large vessel occlusion,
contraindications to alteplase, distances to the hospitals,
and hospital capacities. It should be noted that, in the real
world, economic considerations might also affect policies
regarding trans­port destination.
The question of whether the patient’s head should be
elevated (to avoid aspiration and improve cardiac function)
or kept flat (to increase cerebral blood flow) has been
addressed by one of the largest nursing care trials involving
more than 11 000 patients from 149 hospitals.47 This study
found no significant difference between the two head
positions in outcomes at 90 days. However, it has been
noted that strokes that were mild and not involving large
vessel occlusion were over-represented in this study, and
that head position could still be an issue for patients who
are haemodynamically unstable. A study in 700 patients48
showed that taking relatives along in the ambul­ance was
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beneficial with respect to stroke manage­ ment metrics,
potentially because pres­ence of relatives facilitated history
taking and informed consent procedures.
Prenotification: information is time
Prenotification of the hospital team about the arriving
patient is the most time saving measure in the prehospital
stroke rescue chain.11 This action allows the inhospital
stroke team to begin preparations, such as reserving CT
time or retrieving records, while the patient is still on the
way to the hospital. Several observational studies have
shown that prenotifica­tion, usually in combination with
other process quality improvements, significantly short­
ened time to treatment and increased treatment rates.11
With technological advances, telemedicine with real-
time bidirectional audio and video communication, as well
as exchange of videos, CT images, and other information
between ambulance and hospital, will have an increasing
role in stroke management quality.49 Such com­munica­tion
will be used by emergency medical personnel not only
for prenotification of the hospital but also for obtaining
guidance from hospital experts. Although the reliability
of such telemedicine interaction between ambu­ lances
and hos­pitals has been shown,50–52 its effects on clini­cal
outcomes require further clarification.
Furthermore, smartphone applications for stroke care
are being developed. Such applications are aimed at
both streamlining inhospital stroke management (eg, by
the exchange of clinical and imaging information, auto­
mated imaging analysis, or informed consent procedures
among team members) and supporting prehospital
stroke management. For the emergency medical services,
infor­mation about the time of symptom onset, stroke
severity, history of contraindications, regional hospital
capacities, and even the use of global positioning system
technologies with real-time traffic information have been
integrated into automated triage decision algorithms
based on smartphone technology.53 Apart from allowing
structured assessment and information sharing among
involved health-care professionals and providing assis­
tance in triage decision making, further applications
might facili­tate secondary transfer pro­cedures.54 Previous
studies53,54 have shown the acceptance and feasibility of
tech­nologies based on artificial intelligence and the time
gains that these technologies can achieve; however, their
effect on clinical outcomes still needs to be explored.
Furthermore, the automated recognition of stroke symp­
toms (eg, facial paresis) based on artificial intelligence is
being explored as a potential future aid on scene.55
Structured handover
The handover constitutes the crucial interface between the
prehospital and inhospital settings. Studies have shown
beneficial effects of training emer­gency medical personnel
in structured handover and in obtaining feed­back from
the stroke team.56 An ideal location for the handover of
the patient to the hospital team is the CT room (from

ambulance stretcher to CT stretcher). This room is where,
additionally to imaging, first examination, blood drawing,
and subsequent intra­venous thrombolysis can occur.11,57–59
An observational study59 of the performance of the entire
diagnostic investigation (handover, clinical assessment,
CT, point-of-care laboratory, and angiography) at a localised
entity (a stroke room) found significant reductions in
door-to-thrombectomy times from a median of 117 min
(IQR 89–150; n=81) to 102 min (85–120; n=174; p=0·012). A
protocol for direct transfer of patients with NIHSS scores
of 10 or higher to a hybrid CT and angiography device
had a median door-to-groin puncture time of 20·5 min
(95% CI 17–26) for 30 patients with stroke.60
Secondary interhospital transfer
In adherence to standard guidelines,18,23 patients are
usually transferred to the nearest hospital offering stroke
treatment. In the case of detecting large vessel occlusion
in a centre not capable of thrombectomy, an interhospital
transfer to a thrombectomy-capable centre is required. In
22 patients with severe stroke (Los Angeles Motor Scale
score ≥4), a quality improvement protocol focusing on
the performance of secondary transfer (prenotification to
the thrombectomy-capable centre and cloud-based image
sharing) reduced the door-to-groin puncture time from
151 min (95% CI 141–166) to 111 min (88–130; p<0·001).61
Additionally, this protocol increased rates of patients with
favourable outcomes (modified Rankin Scale [mRS]
score ≤2) from 25% (12 of 48 patients) without to 50%
(11 of 22 patients; p=0·04) with absolving the complete
protocol.61 Similarly, training paramedics about time
awareness significantly reduced median transport times
from 56 min to 44 min.62
Strategies of referral and triage
Several referral strategies for patients with large vessel
occlusion exist in case the nearest hospital offering stroke
treatment does not offer endovascular treat­ment. Research
into referral strategies for patients with acute stroke is a
much needed and rapidly developing field; each strategy
has strengths and weaknesses.
Mothership strategy
At first glance, direct transfer to a hospital offering
all stroke treatment options (ie, a thrombectomy-capable
centre) would be the first choice for patients with
unknown vessel status (the so-called mothership strategy;
figure 2A). However, thrombectomy-capable centres are
much rarer than are non-capable centres, and those that
are capable are usually concentrated in metropolitan
areas.63 In the USA for example, 56% of citizens would
have to drive for at least 60 min to reach a thrombectomy-
capable centre.63 Importantly, patients would receive intra­
venous thrombo­ lysis too late when a nearby centre
not capable of thromb­ectomy is bypassed. Furthermore,
unselected referrals might overwhelm the restricted
capac­ity of thrombectomy-capable centres; however, it has
www.thelancet.com/neurology Vol 19 July 2020 605
Review
A Centre not capable D Scale
of thrombectomy 1...
Thrombectomy-
2...
capable centre
3...
E Mobile
B stroke unit
C
Figure 2: Various referral strategies
(A) The mothership strategy, in which patients with stroke bypass a centre not capable of thrombectomy and are
directly transferred to a thrombectomy-capable centre. (B) The drip and ship strategy, in which patients are
secondarily transferred from a centre not capable of thrombectomy to a thrombectomy-capable centre.
(C) The drive the interventionalist strategy, in which the interventionalist comes from the thrombectomy-capable
centre to the non-capable centre to deliver a thrombectomy. (D) Use of prehospital stroke scales for triage decision
making. (E) Use of results of vascular imaging in a mobile stroke unit for triage decision making.
been noted that this problem could be attenuated by
reinforcing capable centres.64
Drip and ship strategy
Guidelines for stroke management recommend trans­
ferring a patient with stroke to the nearest stroke centre.18,23
If large vessel occlusion is diagnosed in a facility not
capable of thrombectomy, eligible patients should be
secondarily transferred to a thrombectomy-capable centre
if thrombolysis is administered before transport (the so-
called drip and ship strategy; figure 2B).18,23 The main
advantage of the drip and ship approach over the mother­
ship approach is that intravenous thrombolysis can
be initiated sooner in the usually closer centre not capable
of thrombectomy. Because better workflows in some
thrombectomy-capable centres can compensate for longer
travel times than those associated with non-capable
centres, even for symptom onset-to-needle times, the drip
and ship strategy requires a sufficient workflow quality in
centres not capable of thrombectomy.57
The main disadvantage of the drip and ship approach is
that thrombectomy can be delivered with considerable
delay, ranging from 96 min to 111 min.10,57,65–67 Even when
the distance between the two hospitals is only 15 miles,
transfer times of 104 min have been reported.68 A
study69 reported door in-to-door out times of 106 min
(IQR 86–143) in centres not capable of thrombectomy,
underlining the relevance of quality of hospital workflows
in timely secondary transfers.
Importantly, delays due to secondary transfers have
been shown to result in patients’ ineligibility for thromb­
ectomy because of imaging decay57 in up to a third of
patients (13 of 42) with stroke.70 Most studies comparing
the mothership approach with the drip and ship strategy
found that delays before thrombectomy were significantly
 Review
A B Anterior C
Anterior
Anterior
Right Left Right Left Right Left
Posterior
Posterior
Posterior
Figure 3: First reported multimodal imaging for triage decision making at the emergency site
Reproduced from Kostopoulos et al,86 by permission of Neurology. Non-contrast CT (A), CT angiography (B), and
perfusion CT (C) in a mobile stroke unit for a man aged 55 years with facial paresis, dysarthria, and a grade 4
paresis of the right extremities (National Institutes of Health Stroke Scale score 9; modified Rankin Scale score 4;
Barthel Index score 60). The CT scan showing a subacute lacunar stroke (arrow), without obstruction of large
vessels supplying the brain or critically perfused brain tissue detected by prehospital multimodal imaging, allowed
the decision to transfer the patient to a nearby hospital not capable of thrombectomy.
See Online for appendix reduced in the mothership model (appendix pp 1–3).
Some, but not all, of these studies indicated that such
time gains also translated to better functional outcomes
than were associated with the drip and ship strategy. A
study involving 984 patients with large vessel occlusion
showed that patient outcomes (measured by mRS) were
con­siderably better in the mothership model than in the
drip and ship model (appendix p 2).65
Drive the interventionalist strategy
In the so-called drive the interventionalist (also known as
the mobile embolectomy team, drip and drive, trip and
treat, drive and retrieve, or flying intervention­alist) strategy,
an interventionalist comes from the thrombectomy-capable
centre to deliver the intervention, while thrombolysis
and preparations for interventions are done at the centre
not capable of thrombectomy (figure 2C). Obviously,
this approach requires high resources at the non-capable
centre, such as vascular imaging, an angiography suite,
trained technicians, and peri-interventional services. Sev­
eral studies have shown the feasibility and considerable
time gains achieved by this model.71–75
Use of prehospital scales as a strategy for triage of stroke
The use of prehospital scales for triage decision mak­
ing aimed at identifying which patients have a high
probability of large vessel occlusion can be viewed as a
distinct referral strategy (figure 2D). However, of the
many scales (table), only the Los Angeles Motor Scale,24,76
the Rapid Arterial oCclusion Evaluation (RACE) scale,37,77
and the Cincinnati Stroke Triage Assessment Tool78 have
been explored by emergency medical personnel in the
prehospital setting. An evaluation of 71 patients enrolled
in the FAST-MAG trial76 who received vascular imaging
showed that use of the Los Angeles Motor Scale predicted
large vessel occlusion with an accuracy of 72%. A smaller
prospective study24 of 53 patients also supported that the
Los Angeles Motor Scale allowed the diagnosis of large
vessel occlusion with an accuracy of 72%. A prospective
evaluation involving 357 patients31 found that a score
606 www.thelancet.com/neurology Vol 19 July 2020
of 5 or higher on the RACE scale predicted the presence
of large vessel occlusion with a sensitivity of 88% and a
High
specificity of 68%. The large, randomised RACECAT trial
(NCT02795962) is expected to provide clinically impor­
255 tant answers to the question of whether direct transfer
128 to a thrombectomy-capable centre is associated with
0 better outcomes than is transfer to the closest regional
stroke centre.
Low Despite these limitations and deviating from guide­
lines, some hospitals have already implemented the use
of prehospital scales of large vessel occlusion as part of
their emergency medical service policy for triage decision
making. For example, the Los Angeles Motor Scale is in
use in Saarland, Germany,24 Rhode Island, USA,79 and
Moscow, Russia,80 while the RACE scale is used in Ohio77
and Texas,81 USA.
Mobile stroke units for triage of stroke
Another referral strategy is the use of a mobile stroke unit
with onboard vascular imaging (figure 2E).49 This unit is
an ambulance that contains, besides standard equipment,
a CT scanner allowing multimodal imag­ ing (eg, non-
contrast CT, CT angiography, CT perfusion imaging), a
telemedicine system enabling video­ conferencing and
trans­mission of videos and CT scans, and a point-of-care
laboratory system. The concept, initially described in
2003,82 was first introduced into clinical practice in 2008.83
The first randomised trial84 of the mobile stroke unit
system at the Saarland University Medical Center in
Homburg, Germany, not only resulted in the fastest
reported emergency call-to-intravenous thrombo­ lysis
times to date (median 38 min [IQR 34–42]), but also
increased the rates of therapy decisions (end of all required
diagnostic test procedures) during the first golden hour
(30 [57%] of 53 patients at the mobile stroke unit vs
two [4%] of 47 control patients; p<0·001).
Onboard multimodal imaging allows the differential
treatment of ischaemic and haemorrhagic stroke,83–85 as
well as triage decisions based on vascular imaging regard­
ing transfer to hospitals with or without endovascu­lar
treatment options (figure 3),86 with 100% sensitivity and
100% specificity.24 Further studies of the concept of mobile
stroke units, apart from supporting those time gains in
a large study (530 patients who were thrombolysed),87
showed the benefit of this strategy in the US health-care
system88 and the reliability of telemedical communica­
tion between the mobile stroke unit crew and hospital
experts.89,90 Results presented at the International Stroke
Conference 2020 from the Berlin Pre-hospital Or Usual
Delivery of stroke care project (B_PROUD) trial91 done in
Berlin, Germany, showed beneficial effects of the use of a
mobile stroke unit on long-term outcomes of patients
with stroke. mRS scores at day 90 were signi­ficantly better
for 749 patients in a group where a mobile stroke unit
was available than were scores for 794 patients in a
conventional treatment group (in which a mobile stroke
unit was not available). A large study comparing outcomes

and costs associated with the use of mobile stroke units
versus standard treatment is still on­going in Houston,
TX, USA (BEST-MSU, NCT02190500).
Choice of an organisational model in a stroke
network
Stroke management guidelines recom­ mend the imple­
mentation of regional stroke networks with proactive col­
labora­tion between emergency medical services, hospitals
offering various levels of care, and additionally involved
stakeholders.18,23 Successful networks agree on the most
appro­priate organisational model on a regional basis and
develop common standards for triage, prenotification,
vascular imaging, interhospital transfers, repatriation, and
means of communication and imaging sharing (eg, via
telemedicine).92 It can be anticipated that no single referral
model will fit all settings, but that multiple solutions will
be found according to local geographical barriers, health-
care resources, jurisdictions, or reimburse­ment policies.
Cost-effectiveness is a crucial issue that also needs to be
addressed for the various referral models under discussion.
Choice and customisation of organisational models can
be supported by theoretical conditional probability model­
ling, which combines previous trial data with regionally
differing geographical and infra­ structural variables.93–98
Several modelling studies showed that the optimal referral
strategy mainly depended on the probability of large vessel
occlusion, transport times to hospitals offering various
levels of care, workflow quality of the first receiving hos­
pital, and interhospital transport times.93–98
Regarding quality management in a stroke network, the
drip and ship approach assumes that centres not capable
of thrombectomy offer 24/7 availability of vascular imag­
ing, the cornerstone for identifying large vessel occlusion.
In reality, many of these centres might require upgrading
to fulfil this necessity. Key quality measures over the entire
stroke rescue chain are symptom onset-to-call times, call-
to-on-scene times, on-scene times, door-to-imaging and
door-to-needle times, door in-to-door out times, inter­
hospital transfer times, and door-to-groin puncture and
recanalisa­tion times (figure 1).
Future directions
Additional diagnostic and therapeutic options in the
prehospital setting
Additional means of identifying both stroke and stroke
due to large vessel occlusion in the prehospital setting are
being explored, including blood biomarkers (eg, glial
fibrillary acidic protein or neuron-specific enolase) or the
use of physical sensor technologies (eg, auto­mated trans­
cranial Doppler ultrasound, EEG, microwaves, accelero­
meters, near infrared, and volumetric impedance phase
shift spectroscopy).11
Considering the cascade of pathophysiological events
occurring in ischaemic brain injury, neuroprotective treat­
ments would ideally be administered directly at the emer­
gency site, so that the penumbra could be frozen before
www.thelancet.com/neurology Vol 19 July 2020 607
Review
Search strategy and selection criteria
We searched PubMed for articles containing the term
“stroke” in combination with “prehospital” or “emergency
medical service” published between Jan 1, 2000, and
Jan 31, 2020, and applied no language restrictions. We found
982 articles and examined them with a focus on originality,
timeliness, and relevance to the broad scope of this Review.
the delivery of recanalisation. The negative results of two
neuroprotection trials have been explained by the fact that
treatments are administered too late.99,100 Therefore, many
promising candidates are now being reconsidered for
evaluation directly at the emergency site, such as com­
pounds directed against oxidative stress or excitotoxicity.
New hopes are being raised because recanalisation by
thrombectomy resembles mouse models of reversible
occlusion of the middle cerebral artery. Although the
previous prehospital neuroprotective studies99,100 were
negative, they nevertheless underlined the feasibility of
doing prehospital pharmacological trials and the valuable
contribution of paramedics to stroke research.
Access to advanced stroke treatment for people living in
rural regions and low-income countries
Generally, undertreatment of stroke is most pronounced in
rural regions.101 In the thrombectomy era, this treatment
gap widens because thrombectomy-capable centres are
located almost exclusively in metropolitan centres.101 Tele­
medicine might attenuate such urban–rural disparities.92
In specific regions, the pragmatic use of helicopters might
accelerate interhospital transfers;102 however, more evi­
dence is needed.31 Research into transferring the concept of
mobile stroke units to helicopters or planes for pre­hospital
treatment and triage in remote regions is ongoing.103
Approximately 70% of strokes occur in low-income and
middle-income countries, in which mortality is dispropor­
tionately high.104 Patients in low-income countries have
minimal or no access to stroke care services. When there is
a shortage or an absence of emergency medical services,
patients with acute stroke arrive at the hospital after delays
of days or weeks, if at all. A study105 of 105 patients in
prehospital stroke management in The Gambia found
that only four patients (4%) used transportation from
emergency medical services, whereas 40 patients (38%)
used private transportation and 47 patients (45%) used
public transportation to a hospital. Overcoming the huge
gap in advanced stroke treatment will require urgency in
funding of research into affordable diagnostic and thera­
peutic solutions, such as drugs or ultrasound technologies,
that could be effective for patients with large vessel
occlusion. Furthermore, long-term financial support and
coopera­tion between high-income and low-income coun­
tries and institutions should occur, with the aim of bottom-
up building of structures such as health insur­ance systems,
emergency medical services, and stroke services.106
 Review
Conclusion
In the thrombectomy era, each link in the prehospital
stroke rescue chain should be streamlined. Measures
include designing effective public awareness campaigns,
and extensively training emergency medical personnel
in the use of prehospital scales for identifying stroke and
large vessel occlusion and in doing structured prenoti­
fica­
tion, handover, and streamlined secondary inter­
hospital transfer. Novel telecommunication technologies
might be supportive. Delivery of thrombectomy can be
strongly improved by regional networking of emergency
medical services and hospitals offering various levels of
care, with agreement on common referral strategies and
quality standards. The widening treatment gap between
patients living in rural regions and in urban regions,
and especially between patients living in low-income
and high-income countries, should become a focus of
future stroke research aimed at allowing more than a
minority of patients to benefit from advanced treatment
of stroke.
Contributors
All authors contributed to the literature search, writing, revision, and
critique of this Review.
Declaration of interests
KF reports research funding on prehospital stroke management by the
Ministry of Health of Saarland, Germany. JCG reports grants from
the American Heart Association, Patient-Centered Outcomes Research
Institute, and Genentech, the manufacturer of alteplase; and consulting
fees from Frazer, a manufacturer of mobile stroke units, outside of the
Review. All other authors declare no competing interests.
References
1 Feigin VL, Norrving B, Mensah GA. Global burden of stroke.
Circ Res 2017; 120: 439–48.
2 Goyal M, Menon BK, van Zwam WH, et al. Endovascular
thrombectomy after large vessel ischaemic stroke: a meta-analysis
of individual patient data from five randomised trials. Lancet 2016;
387: 1723–31.
3 Thomalla G, Simonsen CZ, Boutitie F, et al. MRI-guided
thrombolysis for stroke with unknown time of onset. N Engl J Med
2018; 379: 611–22.
4 Ma H, Campbell BCV, Parsons MW, et al. Thrombolysis guided by
perfusion imaging up to 9 hours after onset of stroke. N Engl J Med
2019; 380: 1795–803.
5 Albers GW, Marks MP, Kemp S, et al. Thrombectomy for stroke at
6 to 16 hours with selection by perfusion imaging. N Engl J Med
2018; 378: 708–18.
6 Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy
6 to 24 hours after stroke with a mismatch between deficit and
infarct. N Engl J Med 2018; 378: 11–21.
7 Rai AT, Seldon AE, Boo S, et al. A population-based incidence of
acute large vessel occlusions and thrombectomy eligible patients
indicates significant potential for growth of endovascular stroke
therapy in the USA. J Neurointerv Surg 2017; 9: 722–26.
8 Waqas M, Mokin M, Primiani CT, et al. Large vessel occlusion in acute
ischemic stroke patients: a dual-center estimate based on a broad
definition of occlusion site. J Stroke Cerebrovasc Dis 2020; 29: 104504.
9 Aguiar de Sousa D, von Martial R, Abilleira S, et al. Access to and
delivery of acute ischaemic stroke treatments: a survey of national
scientific societies and stroke experts in 44 European countries.
Eur Stroke J 2019; 4: 13–28.
10 Saver JL, Goyal M, van der Lugt A, et al. Time to treatment with
endovascular thrombectomy and outcomes from ischemic stroke:
a meta-analysis. JAMA 2016; 316: 1279–88.
11 Fassbender K, Balucani C, Walter S, Levine SR, Haass A, Grotta J.
Streamlining of prehospital stroke management: the golden hour.
Lancet Neurol 2013; 12: 585–96.
608 www.thelancet.com/neurology Vol 19 July 2020
12 Pulvers JN, Watson JDG. If time is brain where is the improvement
in prehospital time after stroke? Front Neurol 2017; 8: 617.
13 Mochari-Greenberger H, Xian Y, Hellkamp AS, et al. Racial/ethnic
and sex differences in emergency medical services transport among
hospitalized US stroke patients: analysis of the national get with the
guidelines-stroke registry. J Am Heart Assoc 2015; 4: e002099.
14 Fladt J, Meier N, Thilemann S, et al. Reasons for prehospital delay
in acute ischemic stroke. J Am Heart Assoc 2019; 8: e013101.
15 Hickey A, Mellon L, Williams D, Shelley E, Conroy RM.
Does stroke health promotion increase awareness of appropriate
behavioural response? Impact of the face, arm, speech and time
(FAST) campaign on population knowledge of stroke risk factors,
warning signs and emergency response. Eur Stroke J 2018;
3: 117–25.
16 Bray JE, Straney L, Barger B, Finn J. Effect of public awareness
campaigns on calls to ambulance across Australia. Stroke 2015;
46: 1377–80.
17 Müller-Nordhorn J, Wegscheider K, Nolte CH, et al.
Population-based intervention to reduce prehospital delays in
patients with cerebrovascular events. Arch Intern Med 2009;
169: 1484–90.
18 Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 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 2018; 49: e46–110.
19 Williams O, Teresi J, Eimicke JP, et al. Effect of stroke education
pamphlets vs a 12-minute culturally tailored stroke film on stroke
preparedness among black and Hispanic churchgoers: a cluster
randomized clinical trial. JAMA Neurol 2019; 76: 1211–18.
20 Skolarus LE, Zimmerman MA, Bailey S, et al. Stroke ready
intervention: community engagement to decrease prehospital delay.
J Am Heart Assoc 2016; 5: e003331.
21 Williams O, Leighton-Herrmann Quinn E, Teresi J, et al. Improving
community stroke preparedness in the HHS (hip-hop stroke)
randomized clinical trial. Stroke 2018; 49: 972–79.
22 Sequeira D, Martin-Gill C, Kesinger MR, et al. Characterizing
strokes and stroke mimics transported by helicopter emergency
medical services. Prehosp Emerg Care 2016; 20: 723–28.
23 Turc G, Bhogal P, Fischer U, et al. European Stroke Organisation
(ESO)-European Society for Minimally Invasive Neurological
Therapy (ESMINT) guidelines on mechanical thrombectomy in
acute ischaemic stroke endorsed by Stroke Alliance for Europe
(SAFE). Eur Stroke J 2019; 4: 6–12.
24 Helwig SA, Ragoschke-Schumm A, Schwindling L, et al.
Prehospital stroke management optimized by use of clinical
scoring vs mobile stroke unit for triage of patients with stroke:
a randomized clinical trial. JAMA Neurol 2019; 76: 1484–92.
25 Drenck N, Viereck S, Bækgaard JS, Christensen KB, Lippert F,
Folke F. Pre-hospital management of acute stroke patients eligible
for thrombolysis-an evaluation of ambulance on-scene time.
Scand J Trauma Resusc Emerg Med 2019; 27: 3.
26 Puolakka T, Kuisma M, Länkimäki S, et al. Cutting the prehospital
on-scene time of stroke thrombolysis in Helsinki: a prospective
interventional study. Stroke 2016; 47: 3038–40.
27 Brandler ES, Sharma M, McCullough F, et al. Prehospital stroke
identification: factors associated with diagnostic accuracy.
J Stroke Cerebrovasc Dis 2015; 24: 2161–66.
28 Andersson E, Bohlin L, Herlitz J, Sundler AJ, Fekete Z,
Andersson Hagiwara M. Prehospital identification of patients with
a final hospital diagnosis of stroke. Prehosp Disaster Med 2018;
33: 63–70.
29 Brandler ES, Sharma M, Sinert RH, Levine SR. Prehospital stroke
scales in urban environments: a systematic review. Neurology 2014;
82: 2241–49.
30 Oostema JA, Konen J, Chassee T, Nasiri M, Reeves MJ. Clinical
predictors of accurate prehospital stroke recognition. Stroke 2015;
46: 1513–17.
31 Kobayashi A, Czlonkowska A, Ford GA, et al. European Academy of
Neurology and European Stroke Organization consensus statement
and practical guidance for pre-hospital management of stroke.
Eur J Neurol 2018; 25: 425–33.
32 Heldner MR, Hsieh K, Broeg-Morvay A, et al. Clinical prediction of
large vessel occlusion in anterior circulation stroke: mission
impossible? J Neurol 2016; 263: 1633–40.

33 Hastrup S, Damgaard D, Johnsen SP, Andersen G. Prehospital
Acute Stroke Severity Scale to predict large artery occlusion: design
and comparison with other scales. Stroke 2016; 47: 1772–76.
34 Katz BS, McMullan JT, Sucharew H, Adeoye O, Broderick JP.
Design and validation of a prehospital scale to predict stroke severity:
Cincinnati Prehospital Stroke Severity Scale. Stroke 2015; 46: 1508–12.
35 Lima FO, Silva GS, Furie KL, et al. Field assessment stroke triage for
emergency destination: a simple and accurate prehospital scale to
detect large vessel occlusion strokes. Stroke 2016; 47: 1997–2002.
36 Nazliel B, Starkman S, Liebeskind DS, et al. A brief prehospital
stroke severity scale identifies ischemic stroke patients harboring
persisting large arterial occlusions. Stroke 2008; 39: 2264–67.
37 Pérez de la Ossa N, Carrera D, Gorchs M, et al. Design and validation
of a prehospital stroke scale to predict large arterial occlusion:
the rapid arterial occlusion evaluation scale. Stroke 2014; 45: 87–91.
38 Scheitz JF, Abdul-Rahim AH, MacIsaac RL, et al. 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). Stroke 2017; 48: 290–97.
39 Singer OC, Dvorak F, du Mesnil de Rochemont R, Lanfermann H,
Sitzer M, Neumann-Haefelin T. A simple 3-item stroke scale:
comparison with the National Institutes of Health Stroke Scale and
prediction of middle cerebral artery occlusion. Stroke 2005;
36: 773–76.
40 Teleb MS, Ver Hage A, Carter J, Jayaraman MV, McTaggart RA.
Stroke vision, aphasia, neglect (VAN) assessment-a novel emergent
large vessel occlusion screening tool: pilot study and comparison
with current clinical severity indices. J Neurointerv Surg 2017;
9: 122–26.
41 Zhao H, Pesavento L, Coote S, et al. Ambulance clinical triage for
acute stroke treatment: paramedic triage algorithm for large vessel
occlusion. Stroke 2018; 49: 945–51.
42 Turc G, Maïer B, Naggara O, et al. Clinical scales do not reliably
identify acute ischemic stroke patients with large-artery occlusion.
Stroke 2016; 47: 1466–72.
43 Smith EE, Kent DM, Bulsara KR, et al. Accuracy of prediction
instruments for diagnosing large vessel occlusion in individuals
with suspected stroke: a systematic review for the 2018 guidelines
for the early management of patients with acute ischemic stroke.
Stroke 2018; 49: e111–22.
44 Heldner MR, Jung S, Zubler C, et al. Outcome of patients with
occlusions of the internal carotid artery or the main stem of the
middle cerebral artery with NIHSS score of less than 5: comparison
between thrombolysed and non-thrombolysed patients.
J Neurol Neurosurg Psychiatry 2015; 86: 755–60.
45 Pride GL, Fraser JF, Gupta R, et al. Prehospital care delivery and
triage of stroke with emergent large vessel occlusion (ELVO): report
of the Standards and Guidelines Committee of the Society of
Neurointerventional Surgery. J Neurointerv Surg 2017; 9: 802–12.
46 Adeoye O, Nyström KV, Yavagal DR, et al. Recommendations for
the establishment of stroke systems of care: a 2019 update. Stroke
2019; 50: e187–210.
47 Anderson CS, Arima H, Lavados P, et al. Cluster-randomized,
crossover trial of head positioning in acute stroke. N Engl J Med
2017; 376: 2437–47.
48 Ashkenazi L, Toledano R, Novack V, EIluz E, Abu-Salamae I,
Ifergane G. Emergency department companions of stroke patients:
implications on quality of care. Medicine (Baltimore) 2015; 94: e520.
49 Fassbender K, Grotta JC, Walter S, Grunwald IQ,
Ragoschke-Schumm A, Saver JL. Mobile stroke units for prehospital
thrombolysis, triage, and beyond: benefits and challenges.
Lancet Neurol 2017; 16: 227–37.
50 Valenzuela Espinoza A, Van Hooff RJ, De Smedt A, et al.
Development and pilot testing of 24/7 in-ambulance
telemedicine for acute stroke: prehospital stroke study at the
Universitair Ziekenhuis Brussel-project. Cerebrovasc Dis 2016;
42: 15–22.
51 Wu TC, Nguyen C, Ankrom C, et al. Prehospital utility of rapid
stroke evaluation using in-ambulance telemedicine: a pilot
feasibility study. Stroke 2014; 45: 2342–47.
52 Bergrath S, Reich A, Rossaint R, et al. Feasibility of prehospital
teleconsultation in acute stroke–a pilot study in clinical routine.
PLoS One 2012; 7: e36796.
www.thelancet.com/neurology Vol 19 July 2020 609
Review
53 Nogueira RG, Silva GS, Lima FO, et al. The FAST-ED app:
a smartphone platform for the field triage of patients with stroke.
Stroke 2017; 48: 1278–84.
54 Munich SA, Tan LA, Nogueira DM, et al. Mobile real-time tracking
of acute stroke patients and instant, secure inter-team
communication-the Join App. Neurointervention 2017; 12: 69–76.
55 McDonald M, Uribe OA, Zhuang Y, et al. Comparison of human and
machine learning based facial weakness detection. International
Stroke Conference; Honolulu, USA; Feb 6–8, 2019 (abstr TP274).
56 Flynn D, Francis R, Robalino S, et al. A review of enhanced paramedic
roles during and after hospital handover of stroke, myocardial
infarction and trauma patients. BMC Emerg Med 2017; 17: 5.
57 Goyal M, Jadhav AP, Bonafe A, et al. Analysis of workflow and time
to treatment and the effects on outcome in endovascular treatment
of acute ischemic stroke: results from the SWIFT PRIME
randomized controlled trial. Radiology 2016; 279: 888–97.
58 Janssen PM, Venema E, Dippel DWJ. Effect of workflow
improvements in endovascular stroke treatment. Stroke 2019;
50: 665–74.
59 Ragoschke-Schumm A, Yilmaz U, Kostopoulos P, et al. ‘Stroke
room’: diagnosis and treatment at a single location for rapid
intraarterial stroke treatment. Cerebrovasc Dis 2015; 40: 251–57.
60 Psychogios MN, Behme D, Schregel K, et al. One-stop management
of acute stroke patients: minimizing door-to-reperfusion times.
Stroke 2017; 48: 3152–55.
61 McTaggart RA, Yaghi S, Cutting SM, et al. Association of a primary
stroke center protocol for suspected stroke by large vessel occlusion
with efficiency of care and patient outcomes. JAMA Neurol 2017;
74: 793–800.
62 Kodankandath TV, Wright P, Power PM, et al. Improving transfer
times for acute ischemic stroke patients to a comprehensive stroke
center. J Stroke Cerebrovasc Dis 2017; 26: 192–95.
63 Mullen MT, Branas CC, Kasner SE, et al. Optimization modeling to
maximize population access to comprehensive stroke centers.
Neurology 2015; 84: 1196–205.
64 Tatlisumak T. Implication of the recent positive endovascular
intervention trials for organizing acute stroke care: European
perspective. Stroke 2015; 46: 1468–73.
65 Froehler MT, Saver JL, Zaidat OO, et al. Interhospital transfer
before thrombectomy Is asociated with delayed treatment and
worse outcome in the STRATIS registry (systematic evaluation of
patients treated with neurothrombectomy devices for acute
ischemic stroke). Circulation 2017; 136: 2311–21.
66 Sun CH, Nogueira RG, Glenn BA, et al. “Picture to puncture”:
a novel time metric to enhance outcomes in patients transferred for
endovascular reperfusion in acute ischemic stroke. Circulation 2013;
127: 1139–48.
67 Venema E, Boodt N, Berkhemer OA, et al. Workflow and factors
associated with delay in the delivery of intra-arterial treatment for
acute ischemic stroke in the MR CLEAN trial. J Neurointerv Surg
2018; 10: 424–28.
68 Prabhakaran S, Ward E, John S, et al. Transfer delay is a major
factor limiting the use of intra-arterial treatment in acute ischemic
stroke. Stroke 2011; 42: 1626–30.
69 Ng FC, Low E, Andrew E, et al. Deconstruction of interhospital
transfer workflow in large vessel occlusion: real-world data in the
thrombectomy era. Stroke 2017; 48: 1976–79.
70 Mokin M, Gupta R, Guerrero WR, Rose DZ, Burgin WS,
Sivakanthan S. ASPECTS decay during inter-facility transfer in
patients with large vessel occlusion strokes. J Neurointerv Surg 2017;
9: 442–44.
71 Uchiyama N, Misaki K, Mohri M, et al. Treatment result in the
initial stage of Kanazawa mobile embolectomy team for acute
ischemic stroke. Neurol Med Chir (Tokyo) 2016; 56: 737–44.
72 Wei D, Oxley TJ, Nistal DA, et al. Mobile interventional stroke
teams lead to faster treatment times for thrombectomy in large
vessel occlusion. Stroke 2017; 48: 3295–300.
73 Hui FK, El Mekabaty A, Schultz J, et al. Helistroke:
neurointerventionalist helicopter transport for interventional stroke
treatment: proof of concept and rationale. J Neurointerv Surg 2018;
10: 225–28.
74 Seker F, Möhlenbruch MA, Nagel S, et al. Clinical results of a new
concept of neurothrombectomy coverage at a remote hospital-“drive
the doctor”. Int J Stroke 2018; 13: 696–99.
 Review
75 Brekenfeld C, Goebell E, Schmidt H, et al. ‘Drip-and-drive’: shipping
the neurointerventionalist to provide mechanical thrombectomy in
primary stroke centers. J Neurointerv Surg 2018; 10: 932–36.
76 Noorian AR, Sanossian N, Shkirkova K, et al. Los Angeles Motor
Scale to identify large vessel occlusion: prehospital validation and
comparison with other screens. Stroke 2018; 49: 565–72.
77 Zaidi SF, Shawver J, Espinosa Morales A, et al. Stroke care:
initial data from a county-based bypass protocol for patients with
acute stroke. J Neurointerv Surg 2017; 9: 631–35.
78 McMullan JT, Katz B, Broderick J, Schmit P, Sucharew H,
Adeoye O. Prospective prehospital evaluation of the Cincinnati
stroke triage assessment tool. Prehosp Emerg Care 2017; 21: 481–88.
79 Jayaraman MV, Iqbal A, Silver B, et al. Developing a statewide
protocol to ensure patients with suspected emergent large vessel
occlusion are directly triaged in the field to a comprehensive stroke
center: how we did it. J Neurointerv Surg 2017; 9: 330–32.
80 Skrypnik D. How to start an acute stroke program from scratch
in a big city like Moscow. ICCA Stroke; New Delhi, India;
March 11–12, 2019.
81 Dickson RL, Crowe RP, Patrick C, et al. Performance of the RACE
score for the prehospital identification of large vessel occlusion
stroke in a suburban/rural EMS service. Prehosp Emerg Care 2019;
23: 612–18.
82 Fassbender K, Walter S, Liu Y, et al. “Mobile stroke unit” for
hyperacute stroke treatment. Stroke 2003; 34: e44.
83 Walter S, Kostpopoulos P, Haass A, et al. Bringing the hospital to
the patient: first treatment of stroke patients at the emergency site.
PLoS One 2010; 5: e13758.
84 Walter S, Kostopoulos P, Haass A, et al. Diagnosis and treatment
of patients with stroke in a mobile stroke unit versus in hospital:
a randomised controlled trial. Lancet Neurol 2012; 11: 397–404.
85 Zhao H, Coote S, Pesavento L, et al. Prehospital idarucizumab prior
to intravenous thrombolysis in a mobile stroke unit. Int J Stroke
2019; 14: 265–69.
86 Kostopoulos P, Walter S, Haass A, et al. Mobile stroke unit for
diagnosis-based triage of persons with suspected stroke. Neurology
2012; 78: 1849–52.
87 Ebinger M, Winter B, Wendt M, et al. Effect of the use of
ambulance-based thrombolysis on time to thrombolysis in acute
ischemic stroke: a randomized clinical trial. JAMA 2014;
311: 1622–31.
88 Parker SA, Bowry R, Wu TC, et al. Establishing the first mobile
stroke unit in the United States. Stroke 2015; 46: 1384–91.
89 Itrat A, Taqui A, Cerejo R, et al. Telemedicine in prehospital stroke
evaluation and thrombolysis: taking stroke treatment to the
doorstep. JAMA Neurol 2016; 73: 162–68.
90 Wu TC, Parker SA, Jagolino A, et al. Telemedicine can replace the
neurologist on a mobile stroke unit. Stroke 2017; 48: 493–96.
91 Audebert HJ. Effects of pre-hospital acute stroke treatment as
measured with the modified rankin scale; the Berlin Pre-hospital
Or Usual Delivery of stroke care project (B_PROUD) trial.
International Stroke Conference; Los Angeles, CA, USA;
Feb 19–21, 2020.
610 www.thelancet.com/neurology Vol 19 July 2020
92 Wechsler LR, Demaerschalk BM, Schwamm LH, et al. Telemedicine
quality and outcomes in stroke: a scientific statement for healthcare
professionals from the American Heart Association/American
Stroke Association. Stroke 2017; 48: e3–25.
93 Katz BS, Adeoye O, Sucharew H, et al. Estimated impact of
emergency medical service triage of stroke patients on
comprehensive stroke centers: an urban population-based study.
Stroke 2017; 48: 2164–70.
94 Parikh NS, Chatterjee A, Díaz I, et al. Modeling the impact of
interhospital transfer network design on stroke outcomes in a large
city. Stroke 2018; 49: 370–76.
95 Milne MS, Holodinsky JK, Hill MD, et al. Drip ‘n ship versus
mothership for endovascular treatment: modeling the best
transportation options for optimal outcomes. Stroke 2017; 48: 791–94.
96 Benoit JL, Khatri P, Adeoye OM, et al. Prehospital triage of acute
ischemic stroke patients to an intravenous tPA-ready versus
endovascular-ready hospital: a decision analysis. Prehosp Emerg Care
2018; 22: 722–33.
97 Mullen MT, Pajerowski W, Messé SR, et al. Geographic modeling to
quantify the impact of primary and comprehensive stroke center
destination policies. Stroke 2018; 49: 1021–23.
98 Holodinsky JK, Williamson TS, Demchuk AM, et al. Modeling
stroke patient transport for all patients with suspected large vessel
occlusion. JAMA Neurol 2018; 75: 1477–86.
99 Bath PM, Scutt P, Anderson CS, et al. Prehospital transdermal
glyceryl trinitrate in patients with ultra-acute presumed stroke
(RIGHT-2): an ambulance-based, randomised, sham-controlled,
blinded, phase 3 trial. Lancet 2019; 393: 1009–20.
100 Saver JL, Starkman S, Eckstein M, et al. Prehospital use of
magnesium sulfate as neuroprotection in acute stroke. N Engl J Med
2015; 372: 528–36.
101 Gonzales S, Mullen MT, Skolarus L, Thibault DP, Udoeyo U,
Willis AW. Progressive rural-urban disparity in acute stroke care.
Neurology 2017; 88: 441–48.
102 Leira EC, Stilley JD, Schnell T, Audebert HJ, Adams HP Jr. Helicopter
transportation in the era of thrombectomy: the next frontier for acute
stroke treatment and research. Eur Stroke J 2016; 1: 171–79.
103 Walter S, Zhao H, Easton D, et al. Air-mobile stroke unit for access to
stroke treatment in rural regions. Int J Stroke 2018; 13: 568–75.
104 Wang H, Naghavi M, Allen C, et al. Global, regional, and national
life expectancy, all-cause mortality, and cause-specific mortality for
249 causes of death, 1980-2015: a systematic analysis for the Global
Burden of Disease Study 2015. Lancet 2016; 388: 1459–544.
105 Jaiteh LES, Helwig SA, Jagne A, et al. Standard operating
procedures improve acute neurologic care in a sub-Saharan African
setting. Neurology 2017; 89: 144–52.
106 Ogungbo B, Finkel MF, Ogun Y. Building foundations for
improving health opportunities in sub-Saharan Africa. Neurology
2013; 81: 2134–35.
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