How to do it
Management of a wake-up stroke
1
Department of Neurology, St.
George's University Hospitals
NHS Foundation Trust, London,
UK
2
Royal Cornwall Hospitals NHS
Trust, Truro, UK
Correspondence to
Dr Xuya Huang, Neurology,
St George's Hospital, London
SW17 0QT, UK; ​xuya.​huang@​
nhs.​net
Accepted 15 January 2019
© Author(s) (or their
employer(s)) 2019. No
commercial re-use. See rights
and permissions. Published
by BMJ.
To cite: Huang X,
Alakbarzade V,
Khandanpour N, et al.
Pract Neurol Epub ahead of
print: [please include Day
Month Year]. doi:10.1136/
practneurol-2018-002179
Xuya Huang,1 Vafa Alakbarzade,‍
Anthony C Pereira1
Abstract
Current national guidelines advocate intravenous
thrombolysis to treat patients with acute
ischaemic stroke presenting within 4.5 hours
from symptom onset, and thrombectomy for
patients with anterior circulation ischaemic
stroke from large vessel occlusion presenting
within 6 hours from onset. However, a
substantial group of patients presents with acute
ischaemic stroke beyond these time windows
or has an unknown time of onset. Recent
studies are set to revolutionise treatment for
these patients. Using MRI diffusion/FLAIR (fluid-
attenuated inversion recovery) mismatch, it is
possible to identify patients within 4.5 hours
from onset and safely deliver thrombolysis. Using
CT perfusion imaging, it is possible to identify
subjects with a middle cerebral artery syndrome
who have an extensive area of ischaemic brain
but as yet have only a small area of infarction
who may benefit from urgent thrombectomy in
up to 24 hours. Here, we highlight the recent
advances in late window stroke treatment and
their potential contribution to clinical practice.
Introduction
Intravenous thrombolysis with recombi-
nant tissue plasminogen activator (rtPA)
has been the standard reperfusion therapy
for acute ischaemic stroke for almost two
decades. It provides modest benefit with a
‘number needed to treat’ to achieve func-
tional independence of 9 by 3 hours and
of 14 by 4.5 hours.1 It carries a small but
significant risk of intracerebral haemor-
rhage and has to be given in a time-crit-
ical fashion.2 Intravenous thrombolysis
alone was often ineffective in patients
with a large, proximal vessel occlusion,3 4
which led to the hypothesis that mechan-
ical extraction of the occluding thrombus
may be needed to achieve reperfusion and
improve clinical outcome. This approach
revolutionised stroke care with a series of
landmark trials led by MR CLEAN.5 In
2015, five of these studies were combined
in the HERMES collaboration, including
more than 1000 patients with acute
Huang X, et al. Pract Neurol 2019;0:1–6. doi:10.1136/practneurol-2018-002179
Pract Neurol: first published as 10.1136/practneurol-2018-002179 on 14 March 2019. Downloaded from http://pn.bmj.com/ on 14 March 2019 by guest. Protected by copyright.
‍ 1,2
Nader Khandanpour,1
ischaemic stroke with large vessel occlu-
sion. The conclusion was that mechan-
ical thrombectomy performed within
7.3 hours from symptoms onset resulted
in significant improved independence at
90 days compared with controls, with a
number needed to treat of about five.1
While both thrombolysis and throm-
bectomy offer significant benefits, only
a small proportion of patients with acute
stroke with or without large vessel occlu-
sion present within conventional time
windows. Up to 27% of patients with
ischaemic stroke have an unknown time
of onset.6 7 On the other hand, informa-
tion provided by bystanders regarding
the time the patient was last seen well is
sometimes unreliable. Moreover, not all
patients presenting with ischaemic stroke
secondary to large vessel occlusion who
currently reach local hospitals within the
early time window can be transferred to
the thrombectomy hub rapidly.8
All stroke physicians will recognise the
feeling of disappointment when admitting
a patient who has woken up with a signif-
icant stroke syndrome and has a normal
looking CT scan, knowing the uncertain
time of onset means they cannot offer
treatment. However, this is starting to
change. Prospective studies suggest that
many wake-up strokes probably occur
close to waking up.9 Recent late window
trials have shown that neuroimaging can
successfully estimate the stroke onset
time or identify a favourable perfusion
pattern in patients with an unclear onset
time or wake-up stroke, who may still
benefit from intravenous thrombolysis or
thrombectomy.
The pathophysiology of acute ischaemic
stroke (figure 1)
Occlusion of an intracranial artery results
in ischaemia and reduced cerebral blood
flow (. As cerebral blood flow falls, normal
cellular processes start to switch off.
These may be recoverable until the blood
flow reaches a very low level. However,
at less than 45% of normal cerebral blood
1
How to do it

Pract Neurol: first published as 10.1136/practneurol-2018-002179 on 14 March 2019. Downloaded from http://pn.bmj.com/ on 14 March 2019 by guest. Protected by copyright.
Figure 1  The pathophysiology of acute ischaemic stroke and corresponding imaging examples. DWI, diffusion-weighted imaging;
FLAIR, fluid-attenuated inversion recovery.

flow, cells may be irreversibly damaged and inevitably
progress to infarction. Simplified, very low cerebral
blood flow at the cellular level results in deprivation
of energy causing membrane pump failure, influx of
sodium, water and cell depolarisation. Cells swell
due to the redistribution of water. This is cytotoxic
oedema. Cells seldom, if ever, recover from this. Plain
CT scan of head is not reliable at this stage, identi-
fying only 50%–70% cases10 during the first 3 hours,
whereas MR diffusion-weighted imaging (DWI) is very
sensitive at detecting cytotoxic oedema11 showing a
hyperintense area (with corresponding apparent diffu-
sion coefficient hypointensity (restricted diffusion))
within minutes of onset. This improves hyperacute
stroke detection to 95%.12
The next stage is ionic oedema. Here, sodium and
water influx depletes them from the extracellular space,
creating a sodium gradient that pulls fluid from capil-
laries into the extracellular space.13 At this stage, there
should be some swelling of the infarcted tissue but it
may not be very obvious on CT scanning. This marks
a transition between cytotoxic oedema and vasogenic
oedema. As ionic and early vasogenic oedema develop,
ischaemic changes—such as loss of grey and white
matter differentiation and hypo-attenuation may
become visible on CT. On MRI, the T2 or fluid-at-
tenuated inversion recovery (FLAIR) sequence may
start to show hyperintensity, while DWI is clearly posi-
tive. The hyperintense DWI signal change correlates
to ‘core infarction’. However some conditions causing

Figure 2  Example of perfusion imaging showing a disproportionately large region of hypoperfusion as compared with the size of
early infarction.

2 Huang X, et al. Pract Neurol 2019;0:1–6. doi:10.1136/practneurol-2018-002179

 How to do it

Table 1  The summary of three reperfusion studies for late presentation of ischaemic stroke up to 24 hours

Pract Neurol: first published as 10.1136/practneurol-2018-002179 on 14 March 2019. Downloaded from http://pn.bmj.com/ on 14 March 2019 by guest. Protected by copyright.
mRS 0–2 at
Inclusion criteria Imaging criteria Treatment Number day 90
WAKE-UP25 Wake-up stroke Positive DWI Alteplase vs 254 vs 249 74% vs 65%
Stroke with unknown time of Negative FLAIR placebo
onset
DEFUSE-327 6–16 hours from symptoms onset Large vessel occlusion on CT Thrombectomy 92 vs 90 44% vs 16%
angiogram or MR angiogram vs standard care
CT perfusion or MR perfusion:
Core<70 mL
Mismatch ratio≥1.8
Penumbra≥15 mL
DAWN28 6–24 hours from symptoms onset Large vessel occlusion on CT Thrombectomy 107 vs 99 49% vs 13%
a. Age≥80 years, NIHSS≥10 angiogram or MR angiogram vs standard care
b. Age<80 years, NIHSS≥10 CT perfusion or DWI
c. Age<80 years, NIHSS≥20 a. Infarct volume <21 mL
b. Infarct volume< 31 mL
c. 31mL<Infarct volume<51 mL
DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery;mRS, modified Rankin Scale; NIHSS, National Institute Health Stroke Scale.

diffusion abnormalities, such as transient ischaemic
attack or migraine, might be reversible.
As the ischaemic cascade continues, the brain–
blood barrier breaks down, and macromolecules such
as albumin and plasma proteins leak into the extra-
cellular space along with water. This stage is called
‘vasogenic oedema’ and is normally visible on imaging
(hypointense on CT or hyperintense on T2 and
FLAIR), often with obvious swelling and sometimes
with additional evidence of haemorrhage.
It is important to note that while DWI becomes posi-
tive almost immediately after stroke onset, the FLAIR
does not become positive until oedema has devel-
oped. The T2 signal value correlates closely with time
from stroke symptom onset.14 Imaging studies12 15–17
tested the utility of DWI/FLAIR mismatch as a ‘tissue
clock’ to identify those whose stroke likely occurred
within 3–4.5 hours from symptoms onset. A positive
DWI lesion and a negative FLAIR sequence showed a
78%–93% specificity and 65% sensitivity to predict
that stroke onset was less than 4.5 hours previously.17
This therefore supported the hypothesis that MRI
could be used as a tissue clock to identify infarcts less
than 4.5 hours old.
Core, perfusion lesion and penumbra
Consider the acute occlusion of a middle cerebral
artery. The cerebral blood flow will drop in the affected
part of brain, usually with appropriate symptoms in
the patient. The volume of brain affected by hypoper-
fusion is known as the perfusion lesion. The cerebral
blood flow will not be uniformly low throughout the
whole perfusion lesion. There is likely to be a deeply
ischaemic region that has been irreversibly damaged.
That volume is known as the core. The rest of the
perfusion lesion will contain areas that may or may
not go on to infarct, depending on the length of time
they are ischaemic or the severity of the ischaemia.
These areas may be recoverable if adequate perfusion
is re-established rapidly and constitute the penumbra.
The question is, why does part of the perfusion
lesion survive longer than the core? The answer is the
collateral circulation. Blood may be able to access the
ischaemic area through other arterial channels (such as

Figure 3  An example of wake-up stroke MRI :A. DWI showed an area of hyperintensity in the right MCA territory; B. Correspoding
restricted diffusion on ADC map; C. FLAIR is still negative.

Huang X, et al. Pract Neurol 2019;0:1–6. doi:10.1136/practneurol-2018-002179 3

How to do it

Pract Neurol: first published as 10.1136/practneurol-2018-002179 on 14 March 2019. Downloaded from http://pn.bmj.com/ on 14 March 2019 by guest. Protected by copyright.
Figure 4  The comparison of NNT in thrombolysis and thrombectomy studies with or without imaging selection. Note that studies
that recruited using more detailed neuroimaging yielded better results. NNT, number needed to treat; MT, mechanic thrombectomy;
rtPA, recombinant tissue plasminogen activator.

the pial collaterals). If the collateral circulation is very
good, blood may even be able to reach the distal end
of the occluding thrombus with only a few seconds
delay from normal perfusion. Collaterals are critically
important for the survival of brain tissue. Better collat-
erals are associated with better clinical outcome18 and
smaller infarcts.19
CT or MR angiography are very sensitive and
specific in identifying a large proximal vessel occlu-
sion.20 21 CT angiography can also be used to assess
the collateral circulation. However, modern CT angi-
ography is so fast that while it may show the occlusion,
insufficient time may have elapsed to demonstrate the
collaterals. Therefore, multiphase CT angiography,
where the subject moves back and forth a couple of
times through the scanner, is a more sensitive and
specific method for identifying collaterals.22 23
Identifying the core and perfusion lesion is more
difficult. Consider the core first. Most authorities
agree that the DWI lesion represents the core and is
probably the best method to use. However, CT or MR
perfusion scans can also identify the core by setting
parameters to identify tissue that has been very isch-
aemic and therefore, has little probability of recovery.
The ischaemic core or DWI lesion may evolve
quickly—within minutes in some patients—whereas in
those patients with a good collateral supply or tissue
that is inherently more tolerant of ischaemia, evolution
may be slower. Therefore, some patients with a clini-
cally significant stroke have a big perfusion lesion but
still only a small ischaemic core. There may be quite
a large mismatch between the core and the perfusion
lesion. National Institute Health Stroke Scale (NIHSS)
is a good surrogate for tissue at risk, as is CT perfusion
or MR perfusion. The higher the NIHSS, the larger
the perfusion lesion. Figure 2 shows an example that
illustrated this well. The RAPID software was created
as an application to quantify tissue that comprised
the ischaemic core and tissue at risk. It was used to
identify core and penumbra in DEFUSE-3 and the core
in DAWN. The core was defined as having a relative
cerebral blood flow of <30% of contralesional blood
flow and the penumbra as having a Tmax>6 s with a
relative cerebral blood flow of >30% of the contrale-
sional side.
Common measurements used in perfusion imaging
to define core and penumbra
►► Cerebral blood flow is a measure of blood flow and is
defined as the volume of blood flowing through a given
volume of brain per unit time.
►► Tmax represents the time from the start of the scan until
the maximum intensity of contrast material arrives at
each voxel. The longer the Tmax, the more hypoperfused
Box 1  Treatment paradigm: rtPA, recombinant
tissue plasminogen activator.
Acute stroke with known time of onset 0–4.5 hours
►► Ifno thrombectomy target, intravenous rtPA (NINDS
Trial, ECASS III Trial).
►► Thrombectomy target, intravenous rtPA and then
thrombectomy (MR CLEAN et al).
Acute stroke with known time of onset 4.5–6 hours
►► Thrombectomy target, proceed to thrombectomy (MR
CLEAN et al.).
Presents with no known time of onset (but <24
hours).
►► If there is no thrombectomy target, MRI DWI/FLAIR
mismatch, intravenous rtPA (WAKE-UP).
►► Thrombectomy target determine the core and
penumbra.
►► CT (or MR) perfusion and treat up to 16 hours
(DEFUSE-3 Trial).
►► MRI DWI with NIHSS and treat up to 24 hours (DAWN
Trial).

4 Huang X, et al. Pract Neurol 2019;0:1–6. doi:10.1136/practneurol-2018-002179


of the tissue.24 Other similar parameters used are time to
peak and mean transient time.
►► Cerebral blood volume is the total volume of flowing
blood in a given volume in the brain; low flow is consid-
ered a marker of already infarcted tissue.
Putting theory into practice
The question is, can we use our understanding of
pathophysiology of stroke with modern imaging to
identify candidates for thrombolysis or thrombec-
tomy? Can we make decisions based on pathophysi-
ology rather than simple strict time criteria? Over the
last year, three landmark studies have answered that
question with a resounding, ‘Yes’. They are WAKE-UP,
DEFUSE-3 and DAWN, summarised in table 1.
The WAKE-UP study25 used MRI DWI/FLAIR
mismatch to identify those who were likely to be within
4.5 hours of stroke onset, among patients with strokes
on waking or with unknown time of onset (figure 3).
It successfully showed that it is feasible in practice to
use DWI/FLAIR mismatch as a ‘tissue clock’ to identify
those whose stroke occurred less than 4.5 hours before
the examination and that intravenous thrombolysis is
safe and effective in these selected patients (number
needed to treat was nine).
DEFUSE-3 and DAWN were similar studies in that
they each hypothesised that if one could identify
patients with large vessel occlusion who had large
perfusion lesions but still only a small core volume,
they may benefit from thrombectomy performed at up
to 16 hours (DEFUSE-3) or 24 hours (DAWN). Both
studies were stopped early because of efficacy. There
was no significant difference in adverse events between
the thrombectomy group and the best medical group.
The number needed to treat to yield one extra person
independent (modified Rankin Scale 0–2) at 90 days
after stroke was 3.6 in DEFUSE-3 and 2.8 in DAWN.
Intriguingly, DEFUSE-3 and DAWN had better effi-
cacy up to 24 hours than studies recruiting patients up
to 6 hours. The population in each of the two studies
was highly selected. The median volume of ischaemic
core was around 10 mL for DEFUSE-3 and<10 mL
in DAWN. Their strict selection criteria yielded a
small core volume with a large penumbra: a group of
patients with an excellent imaging profile. This may
explain why patients presenting between 12 and 16
hours had similar or even better outcome than those
presenting between 6 and 12 hours from symptom
onset. However, both studies confirmed benefit of
treating patients who presented between 6 and 24
hours, and the American Heart and Stroke Association
guidelines both have already endorsed them.26 The
studies also emphasised the role of advanced stroke
imaging in future clinical practice. MRI and perfusion
imaging should be readily available to all patients with
late presentation in order to select potential candi-
dates for reperfusion therapy. Other studies that are
currently recruiting a similar patient group include
Huang X, et al. Pract Neurol 2019;0:1–6. doi:10.1136/practneurol-2018-002179
How to do it
ECASS 4, EXTEND and TWIST. It is worth noting
Pract Neurol: first published as 10.1136/practneurol-2018-002179 on 14 March 2019. Downloaded from http://pn.bmj.com/ on 14 March 2019 by guest. Protected by copyright.
that TWIST uses CT scanning only to screen wake-up
stroke.
The evidence suggests that modern imaging tech-
niques that increase the precision of patient selection
could allow clinicians better to identify subjects who
are likely to respond to treatment (figure 4).
Treatment paradigm
Below we suggest a paradigm treating patients with
acute stroke with or without large vessel occlusion
presenting within 24 hours of symptoms onset. Box 1
summarises the evidence.
Conclusion
A very exciting new era in stroke management has
dawned. In patients with no clear time of onset of
stroke, many of whom suffered a stroke while asleep,
it is possible to use CT scanning and CT angiography
first to confirm that there is no established infarct
and then to decide whether or not there is a poten-
tial target for thrombectomy. If the CT scan looks
normal and there is no thrombectomy target, DWI/
FLAIR mismatch can serve as a tissue clock to allow
thrombolysis administered if there is no contraindica-
tion. Where there is a thrombectomy target, perfusion
imaging either alone or combined with clinical assess-
ment can identify brain at risk of infarction; provided
the core remains small, thrombectomy will have a high
chance of success. In the future, these techniques may
Key Points
►► Consider using CT and CT angiography in all patients
with suspected stroke who present with unclear
onset time up to 24 hours, to exclude haemorrhage
and to identify a proximal occlusion and potential
thrombectomy target.
►► Consider using DWI (diffusion-weighted imaging)/
FLAIR (fluid-attenuated inversion recovery) mismatch
as a ‘tissue clock’ to identify those whose stroke
occurred within 4.5 hours when there is no clear time
of onset, such as on waking.
►► Consider using perfusion imaging to complement CT
scanning and CT angiography and select patients with
a favourable ischaemic core and penumbra pattern for
potential thrombectomy up to 24 hours.
►► Intravenous thrombolysis or thrombectomy can have
a high success rate in patients selected by the above
means and WAKE-UP or DEFUSE-3 or DAWN inclusion
and exclusion criteria.
►► Time is brain: patients with suspected stroke who
present with an unclear onset time up to 24 hours
may be potential candidates for thrombolysis and/or
thrombectomy and should be investigated and treated
as quickly as possible.
5
 How to do it
be used to select patients better for treatment within
the traditional 6-hour timeframe.
Acknowledgements  We are very grateful to Dr Ajay Bhalla
(Consultant stroke physician) and Dr Arani Nitkunan
(consultant neurologist) for reading and commenting on the
manuscript.
Contributors  XH wrote the first draft and did subsequent
revision. VA and NK reviewed the article, provided
comments and revisions. ACP oversaw the writing process,
the organisation and the direction of the paper and provided
revision of the paper.
Funding  The authors have not declared a specific grant for this
research from any funding agency in the public, commercial or
not-for-profit sectors.
Competing interests  None declared.
Patient consent for publication  Not required.
Provenance and peer review  Commissioned. Externally peer
reviewed by Tom Hughes, Cardiff, UK.
References
1 Brunström M, Carlberg B. Thrombolysis in acute stroke. The
Lancet 2015;385:1394–5.
2 Whiteley WN, Emberson J, Lees KR, et al. Risk of
intracerebral haemorrhage with alteplase after acute ischaemic
stroke: a secondary analysis of an individual patient data meta-
analysis. Lancet Neurol 2016;15:925–33.
3 Riedel CH, Zimmermann P, Jensen-Kondering U, et al. The
importance of size: successful recanalization by intravenous
thrombolysis in acute anterior stroke depends on thrombus
length. Stroke 2011;42:1775–7.
4 Sims JR, Rordorf G, Smith EE, et al. Arterial occlusion
revealed by CT angiography predicts NIH stroke score and
acute outcomes after IV tPA treatment. AJNR Am J Neuroradiol
2005;26.
5 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.
The Lancet 2016;387:1723–31.
6 Fink JN, Kumar S, Horkan C, et al. The stroke patient who
woke up: clinical and radiological features, including diffusion
and perfusion MRI. Stroke 2002;33:988–93.
7 Mackey J, Kleindorfer D, Sucharew H, et al. Population-based
study of wake-up strokes. Neurology 2011;76:1662–7.
8 Froehler MT, Saver JL, Zaidat OO, et al. Interhospital
transfer before thrombectomy is associated 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.
9 Rimmele DL, Thomalla G, Thomalla G. Wake-up stroke:
clinical characteristics, imaging findings, and treatment option
- an update. Front Neurol 2014;5.
10 Demchuk AM, Hill MD, Barber PA, et al. Importance of early
ischemic computed tomography changes using aspects in
NINDS rtPA stroke study. Stroke 2005;36:2110–5.
6 Huang X, et al. Pract Neurol 2019;0:1–6. doi:10.1136/practneurol-2018-002179
11 Loubinoux I, Volk A, Borredon J, et al. Spreading of vasogenic
Pract Neurol: first published as 10.1136/practneurol-2018-002179 on 14 March 2019. Downloaded from http://pn.bmj.com/ on 14 March 2019 by guest. Protected by copyright.
edema and cytotoxic edema assessed by quantitative diffusion
and T2 magnetic resonance imaging. Stroke 1997;28:419–27.
12 Thomalla G, Rossbach P, Rosenkranz M, et al. Negative fluid-
attenuated inversion recovery imaging identifies acute ischemic
stroke at 3 hours or less. Ann Neurol 2009;65:724–32.
13 Simard JM, Kent TA, Chen M, et al. Brain oedema in focal
ischaemia: molecular pathophysiology and theoretical
implications. Lancet Neurol 2007;6:258–68.
14 Siemonsen S, Mouridsen K, Holst B, et al. Quantitative T2
values predict time from symptom onset in acute stroke
patients. Stroke 2009;40:1612–6.
15 Petkova M, Rodrigo S, Lamy C, et al. MR imaging helps
predict time from symptom onset in patients with acute stroke:
implications for patients with unknown onset time. Radiology
2010;257:782–92.
16 Ebinger M, Galinovic I, Rozanski M, et al. Fluid-attenuated
inversion recovery evolution within 12 hours from stroke
onset: a reliable tissue clock? Stroke 2010;41:250–5.
17 Thomalla G, Cheng B, Ebinger M, et al. DWI-FLAIR mismatch
for the identification of patients with acute ischaemic stroke
within 4·5 H of symptom onset (PRE-FLAIR): a multicentre
observational study. Lancet Neurol 2011;10:978–86.
18 Maas MB, Lev MH, Ay H, et al. Collateral vessels on CT
angiography predict outcome in acute ischemic stroke. Stroke
2009;40:3001–5.
19 Iwasawa E, Ichijo M, Ishibashi S, et al. Acute development of
collateral circulation and therapeutic prospects in ischemic
stroke. Neural Regen Res 2016;11:368–71.
20 Lev MH, Farkas J, Rodriguez VR, et al. CT angiography in the
rapid triage of patients with hyperacute stroke to intraarterial
thrombolysis: accuracy in the detection of large vessel
thrombus. J Comput Assist Tomogr 2001;25:520–8.
21 Barlinn K, Alexandrov AV. Vascular imaging in stroke:
comparative analysis. Neurotherapeutics 2011;8:340–8.
22 Kortman HG, Smit EJ, Oei MT, et al. 4D-CTA in
neurovascular disease: a review. AJNR Am J Neuroradiol
2015;36:1026–33.
23 Frölich AM, Wolff SL, Psychogios MN, et al. Time-resolved
assessment of collateral flow using 4D CT angiography in
large-vessel occlusion stroke. Eur Radiol 2014;24:390–6.
24 Wing SC, Markus HS. Interpreting CT perfusion in stroke.
Pract Neurol 2018. [Epub ahead of print: 13 Nov 2018].
25 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.
26 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:e46–99.
27 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.
28 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.