Key-words:
Acute ischemic stroke - anterior circulation large vessel occlusion - beyond 24 h
from stroke onset - endovascular treatment
Introduction
The DAWN (Diffusion-weighted Imaging (DWI) or Computed Tomography Perfusion Assessment
with Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing
Neurointervention with Trevo)[[1]] and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke[[2]] trials have demonstrated that endovascular treatment (EVT) is effective in select
patients well beyond conventional time windows. However, the effect of EVT for large
vessel occlusion (LVO) beyond 24 h from the onset of stroke is unclear.
Materials and Methods
Between May 2017 and July 2020, patients with acute ischemic stroke due to anterior
circulation LVO were treated in our hospital. Our eligibility criteria for EVT were
as follows: (1) LVO involving the internal cerebral artery (ICA), middle cerebral
artery (MCA) segment 1 (M1), and MCA segment 2 (M2) on magnetic resonance angiography
(MRA); (2) ischemic changes involving <1–3rd of the MCA territory on magnetic resonance
imaging (MRI); and (3) significant mismatch between stroke severity and infarct volume.
There was no time limit from stroke onset, or cutoff score using the Alberta Stroke
Program Early Computed Tomography Score-Diffusion Weighted Imaging (ASPECTS DWI) and
National Institutes of Health Stroke Scale (NIHSS) scores. Based on this, 40 cases
of EVT for anterior circulation LVO were performed during the study period. Median
age, median ASPECTS-DWI, and median NIHSS score were 83 years, 9, and 19.5, respectively.
Three of the 40 cases (7.5%) received EVT after 24 h from stroke onset. Herein, we
describe three cases with favorable outcomes.
Case Reports
Case 1
An 80-year-old male known to have dementia without atrial fibrillation (AF) arrived
at our hospital with a 10-day history of left hemispatial neglect and 3-day history
of gait disturbance. He was not taking antithrombotic drugs. His initial examination
findings confirmed a left hemiparesis, dysarthria, and left hemispatial neglect, and
his initial NIHSS score was 7. MRI-DWI and MRA showed acute ischemic changes in the
right parieto-occipital lobe [[Figure 1]]a with occlusion of the right ICA [[Figure 1]]b. The pyramidal tract was not severely affected on the initial MRI scan. Urgent
EVT with systemic heparinization was performed. Angiography confirmed collateral circulation
through the anterior cerebral artery [[Figure 1]]c and ophthalmic artery [[Figure 1]]d and [[Figure 1]]e. The occlusion site of the ICA was the petrous portion [[Figure 1]]d and [[Figure 1]]e. Angiography of the posterior circulation was not performed. Given that the pathophysiology
was considered to be LVO with underlying atherosclerosis, a loading dose of aspirin
(200 mg) was administered. After four cycles of percutaneous transluminal angioplasty
(PTA) [PTA; [[Figure 1]]f] using a 2.5-mm balloon (Gateway OTW [Stryker Neurovascular]), revascularization
with mild stenosis [[Figure 1]]g and [[Figure 1]]h was obtained. The next day, NIHSS score reduced to 2, and MRI-DWI and MRA showed
no ischemic changes [[Figure 1]]i and successful revascularization with residual stenosis [[Figure 1]]j. Antiplatelet drugs were continued after the EVT procedure. Two days later, stenting
was performed under local anesthesia for the residual stenosis. Three months later,
the patient recovered, with a modified Rankin Scale (mRS) score of 1. No ischemic
events or stenotic change in relation to the right ICA lesion occurred during the
1-year follow-up.
Figure 1: Case 1: (a) Initial magnetic resonance imaging (MRI)-diffusion-weighted images (DWI)
show acute ischemic changes in the right parieto-occipital lobe. b) Initial magnetic
resonance angiography (MRA) shows right internal cerebral artery (ICA) occlusion.
(c) Left internal cerebral angiography shows leptomeningeal collateral flow through
the anterior cerebral artery (white arrowheads). (d and e) Right internal cerebral
angiography shows occlusion of the petrous portion of the ICA (white arrow) and collateral
flow through the ophthalmic artery (white arrow heads). (f) Radiography image shows
the percutaneous transluminal angioplasty balloon (white arrow). (g and h) Right internal
cerebral angiography shows revascularization of the right ICA with mild stenosis.
(i) Posttreatment MRI-DWI show no ischemic change. (j) Posttreatment MRA shows revascularization
of the right ICA.
Case 2
A 97-year-old wheelchair-bound woman (mRS score 4) with chronic heart failure, dementia,
and arteriosclerosis obliterans without AF visited our hospital after a 2-day history
of reduced activity and 1 day of motor aphasia and right-sided hemiparesis. She was
not taking antithrombotic drugs. Her initial assessment confirmed the presence of
a right-sided hemiparesis, motor aphasia, and right hemispatial neglect, and her initial
NIHSS score was 18. MRI-DWI and MRA demonstrated acute ischemic changes in the left
corona radiata, frontal lobe, and parietal lobe [[Figure 2]]a with the occlusion of the left MCA [[Figure 2]]b. The pyramidal tract was not severely affected on the initial MRI. Urgent EVT
with systemic heparinization was performed. Given that the pathophysiology of her
stroke was considered LVO with underlying atherosclerosis, aspirin (200 mg) and clopidogrel
(300 mg) were administered through a nasogastric tube. Anterior angiography confirmed
occlusion of the left proximal MCA [[Figure 2]]c and reduced blood supply to the basal ganglia from the anterior choroidal artery
[[Figure 2]]d. After one thrombectomy using a 4.0-mm retrieval stent (Solitaire 4.0 mm × 40
mm clot retrieval stent [Medtronic, Minneapolis, MN, USA]), revascularization with
stenosis of the M1 portion and distal perfusion delay was confirmed [[Figure 2]]e, and a small amount of red clot was retrieved. Subsequently, after three cycles
of PTA [[Figure 2]]f using a 1.5-mm balloon (Gateway OTW [Stryker Neurovascular]), the stenosed artery
was revascularized, and distal perfusion improved [[Figure 2]]g and [[Figure 2]]h. One week after EVT, her NIHSS score reduced to 4, and MRI-DWI and MRA confirmed
the presence of minor ischemic changes [[Figure 2]]i and successful revascularization with mild residual stenosis [[Figure 2]]j. Antiplatelet drugs were continued after the EVT procedure. Three months later,
the patient recovered to prestroke mRS score of 4. No ischemic events or stenotic
changes occurred during the 4-month follow-up.
Figure 2: Case 2: (a) Initial magnetic resonance imaging (MRI)-diffusion-weighted images (DWI)
show acute ischemic changes in the left corona radiata, frontal lobe, and parietal
lobe. (b) Initial magnetic resonance angiography (MRA) shows left middle cerebral
artery (MCA) occlusion. (c and d) Left internal cerebral angiography shows the proximal
MCA occlusion (white arrow) and blood supply to the basal ganglia through the anterior
choroidal artery (white arrow heads). (e) Left internal cerebral angiography shows
revascularization of the left MCA with stenosis (white arrow) of the M1 portion and
distal perfusion delay. (f) Radiography image shows the percutaneous transluminal
angioplasty balloon (white arrow). (g and h) Left internalcerebral angiography shows
revascularization of the left MCA with mild stenosis. (i) Posttreatment MRI-DWI show
mild ischemic changes. (j) Posttreatment MRA shows revascularization of the left MCA.
Case 3
A 66-year-old woman with a history of hypertension without AF visited our hospital
30 h after the onset of dysarthria and gait disturbance. She was not taking antithrombotic
drugs. The initial assessment confirmed the presence of right-sided hemiparesis and
motor aphasia, and her initial NIHSS score was 3. MRI-DWI and MRA showed acute ischemic
changes in the left frontal lobe and basal ganglia [[Figure 3]]a with occlusion of the left ICA [[Figure 3]]b. The pyramidal tract was not severely affected on the initial MRI. Urgent angiography
confirmed occlusion of the left ICA [[Figure 3]]c and [[Figure 3]]d and blood supply to the left MCA through the anterior communicating artery [[Figure 3]]e. Since the symptoms were mild, she did not proceed to EVT and was administered
2.5 mg/h argatroban hydrate and 100 mg aspirin daily. However, 6 h later, her hemiparesis
and aphasia deteriorated (NIHSS score increased to 8); thus, EVT with systemic heparinization
was performed. Initially, ADAPT[[3]] was planned to avoid crossing lesion of unknown pathology, but thrombectomy using
a retrieval stent was ultimately performed because the clot was not aspirated. After
one thrombectomy using a 6.0-mm retrieval stent (Solitaire 6.0 mm × 40 mm clot retrieval
stent [Medtronic, Minneapolis, MN, USA)]) [[Figure 3]]f, revascularization with a small amount of red clot [[Figure 3]]g and [[Figure 3]]h was achieved. One day later, NIHSS score reduced to 4, and MRI-DWI and MRA showed
no ischemic changes [[Figure 3]]i as well as successful revascularization [[Figure 3]]j. Transthoracic echocardiography post-EVT showed no intracardiac thrombus. Transesophageal
echocardiography was not available at our hospital. Anticoagulant drugs were initiated,
and the cause of the stroke was diagnosed as cryptogenic embolism. Three months later,
the patient recovered with an mRS score of 1. No ischemic events or stenotic changes
occurred during the 4-month follow-up.
Figure 3: Case 3: (a) Initial magnetic resonance imaging (MRI)-diffusion-weighted images (DWI)
show acute ischemic changes in the left corona radiata and frontal lobe. (b) Initial
magnetic resonance angiography (MRA) shows the left internal cerebral artery (ICA)
occlusion and cross-flow to the left middle cerebral artery (MCA) through the anterior
communicating artery. (c and d) Left internal cerebral angiography showing the ICA
occlusion (white arrow). (e) Right internal cerebral angiography shows the collateral
flow for the left MCA through the anterior communicating artery. (f) Radiography image
showing the retrieval stent (white arrowheads). (g and h) Left internal cerebral angiography
shows revascularization of the left ICA with a small amount of red clot. (i) Posttreatment
MRI-DWI show no ischemic changes. (j) Posttreatment MRA shows revascularization of
the left ICA.
Discussion
In the DEFUSE 3 trial,[[2]] about 20% of patients with MCA or ICA occlusion who presented in an extended time
window and were not treated with EVT had a persistent mismatch for at least an additional
24 h.[[4]] Desai et al.[[5]] reported results of EVT beyond 24 h from stroke onset in 21 patients with ICA or
MCA (M1) occlusions, finding a revascularization rate of 81% and a favorable outcome
in 43%. However, it is not clear exactly what hemodynamics had a persistent mismatch.
In case 1, the patient had an LVO with underlying atherosclerosis. This condition
generally results in lower NIHSS score and smaller infarct volume due to good collateral
flow,[[6]] which we observed. The good collateral flow of the leptomeningeal and ophthalmic
arteries was identified on angiography. Since LVO with underlying atherosclerosis
was suspected, PTA was performed instead of thrombectomy. The proximal end of the
ICA occlusion was 4.0 mm in diameter and a 2.5 mm balloon was chosen as the most suitable
size for PTA. A method of using a retrieval stent as the first approach to LVO with
underlying atherosclerosis may led to injury of the intima, resulting in re-occlusion
and hemorrhagic complications.[[7]] The use of a retrieval stent as the first approach to LVO with underlying atherosclerosis
has been discussed previously.[[8]],[[9]],[[10]]
In case 2, the patient received PTA for residual stenosis after thrombectomy. Since
the crab crow sign[[11]] was found at the occlusion site, thrombectomy was initially performed. Although
it was unclear whether there was atherosclerosis or a dissection underlying the residual
stenosis, PTA was performed secondarily. Although leptomeningeal collateral flow from
the posterior circulation could not be evaluated in this case, it is possible that
there was a collateral blood supply from the posterior circulation to explain the
reduced cortical damage. With regard to postoperative medication, an antiplatelet
drug was used to prevent residual stenosis.
Case 3 was a patient with mild neurological symptoms and good cross flow through the
anterior communicating artery. Six hours after starting medication, EVT was needed
because her symptoms worsened. One-third of patients with mild LVO have neurological
symptoms worsening within 24 h without EVT.[[12]] Since red clots were retrieved by thrombectomy, and no residual stenosis was observed,
she received an anticoagulant drug postoperatively.
Kim et al.[[13]] suggested that patients with underlying atherosclerosis had better collateral flow
than those with other stroke subtypes, presumably because a longer time is required
for complete arterial occlusion, allowing the development of adequate collateral flow
before acute stroke onset. Abundant collateral flow is significantly associated with
better clinical outcomes. In other words, LVO with underlying atherosclerosis may
be a prognostic predictor of EVT beyond 24 h from the onset of stroke. All 21 cases
of EVT for anterior circulation LVO beyond 24 h from the onset of stroke reported
by Desai et al.[[5]] had no underlying atherosclerosis. In patients with thromboembolic stroke where
the collateral circulation is developed, as was observed in Case 3, favorable outcomes
can be expected even when performing EVT beyond 24 h from stroke onset.
In all 3 cases, the damage to the pyramidal tract was relatively minor. Even if the
infarct volume is relatively small, or if the pyramidal tract—including the corona
radiata—is profoundly affected, a favorable outcome cannot be expected. Salvage of
the pyramidal tract through reperfusion was associated with improved outcome, independent
of overall salvage of ischemic tissue in anterior circulation stroke.[[14]] Furthermore, the infarct area was not large in all cases. Intracerebral hemorrhage
(ICH) after EVT for ischemic stroke is a well-known complication, with increase in
morbidity and mortality. Large infarct volume has been shown to be associated with
increased risk of ICH.[[15]] The symptoms of all three patients in our study continued to worsen from the time
of stroke onset. In the DEFUSE 3 trial,[[2]] the incidence of persistent mismatch in patients who presented 24–40 h after onset
with an anterior circulation LVO was as high as 10%.[[4]] There are reports that the infarct volume continues to expand for several days
in cases where revascularization is not achieved.[[15]],[[16]]
Conclusions
The pathophysiology of LVO beyond 24 h from the onset of stroke varies and may require
multimodal treatment. Preserving the pyramidal tract may lead to favorable outcomes,
even in cases of anterior circulation LVO beyond 24 h from stroke onset. EVT may be
effective because there are cases in which infarct volume continues to increase more
than 24 h from anterior circulation LVO onset.
Authors' note
Informed consent has been obtained from the patients for this study and publication
of this case report with accompanying images.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form, the patients have given their consent for their images and other clinical
information to be reported in the journal. The patients understand that name and initials
will not be published and due efforts will be made to conceal their identity, but
anonymity cannot be guaranteed.
