We sought to verify the benefit of mechanical thrombectomy in patients with
acute ischemic stroke due to large vessel occlusion in the anterior circulation
and low National Institute of Health stroke scale score at presentation. The
prospective database of our stroke center was screened for patients with acute
ischemic stroke due to large vessel occlusion and a baseline National Institute
of Health stroke scale score
Results from randomized trials have shown the superiority of mechanical
thrombectomy (MT) over medical treatment (including intravenous thrombolysis—IVT) in patients with acute ischemic stroke (AIS) due to large vessel
occlusion (LVO) [1, 2, 3, 4, 5, 6]. Current guidelines recommend MT in AIS with causative
occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), a
baseline National Institute of Health Stroke Scale (NIHSS) score of
In this observational retrospective study, we screened the prospective database
of our high-volume tertiary stroke center for patients with AIS due to LVO that
had undergone MT from 1 June 2016 to 30 June 2020. All patients were diagnosed
with a comprehensive head and neck CT protocol that included a basal scan with
determination of the Alberta Stroke Program Early CT (ASPECT) score [15] followed
by multiphase CT angiography to define the site of occlusion and calculate the
pial arterial filling score [16]. In addition, a CT perfusion protocol was also
performed in patients with AIS in the anterior circulation admitted beyond 6
hours from the onset or with unknown time of onset (wake-up strokes) to determine
eligibility to MT in accordance with the advanced neuroimaging criteria [17, 18, 19].
Patients with an occlusion site other than the MCA, segment M1 or M2, or a
pre-event modified Rankin Scale (mRS) score
Flow chart of the patient inclusion criteria.
When applicable, administration of intravenous tissue plasminogen activator (tPA) was performed before MT according to standard protocols and at the discretion of the treating physicians. An endovascular treatment option aimed to re-establish the occluded vessel’s patency and avoid possible clinical deterioration had appropriately been discussed with each eligible patient and/or family member. Flow restoration at the end of each procedure was graded using the modified Treatment In Cerebral Infarction (mTICI) scale [20]. Clinical outcome was measured through the mRS score at 90 days. Two expert neuroradiologists reviewed all baseline CTs, multiphase CTAs and angiographic data, blinded to clinical outcome. Safety data were (1) brain bleeding events following reperfusion therapies, assessed by CT or MRI scan after 24–96 hours and defined according to the Heidelberg Bleeding Classification [21], and (2) death within 90 days after stroke.
Out of 459 patients, 17 (12 females, mean age 70
Representative cases. Axial non-contrast CT image (A) showing a
hyperdense vessel sign (arrowhead) and a small core of infarction in the right
temporal lobe. The CTA (B) shows the M1 segment (arrowhead) occlusion and
prominent collateral circulation. The T
Sex (females/ total patients) | 12/17 |
Mean age, years |
70 |
Median NIHSS score at the time of groin puncture [IQR] | 3 [2–5] |
Median ASPECT score at admission [IQR] | 9 [9–10] |
Site of arterial occlusion | |
MCA, M1 segment, patients/total (%) | 10/17 (56%) |
MCA, M2 segment, patients/total (%) | 7/17 (44%) |
Median pial arterial filling score [IQR] | 5 [4–5] |
Intravenous thrombolysis, patients/total (%) | 2/17 (12%) |
Onset-to-groin time | |
Onset-to-groin time |
8/17 (47%) |
Median onset-to-groin time [IQR] minutes | 222 [202–240] |
Onset-to-groin time |
5/17 (29%) |
Median onset-to-groin time [IQR] minutes | 565 [440–840] |
Unknown onset-to-groin time (wake-up stroke), patients/total (%) | 4/17 (24%) |
mTICI score 2b–3, patients/total (%) | 16/17 (94%) |
3-month mRS score 0–1, patients/total (%) | 13/17 (76%) |
Brain-bleeding events | |
Asymptomatic hemorrhagic transformation*, patients/total (%) | 2/17 (12%) |
Symptomatic parenchymal hematoma type-2*, patients/total (%) | 1/17 (6%) |
Death at 3 months, patients/total (%) | 1/17 (6%) |
SD, standard deviation; IQR, interquartile range; NIHSS, National Institute of Health Stroke Scale; ASPECT, Alberta Stroke Program Early CT score; MCA, middle cerebral artery; mTICI, modified treatment in cerebral infarction; mRS, modified Rankin Scale; * defined according to von Kummer and Colleagues [15]. |
The appropriateness of MT in patients with AIS due to LVO and a low NIHSS score
at presentation is currently debated since conclusive evidence is still ahead to
be clarified. Indeed, the limited number of randomized patients with a low
baseline NIHSS score in the main MT trials has hampered the possibility of
addressing this issue [22]. Skepticism may arise from the risks of an invasive
procedure not being counterbalanced by the possible benefits in patients
presenting with a so-called ‘minor stroke’. However, the definition of ‘minor’
stroke may vary considerably. It cannot simply be based on an NIHSS score cutoff
value without considering the type of symptoms (disabling or non-disabling) and
the association with a long-term effect favorable outcome [23]. Following this
consideration, setting an NIHSS score threshold for MT eligibility may also
appear arbitrary. Nonetheless, current guidelines recommend MT in patients with a
baseline NIHSS score
However, to date, a growing body of evidence is available on the feasibility of MT in patients with stroke due to LVO and a low NIHSS score away from the criteria mentioned above. In real-world practice, such an option is usually considered after careful evaluation of case-by-case clinical and radiological features and assessing risks and benefits. This comes along also with the increasing expertise of interventionists on MT and a better safety profile of the last-generation thrombectomy devices [25].
Here we report the experience of our high-volume stroke center on MT in patients
with anterior circulation AIS and a baseline NIHSS to score
Endovascular treatment in patients with AIS due to LVO in the anterior
circulation and mild neurological symptoms is of particular interest as they
constitute a variable, but not negligible, percentage of total patients [8, 9, 10, 11, 12].
Despite LVO, in these patients, lack of symptoms is sustained by deploying a
robust leptomeningeal collateral network [26], as confirmed in our cohort of
patients with a median pial arterial filling score showing overall good
collaterally. As these patients have higher odds of not receiving MT, they
possibly face worsening their clinical condition upon failure of the
leptomeningeal network [12]. In a recent single-center retrospective study, an
unfavorable clinical evolution was documented in a fifth of patients with stroke
due to LVO and mild symptoms that could be limited by rescue MT [12]. The
potential benefit of MT has been proposed in a retrospective study also when
performed before neurological deterioration. Indeed, MT in patients with baseline
NIHSS scores
On the other hand, a recent multicenter retrospective study has failed to
demonstrate significant differences in terms of functional outcome between MT and
best medical therapy (including IVT) in patients with a baseline NIHSS score
Given that the persistence of a minimal neurological impairment in patients with LVO is due to the recruitment of efficient leptomeningeal collaterals, these patients may also benefit from a prolonged time window for MT [11, 12, 17, 19, 26, 27, 33] as they can maintain a small ischemic core and a significant amount of salvageable brain tissue beyond 6 hours from onset (the so-called “slow progressors”) [34, 35]. Indeed, in our series, 9 out of 17 patients (53%) were treated beyond the initial 6 hours from onset. The sum of these observations also underlines the relevance of extending a multimodal vessel imaging protocol to all patients with AIS despite their baseline NIHSS score. Indeed, although an NIHSS score threshold can be set to yield a high sensitivity for detecting LVO, this diagnostic approach would inevitably miss a relevant number of patients harboring a large area of at-risk tissue and who would be otherwise good candidates for MT [36].
The main limitations of our report derive from being a retrospective observational study. The results should be viewed as preliminary from the small sample size and to be used with caution in real-world clinical practice. In consideration of the sparse evidence available to date, it is expected that open randomized controlled trials, such as the MOSTE (MinOr Stroke Therapy Evaluation) study of the IN EXTREMIS trial (https://www.inextremis-study.com), will clarify whether MT is beneficial also in patients with LVO and a low baseline NIHSS score.
The efficacy of MT in patients with AIS due to LVO and low NIHSS score at presentation has been insufficiently studied in the main randomized clinical trials. Our findings favor a potential benefit of MT also in this category of patients. Nonetheless, this issue still remains open for clarification and the need for an unambiguous recommendation in clinical practice is urgent.
MT, mechanical thrombectomy; IVT, intravenous thrombolysis; AIS, acute ischemic stroke; LVO, large vessel occlusion; ICA, internal carotid artery; MCA, middle cerebral artery; NIHSS, National Institute of Health Stroke Scale; ASPECT, Alberta Stroke Program Early CT; mRS, modified Rankin scale; tPA, tissue plasminogen activator; mTICI, modified Treatment In Cerebral Infarction; IQR, interquartile range.
AMA, IV and AB conceived and designed the experiments; GF, RM, FD, DG, ABA, RG, CR and LS performed the treatments; FC, GFR and AMA analyzed the data; PC, GDM and AP supervised the study. AMA and AB wrote the paper.
This work is part of a nonprofit study protocol approved by Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Institutional Ethics Committee: protocol number 6410/20, ID 3004. Informed consent for participation in the study was obtained in patients who were neurologically able to give it; for the other patients, the informed consent was obtained from a legal representative.
Not applicable.
This research received no external funding.
The authors declare no conflict of interest.