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Treatment of Acute Ischemic Stroke due to Large Vessel Occlusion With COVID-19

Experience From Paris
Originally publishedhttps://doi.org/10.1161/STROKEAHA.120.030574Stroke. 2020;51:2540–2543

Abstract

Background and Purpose:

Higher rates of strokes have been observed in patients with coronavirus disease 2019 (COVID-19), but data regarding the outcomes of COVID-19 patients suffering from acute ischemic stroke due to large vessel occlusion (LVO) are lacking. We report our initial experience in the treatment of acute ischemic stroke with LVO in patients with COVID-19.

Methods:

All consecutive patients with COVID-19 with acute ischemic stroke due to LVO treated in our institution during the 6 first weeks of the COVID-19 outbreak were included. Baseline clinical and radiological findings, treatment, and short-term outcomes are reported.

Results:

We identified 10 patients with confirmed COVID-19 treated for an acute ischemic stroke due to LVO. Eight were men, with a median age of 59.5 years. Seven had none or mild symptoms of COVID-19 at stroke onset. Median time from COVID-19 symptoms to stroke onset was 6 days. All patients had brain imaging within 3 hours from symptoms onset. Five patients had multi-territory LVO. Five received intravenous alteplase. All patients had mechanical thrombectomy. Nine patients achieved successful recanalization (mTICI2B-3), none experienced early neurological improvement, 4 had early cerebral reocclusion, and a total of 6 patients (60%) died in the hospital.

Conclusions:

Best medical care including early intravenous thrombolysis, and successful and prompt recanalization achieved with mechanical thrombectomy, resulted in poor outcomes in patients with COVID-19. Although our results require further confirmation, a different pharmacological approach (antiplatelet or other) should be investigated to take in account inflammatory and coagulation disorders associated with COVID-19.

Higher rates of strokes have been observed in patients with coronavirus disease 2019 (COVID-19),1 and large-vessel stroke has been reported as a presenting feature of COVID-19 in the young.2 Here, we describe our initial experience in the treatment of patients with COVID-19 presenting with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) during the first 6 weeks of the COVID-19 outbreak in Paris, France.

Methods

According to the Transparency and Openness Promotion Guidelines, the authors declare that the data which support the findings of this study are available from the corresponding author upon reasonable request.

All consecutive patients with COVID-19 with AIS due to LVO treated in our institution during the 6 first weeks of the COVID-19 outbreak, between March 1st and April 15th, 2020, were included. All patients had RT-PCR confirmed COVID-19. Patients could have a Chest computed tomography at admission to provide early screening before mechanical thrombectomy (MT). Baseline clinical and radiological findings, treatment, and short-term outcomes were prospectively gathered. Our local ethics committee approved the use of patient data for this research protocol. In accordance with French legislation, informed consent was not needed from patients because this study analyzed anonymized data collected prospectively as a part of routine clinical care.

Results

Among 37 patients treated for an AIS with LVO in our institution between March 1st and April 15th, 2020, 10 patients with confirmed COVID-19 were included. All data regarding clinical and radiological features and medical management are reported in the Table. The median age of patients with COVID-19 with AIS and LVO was 59.5 years, 8 patients were men.

Table. Characteristics of Patients With and Without COVID-19 and Acute Ischemic Stroke due to Large Vessel Occlusion*

Total (n=37)COVID-19 (n=10)Non COVID-19 (n=27)
Characteristics
 Median age (IQR), y70 (57–79)59.5 (54–71.5)72 (60–81.5)
 Male sex, no. (%)21 (57)8 (80)13 (48)
 Median baseline mRS (IQR)0 (0–1)1 (0–1)0 (0–1)
Risk factor
 Hypertension, no. (%)20 (54)5 (50)15 (55)
 Diabetes melitus, no. (%)10 (27)4 (40)6 (22)
 Hypercholesterolemia, no. (%)13 (35)3 (30)10 (37)
 Smoking, no. (%)8 (22)1 (10)7(26)
 Atrial fibrillation, no. (%)9 (24)1 (10)8 (30)
 Prestroke anticoagulation, no. (%)8 (22)4 (40)5 (18)
Symptoms of COVID-19 and chest computed tomography around the time of stroke
 Fever, no. (%)5 (13)5 (50)0
 Cough, shortness of breath, respiratory distress, no. (%)9 (24)7 (70)2 (7)
 No or mild symptoms / no oxygen requirement, no. (%)32 (86)7 (70)25 (93)
 Dyspnea with saturation <94% on room air, no. (%)5 (13)3 (30)2 (7)
 Anosmia, no. (%)000
  No symptom, no. (%)27 (73)2 (20)25 (93)
  Time from COVID-19 symptoms onset (range), d6 (2–18)
Chest computed tomography8 (80)2 (7)
 Opacities consistent with a COVID-19 infection8 (100)0
Stroke characteristics
 Median NIHSS (IQR)18 (13–22)22 (19–25.7)16 (12.5–19.5)
 Diagnosis imaging
  MRI, no. (%)29 (78)8 (80)21 (78)
  Computed tomography, no. (%)8 (22)2 (20)6 (22)
  Median ASPECTS (IQR)7 (5–8.5)5 (3–7)7 (6–8.75)
  Occlusion site
   Carotid terminus, no. (%)9 (24)3 (30)6 (22)
   M1, no. (%)15 (40)6 (60)9 (33)
   M2, no. (%)11 (30)011 (41)
   Basilar, no. (%)2 (5)1 (10)1 (4)
   Multiterritory LVO, no. (%)7 (19)5 (50)2 (7)
 Median Clot Burden Score (IQR)7 (5–9)6 (5–7)7 (5–9)
 Median time from onset to imaging (IQR), min152 (115–216)119 (104–143)177 (128–228)
 Intravenous thrombolysis, no. (%)18 (49)5 (50)14 (52)
 Median time from onset to IV-thrombolysis (IQR), min175 (137–192)175 (160–185)175 (120–195)
Mechanical thrombectomy
 Median time from onset to arterial puncture (IQR), min321 (258–399)251 (220–303)334 (278–450)
 Median time from onset to recanalization (IQR), min340 (294–430)302 (277–340)392 (309–438)
 Median number of passes (IQR)2 (1–4)3.5 (3–4.75)3 (1–4)
 First pass effect, no. (%)9 (24)09 (33)
 Successful recanalization, no. (%)32 (86)9 (90)23 (85)
Follow-up and outcome
 Median 24 h NIHSS (IQR)18 (8–22)25 (19.75–42)15 (5–20)
 Dramatic early neurological improvement, no. (%)6 (16)06 (22)
 In-hospital all-cause mortality, no. (%)9 (24)6 (60)3 (11)
 Sepsis associated mortality, no. (%)2 (5)2 (20)0
 Malignant brain edema associated mortality, no. (%)4 (11)2 (20)2 (7)
 Acute respiratory failure associated mortality, no. (%)2 (5)2 (20)0
 Early cerebral re-occlusion, no. (%)4 (11)4 (40)0
 Symptomatic intracranial hemorrhage, no. (%)1 (3)01 (4)

Successful recanalization was defined by a TICI (Thrombolysis in Cerebral Infarction) score of 2B-3, first pass effect was defined as a successful recanalization achieved after one pass, dramatic early improvement was defined as an improvement of ≥8 NIHSS points, symptomatic intracranial hemorrhage was defined as intracranial hemorrhage associated with an increase by ≥4 points on the NIHSS. ASPECTS indicates Alberta Stroke Program Early CT Score; COVID-19, coronarivus disease 2019; IQR, interquartile range; LVO, large vessel occlusion; MRI, magnetic resonance imaging; mRS, modified Rankin Scale; and NIHSS, National Institutes of Health Stroke Scale.

*Percentages may not total 100 because of rounding.

†Two non COVID-19 patients had acute pulmonary edema resulting in dyspnea.

Two patients were asymptomatic, and 5 had mild symptoms of COVID-19 before stroke onset. All patients with chest computed tomography at admission (80%) had radiological findings consistent with a COVID-19 infection. Median time from COVID-19 symptoms onset to stroke onset was 6 days (range 2–18 days). Three patients had a stroke during hospitalization for COVID-19.

Eight patients (80%) had at least one risk factor for stroke. Two patients were younger than 50 years old and had no known risk factor for stroke. The median National Insitutes of Health Stroke Scale at admission was 22. AIS diagnosis imaging was performed within 3 hours from stroke onset for all patients. Five patients (50%) had multi-territory LVO at baseline (with proximal middle cerebral artery occlusion and either anterior cerebral artery or posterior cerebral artery occlusion), with a median admission Alberta Stroke Program Early CT Score of 5.

Five patients (50%) were treated with intravenous thrombolysis, within a median time of 175 minutes.

All 10 patients were treated with MT, all procedures were started within 6 hours from stroke onset. Overall, 9 patients (90%) had successful recanalization defined by a modified Thrombolysis in Cerebral Infarction score ≥2B, with a median time from stroke-onset to recanalization of 302 minutes. None of our patients achieved complete recanalization after one pass (ie, first-pass effect), with a median number of 3.5 passes per patient.

Overall, 4 patients had early intracranial proximal artery reocclusion within 24 hours. Altogether, 6 patients (60%) died during hospitalization. Despite high angiographic recanalization rates and timeframes, none of our patients had dramatic neurological improvement 24 hours after MT. No patient experienced symptomatic intracranial hemorrhage at 24 hours.

Discussion

Our series highlights new important insights into patients with COVID-19 who suffer from AIS due to an LVO. First, most of them (70%) had mild or no respiratory signs at the time of stroke, which could suggest the absence of correlation between the severity of respiratory symptoms and the risk of AIS with LVO. Second, all patients for whom a Chest computed tomography was performed (80%) at the time of admission had radiological features consistent with a COVID-19 infection, suggesting that Chest computed tomography could be relevant for early screening of COVID-19 in patients with AIS. Half of them presented with multiple LVO on initial imaging, which is much higher than what is usually observed in patients with LVO,3 and could be explained by the coagulation and microcirculation disorders described in patients with COVID-19.4,5

More important, our series shows the devastating prognosis of patients with COVID-19 with AIS due to LVO and is in line with a recent publication displaying COVID-19 cardiovascular impact.4 Indeed, although successful recanalization rates reached 90%, which seems in line with everyday practice,6,7 MT procedures were more complex with 50% multi-territory LVO, no first-pass effect and 4 patients with early reocclusions, altogether resulting in high in-hospital mortality rates (60%) and no clinical improvement among survivors. Of note, 4 of our patients had prestroke anticoagulation (1 patient under oral anticoagulant combined with dual antiplatelet therapy for recent acute coronary syndrome, 3 patients were treated with therapeutic dose of heparin in hospital for COVID-19), which did not prevent the occurrence of an AIS with LVO in the particular setting of COVID-19. Recent works have shed light on the endothelial cell and neutrophil extracellular traps involvement of COVID-19,8,9 suggesting that our patients have been recanalized without successful reperfusion, possibly due to microvascular thromboinflammation damages or endotheliitis.9 In addition, reocclusions might be promoted by a procoagulant state, an association that has already been described with infections.10,11 In the COVID-19 setting, a recent study highlighted this finding with venous and arterial thromboembolic complications.12

Our study does not support the fact that COVID-19 was primarily responsible for AIS with LVO as most of our patients had at least one known risk factor for stroke and no proper etiological investigations could be performed (mostly due to rapid clinical deterioration leading to death). Nevertheless, further studies are urgently needed to assess the potential role of microthrombotic disorders in the occurrence of strokes and the relevance in this setting of a combined approach with a MT and medical treatment (ie, antiplatelet therapy or neutrophil extracellular traps targeting therapy), to limit neurological disabilities for COVID-19 survivors.

Nonstandard Abbreviations and Acronyms

AIS

acute ischemic stroke

COVID-19

coronavirus disease 2019

LVO

large vessel occlusion

MT

mechanical thrombectomy

Footnotes

*Drs Escalard and Maïer contributed equally.

For Sources of Funding and Disclosures, see page 2543.

Correspondence to: Simon Escalard, MD, Interventional Neuroradiology Department, Rothschild Foundation Hospital, 25 rue Manin 75019 Paris, France. Email

References

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