Mechanical thrombectomy for reperfusion of acute ischemic stroke in a Stroke Unit in Argentina

Abstract Stroke is an important cause of morbidity and mortality worldwide. Reperfusion therapy with intravenous tissue plasminogen activator (IV-tPA) was first implemented in 1996. More recently, endovascular reperfusion with mechanical thrombectomy (MT) demonstrated a robust beneficial effect, extending the 4.5 h time window. In our country, there are difficulties to achieve the implementation of both procedures. Objective: Our purpose is to report the early experience of a Comprehensive Stroke Center in the use of MT for acute stroke. Methods: Analysis of consecutive patients from January 2015 to September 2018, who received reperfusion treatment with MT. Demographic data, treatment times, previous use of IV-tPA, site of obstruction, recanalization, outcomes and disability after stroke were assessed. Results: We admitted 891 patients with acute ischemic stroke during this period. Ninety-seven received IV-tPA (11%) and 27 were treated with MT (3%). In the MT group, mean age was 66.0±14.5 years. Median NIHSS before MT was 20 (range:14‒24). The most prevalent etiology was cardioembolic stroke (52%). Prior to MT, 16 of 27 patients (59%) received IV-tPA. Previous tPA treatment did not affect onset to recanalization time or door-to-puncture time. For MT, door-to-puncture time was 104±50 minutes and onset to recanalization was 289±153 minutes. Successful recanalization (mTICI grade 2b/3) was achieved in 21 patients (78%). At three-month follow-up, the median NIHSS was 5 (range:4‒15) and mRS was 0‒2 in 37%, and ≥3 in 63%. Conclusions: With adequate logistics and strict selection criteria, MT can be implemented in our population with results like those reported in large clinical trials.


Mechanical thrombectomy for reperfusion of acute ischemic stroke in a Stroke Unit in Argentina
Trombectomía mecánica para la reperfusión en el accidente cerebrovascular agudo en una Unidad Cerebrovascular de Argentina Recently, the DAWN trial demonstrated the clinical efficacy of MT in proximal occlusions in highly selected patients, with stroke occurring between 6 and 24 hours after the onset of symptoms 11 . These benefits were confirmed by DEFUSE III trial, which included patients with NIHSS≥6 and treatment 6 to 16 hours after symptoms onset 12 .
In our country, MT for acute stroke is being used in a few selected centers, and there are difficulties to achieve the adequate implementation of acute stroke treatment programs throughout most of the country.
We report the initial experience of a Comprehensive Stroke Center in the use of MT as a reperfusion treatment for acute ischemic stroke.

METHODS
We assessed consecutive patients with ischemic stroke who received reperfusion treatment with MT in our center, between January 2015 and September 2018. We assessed demographic data, vascular risk factors, time elapsed between the onset of symptoms and of MT, use of IV-tPA prior to MT, severity of stroke measured through the National Institute of Health Stroke Scale (NIHSS) 13 prior to MT, site of obstruction, symptoms to puncture time and door to puncture time. The degree of recanalization was measured using the modified Thrombolysis in Cerebral Infarction scale (mTICI), and successful recanalization was defined as grade 2b (i.e., antegrade reperfusion of more than half of the previously occluded target artery ischemic territory) or grade 3 (complete antegrade reperfusion) 14 . The evolution was evaluated through the NIHSS scale at three months and the degree of disability measured by the Modified Rankin Scale (mRS) at 90 days. The presence of a mRS≤2 was considered a good outcome.
Every patient underwent cerebral tomography (CT) and/ or magnetic resonance image (MRI) of the brain at the time of admission, followed by a vascular imaging to define the precise site of obstruction. Depending on the availability and/or characteristics of the patient, control brain CT or MRI were performed 24 hours after the procedure.

Treatment protocol
All patients were treated according to a standardized protocol for acute ischemic stroke in our center. For those cases eligible for performing intravenous thrombolysis, IV-tPA was administered, and if occlusion of an intracranial artery (internal carotid, proximal middle cerebral artery -M1 or M2-, proximal anterior cerebral artery, proximal posterior cerebral artery or basilar artery) was present, we considered MT following IV-tPA. For those patients who were not candidates for IV-tPA (time window after 4.5 hours or contraindications to IV-tPA), MT was directly implemented.
Selection criteria for MT were occlusion of an intracranial artery; age≥18 years; NIHSS score≥6; and treatment feasible to be initiated (groin puncture) within 6 hours of symptom onset. MT was performed with Stent Retriever Solitaire™ or Trevo™.

Data analysis
Categorical variables are presented as numbers or percentages. Quantitative variables are expressed as means and standard deviations (SD), or medians and interquartile ranges (IQR), according to their distribution. Parametric and nonparametric tests were used, as appropriate. In the comparative evaluation of proximal and distal occlusions, the means of the nonparametric variables were analyzed with Fisher's test. The differences were considered significant for p<0.05 values.
The statistical analysis was performed with the SPSS software, version 20.0 (IBM Corp., Armonk, NY).

RESULTS
Overall, 891 patients were admitted with a diagnosis of acute ischemic stroke from January 2015 to September 2018. IV-tPA was administered to 97 patients (11%), while 27 patients (3%) were treated with MT according to predetermined selection criteria. Table 1 summarizes the demographic, clinical and imaging characteristics of MT cases.    In a comparative analysis between patients with proximal occlusions (intracranial carotid artery and middle cerebral artery at M1 level) and distal occlusions (middle cerebral artery at M2 level or posterior circulation), the only statistically significant difference was the younger age in patients with distal occlusions (51±15 vs. 71±12; p=0.003). There were four times more cases of left MCA -M1 occlusions than right MCA -M1 occlusions.
We also performed a comparative analysis between patients who did and did not receive IV-tPA before the MT. No statistically significant differences were found in relation to demographic data, site of occlusion, treatment times, or stroke etiology. The group that did not receive IV-tPA had a tendency for better median NIHSS at three months (4.5 vs 10), but without reaching statistical significances.

DISCUSSION
We report the use of MT in 3% of patients admitted to our Stroke Unit with diagnosis of acute ischemic stroke. We obtained a high rate of recanalization, performing the procedure within the recommended times, with a low number of serious complications and good functional recovery at three months.
Our center is a non-profit clinical and research Neurology and Neurosurgical institution, with 113 inpatient beds. We have a Vascular Neurology section since 1996, with eight vascular neurologists in the staff and two fellows. We incorporated the fibrinolytic treatment in 1997. In 2012, we opened our Stroke Unit with five beds and written admission criteria. We have been performing endovascular acute stroke treatments since 2015. We have a neurologist on call 24 hours a day. Our catchment area is variable. Most patients live in the city of Buenos Aires and its suburbs (population=14.8 million). We receive some patients with EMS pre-notification, and many come to our emergency room using their own transportation.
The most frequent occlusion site was the M1 segment of MCA, and we found four times more cases of left MCA than right MCA. This result is likely caused by chance, although we cannot rule out a bias introduced by the presence of hemineglect in right MCA strokes, causing delay in consultation. Cardioembolic stroke was the most frequent etiology in these patients. A combined treatment with IV-tPA was done in approximately half of the cases, without affecting time to MT.
In comparison to published data from clinical trials, our population had higher NIHSS score at admission, similar times from stroke to groin puncture, similar recanalization rates and equal good functional outcome at three months 15 .
In Latin America, thrombolysis for patients with acute ischemic stroke is available in all countries, but only for a relatively small proportion of patients (usually<1%). An even smaller proportion of eligible patients received thrombectomy 16 .
Only few case series of the use of MT for acute ischemic stroke are reported in South America. Two studies from Brazil reported an acceptable efficacy and good safety results 17,18 . Another study from Colombia found high impacts in functional independency at three months, without increase in mortality 19 . Finally, a case series from another center in Argentina showed a good recanalization rate (73%) with a three-month mortality of 27.3% 20 ( Table 2). With the establishment of endovascular treatment as a standard of care and its increased use, it is important to encourage institutional initiatives to monitor and improve procedural metrics of safety and efficacy 21 .
In the Declaration of Gramado, stroke experts from 13 Latin American countries agreed on the need to increase the development of stroke units and to implement evidence-based treatments of thrombolysis as a first step, and thrombectomy in comprehensive centers as the next step 16 . Our report adds to these data, suggesting the feasibility of the implementation of MT protocols in Latin America.
In conclusion, MT is feasible in our environment. The use of strict protocols and the training of a multidisciplinary team is a key factor in the identification of patients who can benefit from this treatment.