- Department of Neurosurgery, Brain and Spine Center, Invision Health, Buffalo, New York, USA
- University of Illinois College of Medicine at Peoria, Peoria, IL, USA
- Department of Neurosurgery, SUNY Upstate Medical University, Curitiba, Brazil
- Instituto de Neurologia de Curitiba, Curitiba, Brazil
Tobias A. Mattei
Instituto de Neurologia de Curitiba, Curitiba, Brazil
DOI:10.4103/2152-7806.183522Copyright: © 2016 Surgical Neurology International This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Mattei TA, Rehman AA, Goulart CR, Marília G. Sória, Rizelio V, Meneses MS. Successful outcome after endovascular thrombolysis for acute ischemic stroke with basis on perfusion-diffusion mismatch after 24 h of symptoms onset. Surg Neurol Int 03-Jun-2016;7:
How to cite this URL: Mattei TA, Rehman AA, Goulart CR, Marília G. Sória, Rizelio V, Meneses MS. Successful outcome after endovascular thrombolysis for acute ischemic stroke with basis on perfusion-diffusion mismatch after 24 h of symptoms onset. Surg Neurol Int 03-Jun-2016;7:. Available from: http://surgicalneurologyint.com/surgicalint_articles/successful-outcome-after-endovascular-thrombolysis-for-acute-ischemic-stroke-with-basis-on-perfusion-diffusion-mismatch-after-24-h-of-symptoms-onset/
Background:Although intravenous thrombolysis is the Food and Drug Administration-approved treatment for acute ischemic stroke (AIS) within 3 h, combined intravenous and intra-arterial thrombolysis with endovascular techniques may be able to extend this traditional time window.
Case Description:We present the clinical evolution of a 45-year-old male presenting with acute left hemiparesis. Magnetic resonance imaging revealed a small diffusion restriction at the right basal ganglia with perfusion compromise in the entire right middle cerebral artery (MCA) territory. Angiography revealed a complete occlusion of MCA at its M1 segment. The patient underwent endovascular mechanical thrombectomy with additional intra-arterial thrombolysis more than 24 hours after the onset of the initial symptoms and experienced complete vessel recanalization. At 1 year, the patient had global independence with minor residual motor impairment in the left arm.
Conclusions:We report the case of a successful thrombolytic therapy following AIS performed more than 24 h after the initial symptoms based on the presence of a perfusion-diffusion mismatch. This report is expected to stimulate the development of future prospective studies with special focus on the role of perfusion-diffusion mismatch in patient selection for treatment of AIS, especially in those presenting outside the traditional time window.
Keywords: Acute ischemic stroke, intra-arterial thrombolysis, mechanical thrombectomy, perfusion-diffusion mismatch, thrombolysis
Administration of recombinant tissue plasminogen activator (rt-PA/alteplase) is currently approved by the US Food and Drug Administration for intravenous (IV) use in the treatment of acute ischemic stroke (AIS) only within 3 h after the onset of symptoms.[
According to an observational study from the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry, the time window for IV rt-PA treatment can be safely extended from 3 h to 4.5 h after stroke onset with no difference in the outcome measures between both timeframes.[
Regarding the available methods of thrombolysis, several protocols of rt-PA administration (such as intra-arterial thrombolysis, combined IV and intra-arterial salvage thrombolysis) as well as endovascular techniques (such as mechanical thrombolysis with or without angioplasty) have been proposed as alternatives to IV thrombolysis for patients presenting with significant PWI/DWI mismatch and outside of the classic 3-h window.[
An institutional protocol was recently adopted in our stroke center with the purpose of implementing endovascular mechanical thrombolysis followed by low doses of intra-arterial thrombolytic therapy (4U of rt-PA plus incremental doses of 1U via super-selective catheterization) as a salvage therapy for patients with AIS presenting after 3 h from symptoms onset and in whom the magnetic resonance imaging (MRI) demonstrates a significant PWI/DWI mismatch.
In this case report, we present a patient with AIS from a right middle cerebral artery (MCA) occlusion who was submitted to salvage therapy with mechanical thrombolysis and intra-arterial rt-PA more than 24 h after the onset of initial symptoms on the basis of PWI/DWI mismatch. In the sequence, we discuss recent advances in stroke imaging relevant to such a case with particular attention to the concept of ischemic penumbra and the MRI PWI/DWI mismatch model.
A 45-year-old male presented to the Emergency Department with an acute episode of central left facial palsy (House–Brackmann Grade III and National Institutes of Health Stroke Scale of 9) 10 h after the symptoms onset. No other abnormalities were identified on the initial neurological exam. The MRI performed at the Emergency Department demonstrated diffusion restriction on the right globus pallidus and head of the caudate nucleus. There was no PWI/DWI mismatch at that time [Figure
(a and b) Magnetic resonance imaging performed 12 h after initial symptoms revealing diffusion-weighted imaging-restriction at the right basal ganglia with perfusion compromise only in this area. No significant perfusion-diffusion mismatch was identified. (c) Perfusion-weighted imaging performed after neurologic decline 22 h after the initial symptoms demonstrating increased perfusion-weighted imaging compromise affecting the entire right middle cerebral artery territory. (d and e) Magnetic resonance angiography suggesting an acute thrombus in right middle cerebral artery (M1 segment). (f) Follow-up magnetic resonance imaging 12 months after the stroke demonstrating the final infarct area, which includes the basal ganglia area which initially presented the diffusion restriction plus an additional cortical region, likely representing a borderline-zone of perfusion
The case was presented to the endovascular team which decided to submit the patient to a digital subtraction angiography which confirmed complete occlusion of the proximal MCA [
After the interventional procedure, the patient was transferred to the Intensive Care Unit. A control angiography performed 7 days later confirmed the sustained recanalization of the right MCA, with the presence of some residual stenosis [Figure
Control digital subtraction angiography performed 7 days after the thrombolysis confirming the sustained recanalization of the right middle cerebral artery (a: Anteroposterior and b: Lateral views) as well as the absence of flow in the capillary phase (arrows) at the area of diffusion-weighted imaging-restriction that progressed to infarction (c: Anteroposterior and d: Lateral)
According to the family, the patient currently has an independent life with minor restrictions for his daily activities, especially regarding activities demanding fine movements with the left hand. The MRI performed 12 months after the procedure demonstrated the final infarction area (as revealed by the fluid-attenuated inversion recovery [FLAIR] sequence) consisting of the initial area of diffusion restriction before the thrombolysis with an additional cortical zone which likely represented an area of borderline perfusion [
Imaging in acute ischemic stroke
Imaging has become one of the main cornerstones of AIS management. Due to its availability, computed tomography (CT-scan) still remains the standard imaging modality for initial assessment of patients arriving within 3 h of symptom onset in most of centers around the world.[
In the last decades, DWI and perfusion-weighted imaging (PWI) MRI techniques have significantly expanded the role of MRI in the initial evaluation of patients with AIS. In simple terms, by quantifying the isotropic diffusivity of water (a putative measure of intracellular edema), DWI sequences can determine the areas under significant bioenergetic compromise during AIS. On the other hand, PWI, a functional imaging method which is able to provide a comparative assessment of the changes in blood flow between both hemispheres, provides additional information on the regional measures of hemodynamic impairment, enabling an indirect inference of local metabolism. Combining the data from these two imaging modalities, it is possible not only to delineate the area under acute ischemic compromise but also to identify those regions under high-risk of ischemic injury due to impaired cerebral blood flow.[
The concept of PWI/DWI mismatch, which arose from early studies on multimodal MRI for AIS, has proven to be an important diagnostic tool as it is able to provide a simple and feasible means for identification of the so-called “ischemic penumbra.”[
It is important to emphasize that the PWI/DWI mismatch has been successfully used in the literature as an accurate surrogate marker of penumbra and ischemic core not only in the presence of total proximal arterial obstruction but also in cases of partial arterial obstructions and oscillating neurological symptoms.[
It has already been demonstrated that most patients presenting with AIS have an area of penumbra (PWI/DWI mismatch) within the first 6 h from symptoms onset.[
Although such initial concepts of core infarct, penumbra area, and perfusion compromise region have significantly improved the understanding of the pathophysiology of AIS, there is sufficient data to support a possible major paradigm shift in some classic concepts regarding the DWI/PWI mismatch model.[
Based on such data, several authors have suggested that, in selected patients, the time window available for reperfusing the penumbra area may be much longer than the traditional 3 or 6 h.[
In the presented case, for example, the PWI/DWI mismatch was very sensitive in identifying the penumbra area, which was successfully reperfused (compare the DWI restriction [
Several trials have already demonstrated that mechanical thrombolysis (with or without intra-arterial rt-PA infusion) may be a safe and efficacious salvage therapy for treatment of AIS due to proximal arterial occlusion in patients presenting outside of the classic 3 h time window for IV thrombolysis.
In this report, we present the case of a successful thrombolytic therapy in a patient with AIS due to proximal arterial occlusion performed more than 24 h after the initial symptoms. Although the anecdotic evidence provided by this case report does not support the overall safety and efficacy of mechanical thrombolysis outside the standard 3 or 6 h window, it is expected to stimulate the development of future prospective studies with special focus on the role of PWI/DWI mismatch in patient selection for treatment of AIS, as well as the possible associated nuances of such imaging tool (such as the use of perfusion maps based on time-to-peak or on cerebral blood volume, for example). Ultimately, due to the significant heterogeneity regarding the initial presentation and evolution of AIS patients, future trials may find more useful to employ objective measures of ischemic core and penumbra areas (such as MRI PWI/DWI mismatch), instead of basing the decision-making exclusively on the time from initial symptoms.
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Conflicts of interest
There are no conflicts of interest.
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