New Mechanical Recanalization Devices — The Future in Pediatric Stroke Treatment?

ABSTRACT: Objective. To evaluate the recanalization rate and clinical outcome in children with acute ischemic stroke following treatment with innovative mechanical thrombectomy devices. Patients and Methods. Three subjects aged 7–16 years presenting with acute cerebral vascular occlusions (thrombolysis in myocardial infarction [TIMI] 0) were treated with either the Penumbra System, operating on an aspiration platform, or the Phenox clot retriever device, a flexible wire compound with perpendicularly-oriented polyamid microfilaments. Target vessels were the internal carotid artery, the middle cerebral artery and the basilar artery. Results. Successful recanalization (TIMI 3) was attained in all cases. No device-related complications or intracranial hemorrhage occurred. Follow up was conducted for up to 30 days. A 10- to 26-point improvement in the National Institutes of Health Stroke Scale (NIHSS) score was achieved. Conclusions. Mechanical thrombectomy devices possess a dual advantage whereby they can achieve instant recanalization as well as minimize the number of bleeds that customarily accompany intravenous and intra-arterial therapy. These new devices could contribute greatly to treatment decisions in a field not yet clearly defined by current guidelines.

J INVASIVE CARDIOL 2010;22:63–66

Key words: acute stroke, children, mechanical recanalization

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Due to the inadequate availability of evidence-based data in the treatment modalities for acute ischemic stroke in children, therapeutic judgments are often based on expert opinion. The aim of our study was to evaluate the feasibility and clinical outcome in children treated with the newest currently available mechanical recanalization devices, namely the Penumbra System (Penumbra, Inc., Alameda, California) and the Phenox Clot Retriever (pCR) (Phenox GmbH, Essen, Germany).

Patients and Methods

We used the Penumbra System, a nonpharmacological tool comprised of an aspiration platform, and included 0.032 inch and 0.041 inch microcatheters. The microcatheters were connected to an aspiration pump source, which generated a suction force of ~700 mmHg. The second mechanical recanalization device used was the Phenox system. Here, a 3–5 pCR brush, made up of a flexible wire compound with perpendicularly oriented microfilaments, was used. The device was inserted through a Rebar 0.027 inch microcatheter (eV3, Inc., Plymouth, Minnesota). All subjects were examined by an experienced neurologist and pediatrician prior to and following treatment. Three children presented to our university with symptoms of acute cerebral vessel occlusions. The mean time from presentation to treatment was 4 hours 20 minutes. The baseline patient characteristics, demographic data and history are described below. Case 1. A 16-year-old comatose girl (46 kg) presented to our hospital 8 hours following stroke symptom onset. The National Institutes of Health Stroke Scale (NIHSS) score was 36. A positive Babinski sign was present. Basilar artery thrombosis was diagnosed by magnetic resonance imaging (MRI). Following an interdisciplinary consultation, intra-arterial thrombolysis with 50 mg of rt-PA was administered. Since recanalization was not achieved, the decision was made to proceed with the Penumbra System using a .041 inch catheter via a 5 French (Fr) guide catheter (Envoy®, Cordis Corp., Miami Lakes, Florida). The patient’s treatment was performed under the guidelines and protocol set forth in the international, multicenter, prospective, single-arm phase 1 trial that was conducted to evaluate the safety and performance of the Penumbra System.¹ Case 2. A 7-year-old boy (23 kg) presented with right-sided hemiplegia and a NIHSS score of 26. Time from stroke symptom onset was 3 hours and a magnetic resonance imaging scan (MRI) diagnosed an occlusion of the left internal carotid artery. A decision was made to proceed with mechanical thrombectomy using the Penumbra System aspiration catheter (0.041 inch) via a 5 Fr access and 5 Fr guiding catheter (Envoy). The child was not administered any intra-arterial thrombolytics. This patient was enrolled in the pivotal Phase 2 Penumbra Trial, a multicenter, prospective, single-arm study that was conducted to evaluate the safety and effectiveness of the Penumbra System.² Case 3. A 16-year-old girl (55 kg) presented to our department three and a half hours after sudden onset of a headache and right-sided paresis. MRI revealed an occlusion of the left M1 segment of the middle cerebral artery (MCA). Her NIHSS score was 26. After unsuccessful intra-arterial thrombolytic administration of 14 mg rt-PA, the Phenox device was used via a long 6 Fr sheath.

Results

Complete recanalization was successfully achieved in 2 of the above cases. In 1 case, only partial recanalization was observed post treatment. However, complete recanalization was seen in a control angiogram 10 hours later. There were no cases of vessel perforation or device-related malfunction. Time from microcatheter deployment to recanalization of the occluded vessel was Case 1. Recanalization of the basilar artery was achieved within 2 minutes following deployment of the 0.041 inch catheter. The NIHSS score was 3 at 24 hours and 23 at 30 days. No intracranial hemorrhage occurred. The patient had no previously identified risk factors. No cardiac, vascular or genetic risk factors were found. Furthermore, a detailed family history revealed no cerebrovascular disease among first-degree relatives. There was no suspicion of drug abuse and no causes for primary or secondary hypercoagulable states were found. No previous head trauma or infectious disease was reported. Case 2. We achieved recanalization of the internal carotid artery first, followed by the middle cerebral artery. Time from arterial puncture to recanalization was 11 minutes in the second case. The NIHSS score improved to 0 at 30 days. There were no neurological deficits on examination. The boy had become symptomatic while hospitalized for chronic heart failure, cardiomegaly and pulmonary vein congestion. This presumably led to an embolic stroke. The boy was kept on anticoagulants (acetylsalicylic acid) after the intervention. Case 3. Only partial recanalization of the left M1 segment (TIMI 1) could be achieved. However, control digital subtraction angiography (DSA) revealed complete recanalization of the middle cerebral artery 10 hours post treatment, possibly due to a delayed effect of rt-PA. The patient’s NIHSS score was 0 at 30 days. In this girl, the only risk factor identified was the use of birth control pills. No preexisting illnesses such as congenital or acquired cardiac disease, sickle cell or infectious disease were found.

Discussion

Despite the fact that stroke is being increasingly recognized in children in recent years, only two skeletal guidelines set forth by the American College of Chest Physicians (ACCP) and the Royal College of Physicians (RCP) exist.^3,4 These guidelines do not provide sufficient recommendations for the acute management of ischemic stroke, rather, they are mainly based on consensus and expert opinion.^5,6 The primary therapeutic focus continues to remain on an antithrombotic approach. The NINDS study was the first randomized, double-blind trial to demonstrate the efficacy of intravenous rt-PA in acute ischemic stroke.⁷ However, as is the case with most trials, children were excluded for ethical reasons. Because of the rarity of the disease, stroke in children is often underrecognized and therefore underdiagnosed, resulting in a considerable delay in treatment and consequently poor outcomes.⁸ Furthermore, there is often a substantial lag time in bringing the child in for medical treatment, which precludes the use of intravenous and intra-arterial therapy. In these situations, mechanical embolectomy devices are the only treatment options that can be considered. Encouraged by the belief that a recanalized vessel can considerably augment the likelihood of a better clinical outcome, various investigators have published single-center experiences describing aggressive methods of mechanical clot disruption in adults.^9,10 However, these approaches have been hindered by persistent safety concerns including vessel perforation, dissection or rupture.^11,12 A limiting factor in the early days of devices was the lack of flexibility or the size of the introducer sheath, which hindered its navigation in the intracranial vasculature, especially in children. One of the first devices was the Merci Clot Retriever (Concentric Medical, Inc; Mountain View, California). It is an intra-arterially delivered corkscrew-shaped flexible nitinol (nickel titanium) wire that traverses and ensnares the thrombus, which is then removed by traction. The Multi-Merci study revealed a recanalization rate of 57.3% with the new-generation L5 Retriever and 69.5% after adjunctive intra-arterial therapy, as proved by conventional angiography.¹³ We would like to draw attention to two mechanical recanalization devices that have evolved over the past year: the Phenox Clot Retriever and the Penumbra System. The Phenox Clot Retriever consist of two embodiments: pCR (CE mark in 2006) and CRC (CE mark in 2008)14 (Figure 6). Both systems have a highly flexible core wire compound resembling a pipe cleaner with perpendicularly oriented polyamide microfilaments that create a dense palisade. Additionally, nitinol wire braiding, which offers more radial strength for mobilizing clots surrounds the proximal portion of the CRC. The device is attached to the corpus of a microguidewire and is available in different sizes for vessels ranging from 1 to approximately 4 mm, and can be inserted through a 0.021 inch or 0.027 inch microcatheter, depending on the device size. It is deployed distal to the clot and slowly pulled back under continuous aspiration via the guiding catheter. The Penumbra System has been designed to improve the safety and effectiveness of mechanical recanalization and is based on an aspiration platform (Figure 7). This includes reperfusion microcatheters in four sizes (0.026 inch, 0.032 inch, 0.041 inch and 0.054 inch) that are connected to an aspiration pump through aspiration tubing, generating a suction force of ~700 mmHg. A teardrop-shaped separator is advanced and retracted within the lumen of the reperfusion catheter to debulk the clot for ease of aspiration. As a nonpharmacologic tool, it has the potential of reopening a vessel without the use of adjunctive thrombolytics. In addition, the Penumbra System is designed to minimize the need to blindly penetrate the occluded vascular segment. The proximal approach to the embolus facilitates embolectomy without destructive maceration of the embolic material, thus allowing histopathologic examination of the extracted tissue.15 Due to the flexibility and variety of available sizes of aspiration microcatheters, even distal branches such as the M2 and A2 can be successfully maneuvered. It is especially important to note that in infants, no additional guiding catheter is required for either device. The first core lab-controlled feasibility Penumbra trial for the treatment of acute stroke1 showed a 100% revascularization rate, with TIMI 2 or 3 results. The pivotal phase 2 trial completed in June 2007 showed a recanalization rate of 81.6% in the 125 enrolled patients.² Recanalization is an immediate parameter for assessing treatment success, and time to recanalization is perhaps the most important predictor of clinical outcome, regardless of the treatment method used.^12,16 In the case where intra-arterial lysis failed to open the occluded basilar artery, we were successful with the Penumbra System. In addition, when there is a need to deliver intra-arterial lytics to soften a clot of varying consistency, they can be administered through the Penumbra System microcatheters. Time from arterial puncture to recanalization was 11 minutes in the second case. These examples serve to highlight the unique advantages of the Penumbra System and the Phenox Clot Retriever.

Conclusion

There remains a dire need to administer treatment in children when they present with acute ischemic stroke. This is a first clinical report using a novel mechanical recanalization platform to remove an occluding thrombus in the setting of acute thrombo-embolic stroke in children. Early consideration of mechanical clot extraction techniques in children with acute stroke secondary to large-vessel cerebro-occlusion may improve recanalization rates and clinical outcomes. Mechanical recanalization devices could find their niche in the treatment of acute stroke in children, which is not well covered by current guidelines.

References

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___________________________________________ From the ^*Acute Vascular Imaging Centre, Oxford, United Kingdom, the ^**Clinic for Neurology, University of Saarland, the ^§University Children's Hospital, Department of Pediatrics, Section of Neuropediatrics University of Saarland, the ^£Department for Interventional and Diagnostic Neuroradiology, University of Saarland, the ^†Clinic for Neurology, University of Saarland. Disclosure: One or more of the authors has disclosed a potential conflict of interest that is not financial in nature. Manuscript submitted August 6, 2009, provisional acceptance given September 3, 2009, final version accepted September 21, 2009. Address for correspondence: Iris Quasar Grunwald, Md, PhD, Associate Professor, Acute Vascular Imaging Centre, Biomedical Research Centre, Oxford OX3 9DU, United Kingdom. E-mail: i.grunwald@web.de