Clinical Neurology and Neurosurgery 111 (2009) 913–917 Contents lists available at ScienceDirect Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro Case report and reviews of the literature Endovascular treatment for moyamoya disease in a Caucasian twin with angioplasty and Wingspan stent Doniel Drazin 1 , Mark Calayag 1 , Edward Gifford, John Dalfino, Junichi Yamamoto, Alan S. Boulos ∗ Division of Neurosurgery, Albany Medical Center, 47 New Scotland Avenue, Albany, NY 12208, United States a r t i c l e i n f o Article history: Received 26 January 2009 Received in revised form 12 August 2009 Accepted 15 August 2009 Available online 7 October 2009 Keywords: Moyamoya Endovascular Interventional Stent Twins Angioplasty Wingspan STA-MCA bypass Caucasian a b s t r a c t The pathogenesis and genetics of moyamoya disease (MMD) remain a mystery. Here we report a case of female Caucasian adult twins with similar presentations of bilateral MMD that were treated with different surgical modalities. One twin was treated with a bypass and remains event free (defined as either transient ischemic event or stroke) at her 4-year follow-up. The second twin underwent angioplasty to treat a left middle cerebral artery stenosis as well as the placement of a Wingspan stent to treat a right supraclinoid ICA stenosis on separate occasions. The left middle cerebral artery angioplasty thrombosed due to the discontinuation of clopidogrel resulting in recurrent symptoms, principally aphasia, and the Wingspan stent underwent angioplasty for in-stent stenosis. Despite this, the stent has been patent and the patient has remained event free at her 2-year follow-up, post-placement. The relatively new Wingspan stent has been used in the past for intracerebral atherosclerotic lesions, however, this is the first report of it being used in a case of MMD. An overview of the MMD literature in twins and endovascular therapy is given. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Moyamoya disease (MMD) is a rare cerebrovascular entity that is characterized by the spontaneous stenosis or occlusion of the internal carotid artery (ICA) and/or vertebral artery or its terminal branches, along with the development of an aberrant network of collateral vasculature. MMD primarily affects Asians, with an incidence and prevalence of 0.35–0.94 and 3.2–10.5 per 100,000 among the Japanese population, respectively [1–3]. This disorder occurs even less frequently among Caucasians, with an incidence of 0.06 per 100,000 [4]. The etiology of MMD is still unclear, however, a high rate of familial occurrence suggests a genetic component to this disease [5]. The 80% incidence among Japanese monozygotic twins further reinforces this notion. Interestingly, there has been only one reported case of Caucasian twins with MMD [6]. MMD is typically diagnosed by cerebral angiography. Suzuki and Takaku [7] first characterized the angiographic staging of the disease. Briefly, this classification delineates angiographic stages of progressive ICA stenosis or occlusion from stage 1 to stage 6. Traditionally, the treatment of MMD involves surgical revascularization of the affected region either directly (e.g., superficial temporal ∗ Corresponding author. Tel.: +1 518 262 5088; fax: +1 518 262 5400. E-mail address: alan.boulos@gmail.com (A.S. Boulos). 1 Co-first authors. 0303-8467/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2009.08.012 artery, STA, to middle cerebral artery, MCA, bypass) or indirectly (e.g., encephaloduroarteriosynangiosis, EDAS). However, recently, Kornblihtt et al. [8] was able to successfully treat an adolescent with MMD with an endovascular placement of a carotid stent. Here we present a rare case of monozygotic Caucasian twins with MMD that had nearly identical presentations and underwent different treatments. One twin was treated with a STA-MCA bypass, while the other twin was treated with a Wingspan stent. The relatively new Wingspan stent has been used in the past for intracerebral atherosclerotic lesions, however, this is the first report of it being used in a case of MMD. 2. Clinical report 2.1. Case 1 A 39-year-old female was referred for a possible revascularization procedure after presenting to an outside hospital with a left hemispheric stroke several weeks prior. A CT-angiogram done at that time demonstrated a left internal carotid artery occlusion, poor flow through the MCA, and an angiographic blush typical of stage 1 MMD. A left STA-MCA bypass, as well as an EDAS was successfully performed several weeks after the office visit. A follow-up angiogram 9 months later showed improved blood flow to the left hemisphere. The patient has not had any 914 D. Drazin et al. / Clinical Neurology and Neurosurgery 111 (2009) 913–917 Fig. 1. Diffusion weighted imaging sequences of a watershed infarct in the right hemisphere 22 months after the initial left-sided stroke. The old left infarct was most probably from the discontinuation of antiplatelet therapy after initial angioplasty. other events since. More recently, a repeat CT-angiogram 4 years later demonstrated flow through the STA-MCA bypass, as well as, indirect flow through the EDAS operation. Her right internal carotid artery remains nearly occluded with evident moyamoya collaterals similar to its appearance on the angiogram 4 years prior. 2.2. Case 2 A 40-year-old monozygotic twin of the above patient was transferred to Albany Medical Center after initially presenting to an outside hospital with right-sided weakness and sensory changes, as well as an expressive aphasia and radiographic evidence of a left MCA stroke. At that time, she was found to have an 85% focal stenosis of the left distal ICA and proximal MCA spanning 3 mm and was diagnosed with stage 1 MMD. Because of the acute nature of her symptoms, she came within the therapeutic window of time for emergent treatment of her stroke. In moyamoya disease, emergent bypass procedures are not often used to reverse deficits. For this reason, angioplasty or endovascular treatment in the emergent condition of new neurologic symptoms was attempted. Subsequently, the patient underwent angioplasty of the left MCA with good improvement of flow. The patient was placed on aspirin and clopidogrel and she slowly improved. She re-presented within 3 months with a new aphasia, a new left middle cerebral artery territory stroke, and an occlusion of the angioplasty site on imaging. Her antiplatelet agents were discontinued for hypermenorrhagia 2 weeks prior to this event. Direct revascularization was considered but was felt to be dangerous considering the area and extent of brain infarct. Twenty-two months later, the patient presented with a new right hemisphere stroke (Fig. 1). CT angiography showed progression of her contralateral internal carotid artery stenosis to 80% stenosis in the supraclinoid portion of the right internal carotid (Fig. 2). This time, we considered angioplasty and stent placement because there continued to be antegrade flow with a focal stenosis that had an appearance amenable to endovascular therapy. She already had a significant left hemispheric stroke which resulted in a disabling hemiparesis and aphasia, so a less invasive approach was felt to be worthwhile given her current neurologic comorbidities. Also, her aphasia was exacerbated by the new right hemispheric strokes. For these reasons, endovascular therapy was thought to be less likely to exacerbate the current symptoms by avoiding prolonged anesthesia and fluctuations in blood pressure. An angioplasty and placement of a Wingspan stent (Boston Scientific, Natick, USA) were performed successfully, with a post-stent residual stenosis of 30% (Fig. 3). Unfortunately, a follow-up CTangiogram 3 months later showed 60% restenosis of the stent. Angioplasty was performed on the in-stent stenosis without any complications (Fig. 4). She had undergone surgical treatment for hypermenorrhagia so she could be kept on clopidogrel and aspirin for a longer period of time without adverse consequences. The clopidogrel was discontinued 6 months after angioplasty of the restenosed stent. The patient has been both clinically and radiologically stable on both her radiographic follow-up 15 months after the last angioplasty and during the 2 years of clinical follow-up since the right-sided stroke occurred. Fig. 2. (A) AP oblique image showing high grade stenosis (80%) in the right supraclinoid ICA (white arrow). (B) Angioplasty using a 2 mm × 20 mm balloon (black arrows). (C) Oblique image after stent deployment using a 3 mm × 15 mm Wingspan stent (asterisks) with low grade (30%) residual stenosis (black arrow). D. Drazin et al. / Clinical Neurology and Neurosurgery 111 (2009) 913–917 915 Fig. 3. AP (A) and lateral (B) images showing restenosis in the supraclinoid ICA (black arrows). (C) Angioplasty within the Wingspan stent (asterisks) using a 2 mm × 15 mm balloon (white arrows). 3. Discussion 3.1. History of twins with moyamoya Familial moyamoya disease in Japan has been reported to be in the range of 6.7–12% [5,9–11]. The first case of MMD in monozygotic twins to be presented was in 1978 at the 6th annual meeting of the Japanese Pediatric Neurosurgery Society [12]. However, the incidence of the disease was not reported until the following year in a separate study [13]. The existence of MMD in monozygotic twins reinforces a genetic component to MMD, and suggests a potential mode of inheritance [14–20]. Mineharu et al. [21] suggested that familial MMD may be autosomal dominant with incomplete penetrance. Furthermore, they showed that transmission was predominantly maternal and that females of affected mothers tended to have either late onset or were asymptomatic. The authors hypothesized genetic imprinting as the cause of this phenomenon. Another study found a familial case of MMD in a mother, two of her children who were monozygotic twins, and two additional children with the disease who were not twins [20]. No identifying environmental factors were isolated to the family, no signs of consanguinity were identified, and the birth history was noncontributory for all four of the children. However, the lack of any additional family members in the maternal line with MMD suggests that the grouping of disease may have been due to a spontaneous mutation [20]. There has been only one previous report of Caucasian monozygotic twins in the literature [6]. In the case presented by Andreone et al. [6], the twins were female, with one twin having a late presentation (ischemic stroke) of MMD while the other had angiographic evidence of MMD, but was asymptomatic. This has been seen in other studies of familial MMD where siblings of symptomatic patients remain asymptomatic despite having severe disease on angiography [20,23]. To further confuse the issue, there have been isolated incidences of MMD in a single member of twin siblings, both fraternal and identical [22–24]. All of these studies, from an overwhelming incidence in identical twins to variable expressivity of the disease, point to a potential multifactorial etiology. 3.2. Endovascular approaches to moyamoya In the treatment of intracerebral lesions, endovascular techniques have the obvious advantage of being less invasive than open procedures. The successful use of a coronary balloon expandable stent in the treatment of MMD has been already described by Kornblihtt et al. [8]. The patient treated in the case report was an 18-year-old Caucasian female who was found to have MMD Fig. 4. AP (A) and lateral (B) images showing improvement of the supraclinoid ICA stenosis after re-treatment. The ends of the Wingspan stent are marked with asterisks. 916 D. Drazin et al. / Clinical Neurology and Neurosurgery 111 (2009) 913–917 with underlying essential thrombocythemia and severe stenosis of her left supraclinoid ICA. She was treated with an AVE INX 3 mm × 12 mm stent (Medtronic, Minneapolis, USA) with a cerebrovascular protection device. Angiographic results at 46 months post-procedure showed vessel patency with no stent restenosis and her MMD had remained clinically stable [8]. Lee and Ahn [25] describe stent placement in the External Carotid Artery (ECA) of a 55-year-old Japanese female to preserve collateral function after total, bilateral ICA occlusion. A 5 mm × 43 mm Easy Wall stent (Boston Scientific Co., Natick, USA) was expanded in the left ECA with balloon angioplasty. An angiogram at 1 year showed mild stent restenosis with no new clinical symptoms. This patient was suspected for potential atherosclerotic involvement of the ECA, as proximal ECA stenosis is an uncommon presentation with MMD [25]. One additional case report by Rodriguez et al. [26] describes angioplasty treatment of MMD in a Filipino male. Angioplasty of the left MCA and left ICA were performed following multiple TIAs. The patient did well at 6 months and yearly follow-up angiograms up to 2 years with no vessel restenosis. On continued evaluation, the patient was specifically noted to have decreased collaterialization seen from the ECA, a atypical MMD pattern on angiogram [26]. The use of coronary and balloon expandable stents in the treatment of atherosclerotic lesion is well known. The relatively recent development of the self-expanding Wingspan system stent tries to improve upon the shortcomings of angioplasty and balloon expandable stents by increasing the flexibility of the delivery system, using less inflation pressure for deployment of the stent, and making it easier to size the balloon and stent to the target vessel [27]. Several studies have shown Wingspan efficacy in treating intracranial atherosclerotic lesions over the balloon expandable and coronary stent systems [27–29]. Despite this, in-stent restenosis remains to be a problem with the Wingspan system [29,30]. In fact, younger patients (<55 years old) with anterior circulation Wingspan stent placement had a high restenosis rate. Specifically, 88% of ICA treated lesions in patients less than 55 years old suffered in-stent restenosis [31]. However, Levy et al. [30] observed that in-stent restenosis was typically asymptomatic, and that re-angioplasty resolved symptomatic restenosis without complications. The natural progression of an asymptomatic in-stent restenosis remains to be seen. In a previously reported patient series of Wingspan stent placement, it is possible that several of these patients had early (stage 1) moyamoya disease rather than intracranial atherosclerosis. In the currently reported case, it is highly unlikely to be intracranial atherosclerosis given the patient’s twin development of the same disease process at similar ages. This may also help explain the propensity of the treatment to lead to restenosis. Stent placement for moyamoya disease may not prevent further progressive hyperplasia of the intima that is inherent to the disease. Indeed, stent placement is known to induce intimal hyperplasia as a response to its placement [32]. One important lesson for the senior author (ASB) was the need to more closely monitor progression of the contralateral side. The second patient may have benefited from more aggressive surveillance imaging of her intracranial vasculature and earlier intervention for the contralateral stenosis may have prevented recurrent ischemic events. The choice of endovascular therapy remains controversial. However, in the authors’ practice, we have rarely used bypass as an emergency therapy for new neurologic symptoms except in the setting of a symptomatic occlusion. In her case, both endovascular treatments were instituted when there remained some antegrade flow. The periprocedural complications are likely reduced when endovascular techniques are used in patients where antegrade flow is still present. In addition, with bypass surgery in this setting, there is a risk of causing thrombosis of the stenotic segment of the vessel and this can lead to neurologic symptoms from perfora- tor occlusion along the internal carotid or middle cerebral arteries [33]. Though she underwent multiple endovascular procedures, the patient remains in good condition and has not had any further symptoms in the past 2 years. 4. Conclusion The preferred treatment for moyamoya disease is either a direct or indirect bypass procedure. However, endovascular techniques have evolved that could potentially treat this progressive disease. Though this case report also delineates many of the limitations for endovascular therapy, including restenosis and re-occlusions, surgical treatments also carry some potential neurological risks, namely stroke or TIAs. In many patients with moyamoya, endovascular therapy is a poor option, particularly if the vessel is fully occluded. 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