Case Studies Brain Stem Infarction Due to Basilar Artery Dissection in a Patient with Moyamoya Disease Four Years after Successful Bilateral Revascularization Surgeries Takatsugu Abe, MD,* Miki Fujimura, MD, PhD,* Shunji Mugikura, MD, PhD,† Hidenori Endo, MD, PhD,* and Teiji Tominaga, MD, PhD* Moyamoya disease (MMD) is a rare cerebrovascular disease with an unknown etiology and is characterized by intrinsic fragility in the intracranial vascular walls such as the affected internal elastic lamina and thinning medial layer. The association of MMD with intracranial arterial dissection is extremely rare, whereas that with basilar artery dissection (BAD) has not been reported previously. A 46year-old woman developed brain stem infarction due to BAD 4 years after successful bilateral superficial temporal artery–middle cerebral artery anastomosis with indirect pial synangiosis for ischemic-onset MMD. She presented with sudden occipitalgia and subsequently developed transient dysarthria and mild hemiparesis. Although a transient ischemic attack was initially suspected, her condition deteriorated in a manner that was consistent with left hemiplegia with severe dysarthria. Magnetic resonance (MR) imaging revealed brain stem infarction, and MR angiography delineated a double-lumen sign in the basilar artery, indicating BAD. She was treated conservatively and brain stem infarction did not expand. One year after the onset of brain stem infarction, her activity of daily living is still dependent (modified Rankin Scale of 4), and there were no morphological changes associated with BAD or recurrent cerebrovascular events during the follow-up period. The association of MMD with BAD is extremely rare. While considering the common underlying pathology such as an affected internal elastic lamina and fragile medial layer, the occurrence of BAD in a patient with MMD in a stable hemodynamic state is apparently unique. Key Words: Basilar artery dissection—moyamoya disease—brain stem infarction—magnetic resonance imaging. © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved. From the *Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan; and †Department of Radiology, Tohoku University Graduate School of Medicine, Sendai, Japan. Received March 1, 2016; accepted March 15, 2016. Grant support: This research was partially supported by a grant (J150001575) from the Japan Agency for Medical Research and Development (AMED). Address correspondence to Miki Fujimura, MD, PhD, Department of Neurosurgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Miyagi, Sendai 980-8574, Japan. E-mail: fujimur@nsg.med.tohoku.ac.jp. 1052-3057/$ - see front matter © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.03.024 Introduction Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease with an unknown etiology and is characterized by steno-occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain.1,2 Regarding the basic pathology of MMD, its histological characteristics include intimal hyperplasia and medial layer thinness in all intracranial arteries.2-4 Combined with the waviness and duplication of the internal elastic lamina,3 intracranial arteries in patients with MMD are considered to have intrinsic fragility. Regarding biomarkers related Journal of Stroke and Cerebrovascular Diseases, Vol. 25, No. 6 (June), 2016: pp e79–e82 e79 T. ABE ET AL. e80 to the vulnerability of intracranial vessels, the expression of extracellular matrix proteins such as matrix metalloproteinase-9, which degrades components of vascular wall structures including type-IV collagen and laminin, has been reported to be increased in patients with MMD, further supporting the intrinsic fragility of the vascular walls in MMD patients.5,6 Intracranial arterial dissection is also a rare cause of stroke among East Asian populations and may be derived from the vulnerability of vascular wall structures.7 However, the association of MMD with intracranial arterial dissection is extremely rare,8,9 whereas that with basilar artery dissection (BAD) has not been reported previously. We herein report an adult case of MMD that developed brain stem infarction due to BAD 4 years after successful bilateral revascularization surgeries. Case Report A 46-year-old woman developed brain stem infarction due to BAD 4 years after successful bilateral superficial temporal artery (STA)–middle cerebral artery (MCA) anastomosis with indirect pial synangiosis for ischemiconset MMD. She had a previous history of hypertension and diabetes mellitus. Magnetic resonance angiography (MRA) performed 2 years after the last surgery revealed the patency of the bilateral STA–MCA anastomosis site (Fig 1, D). She presented with sudden occipitalgia in the emergency department of our institute 4 years after bilateral revascularization surgeries and subsequently developed transient dysarthria and mild hemiparesis. Manual muscle testing showed 4/5 at the left upper and lower extremities. Noncontrast computed tomography imaging did not detect any of the early signs of stroke or hemorrhage. The initial findings of magnetic resonance imaging (MRI) were unremarkable, and MRA showed the patency of the bilateral STA–MCA anastomosis site. Based on these results, a transient ischemic attack was initially suspected because of improvements in her neurological symptoms. She was treated conservatively with ozagrel sodium (80 mg/day) and edaravone, a free radical scavenger. One hundred milligrams of cilostazol was also continued. After a few hours, her neurological symptoms markedly deteriorated in a manner that was consistent with left hemiplegia with severe dysarthria. Diffusionweighted imaging of MRI ultimately delineated a highintensity signal lesion at the right medial pons (Fig 1, A). MRA showed an apparent double-lumen sign in the basilar artery (Fig 1, D,E), indicating the presentation of BAD as a cause of brain stem infarction. Axial views of T1-weighted and T2-weighted images further confirmed the double-lumen sign in the basilar artery (Fig 1, B,C). Because of the absence of the aneurysmal dilatation of BAD and the lack of evidence for subarachnoid Figure 1. (A-C) MRI at the progression of neurological symptoms of left hemiplegia and dysarthria. DWI (A) revealed a high-intensity signal lesion in the right medial pons, indicating the occurrence of acute brain stem infarction. T1-weighted (B) and T2-weighted MRI (C) showed a doublelumen sign (arrows), suggesting BAD as the cause of brain stem infarction. (D-H) MRA before (D) and after (E, F) the occurrence of BAD, which demonstrated an apparently patent STA–MCA bypass bilaterally (asterisks in D and E). Two years before the onset of BAD, the basilar artery was morphologically intact (D), while the double-lumen sign became evident after the onset of brain stem infarction (arrows in E-H). Abbreviations: BAD, basilar artery dissection; DWI, diffusion-weighted imaging; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging; STA– MCA, superficial temporal artery–middle cerebral artery; T1WI, T1weighted imaging; T2WI, T2-weighted imaging. hemorrhage, the patient was treated conservatively with strict blood pressure control. Brain stem infarction did not expand during the acute stage, and there were no morphological changes associated with BAD by MRA 1 month after the onset (Fig 1, G). The patient manifested severe left hemiparesis and was transferred to another institution for continuous rehabilitation 2 months after the onset of BAD. Her activity of daily living was still dependent (modified Rankin Scale of 4) 1 year after the onset of BAD, while there were no morphological changes associated with BAD or recurrent cerebrovascular events during the follow-up period (Fig 1, H). Discussion Intracranial arterial dissection has been identified as a rare cause of stroke among East Asian populations, although recent advances in diagnostic modalities have BAD ASSOCIATED WITH MOYAMOYA DISEASE provided more opportunities to diagnose this rare condition.10 However, cases of isolated BAD are reported less frequently, with its incidence accounting for as little as 4.5%-7.0% of intracranial artery dissection cases.10,11 Patients with BAD have been reported to have poorer prognoses, particularly hemorrhagic-onset cases, with a mortality rate of 25%.12 Difficulties are associated with accurately diagnosing BAD and a management strategy has not yet been determined, both of which may contribute to the poor prognosis of BAD.7,11-13 Surgical or endovascular occlusion of the parent artery with or without extracranial–intracranial bypass is the treatment of choice for hemorrhagic-onset BAD patients,12,13 while ischemiconset patients are generally managed conservatively.7,12 In the present case, we failed to make a definitive diagnosis of BAD by initial MRI/MRA because transient hemiparesis, dysarthria, and headache14 were attributed to the pathophysiology of MMD. Repeated MRI after the progression of her symptoms showed acute brain stem infarction, and MRA ultimately revealed BAD based on the double-lumen sign. Regarding the management strategy adopted, we conservatively treated this ischemiconset BAD patient in light of the absence of the aneurysmal dilatation of BAD and the lack of evidence for subarachnoid hemorrhage. The exact mechanism by which this extremely rare association of MMD with BAD occurs has not yet been determined. On one hand, intraoperative findings show that the MCA of MMD has a thin and transparent wall, whereas histological investigations of autopsy specimens have demonstrated that the main vessel in MMD is stenotic or occluded due to fibroelastic intimal thickening.15,16 Furthermore, a previous histological analysis of the MCA wall obtained from patients treated for MMD showed that the media was significantly thinner and the internal elastic lamina was normal, disrupted, or thin.4 On the other hand, histological investigations of autopsies performed on BAD patients revealed that the intima was thick due to rich plaques and the media exhibited degenerative changes due to atherosclerosis.17-19 Therefore, these similar backgrounds of vascular wall fragility may contribute, at least in part, to this rare association. In light of distinct hemodynamic stress in the posterior circulation of patients with MMD,20 excessive hemodynamic stress in the vertebral–basilar system for long periods of time may also contribute to the occurrence of BAD in the present case, even after successful revascularization surgery. While considering the elongated morphology of the basilar artery in our case, future studies with larger numbers of patients using computational fluid dynamics may address this critical question. We encountered an extremely rare association of MMD with BAD. While considering the common underlying pathology such as an affected internal elastic lamina and fragile medial layer, the occurrence of BAD in a patient e81 with MMD in a stable state of hemodynamics is apparently unique. References 1. Suzuki J, Takaku A. Cerebrovascular “moyamoya” disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol 1969;20:288-299. 2. 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