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Microembolic signals are associated with progression of arterial lesion in Moyamoya disease: A case report
Journal of the Neurological Sciences 260 (2007) 253 – 255 www.elsevier.com/locate/jns
Short communication
Microembolic signals are associated with progression of arterial lesion in Moyamoya disease: A case report Yasuyuki Iguchi ⁎, Kazumi Kimura, Youhei Tateishi, Kensaku Shibazaki, Takeshi Iwanaga, Takeshi Inoue Department of Stroke Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki-city, Okayama, 701-0192, Japan Received 2 January 2007; received in revised form 30 March 2007; accepted 2 April 2007 Available online 1 May 2007
Abstract Transcranial Doppler ultrasonography (TCD) and magnetic resonance angiography (MRA) confirmed a rapid progression of arterial lesion in Moyamoya disease after the patient gave birth. TCD could initially detect a large number of microembolic signals (MES) at the distal portion of stenotic lesions. After MRA showed the development of stenotic lesions 10 days after first TCD monitoring, MES were absent. MES may be related to the clinical activity of Moyamoya disease. © 2007 Elsevier B.V. All rights reserved. Keywords: Transcranial Doppler; Moyamoya disease; Microembolic signals; Diffusion weighted magnetic resonance imaging; Pregnancy
1. Introduction Moyamoya disease (MMD) is characterized by slow progression at bilateral carotid forks accompanied by cerebral ischemia and hemorrhage [1]. After initiating medical treatment, the 5-year risk of recurrent stroke is 65% after initial symptoms and 27% after angiographic diagnosis, respectively [2]. However, even if high frequency of cerebral ischemia is observed, no reports have precisely described whether embolic stroke from arterial lesions occurs in cases with MMD. We herein report evidence of embolism using transcranial Doppler ultrasonography (TCD) and diffusion-weighted magnetic resonance imaging (DWI) in an adult case of MMD. 2. Case report A 28-year-old pregnant woman was admitted to our hospital in order to manage a premature labor in January ⁎ Corresponding author. Tel.: +81 86 462 1111; fax: +81 86 462 1199. E-mail address: [email protected] (Y. Iguchi). 0022-510X/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2007.04.004
2006. Previous history was probable MMD based on cerebral angiography in 2001 after transient dysesthesia of the right hand (Fig. 1A) [3]. The patient had no history of hypertension, diabetes, hyperlipidemia or eclampsia. Neither antiplatelet treatment nor anticoagulation had ever been used. During hospitalization, transient dysarthria and dysesthesia of the left hand and leg were noted. She was referred to the department of stroke medicine 1 week after delivery without any symptoms. On admission, she did not complain of headache, dizziness, diplopia or numbness. Height was 163 cm and body weight was 76 kg. Body temperature was 36.5 °C, blood pressure was 120/60 mm Hg and heart rate was 74 beats/min with regular sinus rhythm. No neck or orbital bruits were present. Heart sounds were clear. Neurological findings were normal and transient ischemic attack was diagnosed. Laboratory examinations on admission showed: erythrocyte count, 476 × 104/mm3; hemoglobin, 13.9 g/dl; hematocrit, 43.1%; leukocyte count, 8790/mm3; platelets 23.9 × 104/mm3. D-dimer level was 2.1 μg/ml (normal, ≤ 1.0 μg/ml) and level of thrombin–antithrombin III complex was 3.4 ng/ml (normal, ≤ 3.0 ng/ml). Von Willebrand
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Y. Iguchi et al. / Journal of the Neurological Sciences 260 (2007) 253–255
Fig. 1. A) Initial conventional angiography (anterior–posterior projection) of bilateral internal carotid arteries shows a stenotic lesion at the proximal left middle cerebral artery (MCA). B) Five years after diagnosing probable Moyamoya disease, severe stenotic lesions at both right and left middle cerebral arteries were observed with slight basal Moyamoya vessels after delivery.
factor was 241% (normal, 60–170%). Urinalysis revealed no abnormalities. Hepatic and renal functions were normal. The patient was examined using a commercially available echo planner operation on a 1.5-T MR unit (Signa EchoSpeed Horizon; GE Medical Systems, Milwaukee, WI). DWI demonstrated a hyper-intense lesion in the right frontal cortex (Fig. 2). However, no abnormalities in the basal ganglia, brainstem or cerebellum were noted on either DWI or T2-weighted imaging. Time-of-flight magnetic resonance angiography (MRA) showed severe stenosis in both right terminal internal carotid artery (ICA) and the left middle cerebral artery (MCA) (Fig. 3A). To confirm the arterial lesion, cerebral angiography was followed by first MRA (Fig. 1B). The horizontal portion of the left MCA
displayed severe stenosis and the distal left MCA was incompletely patent. Abnormal vascular networks bilaterally were seen in the vicinity of the arterial lesions. Finally, she was diagnosed as definite MMD with late stage [3,4]. TCD was conducted using a Pioneer TC 8080 system (Nicolet Vascular, Madison, WI) to detect microembolic signals (MES). TCD was recorded for 20 min. Doppler audio and spectrum signals were recorded on the hard disc of the TCD machine. MES were identified by the typical visual appearance on the spectral display and the characteristic sound, according to standard consensus criteria [5]. TCD demonstrated numerous MES in both right and left MCAs (Fig. 3A). However, no MES were identified in either posterior cerebral artery (Fig. 3A). At 10 days after first TCD, TCD detected only a minimal flow signal in the proximal right MCA without any MES (Fig. 3B). MRA showed narrowing of the entirety of both MCAs, particularly the left MCA (Fig. 3B). The patient was subsequently transferred to the neurosurgery unit for consideration of surgical treatment. 3. Discussion
Fig. 2. Diffusion-weighted magnetic resonance imaging shows highintensity areas in the right frontal cortex (white arrow).
The present case demonstrated the angiographical changes from unilateral to bilateral MMD for a five-year period. The rapid progression of MMD after delivery was observed by MRA for 2 weeks. TCD could detect numerous MES in the distal portions of stenotic MCAs. After rapid progression of MCA stenosis, MES disappeared during TCD monitoring. At 5 years after probable diagnosis of MMD with ipsilateral ICA-MCA stenosis, contralateral MCA stenosis was confirmed by cerebral angiography. This case was compatible with a previous report by Kuroda et al. that all adult patients who showed slowly progression of arterial lesion from uni- to bilateral MMD were women at about
Y. Iguchi et al. / Journal of the Neurological Sciences 260 (2007) 253–255
255
Fig. 3. A) Magnetic resonance angiography (MRA) shows severe stenosis of the left MCA on admission. Transcranial Doppler ultrasonography (TCD) demonstrates microembolic signals (MES) in both right and left middle cerebral arteries (arrows head) even if no MES are present in posterior cerebral arteries. B) About 10 days after first MRA and TCD, stenotic lesions in the proximal right MCA have progressed and flow signals of the left MCA are incomplete. Doppler spectral waveforms at both MCAs are minimal without MES.
5 years after initial diagnosis [6]. According to previous surveys, unilateral MMD has been recognized as stable in adults [7]. However, a third of MMD patients with long follow-up period progress to definite MMD and around 87% are female [6]. We thus consider that conditions specific to women, such as pregnancy and menopause, may contribute to the progression of MMD. Concerning the presence of MES, Horn et al. reported that TCD could detect MES in only 3 of 24 patients with early stage of MMD [4]. However, our case demonstrated the presence of MES in not early but late stage of MMD, and the frequency of MES abruptly diminished within 2 weeks during serial MRA studies. This result implies important information about the mechanism of cerebral hemodynamics in MMD. Firstly, the thrombus formation occurred in the progressive stenosis of the proximal MCAs at active stage of MMD. Initial TCD showed the multiple MES, which were reflected in thrombi formation at arterial lesions [8] Then, the arterial lesions proceeded to near occlusion, and follow-up TCD demonstrated the reduced MCA flow and disappearance of MES. Therefore, we consider that the presence of MES in MMD case may indicate the active stage of MMD. Since ischemic stroke in MMD has been considered to be caused by hemodynamic mechanisms, revascularization has been conducted in a case with severe hypo-perfusion [9]. Nevertheless, cerebral ischemia is likely to be caused by a combination of hypo-perfusion and embolization with reduced washout of emboli because of activation of both mechanisms [10]. In the present case, TCD was able to detect numerous MES in bilateral MCAs. We were also able to identify a new ischemic lesion in the right frontal cortex without neurological symptoms using DWI. These results indicate that the mechanism of cerebral ischemia in MMD could involve not only hemodynamics, but also embolism.
References [1] Suzuki J, Takaku A. Cerebrovascular “moyamoya” disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol 1969;20(3):288–99. [2] Hallemeier CL, Rich KM, Grubb Jr RL, Chicoine MR, Moran CJ, Cross III DT, et al. Clinical features and outcome in North American adults with moyamoya phenomenon. Stroke 2006;37(6):1490–6. [3] Fukui M. Guidelines for the diagnosis and treatment of spontaneous occlusion of the circle of Willis (‘moyamoya’ disease). Research Committee on Spontaneous Occlusion of the Circle of Willis (Moyamoya Disease) of the Ministry of Health and Welfare, Japan. Clin Neurol Neurosurg 1997;99(Suppl 2):S238–40. [4] Horn P, Lanczik O, Vajkoczy P, Daffertshofer M, Bueltmann E, Werner A, et al. Hemodynamic reserve and high-intensity transient signals in moyamoya disease. Cerebrovasc Dis 2005;19(3):141–6. [5] Ringelstein EB, Droste DW, Babikian VL, Evans DH, Grosset DG, Kaps M, et al. Consensus on microembolus detection by TCD. International Consensus Group on Microembolus Detection. Stroke 1998;29(3):725–9. [6] Kuroda S, Ishikawa T, Houkin K, Nanba R, Hokari M, Iwasaki Y. Incidence and clinical features of disease progression in adult moyamoya disease. Stroke 2005;36(10):2148–53. [7] Houkin K, Abe H, Yoshimoto T, Takahashi A. Is “unilateral” moyamoya disease different from moyamoya disease? J Neurosurg 1996;85(5):772–6. [8] Ikeda E, Hosoda Y. Distribution of thrombotic lesions in the cerebral arteries in spontaneous occlusion of the circle of Willis: cerebrovascular moyamoya disease. Clin Neuropathol 1993;12(1):44–8. [9] Isono M, Ishii K, Kobayashi H, Kaga A, Kamida T, Fujiki M. Effects of indirect bypass surgery for occlusive cerebrovascular diseases in adults. J Clin Neurosci 2002;9(6):644–7. [10] Sedlaczek O, Caplan L, Hennerici M. Impaired washout-embolism and ischemic stroke: further examples and proof of concept. Cerebrovasc Dis 2005;19(6):396–401.
Short communication
Microembolic signals are associated with progression of arterial lesion in Moyamoya disease: A case report Yasuyuki Iguchi ⁎, Kazumi Kimura, Youhei Tateishi, Kensaku Shibazaki, Takeshi Iwanaga, Takeshi Inoue Department of Stroke Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki-city, Okayama, 701-0192, Japan Received 2 January 2007; received in revised form 30 March 2007; accepted 2 April 2007 Available online 1 May 2007
Abstract Transcranial Doppler ultrasonography (TCD) and magnetic resonance angiography (MRA) confirmed a rapid progression of arterial lesion in Moyamoya disease after the patient gave birth. TCD could initially detect a large number of microembolic signals (MES) at the distal portion of stenotic lesions. After MRA showed the development of stenotic lesions 10 days after first TCD monitoring, MES were absent. MES may be related to the clinical activity of Moyamoya disease. © 2007 Elsevier B.V. All rights reserved. Keywords: Transcranial Doppler; Moyamoya disease; Microembolic signals; Diffusion weighted magnetic resonance imaging; Pregnancy
1. Introduction Moyamoya disease (MMD) is characterized by slow progression at bilateral carotid forks accompanied by cerebral ischemia and hemorrhage [1]. After initiating medical treatment, the 5-year risk of recurrent stroke is 65% after initial symptoms and 27% after angiographic diagnosis, respectively [2]. However, even if high frequency of cerebral ischemia is observed, no reports have precisely described whether embolic stroke from arterial lesions occurs in cases with MMD. We herein report evidence of embolism using transcranial Doppler ultrasonography (TCD) and diffusion-weighted magnetic resonance imaging (DWI) in an adult case of MMD. 2. Case report A 28-year-old pregnant woman was admitted to our hospital in order to manage a premature labor in January ⁎ Corresponding author. Tel.: +81 86 462 1111; fax: +81 86 462 1199. E-mail address: [email protected] (Y. Iguchi). 0022-510X/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2007.04.004
2006. Previous history was probable MMD based on cerebral angiography in 2001 after transient dysesthesia of the right hand (Fig. 1A) [3]. The patient had no history of hypertension, diabetes, hyperlipidemia or eclampsia. Neither antiplatelet treatment nor anticoagulation had ever been used. During hospitalization, transient dysarthria and dysesthesia of the left hand and leg were noted. She was referred to the department of stroke medicine 1 week after delivery without any symptoms. On admission, she did not complain of headache, dizziness, diplopia or numbness. Height was 163 cm and body weight was 76 kg. Body temperature was 36.5 °C, blood pressure was 120/60 mm Hg and heart rate was 74 beats/min with regular sinus rhythm. No neck or orbital bruits were present. Heart sounds were clear. Neurological findings were normal and transient ischemic attack was diagnosed. Laboratory examinations on admission showed: erythrocyte count, 476 × 104/mm3; hemoglobin, 13.9 g/dl; hematocrit, 43.1%; leukocyte count, 8790/mm3; platelets 23.9 × 104/mm3. D-dimer level was 2.1 μg/ml (normal, ≤ 1.0 μg/ml) and level of thrombin–antithrombin III complex was 3.4 ng/ml (normal, ≤ 3.0 ng/ml). Von Willebrand
254
Y. Iguchi et al. / Journal of the Neurological Sciences 260 (2007) 253–255
Fig. 1. A) Initial conventional angiography (anterior–posterior projection) of bilateral internal carotid arteries shows a stenotic lesion at the proximal left middle cerebral artery (MCA). B) Five years after diagnosing probable Moyamoya disease, severe stenotic lesions at both right and left middle cerebral arteries were observed with slight basal Moyamoya vessels after delivery.
factor was 241% (normal, 60–170%). Urinalysis revealed no abnormalities. Hepatic and renal functions were normal. The patient was examined using a commercially available echo planner operation on a 1.5-T MR unit (Signa EchoSpeed Horizon; GE Medical Systems, Milwaukee, WI). DWI demonstrated a hyper-intense lesion in the right frontal cortex (Fig. 2). However, no abnormalities in the basal ganglia, brainstem or cerebellum were noted on either DWI or T2-weighted imaging. Time-of-flight magnetic resonance angiography (MRA) showed severe stenosis in both right terminal internal carotid artery (ICA) and the left middle cerebral artery (MCA) (Fig. 3A). To confirm the arterial lesion, cerebral angiography was followed by first MRA (Fig. 1B). The horizontal portion of the left MCA
displayed severe stenosis and the distal left MCA was incompletely patent. Abnormal vascular networks bilaterally were seen in the vicinity of the arterial lesions. Finally, she was diagnosed as definite MMD with late stage [3,4]. TCD was conducted using a Pioneer TC 8080 system (Nicolet Vascular, Madison, WI) to detect microembolic signals (MES). TCD was recorded for 20 min. Doppler audio and spectrum signals were recorded on the hard disc of the TCD machine. MES were identified by the typical visual appearance on the spectral display and the characteristic sound, according to standard consensus criteria [5]. TCD demonstrated numerous MES in both right and left MCAs (Fig. 3A). However, no MES were identified in either posterior cerebral artery (Fig. 3A). At 10 days after first TCD, TCD detected only a minimal flow signal in the proximal right MCA without any MES (Fig. 3B). MRA showed narrowing of the entirety of both MCAs, particularly the left MCA (Fig. 3B). The patient was subsequently transferred to the neurosurgery unit for consideration of surgical treatment. 3. Discussion
Fig. 2. Diffusion-weighted magnetic resonance imaging shows highintensity areas in the right frontal cortex (white arrow).
The present case demonstrated the angiographical changes from unilateral to bilateral MMD for a five-year period. The rapid progression of MMD after delivery was observed by MRA for 2 weeks. TCD could detect numerous MES in the distal portions of stenotic MCAs. After rapid progression of MCA stenosis, MES disappeared during TCD monitoring. At 5 years after probable diagnosis of MMD with ipsilateral ICA-MCA stenosis, contralateral MCA stenosis was confirmed by cerebral angiography. This case was compatible with a previous report by Kuroda et al. that all adult patients who showed slowly progression of arterial lesion from uni- to bilateral MMD were women at about
Y. Iguchi et al. / Journal of the Neurological Sciences 260 (2007) 253–255
255
Fig. 3. A) Magnetic resonance angiography (MRA) shows severe stenosis of the left MCA on admission. Transcranial Doppler ultrasonography (TCD) demonstrates microembolic signals (MES) in both right and left middle cerebral arteries (arrows head) even if no MES are present in posterior cerebral arteries. B) About 10 days after first MRA and TCD, stenotic lesions in the proximal right MCA have progressed and flow signals of the left MCA are incomplete. Doppler spectral waveforms at both MCAs are minimal without MES.
5 years after initial diagnosis [6]. According to previous surveys, unilateral MMD has been recognized as stable in adults [7]. However, a third of MMD patients with long follow-up period progress to definite MMD and around 87% are female [6]. We thus consider that conditions specific to women, such as pregnancy and menopause, may contribute to the progression of MMD. Concerning the presence of MES, Horn et al. reported that TCD could detect MES in only 3 of 24 patients with early stage of MMD [4]. However, our case demonstrated the presence of MES in not early but late stage of MMD, and the frequency of MES abruptly diminished within 2 weeks during serial MRA studies. This result implies important information about the mechanism of cerebral hemodynamics in MMD. Firstly, the thrombus formation occurred in the progressive stenosis of the proximal MCAs at active stage of MMD. Initial TCD showed the multiple MES, which were reflected in thrombi formation at arterial lesions [8] Then, the arterial lesions proceeded to near occlusion, and follow-up TCD demonstrated the reduced MCA flow and disappearance of MES. Therefore, we consider that the presence of MES in MMD case may indicate the active stage of MMD. Since ischemic stroke in MMD has been considered to be caused by hemodynamic mechanisms, revascularization has been conducted in a case with severe hypo-perfusion [9]. Nevertheless, cerebral ischemia is likely to be caused by a combination of hypo-perfusion and embolization with reduced washout of emboli because of activation of both mechanisms [10]. In the present case, TCD was able to detect numerous MES in bilateral MCAs. We were also able to identify a new ischemic lesion in the right frontal cortex without neurological symptoms using DWI. These results indicate that the mechanism of cerebral ischemia in MMD could involve not only hemodynamics, but also embolism.
References [1] Suzuki J, Takaku A. Cerebrovascular “moyamoya” disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol 1969;20(3):288–99. [2] Hallemeier CL, Rich KM, Grubb Jr RL, Chicoine MR, Moran CJ, Cross III DT, et al. Clinical features and outcome in North American adults with moyamoya phenomenon. Stroke 2006;37(6):1490–6. [3] Fukui M. Guidelines for the diagnosis and treatment of spontaneous occlusion of the circle of Willis (‘moyamoya’ disease). Research Committee on Spontaneous Occlusion of the Circle of Willis (Moyamoya Disease) of the Ministry of Health and Welfare, Japan. Clin Neurol Neurosurg 1997;99(Suppl 2):S238–40. [4] Horn P, Lanczik O, Vajkoczy P, Daffertshofer M, Bueltmann E, Werner A, et al. Hemodynamic reserve and high-intensity transient signals in moyamoya disease. Cerebrovasc Dis 2005;19(3):141–6. [5] Ringelstein EB, Droste DW, Babikian VL, Evans DH, Grosset DG, Kaps M, et al. Consensus on microembolus detection by TCD. International Consensus Group on Microembolus Detection. Stroke 1998;29(3):725–9. [6] Kuroda S, Ishikawa T, Houkin K, Nanba R, Hokari M, Iwasaki Y. Incidence and clinical features of disease progression in adult moyamoya disease. Stroke 2005;36(10):2148–53. [7] Houkin K, Abe H, Yoshimoto T, Takahashi A. Is “unilateral” moyamoya disease different from moyamoya disease? J Neurosurg 1996;85(5):772–6. [8] Ikeda E, Hosoda Y. Distribution of thrombotic lesions in the cerebral arteries in spontaneous occlusion of the circle of Willis: cerebrovascular moyamoya disease. Clin Neuropathol 1993;12(1):44–8. [9] Isono M, Ishii K, Kobayashi H, Kaga A, Kamida T, Fujiki M. Effects of indirect bypass surgery for occlusive cerebrovascular diseases in adults. J Clin Neurosci 2002;9(6):644–7. [10] Sedlaczek O, Caplan L, Hennerici M. Impaired washout-embolism and ischemic stroke: further examples and proof of concept. Cerebrovasc Dis 2005;19(6):396–401.