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Published in: BMC Neurology 1/2017

Open Access 01-12-2017 | Research article

Prevalence of and risk factors for enlarged perivascular spaces in adult patients with moyamoya disease

Authors: Tomoyoshi Kuribara, Takeshi Mikami, Katsuya Komatsu, Hime Suzuki, Hirofumi Ohnishi, Kiyohiro Houkin, Nobuhiro Mikuni

Published in: BMC Neurology | Issue 1/2017

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Abstract

Background

Enlarged perivascular spaces (EPVS) are often observed with magnetic resonance imaging in patients with small vessel disease. However, the risk factors, radiological features, and clinical relevance of EPVS in patients with moyamoya disease are poorly understood. The purpose of this study was to evaluate EPVS, the risk factors of many EPVS, and the pathophysiology of EPVS in adult patients with moyamoya disease.

Methods

One hundred cerebral hemispheres of 50 adult patients with moyamoya disease were examined. The control group consisted of 50 age/sex-matched patients without ischemic disease. The numbers of EPVS at the level of the centrum semiovale per hemisphere were compared between the moyamoya disease and control groups. In each hemisphere, the total numbers of EPVS were categorized into five grades (0–4), and the clinical and radiological characteristics of the predictive factors in patients in the high EPVS grade group (EPVS grade = 4) were assessed.

Results

The EPVS counts and grades were significantly higher in the moyamoya disease group. Analyses of the background characteristics of the patients with moyamoya disease revealed that significantly higher prevalence of high EPVS grades were associated with the female sex, hypertension, high magnetic resonance angiography scores, high numbers of flow voids in the basal ganglia, high brain atrophy scores, ivy signs, and white matter lesions. A logistic multivariate analysis of the patients with high EPVS grades revealed significant associations with the female sex, hypertension, and flow voids in the basal ganglia.

Conclusions

Increased EPVS were confirmed in adult patients with moyamoya disease, and the associated clinical and radiological factors were identified. The presence of hypertension, the female sex, and flow voids in the basal ganglia were important for predicting high EPVS grades in patients with moyamoya disease. Reductions in arterial pulsations with steno-occlusive changes can inhibit the flow of interstitial fluid, which can increase the number of EPVS in patients with moyamoya disease. Other clinical factors, such as the female sex and hypertension, may promote secondary brain damage in patients with moyamoya disease. Further evaluations of EPVS in patients with moyamoya disease are needed to better understand their pathophysiological importance.
Literature
1.
go back to reference Nishimoto A, Takeuchi S. Abnormal cerebrovascular network related to the internal cartoid arteries. J Neurosurg. 1968;29(3):255–60.CrossRefPubMed Nishimoto A, Takeuchi S. Abnormal cerebrovascular network related to the internal cartoid arteries. J Neurosurg. 1968;29(3):255–60.CrossRefPubMed
2.
go back to reference Suzuki J, Takaku A. Cerebrovascular “moyamoya” disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol. 1969;20(3):288–99.CrossRefPubMed Suzuki J, Takaku A. Cerebrovascular “moyamoya” disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol. 1969;20(3):288–99.CrossRefPubMed
3.
go back to reference Ogawa A, Yoshimoto T, Suzuki J, Sakurai Y. Cerebral blood flow in moyamoya disease. Part 1: Correlation with age and regional distribution. Acta Neurochir. 1990;105(1–2):30–4.CrossRefPubMed Ogawa A, Yoshimoto T, Suzuki J, Sakurai Y. Cerebral blood flow in moyamoya disease. Part 1: Correlation with age and regional distribution. Acta Neurochir. 1990;105(1–2):30–4.CrossRefPubMed
4.
5.
go back to reference Komatsu K, Mikami T, Noshiro S, Miyata K, Wanibuchi M, Mikuni N. Reversibility of White Matter Hyperintensity by Revascularization Surgery in Moyamoya Disease. J Stroke Cerebrovasc Dis. 2016;25(6):1495–502.CrossRefPubMed Komatsu K, Mikami T, Noshiro S, Miyata K, Wanibuchi M, Mikuni N. Reversibility of White Matter Hyperintensity by Revascularization Surgery in Moyamoya Disease. J Stroke Cerebrovasc Dis. 2016;25(6):1495–502.CrossRefPubMed
6.
go back to reference Kikuta K, Takagi Y, Nozaki K, Hanakawa T, Okada T, Mikuni N, Miki Y, Fushmi Y, Yamamoto A, Yamada K, et al. Asymptomatic microbleeds in moyamoya disease: T2*-weighted gradient-echo magnetic resonance imaging study. J Neurosurg. 2005;102(3):470–5.CrossRefPubMed Kikuta K, Takagi Y, Nozaki K, Hanakawa T, Okada T, Mikuni N, Miki Y, Fushmi Y, Yamamoto A, Yamada K, et al. Asymptomatic microbleeds in moyamoya disease: T2*-weighted gradient-echo magnetic resonance imaging study. J Neurosurg. 2005;102(3):470–5.CrossRefPubMed
7.
8.
9.
go back to reference Potter GM, Chappell FM, Morris Z, Wardlaw JM. Cerebral perivascular spaces visible on magnetic resonance imaging: development of a qualitative rating scale and its observer reliability. Cerebrovasc Dis. 2015;39(3–4):224–31.CrossRefPubMedPubMedCentral Potter GM, Chappell FM, Morris Z, Wardlaw JM. Cerebral perivascular spaces visible on magnetic resonance imaging: development of a qualitative rating scale and its observer reliability. Cerebrovasc Dis. 2015;39(3–4):224–31.CrossRefPubMedPubMedCentral
10.
go back to reference Doubal FN, MacLullich AM, Ferguson KJ, Dennis MS, Wardlaw JM. Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease. Stroke. 2010;41(3):450–4.CrossRefPubMed Doubal FN, MacLullich AM, Ferguson KJ, Dennis MS, Wardlaw JM. Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease. Stroke. 2010;41(3):450–4.CrossRefPubMed
11.
go back to reference Rouhl RP, van Oostenbrugge RJ, Knottnerus IL, Staals JE, Lodder J. Virchow-Robin spaces relate to cerebral small vessel disease severity. J Neurol. 2008;255(5):692–6.CrossRefPubMed Rouhl RP, van Oostenbrugge RJ, Knottnerus IL, Staals JE, Lodder J. Virchow-Robin spaces relate to cerebral small vessel disease severity. J Neurol. 2008;255(5):692–6.CrossRefPubMed
12.
go back to reference Yao M, Herve D, Jouvent E, Duering M, Reyes S, Godin O, Guichard JP, Dichgans M, Chabriat H. Dilated perivascular spaces in small-vessel disease: a study in CADASIL. Cerebrovasc Dis. 2014;37(3):155–63.CrossRefPubMed Yao M, Herve D, Jouvent E, Duering M, Reyes S, Godin O, Guichard JP, Dichgans M, Chabriat H. Dilated perivascular spaces in small-vessel disease: a study in CADASIL. Cerebrovasc Dis. 2014;37(3):155–63.CrossRefPubMed
13.
go back to reference Zhu YC, Tzourio C, Soumare A, Mazoyer B, Dufouil C, Chabriat H. Severity of dilated Virchow-Robin spaces is associated with age, blood pressure, and MRI markers of small vessel disease: a population-based study. Stroke. 2010;41(11):2483–90.CrossRefPubMed Zhu YC, Tzourio C, Soumare A, Mazoyer B, Dufouil C, Chabriat H. Severity of dilated Virchow-Robin spaces is associated with age, blood pressure, and MRI markers of small vessel disease: a population-based study. Stroke. 2010;41(11):2483–90.CrossRefPubMed
14.
go back to reference Hiroki M, Miyashita K. Linear hyperintensity objects on magnetic resonance imaging related to hypertension. Cerebrovasc Dis. 2001;11(3):164–8.CrossRefPubMed Hiroki M, Miyashita K. Linear hyperintensity objects on magnetic resonance imaging related to hypertension. Cerebrovasc Dis. 2001;11(3):164–8.CrossRefPubMed
15.
go back to reference Patankar TF, Mitra D, Varma A, Snowden J, Neary D, Jackson A. Dilatation of the Virchow-Robin space is a sensitive indicator of cerebral microvascular disease: study in elderly patients with dementia. AJNR Am J Neuroradiol. 2005;26(6):1512–20.PubMed Patankar TF, Mitra D, Varma A, Snowden J, Neary D, Jackson A. Dilatation of the Virchow-Robin space is a sensitive indicator of cerebral microvascular disease: study in elderly patients with dementia. AJNR Am J Neuroradiol. 2005;26(6):1512–20.PubMed
16.
go back to reference Suzuki H, Mikami T, Komatsu K, Noshiro S, Miyata K, Hirano T, Wanibuchi M, Mikuni N. Assessment of the cortical artery using computed tomography angiography for bypass surgery in moyamoya disease. Neurosurg Rev. 2017;40(2):299–307.CrossRefPubMed Suzuki H, Mikami T, Komatsu K, Noshiro S, Miyata K, Hirano T, Wanibuchi M, Mikuni N. Assessment of the cortical artery using computed tomography angiography for bypass surgery in moyamoya disease. Neurosurg Rev. 2017;40(2):299–307.CrossRefPubMed
17.
go back to reference Maclullich AM, Wardlaw JM, Ferguson KJ, Starr JM, Seckl JR, Deary IJ. Enlarged perivascular spaces are associated with cognitive function in healthy elderly men. J Neurol Neurosurg Psychiatry. 2004;75(11):1519–23.CrossRefPubMedPubMedCentral Maclullich AM, Wardlaw JM, Ferguson KJ, Starr JM, Seckl JR, Deary IJ. Enlarged perivascular spaces are associated with cognitive function in healthy elderly men. J Neurol Neurosurg Psychiatry. 2004;75(11):1519–23.CrossRefPubMedPubMedCentral
18.
go back to reference Mikami T, Sugino T, Ohtaki S, Houkin K, Mikuni N. Diagnosis of moyamoya disease on magnetic resonance imaging: are flow voids in the basal ganglia an essential criterion for definitive diagnosis? Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2013;22(6):862–8.CrossRef Mikami T, Sugino T, Ohtaki S, Houkin K, Mikuni N. Diagnosis of moyamoya disease on magnetic resonance imaging: are flow voids in the basal ganglia an essential criterion for definitive diagnosis? Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2013;22(6):862–8.CrossRef
19.
go back to reference Zhang X, Ding L, Yang L, Qin W, Yuan J, Li S, Hu W. Brain Atrophy Correlates with Severe Enlarged Perivascular Spaces in Basal Ganglia among Lacunar Stroke Patients. PLoS One. 2016;11(2):e0149593.CrossRefPubMedPubMedCentral Zhang X, Ding L, Yang L, Qin W, Yuan J, Li S, Hu W. Brain Atrophy Correlates with Severe Enlarged Perivascular Spaces in Basal Ganglia among Lacunar Stroke Patients. PLoS One. 2016;11(2):e0149593.CrossRefPubMedPubMedCentral
20.
go back to reference Farrell C, Chappell F, Armitage PA, Keston P, Maclullich A, Shenkin S, Wardlaw JM. Development and initial testing of normal reference MR images for the brain at ages 65–70 and 75–80 years. Eur Radiol. 2009;19(1):177–83.CrossRefPubMed Farrell C, Chappell F, Armitage PA, Keston P, Maclullich A, Shenkin S, Wardlaw JM. Development and initial testing of normal reference MR images for the brain at ages 65–70 and 75–80 years. Eur Radiol. 2009;19(1):177–83.CrossRefPubMed
21.
go back to reference Houkin K, Nakayama N, Kuroda S, Nonaka T, Shonai T, Yoshimoto T. Novel magnetic resonance angiography stage grading for moyamoya disease. Cerebrovasc Dis. 2005;20(5):347–54.CrossRefPubMed Houkin K, Nakayama N, Kuroda S, Nonaka T, Shonai T, Yoshimoto T. Novel magnetic resonance angiography stage grading for moyamoya disease. Cerebrovasc Dis. 2005;20(5):347–54.CrossRefPubMed
22.
go back to reference Weller RO, Djuanda E, Yow HY, Carare RO. Lymphatic drainage of the brain and the pathophysiology of neurological disease. Acta Neuropathol. 2009;117(1):1–14.CrossRefPubMed Weller RO, Djuanda E, Yow HY, Carare RO. Lymphatic drainage of the brain and the pathophysiology of neurological disease. Acta Neuropathol. 2009;117(1):1–14.CrossRefPubMed
23.
go back to reference Carare RO, Bernardes-Silva M, Newman TA, Page AM, Nicoll JA, Perry VH, Weller RO. Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology. Neuropathol Appl Neurobiol. 2008;34(2):131–44.CrossRefPubMed Carare RO, Bernardes-Silva M, Newman TA, Page AM, Nicoll JA, Perry VH, Weller RO. Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology. Neuropathol Appl Neurobiol. 2008;34(2):131–44.CrossRefPubMed
24.
go back to reference Schley D, Carare-Nnadi R, Please CP, Perry VH, Weller RO. Mechanisms to explain the reverse perivascular transport of solutes out of the brain. J Theor Biol. 2006;238(4):962–74.CrossRefPubMed Schley D, Carare-Nnadi R, Please CP, Perry VH, Weller RO. Mechanisms to explain the reverse perivascular transport of solutes out of the brain. J Theor Biol. 2006;238(4):962–74.CrossRefPubMed
25.
go back to reference Iliff JJ, Wang M, Zeppenfeld DM, Venkataraman A, Plog BA, Liao Y, Deane R, Nedergaard M. Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2013;33(46):18190–9.CrossRef Iliff JJ, Wang M, Zeppenfeld DM, Venkataraman A, Plog BA, Liao Y, Deane R, Nedergaard M. Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2013;33(46):18190–9.CrossRef
26.
go back to reference Weller RO, Preston SD, Subash M, Carare RO. Cerebral amyloid angiopathy in the aetiology and immunotherapy of Alzheimer disease. Alzheimers Res Ther. 2009;1(2):6.CrossRefPubMedPubMedCentral Weller RO, Preston SD, Subash M, Carare RO. Cerebral amyloid angiopathy in the aetiology and immunotherapy of Alzheimer disease. Alzheimers Res Ther. 2009;1(2):6.CrossRefPubMedPubMedCentral
27.
go back to reference Kyrtsos CR, Baras JS. Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer's Disease Pathogenesis. PLoS One. 2015;10(10):e0139574.CrossRefPubMedPubMedCentral Kyrtsos CR, Baras JS. Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer's Disease Pathogenesis. PLoS One. 2015;10(10):e0139574.CrossRefPubMedPubMedCentral
28.
go back to reference van Swieten JC, van den Hout JH, van Ketel BA, Hijdra A, Wokke JH, van Gijn J. Periventricular lesions in the white matter on magnetic resonance imaging in the elderly. A morphometric correlation with arteriolosclerosis and dilated perivascular spaces. Brain J Neurol. 1991;114(Pt 2):761–74.CrossRef van Swieten JC, van den Hout JH, van Ketel BA, Hijdra A, Wokke JH, van Gijn J. Periventricular lesions in the white matter on magnetic resonance imaging in the elderly. A morphometric correlation with arteriolosclerosis and dilated perivascular spaces. Brain J Neurol. 1991;114(Pt 2):761–74.CrossRef
29.
go back to reference Kuroda S, Houkin K, Kamiyama H, Abe H, Mitsumori K. Regional cerebral hemodynamics in childhood moyamoya disease. Child's nervous system : ChNS. 1995;11(10):584–90.CrossRefPubMed Kuroda S, Houkin K, Kamiyama H, Abe H, Mitsumori K. Regional cerebral hemodynamics in childhood moyamoya disease. Child's nervous system : ChNS. 1995;11(10):584–90.CrossRefPubMed
30.
go back to reference Yamada I, Himeno Y, Matsushima Y, Shibuya H. Renal artery lesions in patients with moyamoya disease: angiographic findings. Stroke. 2000;31(3):733–7.CrossRefPubMed Yamada I, Himeno Y, Matsushima Y, Shibuya H. Renal artery lesions in patients with moyamoya disease: angiographic findings. Stroke. 2000;31(3):733–7.CrossRefPubMed
31.
go back to reference Togao O, Mihara F, Yoshiura T, Tanaka A, Kuwabara Y, Morioka T, Matsushima T, Sasaki T, Honda H. Prevalence of stenoocclusive lesions in the renal and abdominal arteries in moyamoya disease. AJR Am J Roentgenol. 2004;183(1):119–22.CrossRefPubMed Togao O, Mihara F, Yoshiura T, Tanaka A, Kuwabara Y, Morioka T, Matsushima T, Sasaki T, Honda H. Prevalence of stenoocclusive lesions in the renal and abdominal arteries in moyamoya disease. AJR Am J Roentgenol. 2004;183(1):119–22.CrossRefPubMed
32.
go back to reference Koizumi A, Kobayashi H, Liu W, Fujii Y, Senevirathna ST, Nanayakkara S, Okuda H, Hitomi T, Harada KH, Takenaka K, et al. P.R4810K, a polymorphism of RNF213, the susceptibility gene for moyamoya disease, is associated with blood pressure. Environ Health Prev Med. 2013;18(2):121–9.CrossRefPubMed Koizumi A, Kobayashi H, Liu W, Fujii Y, Senevirathna ST, Nanayakkara S, Okuda H, Hitomi T, Harada KH, Takenaka K, et al. P.R4810K, a polymorphism of RNF213, the susceptibility gene for moyamoya disease, is associated with blood pressure. Environ Health Prev Med. 2013;18(2):121–9.CrossRefPubMed
33.
go back to reference Khan N, Achrol AS, Guzman R, Burns TC, Dodd R, Bell-Stephens T, Steinberg GK. Sex differences in clinical presentation and treatment outcomes in Moyamoya disease. Neurosurgery. 2012;71(3):587–93. discussion 593CrossRefPubMed Khan N, Achrol AS, Guzman R, Burns TC, Dodd R, Bell-Stephens T, Steinberg GK. Sex differences in clinical presentation and treatment outcomes in Moyamoya disease. Neurosurgery. 2012;71(3):587–93. discussion 593CrossRefPubMed
34.
go back to reference Hallemeier CL, Rich KM, Grubb RL Jr, Chicoine MR, Moran CJ, Cross DT 3rd, Zipfel GJ, Dacey RG Jr, Derdeyn CP. Clinical features and outcome in North American adults with moyamoya phenomenon. Stroke. 2006;37(6):1490–6.CrossRefPubMed Hallemeier CL, Rich KM, Grubb RL Jr, Chicoine MR, Moran CJ, Cross DT 3rd, Zipfel GJ, Dacey RG Jr, Derdeyn CP. Clinical features and outcome in North American adults with moyamoya phenomenon. Stroke. 2006;37(6):1490–6.CrossRefPubMed
35.
go back to reference Barrett KM, Worrall BB. Sex and stroke: are they really different in midlife? Neurology. 2007;69(20):1894–5.CrossRefPubMed Barrett KM, Worrall BB. Sex and stroke: are they really different in midlife? Neurology. 2007;69(20):1894–5.CrossRefPubMed
36.
go back to reference Williams JE, Chimowitz MI, Cotsonis GA, Lynn MJ, Waddy SP. Gender differences in outcomes among patients with symptomatic intracranial arterial stenosis. Stroke. 2007;38(7):2055–62.CrossRefPubMed Williams JE, Chimowitz MI, Cotsonis GA, Lynn MJ, Waddy SP. Gender differences in outcomes among patients with symptomatic intracranial arterial stenosis. Stroke. 2007;38(7):2055–62.CrossRefPubMed
37.
go back to reference Kaku Y, Iihara K, Nakajima N, Kataoka H, Fukushima K, Iida H, Hashimoto N. The leptomeningeal ivy sign on fluid-attenuated inversion recovery images in moyamoya disease: positron emission tomography study. Cerebrovasc Dis. 2013;36(1):19–25.CrossRefPubMed Kaku Y, Iihara K, Nakajima N, Kataoka H, Fukushima K, Iida H, Hashimoto N. The leptomeningeal ivy sign on fluid-attenuated inversion recovery images in moyamoya disease: positron emission tomography study. Cerebrovasc Dis. 2013;36(1):19–25.CrossRefPubMed
38.
go back to reference Vuignier S, Ito M, Kurisu K, Kazumata K, Nakayama N, Shichinohe H, Shiga T, Kiss JZ, Tamaki N, Houkin K. Ivy sign, misery perfusion, and asymptomatic moyamoya disease: FLAIR imaging and (15)O-gas positron emission tomography. Acta Neurochir. 2013;155(11):2097–104.CrossRefPubMed Vuignier S, Ito M, Kurisu K, Kazumata K, Nakayama N, Shichinohe H, Shiga T, Kiss JZ, Tamaki N, Houkin K. Ivy sign, misery perfusion, and asymptomatic moyamoya disease: FLAIR imaging and (15)O-gas positron emission tomography. Acta Neurochir. 2013;155(11):2097–104.CrossRefPubMed
39.
go back to reference Maeda M, Tsuchida C. “Ivy sign” on fluid-attenuated inversion-recovery images in childhood moyamoya disease. AJNR Am J Neuroradiol. 1999;20(10):1836–8.PubMed Maeda M, Tsuchida C. “Ivy sign” on fluid-attenuated inversion-recovery images in childhood moyamoya disease. AJNR Am J Neuroradiol. 1999;20(10):1836–8.PubMed
40.
go back to reference Takanashi J, Suzuki H, Barkovich AJ, Sugita K, Saeki N, Kobayashi E, Fujii K, Kohno Y. Medullary streaks: dilated medullary vessels in chronic ischemia in children. Neurology. 2003;61(4):583–4.CrossRefPubMed Takanashi J, Suzuki H, Barkovich AJ, Sugita K, Saeki N, Kobayashi E, Fujii K, Kohno Y. Medullary streaks: dilated medullary vessels in chronic ischemia in children. Neurology. 2003;61(4):583–4.CrossRefPubMed
41.
go back to reference Suzuki H, Mikami T, Kuribara T, Yoshifuji K, Komatsu K, Akiyama Y, Ohnishi H, Houkin K, Mikuni N. Pathophysiological consideration of medullary streaks on FLAIR imaging in pediatric moyamoya disease. J Neurosurg Pediatr. 2017;19(5):560–6.CrossRefPubMed Suzuki H, Mikami T, Kuribara T, Yoshifuji K, Komatsu K, Akiyama Y, Ohnishi H, Houkin K, Mikuni N. Pathophysiological consideration of medullary streaks on FLAIR imaging in pediatric moyamoya disease. J Neurosurg Pediatr. 2017;19(5):560–6.CrossRefPubMed
42.
go back to reference Charidimou A, Boulouis G, Pasi M, Auriel E, van Etten ES, Haley K, Ayres A, Schwab KM, Martinez-Ramirez S, Goldstein JN, et al. MRI-visible perivascular spaces in cerebral amyloid angiopathy and hypertensive arteriopathy. Neurology. 2017;88(12):1157–64.CrossRefPubMed Charidimou A, Boulouis G, Pasi M, Auriel E, van Etten ES, Haley K, Ayres A, Schwab KM, Martinez-Ramirez S, Goldstein JN, et al. MRI-visible perivascular spaces in cerebral amyloid angiopathy and hypertensive arteriopathy. Neurology. 2017;88(12):1157–64.CrossRefPubMed
Metadata
Title
Prevalence of and risk factors for enlarged perivascular spaces in adult patients with moyamoya disease
Authors
Tomoyoshi Kuribara
Takeshi Mikami
Katsuya Komatsu
Hime Suzuki
Hirofumi Ohnishi
Kiyohiro Houkin
Nobuhiro Mikuni
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2017
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-017-0935-x

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