Editorial Open Access
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jan 26, 2024; 12(3): 466-473
Published online Jan 26, 2024. doi: 10.12998/wjcc.v12.i3.466
Is medical management useful in Moyamoya disease?
Sombat Muengtaweepongsa, Center of Excellence in Stroke, Division of Neurology, Department of Medicine, Faculty of Medicine, Thammasat University, Rangsit Campus, Klonglaung 12120, Pathum Thani, Thailand
Vatcharasorn Panpattanakul, Division of Neurology, Department of Internal Medicine, School of Medicine, University of Phayao, Phayao 56000, Thailand
ORCID number: Sombat Muengtaweepongsa (0000-0003-3715-4428).
Co-first authors: Sombat Muengtaweepongsa and Vatcharasorn Panpattanakul.
Author contributions: Muengtaweepongsa S and Panpattanakul V contributed equally to this work; Muengtaweepongsa S contributed to conception and design of the work, drafting and critical revision of the article, and gave final approval; Panpattanakul V contributed to conception and design of the work, data collection, drafting and critical revision of the article.
Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sombat Muengtaweepongsa, MD, Professor, Center of Excellence in Stroke, Division of Neurology, Department of Medicine, Faculty of Medicine, Thammasat University, Rangsit Campus, No. 99/209 Paholyothin Rd., Klonglaung 12120, Pathum Thani, Thailand. musombat@tu.ac.th
Received: October 13, 2023
Peer-review started: October 13, 2023
First decision: November 22, 2023
Revised: November 24, 2023
Accepted: January 5, 2024
Article in press: January 5, 2024
Published online: January 26, 2024
Processing time: 96 Days and 17.4 Hours

Abstract

Moyamoya disease (MMD), characterized by progressive internal carotid artery stenosis and collateral vessel formation, prompts cerebral perfusion complications and is stratified into idiopathic and Moyamoya syndrome subtypes. A multifaceted approach toward MMD management addresses cerebral infarctions through revascularization surgery and adjunctive medical therapy, while also navigating risks such as intracranial hemorrhage and cerebral infarction resulting from arterial stenosis and fragile collateral vessels. Addressing antithrombotic management reveals a potential role for treatments like antiplatelet agents and anticoagulants, despite the ambiguous contribution of thrombosis to MMD-related infarctions and the critical balance between preventing ischemic events and averting hemorrhagic complications. Transcranial doppler has proven useful in thromboembolic detection, despite persisting challenges concerning the efficacy and safety of antithrombotic treatments. Furthermore, antihypertensive interventions aim to manage blood pressure meticulously, especially during intracerebral hemorrhage, with recommendations and protocols varying based on the patient’s hypertension status. Additionally, lipid-lowering therapeutic strategies, particularly employing statins, are appraised for their possible beneficial role in MMD management, even as comprehensive data from disease-specific clinical trials remains elusive. Comprehensive guidelines and protocols to navigate the multifaceted therapeutic avenues for MMD, while maintaining a delicate balance between efficacy and safety, warrant further meticulous research and development. This protocol manuscript seeks to elucidate the various aspects and challenges imbued in managing and navigating through the complex landscape of MMD treatment.

Key Words: Moyamoya disease, Cerebral infarction, Antithrombotic management, Transcranial doppler, Revascularization, Intracerebral hemorrhage, Antihypertensive intervention, Lipid-lowering therapies

Core Tip: Moyamoya disease (MMD) involves progressive arterial stenosis, leading to cerebral infarctions and hemorrhages. Key treatments include revascularization surgery and supplementary medical therapy. Antithrombotic management, crucial for ischemic stroke prevention in MMD, requires a careful balance due to bleeding risks. Understanding cerebral infarction pathways, involving hemodynamic impairment and thromboembolism, is essential. Transcranial doppler is useful for emboli detection and screening. Antiplatelet therapy, especially Acetylsalicylic acid, is common, but its efficacy varies. Antihypertensive management is recommended during initial hemorrhage phases, while lipid-lowering strategies like statins show potential but need more research for specific guidelines in MMD.



INTRODUCTION

Moyamoya disease (MMD) is delineated by progressive stenosis of the internal carotid arteries intracranially, consequentially instigating impeded cerebral perfusion. This chronic cerebrovascular disorder encompasses the gradual occlusion of both distal internal carotid arteries, which is somewhat mitigated by the proliferation of collateral vessels at the brain’s base. Cerebral infarction may manifest due to reduced blood flow incited by arterial stenosis and occlusion. Furthermore, the fragility of compensatory collateral vessels poses a risk of rupture, thereby precipitating intracranial hemorrhage[1]. MMD is categorized into two subtypes: idiopathic (primary) and Moyamoya syndrome (secondary)[2]. The pathogenesis of the primary form is largely idiopathic, albeit associations with the RFN213 (ring finger protein 213) on chromosome 17q25.3 have been posited[3]. Contrarily, Moyamoya syndrome, while sharing angiographic characteristics with the primary subtype, is concurrently associated with additional pathologies, including but not limited to head and neck radiation, atherosclerosis, and systemic lupus erythematosus[4]. Key angiographic indicators of MMD encompass: (1) stenosis or occlusion of the distal internal carotid artery or the anterior/middle cerebral artery's proximal segment; (2) a smoky appearance in collateral vessels distal to the associated stenosis; and (3) bilateral involvement[5].

The incremental arterial constriction within the Circle of Willis in MMD ultimately progresses to total occlusion, thus diminishing blood flow and culminating in potential cerebral infarction[6]. A longitudinal study executed in Japan (2007) revealed a 3.2% annual stroke rate amongst 34 primary MMD patients without surgical intervention, with a mean follow-up duration of 44 mo[7,8]. Addressing the attenuated blood flow through revascularization surgery is the primary modality for cerebral infarction management, rendering surgical intervention indispensable, whereas medical therapy functions as an adjunct treatment in MMD scenarios[9].

"Moyamoya", linguistically derived from Japanese, metaphorically describes the “puff-of-smoke” visual evident in angiography, corresponding to the collateral vessels formed subsequent to stenosis. These fragile collateral vessels, while compensatory, introduce a pronounced susceptibility to rupture and intracerebral hemorrhage. Notably, revascularization techniques can alleviate the stresses on these collaterals, thus mitigating rupture risk[10]. Contrastingly, spontaneous intracerebral hemorrhage predominantly originates from microaneurysm rupture, frequently corollary to chronic hypertension[11]. The meticulous management of blood pressure is imperative in spontaneous intracerebral hemorrhage cases[12,13], with antihypertensive medications occupying a pivotal role in therapeutic strategies[13]. Nonetheless, the efficacy of blood pressure reduction via antihypertensive medications remains to be elucidated in the context of intracerebral hemorrhage among MMD patients.

ANTITHROMBOTIC MANAGEMENT IN MMD

Antithrombotic interventions in ischemic stroke fundamentally aim at hindering the development of blood clots[14]. A spectrum of such treatments incorporates antiplatelet agents, anticoagulants, and thrombolytic drugs. In the context of MMD, where hemodynamic impairment is pivotal in brain ischemia[15], there emerges an ambiguity regarding the degree to which thrombosis contributes to infarction events within this disease profile. Despite this, the potential for thromboembolism with ensuing clot formation in infarction events in MMD necessitates consideration[16], rendering the role of antithrombotic treatments potentially significant in preemptively addressing infarctions[17].

Elucidation of cerebral infarction pathways

Various research delineates that cerebral infarction in MMD is not exclusively the consequence of hemodynamic impairment. Larson et al[18] elucidated a propensity of Moyamoya patients towards a pro-thrombotic state. While Shulman et al[19] exhibited evidence of emboli connected to stenotic arteries in distinct Moyamoya cases. Furthermore, Jeon et al[20] identified that emboli, detected as high-intensity transient signals and distal to high-grade stenotic arteries, were etiological in recent cerebral infarctions. These revelations underscore that both hemodynamic impairment and thromboembolism are instrumental in cerebral infarction within MMD[21].

Transcranial doppler in thromboembolic detection

Transcranial doppler (TCD) has proven to be a dependable point-of-care tool for detecting emboli[22]. Several studies amplify the significance of TCD in unveiling thromboembolic occurrences in MMD. Since the 1980s, TCD has been entrenched as a methodological approach for screening individuals with sickle cell disease and Moyamoya syndrome, particularly regarding the necessity for blood transfusions as a primary stroke preventative strategy[23]. It has also been propounded that TCD could be potentially efficacious for screening asymptomatic Moyamoya patients to discern the necessity for antiplatelet treatment as a preemptive measure against stroke.

Challenges in antithrombotic treatment efficacy

Although devoid of robust evidence from randomized controlled trials (RCTs), the administration of antiplatelet treatment persists among physicians treating Moyamoya patients with cerebral infarction or transient ischemic attacks (TIAs)[24,25]. The prevalent pharmacologic inclination predominantly resides with a single antiplatelet treatment utilizing Acetylsalicylic acid (ASA). Contrastingly, primary stroke prevention employing antithrombotic treatment often goes unacknowledged for asymptomatic Moyamoya patients[24]. A retrospective study did not validate the utilization of antiplatelet therapy as a predominant prophylactic measure for ischemic events in MMD under conditions of stable hemodynamic status[26].

In managing MMD, surgical intervention is the predominant therapeutic strategy. Notwithstanding, surgeons frequently elect to administer antiplatelet pharmaceuticals subsequent to revascularization procedures[24,27-30]. The deployment of antithrombotic treatment post-surgical revascularization is quintessential, engendering improvements in circulation, the preservation of cerebral perfusion, thrombus prevention, and the maintenance of hemodynamic stability through the bypass system[24,29-31]. ASA remains the preferred post-operative antiplatelet agent among surgeons[30,32]. In an investigation by Onozuka et al[33], approximately 2000 Japanese patients, hospitalized due to non-hemorrhagic events associated with MMD, demonstrated improved functional outcomes when pre-admitted antiplatelet medication was administered.

Alternative antiplatelet agents, namely Clopidogrel and Cilostazol, have demonstrated propitious outcomes in averting ischemic stroke among individuals diagnosed with MMD[24]. Cilostazol, frequently prescribed in Japan and Korea, is utilized to shield against ischemic stroke in patients with MMD[24,34], while ASA and Clopidogrel are more prevalent recommendations outside these regions[35]. According to a study by Seo et al[34], a cohort of nearly 10000 Korean Moyamoya patients showcased augmented survival rates when administered any antiplatelet drug, with a particular inclination toward Cilostazol. Additionally, research by Kim et al[36] implies that Cilostazol may decelerate the progression of intracranial vessel constriction in Moyamoya patients. Notably, the application of Cilostazol seems to amplify cerebral blood flow and cognitive functionality in Moyamoya patients more substantially than Clopidogrel[37,38]. However, a study by Yamada et al[29] did not identify tangible benefits of any antiplatelet therapy in precluding recurrent ischemic stroke among 344 Moyamoya patients with a history of TIA or preceding infarct events in Japan.

In the context of MMD, evidence supporting the utilization of a dual antiplatelet regimen is absent. Given the amplified risk of intracranial hemorrhage, such a regimen might be unsuitable for patients with MMD, even in scenarios where a single regimen proves ineffectual. Nonetheless, there have been documented instances wherein a dual antiplatelet regimen was implemented for patients who either refused revascularization surgery or were awaiting the procedure[39,40]. The most recent Japanese management guidelines for MMD advocate for the employment of antiplatelet therapy as a secondary preventive measure against cerebral infarction, albeit with a grade C recommendation level, signifying a potential consideration in the absence of substantial scientific justification[41,42]. The protracted utilization of antiplatelet therapy for the secondary prevention of ischemic events continues to be a subject of debate due to the elevated risk of intracranial hemorrhage[25,41,43].

Navigating through anticoagulants and thrombolysis

Delving into the anticoagulant spectrum, which consists of warfarin, unfractionated heparin, low-molecular-weight heparin, and direct oral anticoagulants, these potent antithrombotic agents present a conspicuous risk of inducing bleeding complications. Hence, in MMD, which intrinsically carries a heightened risk of intracerebral hemorrhage, the employment of anticoagulants to preempt ischemic stroke is generally contraindicated[44,45], albeit with exceptions noted in scenarios where MMD coexists with conditions endorsing a hypercoagulable state[46-48]. Concerning thrombolysis, while intravenous recombinant tissue plasminogen activator (rt-PA) is conventionally utilized in acute ischemic stroke[49], its application within the thromboembolic mechanisms of MMD raises concerns due to the significantly elevated incidence of associated intracranial bleeding[50] and warrants cautious contemplation[41,42].

For Moyamoya patients confronting cerebral infarction or TIA, and seeking secondary stroke prevention, a single antiplatelet regimen comprising ASA, Clopidogrel, or Cilostazol may be proposed. Additionally, selective Moyamoya patients demonstrating embolic detection via TCD monitoring might benefit from antiplatelet treatment for primary ischemic stroke prevention. Nevertheless, the prudent utilization of certain anticoagulants and intravenous rt-PA, especially in Moyamoya patients enduring acute ischemic episodes, necessitates meticulous evaluation due to potential adverse impacts.

Table 1 provides a succinct overview of recommended antithrombotic treatment modalities in MMD, emphasizing a cautious approach in the management and treatment selection for these patients, given the delicate balance between preventing ischemic events and avoiding hemorrhagic complications.

Table 1 The antithrombotic treatment for Moyamoya disease.
Antithrombotic treatment
Rationale
Single antiplatelet regimen [agents: ASA (50-325 mg) per day; clopidogrel (75 mg) per day; cilostazol (200 mg) per day]Primary stroke prevention in embolic detection by TCD; Secondary stroke prevention
Dual antiplatelet regimenNo role
    AnticoagulantContra-indicated
    ThrombolysisUse with caution
ANTIHYPERTENSIVE INTERVENTION IN MMD

A meticulous scrutiny of the 2012 and 2021 Japanese MMD management guidelines postulates a recommendation to administer antihypertensive pharmacological agents during the incipient phase of intracerebral hemorrhage with the objective of mitigating hematoma expansion. However, a specificity pertaining to target blood pressure (BP) during this phase is conspicuously absent[41,42].

Antihypertensive recommendations during intracerebral hemorrhage

Within the confines of the aforementioned guidelines, a systolic BP < 180 mmHg and a diastolic BP < 105 mmHg are propounded for Moyamoya patients undergoing an intracerebral hemorrhage during the initial phase, substantiated by level III evidence[41]. Subsequent recommendations from the 2021 guidelines imply that attenuation of systolic BP during the acute stage of hemorrhagic events may be judicious, cognizant of the concomitant risk of cerebral ischemia. The recommendation is assigned a grade C, with a concomitant low level of evidence[42].

BP management and clinical outcomes

Extrapolating data from clinical outcomes of Moyamoya patients in China suggests a pronounced correlation between severe uncontrolled hypertension and unfavorable results, establishing severe uncontrolled BP as an independent risk factor[51]. An elevation in BP ostensibly exacerbates the risk of cerebrovascular events even in asymptomatic Moyamoya patients[52].

Antihypertensive protocols for moyamoya patients with hypertension

Employing antihypertensive treatment, particularly in Moyamoya patients manifesting hypertension, ostensibly aids in obviating unfavorable outcomes. For these patients, a protracted antihypertensive treatment is prudent, with targets conforming to hypertensive management guidelines. First-line antihypertensive agents, including Angiotensin-converting enzyme inhibitors, Angiotensin receptor blockers, Thiazide diuretics, and dihydropyridine Calcium-channel blockers, are reiterated by standard guidelines for hypertension management in this context[53].

Caution against prophylactic antihypertensive use

Conversely, a methodical administration of antihypertensive agents in Moyamoya patients without a definitive hypertension diagnosis is not advocated[41].

Table 2 provides a succinct overview of antihypertensive interventions and their respective rationale in the management of MMD.

Table 2 Delineation of antihypertensive strategies in Moyamoya disease.
Antihypertensive treatment
The rationale of treatment in Moyamoya disease
Nicardipine 5-15 mg/h; Labetalol 10 mg IV over 1-2 min followed by infusion of 2-8 mg/minThe early stage of intracerebral hemorrhage
Angiotensin-converting enzyme inhibitors; Angiotensin receptor blockers; Calcium channel blockers (highly lipophilic); DiureticsPresenting concurrent hypertension: primary and secondary prevention for cerebral ischemia or hemorrhage
LIPID-LOWERING THERAPEUTIC STRATEGIES IN MMD

The potential efficacy of lipid-lowering interventions in MMD invites further scrutiny, given the insufficiency of direct, disease-specific clinical trial data to substantiate this therapeutic approach. Within the context of lipid-lowering agents, statins emerge as a notably beneficial category, demonstrating prophylactic utility against both primary and secondary ischemic strokes in cohorts presenting with extant atherosclerotic disease[54,55]. Insight derived from Church et al[56] infers that statins, recognized for their pivotal role in atherosclerosis management, might also modulate the trajectory of unilateral MMD, thereby attenuating its progression. Moreover, following encephaloduroarteriosynangiosis surgery, atorvastatin has been implicated in fostering collateral blood vessel formation in patients with MMD[57]. Although Japanese guidelines advocate for lipid-lowering therapy in Moyamoya patients concomitant with dyslipidemia, a precise target lipid profile is requisite for such treatment modality yet awaits rigorous establishment[41]. Tentatively, aligning low-density lipoprotein levels below 100 mg/dL via statin administration could be considered a rational objective in Moyamoya patients, mirroring recommendations applicable to alternate stroke patients with confirmed atherosclerotic disease.

Table 3 elucidates specific lipid-lowering agents and their respective rationales in managing MMD, thereby highlighting the complexities and considerations intrinsic to this therapeutic domain. Future research endeavors necessitate a focus on delineating the intricacies of lipid management in this pathological context, thereby paving the way for enhanced, evidence-based clinical practices and patient outcomes.

Table 3 Analyzing lipid-lowering therapeutic interventions in Moyamoya disease.
Lipid-lowering agent
Corresponding rationale in Moyamoya disease treatment
StatinsAddressing concurrent dyslipidemia (LDL > 100)
Facilitating collateral development post-EDAS
FibrateLiterature provides no extant findings
CONCLUSION

The primary treatment approach for MMD is surgical revascularization, while medical therapy is used as a supplementary treatment. Antithrombotic therapy, such as antiplatelet medications, anticoagulants, and thrombolytic drugs, may be employed to prevent infarctions in MMD. Although hemodynamic impairment is the primary cause of infarction, thromboembolism can also contribute. TCD monitoring can aid in detecting emboli and guide the use of antiplatelet treatment. Commonly used antiplatelet medications include ASA, clopidogrel, and cilostazol. However, the routine use of antithrombotic drugs in MMD lacks strong evidence from RCTs. Antihypertensive treatment is recommended for Moyamoya patients, particularly during the early phase of intracerebral hemorrhage, to prevent hematoma expansion. The target blood pressure remains uncertain, but it is suggested to maintain systolic blood pressure below 180 mmHg and diastolic blood pressure below 105 mmHg. Hypertension is a risk factor for poor outcomes in Moyamoya patients, and long-term antihypertensive treatment is advised for those with established hypertension. First-line antihypertensive agents include angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, diuretics, and calcium channel blockers. The effectiveness of lipid-lowering treatment in MMD is not well-established. However, statins have demonstrated benefits in preventing ischemic strokes in patients with atherosclerotic disease and may also slow the progression of MMD. Further research is necessary to determine the role of lipid-lowering therapy in MMD.

ACKNOWLEDGEMENTS

The authors would like to acknowledge Michael Jan Everts, from the Clinical Research Center, Faculty of Medicine, Thammasat University, for English editorial assistance.

Footnotes

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Medicine, research and experimental

Country/Territory of origin: Thailand

Peer-review report’s scientific quality classification

Grade A (Excellent): A

Grade B (Very good): 0

Grade C (Good): 0

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Sun W, China S-Editor: Lin C L-Editor: A P-Editor: Cai YX

References
1.  Mertens R, Graupera M, Gerhardt H, Bersano A, Tournier-Lasserve E, Mensah MA, Mundlos S, Vajkoczy P. The Genetic Basis of Moyamoya Disease. Transl Stroke Res. 2022;13:25-45.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 49]  [Article Influence: 16.3]  [Reference Citation Analysis (0)]
2.  Unda SR, Antoniazzi AM, Miller R, Klyde D, Javed K, Fluss R, Holland R, De la Garza Ramos R, Haranhalli N, Altschul DJ. Moyamoya Disease and Syndrome: A National Inpatient Study of Ischemic Stroke Predictors. J Stroke Cerebrovasc Dis. 2021;30:105965.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 4]  [Cited by in F6Publishing: 7]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
3.  Roy V, Ross JP, Pépin R, Cortez Ghio S, Brodeur A, Touzel Deschênes L, Le-Bel G, Phillips DE, Milot G, Dion PA, Guérin S, Germain L, Berthod F, Auger FA, Rouleau GA, Dupré N, Gros-Louis F. Moyamoya Disease Susceptibility Gene RNF213 Regulates Endothelial Barrier Function. Stroke. 2022;53:1263-1275.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5]  [Cited by in F6Publishing: 22]  [Article Influence: 11.0]  [Reference Citation Analysis (0)]
4.  Kuroda S, Fujimura M, Takahashi J, Kataoka H, Ogasawara K, Iwama T, Tominaga T, Miyamoto S; Research Committee on Moyamoya Disease (Spontaneous Occlusion of Circle of Willis) of the Ministry of Health, Labor, and Welfare, Japan. Diagnostic Criteria for Moyamoya Disease - 2021 Revised Version. Neurol Med Chir (Tokyo). 2022;62:307-312.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 66]  [Article Influence: 33.0]  [Reference Citation Analysis (0)]
5.  Gupta A, Tyagi A, Romo M, Amoroso KC, Sonia F. Moyamoya Disease: A Review of Current Literature. Cureus. 2020;12:e10141.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 9]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
6.  Caplan LR, Simon RP, Hassani S. Chapter 27 - Cerebrovascular disease—stroke*. In: Zigmond MJ, Wiley CA, Chesselet MF, editors. Neurobiol Brain Disord (Second Ed). 2023;457-76.  [PubMed]  [DOI]  [Cited in This Article: ]
7.  Kim JS. Moyamoya Disease: Epidemiology, Clinical Features, and Diagnosis. J Stroke. 2016;18:2-11.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 213]  [Cited by in F6Publishing: 257]  [Article Influence: 32.1]  [Reference Citation Analysis (0)]
8.  Kim T, Oh CW, Bang JS, Kim JE, Cho WS. Moyamoya Disease: Treatment and Outcomes. J Stroke. 2016;18:21-30.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 114]  [Cited by in F6Publishing: 140]  [Article Influence: 17.5]  [Reference Citation Analysis (0)]
9.  Guey S, Tournier-Lasserve E, Hervé D, Kossorotoff M. Moyamoya disease and syndromes: from genetics to clinical management. Appl Clin Genet. 2015;8:49-68.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 37]  [Cited by in F6Publishing: 60]  [Article Influence: 6.7]  [Reference Citation Analysis (0)]
10.  Yu S, Zhang N, Liu J, Li C, Qian S, Xu Y, Yang T, Li N, Zeng M, Li D, Xia C. Surgical revascularization vs. conservative treatment for adult hemorrhagic moyamoya disease: analysis of rebleeding in 322 consecutive patients. Neurosurg Rev. 2022;45:1709-1720.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 2]  [Article Influence: 0.7]  [Reference Citation Analysis (0)]
11.  Thabet AM, Kottapally M, Hemphill JC 3rd. Management of intracerebral hemorrhage. Handb Clin Neurol. 2017;140:177-194.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 48]  [Cited by in F6Publishing: 46]  [Article Influence: 6.6]  [Reference Citation Analysis (0)]
12.  Muengtaweepongsa S, Seamhan B. Predicting mortality rate with ICH score in Thai intracerebral hemorrhage patients. Neurol Asia. 2013;18: 131-135.  [PubMed]  [DOI]  [Cited in This Article: ]
13.  Greenberg SM, Ziai WC, Cordonnier C, Dowlatshahi D, Francis B, Goldstein JN, Hemphill JC 3rd, Johnson R, Keigher KM, Mack WJ, Mocco J, Newton EJ, Ruff IM, Sansing LH, Schulman S, Selim MH, Sheth KN, Sprigg N, Sunnerhagen KS; American Heart Association/American Stroke Association. 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2022;53:e282-e361.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 13]  [Cited by in F6Publishing: 332]  [Article Influence: 166.0]  [Reference Citation Analysis (0)]
14.  Blann AD, Landray MJ, Lip GY. ABC of antithrombotic therapy: An overview of antithrombotic therapy. BMJ. 2002;325:762-765.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 85]  [Cited by in F6Publishing: 78]  [Article Influence: 3.5]  [Reference Citation Analysis (0)]
15.  Kim JM, Lee SH, Roh JK. Changing ischaemic lesion patterns in adult moyamoya disease. J Neurol Neurosurg Psychiatry. 2009;80:36-40.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 43]  [Cited by in F6Publishing: 40]  [Article Influence: 2.7]  [Reference Citation Analysis (0)]
16.  Kim DY, Son JP, Yeon JY, Kim GM, Kim JS, Hong SC, Bang OY. Infarct Pattern and Collateral Status in Adult Moyamoya Disease: A Multimodal Magnetic Resonance Imaging Study. Stroke. 2017;48:111-116.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 24]  [Cited by in F6Publishing: 27]  [Article Influence: 3.4]  [Reference Citation Analysis (0)]
17.  Uransilp N, Puengcharoen S, Muengtaweepongsa S.   Medical Management in Moyamoya Disease. London: Intech Open, 2021.  [PubMed]  [DOI]  [Cited in This Article: ]
18.  Larson A, Rinaldo L, Lanzino G, Klaas JP. High prevalence of pro-thrombotic conditions in adult patients with moyamoya disease and moyamoya syndrome: a single center study. Acta Neurochir (Wien). 2020;162:1853-1859.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 11]  [Cited by in F6Publishing: 5]  [Article Influence: 1.3]  [Reference Citation Analysis (0)]
19.  Shulman JG, Snider S, Vaitkevicius H, Babikian VL, Patel NJ. Direct Visualization of Arterial Emboli in Moyamoya Syndrome. Front Neurol. 2017;8:425.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6]  [Cited by in F6Publishing: 6]  [Article Influence: 0.9]  [Reference Citation Analysis (0)]
20.  Jeon C, Yeon JY, Jo KI, Hong SC, Kim JS. Clinical Role of Microembolic Signals in Adult Moyamoya Disease With Ischemic Stroke. Stroke. 2019;50:1130-1135.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 12]  [Cited by in F6Publishing: 17]  [Article Influence: 4.3]  [Reference Citation Analysis (0)]
21.  Pompsch M, Veltkamp R, Diehl RR, Kraemer M. Microembolic signals and antiplatelet therapy in Moyamoya angiopathy. J Neurol. 2022;269:6605-6612.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
22.  Hutayanon P, Muengtaweepongsa S. The Role of Transcranial Doppler in Detecting Patent Foramen Ovale. J Vasc Ultrasound. 2022;47.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
23.  Larovere KL, O’Brien NF.   Applications of Transcranial Doppler Ultrasonography in Sickle Cell Disease, Stroke, and Critical Illness in Children. In: Ziai WC, Cornwell CL, editors. Neurovascular Sonography. Cham: Springer International Publishing, 2022: 291-309.  [PubMed]  [DOI]  [Cited in This Article: ]
24.  Oki K, Katsumata M, Izawa Y, Takahashi S, Suzuki N, Houkin K; Research Committee on Spontaneous Occlusion of Circle of Willis (Moyamoya disease). Trends of Antiplatelet Therapy for the Management of Moyamoya Disease in Japan: Results of a Nationwide Survey. J Stroke Cerebrovasc Dis. 2018;27:3605-3612.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 18]  [Cited by in F6Publishing: 19]  [Article Influence: 3.2]  [Reference Citation Analysis (0)]
25.  Kraemer M, Berlit P, Diesner F, Khan N. What is the expert's option on antiplatelet therapy in moyamoya disease? Results of a worldwide Survey. Eur J Neurol. 2012;19:163-167.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 56]  [Cited by in F6Publishing: 56]  [Article Influence: 4.3]  [Reference Citation Analysis (0)]
26.  Pang CH, Cho WS, Kang HS, Kim JE. Benefits and risks of antiplatelet medication in hemodynamically stable adult moyamoya disease. Sci Rep. 2021;11:19367.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 1]  [Article Influence: 0.3]  [Reference Citation Analysis (0)]
27.  Agarwalla PK, Stapleton CJ, Phillips MT, Walcott BP, Venteicher AS, Ogilvy CS. Surgical outcomes following encephaloduroarteriosynangiosis in North American adults with moyamoya. J Neurosurg. 2014;121:1394-1400.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 21]  [Cited by in F6Publishing: 22]  [Article Influence: 2.2]  [Reference Citation Analysis (0)]
28.  Houkin K, Kamiyama H, Abe H, Takahashi A, Kuroda S. Surgical therapy for adult moyamoya disease. Can surgical revascularization prevent the recurrence of intracerebral hemorrhage? Stroke. 1996;27:1342-1346.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 171]  [Cited by in F6Publishing: 177]  [Article Influence: 6.3]  [Reference Citation Analysis (0)]
29.  Yamada S, Oki K, Itoh Y, Kuroda S, Houkin K, Tominaga T, Miyamoto S, Hashimoto N, Suzuki N; Research Committee on Spontaneous Occlusion of Circle of Willis (Moyamoya Disease). Effects of Surgery and Antiplatelet Therapy in Ten-Year Follow-Up from the Registry Study of Research Committee on Moyamoya Disease in Japan. J Stroke Cerebrovasc Dis. 2016;25:340-349.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 45]  [Cited by in F6Publishing: 49]  [Article Influence: 5.4]  [Reference Citation Analysis (0)]
30.  Zhao Y, Zhang Q, Zhang D, Zhao Y. Effect of Aspirin in Postoperative Management of Adult Ischemic Moyamoya Disease. World Neurosurg. 2017;105:728-731.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 29]  [Cited by in F6Publishing: 30]  [Article Influence: 4.3]  [Reference Citation Analysis (0)]
31.  Zakeri AS, Nimjee SM. Use of Antiplatelet Agents in the Neurosurgical Patient. Neurosurg Clin N Am. 2018;29:517-527.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 3]  [Article Influence: 0.5]  [Reference Citation Analysis (0)]
32.  Schubert GA, Biermann P, Weiss C, Seiz M, Vajkoczy P, Schmiedek P, Thomé C. Risk profile in extracranial/intracranial bypass surgery--the role of antiplatelet agents, disease pathology, and surgical technique in 168 direct revascularization procedures. World Neurosurg. 2014;82:672-677.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 23]  [Cited by in F6Publishing: 26]  [Article Influence: 2.6]  [Reference Citation Analysis (0)]
33.  Onozuka D, Hagihara A, Nishimura K, Kada A, Nakagawara J, Ogasawara K, Ono J, Shiokawa Y, Aruga T, Miyachi S, Nagata I, Toyoda K, Matsuda S, Suzuki A, Kataoka H, Nakamura F, Kamitani S, Nishimura A, Kurogi R, Sayama T, Iihara K; J-ASPECT Study Collaborators. Prehospital antiplatelet use and functional status on admission of patients with non-haemorrhagic moyamoya disease: a nationwide retrospective cohort study (J-ASPECT study). BMJ Open. 2016;6:e009942.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 23]  [Cited by in F6Publishing: 20]  [Article Influence: 2.5]  [Reference Citation Analysis (0)]
34.  Seo WK, Kim JY, Choi EH, Kim YS, Chung JW, Saver JL, Bang OY, Kim GM. Association of Antiplatelet Therapy, Including Cilostazol, With Improved Survival in Patients With Moyamoya Disease in a Nationwide Study. J Am Heart Assoc. 2021;10:e017701.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 26]  [Article Influence: 8.7]  [Reference Citation Analysis (0)]
35.  Ye F, Li J, Wang T, Lan K, Li H, Yin H, Guo T, Zhang X, Yang T, Liang J, Wu X, Li Q, Sheng W. Efficacy and Safety of Antiplatelet Agents for Adult Patients With Ischemic Moyamoya Disease. Front Neurol. 2020;11:608000.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6]  [Cited by in F6Publishing: 6]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
36.  Kim JY, Kim HJ, Choi EH, Pan KH, Chung JW, Seo WK, Kim GM, Jee TK, Yeon JY, Kim JS, Hong SC, Seong MJ, Cha J, Kim KH, Jeon P, Bang OY. Vessel Wall Changes on Serial High-Resolution MRI and the Use of Cilostazol in Patients With Adult-Onset Moyamoya Disease. J Clin Neurol. 2022;18:610-618.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
37.  Chiba T, Setta K, Shimada Y, Yoshida J, Fujimoto K, Tsutsui S, Yoshida K, Kobayashi M, Kubo Y, Fujiwara S, Terasaki K, Ogasawara K. Comparison of Effects between Clopidogrel and Cilostazol on Cerebral Perfusion in Nonsurgical Adult Patients with Symptomatically Ischemic Moyamoya Disease: Subanalysis of a Prospective Cohort. J Stroke Cerebrovasc Dis. 2018;27:3373-3379.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 15]  [Cited by in F6Publishing: 10]  [Article Influence: 1.7]  [Reference Citation Analysis (0)]
38.  Ando S, Tsutsui S, Miyoshi K, Sato S, Yanagihara W, Setta K, Chiba T, Fujiwara S, Kobayashi M, Yoshida K, Kubo Y, Ogasawara K. Cilostazol may improve cognition better than clopidogrel in non-surgical adult patients with ischemic moyamoya disease: subanalysis of a prospective cohort. Neurol Res. 2019;41:480-487.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 9]  [Cited by in F6Publishing: 6]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
39.  Sapra A, Bhandari P, Dix R, Sharma S, Ranjit E. An Interesting Case of Moyamoya Disease, a Rare Cause of Transient Ischemic Attacks. Cureus. 2020;12:e9736.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
40.  Yadav R, Pokhriyal SC, Yadav V, Idries I, Berekashvili K, Panigrahi K, Wasifuddin M. The Role of Dual Antiplatelet Therapy (DAPT) vs Surgery in a Case of Moyamoya Disease: A Case Report and Review of the Literature. Cureus. 2023;15:e39694.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
41.  Research Committee on the Pathology and Treatment of Spontaneous Occlusion of the Circle of Willis; Health Labour Sciences Research Grant for Research on Measures for Infractable Diseases. Guidelines for diagnosis and treatment of moyamoya disease (spontaneous occlusion of the circle of Willis). Neurol Med Chir (Tokyo). 2012;52:245-266.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 566]  [Cited by in F6Publishing: 601]  [Article Influence: 50.1]  [Reference Citation Analysis (0)]
42.  Fujimura M, Tominaga T, Kuroda S, Takahashi JC, Endo H, Ogasawara K, Miyamoto S; Research Committee on Moyamoya Disease (Spontaneous Occlusion of Circle of Willis) of the Ministry of Health, Labor Welfare, Japan;  Guideline Committee 2021 of the Japan Stroke Society. 2021 Japanese Guidelines for the Management of Moyamoya Disease: Guidelines from the Research Committee on Moyamoya Disease and Japan Stroke Society. Neurol Med Chir (Tokyo). 2022;62:165-170.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6]  [Cited by in F6Publishing: 71]  [Article Influence: 35.5]  [Reference Citation Analysis (0)]
43.  Vaccarino V, Horwitz RI, Meehan TP, Petrillo MK, Radford MJ, Krumholz HM. Sex differences in mortality after myocardial infarction: evidence for a sex-age interaction. Arch Intern Med. 1998;158:2054-2062.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 138]  [Cited by in F6Publishing: 138]  [Article Influence: 5.3]  [Reference Citation Analysis (0)]
44.  Scott RM. Surgery for moyamoya syndrome? Yes. Arch Neurol. 2001;58:128-129.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 25]  [Cited by in F6Publishing: 29]  [Article Influence: 1.3]  [Reference Citation Analysis (0)]
45.  Goldenberg NA, Bernard TJ, Fullerton HJ, Gordon A, deVeber G; International Pediatric Stroke Study Group. Antithrombotic treatments, outcomes, and prognostic factors in acute childhood-onset arterial ischaemic stroke: a multicentre, observational, cohort study. Lancet Neurol. 2009;8:1120-1127.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 140]  [Cited by in F6Publishing: 116]  [Article Influence: 7.7]  [Reference Citation Analysis (0)]
46.  Wang Z, Fu Z, Wang J, Cui H, Zhang Z, Zhang B. Moyamoya syndrome with antiphospholipid antibodies: a case report and literature review. Lupus. 2014;23:1204-1206.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 12]  [Cited by in F6Publishing: 12]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
47.  Chen H, Jiang X, Shi Y, Yuan F, Hu Z. Systemic sclerosis associated with moyamoya syndrome: A case report and literature review. Immunobiology. 2020;225:151882.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 1]  [Article Influence: 0.2]  [Reference Citation Analysis (0)]
48.  Jabbour R, Taher A, Shamseddine A, Atweh SF. Moyamoya syndrome with intraventricular hemorrhage in an adult with factor V Leiden mutation. Arch Neurol. 2005;62:1144-1146.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 1]  [Article Influence: 0.1]  [Reference Citation Analysis (0)]
49.  . Correction to: Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019;50:e440-e441.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 38]  [Cited by in F6Publishing: 33]  [Article Influence: 6.6]  [Reference Citation Analysis (0)]
50.  Lokeskrawee T, Muengtaweepongsa S, Patumanond J, Tiamkao S, Thamangraksat T, Phankhian P, Pleumpanupatand P, Sribussara P, Kitjavijit T, Supap A, Rattanaphibool W, Prisiri J. Prognostic Parameters for Symptomatic Intracranial Hemorrhage after Intravenous Thrombolysis in Acute Ischemic Stroke in an Asian Population. Curr Neurovasc Res. 2017;14:169-176.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 4]  [Cited by in F6Publishing: 4]  [Article Influence: 0.6]  [Reference Citation Analysis (0)]
51.  Ma Y, Zhao M, Deng X, Zhang D, Wang S, Zeng Z, Zhang Q, Zhao J. Comparison of clinical outcomes and characteristics between patients with and without hypertension in moyamoya disease. J Clin Neurosci. 2020;75:163-167.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 3]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
52.  Hirano Y, Miyawaki S, Imai H, Hongo H, Ohara K, Dofuku S, Teranishi Y, Nakatomi H, Saito N. Association Between the Onset Pattern of Adult Moyamoya Disease and Risk Factors for Stroke. Stroke. 2020;51:3124-3128.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 17]  [Cited by in F6Publishing: 28]  [Article Influence: 7.0]  [Reference Citation Analysis (0)]
53.  James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC Jr, Svetkey LP, Taler SJ, Townsend RR, Wright JT Jr, Narva AS, Ortiz E. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507-520.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5429]  [Cited by in F6Publishing: 5299]  [Article Influence: 529.9]  [Reference Citation Analysis (0)]
54.  Meschia JF, Bushnell C, Boden-Albala B, Braun LT, Bravata DM, Chaturvedi S, Creager MA, Eckel RH, Elkind MS, Fornage M, Goldstein LB, Greenberg SM, Horvath SE, Iadecola C, Jauch EC, Moore WS, Wilson JA; American Heart Association Stroke Council;  Council on Cardiovascular and Stroke Nursing;  Council on Clinical Cardiology;  Council on Functional Genomics and Translational Biology;  Council on Hypertension. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:3754-3832.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1049]  [Cited by in F6Publishing: 973]  [Article Influence: 97.3]  [Reference Citation Analysis (0)]
55.  Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, Fang MC, Fisher M, Furie KL, Heck DV, Johnston SC, Kasner SE, Kittner SJ, Mitchell PH, Rich MW, Richardson D, Schwamm LH, Wilson JA; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160-2236.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2779]  [Cited by in F6Publishing: 2837]  [Article Influence: 283.7]  [Reference Citation Analysis (0)]
56.  Church EW, Bell-Stephens TE, Bigder MG, Gummidipundi S, Han SS, Steinberg GK. Clinical Course of Unilateral Moyamoya Disease. Neurosurgery. 2020;87:1262-1268.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 10]  [Article Influence: 2.5]  [Reference Citation Analysis (0)]
57.  Wang QN, Bao XY, Zou ZX, Wang XP, Zhang Q, Li DS, Zhao YQ, Duan L. The role of atorvastatin in collateral circulation formation induced by encephaloduroarteriosynangiosis: a prospective trial. Neurosurg Focus. 2021;51:E9.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 3]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]