A Practical Questionnaire and Literature Review: Dose Suzuki Grading Still the Gold Standard for the Diagnosis of Moyamoya Disease?


 The traditional grading method of moyamoya disease represented by Suzuki grading system has always been the gold standard for most neurosurgeons in the diagnosis of moyamoya disease. However, in recent years, more and more studies have raised questions about Suzuki grading. The purpose of this study is to describe and summarize the questions raised about the Suzuki grading and reconsider its authority, using a questionnaire and literature review. The questionnaire showed that 73.61% of neurosurgeons had questioned the Suzuki grading, among which the main problems included "unclear boundaries between grades" and "inconsistent grading between the left and right cerebral hemispheres". From December 1969 to March 2021, 105 of the 773 references raised the same questions as in the questionnaire, and 27 of the 773 references raised different questions. Some of the questioned studies hope to take multiple imaging methods into consideration for grading of moyamoya disease, and some of the studies hope to include more quantifiable imaging indicators and establish a new grading system for moyamoya disease. In summary, the clinical utility of the Suzuki grading has been questioned by most neurosurgeons and some researchers, part of the research put forward some pertinent opinions.


Introduction
Moyamoya disease (MMD) is a chronic progressive cerebral arterial ischemic disease characterized by progressive stenosis or unilateral or bilateral occlusion of the internal carotid artery and uncontrolled compensatory proliferation of "cloud" vessels (Shang, Zhou et al. 2020). Its etiology is not yet clear. The Since Suzuki grading was proposed by Suzuki et al in the 1960s, it has gradually become the main means for neurosurgeons around the world to diagnose and classify MMD. According to the change characteristics of internal and external carotid arteries in patients with MMD in digital subtraction angiography (DSA), as well as the characteristic changes of vascular network in the brain base, patients with MMD were divided into six stages by Suzuki stage (Suzuki and Takaku 1969). Although DSA is the gold standard for the diagnosis and grading of MMD, the familiarity of neurosurgeons with MMD and their understanding of Suzuki grading also affect the nal diagnosis and treatment results. There has not been a comprehensive summary of the questions raised about the Suzuki grading system, nor has there been a summary of the better suggestions for these questions. The purpose of this study is to observe the subjective impression and application of Suzuki grading system by clinicians in various professional elds through a questionnaire survey, and to review the recent studies that questioned Suzuki grading or proposed new grading methods for MMD.

Survey Design
From February to June 2020, physicians from Beijing Tiantan Hospital, Peking Union Medical College Hospital, Peking University Hospital, and other large hospitals with high authority in the eld of neurosurgery were invited to complete an online survey. The survey was prepared and published through a web-based anonymous survey platform (WJx.cn). The interviewees were mainly Chief Surgeon, Attending Surgeon, Resident, Continuing Doctor or Master/PhD candidate. This survey will focus on the responses of neurosurgeons in various specialties, including those specializing in cerebrovascular diseases or neurointerventional therapy, and other neurosurgical elds. In order to accurately locate and classify the respondents, we set a series of basic information questions, including respondents' age, familiarity with MMD/Suzuki grading, subjective impression of MMD/Suzuki grading and so on. In the main part of this study, seven groups of DSA image data of patients with MMD were set and the options from Level 1 to Level 6 were set. The judgments made by neurosurgeons in various professional elds were mainly observed. In addition, in order to guarantee the validity of the paper, we will be the rst problem set grading tests suzuki access standards for testing, (Fig. 1), from the perspective of DSA images, visible: the end of the internal carotid artery occlusion, cerebral artery and middle cerebral artery imaging before bad, skull base (circulating blood vessels) and posterior circulation obvious smoke sample blood vessels. The above signs were in line with the characteristics of Suzuki grading level 3 and 4, and were veri ed by Dr. Wang and Dr. Qin to determine (Shang, Zhou et al. 2020, Suzuki andTakaku 1969). (Table 1)

Selection Criteria
The rst question in the Suzuki grading test is the inclusion criteria of the questionnaire, which is very representative. The purpose of this question is to test the basic ability of the subjects to diagnose MMD. The images showed that this case had characteristic signs of terminal internal carotid artery stenosis/occlusion, poor imaging of the anterior and middle cerebral arteries, and obvious smoky vessels in the skull base. According to the Suzuki grading, this question is the standard Grade 3 sign of MMD, and may be Grade 4. We have eliminated the failed answers to the standard questions. (Fig. 1)

Search Strategy
In this study, all original articles, literature reviews, case reports and letters to editors on PubMed and Google Scholar regarding grading methods of MMD were retrieved. In addition, the literature retrieved and its references or reviews were screened. Key words: "MMD/MMD grading", "suzuki grading", "MMD/MMD" (phrase or combination

Results
The questionnaire survey Our questionnaire was sent to clinicians in more than ten authoritative neurosurgery hospitals in China, and 466 valid questionnaires were collected. Those with excessive deviation were removed as not meeting the admission criteria of Suzuki grading test, and then we obtained a total of 341 Suzuki grading test answers. There was no signi cant difference in the frequency of use of Suzuki grading among specialized elds P>0.05 . In terms of subjective impression, most of the respondents have questioned the Suzuki grading (73.61%). The most focused questions is "Boundaries between unknown at all levels" 67.33% and "Grade of the brain hemispheres appear inconsistent" 52.99% . Table2   Suzuki grading test     The interobserver reliability of the questionnaire results Most neurosurgeon want to work through the use of a variety of clinical grading suzuki, such as "condition" (61.88%), "diagnosis MMD" (61.29%), there are more than half of the neurosurgeon will suzuki grading for "academic discussion" (57.60%), which can be good, traditional classi cation methods of MMD, seems to be no need for the "gold standard" too much to discuss.
However, our survey results show that most neurosurgeons (73.61%) have questioned the Suzuki grading, the focus of which is "unclear boundaries between grades" and "inconsistent grading between the left and right We set the Suzuki grading test questions, no one question answer more than half of the respondents choose.
As can be seen from Figure 2 and Figure 3, since there is no clear quantitative standard, most interviewees can hardly distinguish the degree of posterior cerebral circulation stenosis in cases 2, 4 and 7. Therefore, when interviewees judge Suzuki grading in cases 2, 4 and 7, there is almost no difference between grade 4 and grade 5.Similarly, the Suzuki grading did not clearly quantify the extent of the proliferation and dissipation of smoky blood vessels. In cases 3 and 6, it was also di cult for respondents to make a judgment on levels 3 and 4.

(Fig2\Fig3)
The purpose of setting up the access question is to include a questionnaire of subjects with basic diagnostic ability of MMD. The imaging ndings presented in this topic were highly consistent with the Suzuki grading's Level 3 de nition, and subjects only needed to identify poorly developed anterior cerebral arteries, middle cerebral arteries, and su ciently signi cant smoky vessels. However, in the original summary of the questionnaire results, only less than 50% of the 466 respondents chose Level 3, and no less than 30% of the respondents believed that it met the de nition of Level 4.The fourth and seventh test questions we set showed almost the same signs as the access question, with no more than half of the respondents choosing level 3.
Obviously, because there is no clear quantitative standard for Suzuki classi cation, the degree of hyperplasia of smoky blood vessels and the degree of internal carotid artery branch stenosis cannot be accurately assessed. Perhaps this is why the answers to our quiz questions are so widely distributed. (Table3) Literature review of grading methods for MMD Among the numerous literatures, the questions raised by researchers on the traditional grading methods of MMD have a high coincidence with the results of our questionnaire. "unclear boundaries between grades" and "inconsistent grading between the left and right cerebral hemispheres", the former more re ected in our literature review, most of the research puts forward a new grading method were think traditional grading methods for MMD, lack of quanti able indicators to grading of imaging signs, these studies are also by introducing a new concept or imaging methods, rebuilding or improving grading system, most of their point of view has been clinical test and verify. Studies that review one hemisphere as a unit also raise the same questions that we found. Most of them use double-blind case reviews conducted by senior experts to make it easier to diagnose and grade both hemispheres as a whole(Table5). We found that neurosurgeons of different ages and elds of expertise had little difference in grading cases using the Suzuki grading system(P>0.05), but there were signi cant differences in questions raised by neurosurgeons of different ages(P<0.05). Therefore, we believe that there is little difference in the level of knowledge of the Suzuki grading method among the broad neurosurgeon community, perhaps because of the defects in the Suzuki grading system itself.
Our literature review also shows that there are more studies suggest that the traditional grading method of MMD clinical practicability, lack of the practical mainly includes: analysis of prognosis, explain the illness, to predict risk factors, our investigation, according to the results of clinical application, is the purpose of the neurosurgeon use grading system, perhaps the traditional grading methods for MMD don't have advantage and authority in this eld. With the development of imaging technology, many researchers are not satis ed with only using a single, nonlinear method that cannot re ect hemodynamic changes to diagnose such a complex and progressive disease as MMD ( grading system, is considered the beginning of the design may appear "the brain hemispheres inconsistent grading", only to begin the design idea is better than the two hemispheres as a uni ed whole, more importantly, the study may be rst consider differences in the incidence of target population, when as an object in the study to east Asian patients with MMD validation to make the corresponding changes ( Most neurosurgical clinicians routinely use DSA and MRI as the diagnosis and grading means of MMD.
However, studies in recent years have shown that the use of multimodal imaging means can enable clinicians to obtain more risk prediction information, and can also better summarize the pathogenesis factors and symptoms of MMD. Based on noninvasive arterial and venous phase, for example, CTP -Sis of MMD grading system, not only has the advantage of noninvasive, convenient, and in the evaluation of unilateral MMD in or out of the blood group MMD has the superiority, such research, with the help of the collateral vessels in blood both in arterial and venous phase ow more slowly, and is veri ed with the help of the DSA technique and revision, with lower layers spiral CT scanner to rapid and continuous scanning, nally to difference in the level of regional cortical blood vessels are damaged, the damaged brain hemispheres are divided into more

Limitations and disadvantages
Our questionnaire distribution scope is relatively limited, 341 of the answers passed the admission question we set , which seems a little weak for a large population of MMD like China. However, neurosurgeons especially full-time neurosurgeons in the eld of cardiovascular disease, even in China is very few, and, this survey focused by many authoritative hospital neurosurgery almost covers all over the world the highest incidence of MMD area, namely the northern coastal areas and the central plains region, this greatly reduced the investigation and research of sampling error and system error. We did not validate the new grading methods or improved methods in the literature review, and the validation methods in the literature only included prospective validation on a small grading and sample size. Therefore, we cannot completely abandon the traditional grading method of MMD, nor can we completely apply the new grading method independently.

Conclusion
In conclusion, the clinical utility of the Suzuki grading system has been questioned by most Chinese neurosurgeons and a growing number of researchers. Questions have focused on the lack of strict grading standards and the lack of meeting speci c clinical requirements. Comprehensive reference to more advanced or non-invasive imaging examination methods can better diagnose and grade MMD. The diagnostic e ciency of MMD can be improved by de ning more quanti able imaging signs.

Con icts of interest
The authors declare that they have no competing interests.

Availability of data and material
Data and material not provided in the article will be shared at the request of other investigators for purposes of replicating procedures and results. For data access, researchers can contact corresponding author.  The rst question in the Suzuki grading test is the inclusion criteria of the questionnaire, which is very representative.

Figure 3
Suzuki grading test