lNTRODUCTlON

Brain arteriovenous malformation (AVM) is one of the main causes of spontaneous cerebral hemorrhage in children[1] and accounts for 30%-50% of spontaneous cerebral hemorrhage in children[1,2]. It is generally believed that AVM is a kind of congenital vascular disease[3]. The abnormality is formed in the third to fourth week of embryonic development, when the length is about 40-80 mm, during the process of cerebrovascular development and manifests as abnormal coiled and interlaced vascular clusters[4]. Arteries and veins are directly connected by malformed vascular clusters. At present, the mechanism of the occurrence and development of AVM is not clear, and there have been very few case reports that have documented the progression of abrain AVM[5-7]. Here, we have documented for the first time a case of a child with abrain AVM that progressed and ruptured twice within 6 years. We have also reported for the first time the potential role of heterozygous mutations in thegene in the pathogenesis of AVM.

CASE PRESENTATlON

Chief complaints

A 15-year-old boy was admitted to the hospital in November 2019 with complaints of an acute headache for 3 h.

The boy had normal growth and development and no history of other special diseases. In August 2011,the child presented at another hospital with complaints of a headache for more than 1 wk. At that time,magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and magnetic resonance venography (MRV) were performed. The scans revealed that there was no vascular abnormality,abnormal signal intensity, or any other findings suggestive of an AVM (Figure 1A-C). At that time, the doctor did not administer any treatment, and the headache was ameliorated by itself. In October 2013,the child again presented at another hospital with headache and nausea for 2 d. His MRA scan revealed a small right temporal AVM, the size of which was 6.2 mm × 1.9 mm (Figure 1C). Digital subtraction angiography revealed the presence of a suspicious lesion in the right temporal lobe (Figure 1D). The boy was treated for headaches and was not examined further. In February 2019, the boy presented at our hospital complaining of a sudden headache and vomiting for 2 h. He was conscious when he came to our hospital. His Glasgow coma scale score was 14, and National Institutes of Health Stroke Scale score was 1. Computed tomography of the head demonstrated acute intracerebral hemorrhage in the right temporal lobe. The MRA revealed a small AVM in the right temporal lobe (Figure 1E). Symptomatic treatment was given to the child during hospitalization, and gamma knife radiosurgery was suggested.Unfortunately, the child’s parents rejected radiotherapy.

History of present illness

[3] 吳擁政,何 杰,司林坡,等.義馬礦區(qū)深部礦井地應(yīng)力分布規(guī)律研究[J].煤炭科學(xué)技術(shù),2018,46(10):16-21.

History of past illness

你說什么都白搭。你根本不可能說服我，一點希望也沒有。西雙攤開兩手，說，她病了，我去看她，這件事就算完了。她以后再有什么事，都與我無關(guān)……如果你想把這頓飯吃得不痛快，你就繼續(xù)勸我，我反正充耳不聞。不過，如果你能讓我安安靜靜把這頓飯吃完，我會很感激你。

Personal and family history

通過飽和砂巖流固耦合蠕變試驗，簡單描述了砂巖在不同孔隙水壓蠕變變形的特性及變形破壞所需時間，根據(jù)改進(jìn)后Druck-Prager屈服函數(shù)求出巖石蠕變本構(gòu)模型，并在此基礎(chǔ)上進(jìn)一步推導(dǎo)三維狀態(tài)下本構(gòu)方程，得到了4條結(jié)論。

Physical examination

The patient was conscious when examined at our hospital in November 2019. His Glasgow coma scale score was 15 and his National Institutes of Health Stroke Scale score was 1.

Laboratory examinations

We thank the Department of Neurosurgery and the Department of Radiology of The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University for the diagnosis and treatment of the patient.

Imaging examinations

A small AVM within the right temporal lobe was visualized in the MRA (Figure 1G), and cerebral angiogram revealed the presence of a 21.6 mm × 21.2 mm right temporal AVM, which was supplied by the inferior temporal branches of the right posterior cerebral artery. Venous drainage occurred through superficial cerebellar veins into the right sigmoid sinus. It was classified as Spetzler-Martin grade 1(Figure 1H).

In November 2019, computed tomography of the head demonstrated the presence of an acute intracerebral hemorrhage in the right temporal lobe (Figure 1I). Digital subtraction angiography displayed abnormal vascular clusters, which were slightly larger than those seen 10 mo ago. The size of these clusters was 24.3 mm × 22.8 mm. The AVM was classified as a Spetzler-Martin grade 1 (Figure 1J).

Further diagnostic work-up

After receiving consent from the child’s parents, we conducted genetic analysis for the child and his parents. We discovered a mutation that might be related to the incidence of AVM,heterozygous mutation [NM_024408.3; c.1418A＞T; p.Asp473Val]. The mutation was only found in the child.

FlNAL DlAGNOSlS

Brain AVM, Spetzler-Martin grade 1.

制定規(guī)范與流程[8] 實驗室依據(jù)國家和學(xué)校相關(guān)制度制定并頒布院級儀器設(shè)備開放共享暫行辦法、儀器設(shè)備開放共享收費標(biāo)準(zhǔn)、儀器設(shè)備開放預(yù)約實驗指南、校內(nèi)轉(zhuǎn)賬流程等。開放共享初期對放置在各大實驗室的儀器設(shè)備強行開放共享，鼓勵放在各個課題組教師實驗室的10萬元以上的大型儀器設(shè)備開放共享，采取自愿原則。

TREATMENT

The parents refused to conduct further interventional treatment. Supportive treatment was administered during the hospitalization period, and the boy was discharged after 10 d in good clinical condition.

The patient underwent MRI, MRA, and MRV scans in August 2011, at the age of 5 years and 2 mo for nonspecific headaches. No abnormal vascular lesions or secondary signs of brain AVM were observed.A brain AVM was first identified in October 2013. Bleeding occurred for the first time in February 2019 and occurred again in November 2019. The malformed vascular clusters progressed significantly during this period. No risk factors were associated with AVM in this case. Literature review revealed that most of the reported AVM cases had underlying pathology, and only a few of them had no cause ofAVM[5,8]. Our case report is the first to define the progression and eventual rupture within 6 years following its primary discovery. We also report for the first time that heterozygous mutations in thegene might be playing a role in the pathogenesis of AVM.

OUTCOME AND FOLLOW-UP

The clinical condition of the child was good during the final follow-up, which was performed on January 2021. The child was in good general condition at the time. After January 2021, he was lost to follow-up.

DlSCUSSlON

原因何在？我們可以從平頂山環(huán)境污染防治攻堅戰(zhàn)領(lǐng)導(dǎo)小組辦公室印發(fā)的一份通知中得到答案。該通知針對改善空氣質(zhì)量共提出了25項重點任務(wù)，其中涉及“科學(xué)規(guī)劃營運加油站點”：要求6月底前，市內(nèi)四個國控空氣質(zhì)量自動監(jiān)測站點周邊2公里范圍內(nèi)營運加油站完成選址搬遷……搬遷前，即日起范圍內(nèi)加油站營業(yè)時間改為每日19時至次日8時。

Currently, the pathogenesis of brain AVM is not clearly understood. The imbalance of some signal molecules during embryonic development is believed to be the most likely reason for no capillary formation between the arteries and veins[9]. This balance is dependent on the strict regulation of various angiogenic factors, and any interference for these automatic regulation factors may lead to the formation of AVM[10,11]. There was no high-risk factor for AVM in this case, and the only high-risk factor that may have a relation in the development of AVM was the heterozygous mutation of thegene. The NOTCH2 protein is the receptor of the Notch signaling pathway, and its activity can directly affect Notch signaling[12]. However, the Notch signaling pathway has complex and contextdependent effects on angiogenesis[13,14]. Studies have demonstrated that abnormal activation of Notch signaling in human brain AVM was associated with AVM bleeding[15]. The inhibition and activation of Notch signaling were both associated with AVM formation. The mutation in this case (p.Asp473Val)was first described by Gilbert[16]. The mutation is located in exon 8, and exon 8 encodes the epidermal growth factor-12 domain of[16,17]. Unfortunately, there has been no research on the effect of this mutation on the function of the NOTCH2 protein.

在調(diào)整糧食統(tǒng)計口徑數(shù)據(jù)出臺之前，要完成原口徑糧食統(tǒng)計歷史數(shù)據(jù)的調(diào)整工作，確保統(tǒng)計口徑調(diào)整前后數(shù)據(jù)之間的銜接性和連續(xù)性，避免出現(xiàn)調(diào)整前后數(shù)據(jù)出現(xiàn)“斷崖”。在調(diào)整過程中，要核實各省(直轄市、自治區(qū))統(tǒng)計數(shù)據(jù)與國家統(tǒng)計數(shù)據(jù)長期存在的數(shù)據(jù)差異情況，盡量減小差異，保證國家與各省(直轄市、自治區(qū))之間數(shù)據(jù)的銜接性。

CONCLUSlON

We report for the first time a case ofAVM formation in a child, which progressed and eventually ruptured within 6 years. Our case contests the traditional view that brain AVM is congenital, and our case once again confirms the view that brain AVM is an acquired disease that is the result of an interaction of genes, environment, and molecules.

The child presented with a sudden severe headache for 3 h with no inducing factors. He was conscious and had no history of nausea, dizziness, or fever.

ACKNOWLEDGEMENTS

Laboratory examinations showed no significant abnormality.

FOOTNOTES

Li DD was in charge of case review and preparation of the manuscript; Huang H, Wang X, Guo AN, and Li W collected clinical opinions regarding this case and drafted the manuscript; Duan RH, Fang JH, and Yin B participated in the coordinating the manuscript; Huang H and Li DD revised the manuscript; All authors read and approved the final manuscript.

the Science and Technology Program of Wenzhou, China, No. Y20190145 to Huan Huang; and the Beijing New Health Industry Development Foundation, No. XM2020-02-002 to Bo Yin.

Written informed consent was obtained from the patient’s parents.

The patient did not have any personal or family history of brain AVM.

The authors declare there are no conflicts of interest.

The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

一篇教育類文章中有這樣一段話：“美國式的教育注重培養(yǎng)學(xué)生的開放型思維和質(zhì)疑精神，鼓勵學(xué)生質(zhì)疑他們所學(xué)到的東西，但是忽略了基礎(chǔ)知識的傳授；中國學(xué)生則具備扎實的理論基礎(chǔ)，踏實嚴(yán)謹(jǐn)?shù)那髮W(xué)態(tài)度，但在開放型思維和獨立思考的能力方面還有一定欠缺。”在此，我不對中美教育進(jìn)行評論，也不對中國的教育進(jìn)行批判，只想從自己的教育工作入手，思考一個與語文教學(xué)相關(guān)的問題：如何在語文教學(xué)中培養(yǎng)學(xué)生的質(zhì)疑精神。

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 BYNC 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 noncommercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

China

Huan Huang 0000-0001-8842-2424; Xue Wang 0000-0001-6178-6316; An-na Guo 0000-0003-3631-1401;Wei Li 0000-0002-3401-0077; Ren-Hua Duan 0000-0003-2776-7060; Jun-Hao Fang 0000-0002-1395-0756; Bo Yin 0000-0002-5487-0197; Dan-Dong Li 0000-0003-4973-8818.

該量表由我國學(xué)者叢中、高文鳳[20]編制，共16個項目，包括自我評價與自我接納兩個因子.量表總分越高,自我接納程度越高；反之越低.自我接納和自我評價兩因子的內(nèi)部一致性系數(shù)分別為0.93和0.91，重測信度為0.76.

Gong ZM

Filipodia

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