lNTRODUCTlON

Immunoglobulin G4 related disease (IgG4-RD) was initially noticed in patients with autoimmune pancreatitis in 2001 and formally named in 2010, classified as sarcoidosis with different manifestations in several organs and the same pathological characteristics[1,2]. The main characteristic of IgG4-RD is elevated levels of serum IgG4. Moreover, the lesions are often tumescent with abundant IgG4-positive plasma cells and fibrosis. Such inflammatory lesions can be seen in the pancreas, kidney, lungs, salivary glands, and other organs. Specifically, the conditions of IgG4-RD in the central nervous system are meningitis and hypophysitis[3]. As for the IgG4-related hypertrophic pachymeningitis (IgG4-RHP), the clinical and imaging manifestation is similar to that of meningioma, posing a challenge for preoperative diagnosis[4,5]. Additionally, the time and scope of operation should be considered carefully. Finally,this disease is related to some bacterial infections, such as tuberculosis. And we need to weight the pros and cons between these infections and corticosteroid therapy for IgG4-RD. Herein, we report a rare case with IgG4-RHP at the clivus area mimicking meningioma and discuss the relevant literature.

CASE PRESENTATlON

Chief complaints

A 40 year-old man was admitted for headache, bilateral temporal visual field defect, and limited abduction in both eyes.

History of present illness

Five years before the present admission, the patient started to experience discontinuous and aggravating headache. Owing to symptomatic deterioration, the patient was admitted to the neurology department of a local hospital. Because the patient also had a history of pulmonary tuberculosis, he was suspected of having tuberculosis meningitis and treated with anti-tuberculosis drugs at the local hospital. However, the symptom did not alleviate. Upon presentation to our hospital, the patient underwent a brain magnetic resonance imaging (MRI) scan that showed the presence of a clival lesion measuring 2.6 × 1 cmwith isointense signal on T1-weighted (T1WI) and T2-weighted (T2WI) imaging;accordingly, he was diagnosed with meningioma. The lesion was homogenously enhanced on contrast MRI with a dural tail sign (Figure 1). Because there was no cranial nerve function defect, the patients chose to undergo Gamma Knife Surgery at a dose of 11 Gy at the 45% isodose line, and regular followup was planned.

History of past illness

The patient had suffered from pulmonary tuberculosis 11 years ago and accepted standard antituberculosis treatment for 1 year.

Case 1.The two sources exhibit both uniform distribution.

Personal and family history

No other particular personal and family history was reported.

Physical examination

This patient showed right abducens paralysis, hoarse voice, bitemporal hemianopsia, and slight swallowing difficulty. No other positive signs were found.

Laboratory examinations

Lumbar puncture was performed and we found that the number of karyocytes (mainly mononuclear cells) and protein levels in cerebrospinal fluid had risen (Table 1).

After pathological results showed IgG4-RD, further systemic evaluation was performed to find other lesions associated with IgG4-RD. The serum IgG level was 17.20 g/L (reference range: 8.00-15.50 g/L),and the serum level of IgG4 was 1.90 g/L (reference range: 0.035-1.500 g/L). Tuberculosis associated gamma interferon release assay showed positive results with TB-IGRA (T-N) at 414.21 pg/mL.

Imaging examinations

After admission, routine laboratory testing and preoperative preparation were carried out. A repeat brain MRI scan showed that the lesion became larger, measured 3.8 cm × 2.9 cm × 2.9 cm, and compressed the adjacent brain stem (Figure 1). Further, small pneumatoceles in the upper lobe of the right lung were detected by thorax computed tomography (CT). Moreover, the examination of visual field confirmed binocular hemianopia (Figure 2). No other positive results were found.

由表4數(shù)據(jù)可以看出，銣和鈮鉭在各粒級中分布大致上是均勻的，沒有相對富集的情況，據(jù)此可以認(rèn)為銣和鈮鉭均勻地分布于各粒級中。

FlNAL DlAGNOSlS

The postoperative pathology confirmed the proliferation of fibrous tissue accompanied by numerous lymphocytes and plasma cells, which is displayed in Figure 3. Immunohistochemical staining showed positive results for CD138 and IgG4. Gene rearrangement test showed negative results for IgH. Thus,IgG4-RD was finally diagnosed.

長江之旅，穩(wěn)居大江之上，睥睨兩岸風(fēng)光，乘風(fēng)破浪前行。貴州西洋也正攜手優(yōu)秀經(jīng)銷商，順應(yīng)肥料行業(yè)發(fā)展浪潮，積極抓住機(jī)遇、應(yīng)對挑戰(zhàn)，向著助力中國農(nóng)業(yè)發(fā)展、實(shí)現(xiàn)企商共贏、成就中國復(fù)合肥“航母”企業(yè)的廣闊海天劈波斬浪不斷前進(jìn)。

TREATMENT

?OECD，Competitive Neutrality:Maintaining a level playing field between public and private business，Paris:OECD Publishing，2012，p．53．

For the diagnosis of IgG4-RD, solu medrol was administrated at a dose of 80 mgday, and methotrexate was administrated at 10 mg every week. Famotidine, calcium carbonate, and vitamin D3 tablets were prescribed against adverse reactions during the treatment. After discharge from the hospital, the solu medrol was tapered over 4 wk to 50 mgday.

OUTCOME AND FOLLOW-UP

The purpose of the operation was not only to perform a biopsy but also to alleviate symptoms. We know that the lesion would stretch meninges and then cause headache. Similarly, the lesion compresses cranial nerves to cause relevant symptoms. The resection can reduce meningeal tension, release compression, and finally alleviate headache and nerve deficits. Further, it is suitable to use the transnasal endoscopic approach for a clival lesion in IgG4-RHP. When the lesion is too broad to remove completely, it is sensible to leave some parts in order to maintain the integrity of the dura mater, which can prevent severe complications such as cerebrospinal fluid leakage and intracranial infection.

設(shè)備安裝完成使用至今，基本實(shí)現(xiàn)了橋吊大車與集卡車輛的定位系統(tǒng)、橋吊遠(yuǎn)程監(jiān)控系統(tǒng)、橋吊遠(yuǎn)程操控系統(tǒng)、碼頭入口閘機(jī)與集卡旋鎖聯(lián)動系統(tǒng)功能，達(dá)到了橋吊遠(yuǎn)程智能化操控的目標(biāo)，基本達(dá)到了預(yù)期效果。待改進(jìn)完善后，可進(jìn)一步推廣使用。同時建議開展橋吊小車定位系統(tǒng)的開發(fā)研究。

DlSCUSSlON

傳統(tǒng)的假日購物季通常從黑色星期五開始，即感恩節(jié)第二天，然后一直持續(xù)至圣誕節(jié)。在這期間，零售商會打折，購物者則去尋找禮物、在商店排隊、匆忙跑過通道以獲得最佳優(yōu)惠。這是以前的常態(tài)，當(dāng)然在一些地區(qū)現(xiàn)在仍是常態(tài)，不過由于百貨店和在線零售商不斷更改折扣日期，在很多地方，購物季早在感恩節(jié)之前便已經(jīng)開始，而且成為動態(tài)事件，沒有固定的日期。

IgG4-RD of the CNS is mainly related to IgG4-related hypertrophic pachymeningitis and hypophysitis. Among them, IgG4-RHP is relatively rare, with the primary clinical manifestation of headache and other nerve function disabilities. Moreover, it was apparent that the cranial nerve function could partially recover once the disease was in remission. At the first onset of the disease,multi-organ disease is not widespread (57%)[6]. Therefore, regular follow-up and systemic evaluation is crucial.

2.2.1 師德水平 有的教師師德缺失，對待學(xué)生態(tài)度不端正，甚至辱罵、體罰學(xué)生，這必然導(dǎo)致師生關(guān)系緊張甚至對立。有些教師偏護(hù)優(yōu)秀學(xué)生，對“差生”態(tài)度差，甚至冷嘲熱諷或置之不理，使“差生”產(chǎn)生心理陰影。有些教師上課不嚴(yán)格要求自己，做不到為人師表，難以樹立威信；有些教師備課不認(rèn)真，消極怠工，舉止粗俗，使得一些學(xué)生消極模仿或厭惡排斥。

Through this case, we summarize the differential diagnoses of IgG4-RHP, such as meningioma,tuberculosis meningitis, fungal meningitis, and metastatic tumor. Furthermore, the complete MRI images showed the lesion alteration during treatment. However, there are limited reports of this rare disease in the literature. Higher evidence-based studies are needed to promote the diagnosis and treatment of IgG4-RHP.

Other diseases, such as metastatic tumors and fungal infections, should also be considered. It was observed that metastatic tumors could spread and proliferate along the meninges, causing various severe symptoms. In this situation, the history of malignant tumor provided clues to the diagnosis.Likewise, a CNS fungal infection can show similar features, which can be identified by examining the cerebrospinal fluid.

Measuring the serum concentration of IgG4, radiological examination, and pathological screening are important for diagnosis. It is difficult to distinguish IgG4-RHP and meningioma before the operation and pathologic examination. The serum level of IgG4 can facilitate diagnosis, but it does not always show an increase. As reported by Wallace[12], the sensitivity and specificity of serum IgG4 were 90% and 60%, respectively. Moreover, the negative predictive value and positive predictive value of the serum IgG4 assay were 96% and 34%, respectively, which could be helpful and convenient to exclude the diagnosis of IgG4-RD related to the CNS[12]. It is also helpful to distinguish tuberculosis and IgG4-RD based on the fact that serum IgG4 does not significantly increase in tuberculosis[13]. Further,imaging results could be a crucial clue for preoperative diagnosis. Lumbar puncture provides the necessary information for differentiation from CNS infections and malignant tumors. IgG4 levels in cerebrospinal fluid have been reported to be elevated[14]. However, the concentration of IgG4 in cerebrospinal fluid could not distinguish this disease from other inflammatory pachymeningitis[6].

The patient underwent transnasal endoscopic approach resection which aimed to partially remove the lesion for pathology analysis and alleviate the headache caused by meningeal tension. During the operation, we found that the lesion extended to the sphenoid sinus and nasopharynx without a clear boundary. Notably, the local mucosa was edematous and tight. The clivus bone had been partially damaged, and the clivus epidural was thicker. The intraoperative frozen section examination revealed the proliferation of spindle cells accompanied by many lymphocytes and plasma cells.

Radiology examination plays an essential role in diagnosis. The lesion could be observed as linear dural thickening or a bulging mass. The linear dural thickened lesion appears both in the brain and spine. The tumoral lesion is frequently located in the clivus area. The heterogeneity was observed on MRI because of active inflammation. Typically, T1WI MRI would exhibit a hyperintense or isointense signal. Hypertrophic pachymeningitis usually shows thickening meninges and hypointensity on T2WI MRI, while it would become relative hyperintense when the inflammation aggravates[3,4,6,7,15]. The lesion would be homogenously enhanced on enhanced MRI. In this case, the lesion showed an isointensite signal on T1WI and T2WI and was homogenously enhanced on contrast MRI with a dural tail sign. CT showed that the skull was involved apparently and the lesion appeared hyperdense when contrast-enhanced CT was performed. In case of a meningioma, CT frequently displays that the lesion is isodense or has slightly higher density with a round, leafy, or flat shape[3,6]. Calcification becomes visible in some tumors[6]. Meningioma has similar characteristics as an IgG4-RHP lesion. T1WI often shows isointense or mildly hypointense signal, and T2WI usually shows isointense or mildly hyperintense signal. Besides, the meningioma could be markedly characterized by the tail of the meninges.

It is advisable to focus on some characteristics to help distinguish between meningioma and IgG4-RHP. We noticed that the symptoms of IgG4-RHP were severe and diverse, while those of meningioma were not as varied. These symptoms were due to inflammatory irritation and compression of the adjacent nerves and dura mater[16]. Another characteristic of IgG4-RHP was that the tail signal was broader than meningioma on MRI for the diffuse inflammation along with the dura mater. The meningioma lesion seems relatively confined and phymatoid compared with IgG4-RHP. Moreover, the IgG4-RHP lesion frequently involves extracranial parts.

3.裸車銷售+電池租賃。這種模式是電動汽車生產(chǎn)商只出售裸車，由能源供應(yīng)商提供電池租賃服務(wù)。這種情況下，電動汽車的電池集中于能源供應(yīng)商，所以當(dāng)其進(jìn)行管理時具有規(guī)模效應(yīng)，成本低，效率高，并且專業(yè)程度高。這種情況下大大降低了消費(fèi)者的購車成本和用車成本，使車與電池產(chǎn)生問題的責(zé)任分離，并且電池的使用壽命和使用效率得到提高。但是由于不同的車型對電池的規(guī)格和充電要求的不同，短期內(nèi)難以實(shí)現(xiàn)電池的標(biāo)準(zhǔn)化、統(tǒng)一化，進(jìn)而難以快速的建設(shè)基礎(chǔ)充電設(shè)施，阻礙了電動汽車的推廣發(fā)展。但是，這個問題在電池生產(chǎn)商和電動汽車生產(chǎn)商的合作協(xié)商下，在政府法律法規(guī)和政策的要求下，電池和充電設(shè)施的標(biāo)準(zhǔn)化會得以解決。

CNS tuberculosis is another antidiastole. Patients with tuberculous meningitis often have a fever,headache, and focal neurological symptoms. And tuberculous meningitis is often secondary to pulmonary or intestinal tuberculosis. As for radiology examination, CT often exhibits nodular or punctate calcifications and hydrocephalus, and enhanced scans are often accompanied by meningeal strengthening. MRI frequently shows a hypointense T1WI signal and hyperintense T2WI signal. The enhancement scan could display irregular bar or nodular strengthening lesions of the meninges.Cerebrospinal fluid is essential for the diagnosis of tuberculous meningitis. Moreover, TB-IGRA could facilitate this diagnosis.

The patient confirmed that his headache and hoarse voice gradually improved after 1 mo. The follow-up was arranged 3 mo after the operation, which showed that the abduction movement could be achieved for binocular vision. Brain MRI showed that the residual lesion obviously shrunk (Figure 1). The change for bilateral visual fields is displayed in Figure 2.

Glucocorticoids and immunosuppressants can be used for the non-surgical treatment, such as prednisolone (0.6 mg/kg/d) for 4 wk. The dose of steroid was gradually decreased through 3-6 mo and the dose was finally maintained at 2.5 to 5.0 mg/d for 3 years[17]. Other immunosuppressants should be considered, such as methotrexate, cyclophosphamide, mycophenolate mofetil, and azathioprine[6,7].Another consensus recommended utilizing calcium carbonate and vitamin D3 tablets to prevent glucocorticoid-induced osteoporosis[18,19]. Additionally, it is essential to exclude some latent infections before using glucocorticoids and immunosuppressants. In this case, the patient had a history of tuberculosis and we performed the chest CT and TB-IGRA to ensure the absence of any current underlying infection. In future, when similar patients with the imaging characteristics described in this report are encountered, measurement of serum IgG4 levels may be helpful for diagnosis.

CONCLUSlON

IgG4-RHP is a relatively rare disease that seems complicated to diagnose preoperatively. The purpose of surgery is to obtain the specimens required for pathological examination and plan the follow-up treatment. It is essential to perform a rigorous follow-up and systematic assessment of the whole body.

FOOTNOTES

Yu Y collected the data, contacted with the patient, and wrote the manuscript; Lv L wrote and revised the manuscript; Chen C and Yin SL made the revision to the primary manuscript; Jiang S and Zhou PZ supervised the whole work and made the operation.

反應(yīng)堆壓力容器為核電站反應(yīng)堆冷卻劑系統(tǒng)的主設(shè)備之一，固定和包容堆芯及堆內(nèi)構(gòu)件，使核燃料的裂變反應(yīng)限制在一個密封的空間內(nèi)進(jìn)行。它和一回路管道共同組成高壓冷卻劑的壓力邊界，是防止放射性物質(zhì)外逸的第二道屏障之一。在筒體法蘭上鉆有58個螺孔，用以安裝螺栓與頂蓋密封，螺栓擰入過程中如果發(fā)生螺栓咬死的情況，處理起來比較困難，且影響較大。

IgG4-RD is a condition that affects multiple organs, and its clinical manifestations often vary across different organs. Reportedly, several kinds of bacterial infection can be causative factors for this disease related to stimulation with Toll-like receptor ligands[6,7]. Several previous studies have also reported the comorbidity of IgG4-RD with tuberculosis, as seen in our patient[8-11].

1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project, West China Hospital,Sichuan University, No. 2019HXFH018.

Informed written consent was obtained from the patient for publication of this report and any accompanying images.

The authors declare that they have no conflict of interest to disclose.

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

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

Yang Yu 0000-0002-9901-1310; Liang Lv 0000-0002-5524-7014; Sen-Lin Yin 0000-0003-2241-3749; Cheng Chen 0000-0002-7540-1306; Shu Jiang 0000-0002-6700-7560; Pei-Zhi Zhou 0000-0002-8017-5833.

Fan JR

Wang TQ

Fan JR