我国神经外科事业的开拓者和奠基者之一、复旦大学附属华山医院(以下简称华山医院)神经外科创始人、终身教授史玉泉于 2022 年 3 月17日逝世.史玉泉曾任华山医院神经外科主任、上海医科大学神经病学研究所(今复旦大学神经病学研究所)所长.

BACKGROUND:Epileptic seizures are common symptoms in brain arteriovenous malformation patients and seizure control was an important issue in the treatments. This retrospective study attempted to define the risk factors of seizure presentation and to evaluate the effects of treatment modalities on seizure outcomes. METHODS:Patients receiving single treatment modality during 2013-2016 years, followed up more than 2 years were recruited. Logistic regression analysis was used to detect independent predictors. The factors associated with seizure control were analyzed in patients with pre-treatment seizures, and the factors associated with de novo seizures were analyzed in patents without pre-treatment seizures. RESULTS:Multivariate analysis identified that the independent predictors of seizure presentation were unruptured (ruptured vs. unruptured, OR = 0.314), and in the frontal (frontal vs. parietal, OR = 3.982) or temporal lobe (temporal vs parietal, OR = 3.313). In 47 patients with seizure presentation, good seizure outcomes were achieved in 26 cases. Partial obliteration of nidus (partial vs complete, OR = 32.301) and headache presentation were independent predictors of poor outcome. In 169 patients without seizure presentation, de novo seizures occurred in 22 cases. Treatments of microsurgery or radiosurgery led to a higher incidence of de novo seizures than intravascular embolization. CONCLUSIONS:Patients with unruptured and frontal/temporal lobe located nidus were more likely to manifest seizure presentation. Incomplete nidus obliteration was an independent risk factor of poor outcomes in patients with pre-existing seizures. However, compared to microsurgery or radiosurgery, endovascular embolization was less likely to cause de novo seizures in patients without pre-existing seizures.

OBJECTIVE Malignant meningioma is rare and classified as Grade III in the WHO classification of CNS tumors. However, the presence of estrogen receptor (ER) in WHO Grade III meningiomas and its correlation with patients' outcomes are still unclear. In this single-center cohort study, the authors analyzed clinical features, treatment, and prognosis of these malignant tumors in patients with long-term follow-up. METHODS A total of 87 patients who were pathologically diagnosed with WHO Grade III meningiomas between 2003 and 2008 were enrolled in this study and followed for at least 7 years. Clinical information was collected to analyze the factors determining the prognosis. RESULTS Twelve patients with rhabdoid, 12 with papillary, and 63 with anaplastic meningioma were included. The mean progression-free survival (PFS) and overall survival (OS) were 56.2 ± 49.8 months and 68.7 ± 47.4 months, respectively. No significant differences were observed among the 3 histological subtypes in either PFS (p = 0.929) or OS (p = 0.688). Patients who received gross-total resection had a longer PFS (p = 0.001) and OS (p = 0.027) than those who received subtotal resection. Adjuvant radiotherapy was associated with OS (p = 0.034) but not PFS (p = 0.433). Compared with primary meningiomas, patients with recurrent disease had worse PFS (p < 0.001). For patients who had malignant transformations, the prognosis was poorer than for patients without malignant transformations for both PFS (p = 0.002) and OS (p = 0.019). ER-positive patients had a significantly worse prognosis than ER-negative patients regarding both PFS (p = 0.003) and OS (p < 0.001), whereas no association between progesterone receptor and patients' outcomes was observed. Multivariate analysis demonstrated that ER expression was an independent prognostic factor for both PFS (p = 0.008) and OS (p < 0.001). CONCLUSIONS This retrospective study showed that patients with meningioma with ER-positive expression had a much worse prognosis than those with ER weak-positive or ER-negative status. The results demonstrated that ER is an independent prognostic factor for both PFS and OS of patients with WHO Grade III meningioma. The authors also found that more radical resection of the tumor, as well as postoperative radiotherapy, may prolong patients' survival time.

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Aim To compare the expression level of vascular endothelial growth factor (VEGF) in human cerebral arteriovenous malformation endothelial cells (AVMEC) and normal brain endothelial cell (BECs)in vitro.MethodsThe endothelial cells were isolated and cultured by the vascular tissue explants adherent method. Endothelial cells markers CD31 and vWF were immunohistochemically detected. Expression levels of VEGF mRNA and protein were tested by RT-PCR and Western blot, and were compared.ResultsMore than 95% of the cells were positive for CD31 and vWF staining. Expression levels of VEGF mRNA and protein were significantly higher in AVMEC than in BECs (P<0.05).ConclusionCultured AVMEC expressed higher VEGF than the controlled BEC, implicating angiogenesis played an important role in the pathogenesis of cerebral arteriovenous malformations.

Meningiomas are the most common primary tumors in central nervous system. While recent studies have revealed genetic clues to lower grade human meningiomas, the molecular determinants driving the progression and recurrence of anaplastic meningioma, the most malignant subtype with a low prevalence but high morbidity, are still poorly understood. It has been proposed that high recurrence rates of malignant meningiomas are linked to cancer stem cells. Indeed, tumor stem-like cells have been isolated from various meningioma subtypes, but never been obtained from anaplastic meningioma. In this study, we successfully isolated stem-like cells from human anaplastic meningioma. These cells are capable of forming spheres and initiating xenograft tumors that recapitulate anaplastic meningioma phenotypes, and thus could serve as an in vitro model for malignant meningiomas. KLF4, a transcription factor known for its role in stemness maintenance, was identified as one of the most frequently mutated genes in the benign secretory meningioma. Interestingly, we found that KLF4 is downregulated in anaplastic meningioma compared with low-grade meningioma subtypes. By manipulating KLF4 expression in anaplastic meningioma stem-like cells, we demonstrated that KLF4 acts as a tumor suppressor during malignant progression in meningioma, affecting apoptosis, proliferation, invasion, and cell cycle. These results suggest a potential therapeutic value of KLF4 for clinical intervention of anaplastic meningioma.

Aim Intracerebral hemorrhage (ICH) can lead to tragic disability and mortality. Accumulating evidence has been shown that sodium calcium exchanger (NCX) may contribute to secondary injury of stroke. A novel member of NCX, SLC24A6, was reported, which was involved in brain damage in rats after ICH.MethodsThe time course of expression of SLC24A6 and its mediated intracellular calcium concentration in caudate nucleus tissues of rats after ICH were examined. And the roles of SLC24A6 in regulating calcium concentration under normoxic or hypoxic conditions was also investigated.Results Both mRNA and protein levels of SLC24A6 decreased in hemorrhagic caudate nucleus tissues early after ICH, and reached to the lowest levels at day 3, and then slightly increased at day 5 and day 7. On the contrary, intracellular calcium concentration increased early after ICH, peaking at day 3 followed by declines at day 5 and day 7. Under normoxic conditions, transfection of SLC24A6 led to a significant increase of intracellular calcium concentration in HEK 293 cells. SLC24A6 overexpression, however, inhibited calcium overload and protected cells from death under hypoxic conditions.ConclusionThese data suggested that SLC24A6 could exert a protective role in brain damage after ICH via inhibiting calcium overload.

OBJECTIVE: Angiomatous meningioma (AM) is a rare subtype of meningioma characterized by highly vascular tumor tissue comprising predominantly variable sized hyalinized blood vessels. The aim of this study is to evaluate the clinical radiologic features of AM and the long-term prognosis in a single neurosurgical center. METHODS: A total of 93 patients who underwent surgical resection of AMs between 2003 and 2008 were enrolled for analysis. Clinical information, treatment, and radiologic images were collected and analyzed; follow-up was carried out as well. Expression of estrogen receptor, progesterone receptor, and vascular endothelial growth factor was analyzed by immunohistochemistry. RESULTS: Forty-eight females and 45 males were identified. Forty-four patients (47.31%) manifested as hypersignal in T1-weighted imaging sequences and 68 (73.12%) as hypersignal in T2-weighted imaging, and a characteristic ringlike signal was observed in 28 patients (30.11%). Eighty-one cases (87.10%) showed different degrees of peritumor brain edema and it was significantly correlated with the vascular endothelial growth factor expression (P < 0.001). Simpson I resection was achieved in 63 patients (67.74%), grade II in 27 patients (29.03%), and grade III in 3 patients (3.23%). The extent of resection was not associated with the postoperative neurologic function (P = 0.546). Only 4 patients experienced recurrences during the follow-up and these 4 patients were stable until the last follow-up. CONCLUSIONS: AMs were a special subtype of meningioma with distinctive radiologic features. AMs manifest benign behavior with a satisfying outcome, which makes Simpson grade II resection an option.

OBJECTIVE:The aim of this study was to investigate delayed complications in patients with brain arteriovenous malformation (BAVM) after Gamma Knife stereotactic radiosurgery and to present the salvage therapy experiences of patients with BAVM with radiation-induced changes (RICs) or intracranial hemorrhage (ICH).METHODS:This cohort consisted of 44 patients with BAVM who underwent failed GKRS between 2000 and 2015. These patients were further divided into an RIC group (23 patients) and an ICH group (21 patients) based on their post-GKRS complications. The patients' characteristics, treatment strategies, and long-term outcomes were analyzed. The modified Rankin Scale was used to assess the neurologic status of each patient.RESULTS:In our study, the marginal dose and radiosurgery-based arteriovenous malformation score were not significantly different between the 2 groups. Craniotomy was performed in 26 patients (9 patients with ICH and 17 patients with RICs), and histologic examination showed cavernous angioma changes in 6 patients. In addition, 6 patients underwent repeat radiosurgery in the ICH group, and 7 patients used bevacizumab in the RIC group. Thirty patients showed good outcomes at the last follow-up (modified Rankin Scale score <3).CONCLUSIONS:Salvage therapy for patients with BAVM should be performed based on the latency period and lesion characteristics of each individual. Prompt treatment and a longer follow-up are recommended to achieve good clinical outcomes.

目的 采用CRISPR/Cas9技术编辑小鼠Alk1基因,探讨条件性敲除Alk1建立中枢神经系统动静脉畸形动物模型的可行性.方法 利用CRISPR/Cas9技术在小鼠Alkl基因的特定位点插入两个LoxP序列;经传代并与SM22-Cre小鼠交配后培育出Alk12LoxP/2LoxP/Cre目标小鼠.该目标小鼠8周龄时通过他莫昔芬腹腔注射激活Cre重组酶的表达,从而条件性敲除Alkl基因诱导脑动静脉畸形的生成.2周后取小鼠脑组织标本,进行苏木精-伊红染色和病理分析.结果 7只目标小鼠中,2只脑组织病理切片发现管腔大小不一的异常血管病灶.结论 条件性敲除Alkl基因可初步建立中枢神经系统动静脉畸形动物模型.

BACKGROUND: Intraoperative ultrasonography is widely used in neurosurgery for the management of intracerebral hematoma and brain tumor. However, the clinical value of this method in the surgery of cerebral arteriovenous malformations (AVMs) has not been reported. In this study, the application of intraoperative ultrasonography for AVM surgery was evaluated prospectively.METHODS: This prospective clinical study comprised 41 patients who underwent microsurgical resection of cerebral AVMs at our institute. After routine craniotomy, ultrasonographic imaging with color Doppler ultrasonography and real-time contrast-enhanced ultrasonographic angiography if necessary were applied as navigated images on the monitor during the operation.RESULTS: Ultrasonographic imaging made it easier to understand the vascular architecture during the operation. Color Doppler flow imaging clearly delineated the shape and margin of the AVMs. Intraoperative real-time contrast-enhanced ultrasonographic angiography enabled the surgeons to categorically identify AVM feeders both on the surface and deep in the tissue.CONCLUSIONS: Microneurosurgery with intraoperative ultrasonographic image guidance was a safe, effective, and reliable method for identifying the afferent and efferent vessels and for confirming the complete resection of AVMs. These benefits of image-guided microsurgery were mostly apparent for deep-seated AVMs that were not visible on the surface of the brain.

Meningioma is the most frequently reported primary brain and central nervous system tumor. However, malignant meningioma is rare with the anaplastic subtype the most common. This subtype of meningioma is fatal with a high recurrence rate and poor survival. A retrospective review of anaplastic meningioma patients treated in one of the largest neurosurgical centers in China between 2003 and 2008 was conducted. From 70 identified patients, seven were lost to follow-up, but the remaining 63 patients were studied for prognostic factors. The mean follow-up time was 84.9±standard deviation (SD) of 19.7months. Tumor recurred in 35 out of 63 (55.6%) patients. Thirty-three (52.4%) patients had died by the most recent follow-up, and the median overall survival (OS) was 70.0±9.7months. The 3year and 5year survival rates were 68.3% and 54.7%, respectively. The median progression-free survival (PFS) was 52.0±9.9months, whereas the 3year and 5year PFS rates were 60.2% and 43.9%, respectively. We found that preoperative KPS, extent of tumor resection, radiotherapy, tumor location and previous history of meningioma were factors related to PFS. In the non-recurrent group, the preoperative Karnofsky Performance Scale (KPS), extent of tumor resection and radiotherapy correlated with PFS. However, multivariate analysis identified radiotherapy as the only independent factor affecting PFS (p=0.007). Additionally, MIB-1 proliferation index failed to identify a cut-off point to predict the prognosis for anaplastic meningioma. This study provides an overview of the epidemiology and treatment of anaplastic meningioma in China using a large population.

目的 研究脑动静脉畸形(AVMs)经立体定向放射治疗后不同时期的组织病理变化.方法 对10例脑AVMs立体定向放射治疗后的病理标本进行苏木精-伊红染色,并用平滑肌肌动蛋白(SMA)、血管内皮生长因子(VEGF)及神经胶质酸性蛋白等抗体进行免疫组化研究.结果 经立体定向放射治疗后,早期脑AVMs血管病理变化包括内膜层与血管壁分离,细胞外基质增生;中期可见平滑肌细胞增生,血管壁增厚,管腔狭窄至消失,管壁玻璃样变;晚期病理变化包括血管壁进行性增厚,在完全玻璃样变的区域细胞核固缩.早期放射反应的动脉管壁中VEGF呈阳性表达,在中期放射反应的动脉管壁中SMA呈强阳性表达.结论 立体定向放射治疗后脑AVMs血管中层的平滑肌细胞增生和变性是血管闭塞的关键因素.

目的 将LoxP序列靶向引入小鼠Alk1基因,拟通过Cre/LoxP系统条件性敲除Alk1基因建立脑动静脉畸形小鼠模型.方法 利用CRISPR/Cas9技术编辑小鼠Alk1基因:①设计和选择两个单导向RNA(sgRNA)分别识别外显子3～4和8～9的非编码区位点;②设计带有2个LoxP序列且与靶基因同源的供体载体;③将体外合成的sgRNA,Cas9 mRNA和供体载体注射到小鼠受精卵;④受精卵经假孕小鼠代孕出生后,经PCR和测序筛选目标小鼠.结果 小鼠Alk1等位基因的特定位点插入了LoxP序列.结论 CRISPR/Cas9技术能成功将LoxP序列靶向引入小鼠Alk1基因,为建立脑动静脉畸形小鼠模型创造条件.

Transpalpebral or trans-eyelid approach is a modified trans-orbital access to lesions of anterior cranial fossa and sellar region. But whether this approach is also suitable for tumors extending laterally to the temporal lobe or middle cranial fossa is not clarified. We would like to share our experiences from the cadaveric anatomy study to clinical operations. We used 5 cadavers to study trans-eyelid approaches in a step-by-step fashion. And then assisted by an experienced ophthalmologist for incisions, we treated 3 female patients via this approach: One with spheno-orbital meningioma, one with sellar tuberculum meningioma, and the other with medial sphenoidal wing meningioma. After studying the cadavers, we made several revisions to the previously reported approach: 1) move the incision close to the edge of the eyelid, which resembled the double-eyelid incision. 2) A vascularized periosteum flap was dissected for repairing the opened frontal sinus and reconstruction of the skull base. 3) The dura was sutured up with a slice of temporalis muscle. Then we treated 3 patients by this approach. All tumors were totally resected as Simpson Grade I. Complications included orbital apex syndrome and transient oculomotor paralysis because of tumor invasion into orbit and cavernous sinus. No cerebrospinal fluid leakage. We find that trans-eyelid approach is suitable for lesions not only at anterior cranial base or sellar region, but also extending to middle cranial base, especially around sphenoidal wings within 2 cm range or spheno-orbital region. Thus, we propose whether it appropriate to nominate this approach as 'trans-eyelid pterional approach', since it may treat some anterior and middle cranial fossa lesions with a mini-craniotomy around pterion.

BACKGROUND:Here, we introduced our short experience on the application of a new CUSA Excel ultrasonic aspiration system, which was provided by Integra Lifesciences corporation, in skull base meningiomas resection.METHODS:Ten patients with anterior, middle skull base and sphenoid ridge meningioma were operated using the CUSA Excel ultrasonic aspiration system at the Neurosurgery Department of Shanghai Huashan Hospital from August 2014 to October 2014. There were six male and four female patients, aged from 38 to 61 years old (the mean age was 48.5 years old). Five cases with tumor located at anterior skull base, three cases with tumor on middle skull base, and two cases with tumor on sphenoid ridge.RESULTS:All the patents received total resection of meningiomas with the help of this new tool, and the critical brain vessels and nerves were preserved during operations. All the patients recovered well after operation.CONCLUSIONS:This new CUSA Excel ultrasonic aspiration system has the advantage of preserving vital brain arteries and cranial nerves during skull base meningioma resection, which is very important for skull base tumor operations. This key step would ensure a well prognosis for patients. We hope the neurosurgeons would benefit from this kind of technique.

BACKGROUND:Nocardial brain abscess is a rare central nervous system (CNS) infection with high morbidity and mortality. The infection is acquired through inhalation or direct contact with the bacteria, and could spreads through blood transmission. Nocardial brain abscess is usually associated with immunocompromised patients, but sometimes may appear in healthy individuals. Treatment is based on stereotaxic aspiration or surgical resection, and antibiotics therapy for several months.CLINICAL PRESENTATION:We presented one case of nocardial brain abscess treated at our department with review the literature. The patient was 65-year-old with ANCA polyangitis. She had oral methylprednisolone tablets treatment for over 6 months. The patient was treated with surgical evacuation and long-term antibiotics. The patient recovered well at discharge.CONCLUSION:Nocardial brain abscess is a rare CNS infection that needs to be differentiated from other brain lesions. It could occur in immunocompromised patients or healthy individuals. Treatment includes surgical intervention and long-term antibiotics therapy.