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Background: The application of functional MRI to non-human primates after stroke has not yet been undertaken. This is the first study to explore the functional connectivity changes in non-human primate models during acute stages after stroke onset., Methods: Nineteen healthy male cynomolgus monkeys (4-5 years) were used in this study. The photothrombosis model was employed to induce focal ischemic stroke in F1 area in the monkey's left hemisphere. T1-weighted structural images and resting-state functional magnetic resonance imaging (rs-fMRI) of all subjects were obtained using a 3.0 Tesla MRI system on the third day following stroke. Based on the D99 atlas, the structural and functional changes of bilateral F1 areas in monkeys were analyzed using region of interest (ROI)-based functional connectivity (FC). The bilateral F1 areas were selected as the seed regions due to their crucial role in motor control and their potential to unveil the comprehensive functional reorganization of the motor system at a whole-brain level following stroke., Results: Ischemic lesions were observed after the stroke, with larger lesion volumes associated with poorer neurological dysfunction. Compared with baseline condition, left area F1 demonstrated decreased FC with the left cerebellum, left ventral pons and left 5_(PEa). When the ROI was located in the right area F1, ischemic monkeys showed decreased FC in left ventral pons, left cerebellum, left primary visual cortex and left 5_(PEa), accompanied by increased FC in the right orbitofrontal cortex. Importantly, the degree of altered FC between left area F1 and left cerebellum was associated with upper limb tone., Conclusions: These results provide valuable insights into the early-stage functional connectivity changes in the F1 areas of monkeys under ischemic conditions, highlighting the potential involvement of specific brain regions in the pathophysiology of ischemic injury., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

Background: Central nervous system (CNS) infection is one of the most serious complications after neurosurgery. This study aimed to analyze the effect of penicillin allergy (PA) and alternative prophylactic antibiotics on risk of postoperative CNS infection in patients undergoing neurosurgery., Methods: Data of patients who underwent neurosurgical procedures from January 2015 to December 2021 were analyzed retrospectively. Patients with PA were compared with patients without PA in a 1:1 ratio. A multivariate logistic regression model was used to examine whether PA was a risk factor for postoperative CNS infection., Results: Overall, 15,049 eligible neurosurgical records were reviewed, from which 578 surgical records of 556 patients with PA were matched to 578 records of 570 patients without PA. Patients with PA showed significantly lower probability to receive prophylactic cephalosporins (55.9% vs. 98.8%, P < 0.01), but significantly higher probability to receive clindamycin (41.86% vs. 1.03%, P < 0.01), than patients without PA. Multivariate analysis revealed that patients with PA were more likely to experience postoperative CNS infection than patients without PA (odds ratio = 2.03; 95% confidence interval, 1.15-3.56; P = 0.014). The incidence of postoperative CNS infection returned to a level comparable to that in general population when patients with suspected PA received prophylactic cephalosporins., Conclusions: PA is associated with higher risk of postoperative CNS infection in patients undergoing neurosurgery. This may be attributed to the use of alternative prophylactic antibiotics other than cephalosporins, especially clindamycin., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Aims: Incomplete surgical resection of invasive non-functional pituitary adenomas (NFPAs) produces a risk of the subsequent development of complications which will require treatment with powerful drugs and adjuvant radiotherapy., Materials and Methods: The degree of invasiveness of NFPA can be established using biomarkers to help clinicians choose appropriate treatment for these patients., Results: This research explored transcriptomic and proteomic variations of non-invasive and invasive NFPAs, other forms of pituitary adenomas and evaluated exosomal genetic markers associated with these diseases. Increased expression of matrix metalloproteinase-1 (MMP1) and its formation in exosomes (exo-MMP1) were correlated with the characteristic invasiveness of NFPAs. Changes in the expression of MMP1 in the exosome was synchronized with transduction of NFPA cells. Enrichment of MMP1 stimulated migration, growth and angiogenesis in tumors through the protease-activated receptor-1 signaling pathway in cells., Conclusion: The results revealed that MMP1 activity has obligatory actions in promoting tumor invasion and angiogenesis, and that the exosome-mediated regulatory pathway for MMP1 may be a novel therapeutic target., (Copyright © 2022. Published by Elsevier B.V.)

Objective: Subthalamic deep brain stimulation (STN-DBS) could be an effective alternative treatment for patients with Parkinson's disease (PD). However, the mechanisms of deep brain stimulation (DBS) at different frequencies are still unclear. In this study, diffusion tensor imaging (DTI) was used to detect parameter changes in different regions of rat brains after DBS, and rat exercise capacity and brain tissue immunohistochemistry were evaluated., Materials and Methods: The 6-hydroxydopamine-induced hemi-parkinsonian rat models were made and divided into four groups: a control group, sham group, low-frequency group, and high-frequency group. Low-frequency (30 Hz) and high-frequency (130 Hz) DBS were given to the STN in rats. First, an open-field experiment was used to evaluate changes in exercise performance. Then, the DTI was used to measure parameter changes in the substantia nigra (SN). Finally, immunohistochemistry was used to analyze the expression of tyrosine hydroxylase (TH), NeuN, and α-synuclein (α-syn) in the SN in the rats., Results: There were significant differences in movement distance changes between the high-frequency stimulation (HFS) group and low-frequency stimulation (LFS) group, the HFS group and Ctrl group, and the Sham group and Ctrl group (all p < 0.05) after one week of stimulation. In the HFS group, the fractional anisotropy value of the SN was significantly higher than that of the other groups (p < 0.05), and the apparent diffusion coefficient and radial diffusion coefficient values were significantly lower than those of the other groups (p < 0.01). Immunohistochemical analysis showed that the integral optical density values of SN TH staining (p < 0.01) and NeuN staining (p < 0.05) in the HFS group were both significantly higher than those in the other groups., Conclusion: STN-HFS (130 Hz) and sham operation for one week can significantly improve the exercise performance of PD rats. The exercise performance of PD rats in LFS group (30 Hz) is worse compared with HFS group (130 Hz). HFS plays a role in neuroprotection and improvement of exercise performance of PD rats. Moreover, DTI can be used as an effective technique to assess the therapeutic effects and severity of PD., (© 2020 International Neuromodulation Society.)

Background: Ectopic adrenocorticotropic hormone-secreting pituitary adenomas (EAPAs) are rare adenomas causing Cushing syndrome, which are located in ectopic locations outside the sella turcica. No more than 100 cases of this entity have been reported. Because of its rarity and nonspecific clinical and biochemical features, EAPA is often misdiagnosed, leading to surgical failure and delayed treatment. In the article, the cases of 3 patients with suprasellar EAPAs treated at our institution are reported and a review of the literature is presented., Case Description: All 3 patients with Cushing syndrome had ectopic pituitary adenomas located in the suprasellar region and identifiable on preoperative sellar magnetic resonance imaging. Preoperative laboratory evaluation in all patients showed identical results to those observed in Cushing disease. In 2 patients, craniotomies were performed directly to achieve total tumor resection and clinical remission. One patient, who underwent previous negative transsphenoidal exploration, achieved full remission through a second craniotomy despite pulmonary infection as a postoperative complication., Conclusions: Although EAPA is an extremely rare entity, it should be considered as a differential diagnosis of Cushing disease. Because of its similar clinical and biochemical behavior to intrasellar pituitary adrenocorticotropic hormone adenoma in Cushing disease, careful examination of the potential occurrence of EAPA on preoperative radiologic imaging is of considerable significance to avoid unnecessary surgery and achieve improved outcomes. Surgical resection EAPA remains the first choice of treatment, and the optimal surgical approach ought to be determined according to the adenoma features, the general condition of the patient, and the surgeon's experience., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The role of operation for patients with recurrent diffuse low-grade glioma (DLGG) is controversial. A few studies compared the effectiveness between surgery and other treatments for those patients. We did a systematic review for the effects of reoperation for recurrent DLGG. We searched the following databases from 1990 to 2018: Medline, Cochrane Library, Scopus and Opengrey, including researches about reoperation for recurrent DLGG, regardless of comparison and study design. The Newcastle-Ottawa scale (NOS) was used for quality assessment. Ten studies with 358 participants met the criteria. Due to lack of survival data about non-operated group, we failed to analyze the effect of reoperation. The risk bias of included studies was acceptable except the comparability. However, we found 48.4 % (155/320) of patients underwent gross resection and the safety was acceptable. About 1/3 received adjuvant therapy and 41.9 % (125/298) got histologically progressed. In a word, few studies reported the survival data of recurrent DLGG patients received reoperation. Most were young adults and half of them experienced a histological progress. But there are still a lot of shortages of the existing studies and more researches on the reoperation efficacy in recurrent DLGG are needed., (Copyright © 2020. Published by Elsevier B.V.)

Objective: Many studies have evaluated the safety and efficacy of stem cells as therapeutic agents for ischemic stroke. We aimed to quantitatively assess the research trends of stem cell therapy for ischemic stroke., Patients and Methods: We searched the Web of Science Core Collection to identify relevant publications between 1999 and 2018. We used HistCite to summarize the critical information, including yearly records, authors, countries/regions, and institutions. VOSviewer was applied to map the collaborations between studies. Based on the title and abstract of each publication, MeSH terms were obtained using Medical Text Indexer to demonstrate evolutions of topic hotspots., Results: From 1999-2018, there were a total of 3,741 publications exploring the prospect of stem cells in ischemic stroke. Annual publication outputs grew from six records to 366 records. Stroke was the most high-profile journal because of its ranking first on the top productive and co-cited journal lists. The United States of America and China were the two most contributive countries of stem-cell research of ischemic stroke. Researchers were supposed to follow studies from productive institutions because of their consistent and systematic investigations in this field. Neural stem cells and mesenchymal stem cells were the most recognized cells for clinical translation., Conclusion: With the growth of publications concerning the role of stem cells in ischemic stroke treatment, bibliometrics helps researchers to get insights of academic collaborations, research trends, and hot topics in the study field., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Although the overall publication trends in Parkinson disease (PD) and characteristics of top-cited articles have been reported, there was only 1 literature analysis published in 2012 with a special focus on stem cells. It is necessary to evaluate and update the global publication trends in stem cell research of PD., Methods: We identified the publications designated as "article" about stem-cell research of PD between 1999 and 2018 in the Web of Science Core Collection. We used HistCite to analyze annual outputs, journals, countries/regions, and institutions every 5 years and visualized global collaborations between publications by VOSviewer. Moreover, to track the growing hotspots, MeSH terms of each publication were obtained by Medical Text Indexer according to the title and abstract., Results: We described the publication trends and topic hotspots of stem-cell research of PD by bibliometric analysis of 1709 papers. Researchers showed growing interest in publishing relevant scientific literature in journals associated with stem cells or multidisciplinary science. Stem cell research of PD was more common in developed countries and regions. The United States of America was the most contributive country throughout, accounting for 33% of total publications and ranking first in all 5-year periods. Harvard University was the most productive institution in this area, ranking first during 1999-2003, 2004-2008, and 2009-2013. The application of induced pluripotent stem cells was at the forefront of cell therapies for PD., Conclusions: These bibliometric findings suggest that stem cell research consistently promotes the understanding and treatment of PD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Central nervous system (CNS) diseases are associated with complexity and diversity; as a result, it is urgent to search for a simple approach for effectively improving the clinical decision-making ability and precise treatment currently. Radiomics can collect plenty of quantitative features based on the massive medical image data; meanwhile, related diagnosis and prediction can be performed through quantitative analysis. The main steps of radiomics analysis include image collection as well as reconstruction, segmentation of the region of interest (ROI), feature extraction as well as quantification, and establishment of the predictive as well as prognostic models. Compared with traditional imaging features, radiomics allows to transform the visual image data to the in-depth features, so as to carry out quantitative research. Our findings suggest that radiomics has broad application prospects in the early screening, accurate diagnosis, grading and staging, treatment and prognosis, and molecular characteristics of CNS diseases, which can improve the capacities to diagnose and predict CNS diseases prognosis through complementing and combining with traditional imaging., (Copyright © 2019 Elsevier B.V. All rights reserved.)

To investigate the clinical characteristics of pituitary adenomas in patients under 14 years old. A total of 140 children and adolescents with pituitary adenomas were admitted to Peking Union Medical College Hospital (PUMCH) from December 1987 to December 2014, and their clinical manifestations, hormone secretions, images, pathological types, surgical complications and follow-up characteristics were analyzed. Fifty-eight (41.4%) males and 82 (58.6%) females with a mean age of 12.5 years old (range, 6-14 years old) were included. Regarding tumor type, adrenocorticotropic hormone (ACTH), prolactin (PRL), growth hormone (GH), non-functioning and multiple-secreting adenomas accounted for 35.7%, 25.7%, 12.2%, 25.7%, and 0.7% of the tumors, respectively. Microadenomas, macroadenomas and giant adenomas accounted for 33.6%, 60.0% and 6.4% of the patients, respectively. Approximately 19.3% of the adenomas included in our study were invasive. Trans-sphenoidal approach surgery (TSS) was commonly used and accounted for 97.9% of the cases in our study. Total resection was achieved in 93.6% of the patients, and subtotal resection was performed in the remaining patients. Finally, 113 patients underwent full-term follow-up until 2 years after surgery, and tumors recurred in 32 patients. TSS is the most commonly used surgical procedure in patients younger than 14 years old. No significant differences in surgical outcomes, mortality during the perioperative period or complications were observed between patients younger than 14 years old and similar patients in the general population., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the clinical characteristics of delayed remission (DR) of growth hormone (GH)-secreting pituitary adenoma after transsphenoidal adenectomy and inform follow-up treatments., Methods: We retrospectively reviewed 87 patients who had undergone transsphenoidal surgery for acromegaly. Demographic, radiological, and endocrinological data were reviewed before, immediately after, 3 months after, and in the long term (2.4 ± 1.1 years) after surgery. The definition of DR was that patients did not achieve GH remission immediately, 3 months, or later after surgery, but did so in the long term without any additional postoperative treatment., Results: Fifty-one patients (58.6%) achieved long-term GH remission. There were 24 (27.6%) DR patients immediately postoperatively and 9 (10.3%) DR patients 3 months postoperatively. On average, the 24 DR patients achieved remission at 10.2 (range, 3-32) months. Immediate postoperative random and nadir GH after an oral glucose load were significantly lower in the DR group than in the nonremission group (2.73 ± 3.17 and 2.03 ± 2.59 vs. 8.05 ± 10.35 and 5.55 ± 5.91 μg/L, respectively). Three-month postoperative nadir GH was significantly lower in the DR group than in the nonremission group (1.63 ± 2.82 vs. 3.48 ± 4.25 μg/L, P = 0.007). Immediate postoperative random GH effectively predicted long-term remission (Spearman's ρ = 0.513, area under the curve = 0.905 > 0.90). However, the best predictor of long-term remission was 3-month postoperative nadir GH (Spearman's ρ = 0.728, area under the curve = 0.944 > 0.90), with 76.5% sensitivity and 97.2% specificity., Conclusions: For certain groups of patients likely to achieve DR, additional treatments should not be performed early after surgery. Prolonged follow-up and close observation could help determine the therapeutic effect of surgery and guide postoperative treatments., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Sellar germ cell tumors (GCTs) occur more frequently in childhood. Some will present as malignancy with infiltration and metastasis. However, the association between the timeliness of diagnosis and outcome has been controversial. We investigated the clinical risk factors associated with a diagnostic delay in patients with sellar GCTs in China., Methods: The data from 53 patients aged <18 years with histologically confirmed sellar GCTs at Peking Union Medical College Hospital treated from January 2008 to December 2016 were reviewed retrospectively., Results: The median interval between symptom onset and diagnosis was 25 months. Of the 53 patients, 44 (83%) had a delayed diagnosis. Most patients (86%) with a delayed diagnosis presented with polyuria or polydipsia. Of the 53 patients, 48 (91%) exhibited changes in the pituitary stalk. Patients with a germinoma (odds ratio, 4.1; 95% confidence interval, 2.4-6.9) and slow growth (odds ratio, 5.3; 95% confidence interval, 1.2-24.5) were more likely to have a delayed diagnosis. The overwhelming majority of patients with a delayed diagnosis (96%) had been seen by >1 doctor. No statistically significant differences were found in the mean survival time (P = 0.21) or mean progression-free survival time (P = 0.36) between patients with and without delay in diagnosis, respectively., Conclusions: A significant proportion of patients with sellar GCTs will experience a delay in the time to diagnosis. Although a delay in diagnosis did not reduce the survival time or progression-free survival time for patients with sellar GCTs, it might increase the risk of short stature. Thus, a detailed medical history and an immediate radiological examination are important for the early diagnosis of sellar GCTs in childhood., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disorder caused by the mutation of gene VPS13A. Deep brain stimulation of ChAc has made substantial progress in the recent decades. However, the reports were scattered across centers and performed by different neurosurgeons. Here, we report a case series consisting of six patients diagnosed with ChAc, receiving bilateral high-frequency stimulation of globus pallidus internus (GPi) in a single center., Methods: We report six consecutive patients diagnosed with ChAc and present a review of the literature. All patients received neurological evaluations using the Unified Huntington's Disease Rating Scale (UHDRS) motor score before surgery and during clinical follow-ups. One patient was observed over six months, while five patients were seen over 12 months., Results: All patients underwent high-frequency stimulation ranging from 130 Hz to 175 Hz. In the follow-up period, a general trend was found toward higher amplitude and broader pulse widths, with a mean current range of 2.08 mA to 3.06 mA and a mean pulse width range of 75 μsec to 98 μsec. On preoperative evaluation, the mean UHDRS motor score was 35.7 ± 16.3 and the chorea subscore was 11.3 ± 4.7. At the three-month postoperative follow-up, both UHDRS motor score (13.5 ± 5.8) and chorea subscore (3.0 ± 1.2) reached valley values. Thereafter, the UHDRS motor score and chorea subscore showed a gradual rise, reaching 19.2 ± 5.9 and 4.8 ± 1.7, respectively, at the 12-month follow-up. In addition, adverse events were also seen. Patient 1 developed dysarthria six months after surgery, whereas Patient 6 had a generalized tonic-clonic seizure attack one day after surgery CONCLUSION: High frequency stimulation of the GPi is an effective and safe modality for the treatment of ChAc, with both rapid symptomatic improvements and steady chronic outcomes., (© 2018 International Neuromodulation Society.)

Objective: This study aimed to summarize the diagnosis, therapy, and prognosis of pituitary metastasis., Methods: Ten patients from the Department of Neurosurgery of the Peking Union Medical College Hospital from April 1997 to August 2014 were retrospectively analyzed., Results: The participants included 7 males (70%) and 3 females (30%), with an average age of 60.4 years. The most common initial clinical feature was visual disability (50%). The postoperative pathology reports indicated 1 case (10%) of metastatic large-cell pulmonary carcinoma, 2 cases (20%) of metastatic small cell pulmonary carcinoma, 2 cases (20%) of clear cell renal carcinoma metastasis, and 5 cases (50%) of metastasis of adenocarcinomas from different areas. All the patients underwent a thorough follow-up, and the average survival was 144 days., Conclusions: Pituitary metastasis is a rare disease. Its diagnosis depends on the clinical manifestations and radiologic results. The primary therapeutic method is surgery and subsequent radiotherapy and chemotherapy; however, the prognosis of this disease is poor., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Antiangiogenic therapy is a universal approach to the treatment of malignant gliomas but fails to prolong the overall survival of newly diagnosed or recurrent glioblastoma patients. Imaging biomarkers are quantitative imaging parameters capable of objectively describing biological processes, pathological changes and treatment responses in some situations and have been utilized for outcome predictions of malignant gliomas in anti-angiogenic therapy. Advanced magnetic resonance imaging techniques (including perfusion-weighted imaging and diffusion-weighted imaging), positron emission computed tomography and magnetic resonance spectroscopy are imaging techniques that can be used to acquire imaging biomarkers, including the relative cerebral blood volume (rCBV), K trans , and the apparent diffusion coefficient (ADC). Imaging indicators for a better prognosis when treating malignant gliomas with antiangiogenic therapy include the following: a lower pre- or post-treatment rCBV, less change in rCBV during treatment, a lower pre-treatment K trans , a higher vascular normalization index during treatment, less change in arterio-venous overlap during treatment, lower pre-treatment ADC values for the lower peak, smaller ADC volume changes during treatment, and metabolic changes in glucose and phenylalanine. The investigation and utilization of these imaging markers may confront challenges, but may also promote further development of anti-angiogenic therapy. Despite considerable evidence, future prospective studies are critically needed to consolidate the current data and identify novel biomarkers.

Background: Prolactinomas are the most common functional pituitary adenomas and dopamine agonists are the primary therapy. However, some patients are resistant to dopamine agonists. Recently, metformin has been proposed as a cancer treatment., Case Description: This study is a retrospective review of 2 cases including 1 patient with prolactinoma who was resistant to bromocriptine, diagnosed with impaired glucose tolerance, and administered metformin. Surprisingly, combining the patient's treatment with metformin decreased prolactin (PRL) levels to 12 ng/mL and significantly decreased the size of the tumor after 1 year of combination therapy. As menstruation resumed and galactorrhea resolved, the patient became pregnant and stopped using metformin but continued taking bromocriptine. She gave birth to a healthy boy in August 2016. After delivery, she decided to breastfeed the baby and only took bromocriptine. After 14 months of using bromocriptine alone, her PRL level increased to 208 ng/mL and the tumor reappeared (7 mm × 8 mm × 9 mm). Interestingly, the patient's PRL level decreased from 208 ng/mL to 150 ng/mL 2 months after using combination treatment with bromocriptine and metformin. On the basis of these findings, a second bromocriptine-resistant patient was recruited. After 3 months of combined treatment with bromocriptine and metformin, the patient's PRL level decreased to 2.08 ng/mL, testosterone levels increased significantly, and the tumor size decreased., Conclusions: Although more cases and investigations into the mechanisms underlying these effects are needed, these 2 cases support the hypothesis that the combination of metformin and bromocriptine might be a new treatment for resistant prolactinomas., (Copyright © 2018. Published by Elsevier Inc.)

Background: Lymphocytic hypophysitis is a rare inflammatory lesion in the sellar region. Lymphocytic hypophysitis secondary to ruptured Rathke cleft cyst (RCC) is even more rarely seen. Clinical characteristics, treatment strategies, and prognosis remain elusive., Case Description: A 58-year-old Chinese woman with a 3-year history of intermittent headache and new development of polydipsia, polyuria, and binocular visual acuity decline over the past 4 months was admitted to our hospital. On admission, endocrine results were normal. Ophthalmic testing showed bitemporal visual field deficits and decreased visual acuity of both eyes. Pituitary dynamic magnetic resonance imaging showed a cystic sellar lesion measuring 5.6 × 5.2 × 6.2 mm with tumor shrinkage compared with initial neuroimaging. Transsphenoidal surgery was performed for tumor resection. An additional biopsy of the anterior pituitary lobe was performed because of intraoperative abnormal appearances of the pituitary gland. Pathology examinations revealed the specimen of the cystic lesion to be RCC and exhibited infiltration of massive lymphocytes, diffused plasmocytes, and eosinophils that were diagnostic of lymphocytic hypophysitis in the anterior pituitary lobe. During follow-up, the lesion of lymphocytic hypophysitis showed spontaneous shrinkage in the absence of steroid treatment after RCC resection. Final diagnosis was lymphocytic hypophysitis secondary to ruptured RCC., Conclusions: We present a rare case of lymphocytic hypophysitis secondary to ruptured RCC and provide clinical data of such lesions in the literature. Full understanding of the clinical features plays an important role in diagnosis and treatment of lymphocytic hypophysitis secondary to ruptured RCC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To investigate pituitary abscess (PA) magnetic resonance imaging (MRI) features to improve the neuroradiologic and diagnostic knowledge of this rare disease and guide follow-up treatments., Methods: Clinical data were collected for 51 patients with PA, and MRI data were quantitatively reviewed in a retrospective analysis. Clinical factors were analyzed to investigate their relevance., Results: PA neuroimaging showed special radiologic features, including hypointensity or isointensity on T1-weighted imaging (30 patients, 58.8%), isointensity or hyperintensity on T2-weighted imaging (39 patients, 76.5%), and disappearance of the posterior pituitary bright spot in most patients (44 patients, 86.3%). After gadolinium injection, rim or rimlike enhancement was observed in 82.4% of patients (n = 42). Half of those patients showed typical rim enhancement (profound peripheral enhancement with internal hypointensity); others showed atypical rim enhancement with special signs, such as enhanced, thick abscess wall and hyperintense flocculent or cottonlike foci within the internal hypointense region. Almost all patients (96.1%) presented at least 1 sign of adjacent anatomic structure invasion, including peripheral meninges enhancement, pituitary stalk thickening, and paranasal sinus mucosa enhancement. Rank correlation analysis of the clinical time course and MRI characteristics of PA showed a Spearman correlation coefficient of 0.270, indicating borderline significance (P = 0.055)., Conclusions: Classic MRI characteristics of PA show T1 signal hypointensity or isointensity, T2 signal isointensity or hyperintensity, and peripheral rim enhancement after gadolinium injection. The MRI appearance of PA may reflect the abscess liquefaction and formation. Despite its profound significance for differential diagnosis, adjacent structure invasion is generally ignored by clinicians., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Pituitary abscess (PA) is a rare but serious intrasellar disorder with potentially high disability and mortality. Secondary PA after transsphenoidal surgery (TS) is extremely rare, and only a few case reports have been identified in the literature. This study explored the salient clinical manifestations and etiologies to determine appropriate treatment., Methods: A retrospective review of 6832 consecutive patients who had undergone TS for pituitary diseases in Peking Union Medical College Hospital between 2003 and 2017 was performed. Demographics, previous medical and surgical history, clinical presentation, imaging features, and treatment details of 23 patients who had been diagnosed with secondary PA after TS among the cohort were reviewed., Results: Among these patients, the original pituitary lesion before TS included Rathke's cleft cyst (8 patients, 34.8%), nonfunctioning pituitary adenoma (11 patients, 47.8%), and somatotropic adenoma (4 patients, 17.4%). The diameter of the original pituitary lesion ranged from 11 to 47 mm. About 52% of secondary PAs occurred within a half a year after surgery. Based on the history of TS, clinical presentation, biochemical testing, and typical imaging features, the preoperative diagnosis rate was as high as 78%., Conclusions: Although rare, secondary PA should be included in the differential diagnosis of intrasellar lesions after TS. Patients with an initial diagnosis of Rathke's cleft cyst or pituitary macroadenoma were more likely to have PA after TS. Adequate surgical drainage combined with microbiology-guided antibiotic therapy is the first choice for treatment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Matrix metalloproteinase-9 (MMP-9), pituitary tumor transforming gene (PTTG), and high mobility group A 2 (HMGA2) play important roles in the tumorigenesis of adrenocorticotrophic hormone (ACTH)-secreting pituitary tumors, but their associations with tumor recurrence after transsphenoidal adenomectomy remain unclear. The aim of the study was to investigate the immunohistochemical expression profiles of MMP-9, PTTG, HMGA2, and Ki-67 in recurrent and nonrecurrent ACTH-secreting pituitary tumors and to identify their associations with tumor behavior and recurrence status., Methods: A retrospective study was performed including 55 patients with sporadic Cushing's disease with long-term remission after transsphenoidal adenomectomy. Fifty-five ACTH-secreting pituitary tumor specimens and 2 normal pituitary glands were collected. After an intensive follow-up (33-59 months, mean 41.8 months), patients were divided into 2 groups based on their recurrence status: the nonrecurrent group (n = 28) and the recurrent group (n = 27). The expression of MMP-9, PTTG, HMGA2, and Ki-67 in each sample was examined and quantified by immunohistochemistry. The association between MMP-9, PTTG, HMGA2, and Ki-67 expression and clinicopathologic characteristics and tumor recurrence were evaluated., Results: There was a significantly increased expression of MMP-9 in the recurrent group compared with the nonrecurrent group (P = 0.022), and this was strongly associated with the recurrence-free interval (P = 0.007, correlation coefficient. = -0.354). PTTG, HMGA2, and Ki-67 expression were not significantly different between the recurrent group and the nonrecurrent group. No expression of MMP-9, PTTG, HMGA2, or Ki-67 was detected in the 2normal pituitary glands., Conclusions: ACTH-secreting pituitary tumors with greater levels of MMP-9 were associated with a greater recurrence rate and a shorter recurrence-free interval. MMP-9 could be a valuable tool for predicting recurrence of ACTH-secreting pituitary tumors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The biopsy is recognized as the most accurate method to determine the histologic characterization of sellar germ cell tumors. It is difficult to evaluate the prognosis before histologic confirmation., Objective: This study aimed to evaluate the independent prognostic risk factors of patients with sellar germ cell tumors (GCTs)., Methods: From January 2008 to December 2015, 61 patients who were histologically diagnosed as having sellar GCTs were followed up and were included in this retrospective study., Results: Of 61 patients in this study, 40 (65.6%), 10 (16.4%), and 11 (18.0%) were diagnosed as having pure germinomas, germinomas with syncytiotrophoblastic giant cells and non-germinomatous GCTs (NGGCTs), respectively. The patients with pure germinomas had a significantly better overall survival time than did those with NGGCT (56.47 ± 3.01 months vs. 43.09 ± 10.58 months; P = 0.01). Multivariate analysis showed that the independent poor prognostic risk factors of patients with sellar GCTs were diameters >15 mm (odds ratio [OR], 7.40; 95% confidence interval [CI], 2.01-27.19), octamer-binding transcription positivity (OR, 5.97; 95% CI, 1.40-25.48), and NGGCT (OR, 11.88; 95% CI, 2.37-59.50), whereas the combination of chemotherapy and radiotherapy was associated with a better prognosis (OR, 0.15; 95% CI, 0.04-0.55)., Conclusions: Diameter >15 mm, octamer-binding transcription positivity, or NGGCT was associated with a poorer prognosis for patients with sellar GCTs, whereas the combination of chemotherapy and radiotherapy was associated with a better prognosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To investigate the clinical features of somatotrophic adenoma in children younger than 14 years and to evaluate the short-term and long-term outcomes of transsphenoidal surgery., Methods: This single-center retrospective study included 22 patients with somatotrophic adenoma who were admitted to our institution between January 1997 and January 2017. The patients' demographics, hormone levels, imaging characteristics, surgical outcomes, and follow-up data were summarized., Results: The average age of patients at diagnosis was 10.3 years, and the average disease duration was 42.5 months. Growth acceleration was observed in 90.9% of patients. Mixed somatolactotrophic adenoma was identified in 36.4% of patients. In total, 77.3% of tumors on imaging were macroadenomas or giant adenoma, and 50% were invasive. Twenty-one patients underwent tumor resection, and the remission rate after a single transsphenoidal surgery was 45%. Preoperative growth hormone levels (P = 0.017), growth hormone nadir (P = 0.003), and tumor size (P = 0.026) were the most likely influencing factors associated with the surgical remission rate. Postoperative cerebral spinal fluid leakage (15%) was the main complication of transsphenoidal surgery. During a median follow-up period of 42.5 months, 72.7% of the patients obtained remission after monotherapy or combined treatment, and no recurrence was observed., Conclusions: Somatotrophic adenomas in children younger than 14 years tend to be macroadenomas with a shorter disease duration than that observed in adults. Transsphenoidal surgery is safe and effective and could represent a preferred treatment option. The combination of surgery, medication, and radiation is recommended to achieve optimal long-term outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To investigate the incidence, bacteriologic features, and risk factors of posttranssphenoidal surgery (post-TSS) meningitis and/or bacteremia., Methods: This retrospective study included 3242 patients who underwent TSS for pituitary adenoma at the Department of Neurosurgery of Peking Union Medical College Hospital between January 2012 and December 2016. Clinical data for patients with and without post-TSS meningitis and/or bacteremia were compared and analyzed., Results: Meningitis and bacteremia developed after 27 (0.8%) and 26 (0.8%) procedures, respectively, and 6 patients (0.2%) developed both. Gram-positive organisms (coagulase-negative staphylococci, Streptococcus pneumonia, and S viridans) predominated in meningitis, whereas gram-negative organisms (Klebsiella pneumonia, Enterobacter aerogenes, and Escherichia coli) predominated in bacteremia. All identified species were sensitive to amikacin, imipenem, and meropenem. Antibiotic treatment cured 52 patients (7 died). In a multivariate analysis, the risk of meningitis and/or bacteremia was independently associated with diabetes (P < 0.001; odds ratio [OR], 6.06), previous surgery at the same location (P < 0.001; OR, 4.23), intraoperative cerebrospinal fluid leakage (P < 0.001l; OR, 4.63), and an endoscopic approach (P = 0.001; OR, 2.50)., Conclusions: Meningitis and/or bacteremia remain critical postoperative complications of TSS for pituitary adenoma. The pathogens with drug sensitivity to antibiotics differed between meningitis and bacteremia. Early blood and cerebrospinal fluid bacterial cultures, drug susceptibility analyses, and appropriate antibiotic treatment can help control the rate of infection., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Transsphenoid surgery (TSS) is a standard treatment modality for Cushing's disease (CD). However, postoperative remission and recurrence rates vary among studies. Here we analyze the diagnosis and outcomes of 341 patients with a preoperative diagnosis of CD undergoing TSS in a single center over a 3-year period., Methods: A total of 341 patients were enrolled. Clinical manifestations, imaging results, laboratory workups, and results of inferior petrosal sinus sampling (IPSS) were obtained. Outcomes were obtained with a follow-up length from 12 to 36 months., Results: The tumors were mainly of Knosp level 0 (68.57%). The sensitivity of MRI, combined low-dose and high-dose dexamethasone suppression test and IPSS in the diagnosis were 90.83%, 88.53% and 95.57%. The concordance of lateralization by MRI and by IPSS were 78.96% and 61.34% compared with surgery. 2., Outcomes: The overall remission rate was 78.89% (N = 289). Patients undergoing the first TSS (N = 234) had a remission rate of 86.36% for macroadenomas (N = 22) and 83.2% for microadenomas (N = 212). Patients undergoing a second TSS (N = 55) had lower rate of remission of 50.00% for macroadenomas (N = 6) and 61.22% for microadenomas (N = 49). For patients with invasive tumors, the overall remission rate was 26.92% (N = 26), 20.0% for macroadenomas (n = 20) and 50.0% for microadenomas (N = 6). The recurrence rate was 2.42%., Conclusions: Pituitary imaging, endocrinological workups and IPSS are sensitive and specific diagnostic modalities for CD, but the lateralization efficacy of MRI and IPSS are unsatisfactory. A higher rate of remission relies on gross resections of tumors., (Copyright © 2017. Published by Elsevier Inc.)

Cognitive impairment and psychiatric symptoms are common in patients with Cushing's disease (CD) owing to elevated levels of glucocorticoids. Molecular neuroimaging methods may help to detect changes in the brain of patients with CD. The aim of this study was to investigate the characteristics of brain metabolism and its association with serum cortisol level in CD. We compared brain metabolism, as measured using [ 18 F]-fluorodeoxyglucose positron emission tomography (FDG PET), between 92 patients with CD and 118 normal subjects on a voxel-wise basis. Pearson correlation was performed to evaluate the association between cerebral FDG uptake and serum cortisol level in patients with CD. We demonstrated that certain brain regions in patients with CD showed significantly increased FDG uptake, including the basal ganglia, anteromedial temporal lobe, thalamus, precentral cortex, and cerebellum. The clusters that demonstrated significantly decreased uptake were mainly located in the medial and lateral frontal cortex, superior and inferior parietal lobule, medial occipital cortex, and insular cortex. The metabolic rate of the majority of these regions was found to be significantly correlated with the serum cortisol level. Our findings may help to explain the underlying mechanisms of cognitive impairment and psychiatric symptoms in patients exposed to excessive glucocorticoids and evaluate the efficacy of treatments during follow-up.

Objective: To investigate outcomes and identified risk factors affecting cure and intraoperative cerebrospinal fluid leak after transsphenoidal surgery using a new classification for growth hormone-secreting pituitary adenoma associated with empty sella., Methods: In this retrospective cohort study, 51 patients enrolled from January 2010 to June 2016 were categorized into 3 groups using a new classification scheme: grade A, whole tumor occupation area beneath a horizontal line drawn along the lowest level of empty sella; grade B, tumor occupation area that crossed the horizontal line on 1 side; and grade C, tumor occupation area that crossed the horizontal line on 2 sides. Clinical data were collected and analyzed., Results: Cure rate for grade A patients (88.24%; 15/17) was significantly higher than cure rate for grade B (55.00%; 11/20) and grade C (50.00%; 7/14) patients. Occurrence of cerebrospinal fluid leaks in grade C patients (35.71%; 5/14) was higher than in grade A patients (5.88%; 1/17). Logistic regression analysis indicated that risk factors affecting cure included large maximum tumor diameter (P = 0.009, odds ratio [OR] = 1.222), high preoperative fasting growth hormone level (P = 0.031, OR = 1.088), and high classification (P = 0.017, OR = 4.485). Risk factor affecting intraoperative cerebrospinal fluid leak was high classification (P = 0.039, OR = 3.580)., Conclusions: Transsphenoidal surgery is the current optimal treatment strategy. Empty sella increases the difficulty of surgery with a higher incidence of complications. The new classification scheme was better for predicting the surgical outcome for this disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive genetic disease that leads to extrapyramidal symptoms, such as dystonia, ataxia, dysarthria, and involuntary movements. Treatment of PKAN with deep brain stimulation (DBS) has been reported, but mainly focuses on targeting the globus pallidus internus (GPi). Subthalamic nuclei (STN) may also be a potential target for treatment of PKAN., Methods: In this study, we reviewed three patients with PKAN (two with typical PKAN and one with atypical PKAN) treated by bilateral STN stimulation and present a review of the literature. All patients received neurological evaluation using the Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFMDRS) scoring system before and after surgery. Patients were then subject to regular clinical follow-ups (ranging from 22 to 44 months)., Results: The mean stimulation amplitude, pulse width and frequency was 2.65 ± 0.45 V, 91.7 ± 21.9 μs, and 146.7 ± 12.5 Hz, respectively. BFMDRS scores were improved in all patients after surgery, ranging from 41.6 to 73.1%. Improvements of appendicular symptoms ranged from 46.2 to 94.1%, and improvements of axial symptoms ranged from 27.3 to 33.3%. No side effects were reported in patients 1 and 2; whereas patient 3 exhibited a mild decline in verbal fluency one year after surgery., Conclusion: STN stimulation could serve as a candidate DBS target in the treatment of PKAN, especially for patients with prominent appendicular symptoms., (© 2017 International Neuromodulation Society.)

Chronic exposure to elevated levels of glucocorticoids can exert a neurotoxic effect in patients, possibly manifesting as molecular imaging alterations in patients. The aim of this study was to investigate the potential association between brain metabolism and elevated hormone level using (18)F-fluorodeoxyglucose positron emission tomography. We retrospectively enrolled 92 consecutive patients with confirmed diagnosis of Cushing's disease. A voxel-based analysis was performed to investigate the association between cerebral (18)F-fluorodeoxyglucose uptake and serum cortisol level. Relatively impaired metabolism of specific brain regions correlated with serum cortisol level was found. Specifically, notable correlations were found in the hippocampus, amygdala, and cerebellum, regions considered to be involved in the regulation and central action of glucocorticoids. Moreover, some hormone-associated regions were found in the frontal and occipital cortex, possibly mediating the cognitive changes seen in Cushing's disease. Our findings link patterns of perturbed brain metabolism relates to individual hormone level, thus presenting a substrate for cognitive disturbances seen in Cushing's disease patients, as well as in other conditions with abnormal cortisol levels.

The hippocampus appears commonly affected by aging and various neurologic disorders in humans, whereas little is known about age-related change in overall protein expression in this brain structure. Using the 4-plex tandem mass tag labeling, we carried out a quantitative proteomic study of the hippocampus during normal aging using postmortem brains from Chinese subjects. Hippocampal samples from 16 subjects died of non-neurological/psychiatric diseases were divided into 4 age groups: 22-49, 50-69, 70-89, and >90. Among 4582 proteins analyzed, 35 proteins were significantly elevated, whereas 25 proteins were downregulated, along with increasing age. Several upregulated proteins, including transgelin, vimentin, myosin regulatory light polypeptide 9, and calcyphosin, were further verified by quantitative Western blot analysis of hippocampal tissues from additional normal subjects. Bioinformatic analysis showed that the upregulated and downregulated proteins were largely involved in several important protein-protein interaction networks. Proteins in the electron transport chain and synaptic vesicle fusion pathway were consistently downregulated with aging, whereas proteins associated with Alzheimer's disease showed little change. Our study demonstrates substantial protein profile changes in the human hippocampus during aging, which could be of relevance to age-related loss of hippocampal functions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We previously identified the cell adhesion molecule (CAM) pathway as a consistent signal in 2 Alzheimer's disease (AD) genome-wide association studies (GWAS). However, the genetic mechanisms of the CAM pathway in AD are unclear. Here, we conducted pathway analysis using (1) Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathways; (2) 4 brain expression GWAS datasets; and (3) 2 whole-genome AD case-control expression datasets. Using the 4 brain expression GWAS datasets, we identified that genes regulated by cis-regulatory single-nucleotide polymorphisms (SNPs) were significantly enriched in the CAM pathway (p = 2.05E-06, p = 6.10E-07, p = 2.05E-06, and p = 1.47E-07 for each dataset). Interestingly, CAM is a significantly enriched pathway using down-regulated genes (raw p = 0.0235 and adjusted p = 0.0305) and all differentially expressed genes (raw p = 0.0105 and adjusted p = 0.0156) in dataset 5, and all differentially expressed genes (raw p = 0.0041 and adjusted p = 0.0062) in dataset 6. Collectively, our results show that CAM pathway genes are regulated by cis-regulatory SNPs and show significantly altered expression in AD. We believe that our results advance the understanding of AD mechanisms and will be useful for future genetic studies of AD., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Seizures are a potentially devastating complication of brain tumors. Several studies in the past have attempted to demonstrate that prophylactic antiepileptic drugs (AEDs) in patients with brain tumors can decrease the incidence of seizures. However, it is currently unclear whether AEDs should be routinely administered to patients with brain tumors who have never had a seizure., Objective: A meta-analysis of randomized trials was conducted to estimate the effectiveness of seizure prophylaxis in people with brain tumors., Methods: A range of electronic databases were searched (1966-2014): MEDLINE, the Cochrane Library Database, EMBASE, CINAHL, Web of Science and the Chinese Biomedical Database (CBM) without language restrictions. Two independent reviewers assessed trials for eligibility and quality, and meta-analysis was performed using the STATA 12.0 software. Integrated Odd Ratio (OR) with its corresponding 95% confidence interval (95%CI) was calculated., Results: Six RCTs were included with a total of 547 patients with brain tumors. The meta-analysis results revealed that patients with brain tumors who received prophylactic antiepileptic interventions did not have significantly lower epilepsy incidence than those in controlled groups (OR=0.939, 95%CI=0.609-1.448, z=0.29, P=0.775). Sensitivity analysis suggested the statistical results were robust. No publication bias was detected in this meta-analysis (P>0.05)., Conclusion: Although some past studies indicated AEDs can be used in patients with brain tumors to relieve epilepsy, present integrated evidences cannot show in unequivocal terms that brain tumor patients can benefit from seizure prophylaxis., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Usually, insufficient intratumoral concentration of therapeutic drugs is one of the reasons for tumor treatment failure. However, little is known about intratumoral distribution of bromocriptine in non-responding prolactinomas because of extremely low drug concentration and small prolactinoma tissue samples. In this study, a sensitive, rapid and high-throughput quantitative bioanalytical method has been established by using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for the determination of bromocriptine at trace level in human prolactinoma tissue. As little as 20 mg (wet weight) tissue sample was required and total analysis time was 6 min in this method. The assay quantifies over a linear range of 50 fg/mg to 5 pg/mg, and has a 25 fg/mg limit of detection at a signal/noise ratio of 3. This validated method was successfully used to quantitatively determine bromocriptine in clinical post-operative bromocriptine-sensitive and -resistant prolactinomas. The results revealed bromocriptine concentration in resistant prolactinomas (0.49-1.25 pg/mg) was significantly higher than that in sensitive prolactinomas (0.057-0.47 pg/mg). These results provided direct evidence to demonstrate the reseaon for failure of bromocriptine treatment in some patients with prolactinoma was "intrinsic" tumor (cell) resistence, rather than insufficient drug concentration in tumor tissue. Additionaly, this HPLC-MS/MS method has been shown to be suitable for bromocriptine analysis in small amount tissue sample and could be adapted for therapeutic drug monitoring of other clinical medicine., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To explore possible reasons for the incidence of a pituitary abscess following transsphenoidal surgery and determine the most effective treatment., Methods: A series of 12 patients who had undergone transsphenoidal surgery in other hospitals before being treated at Peking Union Medical College Hospital were reviewed. The presence of a pituitary abscess was confirmed when pus was intraoperatively observed within the sella turcica. All patients were treated with debridement of the abscess, nine among whom through a transsphenoidal approach and the other three via a craniotomy, followed by antibiotic treatment and hormone replacement therapy. The mean follow-up time was 27.0 months (range from 3.0 to 79.0 months)., Results: Headache (92%), panhypopituitarism (58%) and visual disturbance (50%) were the most common clinical indicators of a pituitary abscess. Imaging tests demonstrated a pituitary mass in all patients, with seven (58%) manifested with typical magnetic resonance features of an abscess. Ten patients (83%) were correctly diagnosed preoperatively. During surgical exploration, six presented with severe inflammation or an abscess within the sphenoidal sinus. Causative organisms were identified in five patients (42%). After surgical and antibiotic therapies, all patients fully recovered except for two presenting with severe visual impairment. Six patients (50%) required hormone replacement therapy., Conclusion: Retrograde infection from the sphenoid sinus may be a vital mechanism underlying the formation of a pituitary abscess following transsphenoidal surgery. Debridement of the abscess through surgical approaches combined with antibiotic treatment has been found to yield positive outcomes., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background Aims: Pre-clinical evidence indicates that autologous bone marrow-derived mesenchymal stromal cell (BM-MSC) transplantation improves motor function in patients with central nervous system disorders., Methods: After providing informed consent, 52 patients with cerebral palsy (CP) who met the study criteria received BM-MSC transplantation. Gross motor function was assessed using the Gross Motor Function Measure (GMFM)-88 and GMFM-66 scales at baseline (before transplantation) and at 1 month, 6 months and 18 months post-transplantation. The participants completed the trial without visible side effects. The GMFM-66 percentile (motor growth curves) was used as the control index of motor function to exclude the interference of improvement with age., Results: The score domains A, B, C and D and the total GMFM-88 and GMFM-66 scores in participants increased at 1 month, 6 months and 18 months post-transplantation compared with the baseline value (P < 0.01). The scores of domain E also increased at 6 months and 18 months post-transplantation, although they were not significantly increased at 1 month post-transplantation. There were significant increases in the GMFM-66 score and the GMFM-66 percentile corresponding to patient age and Gross Motor Function Classification System level after cell transplantation., Conclusions: Autologous BM-MSC transplantation appears to be a feasible, safe and effective therapy for patients with CP. The treatment improved the development of children with CP with regard to motor function., (Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)