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Introduction Pituitary growth hormone-secreting (GH) pituitary adenomas (PAs) cause mass effects and dysregulated hypersecretion of GH. However, somatic mutation burden is low in PAs. While progress has been made in identifying the epigenetic changes involved in GH-PA initiation, the precise details of its tumorigenesis in GH-PA patients remains to be elucidated. As N6-methyladenosine (m6A) has been shown to often play a critical role in various tumors, it represents a possible initiation point for the tumorigenesis of pituitary adenomas. However, the role of RNA methylation in GH adenomas remains unclear. Methods Protein expression of m6A regulators was measured by immunohistochemistry. Global levels and distribution of m6A methylation were separately analyzed by m6A enzyme-linked immunosorbent assay and m6A sequencing (m6A-seq). RNA interference and lentivirus knockdown system were used to investigate the role of methyltransferase-like 3 (METTL3) and its m6A- dependent regulatory mechanism in tumor progression and GH secretion. Results We show that both METTL3 messenger RNA and protein expression are elevated in GH-PA samples when compared with both normal pituitary tissue specimens and nonsecreting pituitary adenomas. Levels of m6A modification increased in GH-PAs, and hypermethylated RNAs are involved in hormone secretion and cell development. Knockdown of METTL3 in GH3 cell line resulted in decreased cell growth and GH secretion. Importantly, we found that GNAS and GADD45γ act as the downstream targets in this process. Conclusion Our findings strongly suggest that m6A methyltransferase METTL3 promotes tumor growth and hormone secretion by increasing expression of GNAS and GADD45γ in a m6A-dependent manner. Thus, METTL3 and the methylated RNAs constitute suitable targets for clinical treatment of GH-PAs.

Background Thyrotoxicosis is a rare complication of surgery for Cushing's disease (CD). In clinical practice, given the rarity of this condition, patients may be misdiagnosed, and thus not treated appropriately. This study describes the clinical features and management of thyrotoxicosis in this context. Methods We retrospectively screened a pituitary database for CD patients who underwent surgery at Peking Union Medical College Hospital between 2010 and 2017. The electronic medical records and documentation of 732 patients were searched in order to identify instances of thyrotoxicosis. Results Fourteen patients developed postoperative thyrotoxicosis after CD remission, representing 1.9% of all the CD patients who underwent surgery and 2.5% of the CD patients who were in remission after surgery. The onset of thyrotoxicosis occurred at a median of 3.5 months after surgery. At the onset, 13 patients (92.9%) were on a maintenance dose of hydrocortisone and were managed using a higher dose of hydrocortisone. One patient had normal adrenal function and was managed by observation first, then using anti-thyroid drugs. Thyrotoxicosis was transient in all but one patient, and lasted 1.9±0.7 months (range, 1-3.2 months). Conclusions Thyrotoxicosis is a rare complication that develops during the recovery period following surgery for CD. It occurs only after the surgical resolution of hypercortisolism, and in particular alongside adrenal insufficiency during the 4 months following CD remission. Awareness of this situation should be promoted among physicians, and patients should be managed on the basis of the clinical setting and manifestation.

Biochemical remission after transsphenoidal surgery is still unsatisfied in acromegaly patients with macroadenomas, especially with invasive macroadenomas. Concerning the impact of preoperative somatostatin analogues (SSAs) on surgical outcomes, previous studies with limited cases reported conflicting results. To assess current evidence of preoperative medical treatment, we performed a systematic review and meta-analysis of comparative studies. A literature search was conducted in Pubmed, Embase, and the Cochrane Library. Five randomized controlled trials (RCT) and seven non-RCT comparative studies were included. These studies mainly focused on pituitary macroadenomas though a small number of microadenoma cases were included. For safety, preoperative SSAs were not associated with elevated risks of postoperative complications. With respect to efficacy, the short-term cure rate was improved by preoperative SSAs, but the long-term cure rate showed no significant improvement. For invasive macroadenomas, the short-term cure rate was also improved, but the long-term results were not evaluable in clinical practice because adjuvant therapy was generally required. In conclusion, preoperative SSAs are safe in patients with acromegaly, and the favorable impact on surgical results is restricted to the short-term cure rate in macroadenomas and invasive macroadenomas. Further well-designed RCTs to examine long-term results are awaited to update the finding of this meta-analysis.

Background: The treatment of adult spinal deformity (ASD) remains a significant challenge, especially in elderly patients. This study aimed to evaluate the outcomes of the S2AI screw technique in the treatment of severe spinal sagittal imbalance with a minimum 2-year follow-up.Methods: From January 2015 to December 2018, 23 patients with severe degenerative thoracolumbar kyphosis who underwent placement of S2AI screws for long segment fusion were retrospectively reviewed. Patients were divided into group A (no mechanical complications, 13 cases) and group B (with mechanical complications, 10 cases) according to the occurrence of mechanical complications at the last follow-up. Radiographic parameters were compared between groups preoperatively, 1 month postoperatively and at the last follow-up. Risk factors for mechanical complications were analyzed.Results: The incidence of mechanical complications was 43.5% and the revision rate was 17.4%. At 1 month postoperatively, sagittal correction was better in group A than in group B (pConclusions: A high incidence of mechanical complications was observed in long-segment corrective surgery with the S2AI screw technique for severe spinal sagittal imbalance. Inadequate sagittal correction is a risk factor for the development of mechanical complications.

Pituitary adenomas (PAs) can be classified as non-secreting adenomas, somatotroph adenomas, corticotroph adenomas, lactotroph adenomas, and thyrotroph adenomas. Substantial advances have been made in our knowledge of the pathobiology of PAs. To obtain a comprehensive understanding of the molecular biological characteristics of different types of PAs, we reviewed the important advances that have been made involving genetic and epigenetic variation, comprising genetic mutations, chromosome number variations, DNA methylation, microRNA regulation, and transcription factor regulation. Classical tumor predisposition syndromes include multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4) syndromes, Carney complex, and X-LAG syndromes. PAs have also been described in association with succinate dehydrogenase-related familial PA, neurofibromatosis type 1, and von Hippel–Lindau, DICER1, and Lynch syndromes. Patients with aryl hydrocarbon receptor-interacting protein (AIP) mutations often present with pituitary gigantism, either in familial or sporadic adenomas. In contrast, guanine nucleotide-binding protein G(s) subunit alpha (GNAS) and G protein-coupled receptor 101 (GPR101) mutations can lead to excess growth hormone. Moreover, the deubiquitinase gene USP8, USP48, and BRAF mutations are associated with adrenocorticotropic hormone production. In this review, we describe the genetic and epigenetic landscape of PAs and summarize novel insights into the regulation of pituitary tumorigenesis.

Background: Gray matter (GM) alterations in Parkinson's disease (PD) patients with rapid eye movement sleep behavior disorder (RBD) have been demonstrated in many neuroimaging studies using voxel-based morphometry (VBM). However, the inconsistent findings between studies cannot be applied to clinical practice as a neuroimaging biomarker. We performed a meta-analysis of VBM studies at a whole-brain level to investigate GM differences between PD patients with and without RBD. Methods: A systematic search was conducted in PubMed, Embase, and Web of Science from inception to November 2019 to identify eligible VBM studies. We adopted the latest Seed-based d Mapping with Permutation of Subject Images technique to quantitatively estimate the difference of regional GM volume between PD patients with and without RBD. Results: We included five studies comprising 105 PD patients with RBD and 140 PD patients without RBD. The pooled meta-analysis revealed that PD patients with RBD showed a significant reduction of GM volume in the right superior temporal gyrus (STG) compared with those without RBD. This result was confirmed to be robust by the jackknife sensitivity analysis. Conclusion: Our finding shows significantly and robustly reduced GM volume in the right STG in PD patients with RBD, preliminarily suggesting the association of GM atrophy in this brain region with the occurrence of RBD in PD patients.

Introduction: Sirt1 is a NAD+ dependent deacetylase that is known as an important metabolic regulator for type 2 diabetes melitus. To determine the role of Sirt1 in ischemic stroke-induced metabolic imbalance, we generated the neuronal specific Sirt1 knock-in (nSirt1 KI) and knock-out (Sirt1 KO) mice and examined its effect and mechanism. Methods: To determine the role of Sirt1 in ischemic stroke-induced impaired metabolic actions including insulin and glucose abnormality, we tested the pharmacological effects of Metformin and Sirtinol as Sirt1 activator and inhibitor. To determine the genetic role of neuronal Sirt1 in the brain, we generated the nSirt1 KI mice and Sirt1 KO. We used the Ischemia/Reperfusion (I/R: 1h middle cerebral artery occlusion (MCAO)/23h reperfusion) injury model to induce the abnormal metabolic changes. Infarction volume was measured by TTC staining and we determined neurological deficit score (NDS) at 23h after 1h MCAO. The level of glucose and insulin were measured by a drop of tail blood using test-strip and ELISA Kit before, during (every 10 minutes interval), and after MCAO. Results: Metformin reduced infarction volume and Sirtinol worsened the infarction volume via Sirt1 signaling pathway. Heterozygous Sirt1 KO (Sirt1 +/-) mice showed decreased relative cerebral blood flow (rCBF) and worsen infarction volume in ischemic areas, whereas nSirt1 KI mice exhibited increased rCBF, improved NDS, regulating abnormal blood glucose and insulin, and reduced infarction volume by 42% compare to that of littermate control in I/R injury model (n=7, p Conclusion: These findings indicate that the important neuroprotective effect of neuronal cells is mediated by Sirt1 overexpression and suggest that upregulation of neuronal Sirt1 may be an important therapeutic target for ischemic stroke via regulating metabolic imbalance.

Introduction: The role of neuronal cell specific ROCK2 in ischemic stroke in vivo has been poorly investigated. We investigated the pharmacological effect of selective ROCK2 inhibition by selective ROCK2 inhibitor, KD025 and the genetic effect using neuronal specific ROCK2 knockout (ROCK2Eno2-/-) mice. Methods: Isoflurane-anesthetized littermate control (LC) and ROCK2Eno2-/- mice (20-22 g) underwent ischemia (2h middle cerebral artery occlusion (MCAO)/reperfusion (22h after 2h MCAO) injury model. An 8.0 nylon monofilament coated with a silicone was introduced into the left internal carotid artery up to the anterior cerebral artery. To assess the mechanism of ROCK2 deficiency in neuronal cells, we seeded hippocampal neuronal (HT22) cells in 6-well plates and transfected ROCK2 siRNA. Phosphorylated glycogen synthase kinase 3 beta (pGSK-3β) and Tau proteins which were involved in neuroprotection were measured by western blotting from brain lysates and neuronal cells. Infarction volume was measured by TTC staining and evaluation of behavioral was assessed by neurological deficit score (NDS) at 22h after MCAO. Results: In WT mice, ROCK2 inhibition by KD025 (100 mg/kg, p.o.) decreased infarct volumes and improved the NDS in ischemic stroke. ROCK activity (p-MYPT1 to MYPT1 ratio) of the brain lysates by KD025 was decreased dose-dependently in ischemic mice brain. In genetic modified mice, infarction volume (64.6 ± 10.4 vs. LC (102.3 ± 12.4), n=5) of ROCK2Eno2-/- mice was significantly decreased by 37% and the NDSs (1.8 ± 0.4 vs. LC (2.8 ± 0.5), n=5) were improved by 36% compared to the LC groups. Both pGSK-3β and Tau in HT22 cells with ROCK2 siRNA transfection and ROCK2Eno2-/- mice brain was significantly decreased compared to each respective controls. Conclusion: These findings indicate that neuronal ROCK2 plays important role in ischemic stroke via GSK-3β and Tau signaling pathways and inhibition of neuronal specific ROCK2 may have therapeutic benefits in ischemic stroke.

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.

// Congxin Dai 1, * , Bowen Sun 1, * , Xiaohai Liu 1 , Xinjie Bao 1 , Ming Feng 1 , Yong Yao 1 , Junji Wei 1 , Kan Deng 1 , Chengxian Yang 1 , Xueyuan Li 1 , Wenbin Ma 1 , Renzhi Wang 1 1 Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China * These authors have contributed equally to this work Correspondence to: Renzhi Wang, email: Wangrz@126.com Keywords: pituitary adenomas, MGMT, recurrence, aggressive Received: October 07, 2016 Accepted: December 01, 2016 Published: February 01, 2017 ABSTRACT O-6-methylguanine-DNA methyltransferase (MGMT) reportedly counteracts the cytotoxic effects of the alkylating agent temozolomide. MGMT expression is often low in aggressive pituitary adenomas (PAs) and recurrent PAs. However, because these associations are controversial, we performed this meta-analysis to clarify the involvement of MGMT in the prognosis and clinicopathology of PA. We searched for relevant studies in electronic databases (MEDLINE, the Cochrane Library Database, EMBASE, CINAHL, Web of Science and the Chinese Biomedical Database (CBD)) and calculated/pooled the odds ratios (ORs) or standard mean differences (SMDs) with 95% confidence intervals (95% CIs). Eleven case-control studies with a total of 454 PA patients were included. Our meta-analysis revealed that lower expression of MGMT was associated with PA recurrence (OR=2.09, 95% CI=1.09–4.02; p =0.026). On the other hand, MGMT expression was not associated with PA invasiveness (OR=1.112, 95% CI=0.706–1.753; p =0.646), Unexpectedly, MGMT expression could not be used to distinguish functional from non-functional PA patients (OR=1.766, 95% CI=0.938–3.324; p =0.078). The MGMT expression was not found to be related to other clinicopathological indicators of PA including age, gender or tumor size. No publication bias was detected in this meta-analysis (p>0.05). This meta-analysis suggests that MGMT expression may be associated with PA tumor recurrence, but not be related to invasiveness or other clinicopathological indicators. Thus, detection of MGMT expression may facilitate outcome prediction and guide clinical therapy for PA patients.

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.

There is controversy regarding the surgical route selection for tuberculum sellae meningiomas (TSMs): the transsphenoidal (TS) or transcranial (TC) approach? We conducted a systematic review and meta-analysis to compare clinical outcomes and postoperative complications between two surgical approaches. Literature search was performed. Relevant articles were selected and evaluated. Data were extracted and analyzed. Eight articles comprising 550 patients met the inclusion criteria. Traditionally, the rates of gross total resection, tumor recurrence, visual improvement, and cerebrospinal fluid leakage were the most common outcomes of interest. We demonstrated that the TS approach was significantly associated with better visual outcomes but more frequent cerebrospinal fluid leakage, while the rates of tumor resection and recurrence showed no significant difference between groups. In addition to surgical results that were consistent with previous studies, we further evaluated the impact of approach selection on common postoperative complications, which were closely related to the recovery course and quality of life. We revealed that the risk of dysosmia was significantly higher in the TS group. There was no significant difference between groups regarding infection, intracranial hemorrhage, and endocrine disorders. Because of the relatively low evidence levels of included retrospective studies, it was difficult to reach a categorical conclusion about the optimal surgical approach for TSMs. Finally, we recommended that the TS approach was an alternative option in patients with smaller TSMs (

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.

Though pituitary adenomas are benign tumors in most cases, a considerable fraction of PAs behave in a malignant-like manner and invade to the adjacent structures in sellar region, especially the cavernous sinuses. Cancer-cell invasion and metastasis remain a great challenge for physicians and surgeons in spite of emerging advances in drug therapy and surgical Treatment. matrix metalloproteinases, as a family of zinc-dependent endopeptidases, have long been known to be associated with tumor invasion and metastasis mainly via breaking down basement membrane in different tissues. Aberrant expression and activation of matrix metalloproteinases have been detected in invasive pituitary adenomas as in malignancy and correlated to tumor invasion. Therefore, matrix metalloproteinases are considered as promising biomarkers for predicting tumor behavior and even drug targets for novel therapeutic strategies. In this review, we give an overview of the expression, function, regulation and clinical prospects of matrix metalloproteinases, especially focusing on the biological network in which matrix metalloproteinases may be abnormally activated in promoting pituitary adenoma invasion.

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.

Rationale: Case reports concerning the value of dopamine agonists in the treatment of patients with thyrotropin-secreting pituitary adenoma (TSHoma) are limited. Herein, we present a rare case of octreotide-insensitive TSHoma responding to bromocriptine therapy. Patient concerns: A 45-year-old Chinese man was admitted to Peking Union Medical College Hospital with marked clinical manifestations of hyperthyroidism. Diagnoses: Thyroid function tests demonstrated elevated concentrations of free thyroid hormones in the presence of normal thyrotropin. Magnetic resonance imaging findings showed a pituitary microadenoma on the right side of the sellar region. Based on characteristic endocrine results and neuroimaging findings, the patient was diagnosed with TSHoma. Interventions: Most patients with TSHomas are significantly responsive to somatostatin analog treatment. However, our patient was orally administered with bromocriptine to normalize thyroid function as assessed by suppression tests conducted prior to surgery. A transsphenoidal surgery was performed by an experienced neurosurgeon for tumor removal. Outcomes: The pituitary lesion was totally resected. Following the operation, the results of thyroid function tests were immediately within reference limits. During the follow-up, there was no residual or recurrent tumor. Lessons: Attention should be paid to the role of dopamine agonists such as bromocriptine and cabergoline as adjuvant therapy for TSHomas that are insensitive to traditional medical treatment by somatostatin analogs.

Rationale:Sellar metastasis is a rare and complex disease whose clinical features are strongly associated with the primary malignancy. Here, we present a rare case of giant sellar metastasis spread from renal cell carcinoma (RCC).Patient concerns:A 30-year-old Chinese woman was admitted to o

Rationale: The transsphenoidal surgical (TS) approach to sellar masses is the preferred surgical route in most cases. Secondary pituitary abscess (PA) following TS is an extremely rare but serious postoperative complication with potentially high disability and mortality. Patient concerns: We describe an uncommon case of secondary PA in a 42-year-old woman, who underwent uncomplicated transsphenoidal procedures without cerebrospinal fluid leak, to treat primary Rathke cleft cyst. Without obvious cause, the patient suffered recurrent meningitis with complaints of headache, hyperpyrexia, and chills from 1 month after the operation. Diagnosis: There were no significant imaging findings until a new rim-enhancement lesion was seen in the sellar region on magnetic resonance imaging during the 6th episode of meningitis 11 months after the initial surgery. A diagnosis of secondary PA was considered; Interventions: Therefore, she underwent a 2nd TS with pus evacuation and antibiotic treatment. Outcomes: She improved remarkably and had no recurrence of symptoms during the 9-month follow-up. Lessons: Our aim was to present this rare case and discuss the most likely etiologies and preventive measures for this condition. In patients with recurrent meningitis but dormant imaging manifestations after TS, the possibility of secondary PA should considered. Adequate surgical drainage with microbiology-guided antibiotic therapy is the 1st choice for treatment.

Malignant peripheral nerve sheath tumor (MPNST) is an uncommon neoplasm that rarely involves the head and neck region. Intracranial MPNSTs unrelated to cranial nerves are highly malignant tumors with poor overall survival, probably because of infiltrating growth into surrounding brain tissue. The pathogenesis of MPNST remains unclear. There are no conclusive explanations for the mechanisms underlying the initiation, progression, and metastasis of MPNST. In this paper, we describe a case of MPNST in the pterygopalatine fossa with intracranial metastatic recurrence and review related literatures. Meanwhile, targeted next-generation sequencing (NGS) revealed the presence of both a beta-catenin (CTNNB1) missense mutation p.Ser33Phe and a mediator complex subunit 12 (MED12) frameshift mutation p.Tyr1278fs in the recurrent intracranial tumor. Therapies that target CTNNB1 mutation, MED12 mutation, CTNNB1 activation, or Wnt pathway activation are worth future studying.

To the Editor: A 35-year-old Chinese woman was admitted to our hospital complaining of a 1-year history of bilateral temporal chronic intermittent moderate headache which used to be alleviated by ibuprofen tablets or rest and had increased in intensity in the past 1 month. The patient also presented with the slow development of visual deficit. In January 2012, the patient presented with polyuria and polydipsia suggestive of central diabetes insipidus. Endocrine studies showed no clinically significant results. The patient also underwent a brain magnetic resonance imaging (MRI) which demonstrated an ovoid sellar lesion measuring 6 mm × 6 mm, with hyperintense, with no apparent enhancement after administration of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) on T1-weighted images and iso- to hypo-intense on T2-weighted images [Figure 1a]. The patient was initially diagnosed with Rathke's cleft cyst (RCC) and refused to undergo the operation. By the end of 2013, she once again presented with polyuria and polydipsia that were in spontaneous remission in the following 6 months with no medical intervention. A radiographic follow-up was administrated in July 2014 demonstrating an ovoid sellar lesion measuring 9 mm × 11 mm × 14 mm indicative of enlargement of the former cyst, with hyperintense, with no obvious enhancement after administration of Gd-DTPA on T1-weighted images and iso- to hyper-intense on T2-weighted images [Figure 1b], and apparently, the signal characteristics of the MRI were almost the same as the initial one suggesting likely hemorrhage. From July 2014 to May 2015, she sought for medical services in the Department of Traditional Chinese Medicine and regularly took medicinal herbs aiming to promote circulation and remove stasis. In May 2015, she complained of a slightly blurred vision of her right eye. In November 2015, she was attacked by a severe unbearable headache, a vision's sharp decline of the right eye, and mild right temporal hemianopsia. The pain was diffuse, dull, and persistent for a week and could not be alleviated by tablets or rest as before. Her medical history was otherwise unremarkable. The general physical examination was uneventful. The neurological examination showed an awake, alert, and completely oriented patient with no focal sign. The muscular strength and tension of her four limbs were completely normal. Various physiological reflexes could be elicited in response to external stimulus. Pathological signs were absent. The results of ophthalmologic tests were in accordance with her self-reported symptoms indicating remarkable changes of visual acuity (VA) and visual field. Preoperatively, VA of the right eye was 0.5+, and VA of the left eye was 0.8. Partial temporal hemianopia was observed with no suspect [Figure 1c]. The results of hematologic and biochemical tests were uneventful. Endocrine evaluations were within the normal ranges. MRI studies demonstrated a sellar and suprasellar lesion with hyperintense, with no apparent enhancement after administration of Gd-DTPA on T1-weighted images and hyperintense on T2-weighted images, measuring 16.8 mm × 16.0 mm × 14.6 mm [Figure 1d]. Located in the inferoposterior position of RCC, there was an irregular-shaped lesion showing hypointense on T1-weighted images and hypointense on T2-weighted images suggesting internal apoplexy. The mixed signal intensity was thought to be consistent with the symptom of apoplexy indicating intracystic old hemorrhage of RCC. Repeated MRI findings revealed the rapid enlargement of RCC within