A rare adult case of asymptomatic double aortic arch accompanied by the right vertebral artery directly originating from the aortic arch.

INTRODUCTION: A double aortic arch (DAA) is a rare congenital vascular anomaly. No case of DAA with a direct aortic origin of the right vertebral artery (VA) has been reported in adults. Here, we report a rare case of an asymptomatic DAA accompanied by the right VA directly originating from the right aortic arch in an adult. CASE PRESENTATION: A DAA and right VA directly originating from the right aortic arch were identified in a 63-year-old man using digital subtraction angiography and computed tomography angiography. The patient underwent digital subtraction angiography for evaluation of an unruptured cerebral aneurysm. Intraprocedural selection of vessels branching from the aorta with the catheter was difficult. To confirm the bifurcation of the aorta, aortography was performed, which revealed a DAA. Following digital subtraction angiography, computed tomography angiography was performed, which showed that the right VA originated directly from the right aortic arch. The trachea and esophagus were located in the vascular ring of the DAA; however, they were not compressed by the aorta. This was consistent with the lack of symptoms related to the DAA. CONCLUSIONS: This is the first adult case of an asymptomatic DAA with an unusual origin of the VA. A rare asymptomatic vascular anomaly, such as a DAA, can be incidentally identified using angiography.

Inhibition of VEGF receptors induces pituitary apoplexy: An experimental study in mice.

Anti-vascular endothelial growth factor (VEGF) therapy has been developed for the treatment of a variety of cancers. Although this therapy may be a promising alternative treatment for refractory pituitary adenomas and pituitary carcinomas, the effects of anti-VEGF agents on the pituitary gland are not yet well understood. Here, we found that mice administered with OSI-930, an inhibitor of receptor tyrosine kinases including VEGF receptor 1 and 2, frequently exhibited hemorrhage in the pituitary gland. This is the first report that anti-VEGF therapy can cause pituitary apoplexy. C57BL/6 mice were daily injected intraperitoneally with 100 mg/kg body weight of OSI-930 for one to six days. Pituitary glands were immunohistochemically examined. Four of six mice treated for three days and all of five mice treated for six days exhibited hemorrhage in the pituitary gland. In all cases, the hemorrhage occurred just around Rathke's cleft. In OSI-930-administered mice, the vascular coverage and branching were reduced in the anterior lobe, and capillary networks were also decreased in the intermediate lobe in a treatment-day dependent manner. Few blood vessels around Rathke's cleft of the intermediate lobe express VE-cadherin and are covered with platelet-derived growth factor receptor-ß (PDGFR-ß)-positive cells, which suggests that capillaries around Rathke's cleft of the intermediate lobe were VE-cadherin-negative and not covered with pericytes. The reduction of capillary plexus around Rathke's cleft was observed at the site where hemorrhage occurred, suggesting a causal relationship with the pathogenesis of pituitary hemorrhage. Our study demonstrates that anti-VEGF agents have a risk of pituitary apoplexy. Pituitary apoplexy should be kept in mind as an adverse effect of anti-VEGF therapy.

Ruptured saccular aneurysm of the lenticulostriate artery embolized without parent artery occlusion in a case of moyamoya disease.

In cases of moyamoya disease, an aneurysm of the lenticulostriate artery (LSA) is a rare finding. Preventive management of rebleeding from a ruptured aneurysm of the LSA is important to avoid poor outcomes. Endovascular embolization of a ruptured LSA aneurysm with parent artery occlusion has been reported in previous cases of moyamoya disease; however, to the best of our knowledge, a ruptured aneurysm treated only with coil embolization has not been described. A 42-year-old woman presented with sudden onset of dysarthria and right hemiparesis. Putaminal hemorrhage from a ruptured aneurysm in the left LSA was detected. Angiographically, moyamoya vessels were revealed. The aneurysm in the left LSA was saccular type and seemed to be related to moyamoya disease. As the aneurysm was successfully approached with a microcatheter, coil embolization without parent artery occlusion was performed. Rebleeding from the embolized aneurysm in the LSA did not occur. This is the first report of a ruptured LSA aneurysm embolized using coils through a flow-guiding microcatheter without parent artery occlusion in a case of moyamoya disease.

Cavernous sinus dural arteriovenous fistula embolized via a rare anastomosis between the facial vein and the superficial temporal vein.

A cavernous sinus dural arteriovenous fistula (CSdAVF) is an abnormal communication between the dural branches of the internal and external carotid arteries and the cavernous sinus. Transvenous embolization is the first choice to resolve CSdAVFs, and various venous access routes have been reported. However, transvenous embolization of a CSdAVF through a rare venous anastomosis between the facial and superficial temporal veins using a quadruple coaxial catheter system is scarce in the literature. A 30-year-old woman presented with a typical triad of CSdAVF that was supplied by the inferolateral and meningohypophyseal trunks and several dural branches of the external carotid artery. CSdAVF was solely draining through the right superior ophthalmic vein to the bilateral facial veins. The right facial vein had a rare anastomosis, with the superficial temporal vein terminating in the external jugular vein. Transvenous targeted embolization of CSdAVF was performed through the right superior ophthalmic vein. The rare anastomosis between the right superficial temporal vein and the right facial vein was used as the access route for CSdAVF. The quadruple coaxial catheter system was effective in overcoming the long and tortuous access route and stabilizing the movement of the microcatheter for target embolization. CSdAVF was successfully embolized with microcoils. This is the first report of a CSdAVF embolized via a rare anastomosis between the facial vein and the superficial temporal vein. A quadruple coaxial catheter system can overcome this unusual access route.

Rare anastomosis between the bilateral internal carotid arteries via the recurrent arteries branching from the first segment of the ophthalmic artery.

Although anastomoses between the arterial branches arising from the internal carotid artery (ICA) can develop as collateral pathways between the bilateral ICAs in cases of dysgenesis of the ICA, anastomosis of the recurrent arteries branching from the first segment of the ophthalmic artery (OphA) has not been described. Herein, we report two cases of this rare anastomosis. In a 36-year-old man with left segmental dysgenesis of the ICA, an anastomosis between the bilateral ICAs developed around the sella turcica. In a 39-year-old woman with dysgenesis of the bilateral distal ICAs, an anastomosis between the superior hypophyseal trunk and bilateral ICAs was identified. The anastomoses in both cases were also supplied by recurrent arteries branching from the first segment of the OphAs. This is the first report describing recurrent arteries from the OphAs that form the anastomosis between bilateral ICAs.

Acromegaly accompanied by diabetes mellitus and polycystic kidney disease.

Acromegaly is characterized by autonomous excessive growth hormone (GH) secretion, generally due to GH-producing pituitary adenoma, and is associated with various systemic comorbidities including diabetes mellitus. Polycystic kidney disease (PKD) is characterized by the growth of numerous cysts in the kidneys that deteriorate renal function. While possible renal effects of excessive GH exposure have been a current issue in experimental medicine, only five cases of coexisting acromegaly and PKD have been reported previously, and little is known regarding the influence of acromegaly on renal disease. We treated a 50-year-old male with diabetes mellitus who showed a sudden and rapid decline of renal function along with increasing proteinuria, which led to diagnoses of PKD and acromegaly. His urinary protein levels were increased together with excessive GH secretion and worsening glycemic control. An increase of total kidney volume was also noted. Transsphenoidal surgery for the pituitary adenoma was successfully performed. Marked improvement of hyperglycemia and proteinuria were observed after the surgery, but renal function was unchanged. The patient's clinical course suggested common aspects of excessive GH secretion as an accelerating factor of the progression of diabetic nephropathy and PKD via direct and indirect pathways. Although coexisting acromegaly and PKD is clinically rare, vigilance for early diagnosis of acromegaly is appropriate in patients with diabetes and/or PKD, especially in those showing unexpected exacerbation of renal dysfunction.

Functional Connectivity Analysis and Prediction of Pain Relief in Association with Spinal Decompression Surgery.

BACKGROUND: Although spinal decompression surgery is an effective treatment for myelopathy-induced upper limb pain, some postoperative patients suffer from residual pain in spite of adequate decompression. However, the neural mechanism underlying the poor outcome of pain relief is still unclear. The goal of this study was to explore the brain mechanisms involved in the poor recovery of upper limb pain after the spinal decompression surgery by using functional connectivity (FC) analysis. METHODS: In this cross-sectional study, 17 patients who underwent cervical spinal decompression surgery were included. Functional MRI (fMRI) during a tactile stimulus for each hand was performed at 1 day before and 7 days after the surgery. In total, 34 fMRI scans (17 left and right upper limbs, respectively) were obtained before and after the surgery, respectively. The patients were divided into poor-recovery and good-recovery groups, and then we searched for the FC that was related to poor-recovery. RESULTS: The poor-recovery group (n = 15) showed significantly stronger connectivity between the postcentral gyrus (postCG) and dorsolateral prefrontal cortex (DLPFC) than the good-recovery group (n = 12) preoperatively. When the cutoff value of the preoperative FC between the left postCG and right middle frontal gyrus included in DLPFC was >0.17, the sensitivity and specificity for poor recovery were 73% and 75%, respectively. CONCLUSIONS: Our study showed that FC between the postCG and DLPFC may be a predictor of pain relief. This result suggested that assessing FC can lead to more informed surgical interventions for cervical spondylotic myelopathy.

Daily Habit of Water Intake in Patients with Cerebral Infarction before its Onset; Comparison with a Healthy Population: A Cross-Sectional Study.

BACKGROUND: While water intake is frequently recommended to prevent cerebral infarction (CI), only few studies have been published on this topic. OBJECTIVES: This study retrospectively estimated the daily non-alcohol drink (NAD) intake in CI patients before CI onset and compared it with NAD in healthy subjects. METHODS: We performed a cross-sectional study on CI patients in 3 hospitals and healthy subjects in the Kobe Orthopedic and Biomedical Epidemiologic (KOBE) study. Data from 1,287 subjects (274 CI patients and 1,013 healthy subjects) were used for the analyses. By dividing the CI patients into "increased", "unchanged", and "decreased" groups according to their current NAD intake, we compared the NAD intake between these 3 groups and healthy subjects by analyses of covariance and the post hoc test, adjusting for sex, age, surveyed month, body mass index, alcohol drinking history, and smoking history. Under the assumption that the NAD intake in the "unchanged" group was equal to the NAD intake before CI onset, the OR of less NAD intake for CI adjusting for the relevant variables in the "unchanged" group and the healthy subjects was calculated; the cut-off point was chosen using Youden's index. RESULTS: The mean age (mean ± SD) of the participants was 62.8 ± 9.3 years. One hundred and fifty-one patients (36 women) were included in the "increased" group; 105 (30 women), in the "unchanged" group; 18 (2 women), in the "decreased" group; and 1,013 (706 women), in the "healthy" group. The mean NAD intake was 1,702.5 ± 670.2 mL in the "increased" group, 1,494.2 ± 611.2 mL in the "unchanged" group, 1,268.0 ± 596.1 mL in the "decreased" group, and 1,720.6 ± 686.0 mL in the "healthy" group. After adjusting for the relevant variables, a significant difference in NAD intake between the groups was observed (F = 6.1, p < 0.001), and a post hoc test demonstrated significant differences (p < 0.05) in NAD intake between the "healthy" and "unchanged" groups, and between the "increased" and "unchanged" groups. The OR of less NAD intake (<1,570 mL/day, chosen using Youden's index) for CI was 2.48 (95% CI 1.52-4.07). CONCLUSION: This study showed that daily NAD intake before CI onset in CI patients was less than that in healthy persons, indicating that sufficient intake of NAD may be protective for CI.

The proneural bHLH genes Mash1, Math3 and NeuroD are required for pituitary development

Multiple signaling molecules and transcription factors are required for pituitary development. Activator-type bHLH genes Mash1, Math, NeuroD (Neurod) and Neurogenin (Neurog) are well known as key molecules in neural development. Although analyses of targeted mouse mutants have demonstrated involvement of these bHLH genes in pituitary development, studies with single-mutant mice could not elucidate their exact functions, because they cooperatively function and compensate each other. The aim of this study was to elucidate the roles of Mash1, Math3 and NeuroD in pituitary development. Mash1;Math3;NeuroD triple-mutant mice were analyzed by immunohistochemistry and quantitative real-time RT-PCR. Misexpression studies with retroviruses in pituisphere cultures were also performed. The triple-mutant adenohypophysis was morphologically normal, though the lumen of the neurohypophysis remained unclosed. However, in triple-mutant pituitaries, somatotropes, gonadotropes and corticotropes were severely decreased, whereas lactotropes were increased. Misexpression of Mash1 alone with retrovirus could not induce generation of hormonal cells, though Mash1 was involved in differentiation of pituitary progenitor cells. These data suggest that Mash1, Math3 and NeuroD cooperatively control the timing of pituitary progenitor cell differentiation and that they are also required for subtype specification of pituitary hormonal cells. Mash1 is necessary for corticotroph and gonadotroph differentiation, and compensated by Math3 and NeuroD. Math3 is necessary for somatotroph differentiation, and compensated by Mash1 and NeuroD. Neurog2 may compensate Mash1, Math3 and NeuroD during pituitary development. Furthermore, Mash1, Math3 and NeuroD are required for neurohypophysis development. Thus, Mash1, Math3 and NeuroD are required for pituitary development, and compensate each other.

Differential Diagnosis between Low-Grade and High-Grade Astrocytoma Using System A Amino Acid Transport PET Imaging with C-11-MeAIB: A Comparison Study with C-11-Methionine PET Imaging.

Introductions: [N-methyl-C-11]α-Methylaminoisobutyric acid (MeAIB) is an artificial amino acid radiotracer used for PET study, which is metabolically stable in vivo. In addition, MeAIB is transported by system A neutral amino acid transport, which is observed ubiquitously in all types of mammalian cells. It has already been shown that MeAIB-PET is useful for malignant lymphoma, head and neck cancers, and lung tumors. However, there have been no reports evaluating the usefulness of MeAIB-PET in the diagnosis of brain tumors. The purpose of this study is to investigate the efficacy of system A amino acid transport PET imaging, MeAIB-PET, in clinical brain tumor diagnosis compared to [S-methyl-C-11]-L-methionine (MET)-PET. Methods: Thirty-one consecutive patients (male: 16, female: 15), who were suspected of having brain tumors, received both MeAIB-PET and MET-PET within a 2-week interval. All patients were classified into two groups: Group A as a benign group, which included patients who were diagnosed as low-grade astrocytoma, grade II or less, or other low-grade astrocytoma (n=12) and Group B as a malignant group, which included patients who were diagnosed as anaplastic astrocytoma, glioblastoma multiforme (GBM), or recurrent GBM despite prior surgery or chemoradiotherapy (n=19). PET imaging was performed 20 min after the IV injection of MeAIB and MET, respectively. Semiquantitative analyses of MeAIB and MET uptake using SUVmax and tumor-to-contralateral normal brain tissue (T/N) ratio were evaluated to compare these PET images. ROC analyses for the diagnostic accuracy of MeAIB-PET and MET-PET were also calculated. Results: In MeAIB-PET imaging, the SUVmax was 1.20 ± 1.29 for the benign group and 2.94 ± 1.22 for the malignant group (p < 0.005), and the T/N ratio was 3.77 ± 2.39 for the benign group and 16.83 ± 2.39 for the malignant group (p < 0.001). In MET-PET, the SUVmax was 3.01 ± 0.94 for the benign group and 4.72 ± 1.61 for the malignant group (p < 0.005), and the T/N ratio was 2.64 ± 1.40 for the benign group and 3.21 ± 1.14 for the malignant group (n.s.). For the analysis using the T/N ratio, there was a significant difference between the benign and malignant groups with MeAIB-PET with p < 0.001. The result of ROC analysis using the T/N ratio indicated a better diagnosis accuracy for MeAIB-PET for brain tumors than MET-PET (p < 0.01). Conclusions: MeAIB, a system A amino acid transport-specific radiolabeled agents, could provide better assessments for detecting malignant type brain tumors. In a differential diagnosis between low-grade and high-grade astrocytoma, MeAIB-PET is a useful diagnostic imaging tool, especially in evaluations using the T/N ratio. Clinical trial registration: This trial was registered with UMIN000032498.

Stromal cells of hemangioblastomas exhibit mesenchymal stem cell-derived vascular progenitor cell properties.

Hemangioblastoma is composed of neoplastic stromal cells and a prominent capillary network. To date, the identity of stromal cells remains unclear. Mesenchymal stem cells can give rise to committed vascular progenitor cells, and ephrin-B2/EphB4 and Notch signaling have crucial roles in these steps. The aim of our study was to elucidate that stromal cells of central nervous system hemangioblastomas have mesenchymal stem cell-derived vascular progenitor cell properties. Ten hemangioblastomas were investigated immunohistochemically. CD44, a mesenchymal stem cell marker, was detected in stromal cells of all cases, suggesting that stromal cells have mesenchymal stem cell-like properties. Neither CD31 nor α-SMA was expressed in stromal cells, suggesting that stromal cells have not acquired differentiated vascular cell properties. Both ephrin-B2 and EphB4, immature vascular cell markers, were detected in stromal cells of all cases. Jagged1, Notch1, and Hesr2/Hey2, which are known to be detected in both immature endothelial cells and mural cells, were expressed in stromal cells of all cases. Notch3, which is known to be detected in differentiating mural cells, was also expressed in all cases. These results suggest that stromal cells also have vascular progenitor cell properties. In conclusion, stromal cells of hemangioblastomas exhibit mesenchymal stem cell-derived vascular progenitor cell properties.

Role of Endothelial-to-Mesenchymal Transition in the Pathogenesis of Central Nervous System Hemangioblastomas.

OBJECTIVE: Hemangioblastomas (HBs) are benign vascular tumors of the central nervous system and histologically contain abundant microvessels. Therefore, they clinically exhibit vascular malformation-like characteristics. It has been described that endothelial-to-mesenchymal transition (EndMT) contributes to the pathogenesis of cerebral cavernous malformations. However, it remains unknown whether EndMT contributes to the pathogenesis of central nervous system HBs. The aim of our study was to investigate whether EndMT occurs in central nervous system HBs. METHODS: Ten central nervous system HBs were immunohistochemically investigated. RESULTS: Cluster of differentiation (CD) 31 (an endothelial marker) and EndMT markers, such as α-smooth muscle actin (a mesenchymal marker) and CD44 (a mesenchymal stem cell marker), were expressed in the endothelial layer of microvessels in all cases. These findings suggest that endothelial cells (ECs) of microvessels in central nervous system HBs have acquired mesenchymal and stem cell-like characteristics and undergone EndMT. In all cases, both ephrin-B2 and EphB4, which are not detected in adult normal brain vessels, were expressed in the endothelial layer of microvessels. These data suggest that ECs of microvessels in central nervous system HBs are immature or malformed cells and have both arterial and venous characteristics. CONCLUSIONS: To our knowledge, this is the first report showing the possibility that EndMT contributes to the pathogenesis of central nervous system HBs. It is likely that ECs of microvessels in central nervous system HBs are immature or malformed cells and have both arterial and venous characteristics. EndMT is expected to be a new therapeutic target in central nervous system HBs.

Spinal Meningioma Arising from the Denticulate Ligament.

BACKGROUND: To control bleeding during spinal meningioma surgery, early resection of the dural attachment is important. We report a case of a meningioma where identifying the tumor's dural attachment was difficult because the tumor arose from the denticulate ligament. This report histopathologically and surgically describes this rare occurrence. CASE DESCRIPTION: A 38-year-old man presented with a mass lesion that was found during a follow-up examination for vestibular schwannoma surgery performed 2 years prior. He was neurologically free of symptoms except for right-sided deafness. Magnetic resonance imaging revealed an intradural extramedullary mass at the C1 level. The tumor had homogeneous enhancement after administration of gadolinium; however, no dural tail sign was seen. Schwannoma was diagnosed, and lesion resection was performed. The hard, white tumor was adherent to the denticulate ligament, and no dural attachment was found. The tumor was totally removed after resection of the denticulate ligament. Histopathologic investigation, based on immunoreactivity to epithelial membrane antigen, revealed that the tumor was a meningioma. In addition to normal fibrous tissue, the denticulate ligament was infiltrated by tumor cells. Based on histopathologic findings and the absence of a dural attachment, we suspect that this meningioma originated from the denticulate ligament. CONCLUSIONS: If it is difficult to find the dural attachment during spinal meningioma surgery, the possibility of a denticulate meningioma should be considered, and the attachment should be resected as soon as possible.

Cortical Reorganizations for Recovery from Depressive State After Spinal Decompression Surgery.

BACKGROUND: Depressed mood following neuronal damage not only impedes functional recovery but also negatively affects quality of life for many patients. Depressed patients with cervical myelopathy often show improvement in both mood and motor function after spinal decompression surgery; however, the neural mechanism underlying this psychological benefit from surgery remains unclear. The aim of this study was to clarify the brain sites that relate to alleviation of depression after spinal decompression surgery. METHODS: We compared brain activity of patients with cervical myelopathy (n = 6) with healthy participants (n = 5) using functional magnetic resonance imaging. We then analyzed functional magnetic resonance imaging data to find the brain regions that correlated with depression severity (n = 12; 6 preoperative patients and 6 postoperative patients) and compared preoperative imaging data with postoperative imaging data from patients. RESULTS: Spinal decompression surgery alleviated depression and diminished anterior cingulate cortex activity. Simultaneously, supplementary motor area activity, which was increased in patients with myelopathy compared with control subjects, was diminished after surgery. CONCLUSIONS: Traditionally, surgical indications for myelopathy are determined by the severity of sensorimotor symptoms without considering psychological symptoms. We anticipate our results will lead to more informed surgical decisions for cervical spondylosis myelopathy.

Intraoperative FLOW 800 Analysis for Intramedullary Cystic Lesion: A Technical Case Report.

BACKGROUND AND IMPORTANCE: During intramedullary lesion surgery, the lesion site and the posterior median sulcus (PMS) should be accurately identified prior to myelotomy to avoid severe injury of the posterior funiculus. However, intramedullary lesions are fundamentally invisible until the myelotomy is performed. Furthermore, the PMS location is frequently unclear due to lesion-induced swelling or distortion of the spinal cord. Intraoperative indocyanine green videoangiography (ICG-VA) followed by FLOW 800 analysis, which shows vascularization of the spinal parenchyma, may provide a solution for these problems in specific cases. CLINICAL PRESENTATION: A 61-year-old woman suffering from claudication visited our department. Magnetic resonance imaging (MRI) revealed a cystic lesion at the level of Th11. A solid portion was not detected in the T1-weighted images following gadolinium administration. We made a diagnosis of ventriculus terminalis and performed a lesion resection. Prior to opening the PMS, ICG-VA was performed, which revealed an avascular area representing the intramedullary cyst. The PMS was the most avascular area observed in the time-intensity analysis executed using FLOW 800 software (Zeiss, Oberkochen, Germany). Thus, it was helpful in determining the site for myelotomy, which should be performed at the center of the extent of the lesion. The patient was discharged 23 days after the operation, ambulating independently. CONCLUSION: Intraoperative ICG-VA followed by FLOW 800 analysis was applied to a case of intramedullary cystic lesion. This technique may be helpful in performing safer intramedullary cystic lesion surgery because it enables visualization of the lesion location and confirmation of the PMS.

Discrepancy between radiological and histological findings in ganglioglioma of the optic chasm: Case report.

BACKGROUND: Gangliogliomas involving the optic nerve or chiasm are extremely rare tumors, which can be confused radiologically with other neoplasms. α-[N-methyl-11C]-methylaminoisobutyric acid (11C-MeAIB) is a new artificial amino acid positron emission tomography (PET) tracer, which is metabolically more stable in vivo and may be more specific for tumors than 11C-methionine. However, the utility of 11C-MeAIB PET in the diagnosis of brain tumors has not yet been reported. CASE DESCRIPTION: A 26-year-old man presented with visual field defects and headache, and magnetic resonance imaging demonstrated a suprasellar mass involving the optic chiasm. A biopsy and partial tumor resection were performed via an interhemispheric approach. We diagnosed the tumor as ganglioglioma (WHO grade I) involving the optic chiasm. Although this lesion was histologically benign, 11C-MeAIB PET, 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) PET and proton magnetic resonance spectroscopy indicated malignant features. CONCLUSION: The discrepancy between radiological and histological findings implies that this new amino acid tracer PET may have a limitation in the diagnosis of gangliogliomas. Although further study is necessary, gangliogliomas should be included in the differential diagnosis of suprasellar tumors, even if PET findings show malignant features.

Granulomatous hypophysitis caused by Rathke's cleft cyst mimicking a growth hormone-secreting pituitary adenoma.

We report a case of granulomatous hypophysitis caused by Rathke's cleft cyst (RCC) mimicking a growth hormone (GH)-secreting pituitary adenoma. Neuroradiological and endocrinological evaluations showed abnormal findings consistent with acromegaly: Magnetic resonance imaging demonstrated a pituitary mass lesion, and GH and insulin-like growth factor I levels were markedly elevated, and GH levels were not suppressed in oral glucose tolerance test. Transsphenoidal surgery was performed, but no adenomatous tissue could be detected. Histological examination revealed RCC and concurrent granulomatous giant cell inflammatory reaction of the anterior hypophysis. To the authors' knowledge, this is the first documented case of granulomatous hypophysitis caused by RCC mimicking a GH-secreting pituitary adenoma.

Contribution of Endothelial-to-Mesenchymal Transition to the Pathogenesis of Human Cerebral and Orbital Cavernous Malformations.

BACKGROUND: The analysis of gene-targeted mouse mutants has demonstrated that endothelial-to-mesenchymal transition (EndMT) is crucial to the onset and progression of cerebral cavernous malformations (CMs). It has also been shown that Notch and ephrin/Eph signaling are involved in EndMT. However, their roles in the pathogenesis of human intracranial CMs remain unclear. OBJECTIVE: To elucidate the contribution of EndMT, the Notch pathway, and ephrin-B2/EphB4 signaling to the pathogenesis of human intracranial CMs. METHODS: Eight human intracranial CMs (5 cerebral and 3 orbital CMs) were immunohistochemically investigated. RESULTS: CD31 (an endothelial marker) and EndMT markers, such as α-smooth muscle actin (a mesenchymal marker) and CD44 (a mesenchymal stem cell marker), were expressed in the endothelial layer of vascular sinusoids in all cases, suggesting that endothelial cells (ECs) have acquired mesenchymal and stem-cell-like characteristics and undergone EndMT in all cerebral and orbital CMs. EndMT was observed in about 70% and 35% of ECs in cerebral and orbital CMs, respectively. In all cases, Notch3 was expressed in the endothelial layer, indicating that ECs of vascular sinusoids have acquired mesenchymal features. In all cases, both ephrin-B2 and EphB4 were detected in the endothelial layer, suggesting that ECs of vascular sinusoids are immature or malformed cells and have both arterial and venous characteristics. CONCLUSION: EndMT plays a critical role in the pathogenesis of human cerebral and orbital CMs. Modulating EndMT is expected to be a new therapeutic strategy for cerebral and orbital CMs.

Diffusion tensor imaging of the optic chiasm in patients with intra- or parasellar tumor using readout-segmented echo-planar.

PURPOSE: To evaluate the impact of surgery on the optic pathway of patients with intra- or parasellar mass lesions, as evidenced by readout-segmented DTI. MATERIALS AND METHODS: Twenty-four patients with intra- or parasellar mass lesions were included in the study. Readout-segmented DTI and T2WI were obtained before and after surgery. The ROIs were set on the optic chiasm as well as the anterior and posterior optic tracts. For each ROI, axial diffusivity (AD), radial diffusivity (RD), fractional anisotropy (FA), and ADC values were calculated. DTI parameters in preoperative studies of all patients were compared and related to the presence of tumor compression. In patients who underwent surgery, pre- and postoperative DTI parameters were compared. The correlation between DTI parameters and visual function was determined. RESULTS: In the preoperative studies, the optic chiasm of patients with tumor compression showed significant lower AD and RD values. The optic chiasm of patients with visual field disorder showed significantly lower AD and RD values compared to patients without the disorder. There was a negative correlation with a trend toward significance between FA values and visual field disorder scores. The comparative analysis of patients in pre- and postoperative studies showed that the optic chiasm of patients with tumor compression presented a significant lower FA (0.41 versus 0.30, p=0.0068) and higher RD values after surgery. CONCLUSIONS: DTI is a useful tool to assess the impact of surgery on the optic chiasm and nerve.