Hemorrhage from metastatic brain epithelioid hemangioendothelioma: A case report.

In this report, we describe a very rare case of metastatic epithelioid hemangio-endothelioma (EHE) originating from other organs such as the lung and requiring craniotomy due to subsequent hemorrhage. A 50-year-old man was diagnosed with EHE in the bilateral lungs, the mediastinum, and the right adrenal gland 8 years earlier. One year earlier, he had developed spinal metastasis. Six months earlier, a screening brain MRI had revealed multiple brain metastases of tumor. He developed subcortical hemorrhage from the tumor in the right parietal lobe and successfully underwent removal of hematoma and tumor. Histopathological examinations revealed EHE. Metastatic EHE is very rare but may be at high risk of intracranial hemorrhage. It is quite important to consider the possibility of brain metastasis and subsequent bleeding when treating patients with EHE.

Pituitary apoplexy in endocrinologically silent adenoma during somatostatin analog administration for pancreatic neuroendocrine tumor: A case report.

A dopamine agonist administered for prolactinoma treatment and pituitary stimulation tests are reported as risk factors for pituitary apoplexy. We report a case of an 82-year-old patient who suffered from pituitary apoplexy in an endocrinologically silent adenoma during lanreotide administration. The patient was diagnosed with a pancreatic neuroendocrine tumor with lymph node metastasis and treated with lanreotide for two years. An endoscopic endonasal transsphenoidal approach was used for tumor and hematoma removal. The specimen showed growth hormone and prolactin positivity and was diagnosed as pit1-lineage plurihormonal adenoma. The tumor also showed positivity for somatostatin receptor 2. Thus, lanreotide treatment is a risk factor for pituitary apoplexy even in silent adenoma.

Precise Manipulation of Electron Transfers in Clustered Five Redox Sites.

Electron transfers in multinuclear metal complexes are the origin of their unique functionalities both in natural and artificial systems. However, electron transfers in multinuclear metal complexes are generally complicated, and predicting and controlling these electron transfers is extremely difficult. Herein, we report the precise manipulation of the electron transfers in multinuclear metal complexes. The development of a rational synthetic strategy afforded a series of pentanuclear metal complexes which composed of metal ions and 3,5-bis(2-pyridyl)pyrazole (Hbpp) as a platform to probe the phenomena. Electrochemical and spectroscopic investigations clarified overall picture of the electron transfers in the pentanuclear complexes. In addition, unique electron transfer behaviors, in which the reduction of a metal center occurs during the oxidation of the overall complex, were identified. We also elucidated the two dominant factors that determine the manner of the electron transfers. Our results provide comprehensive guidelines for interpreting the complicated electron transfers in multinuclear metal complexes.

A Catalytic Alkylation of Ketones via sp3 C-H Bond Activation.

We identified a ternary hybrid catalyst system composed of an acridinium photoredox catalyst, a thiophosphoric imide (TPI) catalyst, and a titanium complex catalyst that promoted an intermolecular addition reaction of organic molecules with various ketones through sp3 C-H bond activation. The thiyl radical generated via single-electron oxidation of TPI by the excited photoredox catalyst abstracted a hydrogen atom from organic molecules such as toluene, benzyl alcohol, alkenes, aldehydes, and THF. The thus-generated carbon-centered radical species underwent addition to ketones and aldehydes. This intrinsically unfavorable step was promoted by single-electron reduction of the intermediate alkoxy radical by catalytically generated titanium(III) species. This reaction provided an efficient and straightforward route to a broad range of tertiary alcohols and was successfully applied to late-stage functionalization of drugs or their derivatives. The proposed mechanism was supported by both experimental and theoretical studies.

Differentiation of Fibroblasts Into Myofibroblasts in the Arachnoid Membrane of Moyamoya Disease.

BACKGROUND: Moyamoya disease (MMD) is a very specific disorder in terms of spontaneous development of extracranial-to-intracranial collateral circulation through the dura mater, but the underlying mechanisms are unclear. This study aimed to investigate the role of the arachnoid membrane in this unique angiogenesis in MMD. METHODS: A piece of arachnoid membrane and 1- to 2-mL cerebrospinal fluid were simultaneously harvested during surgery from 26 patients with MMD. The specimens were also collected during surgery as the controls from 6 patients with atherosclerotic carotid artery diseases. The arachnoid membrane was subjected to immunohistochemistry and the cerebrospinal fluid was used to measure the concentration of cytokines using ELISA. RESULTS: The number of cells positive for PDGFR (platelet-derived growth factor receptor) α was significantly higher in MMD than in the controls (5.4±3.1 versus 2.3±2.1 cells/field; P=0.02). The results were same in PDGFRß-positive cells (10.1±4.6 versus 4.8±2.8; P=0.01) and α-SMA (alpha-smooth muscle actin)-positive cells (8.8±3.1 versus 2.0±2.5; P<0.01). On multicolor immunofluorescence, 80.5±15.6% of cells positive for PDGFRα in MMD also expressed α-SMA, being significantly higher than 14.6±7.2% in the controls (P<0.01). The density of collagen in the arachnoid membrane was significantly higher in MMD than in the controls (60.3±15.0% versus 40.1±15.3%; P<0.01). In MMD, advanced disease stage was significantly associated with a larger number of α-SMA-positive cells in the arachnoid membrane (P=0.04). On ELISA, the cerebrospinal fluid concentrations of bFGF (basic fibroblast growth factor), HGF (hepatocyte growth factor), and TGF (transforming growth factor)-ß1 were significantly higher in MMD than in the controls. CONCLUSIONS: Based on these findings, MMD may elevate the concentrations of angiogenic factors in the cerebrospinal fluid and then promote the proliferation of fibroblasts in the arachnoid membrane and their differentiation into myofibroblasts, which may, in turn, enhance the production of collagen essential for spontaneous collateral formation across the arachnoid membrane.

Calcifying pseudoneoplasm of the neuraxis (CAPNON) associated with neurenteric cyst. An autopsy case showing unusual fatal outcome.

A 53-year-old man with a history of an untreated brain mass was taken to Toyama Prefectural Central Hospital by emergency transport. Computed tomography revealed an intracranial hypo-attenuated lesion exhibiting mass effect. Several calcified foci were observed around the lesion. His radiographical diagnosis was meningioma with calcification and edema. He suddenly showed tonic seizure after admission; therefore an emergency craniotomy was performed. However, he unfortunately died due to advanced cerebral edema. Microscopic findings of the surgically obtained materials were consistent with neurenteric cyst (NC). Intracranial hard masses were found adjacent to NCs, and the masses were composed of fibrous cartilage-like matrix with extensive linear calcification and the presence of surrounding round-to-oval epithelioid cells. Thus, calcifying pseudoneoplasm of the neuraxis (CAPNON) associated with NC was considered the most appropriate diagnosis of the present case. To the best of our knowledge, this is the first report of such a case. The present case suggests that delay of treatment might cause a poor outcome, at least in CAPNON associated with NC. Careful investigations, including the underlying pathology, may be essential when considering the etiology of CAPNON and its treatment strategies.

Sebaceous adenoma occurring within an intracranial dermoid cyst.

Among intracranial cystic lesions, dermoid cysts and epidermoid cysts are relatively common benign tumors. In a small number of these tumors, it is known that squamous cell carcinomas arise in the lining epithelium of the cysts. Among tumors derived from the appendage, only one case of hidradenoma within a dermoid cyst and no cases of sebaceous tumor have been reported previously. In the present case, a protruding lesion was present in the cystic wall, and it was composed of two cell types: sebaceous cells (sebocytes) and basaloid/germinated cells, being characteristic of this tumor. It is essential to distinguish it from other sebaceous lesions such as hyperplasia, sebaceoma, sebaceous carcinoma, and basal cell carcinoma with sebaceous differentiation derived from the epidermis. The critical distinguishing points in making a differential diagnosis among these lesions are the ratio of the two cell types and the presence or absence of other components such as hair sacs, invasion or cellular atypia. Immunohistochemical examination revealed that the tumor cells were positive for the epithelial markers, such as cytokeratin (CK)14, p63, p40, high-molecular CK, and adipophilin; these findings are peculiar to sebaceous adenoma. Although there have been several similar case reports of sebaceous tumors associated with dermmoid cysts in the ovaries, most of the intracranial lesions were squamous cell carcinomas that developed within the cysts, and there has been no precedent showing an association with a sebaceous tumor. The present report describes the first case of sebaceous adenoma that occurred in an intracranial dermoid cyst.

A case of intestinal perforation with a residual shunt tube placed during childhood: should we remove the non-functioning tube?

We report a 22-year-old man who had abdominal shunt tube migration into colon. He was diagnosed with pilocytic astrocytoma at optic-chiasm to hypothalamus at age of 7, and treated by resection, chemotherapy, and irradiation. He developed hydrocephalus and had multiple ventriculo-peritoneal shunt surgery. At age of 19, he fell in coma due to the subarachnoid and intra-ventricular hemorrhage due to the aneurysm rupture. The ventricle tube was removed, leaving the shunt valve and abdominal tube. The new shunt system was reconstructed at the contralateral side. He was at bed rest after this episode. At age of 20, he had high fever unable to control with antibiotics. The abdominal computed tomogram showed the shunt tube migration in the descending colon. The tube was removed under laparoscopy, and the inflammation was cured. The abandoned peritoneal shunt tube should be removed in patients with high tube migration risks.

Impact of system approach and personal performance on preventable morbidity and mortality events in neurosurgery patients.

PURPOSE: Adverse events in neurosurgery are a serious problem. The approach for seeking solutions for adverse events has shifted from a personal approach to a systemic approach. However, to some extent, preventable morbidity events could be related to personal performance. This study aimed to clarify the impact of personal performance and systematic failure on the occurrence of morbidity and mortality events in neurosurgery patients. METHODS: All morbidity and mortality conference data stored within our department over a 9-year period were analyzed. There were 4580 admitted patients and 3262 surgical procedures performed. We performed a three-step classification of morbidity and mortality events based on the possibility of prevention, root of the event, and personal or systemic issues. RESULTS: As a result of the first step, 214 preventable and 278 unpreventable events were identified. Of the preventable events, two mortality and 212 morbidity events were analyzed. In the second step, 155 (72.4%), 34 (15.9%), 13 (6.1%), and 12 (5.6%) events were categorized as technical complications, critical events, judgment errors, and human factors, respectively. There were 179 events (83.6%) classified as personal performance issues and 35 events (16.4%) as systemic issues. The ratio of personal performance to systemic issues varied widely, with significant differences among the four categories (P < 0.01). CONCLUSIONS: Among neurosurgery patients who have preventable morbidity, issues related to personal performance were more frequent than systemic issues. Efforts to improve systems should be unwavering. However, the personal responsibility of neurosurgeons to avoid preventable complications should not be ignored.

[Conventional Cranioplasty for Craniosynostosis].

Conventional cranioplasty is a basic operative procedure for craniosynostosis. This procedure is more invasive, but can be completed in shorter treatment period than distraction osteogenesis. This surgery can allow delicate cranial reshaping, and is indicated in most age groups. The operative procedures may differ depending on the skull shape. During this procedure, complete brain release from the skull compression must be achieved. In most patients, bone flaps float from the dura mater after completion of craniotomy. The bone flap must be reshaped to the ideal form, and should be fixed with absorbable plates instead of titanium plates to avoid plate migration. To close the scalp, the galea should be sutured tight to avoid wound trouble. After the operation, patients should be followed up at an out-patient clinic; the skull and face shape should be checked by a neurosurgeon and plastic surgeon as the treated skull has risk of backslide, and development should be regularly checked by a pediatrician.

Dirhodium-Based Supramolecular Framework Catalyst for Visible-Light-Driven Hydrogen Evolution.

The direct conversion of solar energy to clean fuels as alternatives to fossil fuels is an important approach for addressing the global energy shortage and environmental problems. Here, we introduce a new dirhodium-complex-based framework assembly as a heterogeneous molecule-based photocatalyst for hydrogen evolution using visible light. Two dirhodium complexes bearing visible-light-harvesting BODIPY (boron dipyrromethene, BDP) moieties were newly designed and synthesized. The obtained complexes were self-assembled to framework structures (supramolecular framework catalysts), which are stabilized intermolecular noncovalent interactions. These frameworks retained excellent visible-light-harvesting properties of BDP moieties. Investigation of the catalytic performance of the supramolecular framework catalysts revealed that the supramolecular framework catalyst with heavy atoms at BDP moieties exhibited excellent performance in the formation of hydrogen with a reaction rate of 275.8 µmol g-1 h-1 under irradiation of visible light, whereas the supramolecular framework catalyst without heavy atoms at BDP moieties was inactive. Moreover, the system has the additional benefits of high durability (up to 96 h), reusability, and facile removal from the reaction mixture. We also disclosed the effect of heavy atoms at BDP moieties on the catalytic activity and proposed a reaction mechanism.

Cerebrospinal fluid may flow out from the brain through the frontal skull base and choroid plexus: a gold colloid and cadaverine injection study in mouse fetus.

PURPOSE: It has been commonly accepted for a long time that the cerebrospinal fluid (CSF) drains into arachnoid granulations from the subarachnoid space to the dural venous sinus unidirectionally. However, recently, periventricular capillaries and lymphatic concepts have been introduced. The CSF moves along the perivascular space and drains into the capillary vessels or meningeal lymphatic tissues. CSF is involved in removing brain waste out of the brain. In this study, we investigated the outflow mechanism of substances in the CSF from the brain. METHODS: We investigated the movement of CSF by injection of gold colloid conjugates (2, 40, and 200 nm) into the lateral ventricles of mouse fetuses and evaluated the deposition by silver stain with tissue transparency and electron microcopy. Cadaverine was also injected into the lateral ventricle to determine its movement tract. RESULTS: The gold particle deposition was mainly observed in the frontal skull base. Electron microscopic study showed that the gold particle deposition was observed on the choroid plexus and ependyma in the lateral ventricle and also red blood cells in the heart and liver. Two-nanometer particles were exclusively observed in the liver. Cadaverine injection study demonstrated that cadaverine was observed at the extracranial frontal skull base, choroid plexus, ependymal surface, and perivascular area in the brain white matter. CONCLUSION: The particles in the CSF were shown to move from the brain to the frontal skull base and also into the blood stream through the choroid plexus in the fetus. The outflow of particles in the CSF may be regulated by molecular size. This new information will contribute to the prevention of brain degeneration due to brain waste deposition.

Novel biomarker, phosphorylated T-LAK cell-originated protein kinase (p-TOPK) can predict outcome in primary central nervous system lymphoma.

This study aimed to assess whether T-lymphokine-activated killer cell-originated protein kinase (TOPK) can be a potent novel biomarker to predict the outcome in patients with primary central nervous system lymphoma (PCNSL). This study enrolled 20 patients who were histologically diagnosed as having diffuse large B-cell type PCNSL between 2005 and 2015. Using surgical specimens, the expression of TOPK and phosphorylated TOPK (p-TOPK) was analyzed on immunohistochemistry. Clinical features such as age, sex, Karnofsky performance status (KPS), ocular involvement, deep brain structure involvement, the number of lesions, chemotherapy and radiation therapy were also collected. Impacts of TOPK/p-TOPK expression on their progression-free survival (PFS) and overall survival (OS) were examined with multivariate analysis. Median PFS/OS were 24.2 and 39.0 months, respectively. On immunostaining, the mean percentage of TOPK-positive cells was 35.5 ± 20.8%, and the mean number of p-TOPK-positive cells was 13.7 ± 15.7 cells/mm2 . The higher expression of p-TOPK was significantly related to multiple lesions (P = 0.003). Multivariate analysis demonstrated that only the higher expression of p-TOPK was an independent predictor to shorten both PFS (P = 0.029; hazard ratio (HR), 5.5; 95% confidential interval (CI), 1.2-25.3) and OS (P = 0.014; HR, 7.7; 95% CI, 1.5-41.3). These findings strongly suggest that p-TOPK may be a potent biomarker to determine the outcome of patients with PCNSL and to develop novel drugs to treat PCNSL.

Muse Cell: A New Paradigm for Cell Therapy and Regenerative Homeostasis in Ischemic Stroke.

Multilineage-differentiating stress enduring (Muse) cells are one of the most promising donor cells for cell therapy against ischemic stroke, because they can differentiate into any type of cells constructing the central nervous system (CNS), including the neurons. They can easily be isolated from the bone marrow stromal cells (BMSCs), which may also contribute to functional recovery after ischemic stroke as donor cells. In this chapter, we concisely review their biological features and then future perspective of Muse cell transplantation for ischemic stroke. In addition, we briefly refer to the surprising role of Muse cells to maintain the homeostasis in the living body under both physiological and pathological conditions.

Lacunar Stroke, Cavernous Angioma, and Fusiform Aneurysm Due to Irradiation for Pilocytic Astrocytoma-A Case Report.

Radiotherapy is a useful modality for the treatment of brain tumors, but may induce brain degeneration, tumor formation, and vasculopathy in the irradiated field. We describe a rare case of a pediatric patient who presented multiple different types of vascular events consecutively in the irradiated field including lacunar stroke because of occlusion of perforating artery, intraventricular hemorrhage from cavernoma, and subarachnoid hemorrhage because of the rupture of fusiform aneurysm, 6 years after radiotherapy against pilocytic astrocytoma. The life-threatening aneurysm was resected, and its histologic findings revealed the radiation-induced vasculopathy. We should avoid irradiation, and repeat surgical resection for the pediatric cases with pilocytic astrocytoma. Once irradiation was indicated for them, however, we should carefully follow-up not only tumor recurrence but also angiograms to predict any cerebrovascular events.

[Three-Dimensional Skull Model with Vascular Structures for Occipital Expansion in Patients with Developed Occipital Emissary Veins].

We report the application of a three-dimensional skull model with vascular structures for occipital expansion in a patient who had developed occipital emissary veins. A 15-year-old boy visited a dentist for orthodontic treatment and was diagnosed with midface hypoplasia. He had undergone a ventriculo-peritoneal shunt at the age of 10 months. On visiting our institution, he was diagnosed with exophthalmos, low visual acuity, reversed bite, and developmental retardation. Moreover, he had sleep apnea and was supported with continuous positive airway pressure at night. Computed tomography and magnetic resonance imaging demonstrated brachycephalus, chronic tonsillar herniation, midface hypoplasia, and well-developed occipital emissary veins. We chose occipital expansion for lowering intracranial pressure and created a three-dimensional skull model with vascular structures and shunt tube. On this model, we wrote scalp incision and craniotomy lines avoiding injury to the veins and shunt tube. The operation was completed using this plan. Patients with syndromic craniosynostosis frequently have developed emissary veins and previous shunt operation. The three-dimensional skull model with vascular structures will be expected to reduce the risks of surgery.

[Ultrasound-aided Fixation of a Biodegradable Cranial Fixation System:SonicWeld Rx® System in Pediatric Neurosurgery].

PURPOSE: Ultrasound-aided fixation of a biodegradable cranial fixation system called SonicWeld Rx®, has been widely applied in the fields of craniofacial surgery and plastic surgery. However, there are few reports that denote its use in the field of neurosurgery. This study aimed to evaluate the usefulness of SonicWeld Rx® system in pediatric neurosurgery. METHODS: This study included 11 pediatric patients(10 boys, 1 girl), who underwent craniotomy for moyamoya disease, brain tumor, and arachnoid cyst. Their mean age was 6.4 years, ranging from 4 to 10 years. LactoSorb® system was applied in 6 patients and SonicWeld Rx® system in 5. RESULTS: The time required for screw fixation was significantly shorter in the SonicWeld group(6.5±1.4sec)than in the LactoSorb group(13.4±2.8sec), with p<0.05. The quality of fixation strength was adequate in both groups. There were no perioperative complications related to the absorbable fixation device. A 3-D skull CT detected no malposition of the bone flap 3 months postoperatively. There were no scalp complications noted for an average of 21 months. CONCLUSION: SonicWeld Rx® system can be easy and useful in fixing the bone flap to the cranium in the field of pediatric neurosurgery.

Diagnostic value of interleukin-10 in cerebrospinal fluid for diffuse large B-cell lymphoma of the central nervous system.

A biomarker for early diagnosis of central nervous system (CNS) lymphoma would permit early treatment for attenuation of disease progression and neurological deterioration. High interleukin-10 (IL-10) or an IL-10/IL-6 ratio >1.0 are informative parameters for discriminating intraocular lymphomas from uveitis. Recent reports have also shown that CSF IL-10 is a potential diagnostic biomarker for CNS lymphoma. The purpose of this study was to evaluate the diagnostic value of IL-10 in cerebrospinal fluid (CSF) in patients with CNS lymphoma compared with other CNS diseases, including CNS tumors and inflammatory diseases. CSF IL-10, IL-6, beta-2 microglobulin, soluble IL-2 receptor and FDG-PET SUVmax were measured in 19 patients with CNS lymphoma (15 primary and 4 secondary diffuse large B-cell lymphomas) and 26 non-lymphoma patients with various brain tumors and inflammatory diseases. The diagnostic accuracy of the respective examinations for differentiation of CNS lymphomas from non-lymphomas was evaluated by receiver operating characteristic (ROC) curve analysis. The area under the ROC curve (AUC) was calculated. CSF IL-10 was detected at significant levels (median, 28 pg/ml; range <2-4,100 pg/ml) in all except one patient with CNS lymphoma, but not detected in any non-lymphoma patients. CSF IL-10 had the highest diagnostic accuracy with AUC = 0.974. At an IL-10 cutoff of 3 pg/ml, the sensitivity and specificity were 94.7 and 100 %, respectively. These results indicate that CSF IL-10 is a superior biomarker for initial screening for patients with CNS lymphoma.

One-piece bone flap osteotomy using thread wire saw for fronto-orbital advancement with distraction osteogenesis in craniosynostosis.

PURPOSE: The objectives of this study are to describe our new technique of one-piece bone flap osteotomy for fronto-orbital advancement with distraction osteogenesis in craniosynostosis using a thin, flexible, and safe thread wire saw (the T-saw) and to compare the results with those of classic osteotomy using an osteotome. METHODS: Initial osteotomy is performed between two pterion burr holes using a craniotome with a guarded footplate. The outer sphenoid wing and lateral orbital rim are separated using a reciprocating saw. Limited dura dissection from inner cortex between burr holes in the pterion and nasion is performed. The T-saw is inserted through the epidural space behind the superior orbital wall between the lateral orbital rim and nasion burr hole; the osteotomy is performed with gentle reciprocating strokes. Dura protection with a malleable retractor is not absolutely necessary. RESULTS: Five patients underwent one-piece fronto-orbital bone flap osteotomies using a T-saw in 2009-2014. The median age was 26 months (7-132 months), median operation time was 275 min (183-303 min), and median estimated blood loss was 65 mL (20-250 mL). These values did not differ from those of control cases. No complications, including incomplete osteotomy, occurred. CONCLUSIONS: The T-saw creates an osteotomy as a "one-stroke sketch," so incomplete osteotomy never occurs. The osteotomy can be performed safely without protecting the dura. Osteotomy with T-saw does not negate the advantages of fronto-orbital advancement with distraction osteogenesis, including shorter operative time, less intraoperative bleeding, and fewer complications.

[Possible Cerebral Infarction due to Multiple Segmental Cerebral Vasospasms after Carotid Artery Stenting: A Case Report].

A 62-year-old man was admitted due to consciousness disturbance and motor aphasia. Magnetic resonance (MR) images demonstrated watershed infarctions in the territory of the left middle cerebral artery, occlusion of the left internal carotid artery, and severe stenosis of the right internal carotid artery at the neck. He was treated with a recombinant tissue plasminogen activator. One month later, angiography revealed recanalization of the left internal carotid artery with residual severe stenosis at the neck. We attempted carotid artery stenting (CAS) on the left internal carotid artery, but could not pass the guide wire through the stenosis. Therefore, we performed CAS on the right carotid artery instead. At the second day after CAS, the patient showed consciousness disturbance, right hemiparesis, and motor aphasia. MR images showed a new infarction in the left cerebral hemisphere and bilateral multifocal segmental arterial constrictions. By keeping his blood pressure at a high enough level for one week, his symptoms were relieved, and MR images showed resolution of the vessel constrictions. From this case, we can conclude that this kind of multiple segmental vasospasms after CAS require contrasting treatments to those for hyperperfusion syndrome. Interventionalists should be aware of this condition and its treatments.