Solid brain metastasis mimicking intracerebral hematoma on imaging.

A 79-year-old woman with a history of resection of the ascending colon cancer presented with conscious disturbance, dysarthria, nausea, and dizziness. Computed tomography (CT) revealed striking high-density lesions in the left cerebellum and left frontal lobe with slight perifocal edema. These lesions were suspected the coexistence of spontaneous cerebellar hemorrhage and frontal lobe metastasis, or multiple brain metastases with massive hematoma. Because of the mass effect of the cerebellar lesion and impaired consciousness, she underwent emergency resection of the cerebellar lesion which was found to be composed of grayish abnormal soft solid tissue and did not include an obvious hematoma mass. The pathological findings were consistent with brain metastasis from colon cancer. This is an impressive rare case of intraoperative solid brain metastasis with a clearly homogenous hyper-dense CT appearance mimicking intracerebral hematoma.

Mutism due to a massive hematoma after rebleeding of an aneurysmal subarachnoid hemorrhage in the territory of the distal anterior cerebral artery.

Background: The mutism caused by hematoma after subarachnoid hemorrhage (SAH) is extremely rare, and the details of its clinical course have not been clarified. Case Description: A 75-year-old woman who presented with transient loss of consciousness and a subsequent severe headache was transferred to our hospital. She was diagnosed with the World Federation of Neurosurgical Societies Grade II SAH due to the rupture of an aneurysm at the A2-3 junction in the left anterior cerebral artery (ACA). Endovascular coil embolization was successfully performed; however, postoperative computed tomography (CT) confirmed a massive hematoma in the corpus callosum and expansion into the cingulate gyrus, which was suspected to be due to preoperative or intraoperative rebleeding. The patient remained completely mum, which was considered as mutism due to a hematoma in the ACA territory. The postoperative clinical course was favorable, and the patient had fully recovered speech fluency with the disappearance of hematoma on CT scan at 44 days after the occurrence of SAH. Conclusion: This is a rare case of mutism caused by an interhemispheric hematoma due to rebleeding after SAH. No radical evacuation of the hematoma may be desirable for the improvement of mutism because additional structural damage to the ACA territory by surgical stress should be avoided.

[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.

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.

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.

Impact of a novel biomarker, T-LAK cell-originating protein kinase (TOPK) expression on outcome in malignant glioma.

This study aimed to evaluate the biological features of T-lymphokine-activated killer cell-originating protein kinase (TOPK) in vitro and to assess clinical impact of TOPK on the outcome in patients with malignant glioma. TOPK protein level and TOPK mRNA and protein levels in six glioma cell lines were examined using Western blot and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Immunohistochemistry was performed to examine their subcellular localization of TOPK. Using surgical specimens from 57 patients with gliomas, TOPK and Ki-67 expressions were examined by immunohistochemistry. Their co-localization was also examined with double immunofluorescence immunohistochemistry. Impacts of TOPK/Ki-67 expression on the overall survival (OS) and progression-free survival (PFS) in 32 patients with glioblastoma multiforme (GBM) were examined, using Kaplan-Meier and Cox proportion hazard models. Immunohistochemistry revealed that approximately 20-30% of glioma cells were positive for TOPK in vitro. TOPK mRNA was identified in all glioma cell lines on RT-PCR. The value of TOPK/GAPDH was 0.27 ± 0.11. TOPK and Ki-67 expressions were significantly higher in GBM patients than in non-GBM patients. A majority of TOPK-positive cells were also positive for Ki-67 and vice versa. Multivariate analysis revealed that a low TOPK expression (≤ 12.7%) was an independent predictor of longer OS (P = 0.0372), and that gross total removal and a low TOPK expression (≤ 12.7%) were independent predictors of longer PFS (P = 0.0470 and P = 0.0189, respectively). The findings strongly suggest biological and clinical importance of TOPK expression in gliomas, indicating a novel therapeutic potential of TOPK inhibitors to treat malignant gliomas.

BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions are frequent in epithelioid glioblastomas: a histological and molecular analysis focusing on intratumoral heterogeneity.

Epithelioid glioblastoma (E-GBM) is a rare aggressive variant of IDH-wildtype glioblastoma newly recognized in the 2016 World Health Organization classification, composed predominantly of monotonous, patternless sheets of round cells with laterally positioned nuclei and plump eosinophilic cytoplasm. Approximately 50% of E-GBM harbor BRAF V600E, which is much less frequently found in other types of glioblastomas. Most E-GBM are recognized as primary/de novo lesions; however, several E-GBM with co- or pre-existing lower-grade lesions have been reported. To better understand associations between E-GBM and the lower-grade lesions, we undertook a histological and molecular analysis of 14 E-GBM, 10 of which exhibited lower-grade glioma-like components (8 E-GBM with co-existing diffuse glioma-like components, 1 E-GBM with a co-existing PXA-like component and 1 E-GBM with a pre-existing PXA). Molecular results demonstrated that the prevalence of BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions in E-GBM were 13/14 (93%), 10/14 (71%) and 11/14 (79%), respectively, and concurrent BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions were observed in 7/14 (50%) of E-GBM. These alterations were also frequently seen in the lower-grade lesions irrespective of the histology. Genetic analysis including array comparative genomic hybridization performed for 5 E-GBM with co- and pre-existing lower-grade components revealed that all molecular changes found in the lower-grade components were also observed in the E-GBM components, and additional changes were detected in the E-GBM components. In conclusion, E-GBM frequently exhibit BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions and these alterations tend to coexist in E-GBM. Taken together with the facts that only one PXA preceded E-GBM among these lower-grade lesions, and that co-occurrence of BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions have been reported to be rare in conventional lower-grade diffuse gliomas, the diffuse glioma-like components may be distinct infiltrative components of E-GBM, reflecting intratumoral heterogeneity.

[Dermoid Cyst in Meckel's Cave Presenting with Oculomotor Nerve Palsy and Trigeminal Neuralgia:A Case Report].

The authors report a rare case of an intracranial dermoid cyst found in Meckel's cave. A 63-year-old woman developed left oculomotor nerve palsy and was referred to their hospital. Magnetic resonance imaging revealed a cystic lesion in the left Meckel's cave and prepontine cistern, but her symptoms gradually improved during conservative observation. However, three years later she complained of left facial pain in the territory of the second branch of the trigeminal nerve. The left oculomotor nerve palsy exacerbated again. Although her trigeminal neuralgia improved after carbamazepine administration, her oculomotor nerve palsy did not recover. Therefore, she underwent direct surgery through the anterior transpetrosal approach, and the fat-containing tumor cyst was completely resected. The tumor was strongly compressing the left trigeminal nerve and its ganglion in Meckel's cave. After surgery, her facial pain completely resolved and her oculomotor nerve palsy gradually improved. Histological examination revealed that the cyst wall was composed of a single layer of squamous epithelium and contained hair and keratin. A pathological diagnosis of a dermoid cyst was made.

[A Case of Suprasellar Germinoma that Spontaneously Regressed before Endoscopic Biopsy].

We present a very rare case of suprasellar germinoma that spontaneously regressed before endoscopic biopsy. An 8-year-old boy was admitted to our hospital due to headache, polydipsia, and polyuria. Neurological examination performed on admission revealed bitemporal hemianopia. Enhanced MRI demonstrated a homogeneously enhanced tumor mass in the suprasellar region obstructing the foramen of Monro. Tests for all serum tumor markers were negative. Plain X-ray and CT scan were performed once and twice, respectively, for seven days between admission and endoscopic biopsy. The total dose of diagnostic radiation exposure before surgery was 110 mGy. Endoscopic observation during surgery revealed that the tumor had markedly decreased in size and the foramen of Monro had reopened. A very small piece of the tumor was harvested during surgery. Plain CT scan just after surgery showed a marked decrease in the tumor size, compared with the preoperative CT scan. The pathological diagnosis of the tumor was pure germinoma. The patient then underwent chemotherapy(four courses of CARE regimen)followed by radiation therapy with a dose of 24 Gy/15 fr. The tumor completely disappeared after treatment, and no recurrence was observed in the past four years.

[Usefulness of Tablet-Type Device Usage during Neurosurgical Practice].

This study aimed to validate the usefulness of intraoperative use of a tablet-type device in neurosurgical field. This study included 80 patients who underwent direct surgery for complex brain and spinal disorders in our hospital between April 2013 and March 2015. The operated disorders included cerebral aneurysm, intracranial and spinal dural arteriovenous fistula, meningioma, and vestibular schwannoma. By using the OsiriX HD software, the DICOM data were directly transferred to a tablet-type device (Apple iPad). Alternatively, by using the OsiriX HD or Amira software, the DICOM data were loaded to create interactive three-dimensional computer graphics on a personal computer and then transferred to a tablet-type device. The device was covered with sterile, translucent packaging bag. As a result, the surgeons could use the touch screen to browse and access radiological data of the patient undergoing surgery, without needing to leave the operation field or requiring external assistance for image browsing. The incidence of postoperative infection did not increase. In conclusion, intraoperative usage of the tablet-type device was easy and useful for surgeons performing surgeries for complex brain and spinal disorders.

Reversal of cognitive dysfunction by total removal of a large lateral ventricle meningioma: a case report with neuropsychological assessments.

Although cognitive impairment is one of the major symptoms of ventricular tumors, few studies have reported the details of cognitive impairment before and after their surgical removal. The expected effects on cognitive function should also be considered when choosing a surgical approach. We report the case of a large lateral ventricle meningioma in which cognitive impairment was detected on detailed neuropsychological examinations. The tumor was totally removed through the right superior temporal gyrus. Postoperative neuropsychological assessment revealed the reversal of cognitive impairment. As cognitive impairment is complex and easily overlooked, it is important to precisely assess neuropsychological function in patients with large brain tumors.

[Neuroendoscopic surgery for intra- and para-ventricular tumors:impacts on biopsy and hydrocephalus treatment].

In this report, the authors retrospectively review and discuss their results for neuroendoscopic surgery for intra- and para-ventricular tumors. This study included 28 patients who were admitted to our hospital for intra- or para-ventricular tumors between January 2005 and March 2013. There were 17 males and 11 females, and their age varied widely from 1 to 75 years. Using a neuroendoscopic technique, tumor biopsy was attempted in all 28 patients. Biopsy was possible in 25 patients(89.3%)but not in the other 3(10.7%)because of hypervascularity or tumor bleeding. Of these 25 patients, pathological diagnosis was possible in 23(92%), but not in other 2(8%)because of incomplete sampling. In 18 of 28 patients, various forms of hydrocephalus were observed. Neuroendoscopic procedures were quite useful to improve cerebrospinal fluid dynamics in 13 of these patients, including endoscopic third ventriculostomy(ETV)in 9(except for 1 patient with ETV failure), septostomy with ventriculoperitoneal shunting(VPS)in 3, and cystostomy in 1. Simple VPS was performed in the other 4 patients. These results suggest that neuroendoscopic surgery is valuable as a minimally invasive procedure for pathological diagnosis and hydrocephalus treatments in patients with intra- and para-ventricular tumors. Further development of neuroendoscopic equipment is warranted to accurately diagnose tumors with hypervascularity and subependymal tumors.

Management of cytomegalovirus infection in a patient with malignant glioma treated with temozolomide and steroids.

Temozolomide (TMZ) is the standard chemotherapy treatment for glioblastoma. Lymphocytopenia is reported to be the most frequent and severe adverse effect of TMZ and leads to opportunistic infections. Few cases of TMZ-induced cytomegalovirus (CMV) reactivation have so far been reported, and there are no guidelines regarding the use of chemotherapy after recovery from CMV reactivation. We herein report the case of a 45-year-old man with glioblastoma who developed CMV hepatitis following surgery and chemoradiotherapy with concomitant TMZ and steroids. After successful treatment of the CMV infection with an antiviral agent and recovery from the lymphocytopenia were achieved, the patient resumed maintenance therapy with TMZ under careful monitoring of his lymphocyte count and CMV pp65 antigenemia level.

Prognostic significance of sirtuin 2 protein nuclear localization in glioma: an immunohistochemical study.

The sirtuin 2 (SIRT2) protein is a member of the sirtuin family and homologous to Sir2 (silent information regulator 2) of Saccharomyces cerevisiae. To assess the pathobiological significance of SIRT2 protein expression and/or subcellular localization in human glioma, we examined SIRT2 protein expression in human gliomas using a polyclonal anti-SIRT2 antibody and immunohistochemistry. In this study, samples from 23 patients with glioblastoma (GB, grade IV), 8 patients with diffuse astrocytoma (DA, grade II) and 5 healthy individuals were examined. We established a SIRT2 labeling index (SIRT2-LI) that represents the percentage of cells with SIRT2 localized to the nucleus. The mean SIRT2-LI was 65.8±18.6 in GB samples, 41.2±22.8 in DA samples, and 28.6±12.3 in normal control samples. The SIRT2-LI of GB samples was significantly higher than that of normal control samples (P<0.01, Mann-Whitney's U-test) and that of DA samples (P<0.05). Moreover, the SIRT2-LI was positively correlated with malignant progression. Specifically, samples from patients with GB were divided into two groups, low SIRT2-LI (<60%) and high SIRT2-LI (≥60%), and the patients with low SIRT2-LI samples survived significantly longer than patients with high SIRT2-LI samples (P<0.05, Kaplan-Meier method and log-rank test). In conclusion, SIRT2-LI was indicative of glioma malignancy, and it may be predictive of GB patient survival.

Clear cell meningioma with histologically aggressive appearance and clinically aggressive behavior: a case report.

Clear cell meningioma (CCM) is an uncommon variant of meningioma, corresponding to WHO grade II. We present a case of CCM with histologically aggressive appearance and clinically aggressive behavior. The tumor demonstrated rapid regrowth and brain metastasis. The histological progression from the ordinal CCM to the atypical area and higher MIB-1 index was observed. We assume that the short time of recurrence and metastasis may result from atypical histological features in our case. If the CCM has a histologically aggressive appearance as in our case, we suggest that postoperative adjuvant radiotherapy should be performed despite total resection of the tumor.

Role of the cofilin activity cycle in astrocytoma migration and invasion.

The cofilin pathway plays a central role in the regulation of actin polymerization and the formation of cell membrane protrusions that are essential for cell migration. Overexpression of cofilin has been linked to the aggressiveness of a variety of different cancers. In these cancers, the phosphorylation of cofilin at Ser3 is a key regulatory mechanism modulating cofilin activity. The activation status of cofilin has been directly linked to tumor invasion. Accordingly, in this study, we examined the expression of cofilin and its activation status in astrocytoma cell lines and astrocytic tumors. We show that cofilin expression was increased and correlated with increasing grade malignant astrocytoma. In addition, both cofilin and LIMK had elevated expression in astrocytoma cell lines. Knockdown of cofilin by siRNA altered astrocytoma cell morphology and inhibited astrocytoma migration and invasion. Conversely, overexpression of a cofilin phosphorylation mutant in an in vivo intracranial xenograft model resulted in a more highly invasive phenotype than those xenographs expressing wild-type cofilin. Animals harboring astrocytomas stably expressing the cofilin phosphorylation mutant (cofilin-S3A) demonstrated marked local invasiveness and spread across the corpus callosum to the contralateral hemisphere in all animals. Taken together, these data indicate that the cofilin activity pathway may represent a novel therapeutic target to diminish the invasion of these highly malignant tumors.

Thoracic vertebral cavernous hemangioma in a schizophrenic patient--case report.

A 55-year-old man presented with gait disturbance, incontinence, and back pain. He had a medical history of schizophrenia for the past 35 years. Computed tomography (CT) and magnetic resonance imaging suggested thoracic vertebral hemangioma. Dynamic CT incidentally detected a hepatic hemangioma. Laminectomy of T3 and T4, resection of the epidural hemangioma, and rigid instrumentation between T1 and T6 using rod and hook systems were performed. Postoperatively, his symptoms completely disappeared and the histological diagnosis was capillary hemangioma. Schizophrenic patients have diminished sensitivity to pain or other symptoms, so neurological symptoms may become severe. However, early and appropriate treatment can result in satisfactory neurological outcome. The patient had a rare association of vertebral hemangioma and hepatic hemangioma, which may be a chance occurrence.

Consequences of preoperative evaluation of patterns of drainage of the cavernous sinus in patients treated using the anterior transpetrosal approach.

Extradural procedures in an anterior transpetrosal approach (ATPA) may interrupt the route of drainage from the superficial middle cerebral veins (SMCVs) and the cavernous sinus (CS) to the pterygoid venous plexus at the temporal skull base. Patterns of drainage of the SMCV and the CS and the results of surgery were examined in 12 patients with petroclival lesions treated using the ATPA between 2000 and 2008. The angiographic patterns of drainage of the SMCV were examined in 22 sides of the 12 patients. The SMCV drained into the sphenoparietal sinus in 12 sides, the sphenobasal veins in 4 sides, and the cortical veins in 6 sides. The patterns of drainage of the CS were examined on 12 sides in which the SMCV drained into the sphenoparietal sinus. The CS drained into the inferior petrosal sinus (IPS) in 7 sides and equally into the pterygoid plexus and IPS in 3 sides. The CS drained mainly into the pterygoid plexus in 2 sides of 2 patients, who both suffered temporal lobe swelling postoperatively. The pattern of venous drainage of the CS must be considered in planning surgical approaches to petroclival lesions. In patients with a well-developed pterygoid plexus, surgical interruption of this drainage route may be a cause of injury of the temporal lobe.

Synchronous multifocal osteosarcoma involving the skull presenting with intracranial hemorrhage -case report-.

A 40-year-old man presented with a rare case of synchronous multifocal osteosarcoma involving the skull associated with intracerebral hemorrhage, manifesting as sudden headache and left homonymous hemianopia. Computed tomography revealed a skull tumor in the right occipital bone and intracerebral hemorrhage in the right occipital lobe. Gross total resection of the skull tumor with hematoma was performed. The histological diagnosis was osteosarcoma. The tumor cells had invaded into the surrounding brain parenchyma, resulting in intracerebral hemorrhage.

Cavernous sinus cavernous hemangioma largely extending into the sella turcica and mimicking pituitary adenoma: case report.

A 77-year-old female presented with a rare cavernous sinus cavernous hemangioma with extension to the sella turcica, neuroradiologically mimicking nonfunctioning pituitary macroadenoma. The lesion was partially removed via transsphenoidal surgery, and the histological diagnosis was cavernous hemangioma. After stereotactic radiosurgery using a cyber knife, the lesion decreased in size. Stereotactic radiosurgery may be a good option for cavernous sinus cavernous hemangioma with high risk of surgical bleeding.