Masanao Mohri

Expression of multidrug resistance-associated protein (MRP) in human gliomas.

Drug resistance is a major clinical problem in the chemotherapy of human gliomas. The multidrug resistance-associated protein (MRP), a membrane transporter related to non-P-glycoprotein multidrug resistance, is overexpressed in some drug-selected cancer cell lines. To investigate whether MRP is involved in the intrinsic drug resistance of human gliomas, surgical specimens of 20 gliomas (11 glioblastomas, 6 anaplastic astrocytomas, and 3 astrocytomas), 3 normal brain specimens, and 4 glioma cell lines (U87MG, U251MG, U373MG, and T98G) were analyzed. The expression of MRP was studied by RT-PCR and immunohistochemistry in the surgical specimens. The MRP expression levels in the cell lines were assessed by the quantitative RT-PCR and Western blot analyses. Sensitivity to adriamycin (ADM), etoposide (VP-16), cisplatin (CDDP), and 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), were determined by MTT assay, and antisense treatment was evaluated in the cell lines. The expression of MRP was detected in 9 of 11 glioblastomas and 3 of 6 anaplastic astrocytomas. The quantitative analyses of the cell lines revealed that the MRP mRNA and protein levels were increased 4.5-fold in the T98G cells as compared to U87MG. T98G cells showed the highest resistance to all drugs. Western blot analysis revealed that treatment with the antisense oligonucleotide reduced the level of MRP expression to 25% of the sense oligonucleotide treatment in T98G cells. The sensitivity to ADM, VP-16 and CDDP was significantly increased in the antisense-treated cells as compared with the sense-treated cells. These results suggest that the MRP expression may be related to the intrinsic multidrug resistance in human gliomas.

Surgical indications and microsurgical anatomy of the transchoroidal fissure approach for lesions in and around the ambient cistern.

OBJECTIVE Opening the temporal part of the choroidal fissure (CF) makes it possible to expose the crural cistern, the ambient cistern, and the medial temporal lobe. We examined the microsurgical anatomy and the surgical indications for use of the trans-CF approach. METHODS The microsurgical anatomy encountered in the trans-CF approach for lesions in and around the ambient cistern was studied in three cadavers. On the basis of these cadaveric studies, the trans-CF approach was used during surgery in three live patients with such lesions. RESULTS The angiographic “plexal point,” which indicates the entrance of the anterior choroidal artery as it enters the temporal horn of the lateral ventricle, was thought to be a key anatomic landmark of the trans-CF approach. A cortical incision for entry into the temporal horn should be made in the inferior temporal gyrus to minimize the potential damage to the optic radiations and to the speech centers. After the CF is opened posteriorly to the plexal point between the tenia fimbria and the choroid plexus, the posterior cerebral artery (PCA) in the ambient cistern can be observed with minimal caudal retraction of the hippocampus. In this study, surgical procedures using the trans-CF approach were successfully performed on patients with high-positioned P2 aneurysms whose PCA ran close to the plexal point or higher, whose medial temporal arteriovenous malformations were fed mainly by the PCA, and whose tentorial hiatus meningiomas protruded into the temporal horn through the CF, with no resulting postoperative visual or memory disturbances. CONCLUSION The trans-CF approach is especially useful in surgery for lesions in and around the ambient cistern.

Retro-odontoid pseudotumor without atlantoaxial subluxation

A retro-odontoid pseudotumor (ROP) is commonly associated with atlantoaxial subluxation (AAS). Here, we report a patient with ROP but without AAS. The patient was a 72-year-old man who did not have a history of rheumatoid arthritis or trauma to the head and neck. The patient was admitted to our hospital with gait disturbance, progressive motor weakness in both upper extremities and sensory disturbance in all four extremities. MRI showed a retro-odontoid mass with severe compression of the cervical spinal cord. A CT scan showed spondylotic changes in C5, C6, and C7 and bilateral facet fusion between C3 and C4. Dynamic radiography showed no evidence of AAS; there was loss of mobility at C2-C7 and excessive mobility at C1. Intraoperative pathological examination revealed that the lesion was a pseudotumor; therefore, posterior C1-C2 fixation was performed. MRI performed 6 months after the operation revealed that the pseudotumor was markedly reduced. To the best of our knowledge, patients with ROP without AAS are uncommon.

Prediction of carotid artery in-stent restenosis by quantitative assessment of vulnerable plaque using computed tomography

BACKGROUND AND PURPOSE To assess the relationship between plaque volume evaluated by multidetector computed tomographic angiography (MDCT) and in-stent restenosis (ISR) after carotid artery stenting (CAS). MATERIALS AND METHODS From a retrospectively maintained database, data were collected for 52patients with carotid artery stenosis treated with CAS between 2007 and 2012. We defined ISR of≥50% as a peak systolic velocity≥200cm/s on echo-duplex scan. Carotid plaques were subdivided into four components according to radiodensity in Hounsfield units (HU) as follows: <0, 0-60, 60-130, and>600HU. Risk factors that influenced ISR were compared using univariate and multivariate Cox regression analyses. RESULTS During a median follow-up period of 36months, ISR of≥50% was detected in five patients (9.6%). In the univariate Cox proportional hazard regression analysis, renal insufficiency, coronary artery disease, total plaque volume, and plaque volumes with radiodensities<0 and≥600HU increased the risk for ISR (P<0.10). When the significant risk factors determined from the univariate analysis were subjected to a multivariate analysis, only the volumes of the plaque components with radiodensities<0 HU independently predicted the development of ISR (hazard ratio: 1.041; 95% confidence interval: 1.006-1.078; P=0.021). CONCLUSION Our data suggest that the high volume of the plaque components with radiodensities<0HU was independently associated with the increased risk of ISR after CAS. Quantitative and qualitative tissue characterizations of carotid plaques using MDCT might be a useful predictive tool of the development of ISR.

Ganglioglioma of the Thoracolumbar Spinal Cord in a Patient with Neurofibromatosis Type 1: A Case Report and Literature Review

Gangliogliomas of the spinal cord are rare, and the conus medullaris is an extremely rare site for their occurrence. The authors present a case in which a ganglioglioma was found in the thoracolumbar spinal cord, including the conus medullaris, of a 5-year-old female patient with neurofibromatosis type 1 (NF1) who presented with paraparesis and urinary disturbance. MRI revealed an intramedullary lesion within the thoracolumbar spinal cord, including the conus medullaris, which was surgically removed. Pathological investigation showed a ganglioglioma consisting of glioneuronal tumor cells. This is the first report to provide a pathological description of a spinal cord ganglioglioma in a patient with NF1. Because gangliogliomas usually have a good prognosis following resection, it is important to clearly distinguish them from other NF1-associated lesions, even though ganglioglioma of the thoracolumbar spinal cord, including the conus medullaris, is an extremely rare condition.

MGMT promoter methylation and temozolomide response in choroid plexus carcinoma

Choroid plexus carcinoma (CPC) is a malignant tumor with a strong tendency to spread along the cerebrospinal fluid pathway. There is no standardized chemotherapy protocol for this rare tumor. We report a 38-year-old man with CPC in the lateral ventricle with obstructive hydrocephalus. Because of the poor demarcation between thalamus and fornix, subtotal tumor resection was performed. Postoperative spine magnetic resonance (MR) image revealed whole spinal axis dissemination. After diagnosis of CPC, the patient was treated with whole ventricular and spine radiation concomitant with temozolomide chemotherapy, although the O6-methylguanine-DNA methyltransferase (MGMT) promoter was found to be unmethylated. Although MR images revealed transient stable disease during adjuvant therapy, tumor progression was depicted after four cycles of temozolomide therapy. We discuss the ineffectiveness of adjuvant temozolomide therapy for CPC in connection with O6-methylguanine-DNA methyltransferase promoter methylation.

Ependymoma and choroid plexus papilloma as synchronous multiple neuroepithelial tumors in the same patient: a case report and review of literature.

BACKGROUND AND IMPORTANCE:We report the case of a patient with multiple neuroepithelial tumors of different histological cell types. In this patient, synchronous appearance of tumors of the central nervous system, ie, cervical ependymoma and a fourth ventricle choroid plexus papilloma, was noted. CLINICAL PRESENTATION:A 36-year-old man presented with sensory disturbance of the bilateral upper extremities. Magnetic resonance imaging revealed a heterogeneously enhanced mass with syringomyelia in the upper cervical cord and a well-enhanced mass in the fourth ventricle. The patient underwent bilateral suboccipital craniotomy and laminectomy from the level of C1 to C3 for both lesions. The lesions were grossly resected. Histological and immunohistochemical examinations revealed that the cervical tumor was an ependymoma, and the fourth ventricle tumor was a choroid plexus papilloma. CONCLUSION:The appearance of synchronous multiple neuroepithelial tumors of different histological cell types is extremely rare, and this is the first known case of ependymoma occurring synchronously with choroid plexus papilloma, both tumors having different histological cell types. Displacement and maldifferentiation of primitive, multipotent neuroepithelial cells may be a causative factor for this unique presentation.

Delayed asymptomatic coil migrations toward different arteries after aneurysmal embolization: case report.

Delayed coil migration after endovascular treatment with detachable coils, particularly several months after treatment, is extremely rare. In this report, the authors describe a 77-year-old female in whom delayed coil migration to the anterior cerebral artery and posterior communicating artery (PCoA) developed 3 months after an uncomplicated aneurysm embolization. The patient was successfully retreated with a closed-cell stent. Computational fluid dynamics (CFD) revealed high wall shear stress (WSS) and multiple vortices in the residual cavity of the initially treated aneurysm. CFD could be useful to detect and predict this complication, and a stent-assisted technique could be an important treatment option.

Pseudoaneurysm formation caused by the withdrawal of a Trevo ProVue stent at a tortuous cerebral vessel: a case report.

This is the first report on the mechanism of pseudoaneurysm formation after withdrawal of a stent retriever. A 79-year-old woman developed cardiogenic embolization of the distal middle cerebral artery (M2). The deployed stent retriever bent because of vessel tortuosity. After withdrawal of the stent with strong resistance, complete revascularization was achieved, but an extravasation was detected at the site. Eight hours after disappearance of the extravasation, re-bleeding occurred with aneurysm-like pooling of contrast media. Direct surgical observation confirmed a pseudoaneurysm formation. The pseudoaneurysm was likely formed by avulsion of a fine vessel during withdrawal of the stent retriever at a tortuous vessel.

Treatment Result in the Initial Stage of Kanazawa Mobile Embolectomy Team for Acute Ischemic Stroke

Five recent multicenter randomized controlled trials (RCTs) have clearly shown the superiority of mechanical thrombectomy in large vessel occlusion acute ischemic stroke compared to systemic thrombolysis. Although 14 hospitals in Ishikawa prefecture have uninterrupted availability of systemic thrombolysis, mechanical thrombectomy is not available at all of these hospitals. Therefore, we established a Kanazawa mobile embolectomy team (KMET), which could travel to these hospitals and perform the acute reperfusion therapy. In this article, we report early treatment outcomes and validate the effectiveness of a network between affiliated hospitals and KMET. Between January 2014 and December 2015, 48 patients, aged 45–92 years (mean: 73.0 years), underwent acute reperfusion therapy provided by KMET in 10 affiliated hospitals of Kanazawa University Hospital. The pre-treatment NIHSS scores ranged from 5 to 39 (mean: 19.1). ASPECTS+W ranged from 1 to 11 (mean: 7.3). Successful revascularization, defined as thrombolysis in cerebral infarction (TICI) 2b or 3, was achieved in 38/48 cases (80%), and a good outcome, defined as modified Rankin Scale (mRS) score from 0 to 2 at 90 days after the treatment, was achieved in 24/48 cases (50%). There were two cases of intracranial bleeding (4%). Mean time from onset to recanalization was 297 min. These results, which are similar to those of five previous RCTs, suggest that a collaborative network between affiliated hospitals and KMET is effective for acute reperfusion therapy in local areas wherein experienced neuroendovascular specialists are insufficient.