Biomedical subjects
Publications and source records attributed to Y Ushio.
We report a patient with hemichorea following subthalamic hemorrhage. Vo-complex thalamotomy abolished the choreic movements for over 4 years of follow-up.
BACKGROUND: The introduction of modern neuro-imaging techniques, as well as various environmental factors, have been changing the incidence and the proportions of the types of clinically diagnosed intracranial tumors. The aim of this study was to determine recent trends in the occurrence of primary intracranial tumors in the residents of Kumamoto Prefecture, Japan. METHODS: We surveyed 2129 patients who were diagnosed with primary intracranial tumors between 1989 and 1998, with histological diagnosis being obtained in 71% of the patients. RESULTS: Of the 2129 patients, 710 (33.3%) had meningiomas, 390 (18.3%) had pituitary adenomas, 315 (14.8%) had malignant gliomas, and 208 (9.8%) had schwannomas. The overall age-adjusted incidence rates were 10.97/100,000/year (males, 9.70; females, 11.86). One hundred and nine patients (5.1%) were younger than 15 years, and 480 patients (22.5%) were older than 70 years. The most common tumors in children were astrocytomas (37.6%), followed by germ-cell tumors (16.5%) and craniopharyngiomas (11.9%), medulloblastomas (11.0%), and ependymomas (4.6%). Meanwhile, the most common tumors in elderly residents were meningioma (51.7%), followed by malignant glioma (13.7%), pituitary adenoma (11.4%), schwannoma (7.7%), malignant lymphoma (4.6%), and astrocytoma (2.7%). The proportion of asymptomatic tumors increased, from 24.6% in 1989-1994 to 33.0% in 1995-1998; 169 (62.8%) were meningiomas, followed by pituitary adenomas (14.1%).
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BACKGROUND: Vertebral arteriovenous fistulas are relatively rare. Although the common treatment is transarterial embolization, it may be impossible to pass through the fistula (e.g. a microfistula created by a needle puncture). We report two patients with vertebral arteriovenous fistulas due to penetrating trauma who were successfully treated by transvenous embolization. METHOD: We present 2 patients with vertebral arteriovenous fistulas. One patient is presented to demonstrate complications following attempted internal jugular cannulation and the other is presented to demonstrate complications after surgery for a jugular foramen neurinoma. Both patients manifested the sign of a severe bruit. FINDINGS: To identify the fistula point, simultaneous transarterial and transvenous angiography was performed. Using the transvenous approach, microcoils were applied to the fistula and the bruit completely disappeared. Interpretation. Transvenous embolization is a useful technique and a first-choice strategy to treat patients with the vertebral arteriovenous fistula due to penetrating trauma.
BACKGROUND: Since metastatic brain tumours from esophageal carcinoma are essentially rare, previous reports have not determined the common neuro-radiological findings and its clinical aspects. FINDINGS: We report the neuro-imaging and clinicopathological features of our 8 metastatic brain tumours from an esophageal site. Histologically, 6 of our 8 patients had squamous cell carcinoma and 2 had small cell carcinoma, a rare variant form. Both histological types mainly exhibited cystic lesions with a thin enhanced rim on magnetic resonance images (MRI, 4 of 6 squamous cell carcinomas and 1 of 2 small cell carcinomas). Combination therapy (irradiation and chemotherapy) after surgical treatment, the number of metastatic brain tumours, and the interval between their appearance and the diagnosis of the primary lesion could be prognostic factors in our series. INTERPRETATION: Among Japanese, the vast majority of primary esophageal cancers are squamous cell carcinomas. Therefore, MRI findings of a cystic tumour with a thin enhanced rim may alert one to the possibility of a metastatic brain tumour from the esophagus.
BACKGROUND: Hemangioblastoma (HBL) in the suprasellar region is extremely rare. CASE DESCRIPTION: A suprasellar mass was found in a 33-year-old woman with retinal HBL and bilateral adrenal pheochromocytomas. The diagnosis of von Hippel-Lindau (VHL) disease was confirmed preoperatively not only by these clinical manifestations but also by germline mutation study. The existence of VHL disease indicated a diagnosis of HBL for the suprasellar mass. The results of our mutation study indicated that this patient had type II VHL disease, suggesting that careful follow-up is essential for the early detection of renal cell carcinoma, which is often associated with type II VHL disease. Here, we summarize the previously reported features of sellar and suprasellar HBLs. CONCLUSIONS: HBLs in this region may be one manifestation of VHL disease. Genetic testing of the VHL gene of our patient could provide useful information to determine appropriate medical care and management.
BACKGROUND: This study was conducted to define general guidelines for rational clinical decision-making with respect to patients older than 80 years who present with ruptured anterior circulation aneurysms and a Hunt and Hess clinical grade of III. METHODS: The 29 consecutive patients enrolled in this study were treated at 4 participating centers between 1995 and 1998. All were 80 years or older on admission and met 7 eligibility criteria. The decision to treat surgically or non-surgically was made individually at each center. The outcome at discharge was assessed using the Glasgow Outcome Scale (GOS); the Barthel Score (BS) was used to determine the patients' quality of life after discharge. RESULTS: Of 15 surgically treated patients, 4 died before discharge and 8 were discharged in poor condition. Of these, 7 died of unrelated causes within 2 years of the SAH and one is living in a nursing home. Three patients with middle cerebral artery (MCA) aneurysms made a good recovery; they are currently living at home. Of the 14 conservatively treated patients, 10 died during their hospital stay mainly because of rebleeding that occurred within 3 weeks of the subarachnoid hemorrhage (SAH). Three others who were discharged in poor condition died of systemic illness within 2 years. The remaining patient is living in a nursing home with a BS value of 0. CONCLUSIONS: The outcomes for patients treated conservatively were catastrophic. Even in surgically treated patients, favorable outcomes were rare; the best results were achieved in surgically treated patients with MCA aneurysms.
The pineal region is a heterogeneous area that includes the pineal gland and several parapineal structures. Pineal region masses include germ cell tumors (GCTs), pineal parenchymal cell tumors, glioma, meningioma, metastases, and non-neoplastic masses such as pineal cysts, lipoma, epidermoid, vascular malformations. Although MRI has allowed an improvement in distinguishing true pineal masses from parapineal masses impinging into the region of the gland, it is still difficult to differentiate the pineal GCTs from pineal parenchymal tumors with only images, and the clinical informations such as age, sex, and the tumor markers are very important.
BACKGROUND: Although mutational inactivation and allelic loss in the NF2 gene appear to be causal events in the majority of vestibular schwannomas, involvement of another potentially important mechanism, transcriptional inactivation, has not been investigated. RESULTS: We cloned and functionally characterized the 5'-flanking region of the human NF2 gene and identified the molecular mechanisms that regulate NF2 expression. Luciferase assay and site-directed mutagenesis demonstrated that a 70-base pair (bp) region (-591 to -522 bp from the translation start site) was essential for the basic expression of the NF2 gene. A gel mobility shift assay indicated recognition by nuclear protein of the unusually long ( approximately 66 bp) sequences in this region. Recognition was inhibited by either mutation of the binding core sequence or by methylation of three CpG sites. Point mutations at these CpG sites significantly decreased promoter activity, suggesting the importance of these sites. In 14 of 23 vestibular schwannomas, these three CpG sites were methylated in a site-specific manner and the methylation status was consistent with the expression of NF2 mRNA. CONCLUSIONS: Suppressed expression by aberrant methylation or mutation of the promoter elements could be an alternative mechanism for inactivation of the NF2 gene.
Few studies have focused on the relationship between hormone replacement therapy (HRT) for postmenopausal women or those with breast cancer and the occurrence of cerebral embolism. Results are conflicting as to whether there is a link between the two. We describe three patients who experienced cerebral embolism during HRT. A 73-year-old woman had a transient ischemic attack (TIA) 6 years prior to the present admission. She then took HRT oestrogen plus medroxyprogesterone acetate for about 6 years. The HRT had been prescribed by a gynaecologist for amelioration of postmenopausal symptoms. Six years after beginning HRT, she experienced sudden onset left hemiparesis due to cerebral embolism. Two other patients had been taking HRT for breast cancers. One, a 47-year-old woman, had taken medroxyprogesterone acetate for more than one year, for recurrence of breast cancer. She had developed sudden complete left hemiparesis due to an embolism at the carotid bifurcation. The other patient, a 72-year-old woman who was taking tamoxifen citrate for prevention of breast cancer relapse, experienced cerebral embolism just 2 months after beginning tamoxifen. The risk of cerebral embolism in those on HRT should be emphasized, along with the beneficial effects in terms of postmenopausal symptoms and prevention of breast cancer recurrence.
Specialized subsets of early-generated neurons provide the cellular cues that are necessary for the establishment of characteristic cell and fiber interactions in each brain region. During the development of the mammalian cerebral cortex, the early-generated cells line up in the most superficial part of the telencephalic pallium forming the preplate. It has been generally thought that the preplate derivatives are exclusively located in the cortical region and govern the early histogenetic phase of cortical development. However, we here disclose an unexpected evidence that a subset of early-generated neurons of the piriform preplate migrate inward into and disperse within the subcortical structure striatum during the embryonic stage. Their migratory route is unique and its direction is opposite to the ordinary migration of neuronal precursors directed outward from the periventricular germinal zone. After immigrating into the developing striatum, these early-generated cells are closely associated with the intrastriatal fascicules of axons. The majority of these cells are eliminated by apoptotic cell death during the early postnatal stage. Based on these findings, we propose a new concept: the preplate neurons may not only direct cortical histogenesis but also change their location to play a role in the development of subcortical structures.
Apoptosis plays an important role in delayed neuronal cell death after cerebral ischemia. Activation of Akt/protein kinase B has been recently reported to prevent apoptosis in several cell types. In this article the authors examine whether induction of ischemic tolerance resulting from a sublethal ischemic insult requires Akt activation. Sublethal ischemia gradually and persistently stimulated phosphorylation of Akt-Ser-473 in the hippocampal CA1 region after reperfusion. After lethal ischemia, phosphorylation of Akt-Ser-473 showed no obvious decrease in preconditioned gerbils but a marked decrease in nonconditioned gerbils. Changes in Akt-Ser-473 phosphorylation were correlated with changes in Akt activities, as measured by an in vitro kinase assay. Intracerebral ventricular infusion of wortmannin before preconditioning blocked both the increase in Akt-Ser-473 phosphorylation in a dose-dependent manner and the neuroprotective action of preconditioning. These results suggest that Akt activation is induced by a sublethal ischemic insult in gerbil hippocampus and contributes to neuroprotective ischemic tolerance in CA1 pyramidal neurons.
In transient forebrain ischemia, sodium orthovanadate as well as insulinlike growth factor-1 (IGF-1) rescued cells from delayed neuronal death in the hippocampal CA1 region. Adult Mongolian gerbils were subjected to 5-minute forebrain ischemia. Immunoblotting analysis with anti-phospho-Akt/PKB (Akt) antibody showed that phosphorylation of Akt at serine-473 (Akt-Ser-473) in the CA1 region decreased immediately after reperfusion, and in turn transiently increased 6 hours after reperfusion. The decreased phosphorylation of Akt-Ser-473 was not observed in the CA3 region. The authors then tested effects of intraventricular injection of orthovanadate and IGF-1, which are known to activate Akt. Treatment with orthovanadate or IGF-1 30 minutes before ischemia blocked delayed neuronal death in the CA1 region. The neuroprotective effects of orthovanadate and IGF-1 were associated with preventing decreased Akt-Ser-473 phosphorylation in the CA1 region observed immediately after reperfusion. Immunohistochemical studies with the anti-phospho-Akt-Ser-473 antibody also demonstrated that Akt was predominantly in the nucleus and was moderately activated in the cell bodies and dendrites of pyramidal neurons after orthovanadate treatment. The orthovanadate treatment also prevented the decrease in phosphorylation of mitogen-activated protein kinase (MAPK). Pretreatment with combined blockade of phosphatidylinositol 3-kinase and MAPK pathways totally abolished the orthovanadate-induced neuroprotective effect. These results suggest that the activation of both Akt and MAPK activities underlie the neuroprotective effects of orthovanadate on the delayed neuronal death in the CA1 region after transient forebrain ischemia.
The authors report the first case of a solitary xanthogranuloma of the cavernous sinus without systemic manifestation. A 43-year-old woman experienced decreased visual acuity on the right side in association with papilledema and a visual field defect. She was alert and no other neurological sign was observed. She had no family history of hyperlipoproteinemia and no cutaneous and/or systemic xanthomatous lesions. Skull x-ray films showed an enlarged right superior orbital fissure. Computerized tomography revealed a low-density oval mass 2 x 3 cm in diameter in the right cavernous region that was compressing the right optic nerve in the lateral to medial direction. This mass exhibited isointensity on T1-weighted and mixed-pattern hyperintensity on T2-weighted magnetic resonance images with diffuse contrast enhancement. Cerebral angiography demonstrated fine staining in the margin, originating from the right middle meningeal artery. These neuroimaging findings closely mimicked those associated with trigeminal neuroma. The lesion was partially removed via a right-sided zygomatic approach, and her symptoms improved. Clinical characteristics and histopathological features of this rare case are discussed.
OBJECT: The most frequent genetic abnormality in human malignant gliomas is loss of heterozygosity (LOH) on chromosome 10. Candidate genes on chromosome 10 that are associated with the prognosis of patients with anaplastic astrocytoma (AA) and glioblastoma (GBM) were evaluated. METHODS: The authors used 12 fluorescent microsatellite markers on both arms of chromosome 10 to study LOH in 108 primary astrocytic tumors. The LOH on chromosome 10 was observed in 11 (32%) of 34 AAs and 34 (56%) of 61 GBMs. No LOH was detected in 13 low-grade gliomas. Loss of heterozygosity was not detected in any AA in the seven patients younger than 35 years, but it was discovered in 41% of the patients older than 35 years. The prognostic significance of LOH at each locus was evaluated in 89 patients older than 15 years; 33 (37%) had supratentorial AAs and 56 (63%) had supratentorial GBMs. The Cox proportional hazards model, adjusted for patient age at surgery, the preoperative Karnofsky Performance Scale score, and the extent of surgical resection revealed that LOH on marker D10S209 near the FGFR2 and DMBT1 genes was significantly associated with shorter survival in patients with AA. The LOH on markers D10S215 and D10S541, which contain the PTEN/MMAC1 gene between them, was significantly associated with shorter survival in patients with GBM. CONCLUSIONS: In the present study it is found that LOH on chromosome 10 is an age-dependent event for patients with AAs and that LOH on marker D10S209 near the FGFR2 and DMBT1 loci is a significantly unfavorable prognostic factor. It is also reported that LOH on the PTEN/MMAC1 gene is a significantly unfavorable prognostic factor in patients with GBM.
On radiograms, glial tumors are usually seen to invade in a finger-like fashion, while non-central nervous system (CNS) tumors expand in a mass-like fashion. We prepared organotypic brain slice cultures from newborn rats to investigate the invasive behavior of human brain tumors using glial tumor cell lines (U-87MG, U-373MG, U-251MG, and SF-126) and of non-CNS tumors using cell lines; HT-1080 (human malignant fibrosarcoma), RFRF (human lung carcinoma), MIA-PICA (human pancreatic carcinoma), and Colo38 (human malignant melanoma). We selected an area that was centered at a junction between deep cortical layers and the striatum, punched a hole measuring 0.5-0.7 mm in diameter in this area, implanted different rhodamine-labeled tumor cells at that site, and observed their invasive behavior under an inverted fluorescent microscope. Over the course of several days, all glioma cells invaded in a finger-like fashion; U-373 MG cells invaded farthest. Non-CNS tumors expanded in mass-like fashion into adjacent areas. Using the slice cultures, we also investigated the regulatory effect on tumor invasion of forced expression of glial fibrillary acidic protein (GFAP) after gene transfection. The forced expression of GFAP rendered U-87MG and HT-1080 cells less invasive. Our results show that organotypic brain slice cultures are an excellent medium for studying the invasive features of glial and non-CNS tumors.
Simvastatin is one of the competitive inhibitors of HMG-CoA reductase. During clinical trials, it has shown the ability to lower serum cholesterol. We investigated the effect of simvastatin on the growth of malignant gliomas in vitro, semi-in vivo, and in vivo. An in-vitro MTT assay revealed that human malignant glioma cell lines: U-251MG, U-373MG, and U-87MG, and rat malignant glioma cell line C6 were well inhibited in growth in a dose-dependent fashion. An anchorage-independent growth assay showed that the number of colonies (more than 100 microM in size) of human (U-373MG) and rat malignant gliomas (C6) was markedly reduced in a dose-dependent fashion. A flow cytometry analysis revealed that simvastatin treatment led U-251MG cells to accumulate in sub G0-G1. Immunostaining by TUNEL method showed that most glioma cells treated by 10 microM simvastatin had nuclear immunostaining, suggesting apoptotic changes of the treated cells. The human umbilical vein endothelial cells and human lung fibroblasts were inhibited in growth by no more than 20% of controls even with a high dose (10 microM) of simvastatin. In the semi-in vivo model, using newborn rat brain slice cultures, the rhodamine-labeled glioma cells were abolished after 7 days of local simvastatin treatment with fibrin glue probably suggesting that simvastatin led the cells to apoptosis. In rat models using subcutaneously inoculated C6, the local application of simvastatin combined with fibrin glue (spray method) was quite effective in inhibiting the growth of the tumor. These data suggest that simvastatin may be a novel anti-glioma drug, and the local application of simvastatin combined with fibrin glue (by spray method) may be a crucial new clinical strategy against glioma growth.
Facial arteriovenous malformations (FAVM) are difficult to treat because of their highly vascular networks. Intravascular treatment using liquid material to occlude the FAVM occasionally results in skin necrosis after embolization. The use of particulate materials to obliterate the nidus often fails to obtain a permanent cure due to arterial recanalization. We report two patients with FAVM who were successfully treated with endovascular embolization using a new type of particulate material. One patient was treated with embolization only, the other was treated with embolization followed by surgical resection. Both patients showed clinical and angiographic improvement. Intravascular treatment using particles with a smooth surface and optimal size is safe and effective in the treatment of patients with FAVM.