Staged operations for posthemorrhagic hydrocephalus in extremely low-birth-weight infants with preceding stoma creation after bowel perforation: surgical strategy.

CASE REPORT: We report a complicated extremely low-birth-weight (ELBW) infant with posthemorrhagic hydrocephalus after intraventricular hemorrhage and preceding stoma creation after bowel perforation who was treated with staged operations, including shunting and external ventricular drainage. The first operation was a temporary valveless ventriculoperitoneal (VP) shunt placement until the time of the stoma closure. The stoma was successfully closed 3 months after the first operation when the peritoneal tube was drawn out from the chest wall and the VP shunt system was temporarily used as an external drainage with a long subcutaneous tunnel. One month after the second operation, final VP shunt placement was performed after good healing of bowel anastomosis was surely confirmed. The previous peritoneal shunt tube was cut behind the ear, removed, and replaced with a valve-regulated VP shunt system. CONCLUSION: This staged strategy is a safe and feasible option for complicated ELBW infants with preceding stoma and hydrocephalus.

Atypical extraventricular neurocytoma.

Extraventricular neurocytoma (EVN) is a rare brain tumor that poses diagnostic difficulty. Described herein is a case of atypical EVN arising in a 54-year-old woman. A well-circumscribed lesion (3.0 x 3.0 x 3.0 cm) in the right parietal lobe showed diffuse proliferation of monotonous tumor cells with perinuclear clearing within a delicate fibrillary matrix similar to neuropil. Tumor also showed vascular proliferation and high mitotic activity. Immunohistochemically, these tumor cells were strongly positive for synaptophysin both in the neuropil and in the perinuclear cytoplasm, and were negative for glial fibrillary acidic protein and Olig2. Ki-67 labeling index was 13.0% in the most stained areas, but accumulation of p53 was not observed. These findings were compatible with those of EVN with histological atypia. EVN should be considered as a candidate in the differential diagnosis of parenchymal brain tumor, especially oligodendroglioma. The important features are the delicate fibrillary matrix similar to neuropil, diffuse and strong immunoreactivity for synaptophysin, and negative immunoreactivity for Olig2. High proliferative activity without accumulation of p53 suggests that other factors are involved in oncogenesis of atypical EVN.

Role of hepatocyte growth factor activator (HGF activator) in invasive growth of human glioblastoma cells in vivo.

Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional growth factor that is involved in invasive growth of tumor cells via its receptor MET, a protein product of c-met proto-oncogene. HGF activator (HGFA) is a serine proteinase responsible for the activation of proform of HGF/SF (proHGF/SF). In our study, we examined the effects of engineered expression of HGFA on 2 human glioblastoma cell lines (YKG-1 and U251). Both cells expressed MET, while only YKG-1 expressed endogenous proHGF/SF. Enhanced MET phosphorylation and increased migratory activity were induced by the expression of HGFA in YKG-1 cells in vitro in the presence of thrombin, which is a known activator of proHGFA. In contrast, MET phosphorylation was consistently observed in U251 that lacked endogenous HGF/SF, suggesting ligand-independent activation of MET in this cell line. Consequently, the expression of HGFA in U251 did not enhance the MET phosphorylation and following cellular response even with the thrombin treatment. However, addition of exogenous proHGF/SF resulted in enhanced migratory activity of HGFA-expressing U251 cells in the presence of thrombin in vitro. The engineered HGFA expression resulted in significantly enhanced tumor growth with increased vascular density in vivo when YKG-1 cells were implanted in nude mouse brain. This effect was not observed in U251 lacking endogenous proHGF/SF. These results indicate the possible existence of multiple mechanisms of MET activation in glioblastomas and that the activation system of proHGF/SF is important in progression of glioblastomas that express endogenous proHGF/SF and require ligand-dependent MET activation.

Diverse roles of hepatocyte growth factor activator inhibitor type 1 (HAI-1) in the growth of glioblastoma cells in vivo.

Hepatocyte growth factor activator inhibitor type-1 (HAI-1) is an integral-membrane proteinase inhibitor. In this study, we examined the effects of HAI-1 on human glioblastoma cells. Two glioblastoma cell lines (YKG-1, U251) were stably transfected with expression plasmid harboring mature membrane-form or truncated secreted-form HAI-1. Culture characteristics were not altered by the expression of HAI-1, whereas in vitro invasiveness of U251 was suppressed. On the other hand, the expression of membrane-form HAI-1 resulted in significantly enhanced tumorigenicity of both cell lines in vivo. In contrast, secreted-form HAI-1 did not promote the tumorigenicity. These results suggest that HAI-1 may play complex roles in progression of glioblastoma cells, and membrane-form HAI-1 may mediate an undefined important signaling in the cells.

Adenoid glioblastoma arising in a patient with neurofibromatosis type-1.

An unusual case of glioblastoma with adenoid structures arising in a 30-year-old Japanese woman with neurofibromatosis type-1 (NF1) is reported. The patient was admitted to University of Miyazaki Hospital, complaining of headache, nausea and vomiting. From the neuroradiological findings the patient was diagnosed as having glioblastoma, and the tumor was surgically resected. Histologically, the tumor consisted mainly of dark basophilic cells showing prominent tubular or glandular structures surrounded by large eosinophilic cells, in addition to the typical glioblastoma features in the periphery of the tumor. Both cells showed strong stainability with glial fibrillary acidic protein (GFAP) and S-100 protein immunohistochemically, so that the tumor was classified as adenoid glioblastoma. Several cases of glioblastoma have been reported to reveal the adenoid or epithelioid differentiation. The patients with NF1 are prone to develop malignant tumors including glioblastoma, but no cases representing adenoid glioblastoma associated with NF1 have been reported. This report is considered to be the first case of adenoid glioblastoma arising in a patient with NF1. The recognition of the existence of epithelial features of glioblastoma would be important in differential diagnosis of epithelioid tumors of the brain including metastatic carcinomas.

Appearance of early venous filling during intra-arterial reperfusion therapy for acute middle cerebral artery occlusion: a predictive sign for hemorrhagic complications.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the correlation between appearance of angiographic early venous filling during intra-arterial reperfusion therapy and posttherapeutic hemorrhagic complications. METHODS: For the past 7 years, 104 patients prospectively underwent superselective local angiography via a microcatheter before and during intra-arterial reperfusion therapy for acute middle cerebral artery occlusion to evaluate the presence or absence of early venous filling. In principle, reperfusion therapy was discontinued just after appearance of early venous filling for fear of hemorrhage. There were 2 types of early venous filling: early filling of the thalamostriate vein from the lenticulostriate arteries and that of the cortical vein from the cortical arteries. RESULTS: Among these 104 patients, 31 (29.8%) had early venous filling: 19 had early filling of the thalamostriate vein, and the other 12 had early filling of the cortical vein. Eight of the 19 patients (42.1%) and 2 of the 12 patients (16.7%) had massive hematoma with neurological worsening, whereas only 1 of the 73 patients (1.4%) without early venous filling had massive hematoma. There was a significant correlation between early venous filling and massive hematoma in both the deep (P<0.0001) and superficial (P=0.0019) middle cerebral artery territories. The sensitivity and specificity of the presence of early venous filling as an indicator of parenchymal hematoma were 71% and 83%, respectively. None of the 31 ischemic areas with early venous filling could escape cerebral infarction. CONCLUSIONS: Appearance of early venous filling may indicate irreversible brain damage and may be a predictive sign for parenchymal hematoma.

Establishment and characterization of a new human glioblastoma cell line, NYGM.

A cell line designated NYGM was established from a human cerebral glioblastoma multiforme (GBM) obtained from a 75-year-old Japanese woman. The cell line has grown slowly without interruption and has been propagated continuously by serial passages (more than 80 passage) during the past 3 years. The cultured cells were fusiform or polyhedral in shape. The population doubling time was 24 hours. The chromosomal number varied between 77 and 88, with modal chromosomal number of 84. NYGM cells concomitantly expressed MET receptor tyrosine kinase (a product of c-met protooncogene) and its ligand HGF/SF (hepatocyte growth factor/scatter factor), as well as HGF activator and HGF activator inhibitors. The cells might be useful for the study of pericellular regulation of HGF/SF-MET signaling and HGF activation of GBM cells.

Local administration of glial cell line-derived neurotrophic factor improves behavioral and histological deficit of neonatal Erb's palsy in rats.

OBJECTIVE: We sought to evaluate from a behavioral and histological viewpoint the effect of local administration of glial cell line-derived neurotrophic factor (GDNF) on neonatal preganglionic Erb's palsy in rats. METHODS: The Erb's palsy model was produced by transecting the anterior and posterior roots of the left C5-C7 nerves of 7-day-old rats. The rats were divided into GDNF-treated (n = 10) and vehicle-treated groups (n = 11). After we transected the roots, contact in the proximal and distal stumps of the transected nerves was maintained, and the transected point and the entire intraspinal portion of the transected roots were enclosed by Gelfoam soaked with 10 micro g GDNF or saline. The behavioral evaluation consisted of a foot-fault test and a forepaw muscle strength test, all of which were performed from the third to the seventh weeks after the operation. Seven weeks after the operation, all rats were killed, the number of anterior horn cells was counted at C5-C7, and the differences on each side were compared. RESULTS: In the vehicle-treated group, the foot-fault test indicated an abnormality in forelimb function on the root transection side. In the GDNF-treated group, however, significant improvement in forelimb function was observed on the basis of the foot-fault test results obtained in the third to sixth weeks after the operation. In the histological evaluation, the number of anterior horn cells from the side in which the operation took place in the vehicle-treated group was significantly less than that taken from the contralateral side at each segment. In the GDNF-treated group, however, there was no difference in any of the segments, regardless of the side from which they were taken. CONCLUSION: Local administration of GDNF in a neonatal preganglionic Erb's palsy model resulted in significant improvement in deficits on the basis of behavioral and histological evaluations.

Spontaneous regeneration of the corticospinal tract after transection in young rats: collagen type IV deposition and astrocytic scar in the lesion site are not the cause but the effect of failure of regeneration.

In young rats the corticospinal tract regenerated after a single transection of the spinal cord with a sharp blade, but regeneration failed if the transection was repeated to make a more traumatic injury. To identify cells and associated molecules that promote or impede regeneration, we compared expression of collagen type IV, glial fibrillary acidic protein (GFAP), and vimentin immunoreactivity (IR) at the lesion sites in combination with anterograde axonal tracing between animals with two types of transection. Axonal regeneration occurred as early as 18 hours after transection; regenerating axons penetrated vessel-like structures with collagen type IV-IR at the lesion site, while reactive astrocytes coexpressing GFAP- and vimentin-IR appeared in the lesioned white matter. In contrast, when regeneration failed astrocytes were absent near the lesion. By 7 days sheet-like structures with collagen type IV-IR and astrocytic scar appeared in the lesioned white matter and persisted until the end of the observation period (31 days). On the basis of their spatiotemporal appearance, collagen type IV-IR sheet-like structures and the astrocytic scar follow, rather than cause, the failure of regeneration. The major sign, and perhaps cause, of failure of axonal regeneration is likely the prolonged disappearance of astrocytes around the lesion site in the early postinjury period.

Paramedian transmuscular access to C-3 dumbbell-type neurofibroma without paravertebral muscle dissection from the spinous process or facetectomy. Technical note.

The authors devised a paramedian transmuscular approach to the C2-3 facet joint that enabled total removal of C-3 dumbbell-type neurofibroma; dissection of the paravertebral muscles from the spinous process was not required and the facet joint was preserved. Only splitting or retraction of the paravertebral muscles was necessary. The anatomical features and procedures involved in muscle splitting are described.

Correlation of emmprin expression in vascular endothelial cells with blood-brain-barrier function: a study using magnetic resonance imaging enhanced by Gd-DTPA and immunohistochemistry in brain tumors.

In a previous study, we demonstrated that the expression levels in tumor cells of emmprin (CD147) correlated with the grade of astrocytic tumors. Also, we found that emmprin was expressed in vascular endothelial cells of the non-neoplastic brain and hypothesized that emmprin expression could be associated with normal blood-brain-barrier (BBB) function of vascular endothelial cells. In this study, this possibility was examined in non-neoplastic brain, glioma and metastatic carcinoma tissues by comparing emmprin immunohistochemistry with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enhancement of magnetic resonance imaging (MRI), which is a clinical indicator of the BBB function. This study included 10 cases of non-neoplastic brain tissues, 7 of metastatic carcinoma, 7 of diffuse astrocytoma, 4 of anaplastic astrocytoma and 13 of glioblastoma multiforme. In all the cases, MRI with administration of Gd-DTPA was performed. The lesions were resected using the microdissection method with the help of ultrasonography and a neuronavigator. The tissues from Gd-DTPA-enhanced or non-enhanced areas were processed into frozen sections and subjected to immunohistochemistry with anti-emmprin antibody. The expression of emmprin in brain vascular endothelial cells inversely correlated with Gd-DTPA-enhancement of MRI: emmprin was positive in tissues not enhanced by Gd-DTPA and was negative in DTPA-enhanced tissues. Since BBB function presumably remains unimpaired in regions in which MR images are not Gd-DTPA-enhanced, emmprin expression appears to be associated with unimpaired BBB function. This is the first report to demonstrate a possible correlation between emmprin expression and BBB function in humans.

Direct percutaneous transluminal angioplasty for acute middle cerebral artery trunk occlusion: an alternative option to intra-arterial thrombolysis.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the safety and efficacy of direct percutaneous transluminal angioplasty (PTA) for patients with acute middle cerebral artery (MCA) trunk occlusion. METHODS: Over the past 9 years, a total of 70 patients with acute MCA trunk occlusion were treated with intra-arterial reperfusion therapy. In the last 5 years, 34 patients were treated with direct PTA, and subsequent thrombolytic therapy was added if necessary for distal embolization. The other 36 patients, mainly in the first 4 years, were treated with thrombolytic therapy alone and were used as controls. Pretherapeutic neurological status was evaluated with National Institutes of Health Stroke Scale scores. The modified Rankin Scale (mRS) was used to assess clinical outcome at 90 days. RESULTS: There were no significant differences in pretherapeutic National Institutes of Health Stroke Scale score and duration of ischemia between the 2 groups. The rate of partial or complete recanalization in the PTA group was 91.2%, whereas that in the thrombolysis-alone group was 63.9% (P<0.01). The incidence of large parenchymal hematoma with neurological deterioration in the PTA group was 2.9%, while that in the thrombolysis-alone group was 19.4% (P=0.03). Although direct PTA did not improve the rate of favorable outcome (mRS score 0 or 1; 41.7% for the thrombolysis-alone group versus 52.9% for the PTA group; P=0.48), outcome in terms of independence (mRS score 0, 1, 2) was significantly better in the PTA group (73.5%) than in the thrombolysis-alone group (50.0%; P=0.04). CONCLUSIONS: Although definitive conclusions on the comparative merits of these 2 therapies cannot be drawn because of an open trial, direct PTA may be an effective alternative option to intra-arterial thrombolysis for acute MCA trunk occlusion.

Development of a novel experimental rat model for neonatal pre-ganglionic upper brachial plexus injury.

A neonatal upper brachial plexus injury, referred to as Erb's palsy, is a serious obstetric problem. Some surgical methods are used to treat this injury, but they are inadequate. To seek new treatments for Erb's palsy, we used a model for cervical preganglionic root transection in neonate rats and evaluated the behavioral and histological compatibility of this model with Erb's palsy. Two groups were used in this study. In the group, receiving the Erb operation, the left anterior and posterior roots of spinal vertebra C5-C7 were transected at the preganglionic level, and the results were compared with those of a group that received a sham operation. In the group, receiving the Erb operation, walking difficulties and behavioral abnormalities were observed. These observations were noted on the side where the transection took place, and the problems were attributed to proximal muscle weakness in the forelimb. Additionally, the forepaw grip was not impaired. Furthermore, in this group, the number of anterior horn cells in the cervical cord on the transected side was significantly lower than that on the contralateral side (P < 0.001). The results of this study indicate that the model fulfills the criteria for the clinical symptoms of Erb's palsy and that it may also serve as a new method for enabling treatment of the condition.

Clinical features of the localized girdle sensation of mid-trunk (false localizing sign) appeared in cervical compressive myelopathy patients.

Cervical compressive myelopathy patients sometimes show localized girdle sensation in the mid trunk (so-called false localizing sign). This symptom often confuses physicians, but the clinical features and mechanism of this symptom are still unclear. We investigated the clinical features and possible mechanism. In each of five cases of cervical compressive myelopathy disease with and without mid-truncal girdle sensation, the clinical features, degree and shape of cord compression were analysed. The girdle sensation was expressed as a vague or burning sensation, and was localized with a width of 3 or 4 dermatomes from the T3 to T11 level. There was no correlation between the appearance of the girdle sensation and etiology and level of cervical cord compression. Pyramidal tract signs and disturbance of superficial sensation were observed in all cases. Furthermore, on axial MRI, the midline ventral surface of the cervical cord was remarkably compressed in cases with girdle sensation, as if the compressive lesion entered the anterior medial fissure of the cervical cord. From these findings, this false localizing sign may be caused by severe compression of midline ventral structure of the cervical cord. Ischemia of the thoracic watershed zone of the anterior spinal artery from the compression of the anterior spinal artery at the cervical level might also be considered to be a possible cause.

Time-threshold curve determined by single photon emission CT in patients with acute middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: In patients with ischemic stroke, not only the degree of ischemia but also its duration are key determinants of tissue survival. The purpose of this study was to show the synergistic effects of these two factors on tissue survival in humans. METHODS: We retrospectively reviewed findings in 19 patients with middle cerebral artery occlusion who had clearly defined ischemic duration from onset to angiographic complete recanalization and who underwent pretreatment single photon emission CT. Pretreatment single photon emission CT and final CT scans were compared, and hypoperfusion cortices were divided into reversible and irreversible ischemia. Regions of interest were placed in both irreversible and reversible ischemic cortices, and the residual cerebral blood flow was analyzed by side-to-side comparison with a calculated asymmetry index. To show the relationship between the reversibility of ischemia and the ischemic duration/severity, discriminant analyses were conducted. The analyses were conducted separately using data obtained within 3 hours of ischemic duration and data obtained more than 3 hours after ischemic duration. RESULTS: Within 3 hours of ischemic duration, analysis revealed a discriminant line of asymmetry index (%) = 21.53 time (h) - 19.15. After more than 3 hours of ischemic duration, it revealed a discriminant line of asymmetry index = 0.50 time + 48.27. These discriminant lines rose rapidly within the first 3 hours after stroke onset and thereafter reached almost a plateau level. CONCLUSION: These pilot data suggest urgency for treatment, less need for triage based on cerebral blood flow measurement during the first few hours, and more time to triage based on cerebral blood flow measurement for patients with later presentations.

Combined direct percutaneous transluminal angioplasty and low-dose native tissue plasminogen activator therapy for acute embolic middle cerebral artery trunk occlusion.

BACKGROUND AND PURPOSE: In embolic middle cerebral artery (MCA) trunk occlusion, recanalization with direct percutaneous transluminal angioplasty (PTA) may be preferable to time-consuming thrombolysis. However, distal embolization with small crushed fragments is a complication of direct PTA. We prospectively evaluated combined direct PTA and low-dose native tissue plasminogen activator (t-PA) therapy for acute embolic MCA trunk occlusion. METHODS: Fifteen patients underwent direct PTA. The embolus was successfully crushed in 12, who received subsequent native t-PA infusion. Direct PTA was performed with a balloon catheter, which was advanced into the occlusion site and inflated several times until recanalization was established. After PTA, 7.2 mg of native t-PA in 100 mL of isotonic sodium chloride solution was infused for 30 minutes. Neurologic status was evaluated at admission and immediately and 1 month after treatment. In all patients, follow-up CT was performed within 24 hours and 3-7 days after onset, and follow-up MR imaging, 1 month after onset. RESULTS: Direct PTA failed to crush the embolus in three of 15 patients; these three had no clinical improvement. In 11 of 12 patients, combined therapy was successful, with no technical complication. Although no symptomatic intracerebral hemorrhage occurred, one patient had a small hematoma. All patients with successful recanalization had marked clinical improvement. Although angiograms showed distal embolizations in 10, cortical infarctions were confirmed in only three at follow-up. CONCLUSION: Combined direct PTA and IV low-dose native t-PA therapy may be a safe alternative to thrombolytic therapy in some patients with embolic MCA trunk occlusion.