Cerebrospinal fluid membrane-bound tissue factor and myelin basic protein in the course of vasospasm after subarachnoid hemorrhage.

No marker that predicts accurately the time of occurrence of cerebral vasospasm due to subarachnoid hemorrhage (SAH) has been reported. In the present study, membrane-bound tissue factor (mTF) and myelin basic protein (MBP) concentrations in cerebrospinal fluid (CSF) were evaluated as a predictor of the time of occurrence of cerebral vasospasm. The mTF and MBP concentrations were measured in the CSF from 28 patients with SAH due to ruptured aneurysm. Serial assays were performed from day 4 to day 14 after SAH. CSF mTF and MBP concentrations from days 5 to 9 correlated with the volume of cerebral infarction due to vasospasm and outcome three months after SAH. From the serial assays, CSF mTF measurements predicted the time of occurrence and severity and irreversibility of symptoms due to vasospasm. In conclusion, CSF mTF is predictive of the occurrence and the recovery of cerebral vasospasm, while CSF MBP is only an indicator of severity of brain damage due to vasospasm.

Intracranial hemorrhage associated with congenital organic disease in neonates. Report of two cases and review of literature.

We report on two patients with intracranial hemorrhage associated with primary organic lesions who underwent surgery within 24 h after birth. The primary lesions in the two cases were an arteriovenous malformation (AVM) and a brain tumor. The patient with AVM has exhibited normal growth without neurological deficits during follow-up over 18 years, but the patient with brain tumor has exhibited various degrees of neurological deficits and developmental retardation. Timely diagnosis and aggressive surgery may be required for the management of neonatal AVMs with intracerebral hemorrhage.

Effect of a platelet-activating factor receptor antagonist, E5880, on cerebral vasospasm after aneurysmal subarachnoid hemorrhage--open clinical trial to investigate efficacy and safety.

The efficacy and safety of a new platelet-activating factor receptor antagonist, E5880, were investigated for preventing cerebral vasospasm after subarachnoid hemorrhage (SAH) in 71 patients with SAH who underwent surgery for ruptured aneurysms within 3 days. Intravenous E5880 administration (300 micrograms or 1200 micrograms twice daily) was begun within 4 days and continued for 14 days. The incidence of symptomatic vasospasm, low-density area on computed tomography, and angiographic vasospasm was lower than in placebo groups in previous studies. Clinical outcome was favorable compared with previous studies. No clinically important adverse events were observed. These results suggest that E5880 is safe and effective in the treatment of patients with cerebral vasospasm due to SAH.

Transfection of the plasma-type platelet-activating factor acetylhydrolase gene attenuates glutamate-induced apoptosis in cultured rat cortical neurons.

Using an adenoviral vector, we induced overexpression of the plasma type of platelet-activating factor acetylhydrolase in cultured rat neurons. Neurons overexpressing this enzyme showed a decrease in glutamate-induced injury, mainly, apparent as decreased apoptosis. Reduction of lipid peroxidation by this enzyme and protection of mitochondrial function were demonstrated, and these may be the basis of the resistance to glutamate-induced neuronal injury that we observed.

Tissue factor and cancer procoagulant expressed by glioma cells participate in their thrombin-mediated proliferation.

The relationship between coagulation cascade activation and glioma cell proliferation was examined. The human glioma cell lines T98G, TM-1 and normal human astrocyte cell strain (NHA) were examined. Using anti-tissue factor (TF) antibody, immunocytochemical detection of TF antigen was obtained in both cell lines and cell strain. TF antigen in cell lysates was also measured by enzyme linked immunosorbent assay (ELISA). In a one-stage clotting assay, T98G, TM-1 and NHA revealed procoagulant activity (PCA) in normal human plasma and factor VII deficient plasma. PCA in normal human plasma was significantly inhibited by both inhibitory anti-TF antibody and cysteine protease inhibitor HgCl2. This result indicates that T98G, TM-1 and NHA cells express not only TF but also cancer procoagulant (CP) at the same time. In a cell proliferation assay, thrombin induced proliferation in T98G and TM-1 cells in a dose-dependent fashion and in NHA cell in a bell-shaped fashion. This mitogenic stimulant was inhibited by the specific thrombin inhibitor hirudin. The combinations of coagulation factors II, V, and X with or without factor VII induced proliferation in T98G, TM-1, and NHA cells. The maximal mitogenic stimulatory effects were larger in glioma cells than in NHA. These mitogenic stimulatory effects were also inhibited by hirudin. Each coagulation factor on its own or in any other combination of coagulation factors had no proliferative effect. Thus, these mitogenic stimulatory effects were considered to be the effect of thrombin. In conclusion, T98G and TM-1 human glioma cells express two different types of procoagulants TF and CP. In the presence of coagulation factors, these glioma cells can generate thrombin and this thrombin generation is capable of inducing glioma cell proliferation in vitro.

Clinical features in patients requiring reoperation after failed endoscopic procedures for hydrocephalus.

The aim of this study was to clarify the clinical features of patients at risk of secondary obstruction following endoscopic fenestration. Clinical notes and endoscopic findings for 15 patients treated with endoscopic procedures were retrospectively reviewed. Endoscopic third ventriculostomy (ETV) was performed as initial treatment in 4 patients with non-communicating hydrocephalus, including a neonate with myelomeningocele, and as an alternative to shunt revision in 4 patients. Two patients with non-communicating hydrocephalus caused by tumor or arachnoid cyst were also managed with third ventriculostomy. Four patients with loculated hydrocephalus underwent endoscopic septostomy. A child with an isolated fourth ventricle was treated with endoscopic aqueductoplasty. Of the 15 patients undergoing endoscopic procedure, 4 required reoperation. Of the 10 patients treated with ETV, only the neonate with myelomeningocele required a ventriculoperitoneal shunt because of failure of the initial procedure. Of the 4 patients treated with endoscopic septostomy, 2 children with loculated hydrocephalus following intraventricular hemorrhage (IVH) underwent a second septostomy. In a patient with an isolated fourth ventricle following posthemorrhagic hydrocephalus, recurrence was noted 8 months after the initial procedure. He underwent a second procedure using a stent implanted into the aqueduct to maintain CSF circulation. Sufficient stomal size or implantation of a stent may be required in the under-2-year age group with hydrocephalus accompanied by IVH and associated with myelomeningocele, in whom the risk of secondary obstruction may be high.

Correlation of glutamate-induced apoptosis with caspase activities in cultured rat cerebral cortical neurons.

In cultured rat cortical neurons lactate dehydrogenase (LDH) activity in the medium, a cell-death marker, increased gradually after exposure to glutamate (100 microM to 1 mM) for 60 min and reached a plateau at 24 to 30 h. Neuronal death was mainly apoptotic as suggested by typical electron microscopic findings, fluorescent double staining with membrane-permeating and nonpermeating chromatin dyes, nick end labeling, and assessment of DNA fragmentation by agarose gel electrophoresis. After 1 mM glutamate exposure, a rise of interleukin-1beta converting enzyme (ICE)-like protease activity in neurons was parallel to cysteine protease p32 (CPP32)-like protease activity and declined before CPP32-like protease activity reached the peak (at 6 h). LDH activity in the medium of glutamate-exposed neurons was decreased by specific ICE and/or CPP32 inhibitors, acetyl-L-tyrosyl-L-valyl-L-alanyl-L-aspart-1-al (Ac-YVAD-CHO) and acetyl-L-aspartyl-L-glutamyl-L-valyl-L-aspart-1-al (Ac-DEVD-CHO), respectively, in a dose-dependent manner. Fluorescent double staining of nuclei also demonstrated that at 100 microM each inhibitor prevented neuronal apoptosis and that this effect was additive. Among agonists corresponding to various glutamate receptor subtypes, N-methyl-D-aspartate (NMDA) and kainate induced apoptosis in cortical neuronal cultures while alpha-amino-3-hydroxy-5-methylisoxazole-4-propinate (AMPA) did not. The metabotropic glutamate receptor agonist, 1-aminocyclopentane-1S, 3R-dicarboxylate (ACPD) prevented apoptosis. Interestingly, apoptosis at 24 h after agonist or antagonist exposure correlated closely with caspase activity 6 h after exposure.

An experimental model for side-to-side microvascular anastomosis.

Side-to-side microvascular anastomosis may be required in certain clinical situations, although the technique is difficult and the incidence of usage remains low. A new experimental model using rat femoral vessels for side-to-side microvascular anastomosis is presented, in which 100 percent patency was accomplished immediately and was maintained for 7 days after anastomosis. This model can provide a training tool for acquisition of advanced microsurgical technique for side-to-side anastomosis of small vessels.

Suboccipital meningocele presenting as a huge retropharyngeal mass in a patient with neurofibromatosis Type 1. Case report.

The authors report an extremely rare case of neurofibromatosis Type 1 (NF1) with a suboccipital meningocele presenting as a huge retropharyngeal mass. A 73-year-old woman with typical cutaneous manifestations of NF1 presented with nasal obstruction and dysphagia due to a retropharyngeal mass. Magnetic resonance imaging revealed a huge mass lesion extending from the right occipital bone defect to the retropharynx through the right paravertebral region. Computerized tomography scanning after intrathecal administration of contrast material confirmed that the mass was a meningocele protruding through a right occipital bone defect. The authors attempted to ligate this meningocele, most of which was excised via a suboccipital approach, but a second transcervical operation was required. Finally, the meningocele resolved and the patient was discharged without symptoms.

Role of preoperative midsagittal magnetic resonance imaging in endoscopic third ventriculostomy.

We measured the distance between the infundibular recess and the tip of the basilar artery (BA) on midsagittal magnetic resonance (MR) images in 217 subjects (mean age, 54.7 years) without intracranial disorders and 8 patients with hydrocephalus treated neuroendoscopically. The mean distance measured in the 217 subjects without intracranial disorders was 10.5 +/- 2.3 mm. There were no significant differences in this distance among age groups. In 28 of these 217 subjects (12.9%), the tip of the BA had shifted anterior to the mamillary bodies on MR images. Twenty-six of these 28 subjects (93%) were 60 years of age or older. The mean distance between the infundibular recess and the tip of the BA was 12 +/- 3.7 mm in 8 patients with hydrocephalus. There was no significant difference between the subjects without intracranial disorders and the patients with hydrocephalus in this distance. In an elderly patient with aqueductal stenosis for whom the distance between the infundibular recess and the tip of the BA was 6 mm, the tip of the BA had shifted anterior to the mamillary bodies and indented the floor of the third ventricle on preoperative midsagittal MR images, and perforation of the floor of the third ventricle therefore had to be carefully performed in order to avoid injury of the BA. Preoperative midsagittal MR images can clearly reveal neurovascular structures beneath the floor of the third ventricle and increase the safety of endoscopic third ventriculostomy.

Growth inhibition and radiosensitization of cultured glioma cells by nitric oxide generating agents.

The authors examined the effect of nitric oxide (NO) generating agents on the growth and radiosensitivity of cultured glioma cells. Three glioma, rat C6, and human T98G and U87 cell lines were treated with the NO generating agents, S-nitroso-N-acetyl-penicillamine (SNAP) or sodium nitroprusside (SNP). These agents released NO in the cell culture media and inhibited the growth of the glioma cells. Growth-inhibition was attenuated by hemoglobin, a known inhibitor of NO, suggesting it is mediated by NO. When C6 and T98G cells were irradiated in the presence of SNAP or SNP at 100 microM, radiosensitization was observed. SNAP at 100 microM exhibited a sensitizer enhancement ratio (SER) of 1.4 for C6 cells and 1.8 for T98G cells. SNP at 100 microM only radiosensitized T98G cells with a SER of 1.9. The effect of SNP on radiosensitization of C6 cells was unclear. We conclude that NO generating agents are potential growth inhibitors and radiosensitizers for malignant glioma cells. NO mediated radiosensitization of glioma cells by NO generating agents may offer a new therapeutic approach for malignant glioma.

Related changes in sympathetic activity, cerebral blood flow and intracranial pressure, and effect of an alpha-blocker in experimental subarachnoid haemorrhage.

We investigated the changes in sympathetic nerve activity (SNA) and cerebral blood flow (CBF) with or without increase in intracranial pressure (ICP) in the acute stage of experimental subarachnoid haemorrhage (SAH). ICP was increased or controlled by rapid or slow injection of blood and saline, and the effect of an alpha-blocker, phentolamine, was also investigated in each condition. Following marked increase in ICP induced by rapid injection of blood or saline, increase in intracranial and general SNA and decrease in CBF were observed. Both changes were significantly decreased in magnitude by prior administration of phentolamine. When increase in ICP was not induced, by slow injection of blood, both SNA and CBF decreased, and these changes were alleviated by phentolamine. However, when increase in ICP was not induced by saline, neither SNA nor CBF significantly changed. These findings suggest that marked increase in ICP is the primary cause of the pathological changes occurring immediately after SAH, and that the decrease in CBF in mild SAH without increase in ICP is caused by blood itself. Administration of an alpha-blocker may be effective in improving the abnormal sympathetic nervous system induced by marked increase in ICP.

Endoscopic ventriculocystocisternostomy of a quadrigeminal cistern arachnoid cyst. Case report.

The authors present the case of an elderly patient with a quadrigeminal arachnoid cyst who was successfully treated with endoscopic fenestration through the posterior wall of the third ventricle via the anterior horn of the lateral ventricle. This 71-year-old man suffered from progressive gait instability and disorientation. Radiological examination revealed hydrocephalus caused by a quadrigeminal arachnoid cyst. The patient underwent endoscopic fenestration of the quadrigeminal cistern arachnoid cyst and third ventriculostomy via one burr hole placed at the coronal suture. This method is less invasive and is effective for quadrigeminal cistern arachnoid cyst and accompanying hydrocephalus.

Deficient platelet-activating factor and related enzymes in hemimegalencephaly.

Platelet-activating factor (PAF) may influence neuronal migration, and gyral anomaly in hemimegalencephaly is believed to result from a neuronal disorder. A 7-month-old girl with hemimegalencephaly presented with intractable seizures, for which graded hemispherectomy was performed. In the resected specimen, we could not detect PAF, and related enzyme activities were low. These results suggest a role of PAF in neuronal migration.

Extrinsic pathway of blood coagulation and thrombin in the cerebrospinal fluid after subarachnoid hemorrhage.

OBJECTIVE: The involvement of thrombin in the pathophysiology of subarachnoid hemorrhage (SAH) was investigated by comparing thrombin expression and extrinsic pathway activation in the cerebrospinal fluid (CSF) and blood of patients with SAH with the neurological grades, outcome, and presence of delayed cerebral vasospasm. METHODS: Blood and CSF samples were obtained from 38 patients with SAH on Days 3 through 5, 7 through 9, and 12 through 14 after the onset of SAH. CSF samples were also obtained from control patients. Thrombin-antithrombin III complex, prothrombin fragment F1 +2, tissue factor, and tissue factor pathway inhibitor were analyzed using enzyme-linked immunosorbent assay. RESULTS: No markers in the blood or CSF were correlated with neurological grades and outcome. Thrombin-antithrombin III complex and prothrombin fragment F1 +2 levels were significantly higher in the CSF of patients with SAH than in the blood or the CSF of control patients and were significantly higher in patients with vasospasm than in patients without vasospasm on Days 7 through 9. Tissue factor levels were significantly higher in the CSF of patients with SAH than in the blood, but the levels were close to those in the CSF of control patients. Tissue factor pathway inhibitor levels in the CSF of patients with SAH and control patients were under the detection limit. CONCLUSION: Thrombin in the blood may not reflect the pathophysiology of SAH. Imbalance between tissue factor and tissue factor pathway inhibitor in the CSF may tend to thrombin generation under normal physiological conditions and also after SAH. Thrombin in the CSF may be involved in the pathophysiology of vasospasm.

Neurosurgical simulation and navigation with three-dimensional computer graphics.

We developed a pre-operative simulation and intra-operative navigation system with three-dimensional computer graphics (3D-CG). Because the 3D-CG created by the present system enables visualization of lesions via semitransparent imaging of the scalp surface and brain, the expected operative field could be visualized on the computer display pre-operatively. We used two different configurative navigators. One is assembled by an arciform arm and a laser pointer. The arciform arm consists of 3 joints mounted with rotary encoders forming an iso-center system. The distal end of the arm has a laser pointer, which has a CCD for measurement of the distance between the outlet of the laser beam, and the position illuminated by the laser pointer. Using this navigator, surgeons could accurately estimate the trajectory to the target lesion, and the boundaries of the lesion. Because the other navigator has six degrees of freedom and an interchangeable probe shaped like a bayonet on its tip, it can be used in deep structures through narrow openings. Our system proved efficient and yielded an unobstructed view of deep structures during microscopic neurosurgical procedures.

Endoscopic aqueductal plasty via the fourth ventricle through the cerebellar hemisphere under navigating system guidance--technical note.

A 1-year 8-month-old boy presented with isolated fourth ventricle after ventriculoperitoneal shunting for hydrocephalus associated with ventricular and subarachnoid hemorrhage. The therapeutic endoscope was inserted through the thin left cerebellar hemisphere. Endoscopic aqueductal plasty was performed via the enlarged fourth ventricle under guidance from a navigating system. Endoscopic aqueductal plasty via the fourth ventricle under navigating system guidance is a useful procedure enabling less invasive surgery for isolated fourth ventricle associated with slit-like ventricle after shunt placement.

Sequential changes and recoveries of the motor evoked potential in experimental hypertension.

The D- and I-waves of the motor evoked potential (MEP) were investigated as a monitor for acute intracranial hypertension in 20 dogs. Intracranial pressure (ICP) was raised bvy inflation of an extradural balloon. The MEP elicited by electrical transcortical stimulation were recorded during inflation and deflation of the balloon. The D-waves were linearly suppressed according to the ICP level, however, the I-waves and the ICP level did not correlate. Each wave disappeared in the animals kept about 50 mmHg or more, whose pupils were dilated. In the animals kept under 60 mmHg, the amplitude of the D-wave recovered proportionate to the period during which the amplitude was suppressed less than 50%. The changes of the MEP have some relation to histopathological changes. The results demonstrate that the D-wave of MEP is a useful monitor for intracranial hypertension.