Dose-effect relationship for radiotherapy after incomplete resection of atypical neurocytomas.

Neurocytomas with atypical histology or high proliferation activity are named atypical. All reported cases were reviewed. After incomplete resection, radiotherapy improved local-control (P<0.001) and survival (P=0.02). Doses (EQD2) >54 Gy were associated with better 5-year local control (84% versus 55%, P=0.05) and 5-year-survival (84% versus 65%, P=0.18) than doses < or =54 Gy.

Defining the optimal dose of radiation after incomplete resection of central neurocytomas.

PURPOSE: Central neurocytomas are uncommon benign central nervous system tumors. There is uncertainty regarding the most appropriate radiation dose after incomplete resection. This analysis was performed to determine the optimal dose. METHODS AND MATERIALS: All cases reported since 1982 were reviewed for age, gender, resection status, total dose, dose per fraction, local control, and overall survival. Additional data were obtained from the authors. The inclusion criteria were incomplete resection, postoperative irradiation, complete data, and 12 months' minimal follow-up. Two groups were formed according to the equivalent dose in 2-Gy fractions (EQD2): group A (40.0-53.6 Gy) and group B (54.0-62.2 Gy). Local control and survival were compared using Kaplan-Meier analysis and the log-rank test. RESULTS: Eighty-nine patients (group A 42, group B 47) met the inclusion criteria. At 5 years, the local control rate was 98% for group B vs. 69% for group A. At 10 years, it was 89% vs. 65% (p = 0.0066). The 5- and 10-year survival rate was 98% for group B vs. 88% for group A (p = 0.1). CONCLUSIONS: Our data suggest that a EQD2 > or =54 Gy significantly improves local control in patients with subtotally resected neurocytomas. Although the difference in survival was not significant, a trend toward better survival was noted after a EQD2 of > or =54 Gy.

Impaired intracellular signal transduction via cyclic AMP contributes to cerebral vasospasm in rats with subarachnoid hemorrhage.

No drug can completely prevent vasospasm after subarachnoid hemorrhage. Impaired intracellular signal transduction by cyclic nucleotides might be involved. We investigated effects of intravenous isoproterenol and NKH477 on cerebral blood flow in rats with or without intracisternal injection of autologous blood one week previously. In controls without hemorrhage, isoproterenol at 0.01, 0.1, 1, and 10 mg kg(-1) min(-1) increased cerebral blood flow by 1.2%+/-9.5%, 19.7%+/-12.8%, 46.8%+/-23.5%, and 63.8%+/-32.9% respectively; 10mg kg(-1) min(-1) of isoproterenol increased systemic blood pressure by 66.6%+/-58.1%, while other doses decreased blood pressure. In the subarachnoid hemorrhage group, isoproterenol increased cerebral blood flow by -20.0%+/-6.5%, -7.6%+/-8.7%, 8.2%+/-8.8%, and 35.9%+/-83.1% respectively; 10 mg kg(-1) min(-1) of isoproterenol increased systemic blood pressure by 68.8%+/-79.5%, while other doses decreased blood pressure. In controls, NKH477 at 3, 10, and 30 mg kg(-1) increased cerebral blood flow by 2.3%+/-3.6%, 14.4%+/-7.0%, and 50.7%+/-14.6%, respectively; in the subarachnoid hemorrhage group, NKH477 changed cerebral blood flow by -1.3%+/-2.4%, 4.6%+/-2.8%, and -12.6%+/-10.8% (not significant difference from controls). NKH477 at 30 mg kg(-1) min(-1) decreased systemic blood pressure in both groups, but the effect in the hemorrhage group was greater. Either isoproterenol or NKH477 at appropriate doses can increase cerebral blood flow in vasospasm following subarachnoid hemorrhage without decreasing blood pressure.

Type V phosphodiesterase expression in cerebral arteries with vasospasm after subarachnoid hemorrhage in a canine model.

Cyclic GMP (cGMP) mediates smooth muscle relaxation in the central nervous system. In subarachnoid hemorrhage (SAH), decreases in intrinsic nitric oxide (NO) cause cerebral vasospasms due to the regulation of cGMP formation by NO-mediated pathways. As phosphodiesterase type V (PDE V) selectively hydrolyzes cGMP, we hypothesized that PDE V may function in the initiation of vasospasm. This study sought to identify the altered PDE V expression and activity in the vasospastic artery in a canine SAH model. We also used this system to examine possible therapeutic strategies to prevent vasospasm. Using a canine model of SAH, we induced cerebral vasospasm in the basilar artery (BA). Following angiographic confirmation of vasospasm on day 7, PDE V expression was immunohistochemically identified in smooth muscle cells of the vasospastic BA but not in cells of a control artery. The isolation of PDE enzymes using a sepharose column confirmed increased PDE V activity in the vasospastic artery only through both inhibition studies, using the highly selective PDE V inhibitor, sildenafil citrate, and Western blotting. Preliminary in vivo experiment using an oral PDE V inhibitor at 0.83 mg kg(-1) demonstrated partial relaxation of the spastic BA. PDE V activity was increased from control levels within the BA seven days after SAH. PDE V expression was most prominent in smooth muscle cells following SAH. These results suggest that clinical administration of a PDE V inhibitor may be a useful therapeutic tool in the prevention of vasospasm following SAH.

Classification of medullary venous malformations in the temporal lobe: according to location and drainage pathway.

Medullary venous malformation (MVM) is rare in the temporal lobe, and the radiologic characteristics of temporal MVM have not yet been clarified. In 12 previously reported cases with satisfactory angiographic or magnetic resonance information as well as two newly reported here, we analyzed the specific location and hemodynamics of temporal lobe MVMs, particularly with respect to venous drainage. Temporal lobe MVM typically were seen in the superior lateral portion of the temporal lobe near either the atrium or the inferior horn of the lateral ventricle. Venous drainage was classified into two main patterns: deep (three cases) and superficial (11 cases). Superficial drainage could be divided into two subtypes: lateral and anterior. Dilated deep medullary veins converged toward either the lateral wall of the atrium or the inferior horn of the lateral ventricle. In the deep-drainage type, medullary veins drained into subependymal veins such as the inferior ventricular vein and the lateral atrial vein, and then emptied into the basal vein of Rosenthal. The anastomotic lateral mesencephalic vein was involved in one case as a variant of the basal vein. When the subependymal veins and/or the basal vein of Rosenthal or transverse sinus were hypoplasic, the medullary veins drained into either the Sylvian veins (anterior superficial type) or the vein of Labbé (lateral superficial type) through a characteristic large transcerebral vein. Drainage of temporal lobe MVM can be classified as deep, lateral superficial, or anterior superficial.

Effects of single low dose irradiation on subventricular zone cells in juvenile rat brain.

Although the juvenile human brain is relatively radioresistant, irradiation can result in brain growth retardation, progressive mental disturbance, and neurologic abnormalities. As neural stem cells or progenitor cells may be a target of radiation injury and may play an important role in the brain's functional recovery, we examined the effects of whole brain irradiation on these cells in juvenile rat. Six-week-old Wistar rats, where the brain is still growing, were irradiated with single doses of 1, 2, or 3 Gy X-ray. We measured their body and brain weights at 30 or 60 days after irradiation. The chronological changes of the subventricular zone (SVZ) were examined at 6 h, 2, 7, 14, 30, or 60 days after irradiation by immunohistochemistry, specifically looking at the neural stem cells or progenitor cells using anti-nestin antibodies specific for these cells. The rate of brain weight gain of irradiated rats significantly decreased in comparison to controls, although that of body weight gain was similar among them. Multiple apoptotic cells appeared in the SVZ at 6 h after irradiation with simultaneous reduction in nestin-positive cells (69% of the control). The cell levels recovered within a week, with the nestin-positive cells reaching maximal numbers (182%) on Day 14. Nestin-positive cells returned to baseline levels within 30 days (96%) and remained unchanged for the subsequent 60 days. The X-ray dosage did not affect these findings. Our findings revealed that single low dose X-ray administration reversibly affected the levels of neural stem and progenitor cells in the SVZ region. These results suggest that continuous multiple administrations of X-rays in clinical treatment may affect irreversible changes on neural stem or progenitor cells, causing brain growth retardation, or dysfunction.

Unilateral striatal damage following status epilepticus of ipsilateral frontal lobe origin.

A 35-year-old man with an old contusional haematoma in the right frontal lobe developed status epilepticus (SE) of right frontal origin. On magnetic resonance (MR) images 10 days after SE, the right striatum showed signal enhancement with Gd-DTPA administration. Subsequent MR imaging 1 month later indicated prolonged T1 and T2 relaxation times in the right striatum. Prolonged seizure activity in the frontal lobe may have induced excitatory neurotoxicity in the ipsilateral striatum, with occurrence of delayed neuronal damage as a result.

Intradural, extramedullary spinal Ewing's sarcoma in childhood.

We describe an 11 year old girl with progressive paraparesis from a spinal tumour. Magnetic resonance imaging showed an intradural, extramedullary mass extending from the C7 level to T1. Neither osteolytic nor osteosclerotic changes were seen in the vertebral bodies. Extraskeletal Ewing's sarcoma was diagnosed histopathologically.

Magnetic resonance imaging in cases with encephalopathy secondary to immunosuppressive agents.

The neurotoxic effects of immunosuppressive agents used after transplantation are well known. In most cases a decrease in drug dosage results in resolution of the neurotoxicity. At early stages in the post-transplantation clinical course, neurotoxicity and other complications such as infectious disease, encephalopathy and seizures are sometimes difficult to diagnose with neuroimaging. Recently, diffusion weighted imaging (DWI) has been used in patients with ischemic disease, mitochondrial myopathy, encephalopathy and demyelinating disease. We examined the magnetic resonance images (MRI), including DWI and fluid attenuated inversion recovery image (FLAIR), in three cases of post-transplantation neurological complication: two cases of neurotoxicity and a case of acute disseminated encephalomyelitis (ADEM). Hyper-intense lesions representing neurotoxicity were seen on FLAIR but not on DWI in two cases with neurotoxicity induced by an immunosuppressive agent. In ADEM, hyper-intense lesions were seen on both FLAIR and DWI. Neurotoxicity due to the immunosuppressive agent showed a favorable outcome, although the hyper-intense lesions temporally presented on FLAIR. In the state after transplantation, hyper-intense lesions on FLAIR and DWI represented in the brain from the initial stage, we might be care of other severe complications but for neurotoxicity.

Decreased thalamic metabolism without thalamic magnetic resonance imaging abnormalities following shearing injury to the substantia nigra.

A 36-year-old man had fallen about 8 metres. Radiographs showed a mandibular fracture, indicating rotatory force applied to the head. Fluid-attenuated inversion recovery (FLAIR) imaging showed hyperintensity in both medial temporal lobes, left medial midbrain, right midbrain including cerebral peduncle, left pulvinar, left external capsule, fornix, splenium of corpus callosum, and deep white matter of both frontal lobes. Quantitative [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) indicated markedly suppressed glucose metabolism in the left thalamus but not markedly in the striatum. At that time the neurologic examination demonstrated complete left hemiparesis, severe rigidity of the right upper extremity, and inability to move the right hand and fingers. Levodopa at 300-600 mg/day improved movement of the fingers, decreased the rigidity in the extremity, and lessened the metabolic abnormality. Diminished metabolism in the left thalamus may have contributed to symptoms. The case illustrates the usefulness of PET in disclosing symptom causing abnormalities not detected by magnetic resonance imaging.

Gait disturbance in patients with low pressure hydrocephalus.

Using criteria of the classification recently described by Nutt et al., we examined gait disorder in five patients with normal pressure hydrocephalus (NPH). Their cerebrospinal fluid (CSF) pressures were in the normal range, and trials of CSF removal produced temporary improvement of symptoms. Surgical procedures to relieve hydrocephalus improved gait disorders in all patients. No patient showed spasticity, sensory ataxia, cerebellar ataxia, extrapyramidal signs, or limb apraxia. All walked slowly with a wide base and a short stride. The arm swing normally associated with walking was preserved. In standing, patients were unsteady and fell easily when pushed. Four patients showed hesitation in initiating walking and in turning. These clinical features fit Nutt's criteria for frontal gait disorder and frontal disequilibrium. Unlike findings in Parkinson's disease, where similar gait disorders may occur, other extrapyramidal signs, Myerson's sign, and upper limb dysfunction were absent in NPH, and arm swing while walking was preserved. We suspect that ventricular dilatation disturbs neuronal connections between the supplementary motor area and the globus pallidus in NPH patients.

[A case of pineoblastoma primary presenting a pineal hemorrhage causing obstructive hydrocephalus].

A 9-year-old female suddenly developed headache and nausea. Computed tomography (CT) revealed pineal mass lesion and obstructive hydrocephalus. One week after the onset, hydrocephalus spontaneously resolved. Magnetic resonance imaging (MRI) revealed that the mass was a subacute hematoma and that hydrocephalus had improved. Sequential MRI 4 months later revealed an enhanced lesion in the pineal region. Total removal of the tumor by the occipital transtentorial approach established the histopathological diagnosis of pineoblastoma.

[Severe hyponatremia in a case of severe spinal injury: sequential examination of factors affecting water-electrolyte balance].

Although hyponatremia has been known to occur in patients with severe spinal cord injury with highly incidence, its mechanism has not been understood well. We examined a 64-year-old patient with severe hyponatremia after spinal cord injury by sequential measuring of the factors affecting water-electrolyte balance, such as antidiuretic hormone, renin, angiotensin II, atrial natriuretic peptide, and brain natriuretic peptide. The patient showed severe hypotension due to dysfunction of the sympathetic nerve. The hyponatremia gradually resolved with the improvement of sympathetic nerve function. According to those results, the sympathetic nerve dysfunction was thought to correlate with the hyponatremia, and it was suggested that the unknown sympathetic regulation of water-electrolyte balance existed.

Serum alpha1-antitrypsin level and phenotype associated with familial moyamoya disease.

BACKGROUND: Obstructive vascular lesions at the terminal portion of the internal carotid arteries are thought to be the primary and essential lesions in moyamoya disease. The etiology remains unknown. To detect possible mediators of the thickened intima of moyamoya disease, we measured serum alpha-1-antitrypsin (alpha1-AT) levels and characterized the phenotype of patients with familial moyamoya disease. PATIENTS AND METHODS: Fifty-six individuals were examined, including 29 patients with moyamoya disease from 14 families. Serum alpha1-AT levels were analyzed by electroimmunoassay and genomic phenotype by isoelectric focusing. RESULTS: All individuals had a normal alpha1-AT phenotype. The average serum alpha1-AT level in moyamoya disease patients was significantly higher than that of normal individuals, although both were within the normal range. CONCLUSIONS: These findings suggest that serum alpha1-AT level may be a marker, rather than an etiologic factor, indicating the progression of moyamoya disease.

A novel susceptibility locus for moyamoya disease on chromosome 8q23.

Moyamoya disease (MIM 252350) is characterized by stenosis or occlusion of the terminal portions of the bilateral internal carotid arteries and by abnormal vascular networks at the base of the brain. There is a high incidence of moyamoya disease in Asia, especially in Japan. Multifactorial inheritance is estimated with lambda(s)>40. Previous linkage studies have indicated that susceptibility loci for the disease are located on chromosomes 3p, 6q, and 17q. In the present study, we searched for loci linked to the disease in 12 Japanese families using 428 microsatellite markers and found significant evidence for linkage to 8q23 [maximum LOD score (MLS) of 3.6] and suggestive evidence for linkage to 12p12 (MLS=2.3). The present study revealed a novel locus for moyamoya disease.

Diverticular enlargement of the foramina of Luschka and congenital hydrocephalus.

CASE REPORT: We report on a 9-month-old boy with congenital hydrocephalus involving cystic lesions in the bilateral cerebellopontine angle cisterns. Sequential CT cisternography demonstrated congenital obstruction of the fourth ventricular outlet and diverticular enlargement of the foramina of Luschka. DISCUSSION: The possibility of neuroendoscopic third ventriculostomy as a treatment for these pathologies is discussed.

Suppression of Cdc2 dephosphorylation at the tyrosine 15 residue during nitrosourea-induced G2M phase arrest in glioblastoma cell lines.

We examined the mechanism of action of nitrosoureas as represented by 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) with respect to p53 and the G2M cell cycle checkpoint using two glioblastoma cell lines: U251MG and U373MG, with mutated p53. At log-phase cell growth, fresh medium containing ACNU (final concentration, 3, 10, or 30 microg/ml) was added. After 24 h of incubation, cells were harvested for flow cytometric or Western analysis. In both lines, cell numbers in the G0/G1 phase decreased with ACNU treatment. Cells accumulated in G2M and S phases, and the peak was shifted from G2M to the S phase in a concentration-dependent manner. In both cell lines, the amount of Cdc2 protein phosphorylated at the tyrosine 15 residue was increased 2- to 6-fold by treatment with ACNU compared with untreated control cells. Expression of cyclin B protein was suppressed in cells treated with 30 microg/ml ACNU. Protein abundance for total Cdc2, Cdc2 phosphorylated at the threonine 161 residue, Wee 1, Myt 1, Chk 1, and 14-3-3sigma was not affected by treatment with ACNU in either cell line. We suggest that a low concentration of ACNU should be used with adjuvant therapies that act upon cells in the G2M phase. A high concentration of ACNU should be used with adjuvant therapies that act upon cells in the S phase.

Case management of hydrocephalus associated with the progression of childhood brain stem gliomas.

OBJECT: Most patients diagnosed with brain stem glioma become bedridden because of deteriorating brain stem function. Many brain stem glioma patients develop hydrocephalus. Both of these outcomes greatly detract from the quality of life of these patients. We have analyzed the occurrence of hydrocephalus in diffuse brain stem gliomas in children, and we discuss the management of advanced cases. METHODS: Eighteen patients diagnosed with brain stem glioma while under 15 years of age, including 1 with dissemination, were studied retrospectively. The average overall survival was 11.8 +/- 6.5 months (mean +/- SD). Hydrocephalus occurred in 16 (88.9%) of the 18 cases. The patients diagnosed with hydrocephalus all exhibited a rapid decline in consciousness. The average time to onset of hydrocephalus after tumor diagnosis was 5.1 +/- 3.3 months. Twelve of the 16 patients with hydrocephalus were treated with cerebrospinal fluid (CSF) diversion, by means of a Torkildsen shunt, a ventriculoperitoneal shunt, or third ventriculostomy. The level of consciousness and patient performance status improved after CSF diversion except in 2 patients who had received Torkildsen shunts. The patients treated for hydrocephalus survived significantly longer than those patients who did not undergo any intervention for hydrocephalus. CSF diversion may be a therapeutic intervention that significantly improves the quality of life and survival of patients. CONCLUSION: Our results suggest that patients diagnosed with brain stem glioma should be closely monitored for signs of hydrocephalus and be examined by neuroimaging rapidly when indicated. Our results also suggest that once hydrocephalus is diagnosed CSF diversion should be performed promptly.

Diffusion-weighted imaging predicts postoperative persistence in meningioma patients with peritumoural abnormalities on magnetic resonance imaging.

OBJECTIVE: While diffusion-weighted magnetic resonance imaging (MRI) has been used to study malignant brain tumours, this modality has not been used to study MRI abnormalities surrounding meningiomas. METHODS: We examined intensity and apparent diffusion coefficient (ADC) on diffusion weighted imaging (DWI) for predicting postoperative persistence of MRI abnormalities surrounding meningiomas as well as characterizing the tumours. RESULTS: Of 36 meningiomas who underwent gross total resection, 27 (75%) showed hyperintensity on DWI at b=1100s/mm2. No atypical meningiomas were hypointense on DWI. Of the 26 supratentorial meningiomas, 18 (69.0%) had associated MRI abnormality. No significant correlation was seen between tumour intensity on DWI and existence of surrounding MRI abnormality. Meningothelial meningiomas showed a relatively low prevalence of MRI abnormalities surrounding tumour (30%). Of 11 patients who underwent sequential MRI, all MRI abnormalities surrounding tumour showing isointensity and high ADC on preoperative DWI disappeared after surgery (from 3 weeks to 10 months). All MRI abnormalities surrounding tumour showing hyperintensity and low ADC on preoperative DWI persisted on final follow-up MRI (from 6 months to 20 months). CONCLUSION: The postoperative course of MRI abnormality surrounding tumour might be predictable from the intensity and ADC on preoperative DWI. Since MRI abnormalities associated with meningiomas can cause preoperative neurologic deficits. We hypothesise that abnormalities with restricted diffusion will be more likely to be associated with a preoperative deficit, and more likely to remain after removal of the causative meningioma.

Enhanced apoptosis in pilocytic astrocytoma: a comparative study of apoptosis and proliferation in astrocytic tumors.

Both cell proliferation and cell death occur simultaneously in tumor tissue, and extent of tumor growth reflects the net balance of these events. We correlated cell proliferation, spontaneous cell death, and alterations in tumor suppressor proteins with one another and with survival of patients with primary astrocytic tumors. In 39 astrocytic tumor specimens (6 pilocytic astrocytomas, 14 fibrillary astrocytomas, 9 anaplastic astrocytomas, and 10 glioblastomas), we determined the MIB-1 labeling index, the apoptotic ratio according to nick end labeling with morphologic confirmation, the p53 labeling index, and the presence of p53 or PTEN mutations. MIB- I labeling indices of pilocytic astrocytomas, fibrillary astrocytomas, anaplastic astrocytomas, and glioblastomas were 0.30+/-0.32; 1.84+/-1.87; 19.3+/-6.42; and 28.0+/-14.5 (mean +/- SD), respectively. Corresponding apoptotic ratios were 17.9+/-5.16; 3.96+/-3.57; 1.18+/-0.93; and 2.11+/-1.60 (mean +/- SD). The apoptotic ratio in pilocytic astrocytomas was significantly higher than in other astrocytic tumors (fibrillary astrocytomas, p < 0.05; anaplastic astrocytomas and glioblastomas, p < 0.01). MIB-1 showed a significant negative correlation with apoptosis (p < 0.01). MIB- I and apoptosis showed significant negative and positive correlations with patient survival (p < 0.01). Mutations of p53 and PTEN show no correlation with survival and apoptotic ratio. The apoptotic ratio can clearly distinguish pilocytic astrocytomas from other tumors, and this biological feature may reflect less aggressive growth of pilocytic astrocytomas.