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Background: The natural history, including growth and rupture, of unruptured intracranial aneurysms (UIAs) remains unknown. Here, we present the results of serial magnetic resonance angiography (MRA) follow-up study in 111 patients with 136 UIAs. Method: A total of 111 patients with 136 UIAs were followed annually over the past 12 years, using 1.5-Tesla MRA. Follow-up was ended when UIAs were treated surgically, or the patients died of subarachnoid hemorrhage or other causes. Various factors influencing aneurysm rupture or growth were examined statistically. Results: Aneurysm rupture and growth occurred in six and 13 of the 111 patients, respectively. Annual rupture rate was 1.8 % per year and annual growth rate was 3.9 % per year. Aneurysm size was the sole factor influencing rupture(H.R. 1.214, 95 % CI, 1.078-1.368) and multiplicity was the sole factor influencing aneurysm growth (H.R. 5.174, 95 % CI 1.81-14.80). Conclusions: Serial MRA study showed that the incidence of UIA growth was twice as high as that of UIA rupture. As four patients showed aneurysm rupture or growth within 1 year, further investigations are necessary to determine the optimum interval of radiological investigation and to identify which UIAs grow or rupture within a short time. [ABSTRACT FROM AUTHOR]

Background. Image-guided and temperature-controlled radiofrequency thermal ablation techniques were applied to reduce tumor volume and relieve the symptoms caused by extracranial extension of recurrent meningioma.Method. We treated two patients with recurrent meningioma, an 81-year-old woman presenting with bulging of the temple and a 68-year-old woman presenting with visual disturbance, facial disfigurement, and sensory disturbance. Neuroimaging in both patients, revealed a large tumor extending extracranially and involving the infratemporal fossa. To avoid injury to important anatomical structures either compressed or entrapped by the tumor, the spatial relation between the planned ablation volume and these structures was confirmed by 3-D reconstruction of the ablation target. During the ablation procedure, local temperatures over the tissue being cauterized were continuously monitored to limit the ablation area to that within the planned volume adjusting RF power.Finding. Radiofrequency ablation produced tumor necrosis as planned without adverse effects and resulted in swift relief of symptoms and signs with shrinkage of the tumor.Conclusion. This technique may be an effective alternative for recurrent meningiomas extending extracranially and for which radical surgical procedures are not indicated. [ABSTRACT FROM AUTHOR]

Objective.Primary hypertensive intracerebral hemorrhage (PICH) is caused by a rupture of a small endartery, and diagnosis is made either by computed tomography (CT) or magnetic resonance imaging (MRI). Vascular abnormalities are not always evaluated in detail. In this study, we aimed to clarify the incidence of co-existing vascular abnormalities, especially unruptured cerebral aneurysms by reviewing selective intra-arterial digital subtraction angiography (DSA) images in PICH patients.Methods.The cases of 169 hypertensive PICH patients who underwent selective intra-arterial DSA were reviewed. In all cases, CT or MRI showed no abnormality other than PICH, such as subarachnoid hemorrhage, component of arterio-venous malformation or cerebral tumor. The main reason for performing DSA was to exclude other causes of intracerebral hemorrhage such as ruptured cerebral aneurysm or small arterio-venous malformation prior to surgical removal of the hematoma.Results.There were 33 patients with vascular abnormalities: unruptured cerebral aneurysm (n?=?24, 14.2%), major vessels occlusion or stenosis (n?=?8, 4.7%), and dural arterio-venous fistula (n?=?1). Unruptured cerebral aneurysms were found in 9.4% of men and 20.5% of women.Conclusion.Vascular abnormalities co-existing with PICH are not rare, suggesting the necessity for angiographic evaluation. Special attention should be given to female PICH patients who have a high incidence of having an unruptured cerebral aneurysm. [ABSTRACT FROM AUTHOR]

Summary ¶Background. Radiosurgery has been advocated as a primary treatment for hypothalamic hamartoma (HH), but it has a risk of damaging the surrounding structures and does not have an immediate effect for refractory epilepsy, endocrinological and mental disorders. Method. We report on a 13-year-old boy with a large and sessile HH who presented with intractable seizures, precocious puberty and aggressiveness. Stereotactic radiofrequency ablation (SRA) combined with an image fusion technique was performed to make a maximum ablative lesion within the HH via multiple trajectories. Findings. After surgery, we observed rapid cessation of the gelastic seizures and aggressiveness. The ophthalmological function did not get worse, and the hypothalamopituitary function improved. Interpretation. SRA in combination with an image fusion technique is a viable alternative treatment for HH, because it provides precise preoperative simulation and immediate improvement of symptoms can be obtained. [ABSTRACT FROM AUTHOR]

A silicone formulation of ganciclovir (GCV-pellet) was developed to enhance the cytotoxic effects of herpes simplex virus thymidine kinase suicide gene therapy. The effectiveness of this drug delivery system was assessed in a rat 9L gliosarcoma model The GCV-pellets (1 mm in length and in diameter) used in this experiment contained a total amount of 0.15 mg of GCV. In vitro experiments demonstrated that GCV was gradually released over a period of 7 days. Five days after stereotactic tumor inoculation into the right caudate nucleus, a herpes simplex virus type 1 (HSV-1) vector expressing herpes simplex virus thymidine kinase (HSV-tk) (T1, 2 × 10[sup 6] pfu) was administered at the same location. The survival rate of the group treated with the GCVpellet was compared with that of the T1 group injected intraperitoneally (IP) with GCV (30 mg/kg/day for 7 days). The GCV-pellet-treated group had a significantly prolonged survival (a median of more than 80 days) compared with the GCV IP group (a median of 65 days) and with control groups (P < 0.05). The control groups (untreated or receiving only the virus vector) had a survival of 35-38 days. The survival rate of the GCV-pellet group over 80 days was 75%, and aft the rats that survived more than 80 days and did not show tumors upon histological examination of the brain were deemed cured. No toxic effects or immunological reactions were observed histologically around the pellet in brain sections from the rats treated with the GCV-pellet. After GCV-pellet inoculation into the tumor, drug concentrations were kept at 1-10 µg/g tissue for 3-4 days. When the same dose of GCV (0.15 mg) in aqueous solution was injected into the tumor, GCV concentrations reached a peak of 0.5 mg/g tissue after 30 min and decreased below measurable level within 12 h. After IP injections of 3 mg GCV, GCV concentrations in the tumor reached a peak of 5.7 µg/g tissue after 30 min and also decreased below measurable level within... [ABSTRACT FROM AUTHOR]

Herpes simplex virus thymidine kinase (HSV-TK) and Escherichia coli cytosine deaminase (CD) are non-mammalian enzymes capable of converting innocuous prodrugs into cytotoxic metabolites. Both enzymes have been utilized independently, as well as together in 'suicide' gene therapy protocols to eliminate tumor cells in vitro and in vivo. We have used a set of replication defective HSV vectors expressing either or both enzymes to compare the efficacies of single and double suicide gene therapies in the 9L gliosarcoma model in vitro and in vivo. In cell culture experiments at high and low multiplicities of infection, combined expression of the two genes by vector TOCD/TK along with exposure to the matching prodrugs (ganciclovir and 5-fluorocytosine) showed increased cytotoxicity compared with exposure to either prodrug alone. However, the two gene combination was inferior to single gene treatments, suggesting that HSVtk and CD are mutually counteractive in the prodrug-dependent killing of glioma cells. In animal experiments, survival was not significantly prolonged by administration of both prodrugs to TOCD/TK-treated animals, while each single gene/prodrug pair resulted in increased survival. These results indicate that single suicide gene systems employing HSVtk or CD may be preferable over combinations of the two. [ABSTRACT FROM AUTHOR]

A putative tumor suppressor, the PTEN gene at chromosome 10q23, was identified and found to be mutated in many different human tumors. PTEN was recently found to be also involved in focal cell adhesion and cell migration. To identify the role of PTEN gene in malignant gliomas, we used PCR-SSCP and direct sequencing methods to examine 44 malignant gliomas comprising 29 cases without and 15 cases with meningeal gliomatosis. In malignant gliomas without meningeal gliomatosis, 2/29 (7%) of the cases showed alteration of the PTEN gene. In contrast, 5/15 (33%) of malignant gliomas with meningeal gliomatosis cases showed this alteration. These findings indicate that PTEN gene mutation contributes not only to the neoplastic evolution in gliomas but also to the meningeal dissemination of glioma cells. [ABSTRACT FROM AUTHOR]

A 22-year-old woman presented with acute onset of headache and vomiting. Computed tomography (CT) demonstrated hydrocephalus and a huge midline mass with heterogeneous density involving both lateral ventricles. A small amount of hematoma was detected at the bottom of the left trigone. On magnetic resonance imaging (MRI), the mass appeared grossly isointense on Tl-weighted images and slightly hyperintense on T2-weighted images with a clearly demarcated low intensity area at its center. These CT and MRI findings were suggestive of an acute hemorrhagic event within the tumor. The presence of hemorrhage was confirmed at surgery. Sudden hemorrhages within the tumor were considered to cause the acute onset of symptoms. Although central neurocytoma is not commonly known as a tumor-producing intracranial hemorrhage or to cause abrupt clinical deterioration, we found five similar cases in the literature. After reviewing these cases, we concluded that the information on the possible hemorrhagic complication of central neurocytoma is important for correct diagnosis and thus for proper management of this tumor. [ABSTRACT FROM AUTHOR]

Herpes simplex virus (HSV)-mediated delivery of the HSV thymidine kinase (tk) gene to tumor cells in combination with ganciclovir (GCV) administration may provide an effective suicide gene therapy for destruction of malignant glioblastomas. However, because HSV is a highly cytotoxic agent, gene expression from the virus is short-rived which may limit the effectiveness of HSVtk/GCV therapy. Using different replication-defective HSVtk gene vectors, we compared HSV vector backgrounds for their cytotoxic activity on infection of 9L gliosarcoma cells in culture and brain tumors in rats and evaluated the impact of vector toxicity on the effectiveness of tk/GCV-mediated suicide gene therapy. As reported previously for other cell lines, a vector deleted for both copies of the immediate-early (IE) gene ICP4 (SOZ.1) was highly toxic for 9L cells in culture while a vector deleted in addition for the ICP22 and ICP27 IE genes (T.1) reduced or arrested 9L cell proliferation with more limited cell killing. Nevertheless, both vectors supported widespread killing of uninfected cells in the presence of GCV following low multiplicity infections, indicating that vector cytotoxicity did not preempt the production of vector-encoded TK enzyme necessary for the killing of uninfected cells by the HSV-tk/GCV bystander effect. Although an SOZ.1-related vector (SHZ.2) caused tumor cell necrosis in vivo, injection of SHZ.2 at multiple coordinates thoughout the tumor followed by GCV administration failed to prolong markedly the survival of tumorbearing rats. In contrast, a single injection of T.1 produced a life-extending response to GCV. These results indicate that vector cytotoxicity can limit the efficacy of HSV-tk/GCV treatment in vivo, which may be due to premature termination of tk gene expression with attendant abortion of the bystander effect. [ABSTRACT FROM AUTHOR]

Summary Background. The major cause of surgical failure in the treatment of Cushing's disease lies in unsuccessful identification of adenomas. In the present study, we investigated the pathogenesis of negative exploration in transsphenoidal surgery for Cushing's disease by analyzing neuro-imaging studies, endocrinological examination and selective venous sampling. Methods. Thirty patients with ACTH-dependent Cushing's syndrome that met the endocrinological criteria for Cushing's disease were treated by transsphenoidal microsurgery. Depending on positive or negative identification of adenomas during the surgery, selective adenomectomy, partial hypophysectomy or subtotal hypophysectomy was performed. Findings. All nine patients who underwent selective adenomectomy showed endocrinological remission and did not need any hormone replacement therapy. Of the 12 patients who underwent partial hypophysectomy, 11 showed normalization of hypercortisolism but seven needed permanent replacement of hydrocortisone. Four patients underwent subtotal hypophysectomy because no adenoma could be identified in spite of detailed exploration, and three of them showed remission but with permanent requirements of hydrocortisone and other pituitary hormones. Five patients, whose hypercortisolism persisted after initial surgery, underwent total hypophysectomy as secondary transsphenoidal surgery, and only one of them showed endocrinological remission. Of the six patients with surgical failure, four were thought to be rare cases in whom the ACTH-secreting tumours may have occurred ectopically in the cavernous sinus without direct contact with the pituitary gland. Endocrinologically, these four patients showed a low or no response to corticotropin releasing hormone (CRH) stimulation, and for three of them, radiation therapy to the sellar region including the cavernous sinus was effective for persistent hypercortisolemia. Interpretation. Recognition of an ectopic intracavernous sinus ACTH-secreting tumour as a pathological entity for Cushing's disease may not only enhance the diagnostic accuracy but also be important for determining the optimal surgical mode for persistent Cushing's disease. [ABSTRACT FROM AUTHOR]

We attempted in vivo gene transfection into the central nervous system (CNS) of non-human primates using the hemagglutinating virus of Japan (HVJ)-AVE liposome, a newly constructed anionic type liposome with a lipid composition similar to that of HIV envelopes and coated by the fusogenic envelope proteins of inactivated HVJ. HVJ-AVE liposomes containing the lacZ gene were applied intrathecally through the cisterna magna of Japanese macaques. Widespread transgene expression was observed mainly in the neurons. The lacZ gene was highly expressed in the medial temporal lobe, brainstem, Purkinje cells of cerebellar vermis and upper cervical cord (29.0 to 59.4% of neurons). Intrastriatal injection of an HVJ-AVE liposome-lacZ complex made a focal transfection around the injection sites up to 15 mm. We conclude that the infusion of HVJ-AVE liposomes into the cerebrospinal fluid (CSF) space is applicable for widespread gene delivery into the CNS of large animals. [ABSTRACT FROM AUTHOR]

To examine the cellular dynamics of macrophages and microglial cells in response to cerebral injury, we studied the brain adjacent to cortical stab wounds in young adult rats. Brains were obtained 30 min after intravenous infusion of bromodeoxyuridine (BrdU) on one day (day 1) to 28 days (day 28) after wounding. Brain sections were double-labelled immunohistochemically for monocyte/macrophage antigen ED1 and for BrdU. ED1-positive (ED1+) cells were classified morphologically into two groups, ED1+L and ED1+S cells, representing macrophages and microglial cells, respectively. ED1+L cells appeared on day 1 after wounding and rapidly increased in number to reach a maximum on day 3, but quickly disappeared by day 5. ED1+S cells also appeared on day 1, but the increase in number was slower, reaching a maximum only on day 7. ED1+L cells were all negative for BrdU, but some ED1+S cells were stained for BrdU, evidence of proliferation. The present investigation demonstrated different cellular dynamics for macrophages and microglial cells responding to a stab wound, and also indicated differing sources for the two cell type. It may be possible to prevent the accumulation of these cells which are harmful to the brain in reducing the damage suffered. [ABSTRACT FROM AUTHOR]

To identify the cellular targets of TNFα in human gliomas, a total of 30 surgical specimens (12 glioblastomas, 4 anaplastic astrocytomas, 3 astrocytomas, 7 brains adjacent to tumour (BAT), 4 histologically normal-appearing brains) were examined by in vitro binding technique using biotinylated TNFa. The TNF-binding sites (TNF-BS) were recognized in the tumour cells in 8 of the 12 glioblastomas. 3 of the 4 anaplastic astrocytomas and in all the 3 astrocytomas. The TNF-BS were also recognized in the vascular endothelial cells in all these cases. The presence of TNF-BS in blood vessels ranged from 7.7 to 74.4% of the background vessels. This wide range of variation in the presence of TNF-BS within the tumour cells and tumour blood vessels may be relevant to the variable response of individual tumours to TNFα therapy. Since the tissue of normal brain, which lacks TNF-BS, might hardly be affected by this cytokine, administration of TNFa may be considered as an adjuvant therapy in selected groups of patients. [ABSTRACT FROM AUTHOR]

We studied the effect of high-dose single-fraction irradiation on the permeability of the blood-brain barrier (BBB) in rat brains. Immunohistochemistry with an antibody to serum albumin was used as a sensitive method for detecting the extravasation of endogenous serum components. Extravasation of albumin was detected as early as 1 day after irradiation with 20 or 40 Gy. Immunoreactivity reached its maximum after 3 days, gradually decreased during the following few weeks and had disappeared by day 30. Extravasation was much greater after irradiation with 80 Gy and continued to increase during the whole period of the experiment (6 days). Disruption of BBB this early after irradiation has not been previously documented. The time course of observed serum albumin extravasation, however, agrees well with the previous ultrastructural evidence for increased BBB permeability after irradiation with 27 Gy in monkey brains. This transient impairment of BBB may contribute to the reversible neurological symptoms after radiosurgery. It may also allow drugs that normally not pass the BBB to do so and thus disperse in the brain when administered at this time. [ABSTRACT FROM AUTHOR]

A 57-year-old male with primary intracranial malignant melanoma who survived 9 years and 6 months is reported. He underwent surgical removal of the tumour three times during the decade 1978 to 1988, and received chemo-immuno-radiotherapy during that time. Acute tumour growth, suggesting tumour dissemination, was seen in the CT scans after the third removal of recurrent tumour, but then it disappeared after combined chemoradiotherapy with DTIC. He gradually became inactive, probably because of brain atrophy caused by high-dose radiotherapy and chemotherapy, and died of renal failure without any sign of recurrence on CT scans. [ABSTRACT FROM AUTHOR]

Examines the polytetrafluoroethylene (PTFE) fascia patch inlay method for preventing cerebrospinal fluid leakage. Procedure of the PTFE fascia patch inlay method; Examples of intra-dural pathologic abnormalities wherein anterior approach proves to be effective; List of other anterior approach to intra-dural pathological abnormalities.

STUDY DESIGN: A new method for prevention of cerebrospinal fluid leakage was studied. OBJECTIVE: To prevent cerebrospinal fluid leakage, we developed a polytetrafluoroethylene fascia patch inlay method. BACKGROUND: One of the major risks of the anterior approach for intra-dural spinal cord lesions is the cerebrospinal fluid leakage. METHODS: A small hemangioblastoma located on the ventral side of the cervical cord was resected with an anterior approach. The dural closure was performed using this polytetrafluoroethylene fascia patch inlay method. RESULTS: The patient had a satisfactory clinical course with no cerebrospinal fluid leakage. CONCLUSION: This polytetrafluoroethylene fascia patch inlay method is very effective. This method may provide both prevention of CSF leakage and future spinal cord adhesion to the dura. [ABSTRACT FROM AUTHOR]

A 74-year-old man showed a spastic gait and myelopathy in both the hands. Computed tomography revealed an OPLL on C3 and C4, bony spurs on the dorsal side of C4-C6, and an OYL on C3 and C4. We scheduled a two-stage decompression for both the OPLL and OYL. First, we performed laminectomy on the C3-C6 segments and resected the OYL. We did not observe any dural tear or CSF leakage in the dura. The patient's neurological symptoms improved. After the laminectomy, his myelopathy recurred. Postoperative MRI showed a spinal cord herniation. We had the C3/4 anterior cervical disectomy and fusion as we planned. In addition, we performed a surgery to repair the damaged dura mater at the site of spinal cord herniation at the same second surgery. The integrity of the arachnoid membrane was preserved. The patient's myelopathy gradually improved. There have been no reports on postoperative neurological deterioration caused by spinal cord herniation associated with a dural defect at the laminectomy site, without dural tear in the surgery after the resection of a posteriorly located cervical OYL. The possibility of a dural defect in OYL cases should be considered when planning a laminectomy for the resection of the OYL. [ABSTRACT FROM AUTHOR]