Gamma knife surgery for brain metastases: indications for and limitations of a local treatment protocol.

OBJECTIVE: The purpose of this retrospective study was to evaluate results of a local treatment protocol using gamma knife surgery (GKS) for brain metastases without upfront whole brain radiation therapy (WBRT). METHODS: Results for 521 consecutive patients satisfying the following 3 criteria were analysed: 1) a maximum of 3 tumours with a diameter of 25 mm or more; 2) no prior WBRT; 3) no surgically in accessible large (>30 mm) tumours. Large tumours were surgically removed and all smaller lesions were treated by GKS without up front WBRT. New lesions, detected with follow-up MRI, were appropriately treated with repeat GKS. Overall survival (OS), neurological survival (NS), qualitative survival (QS) and new lesion-free survival (NLFS) curves were calculated and the prognostic values of covariates were obtained. OS and NS were compared according to tumour number. RESULTS: In total, 1023 separate sessions were required to treat 4562 lesions. The primary organs were lung in 369 patients, gastro-intestinal tract in 70, breast in 33, urinary tract in 24, and others/unknown in 25. The median OS period was 9.0 months. On multivariate analysis, the significant prognostic factors for OS were found to be extracranial disease (risk factor: active), Karnofsky performance status (KPS) score (<70) and gender (male). NS and QS at one year were 85.6% and 73.0%, respectively. The only significantly poor prognostic factor for NS was carcinomatous meningitis. NLFS at 6 months was 68.9%. For both OS and NS, the differences between a few (10) tumours had a significantly poorer prognosis than those with

Removal of large acoustic neurinomas (vestibular schwannomas) by the retrosigmoid approach with no mortality and minimal morbidity.

OBJECTIVE: To evaluate the safety and efficacy of removing large acoustic neurinomas (> or =3 cm) by the retrosigmoid approach. METHODS: Large acoustic neurinomas (mean (SD), 4.1 (0.6) cm) were removed from 50 consecutive patients by the retrosigmoid suboccipital approach while monitoring the facial nerve using a facial stimulator-monitor. Excision began with the large extrameatal portion of the tumour, followed by removal of the intrameatal tumour, and then removal of the residual tumour in the extrameatal region just outside the porus acusticus. The last pieces of tumour were removed by sharp dissection from the facial nerve bidirectionally, and resected cautiously in a piecemeal fashion. RESULTS: There were no postoperative deaths. The tumour was removed completely in 43 of 50 patients (86%). The facial nerve was anatomically preserved in 92% of the patients and 84% had excellent facial nerve function (House-Brackmann grade 1/2). One patient recovered useful hearing after tumour removal. Cerebrospinal fluid leak occurred in 4%, but there were no cases of meningitis. All but two patients (96%) had a good functional outcome. CONCLUSIONS: The method resulted in a high rate of functional facial nerve preservation, a low incidence of complications, and good functional outcomes, with no mortality and minimal morbidity. Very favourable results can be obtained using the retrosigmoid approach for the removal of large acoustic neurinomas.

Treatment Outcome of Carotid Stenting and CEA in the Same Period.

SUMMARY: Angioplasty with stent deployment is a promising option for the treatment of carotid stenosis. However, the definite treatment indication is still unknown through lack of scientific evidences in the randomized controlled trial, which is now on going. We compared the short-term outcome, such as periprocedural complication rate, cerebral blood flow, subsequent ischemic events and restenosis, between carotid stenting (CS) and carotid endarterectomy (CEA) in the same period to investigate the justice of our present indication for CS. Fifty-five patients with carotid stenosis greater than 70% were treated by CS or CEA in a constant indication. Twenty-five times of CEA were indicated in patients who satisfied the inclusion criteria of NASCET without the exclusion criteria, 30 times of CS in patients with the exclusion criteria. No major procedure-related complication was found in either group. One patient (3.3%) in CS group suffered a minor ischemic stroke during the procedure, just after postdilatation. One patient underwent myocardial infarction in CEA group, and one patient congestive heart failure in CS group within one week after the procedure. During a mean follow-up period of 19 months, no further stroke occurred in either group. There was no lesion-related mortality, but one patient in each group was dead of heart disease. As for restenosis, one patient in each group showed recurrent stenosis on angiogram 12 and 24 months after the treatment. Restenosis rate calculated by the personyear method in CEA and CS group was almost same, 2.3% per year. Stenting seemed to be so safe and effective for cases refractory to CEA that the present indication for CS is thought to be reasonable, though it is necessary to draw a decisive conclusion in randomized trials.

Promising survival for patients with glioblastoma multiforme treated with individualised chemotherapy based on in vitro drug sensitivity testing.

We retrospectively investigated the efficacy and feasibility of individualised chemotherapy based on in vitro drug sensitivity testing (DST) for patients with glioblastoma multiforme. A total of 40 consecutive patients with glioblastoma multiforme (GM) were enrolled into this study between January 1995 and December 2000. The flow cytometric (FCM) detection of apoptosis was used to determine the in vitro sensitivity of tumour cells obtained at surgery to 30 different kinds of anticancer agents. From the results of FCM assay, an in vitro best regimen was prospectively selected. All the patients concurrently received the individualised chemotherapy with the in vitro best regimen and 60 Gy of conventional radiation therapy. Of the 31 assessable patients, eight patients (26%) achieved partial response, and 20 patients (65%) had stable disease. The median survival time was 20.5 months. The individualised chemotherapy based on in vitro DST was associated with favourable survival time for the patients with GM compared with the reported results of conventional therapy regimens. The present result suggests that the currently available anticancer agents could be effective against GM when used in individualised chemotherapy.

MRI of ectopic posterior pituitary bright spot with large adenomas: appearances and relationship to transient postoperative diabetes insipidus.

MRI of large pituitary adenomas has revealed that a posterior pituitary bright spot (PPBS), comprising ADH-containing neurosecretory granules, is commonly ectopic before surgery and attached to the tip of the pituitary stalk late after surgery. Although the PPBS indicates functional integrity of the posterior lobe, transient diabetes insipidus (DI), caused by deficiency of ADH, is frequent early after surgery. We attempted to clarify how the shape, signal intensity and site of the PPBS before surgery are related to transient DI in the early postoperative period. We carried out MRI on 15 patients with a large adenoma and an ectopic PPBS before surgery and then within 1 week (early), 1-2 months (intermediate) and 6 or more months (late) after the operation. There were nine who had transient DI, which subsided by the intermediate study; none had permanent DI. Regardless of transient DI, the PPBS was visible, and its signal intensity was similar, on all postoperative studies. Although 11 did not change in shape, four showed a remarkable change from a flat shape before surgery to a rounded one postoperatively. On the intermediate MRI, the PPBS had descended to the level of the diaphragma as mass effect disappeared.

Potential role of the anterior spinal artery in preventing propagation of thrombus in a therapeutically occluded vertebral artery: angiographic studies before and after endovascular treatment.

Therapeutic occlusion of the vertebral artery (VA) is one of the treatments for unclippable aneurysms and other lesions, although controversy still surrounds the appropriate site for occlusion to attain selective thrombosis of the lesion while avoiding ischaemic complications. The lower two-thirds of the lateral medulla are supplied by perforating branches of both the VA and the posterior inferior cerebellar artery (PICA). However, in patients without a PICA or in whom the origin of the PICA is low (at or below the foramen magnum), the VA is usually the only source of perforating vessels. We retrospectively studied the results of VA occlusion on such anatomically high-risk patients, and propose a safer procedure. Five high-risk patients underwent therapeutic occlusion of the VA for dissecting aneurysms or arteriovenous fistula. A lateral medullary syndrome developed due to propagation of thrombus after the procedure in two patients in whom angiography did not demonstrate the anterior spinal artery (ASA) within the stump of the VA. Ischaemic signs did not develop in the other three patients, in whom the ASA was visible, and retrograde flow was observed proximal to the origin of the ASA. This suggests that the ASA may play a role in preventing propagation of thrombus in the VA distal to the site of occlusion and supply blood to its perforating arteries in high-risk patients. Angiographic assessment of the ASA may be useful for predicting the likelihood of the lateral medullary syndrome developing with therapeutic occlusion of the VA in patients without a PICA or with one whose origin is low.

Heavily T2 weighted MR images of anterior optic pathways in patients with sellar and parasellar tumours - prediction of surgical anatomy.

OBJECTIVE: Location of anterior optic pathways in sellar and parasellar tumours was preoperatively evaluated, by use of heavily T2 weighted MR images. METHODS: Heavily T2 and conventional T1 weighted images were studied in 20 patients with sellar and parasellar tumours who underwent craniotomy. Pathology revealed pituitary adenoma in 5 patients, craniopharyngioma in 8 and parasellar meningioma in 7. Maximum sizes ranged from 15 mm to 58 mm. Sequence parameters of TR/TE for heavily T2 weighted and T1 weighted images were 5800/220 msec and 600/20 msec, respectively, and slice thickness was 3 mm for both. RESULTS: The anterior optic pathway was detected in 95% on heavily T2 weighted images and 50% on T1 weighted images. All preoperative heavily T2 weighted images were compatible with operative findings. The optic chiasms were most commonly supero-posterior in pituitary adenomas, anterior (prefixed) in craniopharyngiomas and posterior in meningiomas. The optic nerves were commonly located superior or lateral to the tumours. However, parasellar meningiomas, off the midline, revealed the optic nerves in various locations, depending on the tumour origin. In such tumours, heavily T2 weighted images provided surgical information on the width of the working space through prechiasmal and/or optico-carotid spaces in the pterional approach. Spatial relation of the tumours to the lamina terminalis, anterior commissure and anterior communicating artery complex was clearly shown in craniopharyngioma patients, who underwent the anterior interhemispheric approach. CONCLUSION: Heavily T2 weighted MR images are useful in determining the location of optic pathways and surgical approach and in individual prediction of the anatomy for even large sellar and parasellar tumours.

Induction of immunity in peripheral tissues combined with intracerebral transplantation of interleukin-2-producing cells eliminates established brain tumors.

Cytokine gene therapy for the induction of potent immune responses against central nervous system tumors has proven to have significant potential. However, this strategy needs improvement in the process of antigen presentation and/or insufficient recruitment of immunocompetent cells to achieve successful eradication of established brain tumors. We investigated the therapeutic potential of induced systemic immunity in peripheral tissues combined with interleukin-2 (IL-2) production in the vicinity of brain tumors to treat established brain tumors. Sequential magnetic resonance image monitoring showed that the combinatory therapy consisting of intracerebral (i.c.) transplantation of IL-2-producing rat gliosarcoma 9L (9L/IL-2) cells and s.c. vaccination using irradiated 9L or 9L/IL-2 cells could cure 9L-bearing rats, whereas either the i.c. injection of 9L/IL-2 cells or the s.c. vaccination produced little or marginal antitumor effects, respectively. Xenogeneic murine neuroblastoma cells secreting IL-2 could substitute for 9L/IL-2 cells, producing significant antitumor effects in the vaccinated rats. Tumor-specific cytotoxic activity was induced in the vaccinated rats but not fully in the rats treated only with i.c. injection of 9L/IL-2 cells. Immunohistochemical analysis revealed that a number of CD4(+) and CD8(+) T cells infiltrated into the brain tumors which were treated with the combinatory therapy. The level of cell infiltration was similar to that found in s.c. 9L/IL-2 tumors which were subsequently rejected. In contrast, the brain tumors treated with either i.c. transplantation of 9L/IL-2 cells or the s.c. vaccination showed only moderate infiltration of T cells. The combinatory strategy, i.c. grafting of IL-2-producing cells, and s.c. immunization of irradiated whole tumor cell vaccine, is, thus, effective for recruiting activated T cells into the brain tumor site and could be a potential therapy for brain tumors.

Long-term Karnofsky performance status and neurological outcome in patients with neurohypophyseal germinomas.

Long-term posttreatment Karnofsky Performance Status (KPS) and neurological status of 16 patients with neurohypophyseal (NH) germinomas were retrospectively analysed, in order to deduce the best treatment modality to achieve a good outcome. The average age at treatment was 15.5 years (rouge 6-26) and they were followed up for 107.3 months (26-209). The KPS averaged 81.5 (0-100). Three patients were below 60 in the KPS. The first one had hemiparesis due to a delayed cerebrovascular accident (CVA), and the second became indifferent and inactive with recent memory loss. The third died from marginal recurrence of tumour and subsequent systemic metastasis. The low scores were all more or less attributable to complications related to irradiation: delayed CVA, diffuse cortical atrophy and inappropriate selection of irradiation field, respectively. The second case had the tumour origin at the hypothalamus, which indicates intraparenchymal tumour location as another factor to worsen the quality of life (QOL). Visual field and acuity, and EOM impairment were observed in eight and five patients, respectively. It improved in all patients but one. The visual and EOM dysfunction recovered satisfactorily and was not a disabling factor. The intraparenchymal lesion resulting in hemiparesis and higher cortical dysfunction due to either irradiation-related complications or tumour invasion is a major determining factor of lower KPS. Irradiation related complications are considered to be avoidable by reducing radiation dosage with appropriate chemotherapy and/or proper selection of irradiation field. Patients with smaller tumour size of less than 20 mm had higher KPS. Accordingly, repeated studies of tumour markers and neuroimages are required in patients with idiopathic diabetes insipidis, in order to detect the tumour, if present, at the small-sized and early stage.

Gene expression analysis in human monocytes, monocyte-derived dendritic cells, and alpha-galactosylceramide-pulsed monocyte-derived dendritic cells.

In vitro proliferation and functional activation of V alpha 24NKT cells following stimulation with alpha-galactosylceramide (alpha-GalCer)-pulsed dendritic cells (DCs) have been observed. Because little is known about the molecular events on DCs following interaction with alpha-GalCer, we performed gene expression profiling of 2400 genes in monocytes and monocyte-derived immature DCs pulsed with alpha-GalCer (alpha-GalCer-imDCs). Overall, the expression levels of 48 genes were up-regulated and 28 were down-regulated in alpha-GalCer-imDCs. Semiquantitative RT-PCR analysis on monocytes, imDCs, alpha-GalCer-imDCs, and mature DCs confirmed the up- and down-regulation of the mRNA expression levels of 28 selected genes. Notably, we identified the specific up-regulation of mRNA expression levels of ribonuclease A and collapsin response mediator protein upon the stimulation of imDC with alpha-GalCer, suggesting a novel immunomodulating effect of alpha-GalCer on imDCs. In this study, we used imDCs prepared by culturing of monocytes with GM-CSF and IL-4 for 5 days and mDCs prepared by further culturing of imDCs with TNF alpha for two extra days.

Computed tomography and magnetic resonance imaging of mild head injury--is it appropriate to classify patients with Glasgow Coma Scale score of 13 to 15 as "mild injury"?

OBJECTIVE: The purpose of this study is to examine the relation between Glasgow Coma Scale (GCS) score and findings on computed tomography (CT) and magnetic resonance (MR) imaging of patients with mild head injury presenting GCS scores between 13 and 15. METHODS: Data were collected from all consecutive patients with mild head injury who were referred to our hospital between July 1 and October 31, 1999. All patients were recommended to undergo CT and MR imaging examinations. Patients younger than 14 years of age were excluded. RESULTS: Ninety patients were recruited into this study. CT scans were obtained in 88 patients and MR imaging were obtained in 65 patients. Of these 90 patients, 2 patients scored 13 points, 5 scored 14 points and 83 (92.2%) 15 points. Patients with GCS score of 13 points demonstrated parenchymal lesions on both CT and MR imaging. Those with 14 points revealed absence of parenchymal abnormality on CT, but presence of parenchymal lesions on MR imaging. Patients in advanced age (chi square test, p<0.0001), and those with amnesia (p=0005, not significant), although scoring 15 points, revealed a tendency to abnormal intracranial lesions on CT scans. CONCLUSION: It is doubtful whether patients with GCS score 13 should be included in the mild head injury category, due to obvious brain damage on CT scans. MR imaging should be performed on patients with GCS score 14, since the parenchymal lesions are not clearly demonstrated on CT scans. Even if patients scored GCS 15, patients with amnesia or of advanced age should undergo CT scans at minimum, and MR imaging when available.

Infarction followed by hemorrhage in pituitary adenoma due to endocrine stimulation test.

A 63-year-old man, who presented with visual field loss due to pituitary tumor, received an intravenous bolus injection of thyrotropin and gonadotropin releasing hormones and insulin as a preoperative evaluation. He complained of severe headache and nausea 2 hours after injection. Emergent CT scan showed no evidence of intratumoral hemorrhage. The next day, his visual field became null. MR images revealed heterogeneous mixed intensity lesions. Under diagnosis of pituitary apoplexy, he underwent transsphenoidal tumor removal 30 hours after onset. Intraoperative and pathological findings showed tumor hemorrhage and adjacent necrotic change. Fourteen cases with sufficient clinical detail in the literature are reviewed: All of the cases had macroadenoma with suprasellar extension. Testing agents were gonadotropin and thyrotropin releasing hormones in 92.9% and 85.7% of cases, respectively. Headache was an initial symptom and started within two hours in all cases but one. Half of the cases showed no change on CT scan. However, tumor hemorrhage was evidenced in 92.9% of cases with or without necrosis due to ischemic change, intraoperatively or pathologically. It is speculated that pituitary apoplexy often starts with infarction possibly due to vasoactive effect of testing agents and later develops into hemorrhage. Therefore, it is necessary to observe patients closely at least a few hours after endocrine stimulation test, and MR imaging may make an earlier diagnosis for the pituitary apoplexy since CT scan often shows no density change in the pituitary adenoma.

Heavily T2-weighted MR imaging of white matter tracts in the hypothalamus: normal and pathologic demonstrations.

BACKGROUND AND PURPOSE: The MR appearance of white matter tracts in the hypothalamus and the role of the hypothalamus as a memory mechanism have not been sufficiently described in clinical settings. Heavily T2-weighted black-and-white reversed (T2R) images were assessed to reveal their visualization and clinical significance. METHODS: One hundred healthy subjects and three patients with hypothalamic lesions underwent fast spin-echo MR imaging to reveal the postcommissural fornix (PF) and mammillothalamic tract (MT). RESULTS: The PF was identifiable in axial and/or coronal sections in all healthy subjects. No remarkable asymmetry of its size or course was evident. Both anteroposterior and vertical dimensions ranged from 10.5 to 14 mm. The MT was visible in one or two axial sections above the mammillary body in 64% of healthy subjects and in a coronal section in 36%. Two patients with glioblastoma multiforme and lacunar infarct at the hypothalamus presented with anterograde amnesia; T2R imaging revealed involvement of both the PF and MT. The third patient had a suprasellar craniopharyngioma with PF injury sparing the MT resulting from surgical manipulation and was free of memory deficit. Anterograde amnesia was evident only when both the PF and MT were injured. CONCLUSION: T2R images have made a high rate of detection of the PF and MT possible and could provide a more detailed correlation of hypothalamic neuroanatomy and memory mechanism in clinical settings.

Heavily T2 weighted MR assessment of fornical injury after anterior interhemispheric approach for large suprasellar tumors.

Fornical injury in transforaminal approach is well known. Its injury in the anterior interhemispheric approach (AIA) has been rarely highlighted. We report 2 cases with a large suprasellar tumor who underwent AIA. Postoperative heavily T2 weighted reversed (T2R) MR images demonstrated its unilateral injury. The clinical significance of symptom-free fornical injury after AIA is discussed. Cases 1 and 2 were a 15 year-old girl with a meningioma and a 49-year-old woman with a craniopharyngioma, respectively. They underwent AIA. Postoperative T2R images revealed unilateral fornical crus atrophy. They did not present associated memory deficits. Case 1 had the injury of both fornical column and anterior commissure. They were speculatively torn by intra-operative lateral retraction of the frontal lobes. Case 2 had unilateral atrophy of the mammillary body and postcommissural fornix, which were probably caused by ischemic damage related to surgical manipulation, since case 2 had an associated anterior thalamic infarct. During the operation for large suprasellar tumors, excessive laterally directed brain retraction should be avoided, since such manipulation may easily tear the overstretched anterior commissure and fornical column. Once we notice or suspect fornical injury on MR studies in cases of re-operation, we have to choose a surgical approach and operative manipulation to preserve an intact fornix. The MR evaluation of fornix should be included in the perioperative radiological assessment, since patients with unilateral fornical injury were free of memory disturbance, and T2R imaging is a useful MR sequence for depicting the anatomy related to the fornix.

Diffuse white matter changes caused by dural arteriovenous fistula.

We present two patients with progressive dementia who showed diffuse white matter changes on magnetic resonance imaging (MRI) associated with dural arteriovenous fistula (DAVF) involving the transverse-sigmoid sinuses. Angiography of both patients revealed that DAVF was associated with multiple occlusive changes in the dural venous sinus. The associated occlusive changes isolated the straight sinus and the DAVF from the other venous sinuses, and concentrated the drainage of the DAVF in the straight sinus. We postulate that the venous hypertension of the straight sinus resulted in the venous ischemia of the white matter, diffuse white matter changes on MRI, and progressive neurological signs including dementia. Treatment of the DAVF reversed white matter changes and neurological signs. Associated with the venous sinus occlusions, the DAVF caused dementia with diffuse white matter changes due to the venous ischemia.

Outcome prediction in severe head injury: analyses of clinical prognostic factors.

Retrospective analysis of 272 patients with severe head injury was performed. Patient age, Glasgow Coma Scale (GCS) score, pupillary abnormalities, impaired oculocephalic response, presence of subarachnoid haemorrhage, and multiplicity of parenchymal lesions on computerised tomography (CT) were examined. The CT findings were divided into 2 groups, diffuse brain injury (DBI) and mass lesion, according to the classification of the Traumatic Coma Data Bank. The DBI, basically, has no high or mixed density lesion more than 25 ml on CT, and was classified into 4 subgroups: DBI I includes injuries where there is no visible pathology; DBI II includes all injuries in which the cisterns are present with a midline shift of less than 5 mm; DBI III includes injuries with swelling where the cisterns are compressed or absent and the midline shift is less than 5 mm; DBI IV includes injuries with a midline shift of more than 5 mm. The mass lesions were categorised into 3 subgroups: epidural haematoma; acute subdural haematoma; and intracerebral haematoma. Outcomes were determined at 6 months following trauma using the Glasgow Outcome Scale. All DBI I patients recovered well. In the DBI II group, age, GCS score and detection of multiple parenchymal lesions on CT were significantly correlated with outcome. For the DBI III and IV groups, the only significant prognostic factor was the GCS score. In patients with a mass lesion, the GCS score was the only significant prognostic factor in the epidural haematoma group, but the GCS score and the presence of subarachnoid haemorrhage were predictive factors in the acute subdural haematoma group. Outcomes were unfavourable in the majority of patients with intracerebral haematoma. GCS score could predict outcome in all groups. The confidence of the outcome prediction ranged from 75.8 to 92.1%, depending on logistic regression analysis.

Demonstration of the postcommissural fibres of the fornix in short-inversion time inversion-recovery imaging on a high-field system.

Short-inversion time inversion-recovery (STIR) imaging using a 3 tesla system was assessed to reveal the postcommissural fibres (PF) of the fornix, which have rarely been highlighted neuroradiologically in the clinical setting. We studied 27 normal subjects. Sequence parameters were TR/TE/TI 8000/52/ 150 ms. STIR was expected to take advantage of the high signal-to-noise ratio of a high-field system, due to the long repetition time. PF were identifiable in axial and coronal slices in all cases. They were bordered anteriorly and superiorly by the anterior commissure and posteriorly and inferiorly by the mamillary body. Behind the anterior commissure, they ran in an arch-shaped posterior and inferior course in the hypothalamic nuclei and joined the mamillary body anterolaterally. They usually extended through three 3-mm slices (with 1 mm interslice gap) in anteroposterior and vertical dimensions. Little variation was observed in their course or size. Demonstration of the PF would provide a more detailed correlation of human neuroanatomy to hypothalamic function and individualised understanding of hypothalamic pathology and influence therapy.