Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study.

BACKGROUND: We aimed to examine whether stereotactic radiosurgery without whole-brain radiotherapy (WBRT) as the initial treatment for patients with five to ten brain metastases is non-inferior to that for patients with two to four brain metastases in terms of overall survival. METHODS: This prospective observational study enrolled patients with one to ten newly diagnosed brain metastases (largest tumour <10 mL in volume and <3 cm in longest diameter; total cumulative volume ≤15 mL) and a Karnofsky performance status score of 70 or higher from 23 facilities in Japan. Standard stereotactic radiosurgery procedures were used in all patients; tumour volumes smaller than 4 mL were irradiated with 22 Gy at the lesion periphery and those that were 4-10 mL with 20 Gy. The primary endpoint was overall survival, for which the non-inferiority margin for the comparison of outcomes in patients with two to four brain metastases with those of patients with five to ten brain metastases was set as the value of the upper 95% CI for a hazard ratio (HR) of 1·30, and all data were analysed by intention to treat. The study was finalised on Dec 31, 2012, for analysis of the primary endpoint; however, monitoring of stereotactic radiosurgery-induced complications and neurocognitive function assessment will continue for the censored subset until the end of 2014. This study is registered with the University Medical Information Network Clinical Trial Registry, number 000001812. FINDINGS: We enrolled 1194 eligible patients between March 1, 2009, and Feb 15, 2012. Median overall survival after stereotactic radiosurgery was 13·9 months [95% CI 12·0-15·6] in the 455 patients with one tumour, 10·8 months [9·4-12·4] in the 531 patients with two to four tumours, and 10·8 months [9·1-12·7] in the 208 patients with five to ten tumours. Overall survival did not differ between the patients with two to four tumours and those with five to ten (HR 0·97, 95% CI 0·81-1·18 [less than non-inferiority margin], p=0·78; pnon-inferiority<0·0001). Stereotactic radiosurgery-induced adverse events occurred in 101 (8%) patients; nine (2%) patients with one tumour had one or more grade 3-4 event compared with 13 (2%) patients with two to four tumours and six (3%) patients with five to ten tumours. The proportion of patients who had one or more treatment-related adverse event of any grade did not differ significantly between the two groups of patients with multiple tumours (50 [9%] patients with two to four tumours vs 18 [9%] with five to ten; p=0·89). Four patients died, mainly of complications relating to stereotactic radiosurgery (two with one tumour and one each in the other two groups). INTERPRETATION: Our results suggest that stereotactic radiosurgery without WBRT in patients with five to ten brain metastases is non-inferior to that in patients with two to four brain metastases. Considering the minimal invasiveness of stereotactic radiosurgery and the fewer side-effects than with WBRT, stereotactic radiosurgery might be a suitable alternative for patients with up to ten brain metastases. FUNDING: Japan Brain Foundation.

Concept of robotic gamma knife microradiosurgery and results of its clinical application in benign skull base tumors.

The availability of advanced computer-aided robotized devices for the Gamma Knife (i.e., an automatic positioning system and PerfeXion) resulted in significant changes in radiosurgical treatment strategy. The possibility of applying irradiation precisely and the significantly improved software for treatment planning led to the development of the original concept of robotic Gamma Knife microradiosurgery, which is comprised of the following: (1) precise irradiation of the lesion with regard to conformity and selectivity; (2) intentional avoidance of excessive irradiation of functionally important anatomical structures, particularly cranial nerves, located both within the target and in its vicinity; (3) delivery of sufficient radiation energy to the tumor with a goal of shrinking it while keeping the dose at the margins low enough to prevent complications. Realization of such treatment principles requires detailed evaluation of the microanatomy of the target area, which is achieved with an advanced neuroimaging protocol. From 2003, we applied the described microradiosurgical concept in our clinic for patients with benign skull base tumors. Overall, 75 % of neoplasms demonstrated shrinkage, and 47 % showed ≥50 % and more volume reduction. Treatment-related complications were encountered in only 6 % of patients and were mainly related to transient cranial nerve palsy. Just 2 % of neoplasms showed regrowth after irradiation. In conclusion, applying the microradiosurgical principles based on advanced neuroimaging and highly precise treatment planning is beneficial for patients, providing a high rate of tumor shrinkage and a low morbidity rate.

Do we really still need an open surgery for treatment of patients with vestibular schwannomas?

BACKGROUND: Gamma Knife surgery (GKS) should be considered a standard treatment option for small and medium-sized vestibular schwannomas (VSs). It results in a tumor control rate similar to that seen with microsurgery and provides better preservation of facial nerve function and hearing. METHODS: From December 2002 to April 2011, a total of 260 patients with VS underwent GKS using Leksell Gamma Knife model 4C with an automatic positioning system. There were 30 Koos stage I tumors, 112 stage II, 100 stage III, and 18 stage IV. All patients were treated with the use of high-resolution magnetic resonance imaging; creation of the highly precise conformal and selective multi-isocenter dose planning with small collimators, carefully sparing adjacent cranial nerves of any excessive irradiation; and creation of a wide 80 % isodose area within the tumor while applying a low marginal dose (mean 11.9 Gy) at the 50 % isodose line. RESULTS: Among 182 patients who were followed for more than 3 years after treatment, the tumor control and shrinkage rates were 98.4 % and 76.4 %, respectively. Volume reduction of >50 % was marked in 54.9 % of VSs. Preservation of facial nerve function and hearing at the pretreatment level was noted in 97.8 % and 87.9 %, respectively. There was marked improvement of facial nerve function and hearing after GKS in 2.2 % and 3.8 %, respectively. There was no major morbidity. CONCLUSION: Due to contemporary technological and methodological achievements GKS can be focused not only on growth control but on shrinking the VS, with possible reversal of the neurological deficit.

Gamma knife treatment strategy for metastatic brain tumors.

From 1993 to 2011, a total of 3,095 patients with brain metastases underwent Gamma Knife radiosurgery (GKS) at Tokyo Women's Medical University. Follow-up information on 2,283 of these patients was available for retrospective analysis. The cases were separated into three groups according to the treatment period, the model of the Gamma Knife used, main goals of treatment, and technical nuances of radiosurgery. In the latest cohort of patients treated with the Leksell Gamma Knife model 4C with automatic positioning system, an optimized treatment strategy was applied. It was based on highly selective dose planning, with the use of multiple small isocenters located within the bulk of the mass, which was done for prevention of the excessive irradiation of the perilesional brain and avoidance of its posttreatment edema. In cases of large cystic tumors, selective coverage of the contrast-enhancing capsule with chain-like application of multiple small isocenters was done. Introduction of the new treatment strategy did not affect the 1-year tumor control rate, which was consistently >90 %. However, it did result in a statistically significant reduction of severe posttreatment peritumoral brain edema (from 15.5 % to 6.3 %; P < 0.0001). In conclusion, recent technical and methodological achievements of GKS seemingly do not affect its high efficacy in cases of brain metastasis with regard to tumor control. However, it may result in a prominent reduction of treatment-associated -morbidity, which is particularly important in patients with large and/or critically located neoplasm.

Optimal visualization of multiple brain metastases for gamma knife radiosurgery.

BACKGROUND: Optimal management of metastatic brain disease requires precise detection and detailed characterization of all intracranial lesions. METHODS: We analyzed an experience with 3200 brain MRI investigations performed at 1.5 T and 3.0 T for identification and/or evaluation of intracranial metastases. Usually axial T1- and T2-weighted images and contrast-enhanced T1-weighted images in axial and coronal and/or sagittal projections were obtained. Fluid-attenuated inversion recovery and diffusion-weighted imaging were sometimes used as well. Routinely, 0.2 mmol/kg of gadoteridol (ProHance®) was administered intravenously, but the dose was reduced to 0.1 mmol/kg in elderly patients or in patients with mild renal dysfunction. FINDINGS: Magnetic resonance imaging (MRI) provided excellent information on tumor location; interrelations with functionally important intracranial structures; type of growth; vascularity; recent, old or multiple hemorrhages within or in the vicinity of the mass; presence of peritumoral edema; necrotic changes; subarachnoid dissemination; meningeal carcinomatosis. However, without administration of gadoteridol or without contrast enhancement, small metastatic tumors could not be reliably distinguished from brain lacunes. Some metastases (malignant melanoma, thyroid cancer, endocrine carcinoma, small cell lung carcinoma) may demonstrate specific neuroimaging features. Non-metastatic -multiple brain lesions caused by vascular, inflammatory, demyelinative or lymphoproliferative diseases require a thorough differential diagnosis with metastatic brain tumors based not only on neuroimaging but on additional analysis of various clinical data. CONCLUSION: Contemporary MRI techniques provide excellent options for detection, detailed characterization, and differential diagnosis of metastatic brain tumors, which is extremely important when choosing the optimal treatment strategy, particularly with Gamma Knife radiosurgery.

Usefulness of the advanced neuroimaging protocol based on plain and gadolinium-enhanced constructive interference in steady state images for gamma knife radiosurgery and planning microsurgical procedures for skull base tumors.

BACKGROUND: Gamma Knife radiosurgery (GKS) is currently performed with 0.1 mm preciseness, which can be designated microradiosurgery. It requires advanced methods for visualizing the target, which can be effectively attained by a neuroimaging protocol based on plain and gadolinium-enhanced constructive interference in steady state (CISS) images. METHODS: Since 2003, the following thin-sliced images are routinely obtained before GKS of skull base lesions in our practice: axial CISS, gadolinium-enhanced axial CISS, gadolinium-enhanced axial modified time-of-flight (TOF), and axial computed tomography (CT). Fusion of "bone window" CT and magnetic resonance imaging (MRI), and detailed three-dimensional (3D) delineation of the anatomical structures are performed with the Leksell GammaPlan (Elekta Instruments AB). Recently, a similar technique has been also applied to evaluate neuroanatomy before open microsurgical procedures. RESULTS: Plain CISS images permit clear visualization of the cranial nerves in the subarachnoid space. Gadolinium-enhanced CISS images make the tumor "lucid" but do not affect the signal intensity of the cranial nerves, so they can be clearly delineated in the vicinity to the lesion. Gadolinium-enhanced TOF images are useful for 3D evaluation of the interrelations between the neoplasm and adjacent vessels. Fusion of "bone window" CT and MRI scans permits simultaneous assessment of both soft tissue and bone structures and allows 3D estimation and correction of MRI distortion artifacts. CONCLUSION: Detailed understanding of the neuroanatomy based on application of the advanced neuroimaging protocol permits performance of highly conformal and selective radiosurgical treatment. It also allows precise planning of the microsurgical procedures for skull base tumors.

Differentiation of tumor progression and radiation-induced effects after intracranial radiosurgery.

A number of intracranial tumors demonstrate some degree of enlargement after stereotactic radiosurgery (SRS). It necessitates differentiation of their regrowth and various treatment-induced effects. Introduction of low-dose standards for SRS of benign neoplasms significantly decreased the risk of the radiation-induced necrosis after -management of schwannomas and meningiomas. Although in such cases a transient increase of the mass volume within several months after irradiation is rather common, it usually followed by spontaneous shrinkage. Nevertheless, distinguishing tumor recurrence from radiation injury is often required in cases of malignant parenchymal brain neoplasms, such as metastases and gliomas. The diagnosis is frequently complicated by histopathological heterogeneity of the lesion with coexistent viable tumor and treatment-related changes. Several neuroimaging modalities, namely structural magnetic resonance imaging (MRI), diffusion-weighted imaging, diffusion tensor imaging, perfusion computed tomography (CT) and MRI, single-voxel and multivoxel proton magnetic resonance spectroscopy as well as single photon emission CT and positron emission tomography with various radioisotope tracers, may provide valuable diagnostic information. Each of these methods has advantages and limitations that may influence its usefulness and accuracy. Therefore, use of a multimodal radiological approach seems reasonable. Addition of functional and metabolic neuroimaging to regular structural MRI investigations during follow-up after SRS of parenchymal brain neoplasms may permit detailed evaluation of the treatment effects and early prediction of the response. If tissue sampling of irradiated intracranial lesions is required, it is preferably performed with the use of metabolic guidance. In conclusion, differentiation of tumor progression and radiation-induced effects after intracranial SRS is challenging. It should be based on a complex evaluation of the multiple clinical, radiosurgical, and radiological factors.

Gamma knife radiosurgery for benign cavernous sinus tumors: treatment concept and outcomes in 120 cases.

Availability of modern computer-aided robotized devices, such as the Automatic Positioning System (APSTM; Elekta Instruments AB, Stockholm, Sweden) and PerfexionTM (Elekta Instruments AB), allowed us to develop the original concept of robotic gamma knife microradiosurgery, which is based on the very precise irradiation of the lesion with regard to conformity and selectivity; intentional avoidance of the excessive irradiation of functionally-important anatomical structures, particularly cranial nerves, located both within and in the vicinity of the target; and delivery of sufficient irradiation energy to the tumor with the intention to attain lesion shrinkage, while keeping the marginal dose sufficiently low for prevention of possible complications. The results of such treatment strategy were evaluated retrospectively in 120 patients with benign cavernous sinus neoplasms (pituitary adenomas, meningiomas, schwannomas, and hemangiomas), who were followed up from 24 to 78 months (mean 47 months) after radiosurgery. Tumor growth control and shrinkage rates were 98% and 68%, respectively. More than 50% volume reduction was noted in 25% of lesions. The most prominent volumetric tumor response was observed in hemangiomas, followed by schwannomas, pituitary adenomas, and meningiomas. Treatment-related complications were marked in 7% of cases, and were mainly related to transient isolated cranial neuropathy appearing within several months after radiosurgery. Major morbidity was limited to one patient (0.8%). Application of microradiosurgical treatment principles provides effective and safe management of benign cavernous sinus tumors and is associated with high probability of lesion shrinkage and minimal risk of complications.

Experience with carbon ion radiotherapy for WHO Grade 2 diffuse astrocytomas.

PURPOSE: To assess outcomes of carbon ion radiotherapy for diffuse astrocytomas in adults. METHODS AND MATERIALS: Between October 1994 and February 2002, 14 patients with diffuse astrocytoma, identified as eligible for carbon ion radiotherapy, were enrolled in a phase I/II clinical trial. Carbon ion radiotherapy was administered in 24 fractions over 6 weeks. The normal tissue morbidity was monitored carefully, and the carbon ion dose was escalated from 50.4 Gy equivalent (GyE) to 55.2 GyE. Patients were divided into two groups according to their carbon ion doses: a low-dose group in which 2 patients were irradiated with 46.2 GyE and 7 patients were irradiated with 50.4 GyE, and a high-dose group in which 5 patients were irradiated with 55.2 GyE. RESULTS: Toxicities were within acceptable limits, and none of the patients developed Grade 3 or higher acute or late reactions. The median progression-free survival (PFS) time was 18 months for the low-dose group and 91 months for the high-dose group (p = 0.0030). The median overall survival (OS) time was 28 months for the low-dose group and not reached for the high-dose group (p = 0.0208). CONCLUSION: High-dose group patients showed significant improvement in PFS and OS rates compared to those in the low-dose group, and both dose groups showed acceptable toxicity.

Stereotactic radiosurgery of essential trigeminal neuralgia using Leksell Gamma Knife model C with automatic positioning system: technical nuances and evaluation of outcome in 130 patients with at least 2 years follow-up after treatment.

The objective of the present study was the evaluation of outcome in 130 patients with essential trigeminal neuralgia, who were treated using Leksell Gamma Knife model C with automatic positioning system and followed at least 24 months thereafter. Radiosurgery was guided by fused thin-sliced magnetic resonance (MR) and "bone window" computed tomographic (CT) images. In all cases, retrogasserian part of the trigeminal nerve at the level of trigeminal incisura was selected as a target, and one 4-mm collimator was used for delivery of the maximum irradiation dose of 90 Gy. The coordinates of the isocenter were adjusted for positioning of the nerve in the center of 80% isodose area, and were corrected in each individual case with regard to presence of distortion artifacts on MR images. Initial relief of the typical paroxysmal facial pain was marked in 127 patients (98%) within a median interval of 3 weeks after treatment. However, in 23 patients the pain re-appeared later on. Overall, at the time of the last follow-up 112 patients (86%) were pain-free, including 86 who remained both pain- and medication-free after initial radiosurgery. In 31 cases (24%), treatment was complicated by facial hypesthesia and/or paresthesia. In conclusion, radiosurgery of essential trigeminal neuralgia results in a high rate of initial pain relief, but pain recurrences and associated complications are not uncommon. The outcome may be influenced by various technical nuances; therefore, treatment should be preferably done in specialized clinical centers with sufficient expertise in the management of this disorder.

Phase I/IIa trial of autologous formalin-fixed tumor vaccine concomitant with fractionated radiotherapy for newly diagnosed glioblastoma. Clinical article.

OBJECT: The objective of the present study was analysis of results of the prospective clinical trial directed toward the evaluation of therapeutic efficacy of the administration of autologous formalin-fixed tumor vaccine (AFTV) concomitant with fractionated radiotherapy in cases of newly diagnosed glioblastoma multiforme. METHODS: Twenty-four patients were enrolled into the clinical trial, while 2 cases were excluded from the final analysis of results. The treatment protocol included aggressive tumor resection, fractionated radiotherapy up to a total dose of 60 Gy, and 3 concomitant courses of AFTV administered with an interval of one week at the late stage of irradiation. Two delayed-type hypersensitivity (DTH) tests were done--one 48 hours before the initial course of vaccination (DTH-1) and one 2 weeks after the third (DTH-2). All but one of the patients received salvage therapy at the time of tumor progression. The defined primary end point was overall survival; secondary end points were progression-free survival and safety of concomitant treatment. RESULTS: The median duration of overall survival was 19.8 [corrected] months (95% CI 13.8-31.3 months). The actuarial 2-year survival rate was 40%. The median duration of progression-free survival was 7.6 months (95% CI 4.3-13.6 months). Overall survival showed a statistically significant association with recursive partitioning analysis class (p < 0.05); progression-free survival showed a statistically significant association with p53 staining index (p < 0.05) and size of DTH-2 response (p < 0.001). AFTV injection concomitant with fractionated radiotherapy was well tolerated by all patients and in no case did treatment-related adverse effects exceed Grade 1 toxicity; adverse effects were limited to local erythema, induration, and swelling at the site of injection. CONCLUSIONS: The results of this study demonstrate that AFTV treatment concomitant with fractionated radiotherapy may be effective in patients with newly diagnosed glioblastoma. Further clinical testing is warranted.

Information-guided surgical management of gliomas using low-field-strength intraoperative MRI.

BACKGROUND: Contemporary technological developments revolutionized management of brain tumors. The experience with information-guided surgery of gliomas, based on the integration of the various intraoperative anatomical, functional, and histological data, is reported. METHODS: From 2000 to 2009, 574 surgeries for intracranial gliomas were performed in our clinic with the use of intraoperative MRI (ioMRI) with magnetic field strength of 0.3T, updated neuronavigation, neurochemical navigation with 5-aminolevulinic acid, serial intraoperative histopathological investigations of the resected tissue, and comprehensive neurophysiological monitoring. Nearly half of patients (263 cases; 45.8%) were followed more than 2 years after surgery. FINDINGS: Maximal possible tumor resection, defined as radiologically complete tumor removal or subtotal removal leaving the residual neoplasm within the vital functionally-important brain areas, was attained in 569 cases (99.1%). The median resection rate constituted 95%, 95%, and 98%, for WHO grade II, III, and IV gliomas, respectively. Actuarial 5-year survival was significantly worse in WHO grade IV gliomas (19%), but did not differ significantly between WHO grade III and II tumors (69% vs. 87%). CONCLUSIONS: Information-guided management of gliomas using low-field-strength ioMRI provides a good opportunity for maximal possible tumor resection, and may result in survival advantage, particularly in patients with WHO grade III neoplasms.

¹H-MRS of intracranial meningiomas: what it can add to known clinical and MRI predictors of the histopathological and biological characteristics of the tumor?

OBJECTIVE: The main goal of the present study was evaluation of proton magnetic resonance spectroscopy (¹H-MRS) in diagnosis of histopathologically aggressive intracranial meningiomas. METHODS: Single-voxel ¹H-MRS of 100 intracranial meningiomas was performed before their surgical resection. Investigated metabolites included mobile lipids, lactate, alanine, N-acetylaspartate (NAA), and choline-containing compounds (Cho). According to criteria of World Health Organization (WHO) 82 meningiomas were assigned histopathological grade I, 11 grade II, and 7 grade III. The MIB-1 index varied from 0% to 27.3% (median, 1.6%). In 43 cases tight adhesion of the tumor to the pia mater or brain tissue was macroscopically identified at surgery. The consistency of 49 meningiomas was characterized as soft, 26 as hard, and 25 as mixed. RESULTS: No one metabolic parameter had statistically significant association with histopathological grade and subtype, invasive growth, and consistency of meningioma. Univariate statistical analysis revealed greater ¹H-MRS-detected Cho content (P=0.0444) and lower normalized NAA/Cho ratio (P=0.0203) in tumors with MIB-1 index 5% and more. However, both parameters lost their statistical significance during evaluation in the multivariate model along with other clinical and radiological variables. It was revealed that non-benign histopathology of meningioma (WHO grade II/III) is mainly predicted by irregular shape (P=0.0076) and large size (P=0.0316), increased proliferative activity by irregular shape (P=0.0056), and macroscopically invasive growth by prominent peritumoral edema (P=0.0021). CONCLUSION: While ¹H-MRS may be potentially used for the identification of meningiomas with high proliferative activity, it, seemingly, could not add substantial diagnostic information to other radiological predictors of malignancy in these tumors.

Gamma knife robotic microradiosurgery for benign skull base meningiomas: tumor shrinkage may depend on the amount of radiation energy delivered per lesion volume (unit energy).

BACKGROUND/AIMS: The objective of the present study was the evaluation of the effectiveness of robotic microradiosurgery of skull base meningiomas using Leksell Gamma Knife model C with an automatic positioning system. METHODS: The results of the management of 66 tumors were analyzed retrospectively. Their volume varied from 0.3 to 50.6 cm³ (mean = 6.6). The treatment plan was based on the use of multiple small isocenters compactly positioned within the border of the lesion with resultant improved homogeneity of high-dose distribution, increased average dose within the target and sharp dose fall outside the treated volume. The marginal dose varied from 10 to 14 Gy (mean = 12). The length of follow-up ranged from 26 to 80 months (mean = 46). RESULTS: The overall tumor growth control was 99%. Reduction of the mass volume was marked in 54 patients (82%), and in 15 of them it constituted ≥ 50%. In other 11 cases (17%) stabilization of the lesion growth was noted. The shrinkage rate significantly correlated with amount of radiation energy delivered per tumor volume, designated as unit energy (p = 0.007). One meningioma (1%) regrew 3.5 years after radiosurgery. The treatment-related morbidity was limited to transient abducens nerve palsy in 1 patient (1%). CONCLUSION: Application of the concept of Gamma Knife robotic microradiosurgery for the management of skull base meningiomas may change the paradigm of their treatment from stabilization of growth to reduction of the volume of the neoplasm. The tumor shrinkage rate may depend on the amount of radiation energy delivered per lesion volume (unit energy).

Gamma Knife surgery for abducent nerve schwannoma. Report of 4 cases.

Abducent nerve schwannomas are extremely rare. The authors recently performed Gamma Knife surgery (GKS) in 4 patients with such tumors and describe their experiences with these cases. The patients consisted of 3 women and 1 man whose ages varied from 31 to 60 years (mean 46 years). Two patients had no symptoms, 1 complained of slight visual disturbances, and the other 1 had abducent nerve palsy. Neurofibromatosis was not diagnosed in any case. All 4 tumors were located in the cavernous sinus: 2 of these tumors within the borders of the sinus, 1 tumor extending into the orbit, and 1 tumor extending into the prepontine cistern. The volume of the neoplasms varied from 1.7 to 4.9 cm(3) (mean 3.0 cm(3)). No patient underwent tumor resection. Treatment was delivered with the aid of a Leksell Gamma Knife model C unit and the automatic positioning system. The dose directed to the tumor margin was 12 Gy in all cases. The dose directed to the anterior visual pathways was kept below 10 Gy and that to the brainstem below 14 Gy. The length of follow-up varied between 7 and 43 months (mean 27 months). There were no acute complications or side effects. Imaging studies showed temporary enlargement of all tumors during the 1st posttreatment year, but thereafter, there was a trend toward reduction in volume. None of the neoplasms displayed regrowth. In the 3 patients who did not have abducent nerve palsy before GKS, it appeared, at least temporarily, after the procedure. Purely intracavernous neoplasms in general followed uneventful posttreatment courses, but dumbbell-shaped tumors were associated with significant morbidity. The cisternocavernous schwannoma underwent cystic degeneration 2 years after GKS, and the patient developed diplopia. After GKS, the patient treated for an orbitocavernous schwannoma experienced a significant deterioration in vision, temporary blindness in 1 eye, and late development of permanent abducent nerve palsy, which were seemingly caused by compression of neurovascular structures within the anulus of Zinn during a temporary increase in the lesion's volume after irradiation. Gamma Knife surgery controls the growth of abducent nerve schwannomas and may be effectively used to manage intracavernous neoplasms. Caution, however, should be used in cases of dumbbell-shaped tumors, particularly those extending through the superior orbital fissure.

Gamma Knife robotic microradiosurgery of pituitary adenomas invading the cavernous sinus: treatment concept and results in 89 cases.

The objective of the present retrospective study was evaluation of results of "robotic microradiosurgery" of pituitary adenomas invading the cavernous sinus. Eighty-nine patients with such tumors underwent management using Leksell Gamma Knife model C with automatic positioning system. There were 77 residual and 12 recurrent neoplasms. The applied radiosurgical treatment plan was based on the use of multiple isocenters, mainly of smaller size, which were positioned compactly within the border of the lesion with resultant improved dose homogeneity, increased average dose within the target, and sharp dose fall outside the treated volume. The marginal dose varied from 12 to 25 Gy (mean, 18.2 Gy) in non-functional pituitary adenomas (43 cases), and from 12 to 35 Gy (mean, 25.2 Gy) in hormone-secreting ones (46 cases). The length of follow-up after treatment ranged from 24 to 76 months (mean, 36 months). Control of the tumor growth was attained in 86 cases (97%), whereas actual shrinkage of the lesion was marked in 57 cases (64%). In 18 out of 46 secreting neoplasms (39%), normalization of the excess of the pituitary hormone production was noted after radiosurgery. Treatment-associated morbidity was limited to transitory cranial nerve palsy in two patients (2%). No patient with either non-functional or hormone secreting tumor exhibited new pituitary hormone deficit after treatment. In conclusion, highly precise microanatomy-based Gamma Knife robotic microradiosurgery provides an opportunity for effective management of pituitary adenomas invading the cavernous sinus with preservation of the adjacent functionally important neuronal structures.

Role of proton magnetic resonance spectroscopy in preoperative evaluation of patients with mesial temporal lobe epilepsy.

A retrospective study was conducted for evaluation of the role of single-voxel proton magnetic resonance spectroscopy (1H-MRS) in preoperative investigation of patients with mesial temporal lobe epilepsy (MTLE). Eighteen cases, including both non-lesional and lesional MTLE, were analyzed. Selective amygdalohippocampectomy was performed in 8 cases, selective amygdalohippocampectomy combined with lesionectomy in 6 cases, lesionectomy in 3 cases, and anterior temporal lobe resection in one case. The length of follow-up varied from 24 to 71 months (median, 35 months). Before surgery, (1)H-MRS disclosed decrease of N-acetylaspartate (NAA) content (P=0.01) and more frequent (P=0.07) presence of lactate (Lac) on the side of the epileptogenic zone. Decrease of NAA content below 0.75 and/or unilateral presence of Lac provided 86% (95% CI: 68%-100%) lateralization accuracy. Metabolic parameters did not differ in subgroups with hippocampal sclerosis and brain tumors. On the long-term follow-up 12 patients (67%) were free of disabling seizures. There was a trend (P=0.05) for worse seizure outcome in cases with significant bilateral metabolic alterations characterized by predominance of choline-containing compounds' peak on 1H-MR spectra on both sides. In conclusion, 1H-MRS-detected reduction of NAA content and unilateral presence of Lac in the mesial temporal lobe structures may serve as additional diagnostic clues for lateralization of the epileptogenic zone in MTLE. Metabolic imaging has limited usefulness for differentiation of the hippocampal sclerosis and low-grade intraaxial brain tumor. Presence of significant bilateral metabolic alterations in the mesial temporal lobe structures is associated with worse postoperative seizure control.