Object: Several studies have revealed that the gross-total resection (GTR) of malignant brain tumors has a significant influence on patient survival. Frequently, however, GTR cannot be achieved because the borders between healthy brain and diseased tissue are blurred in the infiltration zones of malignant brain tumors. Especially in eloquent cortical areas, resection is frequently stopped before total removal is achieved to avoid causing neurological deficits. Interestingly, 5-aminolevulinic acid (5-ALA) has been shown to help visualize tumor tissue intraoperatively and, thus, can significantly improve the possibility of achieving GTR of primary malignant brain tumors. The aim of this study was to go one step further and evaluate the utility and limitations of fluorescence-guided resections of primary malignant brain tumors in eloquent cortical areas in combination with intraoperative monitoring based on multimodal functional imaging data. Methods: Eighteen patients with primary malignant brain tumors in eloquent areas were included in this prospective study. Preoperative neuroradiological examinations included MR imaging with magnetization-prepared rapid gradient echo (MPRAGE), functional MR, and diffusion tensor imaging sequences to visualize functional areas and fiber tracts. Imaging data were analyzed offline, loaded into a neuronavigational system, and used intraoperatively during resections. All patients received 5-ALA 6 hours before surgery. Fluorescence-guided tumor resections were combined with intraoperative monitoring and cortical as well as subcortical stimulation to localize functional areas and fiber tracts during surgery. Results: Twenty-five procedures were performed in 18 consecutive patients. In 24% of all surgeries, resection was stopped because a functional area or cortical tract was identified in the resection area or because motor evoked potential amplitudes were reduced in an area where fluorescent tumor cells were still seen intraoperatively. Grosstotal resection could be achieved in 16 (64%) of the surgeries with preservation of all functional areas and fiber tracts. In 2 patients presurgical hemiparesis became accentuated postoperatively, and 1 of these patients also suffered from a new homonymous hemianopia following a second resection. Conclusions: The authors' first results show that tumor resections with 5-ALA in combination with intraoperative cortical stimulation have the advantages of both methods and, thus, provide additional safety for the neurosurgeon during resections of primary malignant brain tumors in eloquent areas. Nonetheless, more cases and additional studies are necessary to further prove the advantages of this multimodal strategy.

The most important treatment options for meningiomas are microsurgery, radiotherapy, and gamma knife radiosurgery (GKRS). The efficacy of GKRS in terms of local tumor control and tumor volume (TV) reduction can best be determined by accurate analysis of changes in tumor size in pre- and post-GKRS images. In this prospective study, we set the focus on evaluating TV changes and treatment outcome of meningiomas using a quantitative volumetric follow-up protocol after GKRS. Consecutive patients with World Health Organization Grade I and II meningiomas were included in this study. Most patients underwent a microsurgical TV reduction before being treated with GKRS. Follow-up examinations were performed according to a standardized protocol and included magnetic resonance imaging and quantitative volumetric tumor analyses as well as thorough neurological examinations. Complete follow-up data was available for 211 patients (243 tumors) with a mean age of 57.9 years. TVs ranging from 0.1 to 48.3 cm3 were treated with GKRS using prescription doses ranging from 10 to 22 Gy. The achieved overall tumor control rate determined with quantitative TV analyses after GKRS was 93.4%; a mean TV reduction of 42.1% was achieved in 74.5% of all treated patients. Results of this study show that a quantitative volumetric follow-up study of meningiomas is a useful method to demonstrate the efficacy of GKRS for meningiomas. Statistically significant TV reductions with a low rate of side effects can be achieved with GKRS.

Object: Causes of pituitary insufficiencies as a side effect of Gamma Knife surgery (GKS) following irradiation of the hypothalamopituitary axis are still under debate. In an investigation of pituitary insufficiencies after GKS, the authors' main focus is on what role can be attributed to the hypothalamus with regard to endocrinological changes in hypothalamopituitary function following GKS. Methods: A total of 108 patients consecutively treated between April 1992 and July 2003 were included in this retrospective study. All patients had undergone either transsphenoidal or transcranial surgery prior to GKS. The spot dosimetry method was used to determine doses delivered to structures of the hypothalamopituitary axis. For statistical analyses, endocrine insufficiency and deterioration in pituitary function were defined as a decrease in hormonal blood levels below the normal range for 1 or more anterior pituitary lobe hormones. Additionally, an analysis of the rate of patients requiring hormone replacement therapy after GKS due to new endocrinopathies was performed. Results: Complete patient records of 61 male and 47 female patients with a mean age of 51.9 years (range 9.1–81.2 years) were available for our investigation. The overall tumor control rate was 97% and the endocrinological cure rate was 61.2%. Mean treatment doses in patients with and without new endocrine insufficiencies (shown as with/without insufficiencies and followed by probability values) were as follows: 1.3/0.8 Gy to the hypothalamus (p = 0.2); 2.2/1.6 Gy to the median eminence (p = 0.1); 6.5/4.1 Gy to the pituitary stalk (p = 0.004); and 12.4/9.5 Gy to the pituitary gland (p = 0.05). The median overall duration of follow-up after GKS was 6.7 years, with 84 patients (77.7%) whose follow-up was longer than 12 months. The median follow-up time after GKS in patients who developed a new pituitary dysfunction was 79.5 months (6.6 years, SD 3.8 years), and the median follow-up time in patients with no new insufficiencies was 78.4 months (6.5 years, SD 4 years). Conclusions: Gamma Knife surgery is a safe and effective treatment for patients with residual and recurrent pituitary adenomas. The rate of pituitary insufficiencies after GKS is still lower than that after conventional radiotherapy. Very low radiation doses are directed to the hypothalamus, and thus this structure does not play a major role in the development of pituitary insufficiencies after GKS. The results of this study show that patients in whom the pituitary stalk and pituitary gland receive a high mean point dose are more likely to develop pituitary insufficiencies after GKS than those who receive a lower dose.

Object: Glomus jugulare tumors (GJTs) are slow-growing benign tumors arising from paraganglion cells of the superior vagal ganglion. Involvement of cranial nerves and extensive erosion of the jugular foramen and petrous bone are typically seen in patients with GJTs. Advances in microsurgical techniques have improved patient outcomes, but tumors involving the petrous bone remain difficult to treat effectively. The aim of our study was to further evaluate the role of Gamma Knife surgery (GKS) in the management of intracranial GJTs.Methods: Twelve consecutive patients (mean age 51.7 years) with intracranial GJTs were included in this study. The treatment strategy was either multimodal, with microsurgical tumor volume reduction followed by GKS in patients suffering from brainstem compression, or GKS as the only treatment. Follow-up examinations included thorough neurological examinations and neuroradiological quantitative volumetric tumor analysis. Five patients (41.6%) underwent microsurgery before GKS. Tumor volumes ranging from 1.6 to 24.8 cm³ were treated using prescription doses of 14 to 20 Gy (nine–28 isocenters). The achieved overall tumor control rate after GKS was 100% (33 months mean follow up) with only mild side effects observed. A tumor volume reduction (mean 41.1%; 3.2 cm³) was achieved in all patients.Conclusions: Gamma Knife surgery is a safe and effective treatment for intracranial GJTs. The tumor volume reductions achieved are comparable to those achieved using microsurgery but with a much lower rate of side effects. More studies with longer follow-up times are necessary to confirm these very promising results.