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Abstract Although chemotherapy with procarbazine, lomustine and vincristine (PCV) is considered to be well tolerated, side effects frequently lead to dose reduction or even discontinuation of treatment of oligodendroglial brain tumors. The primary objective of the analysis was to retrospectively compare progression-free survival (PFS) after PCV vs. PC chemotherapy (without vincristine to avoid side effects). Patients were retrospectively identified from a database containing our patients between 1990 and 2003. For the selected cases, all histopathology reports were re-evaluated by a local neuropathologist. Based on the updated histology data, patients were included in the study if they had at least one histological diagnosis of an oligodendroglial tumor. PFS after start of PCV (n = 61) and PC (n = 84) chemotherapy identical (median 30 months). Multivariate analysis adjusting for prognostic imbalances favouring the PC group showed a minor, statistically non-significant benefit for PCV (hazard ratio 0.81, 95% confidence interval 0.53–1.25; p = 0.346). Younger age (< 50 y) was a statistically significant predictor of longer PFS. Significant advantages in terms of overall survival after first diagnosis of oligodendroglial tumor (OS, n = 315) were found for patients < 50 y (p < 0.001), oligodendrogliomas versus oligoastrocytomas (p = 0.002), and WHO°II vs. °III (p < 0.001). Three risk groups regarding OS were identified. Findings support the hypothesis that PC may be as effective as PCV chemotherapy, while avoiding the additonal risks of vincristine. Younger age, lower tumor grade and histology of an oligodendroglioma were identified to be favorable prognostic factors.

Clinical neurosurgery is an endangered academic discipline. Neurosurgeons have competition from many directions: orthopedists, ear, nose and throat surgeons, plastic surgeons, radio-oncologists, and interventional radiologists, among others. Academic centers are no longer the only sites of neurosurgical education at the attending level, and neurosurgery is not felt to be an indispensible part of an undergraduate medical curriculum. There are insufficient data to determine if neurosurgical services for the general population are adequate or appropriate. The traditional strengths of academic neurosurgery are gathering data, analysis, research, innovation, and teaching within a context of understanding and tradition. Future healthy development of neurosurgery ideally requires multidisciplinary teams in specialized referral centers. When this consideration is combined with the existing shortage of neurosurgeons across the country, academic neurosurgery departments must logically focus on how best to allocate resources between "routine" clinical services and research objectives. We suggest here that new relationships may be required between university centers and community health care providers. Restructuring of the neurosurgical workforce may be necessary if academic neurosurgery is to develop as a specialty of comprehensive expertise in the challenging neurological disease entities that are its research objectives., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy and the treatment outcome of tumor patients being treated stereotactically with a miniature X-ray generator (Photon Radiosurgery System, PRS)., Methods and Materials: Thirty-five patients with histologically diagnosed cerebral metastases were treated with a single fraction of stereotactic interstitial irradiation (median, 18 Gy). Clinical and neuroimaging evaluation were assessed at 2-, 6-, and 12-week intervals postoperatively and every 3 months thereafter. Survival, local control, and distant and overall brain freedom from progression were obtained using the Kaplan-Meier method., Results: Median survival was 7.37 months and the actuarial survival rates at 6 and 12 months were 60.0% and 34.3%, respectively. Acute complications on six patients were associated with shorter survival. Local tumor control at the initial stage and at the last follow-up were 82% and 50%. Eighteen patients (53%) developed distant brain metastases after treatment. At 1 year, the local control rate and distant and overall brain freedom from progression were 33.0%, 43.3%, and 14.7%, respectively. A shorter local tumor control was observed by PRS treatment of a recurrent tumor and by irregular tumor configuration., Conclusions: Interstitial radiosurgery with the PRS requires continued investigation. It allows for an immediate and potentially cost-efficient treatment for patients with singular, small (

Although intracerebral metastases of malignant melanoma are common, those located in the sellar region and within the pontocerebellar area are extremely rare. Furthermore, to our knowledge, there is no report about melanoma metastasis to the epiphysis published so far. We report here a 46-year-old patient who had metastatic lesions in the sellar region, cerebellopontine area and epiphysial gland, preceded by a primary melanoma at her left shoulder. The diagnosis of sellar metastasis was confirmed histopathologically following a stereotactic biopsy. The patient received whole-brain irradiation therapy combined with chemotherapy. After 10 months, she died from a severe hemorrhage in the cerebellopontine angle. Autopsy findings confirmed melanoma metastases both in the cerebellopontine angle and additionally in the epiphysial gland. To our knowledge, this is the first case of multiple intracranial melanoma metastases including the suprasellar region, the pontocerebellar and epiphysial area.

Here we report a 63-year-old woman with primary cervical dystonia (CD) whose symptoms subsided for more than 30 years following a unilateral stereotactic subthalamotomy contralateral to the overactive left sternocleidomastoid muscle but then gradually recurred over a period of several months. The aim of the present study was to correlate the topography of the stereotactic lesion with the long lasting therapeutic effect. High-resolution magnetic resonance imaging and subsequent stereotactic analysis were performed to determine the anatomical localization of the lesion. The primary coagulation focus comprised the posterior subthalamic white matter in the prelemniscal radiation and field H of Forel. Neighboring structures were implicated to various extents. It is suggested that the posterior subthalamic area, with its abundance of interconnecting fibers and related nuclei, represents an effective target for the neurosurgical treatment of CD that may be explored further with deep brain stimulation., ((c) 2007 Movement Disorder Society.)

Objective: To analyze the role of radiosurgery alone in patients with brain metastases. There were three specific study goals: 1) to determine whether survival of patients selected for this treatment approach can be predicted successfully by use of the recursive partitioning analysis classification defined by the Radiation Therapy Oncology Group; 2) to evaluate local control; and 3) to identify risk factors of cerebral failure., Methods: A total of 101 patients with Karnofsky Performance Scale scores of at least 50 and up to three brain metastases, each 3 cm or less in maximum diameter, were treated with radiosurgery alone. Survival, local control, distant brain freedom from progression (FFP), and overall brain FFP were evaluated according the method of Kaplan and Meier. Risk factors for survival and overall brain FFP were analyzed using the Cox model., Results: Median survival was 13.4 months, 9.3 months, and 1.5 months for patients in recursive partitioning analysis Classes 1, 2, and 3, respectively (P < 0.0001). At 1 year, local control, distant brain FFP, and overall brain FFP were 91, 53, and 51%, respectively. An interval greater than 2 years between diagnosis of the primary tumor and diagnosis of brain metastases and the presence of a single brain metastasis were associated with significantly higher overall brain FFP., Conclusion: Recursive partitioning analysis classification successfully predicted survival. Radiosurgery alone yielded high local control. Overall brain FFP was highest in patients with an interval greater than 2 years between primary diagnosis and diagnosis of a single brain metastasis.

Purpose: The combined loss of genetic material on chromosomes 1p and 19q is strongly associated with favorable outcome in patients with WHO grade 3 anaplastic oligodendroglial tumors. The prognostic value of 1p/19q loss in WHO grade 2 oligodendroglial tumors is less well defined. Importantly, the possible effect of combined 1p/19q loss has not been studied in patients who were not treated with radiotherapy or chemotherapy., Experimental Design: Seventy-six patients with oligodendroglioma (n = 33), oligoastrocytoma (n = 30), anaplastic oligodendroglioma (n = 6), or anaplastic oligoastrocytoma (n = 7) were identified who had not received radiotherapy or chemotherapy after their first operation until the end of follow-up or until the first progression and had tissue for 1p/19q status available. 1p/19q status was assessed by multiplex ligation-dependent probe amplification., Results: After a median follow-up of 3.8 years, progressive disease was documented in 34 patients. The estimated median progression-free survival was 4.6 years. Fifty-eight of the 76 patients had a combined loss of 1p and 19q. The absence or presence of combined 1p/19q loss was not prognostic for progression-free survival using multivariate adjustment for histology, extent of resection, and gender., Conclusions: Combined 1p/19q loss is not a sensitive prognostic biomarker in patients with oligodendroglial tumors who do not receive radiotherapy or chemotherapy. The gene products lost as a consequence of this codeletion may include mediators of resistance to genotoxic therapies. Alternatively, 1p/19q loss might be an early oncogenic lesion promoting the formation of glial neoplasms, which retain high sensitivity to genotoxic stress.

Background: Advances in the treatment of medulloblastoma have largely been attributed to the introduction of chemotherapy, although Phase III trials have shown advantages for chemotherapy only in subgroups. Because the efficacy of chemotherapy depends on tumor vascularization, the vascular physiology of human medulloblastomas was evaluated., Methods: Seven patients with histologically proven medulloblastomas underwent measurements of capillary permeability and vascular plasma volume using contrast-enhanced dynamic computer tomography. Regional blood flow was measured in 5 patients using xenon computed tomography (CT)., Results: The capillary permeability-surface product for water-soluble compounds ranged from 1.7 +/- 5.5 to 17.6 +/- 12.3 muL/g/min with a mean of 10.5 +/- 6.3 microL/g/min. The vascular plasma volume ranged from 0.02 +/- 0.021 to 0.045 +/- 0.049 mL/g with a mean of 0.03 +/- 0.01 mL/g. The efflux rate ranged from 0.012 +/- 0.007 to 0.065 +/- 0.064 1/min with a mean of 0.039 +/- 0.020 1/min. Regional tumoral blood flow showed a mean of 19.86 +/- 6.8 mL/100g/min as compared with normal cerebellum with 45.4 +/- 12.03 mL/100g/min (P < .005)., Conclusions: The current study demonstrated a low capillary permeability and blood flow in medulloblastomas that could explain the limited response rates of partially resected tumors even after aggressive high-dose chemotherapy, as recently reported., ((c) 2006 American Cancer Society.)

Background: We present outcome data of a cohort of 164 immunocompetent PCNSL patients uniformly diagnosed at a single center for stereotactic neurosurgery, and evaluate the acceptance and impact of combination radiotherapy (RT) and chemotherapy (CHT) with high-dose methotrexate (HD-MTX) over time., Method: We assessed choice of treatment and patient survival in a series of 164 PCNSL cases diagnosed from 1989 to 2001, and performed a re-evaluation of histopathology and pre-operative clinical data., Findings: From 1989 to 1993, RT was the predominant therapy, and additional CHT did not improve survival. After 1994, the use of combination CHT/RT increased continuously, consistently contained MTX, and was associated with longer survival than RT only: median survival was 14 months after CHT/RT (2-year survival 35.7%) and 10 months (2-year survival 26.2%) after RT only (not significant). Overall median survival remained poor, increasing from six (1989-1993) to nine months (1994-2001) (p = 0.008). Survival was variable, with a few patients surviving >4 years after diagnosis in the CHT/RT as well as in the RT only group., Conclusions: Despite considerable improvement of PCNSL therapy, the overall benefit of combined CHT/RT versus RT only was lower than that expected from previous phase II clinical trials. The striking variability of survival in either treatment group may suggest a yet undefined biological heterogeneity of PCNSL, which may also include a more aggressive PCNSL subtype in the group of patients with rapidly progressive disease and not eligible for standard therapy.

Diffuse astrocytomas, oligodendrogliomas, and oligoastrocytomas (mixed gliomas) WHO grade II, pleomorphic xanthoastrocytomas (PXAs), pilocytic astrocytomas, and subependymal giant cell astrocytomas (SEGAs) are often referred to as low-grade gliomas. WHO grade II astrocytomas, oligodendrogliomas, and mixed gliomas are characterized by their infiltrative growth, frequent tumor recurrence and a more than 50 % risk for malignant progression. In contrast, pilocytic astrocytomas and SEGAs are circumscribed tumors amenable to a (radio)surgical cure. There are few universally accepted guidelines for the treatment of low-grade gliomas. In this review, three neurosurgeons, a neurologist, a neuropathologist, and a radiation oncologist discuss some of the difficult issues surrounding the diagnosis and treatment of low-grade gliomas from their individual points of view (i. e., classification and neuropathology, MR imaging, stereotactic biopsy, microsurgery, interstitial radiotherapy/brachytherapy, radiotherapy, wait and see strategy).

Background: Detailed long-term outcome data are not available for adult patients with World Health Organization (WHO) Grade 2 astrocytoma or oligoastrocytoma., Methods: A previously published short-term data set of 239 adult patients with circumscribed de novo supratentorial astrocytoma (187 patients) and oligoastrocytoma (52 patients) treated with interstitial iodine-125 ((125)I) radiosurgery as primary treatment (1979-1992) was revisited. Survival, progression-free survival, functionally independent survival, postrecurrence survival, and time to malignant transformation were estimated with the Kaplan-Meier method. Prognostic factors were obtained from the Cox multivariate proportional hazards model., Results: Five-, 10-, and 15-year survival was 56%, 37%, and 26%, respectively (median follow-up, 10.3 yrs). Progression-free survival was 45%, 21%, and 14%, respectively. The corresponding malignant transformation rates were 33%, 54%, and 67%. No leveling off of the Kaplan-Meier curves could be observed for any of the chosen endpoints. Age > 50 years, a tumor volume > 20 mL, and/or a Karnofsky score < or = 80 were associated with decreased survival or progression-free survival. Age > 35 years and/or a tumor volume > 20 mL increased risk of malignant transformation. Prognostic factors determined subsets of patients with 10-year survival ranging from as low as 6% to as high as 55% and progression-free survival ranging 1-31%., Conclusions: Long-term tumor stabilization is rare. As outcome is mainly determined by treatment-independent factors, minimization of any treatment-related risk must be considered essential., ((c) 2006 American Cancer Society.)

To evaluate whether the chemosensitivity of primary central nervous system lymphomas to water-soluble drugs could result from improved drug delivery, we quantitatively assessed pharmacokinetic factors in seven patients. The capillary permeability surface product was found to be significantly increased in central nervous system lymphomas compared with glioblastoma multiforme, medulloblastomas, and metastases. Tumoral blood flow was significantly greater than in normal white matter. Our results suggest favorable pharmacokinetics to water- and lipid-soluble drugs in primary central nervous system lymphomas.

Objective: To present long-term results after interstitial iodine-125 irradiation of adult patients with de-novo World Health Organization (WHO) Grade II astrocytomas and oligoastrocytomas of the insula of Reil with special respect to the treatment-related risk., Methods: 55 consecutively treated patients (from 1979 to 1992) with circumscribed tumors with a diameter < 5 cm (astrocytomas: 46 patients, oligoastrocytomas: 9 patients) were included. The reference dose-calculated to the outer boundary of the tumor-was in the range of 60-100 Gy and the dose rate was low (< 10 cGy/h). Progression-free survival, risk of malignant transformation, survival, and the incidence of radiogenic complications were estimated by the Kaplan-Meier method. Prognostic factors were obtained from the Cox-model., Results: Median follow up for the survivors was > 10 years. 5-year (10-year) progression-free survival was 40.7 % (20.2 %), and 5-year (10-year) survival 54.6 % (28.4 %). Malignant transformation occurred in 42.4 % after 5 years. Neither of the Kaplan-Meier curves showed a leveling off over time. Transient (progressive) radiogenic complications were observed in 13 [4] patients (one-year overall complication rate: 18%), and were significantly associated with a tumor diameter >3.5 cm (p<0.001). No long term side-effects were detected and delayed external beam irradiation (in case of tumor progression) did not enhance the risk. Tumor enhancement on CT was the only unfavorable predictor for survival., Conclusion: A limited overall prognosis for adult patients with insular WHO grade II astrocytomas and oligoastrocytomas was detected. Interstitial I-125 irradiation offers a minimal-invasive and low-risk treatment option for circumscribed tumors with a diameter < 3.5 cm. Larger tumors require further evaluation for optimal treatment.

Holmes tremor is caused by structural lesions in the perirubral area of the midbrain. Patients often present with associated symptoms such as dystonia and paresis, which are usually refractory to medical therapy. Here, the authors describe two patients in whom both tremor and associated dystonia improved markedly following unilateral stimulation of the thalamic nucleus ventralis intermedius.

Objective: To analyze the role of radiosurgery alone in patients with brain metastases. There were three specific study goals: 1) to determine whether survival of patients selected for this treatment approach can be predicted successfully by use of the recursive partitioning analysis classification defined by the Radiation Therapy Oncology Group; 2) to evaluate local control; and 3) to identify risk factors of cerebral failure., Methods: A total of 101 patients with Karnofsky Performance Scale scores of at least 50 and up to three brain metastases, each 3 cm or less in maximum diameter, were treated with radiosurgery alone. Survival, local control, distant brain freedom from progression (FFP), and overall brain FFP were evaluated according the method of Kaplan and Meier. Risk factors for survival and overall brain FFP were analyzed using the Cox model., Results: Median survival was 13.4 months, 9.3 months, and 1.5 months for patients in recursive partitioning analysis Classes 1, 2, and 3, respectively (P < 0.0001). At 1 year, local control, distant brain FFP, and overall brain FFP were 91, 53, and 51%, respectively. An interval greater than 2 years between diagnosis of the primary tumor and diagnosis of brain metastases and the presence of a single brain metastasis were associated with significantly higher overall brain FFP., Conclusion: Recursive partitioning analysis classification successfully predicted survival. Radiosurgery alone yielded high local control. Overall brain FFP was highest in patients with an interval greater than 2 years between primary diagnosis and diagnosis of a single brain metastasis.