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Objective: Since 2009, we have performed skin augmentation using a Gore-Tex patch as a last-resort measure to reduce intracranial pressure (ICP) in uncontrollable brain swelling during decompressive craniectomy (DC). Here, we report our experience and outcome in a consecutive series of patients undergoing DC with skin augmentation (DC+S). Methods: In 2009–2015, a prospective database was created registering all patients who underwent DC+S when ICP increased >25 mm Hg while approximating the skin edges after DC (or when closing the skin was impossible because of uncontrollable brain swelling in patients without an ICP monitoring catheter). Patients' baseline characteristics and 1-year outcome were compared with patients undergoing DC without the need of skin augmentation in the same time frame. Outcome according to the Glasgow Outcome Scale (GOS) was dichotomized into favorable (GOS score 4–5) and unfavorable (GOS 1–3). Results: Of a total of 180 consecutive patients with DC, 20 (11%) underwent DC+S. Four (20%) survived favorably, 2 (10%) unfavorably, and 14 (70%) died (compared with 36%, 22%, and 42%, respectively, in patients with standard DC). Four of 7 patients in whom DC+S was performed ≥24 hours after injury or at second surgery survived favorably, versus none of the 13 patients in whom DC+S was performed

BACKGROUND: Hypothalamic obesity (HO) is a major concern in patients treated for craniopharyngioma (CP). The influence of degree of resection on development of HO, event-free survival (EFS), and neuroendocrine sequelae is an issue of debate.PROCEDURE: A retrospective cohort consisting of all CP patients treated between 2002 and 2012 in two university hospitals was identified. Multivariable logistic regression was used to study the associations between preoperative BMI, age at diagnosis, tumor volume, performed surgical resection, and presence of HO at follow-up.RESULTS: Thirty-five patients (21 children and 14 adults) were included. Median follow-up time was 35.6 months (4.1-114.7). Four patients were obese at diagnosis. HO was present in 19 (54.3%) patients at last follow-up of whom eight were morbidly obese. Thirteen (37.1%) patients underwent partial resection (PR) and 22 (62.9%) gross total resection (GTR). GTR was related to HO (OR 9.19, 95% CI 1.43-59.01), but for morbid HO, obesity at diagnosis was the only risk factor (OR 12.92, 95% CI 1.05-158.73). EFS in patients after GTR was 86%, compared to 42% after PR (log-rank 9.2, P = 0.003). Adjuvant radiotherapy after PR improved EFS (log-rank 8.2, P = 0.004). Panhypopituitarism, present in 15 patients, was mainly seen after GTR.CONCLUSIONS: HO is less frequent after PR than after GTR, but PR cannot always prevent the development of morbid obesity in patients with obesity at diagnosis. PR reduces the occurrence of panhypopituitarism. When developing a treatment algorithm, all these factors should be considered.

Background The ability to preoperatively predict postoperative complication risks is valuable for individual counseling and (post)operative planning, e.g. to select low-risk patients eligible for short stay surgery or those with higher risks requiring special attention. These risks however, are not well established in pituitary surgery. Methods We conducted a systematic review of associations between preoperative characteristics and postoperative complications of endoscopic transsphenoidal surgery according to the PRISMA guidelines. Risk of bias was assessed through the QUIPS tool. Results In total 23 articles were included, containing 5491 patients (96% pituitary adenoma). There was a wide variety regarding the nature and number of risk factors, definitions, measurement and statistics employed, and overall quality of mainly retrospective studies was low. Consistent significant associations were older age for complications in general, and intraventricular extension for cerebrospinal fluid (CSF) leaks. Associations identified in some but not all studies were younger age, increased BMI, female gender, and learning curve for CSF leaks; increased tumor size for complications in general; and Rathke’s cleft cysts for diabetes insipidus. Mortality (incidence rate 1%) was not addressed as a risk factor. Conclusion Based on current literature, of low to medium quality, it is not possible to comprehensively quantify risk factors for complications. Nevertheless, older age and intraventricular extension were associated with increased postoperative complications. Future research should aim at prospective data collection, reporting of outcomes, and uniformity of definitions. Only then a proper risk analysis can be performed for endoscopic pituitary surgery. Electronic supplementary material The online version of this article (doi:10.1007/s11102-017-0839-1) contains supplementary material, which is available to authorized users.

Object In the past decade, the endonasal transsphenoidal approach (eTSA) has become an alternative to the microsurgical transcranial approach (mTCA) for tuberculum sellae meningiomas (TSMs) and olfactory groove meningiomas (OGMs). The aim of this meta-analysis was to evaluate which approach offered the best surgical outcomes. Methods A systematic review of the literature from 2004 and meta-analysis were conducted in accordance with the PRISMA guidelines. Pooled incidence was calculated for gross total resection (GTR), visual improvement, cerebrospinal fluid (CSF) leak, intraoperative arterial injury, and mortality, comparing eTSA and mTCA, with p-interaction values. Results Of 1684 studies, 64 case series were included in the meta-analysis. Using the fixed-effects model, the GTR rate was significantly higher among mTCA patients for OGM (eTSA: 70.9% vs. mTCA: 88.5%, p-interaction

After treatment for a non-functioning pituitary adenoma (NFA) health-related quality of life (HR-QoL) improves considerably. However, the literature about the normalization of HR-QoL after treatment is inconclusive. Some researchers described a persistently decreased HR-QoL compared to reference data, while others did not. Considering this variety in observed HR-QoL outcomes, the aim of the present review was to provide a literature overview of health outcomes in patients with a NFA, using a conceptual HR-QoL model. A concrete conceptualization of the health outcomes of patients with a NFA can be helpful to understand the observed variety in HR-QoL outcomes and to improve clinical care and guidance of these patients. For this conceptualization, the Wilson and Cleary model was used. This model has a biopsychosocial character and has been validated in several patient populations. In the present review, health outcomes of patients with a NFA were described at each stage of the model e.g. biological and physiological variables, symptom status, functional status, general health perceptions and overall HR-QoL. The Wilson-Cleary model elucidates that elements at each stage of the model can contribute to the impairment in HR-QoL of patients with a NFA, which explains the reported variety in the literature. Furthermore, by applying the model, potential interventions targeting these elements can be identified. While optimal biomedical treatment has always been the focus, it is clearly not sufficient for good HR-QoL in patients with a NFA. Further improvement of HR-QoL should be supported by a pituitary specific care trajectory, including psychosocial care (e.g. self-management training), to beneficially affect characteristics of the patient and the (healthcare) environment, with the utmost goal to optimize HR-QoL in patients after treatment.

Background The clinical relevance of Health-Related Quality of Life (HRQoL) in meningioma patients has been increasingly acknowledged in recent years. Various questionnaires have been used. However, almost none of these questionnaires has been particularly developed for and/or validated in this patient group. Therefore, the aim of this study was to assess the relevance and comprehensiveness of existing HRQoL questionnaires used in meningioma research and to assess the agreement between patients and health care professionals (HCPs) on the most relevant and important HRQoL issues. Methods A systematic literature search, following the PRISMA statement, was conducted to identify all HRQoL questionnaires used in meningioma research. Semi-structured interviews were organized with patients and HCPs to (1) assess the relevance of all issues covered by the questionnaires (score 0–3: not relevant–highly relevant), (2) assess the ten most important issues, and (3) identify new relevant HRQoL issues. Results Fourteen different questionnaires were found in the literature, comprising 140 unique issues. Interviews were conducted with 20 patients (median age 57, 71% female) and 10 HCPs (4 neurosurgeons, 2 neurologists, 2 radiotherapists, 1 rehabilitation specialist, 1 neuropsychologist; median experience 13 years). Meningioma patients rated 17–80% of the issues in each of the questionnaires as relevant, HCPs 90–100%. Patients and HCPs agreed on the relevance of only 49 issues (35%, Cohen’s kappa: 0.027). Both patients and HCPs considered lack of energy the most important issue. Patients and HCPs suggested five additional relevant issues not covered by current HRQoL questionnaires. Conclusions Existing HRQoL questionnaires currently used in meningioma patients do not fully cover all relevant issues to these patients. Agreement between patients and HCPs on the relevance of issues was poor. Both findings support the need to develop and validate a meningioma-specific HRQoL questionnaire. Electronic supplementary material The online version of this article (10.1007/s00701-017-3332-8) contains supplementary material, which is available to authorized users.

Purpose Patients with pituitary adenomas often present with visual deficits. While the aim of endoscopic endonasal transsphenoidal surgery (EETS) is to improve these deficits, permanent worsening is a possible outcome. The aim of this meta-analysis was to evaluate the effect of EETS for pituitary adenomas on visual outcomes. Methods A meta-analysis was conducted according to the PRISMA guidelines. Pooled prevalence was calculated for complete recovery, improvement, and deterioration of visual field deficits, visual acuity and unspecified visual function in fixed- and random-effect models, including assessment of heterogeneity (I2) and publication bias (Begg’s test). Results Out of 2636 articles, 35 case series were included in the meta-analysis. Results are described for fixed-effect models. For patients with impaired visual acuity, only one study reported complete recovery (27.2%). Pooled prevalence for improvement was 67.5% (95% CI = 59.1–75.0%), but with considerable heterogeneity (I2: 86.0%), and 4.50% (95% CI = 1.80–10.8%) for patients experiencing deterioration. For patients with visual field deficits, the prevalence was 40.4% (95% CI = 34.8–46.3%) for complete recovery, 80.8% (95% CI = 77.7–83.6%) for improvement, and 2.3% (95% CI = 1.1–4.7%) for deterioration. For the unspecified visual outcomes, pooled prevalence of complete recovery was 32.9% (95% CI: 28.5–37.7%), but with considerable heterogeneity (I2 = 84.2%). The prevalence was 80.9% (95% CI = 77.9–83.6) for improvement and 2.00% (95% CI = 1.10–3.40%) for deterioration. Random-effect models yielded similar results. Publication bias was non-significant for all the outcomes. Conclusion While visual deficits improved after EETS in the majority of patients, complete recovery was only achieved in less than half of the patients and some patients even suffered from visual deterioration. Electronic supplementary material The online version of this article (doi:10.1007/s11102-017-0815-9) contains supplementary material, which is available to authorized users.

A clear visualization of the operative field is of critical importance in endoscopic surgery. During surgery the endoscope lens can get fouled by body fluids (eg, blood), ground substance, rinsing fluid, bone dust, or smoke plumes, resulting in visual impairment. As a result, surgeons spend part of the procedure on intermittent cleaning of the endoscope lens. Current cleaning methods that rely on manual wiping or a lens irrigation system are still far from ideal, leading to longer procedure times, dirtying of the surgical site, and reduced visual acuity, potentially reducing patient safety. With the goal of finding a solution to these issues, a literature review was conducted to identify and categorize existing techniques capable of achieving optically clean surfaces, and to show which techniques can potentially be implemented in surgical practice. The review found that the most promising method for achieving surface cleanliness consists of a hybrid solution, namely, that of a hydrophilic or hydrophobic coating on the endoscope lens and the use of the existing lens irrigation system.

While surgical and radiotherapeutic improvements increased life expectancy of meningioma patients, little is known about these patients' health-related quality of life (HRQoL). Therefore, the objectives of this systematic review were to assess HRQoL in meningioma patients, the methodological quality of the used questionnaires (COSMIN criteria), and the reporting level of patient-reported outcomes (PROs) in the included studies (International Society of Quality of Life Research criteria). Nineteen articles met our inclusion criteria. HRQoL was measured with 13 different questionnaires, 3 validated in meningioma patients. According to our predefined cutoff, HRQoL data were reported sufficiently in 5 out of 19 studies. Both findings hamper interpretation of the PRO results. In general, meningioma patients reported clinically worse HRQoL than healthy controls. Although meningioma patients had better HRQoL than glioma patients, this difference was not clinically relevant. Radiotherapy seemed to improve some domains of HRQoL in the short term, while HRQoL decreased to pre-radiotherapy levels in the long term. Tumor resection increased HRQoL, but long-term follow-up showed persistent reduced HRQoL compared with healthy controls. These results suggest an impaired HRQoL in meningioma patients, even years after anti-tumor treatment. Results of this systematic review warrant high quality prospective studies, better instruments to assess HRQoL, and improved level of reporting for this group of patients.

BACKGROUND: Previous studies reported that meningioma patients have impaired health-related quality of life (HRQoL) and cognitive function up to 5 years after intervention. We aimed to assess the long-term disease burden of meningioma patients. METHODS: In this multicenter cross-sectional study, intracranial meningioma patients at a median of 9.9 years after anti-tumor therapy were included. HRQoL was measured with the SF-36 and EORTC QLQ-BN20, anxiety and depression with the Hospital Anxiety and Depression Scale (11/21 points is indicative for probable anxiety or depression), and objective cognitive functioning on six domains (z-score< -1.5 is defined as a clinically relevant deficit). Generalized linear models were used to compare meningioma patients with healthy controls, corrected for age, sex, educational level and comorbidities, and one-sample t-tests to compare meningioma patients with data of newly diagnosed glioblastoma. Patient recruitment and data collection is still in progress. RESULTS: 164 meningioma patients were included (mean age:63.9 years, WHO grade I:91.7%, surgery:89.2%, radiotherapy:14.6%). Compared with 110 controls, meningioma patients had worse HRQoL scores on 4/10 SF-36 scales/component scores: role limitations due to physical problems and emotional problems, social functioning, and the mental component score (range mean difference: 4.4–13.8, all p0.05), and better on all other items/scales. More patients suffered from probable anxiety (14.3%) and depression (7.5%) than controls (anxiety: 3.7%, p=0.015; depression: 7.5%, p=0.011). Clinically relevant cognitive deficits were found in executive function (10.9%), verbal memory (19.4%), working memory (13.4%), attention (10.3%), information processing (25.0%) and psychomotor speed (14.4%). CONCLUSION: Almost 10 years after the last anti-tumor treatment, meningioma disease burden is still significant. A considerable number of patients have impaired HRQoL, suffer from cognitive deficits and report high levels of anxiety and depression.

The availability of various first-line treatment modalities for acromegaly and evolving surgical techniques emphasize the need for accurately defined predictors of surgical outcome. We retrospectively analysed the outcome of 30 patients with acromegaly after initial endoscopic transsphenoidal surgery in two university hospitals from 2001 until 2009, and reviewed comparable literature investigating predictive tumor characteristics. Medical records were monitored for patient characteristics. Each pituitary magnetic resonance imaging (MRI) scan was revised independently by two neuroradiologists using a standardised analysis form to record distinctive predefined tumor characteristics. All characteristics were independently analysed as predictors for persistent disease, and a multivariable predictive model was created. Literature from 2000 onwards was searched for studies describing tumor characteristics predictive for surgical outcome. The cohort consisted of 27 macroadenomas with 90 % demonstrating signs of parasellar extension. The surgical cure rate overall was 30 %. Independently, next to male sex and increasing tumor size, infrasellar and parasellar extension based on MRI staging tended to increase the risk of persistent disease. In a multivariable analysis, sex and parasellar extension of the tumor were demonstrated to be the variables allowing for the best fitted predictive model for persistent disease. Earlier studies on preoperative tumor characteristics showed comparable results, although these were based on several different tumor classification systems. This retrospective study demonstrates that accurately defined tumor characteristics based on imaging, especially for cavernous sinus invasion, can be helpful in predicting surgical outcome. Comparative studies on different treatment modalities are essential for clinical practice within the scope of re-evaluation of the role of surgery in GH-secreting adenomas. © 2012 The Author(s).

Background Quality of life (QoL) in patients with acromegaly is reduced irrespective of disease state. The contributions of multifactorial determinants of QoL in several disease stages are presently not well known. Objective To systematically review predictors of QoL in acromegalic patients. Methods Main databases were systematically searched using predefined search terms for potentially relevant articles up to January 2017. Inclusion criteria included separate acromegaly cohort, non-hereditary acromegaly, QoL as study parameter with clearly described method of measurement and quantitative results, N ≥ 10 patients, article in English and adult patients only. Data extraction was performed by two independent reviewers; studies were included using the PRISMA flow diagram. Results We identified 1,162 studies; 51 studies met the inclusion criteria: 31 cross-sectional observational studies [mean AcroQoL score 62.7 (range 46.6–87.0, n = 1,597)], 9 had a longitudinal component [mean baseline AcroQoL score 61.4 (range 54.3–69.0, n = 386)], and 15 were intervention studies [mean baseline AcroQoL score 58.6 (range 52.2–75.3, n = 521)]. Disease-activity reflected by biochemical control measures yielded mixed, and therefore inconclusive results with respect to their effect on QoL. Addition of pegvisomant to somatostatin analogs and start of lanreotide autogel resulted in improvement in QoL. Data from intervention studies on other treatment modalities were too limited to draw conclusions on the effects of these modalities on QoL. Interestingly, higher BMI and greater degree of depression showed consistently negative associations with QoL. Hypopituitarism was not significantly correlated with QoL in acromegaly. Conclusion At present, there is insufficient published data to support that biochemical control, or treatment of acromegaly in general, is associated with improved QoL. Studies with somatostatin receptor ligand treatment, i.e., particularly lanreotide autogel and pegvisomant have shown improved QoL, but consensus on the correlation with biochemical control is missing. Longitudinal studies investigating predictors in treatment-naive patients and their follow-up after therapeutic interventions are lacking but are urgently needed. Other factors, i.e., depression and obesity were identified from cross-sectional cohort studies as consistent factors associated with poor QoL. Perhaps treatment strategies of acromegaly patients should not only focus on normalizing biochemical markers but emphasize improvement of QoL by alternative interventions such as psychosocial or weight lowering interventions.

Glioblastoma (GBM) is a highly aggressive brain tumour, where patients respond poorly to radiotherapy and exhibit dismal survival outcomes. The mechanisms of radioresistance are not completely understood. However, cancer cells with an immature stem-like phenotype are hypothesised to play a role in radioresistance. Since the progenitor marker neuron-glial-2 (NG2) has been shown to regulate several aspects of GBM progression in experimental systems, we hypothesised that its expression would influence the survival of GBM patients. Quantification of NG2 expression in 74 GBM biopsies from newly diagnosed and untreated patients revealed that 50% express high NG2 levels on tumour cells and associated vessels, being associated with significantly shorter survival. This effect was independent of age at diagnosis, treatment received and hypermethylation of the O6-methylguanine methyltransferase (MGMT) DNA repair gene promoter. NG2 was frequently co-expressed with nestin and vimentin but rarely with CD133 and the NG2 positive tumour cells harboured genetic aberrations typical for GBM. 2D proteomics of 11 randomly selected biopsies revealed upregulation of an antioxidant, peroxiredoxin-1 (PRDX-1), in the shortest surviving patients. Expression of PRDX-1 was associated with significantly reduced products of oxidative stress. Furthermore, NG2 expressing GBM cells showed resistance to ionising radiation (IR), rapidly recognised DNA damage and effectuated cell cycle checkpoint signalling. PRDX-1 knockdown transiently slowed tumour growth rates and sensitised them to IR in vivo. Our data establish NG2 as an important prognostic factor for GBM patient survival, by mediating resistance to radiotherapy through induction of ROS scavenging enzymes and preferential DNA damage signalling. Electronic supplementary material The online version of this article (doi:10.1007/s00401-011-0867-2) contains supplementary material, which is available to authorized users.

BACKGROUND: Various studies in oncological/neurological patients highlight that informal caregivers suffer from a significant disease burden. We aimed to assess the meningioma caregiver burden, and its effects on caregivers health-related quality of life (HRQoL), and levels of anxiety and depression. METHODS: In a multicentre cross-sectional study informal caregivers of intracranial meningioma patients at a median of 10 years after their last anti-tumour therapy were included. Informal caregivers were family members or close friends and completed the caregiver disease burden scale, SF-36 (HRQoL) and the Hospital Anxiety and Depression Scale. Caregiver burden was assessed as an independent determinant for caregivers HRQoL, and levels of anxiety and depression with multivariable analysis correcting for relevant confounders. Participant recruitment is still in progress. RESULTS: 110 informal caregivers were included (mean age: 64.5, female: 37.2%). Informal caregivers reported any caregiver burden in 35.2% of cases, and clinically relevant burden in 15.7%. More specifically, 20.4% of caregivers suffered from stress, 11.2% from social isolation, 13.0% from feelings of disappointment, 21.0% from emotional problems, and 12.0% from environmental factors complicating the care for the patient. The total caregiver burden score was significantly associated with decreased HRQoL on 6/8 scales and 2/2 component scores: physical function (=-6.53, p=0.071), role limitation due to physical problems (=-13.62, p=0.041), bodily pain (=-13.11, p=0.014), social function (=-11.87, p=0.001), mental health (=-14.32, p

BACKGROUND: Meningioma patients suffer from short- and long-term neurological sequelae and impaired health-related quality of life (HRQoL). However, it is unknown how these impairments affect patients’ work productivity and healthcare consumption on the long-term. MATERIAL AND METHODS: In a multicentre cross-sectional study intracranial meningioma patients of working age (18–67 years) at a median of 10.0 years after anti-tumour therapy were included. Patients completed a validated questionnaire on work productivity (SF-HLQ), and a study-specific questionnaire on healthcare consumption. One-sample t-test was used to compare meningioma patients with normative data of the Dutch population. Generalised linear models were used to compare meningioma patients with a control population, corrected for: age, sex, educational level and comorbidity. Patient recruitment and data collection is still in progress. RESULTS: 106 meningioma patients were included (mean age: 57.7 years, WHO grade I: 93.5%, surgery: 94.2%, radiotherapy: 17.5%). Meningioma patients had a paid job in 48.1% of cases, compared with 71.8% of the Dutch population of working age (p

Background The complexity of temporoparietal anatomy is compounded by inconsistent nomenclature. Objective To provide a comprehensive review of the variations in terminology and anatomic descriptions of the temporoparietal soft tissue layers, with the aim of improving learning and communication across surgical disciplines. Methods MEDLINE (1950-2009) searches were conducted for anatomic studies of the temporoparietal region, and for studies describing temporoparietal anatomy in the context of surgical techniques. Results Sixty-nine articles were included in the review. Naming of the soft tissue layers of the temporoparietal region was inconsistent both within and across surgical disciplines, with several terms utilized for the same layer and occasionally the same term applied to different layers. Studies also varied in their description of the vascular, neural, and soft tissue architecture of the temporoparietal region. Conclusion A uniform, descriptive nomenclature is paramount to facilitating surgical education and interpreting future studies. A naming system based on the Terminologica Anatomica is proposed in this review. From superficial to deep, the proposed terms for the soft tissue layers of the temporoparietal region include: temporoparietal fascia, loose areolar tissue plane, superficial leaflet of temporal fascia, fat pad of temporal fascia, deep leaflet of temporal fascia, fat pad deep to temporal fascia, temporalis or temporal muscle, and pericranium.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. The identification of 'cancer stem cells' (CSC) has shed new light on the potential mechanism of therapy resistance of these tumors. Because these cells appear to be more resistant to conventional treatments, they are thought to drive tumor regrowth after therapy. Therefore, novel therapeutic approaches that target these cells are needed. Tumor cells interact with their microenvironment. It has been reported that close contact between CSCs and tumor microvascular endothelium in GBM is important for CSCs to preserve their undifferentiated state and self-renewal ability. However, our understanding of this interaction is still rudimentary. This is in part due to a lack of suitable in vitro models that accurately represent the in vivo situation. Therefore, we set up a co-culture system consisting of primary brain tumor microvascular endothelial cells (tMVECs) and glioma propagating cells (GPCs) derived from biopsies of GBM patients. We found that tMVECs support the growth of GPCs resulting in higher proliferation rates comparing to GPCs cultured alone. This effect was dependent on direct contact between the 2 cell types. In contrast to GPCs, the FCS-cultured cell line U87 was stimulated by culturing on tMVEC-derived ECM alone, suggesting that both cell types interact different with their microenvironment. Together, these results demonstrate the feasibility and utility of our system to model the interaction of GPCs with their microenvironment. Identification of molecules that mediate this interaction could provide novel targets for directed therapy for GBM. (c) 2009 UICC

Contains fulltext : 81038.pdf (Publisher’s version ) (Closed access) AIM OF THE STUDY: Tumour angiogenesis and invasion are key features of glioblastoma multiforme (GBM). Angiogenesis inhibitors increase progression-free survival (PFS) of recurrent GBM patients. VEGF inhibition controls the bulk tumour growth by inhibition of angiogenesis, but does not inhibit the invasive tumour component. We investigated if invasive tumour growth can be controlled by combining anti-VEGF treatment with irradiation of tumour plus surrounding brain in an orthotopic murine model for GBM. METHODS AND MATERIALS: GBM cell line U251-NG2 was inoculated through a guide screw in the right frontal lobe of 53 athymic nude mice. Pegaptanib (a slow-releasing aptamer against VEGF) was injected in the tumour bed either or not followed by irradiation treatment with implanted I-125 seeds. Pegaptanib and/or irradiation were compared with sham-treated controls, resulting in four groups of 10-15 mice each. After 6 weeks of treatment, histological analysis was performed on all brains. RESULTS: VEGF inhibition by locally deposited pegaptanib decreased tumour blood vessel density, and increased tumour hypoxia. Pegaptanib treatment still allowed the formation of tumour satellites. Irradiation decreased tumour size and suppressed formation of satellites. Combined pegaptanib plus irradiation further increased PFS. Tumour size directly correlated with PFS. CONCLUDING STATEMENT: The anti-tumour effects of local VEGF inhibition are partially circumvented by the formation of invasive tumour satellites. Additional irradiation is effective in slowing down proliferation of these invasive tumour components.

Tumors arising in the sellar region are predominantly benign, non-invasive pituitary adenomas. Invasive pituitary adenomas (approximately 35 % of the pituitary adenomas) and pituitary carcinomas (0.1 – 0.5 %) arise from the same cells in the pituitary gland as the benign tumors, but have different pathology and biological behavior. A wide variety of nonadenomatous lesions involve the sellar region. These include tumors that arise specifically from sellar and suprasellar structures, as well as those that are also found elsewhere in the CNS (e.g. meningioma, glioma, metastasis, etc.). Typical nonadenomatous tumors that originate in the sellar region are craniopharyngioma and Rathke’s cleft cyst. The purpose of this paper is to describe another nonadenomatous tumor specific to the sellar region, a salivary gland-like tumor, and review the literature on this subject. This case report will also illustrate the management decisions regarding a patient with multiple medical issues and an aggressive sellar tumor.

Endoscopic endonasal surgery is currently regarded as the 'gold standard' for operating on pituitary gland tumors, and is becoming more and more accepted for treatment of other skull base lesions. However, endoscopic surgical treatment of most skull base pathologies, including certain pituitary tumors, is severely impaired by current instruments lack of maneuverability. Especially, gaining access to, and visibility of, difficult-to-reach anatomical corners without interference with surrounding neurovascular structures or other instruments, is a challenge. In this context there is the need for instruments that are able to provide a stable shaft position, while both the orientation and the position of the end-effector can be independently controlled. Current instruments that allow for this level of maneuverability are usually mechanically complex, and hence less suitable for mass production. This study therefore focuses on the development of a new actuation technique that allows for the required maneuverability while reducing the construction complexity. This actuation technique, referred to as multi-actuation, integrates multiple cable routings into a single steerable structure. Multi-actuation has been successfully integrated and tested in a handheld prototype instrument called HelixFlex. HelixFlex contains a 4 degrees of freedom maneuverable 5.8 mm (diameter) tip and shows promising results concerning its maneuverability and potential rigidity.

Author Summary Background. Patients with a newly diagnosed glioblastoma multiforme (GBM) have a high risk of recurrent disease with a dismal outcome despite intensive treatment of sequential surgery and chemoradiotherapy with temozolomide (TMZ), followed by TMZ as a single agent. Bevacizumab (BV) may increase response rates to chemotherapy in the recurrent treatment setting of GBM. We hypothesized that a neoadjuvant treatment strategy for patients with newly diagnosed GBM using chemoradiotherapy plus BV would improve resectability and thus survival. We performed a phase II trial of the treatment strategy of BV plus chemoradiation to determine the safety of this combination in patients who had already undergone primary surgery for their GBM. Methods. After a biopsy (6 patients) or a resection (13 patients) of a newly diagnosed GBM, 19 patients received radiotherapy (30 fractions of 2 Gy) in combination with daily TMZ 75 mg/m2 and BV 10 mg/kg on days 1, 14, and 28, followed by 6 monthly cycles of TMZ 150–200 mg/m2 on days 1–5. Results. The overall response rate was 26%. Three patients had a complete response after resection, and in two patients, a complete response after resection followed by chemoradiation plus BV was seen. No grade 3–4 toxicities were observed during combination treatment. The median progression-free survival was 9.6 months (95% confidence interval [CI]: 4.3–14.4 months). The median overall survival was 16 months (95% CI: 8.1–26.3 months), similar to a matched control group that received standard chemoradiotherapy from our institution. Conclusion. Combination of bevacizumab with radiotherapy and TMZ is safe and feasible in patients with newly diagnosed GBM, but because of low response rates, this treatment strategy does not favor a neoadjuvant approach.

OBJECTIVE:The orbitozygomatic approach is a modification and extension of the pterional craniotomy to gain a wider exposure of structures at a cranial base. To simplify the understanding and performance of the approach, we developed a teaching video that follows a systematic approach to the surgical anatomy and technique.METHODS:The authors have incorporated three-dimensional (3D) renderings into the descriptions of the surgical technique and contemporary computer animation is used to demonstrate surgical details and nuances of the procedure.RESULTS:A teaching video was compiled, and it was well received by neurosurgical residents in Europe and Canada.CONCLUSION:With mastery in the surgical laboratory and with guided supervision, the approach can be routinely applied without adding morbidity to a variety of pathologies such as aneurysms and tumors.

Background:In this study, we investigated the feasibility of using a 1.5 Tesla (T) clinical magnetic resonance imaging (MRI) system for in vivo assessment of three histopathologically different brain tumor models in mice.Methods:We selected mouse models in which tumor growth was observed in different intracranial compartments: Patched+/- heterozygous knock-out mice for tumor growth in the cerebellum (n = 5); U87 MG human astrocytoma cells xenografted to the frontal lobe of athymic mice (n =15); and F5 (n = 15) or IOMM-Lee (n = 15) human malignant meningioma cells xenotransplanted to the athymic mouse skull base or convexity. Mice were imaged using a small receiver surface coil and a clinical 1.5 T MRI system. T1- and fast spin echo T2-weighted image sequences were obtained in all animals. Gadolinium was injected via tail vein to better delineate the intracranial tumors. Twenty mice were followed by serial MRI to study tumor growth over time. In these mice, images were typically performed after tumor implantation, and at two week intervals. Mice were euthanized following their last imaging procedure, and their tumors were examined by histopathology. The histopathological preparations were then compared to the last MR images to correlate the imaging features with the pathology.Results:Magnetic resonance imaging delineated the tumors in the cerebellum, frontal lobes and skull base in all mouse models. The detection of intracranial tumors was enhanced with prior administration of gadolinium, and the limit of resolution of brain tumors in the mice was 1-2 mm3. Sequential images performed at different time intervals showed progressive tumor growth in all animals. The MR images of tumor size and location correlated accurately with the results of the histopathological analysis.Conclusion:Magnetic resonance imaging of murine brain tumors in different intracranial compartments is feasible with a 1.5 T clinical MR system and a specially designed surface coil. Tumors as small as 1-2 mm3 can be detected with good image resolution. Mice harbouring nascent brain tumors can be followed sequentially by serial MR imaging. This may allow for a noninvasive means by which tumor growth can be measured, and novel therapies tested without resorting to sacrifice of the mice.

Malignant meningiomas (MMs) are aggressive intracranial neoplasms with a 75% 5-year recurrence rate. Verotoxin 1 (VTi) is an Escherichia coli toxin, which has recently been shown to have anti-neoplastic action by targeting the globotriosylceramide (Gb3) glycolipid on tumor cells and tumor neovasculature. To investigate the potential use of VTi as a clinical agent for MM, we initially tested 16 meningiomas for Gb3 expression. Nine of 11 MMs (82%), but only one of five benign meningiomas (20%), were positive for Gb3. An orthotopic xenograft model was used to test the efficacy of VTi treatment for MM. We first demonstrated that Gb3 was highly expressed by the MM cell line, IOMM-Lee, and that this cell line was highly sensitive to VTi treatment in vitro. A single intratumoral injection of VTi significantly improved survival in nude mice harboring intracranial tumours (P

Object. Patients harboring colloid cysts of the third ventricle can present with acute neurological deterioration, or the first indication of the lesion may appear when the patient suddenly dies. The risk of such an occurrence in a patient already identified as harboring a colloid cyst is unknown. The goal of this study was to estimate the risk of acute deterioration in patients with colloid cysts. Methods. A retrospective study was made of a cohort of patients with newly diagnosed colloid cysts who were recruited in The Netherlands between January 1, 1993, and December 31, 1997. Seventy-eight patients were identified, all of whom displayed symptoms. Twenty-five patients (32%) presented with symptoms of acute deterioration; four patients died suddenly and the cysts were discovered at autopsy. The overall mortality rate was 12%. Results of a multivariate logistic regression analysis demonstrated that no subgroup of patients presenting without acute deterioration could be identified on the basis of patient age, duration of symptoms, cyst size, or the presence of hydrocephalus. The national incidence of colloid cysts in The Netherlands is 1/106 person-years; the prevalence was estimated to be 1800 asymptomatic colloid cysts. Conclusions. Acute deterioration was a frequent presentation among a national cohort of Dutch patients harboring symptomatic colloid cysts. The risk of acute deterioration in a symptomatic patient with a colloid cyst in The Netherlands is estimated to be 34%. The estimated risk for an asymptomatic patient with an incidental colloid cyst is significantly lower. These results strongly advocate the selection of surgical treatment for patients with symptomatic colloid cysts.

The extracellular matrix (ECM) of the central nervous system (CNS) is enriched in hyaluronate (HA). Ubiquitous receptors for HA are CD44 and the Receptor for HA-Mediated Motility known as RHAMM. In the present study, we have investigated the potential role of CD44 and RHAMM in the migration and proliferation of human astrocytoma cells. HA-receptor expression in brain tumor cell lines and surgical specimens was determined by immunocytochemistry and western blot analyses. The ability of RHAMM to bind ligand was determined through cetylpyridinium chloride (CPC) precipitations of brain tumor lysates in HA-binding assays. The effects of HA, CD44 blocking antibodies, and RHAMM soluble peptide on astrocytoma cell growth and migration was determined using MTT and migration assays. Our results show that the expression of the HA-receptors, CD44, and RHAMM, is virtually ubiquitous amongst glioma cell lines, and glioma tumor specimens. There was a gradient of expression amongst gliomas with high grade gliomas expressing more RHAMM and CD44 than did lower grade lesions or did normal human astrocytes or non-neoplastic specimens of human brain. Specific RHAMM variants of 85- and 58-kDa size were shown to bind avidly to HA following CPC precipitations. RHAMM soluble peptide inhibited glioma cell line proliferation in a dose-dependent fashion. Finally, while anti-CD44 antibodies did not inhibit the migration of human glioma cells, soluble peptides directed at the HA-binding domain of RHAMM inhibited glioma migration both on and off an HA-based ECM. These data support the notion that HA-receptors contribute to brain tumor adhesion, proliferation, and migration, biological features which must be better understood before more effective treatment strategies for these tumors can be found.

The discovery of endogenous opioids has markedly influenced the research on the biology of addiction and reward brain processes. Evidence has been presented that these brain substances modulate brain stimulation reward, self-administration of different drugs of abuse, sexual behaviour and social behaviour. There appears to be two different domains in which endogenous opioids, present in separate and distinct brain regions, are involved. One is related to the modulation of incentive motivational processes and the other to the performance of certain behaviours. It is concluded that endogenous opioids may play a role in the vulnerability to certain diseases, such as addiction and autism, but also when the disease is present, such as alcoholism.

We describe a 29-year-old woman who presented with progressive neck pain, sensory deficit and weakness in both arms. Magnetic resonance imaging (MRI) of the cervical spine revealed an extramedullary tumor with severe spinal cord compression. During surgery an intradural extramedullary tumor was found. Further imaging showed a second lumbar spinal tumor. Microscopy of both tumors showed that both tumors were anaplastic ependymomas, which almost never present as extramedullary tumors. Two years after surgery, an intracranial extracerebral metastasis was found, without evidence of spinal recurrence.

Endoscopic surgery of the skull base has been on the rise for several years. Endoscopic access for surgery can be achieved from the frontal sinus anteriorly along the skull base to the odontoid process posterior inferiorly. An endoscope is inserted through one nasal corridor and allows visualization of the working field and up to three surgical instruments can be used to address the lesion. This is called the “two nostrils–four hands technique”. This is a retrospective study of 67 cases. Setting of the study is an Amsterdam University hospital. Cases were identified in the department of otorhinolaryngology and department of neurosurgery database. All patients operated between 1 January, 2008 and 1 February, 2012 with pituitary tumours that extend beyond the sella, sinonasal tumours and all non-pituitary skull-base tumours were included. Mean tumour diameter was 3.8 cm. We performed a near-to-gross total resection in 92 % of cases where we intended to perform a total resection. The most frequent complication was CSF leakage. This study demonstrates that this technique is safe and reliable. What is needed is a dedicated team, which includes a dedicated anesthesiologist, endocrinologist, ophthalmologist, and radiation oncologist.

The Ablative surgery, MOulage brachytherapy and REconstruction) (AMORE) protocol developed in the Academic Medical Center of Amsterdam has been used successfully to treat sarcomas. The use of endoscopic surgery fits well within this framework. A 6-year-old boy presented with Ewing Sarcoma of left ethmoid sinus closest to orbit. The patient underwent neoadjuvant chemotherapy followed by complete endoscopic resection, brachytherapy and reconstruction. Brachytherapy was administered by iridium catheters through limited Lynch-Howarth incision. Skull base defect was reconstructed with a galea flap. The use of endoscopic surgery complemented by neoadjuvant chemotherapy and brachytherapy might maximize tumor control while reducing morbidity.

The sexual motivation and performance of male rats were observed in a bilevel testing chamber after bilateral infusion of 40 pmol β-endorphin, 2.75 nmol naloxone or saline into the ventral tegmental area for four succeeding, weekly tests. In the 5 min prior to introduction of the female rat, the male rat explores the bilevel testing chamber. It was previously shown that the increase over tests of these anticipatory level changes is sexually motivated and a response to olfactory stimuli. Naloxone infusion into the VTA prevented the increase of anticipatory level changes. β-Endorphin failed to affect the anticipatory level-changing behavior. The sexual performance was unaffected by naloxone or β-endorphin treatment, but the number of ejaculating rats decreased with repeated testing after naloxone treatment. It is concluded that endogenous opioid systems in the ventral tegmental area contribute to the stimulation of sexual motivation and/or reward, presumably by stimulating the mesolimbic dopamine system in response to sex-related olfactory stimuli.

We describe two children who presented with extreme weight gain and failure to grow in height, and who were both diagnosed with Cushing's disease. Following preoperative metyrapone treatment, both children successfully underwent curative transsphenoidal surgery. While obesity is a common and increasing problem in childhood, Cushing's disease is rare. The combination of weight gain and growth failure in a child is an alarming sign in which underlying endocrine disease must be ruled out.

Purpose: To assess long-term functional outcome and survival among patients with meningioma World Health Organization (WHO) grade I. Methods: Retrospective analysis of 205 patients after resection of WHO grade I intracranial meningioma from 1985 through 2003. Expected age- and sex-specific survival was calculated by applying Dutch life-table statistics to each patient for the individual duration of follow-up. Long-term functional outcome was assessed using a mailed questionnaire to the general practitioner. Results: The mean duration of follow-up was 11.5 years. Survival at 5, 10, 15, and 20 years was 92%, 81%, 63%, and 53%, respectively, which is significantly lower than the expected survival (94%, 86%, 78%, and 66%, respectively). Survival was worse with higher age (P < .001). Survival among patients younger than 45 years and older than 65 years was comparable to the expected survival but significantly worse among patients aged 45‐65 years. Analysis of the cause of death suggests an excess mortality associated with both brain tumor death and stroke (P 5 .07). Recurrence rates at 5, 10, and 15 years were 18%, 26%, and 32%, respectively. Higher Simpson grade (P < .001) and lower age (P 5 .02) were associated with a higher recurrence rate. In 29 patients (14%) receiving radiotherapy, the 5-year recurrence rate was 18% and the 5-year survival was only 58%. Long-term functioning (≥5 years after last treatment) could be assessed in 89 long-term survivors: 29 patients (33%) showed no deficits, and 60 (67%) showed at least 1 neurological symptom, of whom 24 (27%) were unable to perform normal daily activities. Conclusion: Long-term survival in WHO grade I meningioma is challenged in patients more than 45 years of age. Excess mortality seems to be associated with both tumor recurrence and stroke. The majority of patients have long-term neurological problems.

Aim To evaluate the outcome of surgery and radiotherapy in the treatment of sphenoorbital meningioma (SOM). Method A retrospective study of 66 consecutive cases treated with surgery for SOM with a minimum follow-up of 4 years. Clinical and radiological information were compared before and after the following surgical approaches: frontotemporal craniotomy, frontotemporal craniotomy combined with orbitozygomatic resection and extended lateral orbitotomy alone. Results The median age at presentation was 46 years (range, 26-68 years) and the median follow-up after surgery was 102 months (range, 48-288 months). In total, 48 (73%) patients showed preoperative visual deterioration, with visual field defects. All patients had proptosis at presentation (mean +/- SD=6.4 +/- 3.0 mm). Surgery for patients with SOM arrested visual deterioration in 61% and improved vision in 30% of cases. Furthermore, a substantial reduction of proptosis was achieved in 85% of patients. The proptosis in this group was reduced by 2.6 +/- 2.6 mm. There was no correlation between surgical approach and proptosis reduction (p=0.125). The recurrence rate was 17%. Only 1 out of 15 patients who underwent radiotherapy showed signs of recurrence. Conclusions The surgical aims in the treatment of SOM should be the restoration of visual acuity and reduction of proptosis, rather than complete tumour removal. The surgical approach can be tailored to individual cases. The authors recommend radiotherapy in cases of subtotally removed SOM

To investigate the natural history and the growth rate of spheno-orbital meningiomas (SOMs). Ninety patients with a diagnosis of SOM were included, and patient charts and imaging were evaluated. In a subset of 32 patients, volumetric studies were performed. The median follow-up for the entire group was 4 years (range, 1-15); the mean age was 47.8 (range, 26-93) years; 94% of the patients were female. The most common clinical signs and symptoms were proptosis (93%), visual deterioration (65%), retro-bulbar pain (23%) and diplopia (6%). In 35% of patients in this series, no visual deterioration occurred, and in 30% only mild proptosis was present. The median annual growth rate of the SOMs in the subset of 32 patients was 0.3 cm(3)/year (range, 0.03-1.8 cm(3)/year). We assessed a trend for more rapid tumour growth in younger patients and found the initial volume of the tumour (rho = 0.63) and of the soft tissue component (rho = 074) to be significantly related to the growth rate. SOMs are slow-growing tumours that cause primarily proptosis and visual deterioration. In a significant number of patients, these tumours cause minimal discomfort and symptomatology. Therefore, in the absence of risk factors, we advocate a "wait and see" policy. For patients with large SOMs or with a large soft tissue component at first visit or with fast growing SOMs (> 1cm(3)/year), a follow-up examination every 6 months is indicated.

Background The relevance of angiogenesis inhibition in the treatment of glioblastoma multiforme (GBM) should be considered in the unique context of malignant brain tumours. Although patients benefit greatly from reduced cerebral oedema and intracranial pressure, this important clinical improvement on its own may not be considered as an anti-tumour effect. Discussion GBM can be roughly separated into an angiogenic component, and an invasive or migratory component. Although this latter component seems inert to anti-angiogenic therapy, it is of major importance for disease progression and survival. We reviewed all relevant literature. Published data support that clinical symptoms are tempered by anti-angiogenic treatment, but that tumour invasion continues. Unfortunately, current imaging modalities are affected by anti-angiogenic treatment too, making it even harder to define tumour margins. To illustrate this we present MRI, biopsy and autopsy specimens from bevacizumab-treated patients. Moreover, while treatment of other tumour types may be improved by combining chemotherapy with anti-angiogenic drugs, inhibiting angiogenesis in GBM may antagonise the efficacy of chemotherapeutic drugs by normalising the blood-brain barrier function. Summary Although angiogenesis inhibition is of considerable value for symptom reduction in GBM patients, lack of proof of a true anti-tumour effect raises concerns about the place of this type of therapy in the treatment of GBM.

The combination of irradiation with angiogenic inhibition is increasingly being investigated for treatment of glioblastoma multiforme (GBM). We investigated whether vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitor DC101 affects morbidity and tumor growth in irradiated and non-irradiated intracerebral GBM-bearing mice, controlled with sham treatments. End-points were toxicity, morbidity and histology. Irradiation either or not combined, reduced tumor size strongly, whereas DC101 mono-treatment reduced tumor size by 64%. Irradiation delayed morbidity from 5.8 weeks in sham-treated mice to 10.3 weeks. Morbidity after combined treatment occurred after 5.9 weeks. Treatment with angiogenesis inhibitor DC101 delays tumor growth but it induces morbidity, by itself or combined with irradiation. (C) 2009 Elsevier Ireland Ltd. All rights reserved

Background High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models– high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a stereotactic brachytherapy mouse model for high-dose focal irradiation of experimental intracerebral (orthotopic) brain tumors. Methods Twenty-one nude mice received a hollow guide-screw implanted in the skull. After three weeks, 5 × 105 U251-NG2 human glioblastoma cells were injected. Five days later, a 2 mCi iodine-125 brachytherapy seed was inserted through the guide-screw in 11 randomly selected mice; 10 mice received a sham seed. Mice were euthanized when severe neurological or physical symptoms occurred. The cumulative irradiation dose 5 mm below the active iodine-125 seeds was 23.0 Gy after 13 weeks (BEDtumor = 30.6 Gy). Results In the sham group, 9/10 animals (90%) showed signs of lethal tumor progression within 6 weeks. In the experimental group, 2/11 mice (18%) died of tumor progression within 13 weeks. Acute side effects in terms of weight loss or neurological symptoms were not observed in the irradiated animals. Conclusion The intracerebral implantation of an iodine-125 brachytherapy seed through a stereotactic guide-screw in the skull of mice with implanted brain tumors resulted in a significantly prolonged survival, caused by high-dose irradiation of the brain tumor that is biologically comparable to high-dose fractionated radiotherapy– without fatal irradiation toxicity. This is an excellent mouse model for testing orthotopic brain tumor therapies in combination with radiation therapy.

Glioblastoma multiforme (GBM) is a radioresistant tumor. Tumor neoangiogenesis is an important mechanism for tumor sustenance. Angiogenesis is primarily mediated by vascular endothelial growth factor (VEGF), and earlier studies have suggested that VEGF protects human umbilical vein endothelial cells (HUVECs) against high doses of radiation. We tried to extend these findings to other endothelial cell lines and clinically relevant irradiation doses. Therefore, four different endothelial cell lines (HUVEC-C, primary HUVEC-P, an immortalized HUVEC cell line: EC-RF24, and bovine retina endothelial cells: BREC) were cultured without or with recombinant human VEGF165 (rhVEGF165). Cells were irradiated with gamma-rays from a 137Cs-source. Radiosensitivity was determined by proliferation or clonogenic assay. Apoptosis was assayed by flow cytometric determination of the sub-G1 population or by counting nuclear fragmentation. We found that the biologically active rhVEGF165 was able to improve clonogenic survival of HUVEC-C after 2 and 5 Gy. However, rhVEGF165 could not significantly alter the radiosensitivity of all cell lines studied in proliferation assays. rhVEGF165 only slightly reduced apoptosis in HUVEC-C after 3 Gy. In conclusion, the radioprotective effect from rhVEGF165 was found on different endothelial cell lines after clinically relevant radiation doses was negligible. We therefore hypothesize that the high VEGF-levels found in GBM in vivo do not reduce the radiosensitivity of endothelial cells, which is thought to contribute to the strong radioresistance of the tumor vasculature.

Ruud W.H. Meijneke (1), Antoinette Y.N. Schouten-van Meeteren (2), Liesbeth Reneman (3), Martijn Finken (4), Peter H. Bisschop (5), Wouter van Furth (6) Hanneke M. van Santen (7) (1) Student (UMCG) scientifi c project, department of pediatric oncology and department of pediatric endocrinology, Emma Children’s Hospital, AMC (2) Department of pediatric oncology, Emma Children’s Hospital, AMC (3) Department of radiology, AMC (4) Department of pediatric endocrinology, VUMC (5) Department of endocrinology, AMC (6) Department of neurosurgery, AMC (7) Department of pediatric endocrinology, Emma Children’s Hospital, AMC

The sexual motivation and performance of sexually experienced male rats were tested during the light phase of the diurnal cycle after treatment with saline or 1 mg · kg−1 naloxone in a bilevel testing ☐. The sexual motivation during the light phase, as assessed by the increase in anticipatory level changes prior to introduction of a receptive female on subsequent weekly sessions, was comparable to that during the dark phase. Opioid receptor blockade reduced the increase of level changes, suggesting that endogenous opioids are involved in sexual motivation. The sexual performance was impaired during the light phase. Naloxone treatment failed to affect the sexual performance, other than that the post ejaculatory refractory period was increased. This increased latency to re-initiate copulation may be an expression of the reduced sexual motivation. It is concluded that endogeneous opioids are not involved in the regulation of the impaired sexual performance during the light phase of the diurnal cycle. In contrast, the sexual motivation, which displays no marked diurnal variation, may be stimulated by endogenous opioids.

gamma-Type endorphins mimic neuroleptics in inducing a grasping response in rats. It was studied whether the haloperidol-induced grasping response was altered after blockade of gamma-type endorphin activity in the rat brain. To achieve this blockade rats were injected i.c.v. with gamma-endorphin antiserum or with a monoclonal anti-idiotype desenkephalin-gamma-endorphin antibody, which may bio-inactivate the gamma-type endorphins or block the putative receptors for gamma-type endorphins, respectively. The results showed that both treatments attenuated the haloperidol-induced grasping response, particularly 3 h after haloperidol treatment. The influence of these antibodies appeared to be specific, since other sera were without effect. Thus there may be an interaction between the endogenous gamma-type endorphin activity and the haloperidol-induced grasping response.