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OBJECTIVE Decision-making for intracranial tumor surgery requires balancing the oncological benefit against the risk for resection-related impairment. Risk estimates are commonly based on subjective experience and generalized numbers from the literature, but even experienced surgeons overestimate functional outcome after surgery. Today, there is no reliable and objective way to preoperatively predict an individual patient’s risk of experiencing any functional impairment. METHODS The authors developed a prediction model for functional impairment at 3 to 6 months after microsurgical resection, defined as a decrease in Karnofsky Performance Status of ≥ 10 points. Two prospective registries in Switzerland and Italy were used for development. External validation was performed in 7 cohorts from Sweden, Norway, Germany, Austria, and the Netherlands. Age, sex, prior surgery, tumor histology and maximum diameter, expected major brain vessel or cranial nerve manipulation, resection in eloquent areas and the posterior fossa, and surgical approach were recorded. Discrimination and calibration metrics were evaluated. RESULTS In the development (2437 patients, 48.2% male; mean age ± SD: 55 ± 15 years) and external validation (2427 patients, 42.4% male; mean age ± SD: 58 ± 13 years) cohorts, functional impairment rates were 21.5% and 28.5%, respectively. In the development cohort, area under the curve (AUC) values of 0.72 (95% CI 0.69–0.74) were observed. In the pooled external validation cohort, the AUC was 0.72 (95% CI 0.69–0.74), confirming generalizability. Calibration plots indicated fair calibration in both cohorts. The tool has been incorporated into a web-based application available at https://neurosurgery.shinyapps.io/impairment/. CONCLUSIONS Functional impairment after intracranial tumor surgery remains extraordinarily difficult to predict, although machine learning can help quantify risk. This externally validated prediction tool can serve as the basis for case-by-case discussions and risk-to-benefit estimation of surgical treatment in the individual patient.

Objectives With regard to the generally slow growth of meningioma, it is essential to analyse clinical treatment results in a long-term perspective. The purpose of the present analysis is to provide clinical data after Gamma Knife radiosurgery of meningioma in a 10-year perspective together with a review of the current literature. Methods The current study is a retrospective analysis of 86 consecutive Swedish patients with meningiomas treated using Gamma Knife radiosurgery at the Karolinska Hospital Stockholm between March 1991 and May 2001. A total of 130 tumours were treated in 115 treatment sessions. The median radiological follow-up was 10 years (1.8–16.5 years), and the median clinical follow-up was 9.4 years (2.1–17.4 years). Results After a median follow-up period of 10 years, local tumour control was achieved in 87.8% of meningiomas (108/123 tumours). The median latency between initial treatment and local (in-field) recurrence (n = 15) was 5.8 years (1.9–11.5). Recurrences adjacent but outside the initial radiation field occurred in 15.1% of patients (13/86) at a median of 7.5 years (1.3–15.7). New meningiomas were seen in 10.5% after a median of 5.4 years (0.9–10.8). In 72% of patients, no further treatment was required, 17.4% (15/86) underwent a second Gamma Knife treatment, 4.7% (4/86) required later open surgery and 5.8% (5/86) required both secondary treatments. Eighty-six percent of patients were neurologically unchanged or improved. A significantly lower rate of local (in-field) recurrences was seen in meningiomas treated with a prescription dose of > 13.4 Gy (7.1% vs. 24%, p = 0.02). Conclusions The current retrospective analysis provides a 10-year follow-up and comprises one of the longest available follow-up studies of radiosurgically treated meningiomas. The current series documents a persistent high local tumour control after Gamma Knife treatment, while providing an estimation of a necessary minimum dose for long-term tumour control in meningiomas. The study confirms the validity of previous short-term data in a long-term perspective.

Objective Rathkes cleft cysts are benign, embryological remnants in the pituitary gland. The majority of them are small and asymptomatic but a few may become large, and cause mass effects, pituitary hormone deficiencies and visual impairment. Recommendations for the follow-up of Rathkes cleft cysts vary since data on the natural history are sparse. Patients and Design Data at diagnosis and at 1, 5 and 10 years for patients with a Rathkes cleft cyst (434 at diagnosis, 317 females) were retrieved from the Swedish Pituitary Registry. Cysts = 10 mm that were not operated (n = 174) decreased in size over the years (p < .01). Pituitary hormone deficiencies and visual impairments were more frequent (18% and 5.7%, respectively) but were stable over time. Transphenoidal surgery was performed in 56 patients of whom 51 underwent surgery before the 1-year follow-up. The mean cyst diameter at diagnosis was 18 mm (range: 930 mm), 36% had pituitary hormone deficiency, 45% had visual field defects and 20% had impaired visual acuity. One year after surgery 60% had no cyst remnants, 50% had a pituitary deficiency, 26% had visual field defects and 12% had impaired visual acuity. No major changes were observed after 5 years. Twelve of the operated patients had a follow-up at 10 years, in eight the cyst remnants or recurrences increased in size over time (p < .05). Conclusions Rathkes cleft cysts with a size less than 10 mm rarely grow and our results indicate that radiological follow-up can be restricted to 5 years. In contrast, progression of postoperative remnants or recurrent cysts is more likely and require long-term follow-up.

Background In patients with vestibular schwannomas (VS), tumor control is often achieved, and life expectancy is relatively good. The main risks of surgical treatment are hearing loss and facial nerve function. The occurrence of mood and sleeping disorders in relation to surgery is an important aspect of health that has rarely been studied. Similarly, only limited data exist on the rate of sick leave for patients with VS. In this nationwide registry-based study, we define the use of antidepressants and sedatives and the sick leave pattern before and after VS surgery. Methods Adult patients with histopathologically verified VS were identified in the Swedish Brain Tumor Registry (SBTR) and clinical data were linked to relevant national registries after assigning five matched controls to each patient. We studied patterns of dispensed antidepressants and sedative drugs as well as patterns of sick leave compared to respective controls at 2 years before and 2 years following surgery. Results We identified 333 patients and 1662 matched controls. The rate of antidepressant use was similar between patients and controls 2 years before surgery (6.0% vs 6.3%) and 2 years after surgery (10.1% vs 7.5%). The rate of sedative use was also similar 2 years before surgery (3.9% vs 4.3%) and 2 years after surgery (4.8% vs 5.3%). The rate of sick leave was similar at baseline between patients and controls, but at 2 years after surgery, 75% of patients vs 88% of controls (p p = 0.03), more preoperative sick leave (OR 0.91, 95% CI 0.89–0.93, p p = 0.004). Conclusion This nationwide study shows no significant differences in the use of antidepressants and sedatives between patients and controls, while the rate of postoperative sick leave was higher in patients than in controls after VS surgery. Our findings underpin the importance of avoiding surgical sequelae and facilitating return to normal professional life.

The aim of this retrospective study was to investigate the long-term seizure control and antiepileptic drug (AED) prescriptions, as well as identifying predictors of seizure(s) before and after surgery in a population-based cohort of operated intracranial meningioma patients. A total of 113 consecutive adult (> 18 years old) patients with newly diagnosed meningioma operated at the Karolinska University Hospital between 2006 and 2008 were included and followed up until the end of 2015. Data on seizure activity and AED prescriptions were obtained through chart review and telephone interview. Logistic regression and survival analysis were applied to identify risk factors for pre- and postoperative seizures. A total of 21/113 (18.6%) patients experienced seizures before surgery of which 8/21 (38.1%) went on to become seizure-free after surgery. Thirteen (14%) patients experienced new-onset seizures after surgery. The regression analysis revealed tumor diameter ≥ 3.5 cm as a risk factor for preoperative seizures (OR 3.83, 95% CI 1.14–12.87). Presence of headache (OR 0.19, 95% CI 0.05–0.76) and skull base tumor location (OR 0.14, 95% CI 0.04–0.44) decreased the risk of preoperative seizures. Postoperative seizures were associated with tumor diameter ≥ 3.5 cm (OR 2.65, 95% CI 1.06–6.62) and history of preoperative seizures (OR 3.50, 95% CI 1.55–7.90). Seizures are common before and after intracranial meningioma surgery. Approximately one third of patients with preoperative seizures become seizure-free on long-term follow-up after surgery, while 14% experienced new-onset seizures after surgery. Larger tumor size, absence of headache, and non-skull base location were associated with preoperative seizures, while tumor size and preoperative seizures were associated with postoperative seizures.

Objective To establish the risk of recurrence in patients with chronic subdural hematoma (cSDH) on antithrombotic treatment (AT, i.e., antiplatelets and anticoagulants). Secondary end points were perioperative morbidity and mortality between groups (AT vs. no-AT group) and exploration if timing of resumption of AT treatment (i.e., prophylactic early vs. late resumption) influenced the occurrence of thromboembolism and hematoma recurrence. Materials In a population-based consecutive cohort, we conducted a retrospective review of 763 patients undergoing primary burr hole procedures for cSDH between January 1, 2005, and December 31, 2010, at the Karolinska University Hospital, Stockholm, Sweden. Early AT resumption was ≤30 days and late >30 days after the procedure. Results A total of 308/763 (40.4%) cSDH patients were on AT treatment at the time of diagnosis. There was no difference in cSDH recurrence within 3 months (11.0% vs. 12.0%, p = 0.69) nor was there any difference in perioperative mortality (4.0% vs. 2.0%, p = 0.16) between those using AT compared to those who were not. However, perioperative morbidity was more common in the AT group compared to no-AT group (10.7% vs. 5.1%, p = 0.003). Comparing early vs. late AT resumption, there was no difference with respect to recurrence (7.0% vs. 13.9%, p = 0.08), but more thromboembolism in the late AT resumption group (2.0% vs. 7.0%, p

Objective Chronic subdural hematoma (cSDH) is a prevalent condition often seen in the elderly, with surgery being the treatment of choice when symptomatic. So far, few have explored the surgical outcomes in patients 90 years or older. The aim of this study was to investigate outcome after cSDH surgery in nonagenarians (≥90 y/o group) compared to younger adult patients (

Objectives Adaptive Hybrid Surgery Analysis (AHSA, Brainlab, Munich, Germany) is a software application generating in real-time conceptual dose plans for tumor residuals but has so far not been assessed for usability in a Gamma Knife (Elekta, Stockholm, Sweden) radiosurgery practice. We aimed to compare AHSA stereotactic radiosurgery dose plans with Leksell Gamma Plan (LGP, Elekta, Stockholm, Sweden) plans for adjuvant radiosurgical treatment of Vestibular Schwannoma (VS) residuals. Patients and Methods In this retrospective comparative study, we compared the automatically calculated AHSA dose plans with clinical LGP treatment plans in 13 patients radiosurgically treated for VS residuals. We first created an LGP template based on our specific constraints to organs at risk (OAR), and a tumor prescription volume coverage of minimum 98%. As most proximal anatomy at risk is not manually contoured in our practice, OARs (i.e. brainstem, optic apparatus and cochlea) in the planning images were automatically segmented in Elements Anatomical Mapping and imported into the AHSA software for re-planning and comparison with the LGP dose plans. Results There was no significant difference in tumor coverage and conformity index between the LGP and AHSA dose planning data, with the mean and maximal dose to the brainstem slightly higher in the latter. Conclusion The AHSA dose plans for adjuvant radiosurgical treatment of VS residuals were comparable to those of LGP used in our Gamma Knife practice, confirming the usability of AHSA in for the management of Vestibular Schwannoma in a Gamma Knife practice.

Objectives Venous thromboembolism (VTE) is a serious complication after intracranial meningioma surgery. To what extent systemic prophylaxis with pharmacotherapy is beneficial with respect to VTE risk, or associated with increased risk of bleeding and postoperative hemorrhage, remains debated. The current study aimed to clarify the risk/benefit ratio of prophylactic pharmacotherapy initiated the evening before craniotomy for meningioma. Methods In a Scandinavian population-based cohort, we conducted a retrospective review of 979 operations for intracranial meningioma between 2007 and 2013 at 3 neurosurgical centers with population-based referral. We compared 2 different treatment strategies analyzing frequencies of VTE and proportions of postoperative intracranial hematomas requiring surgery or intensified subsequent observation or care (intensive care unit or other intensified observation or treatment). One neurosurgical center favored preoperative prophylaxis with low-molecular-weight heparin (LMWH) (LMWH routine group) in addition to mechanical prophylaxis, and 2 centers favored mechanical prophylaxis with LMWH only given as needed in cases of delayed mobilization (LMWH as needed group). Results In the LMWH routine group, VTE was diagnosed after 24/626 operations (3.9%), and VTE was diagnosed after 11/353 (3.1%) operations in the LMWH as needed group ( P = 0.56). Clinically relevant postoperative hematomas occurred after 57/626 operations (9.1%) in the LMWH routine group compared with 23/353 (6.5%) in the LMWH as needed group ( P = 0.16). Surgically evacuated postoperative hematomas occurred after 19/626 operations (3.0%) in the LMWH routine group compared with 8/353 operations (2.3%) in the LMWH as needed group ( P = 0.26). Conclusions There is no benefit of routine preoperative LMWH starting before intracranial meningioma surgery. Neither could we for primary outcomes detect a significant increase in clinically relevant postoperative hematomas secondary to this regimen. We suggest that as needed perioperative administration of LMWH, reserved for patients with excess risk because of delayed mobilization, is effective and also appears to be the safest strategy.

BACKGROUND: Traumatic acute subdural hematomas (ASDHs) are associated with high rate of morbidity and mortality, especially in elderly individuals. However, recent reports indicate that the morbidity and mortality rates might have improved.OBJECTIVE: To evaluate postoperative (30-d) mortality in younger vs elderly (≥70 yr) patients with ASDH. Comparing younger and elderly patients, the secondary objectives are morbidity patterns of care and 6 mo outcome according to Glasgow outcome scale (GOS). Finally, in patients with traumatic ASDH, we aim to provide prognostic variables.METHODS: This is a large-scale population-based Scandinavian study including all neurosurgical departments in Denmark and Sweden. All adult (≥18 yr) patients surgically treated between 2010 and 2014 for a traumatic ASDH in Denmark and Sweden will be included. Identification at clinicaltrials.gov is NCT03284190.EXPECTED OUTCOMES: We expect to provide data on potential differences between younger vs elderly patients in terms of mortality and morbidity. We hypothesize that elderly patients selected for surgery have a similar pattern of care as compared with younger patients. We will provide functional outcome in terms of GOS at 6 mo in younger vs elderly patients undergoing ASDH evacuation. Finally, clinical useful prognostic factors for favorable (GOS 4-5) vs unfavorable (GOS 1-3) will be identified.DISCUSSION: An improved understanding of the clinical outcome, treatment and resource allocation, clinical course, and the prognostic factors of traumatic ASDH will allow neurosurgeons to make better treatment decisions.

To investigate predictors of recurrence and moderate to severe complications after burr-hole surgery for chronic subdural hematoma (cSDH).A retrospective review was conducted in a Scandinavian single-center population-based cohort of 759 adult patients with cSDH operated with burr-hole surgery between January 1, 2005 and December 31, 2010. Possible predictors of recurrence and complications, assessed using a standardized reporting system of adverse events, were identified and analyzed in univariable analyses. Variables with a P value0.10 were included in a multivariable regression model.Recurrence was observed in 85 patients (11.2%), whereas moderate to severe complications were observed in 35 patients (4.6%). Bilateral hematoma (odds ratio [OR], 2.05; 95% confidence interval [CI], 1.25-3.35; P 0.01) and largest hematoma diameter in millimeters (OR, 1.05; 95% CI, 1.01-1.09; P0.01) were independent predictors of recurrence in the multivariable model analysis. Glasgow Coma Scale (GCS) score of13 (OR, 6.06; 95% CI, 2.72-13.51; P0.01) and Charlson Comorbidity Index (CCI)1 (OR, 2.28; 95% CI, 1.10-4.75; P = 0.03) were independent predictors of moderate to severe complications.Recurrence after cSDH surgery is more often encountered in patients with radiologically more extensive disease reflected by bilateral hematoma and large hematoma diameter. On the other hand, moderate to severe complications are more often seen in patients in a worse clinical condition, reflected by decreased level of consciousness and more comorbidities.

Objectives Molecular markers provide valuable information about treatment response and prognosis in patients with low-grade gliomas (LGG). In order to make this important information available prior to surgery the aim of this study was to explore if molecular status in LGG can be discriminated by preoperative magnetic resonance imaging (MRI). Patients and methods All patients with histopathologically confirmed LGG with available molecular status who had undergone a preoperative standard clinical MRI protocol using a 3T Siemens Skyra scanner during 2008–2015 were retrospectively identified. Based on Haralick texture parameters and the segmented LGG FLAIR volume we explored if it was possible to predict molecular status. Results In total 25 patients (nine women, average age 44) fulfilled the inclusion parameters. The textural parameter homogeneity could discriminate between LGG patients with IDH mutation (0.12, IQR 0.10-0.15) and IDH wild type (0.07, IQR 0.06-0.09, p = 0.005). None of the other four analyzed texture parameters (energy, entropy, correlation and inertia) were associated with molecular status. Using ROC curves, the area under curve for predicting IDH mutation was 0.905 for homogeneity, 0.840 for tumor volume and 0.940 for the combined parameters of tumor volume and homogeneity. We could not predict molecular status using the four other chosen texture parameters (energy, entropy, correlation and inertia). Further, we could not separate LGG with IDH mutation with or without 1p19q codeletion. Conclusions In this preliminary study using Haralick texture parameters based on preoperative clinical FLAIR sequence, the homogeneity parameter could separate IDH mutated LGG from IDH wild type LGG. Combined with tumor volume, these diagnostic properties seem promising. © 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).

Gamma knife radiosurgery (GKRS) has for the last decades been an established treatment option for patients with small- or medium-sized vestibular schwannomas (VS), although little data is reported on long-term outcome regarding quality of life (QOL) and tumour control in this patient category. The objective of this study was to investigate long-term QOL and tumour control in GKRS-treated VS patients at our institution.Data was reviewed from a consecutive cohort of 128 patients, 62 men and 66 women, diagnosed with VS and treated with GKRS at Karolinska University Hospital between 1997 and 2003. Patients previously treated for VS, patients from abroad, and patients with neurofibromatosis were excluded from the study. Median age at the time of treatment was 66 years (range 23-89), with a median follow-up time of 104 months (range 11-165) and radiological median follow-up of 86 months (range 5-170). Five patients were lost to follow-up.Data on QOL (EQ-5D score) was obtained in 90 % (98/109) of all cases at the end of follow-up, showing low morbidity and a high QOL with median index of 0.91 (max. score 1.0) in these patients. Tumour control was achieved in 92 % (118/128) of patients after a single GKRS treatment. Ten patients had loss of tumour control, either radiologically seen as growth progression, or due to the need for salvage treatment. Neither pre-treatment growth of the vestibular schwannoma, or a large tumour size (Koos grade 34) was correlated with a higher degree of treatment failure (p = 0.695 and p = 0.647, respectively). There was no difference in tumour control in young (60 y/o) vs. elderly (≥60 y/o) patients (p = 0.167).We report a high QOL and low morbidity at long-term follow-up after GKRS treatment in VS patients. Furthermore, a high tumour control rate was achieved independent of tumour size, patient age or pre-treatment evidence of tumour growth.

There is a need to improve outcome in patients with brain abscesses and hyperbaric oxygen therapy (HBOT) is a promising treatment modality. The objective of this study was to evaluate HBOT in the treatment of intracranial abscesses. This population-based, comparative cohort study included 40 consecutive adult patients with spontaneous brain abscess treated surgically between January 2003 and May 2014 at our institution. Twenty patients received standard therapy with surgery and antibiotics (non-HBOT group), while the remaining 20 patients also received adjuvant HBOT (HBOT group). Resolution of brain abscesses and infection was seen in all patients. Two patients had reoperations after HBOT initiation (10 %), while nine patients (45 %) in the non-HBOT group underwent reoperations (p = 0.03). Of the 26 patients who did not receive HBOT after the first surgery, 15 (58 %) had one or several recurrences that lead to a new treatment: surgery (n = 11), surgery + HBO (n = 5) or just HBO (n = 1). In contrast, recurrences occurred in only 2 of 14 (14 %) who did receive HBOT after the first surgery (p

To investigate frequencies of adverse events occurring within 30 days after microvascular decompression (MVD) surgery using a standardized report form of adverse events. We conducted a retrospective review of 98 adult patients (≥16 years) treated with MVD between 1 January 1994 and 1 June 2013. Adverse events occurring within 30 days were classified according to the Landriel Ibanez classification for neurosurgical complications: grade I represents any non-life threatening complication treated without invasive procedures; grade II is complications requiring invasive management; grade III is life-threatening adverse events requiring treatment in an intensive care unit (ICU); grade IV is death as a result of complications. We sought to compare our results with reports from the literature. Patients’ median age was 61 years (range 26–83), and 64 (65 %) were females. Indications for MVD were trigeminal neuralgia (n = 77, 79 %), glossopharyngeal neuralgia (n = 4, 4 %), hemifacial spasm (n = 16, 16 %) and combined trigeminal neuralgia and hemifacial spasm (n = 1, 1 %). The overall 30-day complication rate was 20 %, with 14 % grade I complications, 5 % grade II complications and 1 % grade III complications. The comparison with the literature was hampered by the diverse and unsystematic way of reporting complications. We provide a standardized report of postoperative complications in a consecutive patient series undergoing MVD. Due to the heterogeneous and non-standardized reporting of complications in the literature, it is difficult to know if our 20 % complication rate is low or high. Standardized reporting is a necessity for meaningful and more valid comparisons across studies. The safety of MVD, a fairly standardized neurosurgical procedure, is well suited for comparisons across centers provided that complications are reported in a standardized manner.

Radical surgical resection of cerebral meningiomas involving the dura mater of venous sinuses is challenging, and tumor residuals are frequently left after surgery. This study sought to evaluate the effect of adjuvant stereotactic radiosurgery (aSRS) on the time to significant growth of meningioma residuals requiring retreatment.A total of 119 consecutive patients (2004-2013) receiving primary surgical treatment for a meningioma in proximity to a venous structure were included. The patients were assessed retrospectively, with a focus on retreatments and mortality. Radicality of initial tumor surgery was scored using postoperative magnetic resonance imaging. Three subgroups were identified: 1) radical total resection (RTR); 2) near-total resection (NTR), followed by aSRS (NTR + aSRS); and 3) NTR but no aSRS (NTR - aSRS). In the NTR - aSRS group, intervention was initiated after radiologic (magnetic resonance imaging) findings verified growth of residual tumor, in contrast to the NTR + aSRS group, which received aSRS before regrowth. Time to first retreatment, progression-free survival (PFS), and overall survival were analyzed with the log-rank test and multiple-events Cox regression.RTR was associated with the best prognosis. The patients in the NTR + aSRS group had significantly longer time to first retreatment compared with NTR - aSRS patients (P0.001). There was also a significant difference in mortality (P0.05) and a tendency to prolonged PFS (P = 0.07) in the NTR + aSRS group. The Cox regressions confirmed the positive effects of NTR + aSRS on time to retreatment (hazard ratio, 7.3; P0.01) and PFS (hazard ratio, 3.69; P = 0.055).aSRS of meningioma residuals had a positive effect on tumor control and should be considered in patients with meningioma residuals.

ObjectIntracranial chondrosarcomas have a high risk of recurrence after surgery. This retrospective study of patients with intracranial chondrosarcoma was conducted to determine the long-term results of microsurgery followed by Gamma Knife surgery (GKS) for residual tumor or recurrence.MethodsThe authors treated nine patients whose median age was 36 years. Seven patients had low-grade chondrosarcomas (LGCSs), whereas mesenchymal chondrosarcomas (MCSs) were diagnosed in two. Radiosurgery was performed in eight patients, whereas one patient declined further surgical intervention and tumor-volume reduction necessary for the GKS.The patients were followed up for 15 to 173 months (median 108 months) after diagnosis and 3 to 166 months (median 88 months) after GKS. Seven patients had residual tumor tissue after microsurgery, and two operations appeared radical. In the two latter cases, tumors recurred after 25 and 45 months. Thus, definite tumor control was not achieved after surgery alone in any patient, whereas the addition of radiosurgery allowed tumor control in all six patients with LGCSs. Two of these patients experienced an initial tumor regrowth after GKS; in both cases the recurrences were outside the prescribed radiation field. The patients underwent repeated GKS, and subsequent tumor control was observed. An MCS was diagnosed in the remaining two patients. Complications after microsurgery included diplopia, facial numbness, and paresis. After GKS, one patient had radiation necrosis, which required microsurgery, and two patients had new cranial nerve palsies.Conclusions Tumor control after microsurgery alone was not achieved in any patient, whereas adjuvant radiosurgery provided local tumor control in six of eight GKS-treated patients. Tumor control was not achieved in the two patients with MCS. Similar to other treatments for intracranial chondrosarcoma, morbidity after micro- and radiosurgical combination therapy was high and included severe cranial nerve palsies.

To investigate predictors of complications after intracranial meningioma resection using a standardized reporting system for adverse events.A retrospective review was conducted in a Scandinavian population-based cohort of 979 adult operations for intracranial meningioma performed at 3 neurosurgical centers with population-based referral between January 1, 2007, and June 30, 2013. Possible predictors of severe complications were identified and analyzed in univariable analyses. Variables with a P value0.10 were included in a multivariable model.Severe complications were observed in 68 (7%) operations. Univariable analyses identified patient age 70 years (P0.001), male sex (P = 0.03), Charlson Comorbidity Index1 (P = 0.02), Simpson grade3 (P = 0.03), Karnofsky performance scale score70 (P0.001), and duration of surgery4 hours (P0.001) as significant predictors of severe complications. Age70 (odds ratio = 2.5, P0.01), duration of surgery4 hours (odds ratio = 3.2, P0.001), and Karnofsky performance scale score70 (odds ratio = 2.5, P 0.01) were independent predictors of severe complications in the multivariable regression analysis.Severe complications after meningioma resection are more encountered often in elderly patients (70 years old), dependent patients (Karnofsky performance scale score70), and patients who underwent longer lasting surgery (4 hours). Patient selection, including careful consideration of the individual risk-benefit ratio, is important in improving the safety of intracranial meningioma resection.

Adrenal chromaffin cells have been characterized by the ability to change the phenotype in response to neurotrophic factor stimulation. The adrenal gland expresses numerous trophic factors endogenously, but there is still a lack of knowledge as to how the adrenal medullary cells respond to these factors. Accordingly, we evaluated nerve fiber outgrowth and cell morphology, and measured catecholamine content in adult rat adrenal medullary tissue transplanted to the anterior chamber of the eye after exposure to neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4/5), basic fibroblast growth factor (bFGF), ciliary neurotrophic factor (CNTF), or glial cell line-derived neurotrophic factor (GDNF) compared with the effects after exposure to recombinant human nerve growth factor (rhNGF). The results show that rhNGF was the most potent factor in inducing neurite outgrowth from the grafted chromaffin cells. CNTF was also a powerful inducer of nerve fiber formation, while NT-4/5, GDNF, and bFGF were less potent. NT-3 did not produce neurite outgrowth above that seen in vehicle-treated eyes. Combining two neurotrophins, rhNGF and NT-3, reduced nerve fiber formation. Tyrosine hydroxylase (TH) immunohistochemistry revealed good cell survival in all grafts, and no morphological differences were detected with the different treatments. The adrenaline: noradrenaline: dopamine ratio was approximately 49%: 49%: 2%, independent of treatment, and the catecholamine content was equal irrespective of treatment. In conclusion, all neurotrophic factors used, except for NT-3, promoted neurite outgrowth from adult rat chromaffin transplants. Differences in outgrowth induced by the various trophic factors did not, however, change the catecholamine content in grafts when analyzed together with the graft-derived nerve plexus.

In animal models of Parkinson's disease, transplanted fetal mesencephalic dopaminergic neurons can innervate the dopamine-depleted host brain, but it is unclear why large portions of the host striatum are left uninnervated. During normal development, the dopaminergic innervation first occurs in the form of a dense patchy pattern in the striatum, followed by a widespread nerve fiber network. Using intraocular double grafts we have investigated dopaminergic growth patterns initiated when ventral mesencephalic grafts innervate striatal targets. The fetal lateral ganglionic eminence was implanted into the anterior eye chamber. After maturation in oculo, fetal ventral mesencephalon was implanted and placed in contact with the first graft. In other animals the two pieces of tissue were implanted simultaneously. Tyrosine hydroxylase (TH) immunohistochemistry revealed a pattern of dense TH-positive patches throughout the total volume of the striatal grafts in simultaneously transplanted cografts, while a widespread, less dense, pattern was found when mature striatal transplants were innervated by fetal dopaminergic grafts. To investigate which type or types of growth patterns that developed after grafting to striatum in situ of an adult host, fetal ventral mesencephalic tissue was implanted into the lateral ventricle adjacent to the dopamine-lesioned striatum. After maturation of the mesencephalic graft, the fetal lateral ganglionic eminence was implanted into the reinnervated part of the host striatum. TH immunohistochemistry revealed a few nerve fibers within the striatal graft and the growth pattern was of the widespread type. In conclusion, grafted dopaminergic neurons preferably innervate mature striatum with a widespread sparse nerve fiber network, while the innervation of the immature striatum occurs in the form of dense patches. Furthermore, when the patchy pattern is formed, the total volume of the striatal target is innervated while growth of the widespread type terminates prior to reaching distal striatal parts. Thus, the growth pattern seems essential to the final volume that is innervated. Once the widespread growth pattern is initiated, the presence of immature striatum does not change the dopaminergic growth pattern.

New strategies have recently been developed where infusion of neurotrophic factors into the brain can rescue different populations of neurons. Infusion of nerve growth factor (NGF) has been used in combination with transplants of chromaffin tissue to the striatum in the rat model of Parkinson's disease as well as to patients suffering from Alzheimer's disease. In this study we have evaluated the distribution of recombinant human NGF (rhNGF) in different brain areas and evaluated morphological and electrophysiological effects after continuous infusion for 2 weeks of rhNGF (500 micrograms/ml) into the striatum of normal rats. One week after termination of rhNGF infusion, NGF levels in the infused striata were 10-fold increased while in contralateral striata normal levels were found. Extracellular recordings from striatal neurons revealed a significantly decreased spontaneous firing rate (0.76 +/- 0.07 Hz) in rats infused with rhNGF compared to vehicle-infused control animals (1.36 +/- 0.16 Hz). Local application of rhNGF during recordings showed no direct inhibitory effect of NGF on neuronal discharge rate. Immunohistochemistry, using antibodies against acetyl cholinesterase (AChE) and glial fibrillary acidic protein (GFAP), revealed a 38.7 +/- 7.0% increase in optical density of AChE immunoreactivity close to the NGF source and an increase in GFAP-positive profiles that was restricted close to the implanted dialysis fibre. In situ hybridization showed an increase in mRNAs for choline acetyltransferase, trkA, p75 and muscarinic m2 receptor in the large neurons of rhNGF-infused striatum. Messenger RNAs for m1 and m4 receptors in striatal neurons were not changed. Thus, chronic infusion of rhNGF into the striatum caused a cholinergic hyperinnervation and reduced spontaneous activity of striatal neurons.

Neurotrophic factors, such as nerve growth factor (NGF), have been shown to promote the differentiation of neural crest neuroblasts into sympathetic neurons, whereas glucocorticoids promote the endocrine phenotype of adrenal medullary chromaffin cells. This pluripotency is preserved to some extent in adult chromaffin cells, with NGF and other neurotrophic factors influencing the differentiation of these cells. In this study, the effects of glial cell line-derived neurotrophic factor (GDNF) on explanted chromaffin tissue have been investigated. The localization of mRNAs corresponding to the two components of the GDNF receptor, GDNF family receptor alpha 1 (GFRalpha1) and Ret, were demonstrated in adult adrenal medullary ganglion cells. GFRalpha1 mRNA was expressed in explanted chromaffin tissue at levels dependent on the presence of serum in the medium but decreased on the addition of blocking antibodies against transforming growth factor beta (TGFbeta). However, TGFbeta1 (1 ng/ml) did not upregulate GFRalpha1 mRNA expression when added to serum-free medium. GDNF induced neurite formation from chromaffin cells, as measured by the ratio of neurite-bearing versus total number of chromaffin cells in primary cultures of adult adrenal medulla. The most potent dose inducing neurites from chromaffin cells was 100 ng/ml GDNF. However, this dose was not as efficient as that seen when chromaffin cells were stimulated with NGF (100 ng/ml). Thus, adrenal medullary cells express mRNAs for the GDNF receptor components Ret and GFRalpha1, increase their expression upon being cultured in serum-containing medium and respond to GDNF treatment with an increase in the number of cells that develop nerve processes.

Chromaffin cells have been recognized for their ability to transform into sympathetic ganglion-like cells in response to nerve growth factor (NGF) or to stimulation of other neurotrophic factors. Transforming growth factor beta (TGFbeta) family members have been shown to potentiate the effect of different trophic factors. The aim of this study was to investigate if TGFbeta may influence NGF-induced neuronal transformation and regulation of NGF, TGFbeta1, and their receptors in the adult rat chromaffin tissue after grafting. Intraocular transplantation of adult chromaffin tissue was employed and grafts were treated with TGFbeta1 and/or NGF. Graft survival time was 18 days after which the grafts were processed for TGFbeta luciferase detection assay, NGF enzyme immunoassay, or in situ hybridization. In grafts stimulated with NGF, increased levels of TGFbeta1 and TGFbeta1 mRNA were detected. When grafts instead were treated with TGFbeta1, enhanced levels of NGF protein were found. Furthermore, a positive mRNA signal corresponding to the transforming growth factor II receptor (TbetaRII) was found in the chromaffin cells of the normal adrenal medulla as well as after grafting. No increase of TbetaRII mRNA levels was detected after transplantation or after TGFbeta1 treatment. Instead a reduction of TbetaRII mRNA expression was noted after NGF treatment. NGF stimulation of grafts increased the message for NGF receptors p75 and trkA in the chromaffin transplants. Grafts processed for evaluations of neurite outgrowth were allowed to survive for 28 days and were injected weekly with NGF and/or TGFbeta1. NGF treatment resulted in a robust innervation of the host irides. TGFbeta1 had no additive effect on nerve fiber formation when combined with NGF. Combined treatment of NGF and anti-TGFbeta1 resulted in a significantly larger area of reinnervation. In conclusion, it was found that NGF and TGFbeta1 may regulate the expression of each other's protein in adult chromaffin grafts. Furthermore, TbetaRII mRNA was present in the adult rat chromaffin cells and became downregulated as a result of NGF stimulation. Although no synergistic effects of TGFbeta1 were found on NGF-induced neurite outgrowth, it was found that TGFbeta1 and NGF signaling are closely linked in the chromaffin cells of the adrenal medulla.

Cultured and transplanted adrenal medullary cells respond to ciliary neurotrophic factor (CNTF) with neurite formation and improved cell survival although the presence of the CNTF receptor-alpha (CNTFRalpha) has been unclear. This study show that CNTFRalpha mRNA was expressed in the postnatal day 1 as well as in the adult rat adrenal medulla. The highest CNTFRalpha mRNA signal was found in the ganglion cells of the adrenal medulla. After transplantation of adrenal medullary tissue the CNTFRalpha mRNA levels were down-regulated in the chromaffin cells. CNTF treatment of grafts did not normalize the receptor levels, but treatment with nerve growth factor (NGF) did. Thus, we demonstrate that CNTFRalpha mRNA is expressed in adrenal medulla, the levels becomes down-regulated after transplantation, but normalized after treatment with NGF.

It has previously been shown that the chromaffin cells of the adrenal medulla respond to nerve growth factor (NGF) with neurite outgrowth and increased cell survival in tissue culture or after grafting. In the present study we evaluated the dose dependency in neurite outgrowth from chromaffin tissue to recombinant human NGF (rhNGF). Therefore, pieces of adrenal medullary tissue from adult rat were grafted into the anterior chamber of the eye of previously sympathectomized recepients. Survival time was 4 weeks. At grafting and at Days 7, 14, and 21 postgrafting, the eyes were injected with 5 microliters of rhNGF at concentrations of 10, 30, 60, 100, 150, and 200 micrograms/ml, or with a control solution. All grafts, including the controls, survived well and became vascularized. At the low doses of rhNGF, 10 and 30 micrograms/ml, a small area of the irides was reinnervated and the density of the nerve fiber network was low. The maximal response was obtained at 100 micrograms rhNGF/ml. Using larger concentrations of 150 and 200 micrograms rhNGF/ml, the density of the nerve fiber network did not change, but the reinnervated area of the irides was significantly decreased compared to the outgrowth seen in irides treated with 100 micrograms/ml. In conclusion, adult rat chromaffin tissue responds to rhNGF in a dose-dependent manner. However, at the highest doses used, the outgrowth area was suboptimal, although nerve fiber density was maximal. These results indicate that to obtain maximal effects, the dose of NGF is critical.