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Patients with traumatic brain injury (TBI) regularly require intensive care with prolonged invasive ventilation. Consequently, these patients are at increased risk of pulmonary failure, potentially requiring extracorporeal membrane oxygenation (ECMO). The aim of this work was to provide an overview of ECMO treatment in TBI patients based upon data captured into the TraumaRegister DGU® (TR-DGU).A retrospective multi-center cohort analysis of patients registered in the TR-DGU was conducted. Adult patients with relevant TBI (AIS12,247 patients fulfilled the inclusion criteria. The overall rate of ECMO treatment was 1.1% (134 patients). Patients on ECMO had an overall hospital mortality rate of 38% (51/134 patients) while 13% (1523/12,113 patients) of TBI patients without ECMO therapy died. Male gender (p = 0.014), AISECMO therapy is a potentially lifesaving modality for the treatment of moderate-to-severe TBI when combined with severe chest trauma and pulmonary failure. The in-hospital mortality is increased in this high-risk population, but the majority of patients is surviving.

Pathological synchronisation of beta frequency (12–35 Hz) oscillations between the subthalamic nucleus (STN) and cerebral cortex is thought to contribute to motor impairment in Parkinson's disease (PD). For this cortico-subthalamic oscillatory drive to be mechanistically important, it must influence the firing of STN neurons and, consequently, their downstream targets. Here, we examined the dynamics of synchronisation between STN LFPs and units with multiple cortical areas, measured using frontal ECoG, midline EEG and lateral EEG, during rest and movement. STN neurons lagged cortical signals recorded over midline (over premotor cortices) and frontal (over prefrontal cortices) with stable time delays, consistent with strong corticosubthalamic drive, and many neurons maintained these dynamics during movement. In contrast, most STN neurons desynchronised from lateral EEG signals (over primary motor cortices) during movement and those that did not had altered phase relations to the cortical signals. The strength of synchronisation between STN units and midline EEG in the high beta range (25–35 Hz) correlated positively with the severity of akinetic-rigid motor symptoms across patients. Together, these results suggest that sustained synchronisation of STN neurons to premotor-cortical beta oscillations play an important role in disrupting the normal coding of movement in PD., Highlights • Multi-channel EEG with coincident STN single unit and local field potential recordings • Variable time delays between beta oscillations in different cortical areas and STN neurons. • Frontal/premotor cortical areas have most stable oscillatory synchronisation with STN neurons. • Correlation between cortico-subthalamic beta-frequency synchronisation and clinical scores in PD.

Introduction Chronic subdural hematoma (cSDH) is a common pathology encountered in neurosurgical practice, especially in elderly patients, who frequently require antithrombotic agents. The aim of this study was to investigate the influence of antithrombotic agents on recurrence rates and clinical outcomes in patients operated for cSDH. Methods A cohort of patients operated for cSDH at one center during a 5 years period was analyzed retrospectively. Presenting symptoms, coagulation testing, history of antithrombotic agents and comorbidities were obtained from the patient charts. The standard neurosurgical procedure was a single burr hole under local anesthesia with insertion of a subdural drainage. Questionnaires and telephone interviews were used to assess the clinical outcome using the modified Rankin Scale (mRS). Good outcome was defined as mRS 0 to 3 and poor outcome as mRS 4 to 6. Results 201 patients with cSDH underwent initial surgical treatment and were enrolled in the study. The median follow-up was 81 weeks. 41 patients (20.4%) were on antiplatelet drug and 43 (21.4%) were on phenprocoumon. A recurrent hematoma required surgery in 37 patients (18.4%). A poor outcome was seen in 36 patients (17.9%). Each of older age and administration of phenprocoumon at admission was an independent risk factor predictive of poor outcome, ( p = 0.001 and p = 0.031, respectively)) Administration of antithrombotic agents had no impact on hematoma recurrence. Conclusion Administration of phenprocoumon and older age might increase the risk of poor outcome in patients with cSDH. Neither the administration of phenprocoumon nor antiplatelet drug influenced the recurrence rate of subdural hematoma in our patient cohort.

Summary Background The WHO classification of brain tumours describes 15 subtypes of meningioma. Nine of these subtypes are allotted to WHO grade I, and three each to grade II and grade III. Grading is based solely on histology, with an absence of molecular markers. Although the existing classification and grading approach is of prognostic value, it harbours shortcomings such as ill-defined parameters for subtypes and grading criteria prone to arbitrary judgment. In this study, we aimed for a comprehensive characterisation of the entire molecular genetic landscape of meningioma to identify biologically and clinically relevant subgroups. Methods In this multicentre, retrospective analysis, we investigated genome-wide DNA methylation patterns of meningiomas from ten European academic neuro-oncology centres to identify distinct methylation classes of meningiomas. The methylation classes were further characterised by DNA copy number analysis, mutational profiling, and RNA sequencing. Methylation classes were analysed for progression-free survival outcomes by the Kaplan-Meier method. The DNA methylation-based and WHO classification schema were compared using the Brier prediction score, analysed in an independent cohort with WHO grading, progression-free survival, and disease-specific survival data available, collected at the Medical University Vienna (Vienna, Austria), assessing methylation patterns with an alternative methylation chip. Findings We retrospectively collected 497 meningiomas along with 309 samples of other extra-axial skull tumours that might histologically mimic meningioma variants. Unsupervised clustering of DNA methylation data clearly segregated all meningiomas from other skull tumours. We generated genome-wide DNA methylation profiles from all 497 meningioma samples. DNA methylation profiling distinguished six distinct clinically relevant methylation classes associated with typical mutational, cytogenetic, and gene expression patterns. Compared with WHO grading, classification by individual and combined methylation classes more accurately identifies patients at high risk of disease progression in tumours with WHO grade I histology, and patients at lower risk of recurrence among WHO grade II tumours (p=0·0096) from the Brier prediction test). We validated this finding in our independent cohort of 140 patients with meningioma. Interpretation DNA methylation-based meningioma classification captures clinically more homogenous groups and has a higher power for predicting tumour recurrence and prognosis than the WHO classification. The approach presented here is potentially very useful for stratifying meningioma patients to observation-only or adjuvant treatment groups. We consider methylation-based tumour classification highly relevant for the future diagnosis and treatment of meningioma. Funding German Cancer Aid, Else Kroner-Fresenius Foundation, and DKFZ/Heidelberg Institute of Personalized Oncology/Precision Oncology Program.

Intracranial arteriovenous malformation (AVM) in children is a rare diagnosis. Little is known about factors determining AVM rupture and appropriate treatment strategies to prevent hemorrhage and associated disability. Available data suggest that children are subject to an increased risk for AVM rupture compared with adults.In 46 pediatric patients with AVM, demographic factors, clinical presentation, angioarchitectural features, and treatment regimens as well as clinical and radiologic outcomes were retrospectively analyzed. First-line treatment option was microsurgical resection of the disease, with or without preoperative embolization.Twenty-four boys (52.2%) and 22 girls (47.8%) with a mean age on admission of 12.4 years (4-18 years) were included. Mean follow-up was 4 years (median, 1.5; range, 0.1-16.4). Thirty-one children presented with intracerebral hemorrhage (67.4%). Small AVMs (3 cm) ruptured in 83.3% (n = 25) and were shown to be more prone to hemorrhage than larger ones (P0.01). Small AVM size (P 0.01; odds ratio [OR], 0.12; 95% confidence interval [CI] 0.02-0.59) and exclusive deep venous drainage (P0.01; OR, 29.74; 95% CI, 2.45-4445.34) were independent risk factors for hemorrhage in the presented cohort. Good long-term outcome was associated with a high score on the Glasgow Coma Scale on admittance (P0.05; OR, 0.148; 95% CI, 0.03-0.73).Two-thirds of children with AVM are admitted with intracerebral hemorrhage. Microsurgical resection was successful as confirmed by radiologic studies in 95%, and 79.5% of patients presented in a good clinical condition on follow-up (modified Rankin Scale 0 or 1). Microsurgical treatment is recommended if the lesion is accessible and angioarchitectural risk factors favor definitive treatment.

Secretory meningiomas (SM) represent a rare variant of the most common benign intracranial brain tumor. Defined by the histologic appearance of eosinophilic glandular formations and periodic-acidic Schiff-positive pseudopsammoma bodies, SM are characterized by unique molecular alterations, a disproportional occurrence of reactive peritumoral brain edema, and a clinical course that demands for increased awareness for perioperative complications. The frequent presence of extensive peritumoral edema has become a hallmark of SM and can be associated with life-threatening complications. The exact pathophysiology of edema formation in SM is still unknown.

Objective While motor effects of dopaminergic medication and subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD) patients are well explored, their effects on sensory processing are less well understood. Here, we studied the impact of levodopa and STN-DBS on auditory processing. Methods Rhythmic auditory stimulation (RAS) was presented at frequencies between 1 and 6 Hz in a passive listening paradigm. High-density EEG-recordings were obtained before (levodopa ON/OFF) and 5 months following STN-surgery (ON/OFF STN-DBS). We compared auditory evoked potentials (AEPs) elicited by RAS in 12 PD patients to those in age-matched controls. Tempo-dependent amplitude suppression of the auditory P1/N1-complex was used as an indicator of auditory gating. Results Parkinsonian patients showed significantly larger AEP-amplitudes (P1, N1) and longer AEP-latencies (N1) compared to controls. Neither interruption of dopaminergic medication nor of STN-DBS had an immediate effect on these AEPs. However, chronic STN-DBS had a significant effect on abnormal auditory gating characteristics of parkinsonian patients and restored a physiological P1/N1-amplitude attenuation profile in response to RAS with increasing stimulus rates. Conclusions This differential treatment effect suggests a divergent mode of action of levodopa and STN-DBS on auditory processing. Significance STN-DBS may improve early attentive filtering processes of redundant auditory stimuli, possibly at the level of the frontal cortex.

Cortex-basal ganglia circuits participate in motor timing and temporal perception, and are important for the dynamic configuration of sensorimotor networks in response to exogenous demands. In Parkinson's disease (PD) patients, rhythmic auditory stimulation (RAS) induces motor performance benefits. Hitherto, little is known concerning contributions of the basal ganglia to sensory facilitation and cortical responses to RAS in PD. Therefore, we conducted an EEG study in 12 PD patients before and after surgery for subthalamic nucleus deep brain stimulation (STN-DBS) and in 12 age-matched controls. Here we investigated the effects of levodopa and STN-DBS on resting-state EEG and on the cortical-response profile to slow and fast RAS in a passive-listening paradigm focusing on beta-band oscillations, which are important for auditory–motor coupling. The beta-modulation profile to RAS in healthy participants was characterized by local peaks preceding and following auditory stimuli. In PD patients RAS failed to induce pre-stimulus beta increases. The absence of pre-stimulus beta-band modulation may contribute to impaired rhythm perception in PD. Moreover, post-stimulus beta-band responses were highly abnormal during fast RAS in PD patients. Treatment with levodopa and STN-DBS reinstated a post-stimulus beta-modulation profile similar to controls, while STN-DBS reduced beta-band power in the resting-state. The treatment-sensitivity of beta oscillations suggests that STN-DBS may specifically improve timekeeping functions of cortical beta oscillations during fast auditory pacing., Highlights • High density EEG investigation in patients with PD before and after STN-DBS surgery • Resting state EEG: altered spectral composition following STN-DBS • Rhythmic auditory stimulation (RAS): absence of pre-stimulus beta activity in PD • Fast RAS: normalization of beta (13–30 Hz) activities by L-DOPA and STN-DBS • Altered beta modulation profile may contribute to timekeeping deficits in PD.

Objectives: To analyze the need for surgical intervention in Terson’s syndrome (TS) and the rate of TS, as well as the effect of pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) peeling, complications, correlations between TS and sex, and the influence of the severity of subarachnoid hemorrhage (SAH) expressed by Glasgow Coma Scale (GCS) score and Hunt and Hess grade on the occurrence of TS. Design: Prospective, uncontrolled, interdisciplinary study. Participants: A total of 102 patients with SAH over a period of 24 months. Methods: Patients were examined on days 1 and 14. A PPV was indicated in cases of nonresorbing vitreous hemorrhage (VH). Peeling of the ILM was performed with the help of ILM-BLUE (DORC, Zuidland, The Netherlands) using end-gripping ILM forceps. Main Outcome Measures: Effect of PPV on visual acuity (VA) and timing of intervention in cases of nonresorbing VH. Results: The rate of TS was 19.6% (20/102). The mean age of the patients was 52.1� 11.8 years. Patients presenting with an initial GCS of less than 8 or with high Hunt and Hess grades were more affected by TS. Eight (9 eyes) of the 20 patients with TS (40% of the patients with TS) underwent a PPV for nonclearing vitreous bleeding. In 4 patients (4 eyes; 20% of patients with TS), ILM peeling was considered necessary because of subILM bleeding. The mean interval between SAH and PPV was 4.4 months (range, 3e5 months). Postoperative follow-up was 6.4 months. Visual acuity improved in all patients. Best-corrected VAs at first and at last presentations were 2.2 and 0.0625 logarithm of the minimum angle of resolution (logMAR), respectively. For patients who underwent ILM peeling, these values were 1.725 and 0.05 logMAR, respectively. Conclusions: Pars plana vitrectomy and ILM peeling have beneficial effects on the visual rehabilitation of patients with nonclearing VH after TS. We did not identify any safety concerns after PPV in our patients with dense nonclearing hemorrhage that persisted for more than 3 months. Ophthalmology 2014;121:1628-1633 a 2014 by the American Academy of Ophthalmology.

The aim of this study was to analyze growth rate and identify prognostic factors for progression of postoperative plexiform neurofibromas in patients with neurofibromatosis type 1. We measured postoperative tumor volume change per year on magnetic resonance imaging. Linear regression models were applied to identify risk factors for tumor progression. Fifty-two patients (mean age: 25.4 years (3.2–64.2 years)) with 56 plexiform neurofibromas were analyzed. Initial median tumor volume was 40.3 ml (SD: 1,552 (0–10,800)). Surgical indications included disfigurement (n = 21), pain (n = 20), and functional deficits (n = 16). Sixteen percent of all cases experienced acute surgical complication, and 13% showed late complication. Eight patients (19%; 6 children and 2 adults) with residual tumor had repeat surgery for tumor progression. Median tumor progression was 0.6% change per year (SD ± 27.4; range: −59.2 to 88.1) and 2.9% from baseline (SD ± 163.9; range −1,001.3 to 81.8). Patients aged 21 years and younger had the highest progression rate (P < 0.01). For every year of age, the mean growth rate decreased by −0.463 mean percent (P = 0.03). With age as a continuous variable, age, the site of the tumor, and depth were the only factors associated with tumor progression. Fourteen plexiform neurofibromas (10 nodular and 4 diffuse) in 13 patients (5 children and 8 adults) were completely resected (by visualization) and did not relapse during observation (mean: 2.9 years; range: 1.1–5.8 years). Age, tumor type, location, and depth are helpful to estimate the progression of plexiform neurofibromas after surgery. Patients benefit from elective surgery of small and completely removable plexiform neurofibromas. Genet Med 15 9, 691–697.

Summary Background Besides the use of temozolomide and radiotherapy for patients with favourable methylation status, little progress has been made in the treatment of adult glioblastoma. Local control of the disease by complete removal increases time to progression and survival. We assessed the efficacy and safety of a locally applied adenovirus-mediated gene therapy with a prodrug converting enzyme (herpes-simplex-virus thymidine kinase; sitimagene ceradenovec) followed by intravenous ganciclovir in patients with newly diagnosed resectable glioblastoma. Methods For this international, open-label, randomised, parallel group multicentre phase 3 clinical trial, we recruited patients from 38 sites in Europe. Patients were eligible if they were aged 18–70 years, had newly diagnosed supratentorial glioblastoma multiforme amenable to complete resection, and had a Karnofsky score of 70 or more at screening. We used a computer-generated randomisation sequence to allocate patients in a one-to-one ratio (with block sizes of four) to receive either surgical resection of the tumour and intraoperative perilesional injection of sitimagene ceradenovec (1 × 10 12 viral particles) followed by ganciclovir (postoperatively, 5 mg/kg intravenously twice a day) in addition to standard care or resection and standard care alone. Temozolomide, not being standard in all participating countries at the time of the study, was allowed at the discretion of the treating physician. The primary endpoint was a composite of time to death or re-intervention, adjusted for temozolamide use, assessed by intention-to-treat (ITT) analysis. This trial is registered with EudraCT, number 2004-000464-28. Findings Between Nov 3, 2005, and April 16, 2007, 250 patients were recruited and randomly allocated: 124 to the experimental group and 126 to the standard care group, of whom 119 and 117 patients, respectively, were included in the ITT analyses. Median time to death or re-intervention was longer in the experimental group (308 days, 95% CI 283–373) than in the control group (268 days, 210–313; hazard ratio [HR] 1·53, 95% CI 1·13–2·07; p=0·006). In a subgroup of patients with non-methylated MGMT , the HR was 1·72 (95% CI 1·15–2·56; p=0·008). However, there was no difference between groups in terms of overall survival (median 497 days, 95% CI 369–574 for the experimental group vs 452 days, 95% CI 437–558 for the control group; HR 1·18, 95% CI 0·86–1·61, p=0·31). More patients in the experimental group had one or more treatment-related adverse events those in the control group (88 [71%] vs 51 [43%]). The most common grade 3–4 adverse events were hemiparesis (eight in the experimental group vs three in the control group) and aphasia (six vs two). Interpretation Our findings suggest that use of sitimagene ceradenovec and ganciclovir after resection can increase time to death or re-intervention in patients with newly diagnosed supratentorial glioblastoma multiforme, although the intervention did not improve overall survival. Locally delivered gene therapy for glioblastoma should be further developed, especially for patients who are unlikely to respond to standard chemotherapy. Funding Ark Therapeutics Ltd.

Background The incidence of extraneural metastases of glioma is low. Metastases occur at different sites and, infrequently, as diffuse bone marrow infiltration. Direct contact of a glioma with extrameningeal tissues might be a reason for extraneural metastases. However, the role of haematogenous spread remains unclear. Methods We report on a young patient who suffered from a left frontal anaplastic WHO grade III astrocytoma, which was treated with gross total resection and irradiation (60 Gy). No local relapse occurred during the following course, but a diffuse infiltration of the bone marrow was diagnosed 12 months after the initial diagnosis. The patient died 6 months later, as a result of hypercalcaemia and pancytopenia. The histopathological properties of the tumour and its bone metastases were analysed, as well as the mutations of the isocitrate dehydrogenase 1 gene (IDH1). To study the route of tumour dissemination, the peripheral blood of the patient was analysed for circulating tumour cells (CTCs). Results This study describes a rare case of an extraneurally metastasised WHO grade III anaplastic astrocytoma. The occurrence of bone marrow infiltration coinciding with the finding of a stable intracranial tumour is a notably unusual situation. The properties of the primary tumour were maintained within the metastases in our patient. No CTCs were found in the peripheral blood at one random time point after the diagnosis of bone metastases. Conclusions Despite young patient age, a stable intracranial course with a single location and mutations in the IDH1 gene, the patient's overall survival was short at 18 months after diagnosis. This finding illustrates the therapeutic dilemma in patients with bone marrow involvement complicating the use of alkylating agents, such as temozolomide. Repeated and systematic blood sampling in a large cohort of patients is needed for the detection of CTCs in glioma patients with systemic tumour spread. Future studies investigating how intrinsic factors in glioma cell biology cause rare metastases in these tumours are needed.

Intrathecal delivery methods have been used for many decades to treat a broad range of central nervous system disorders. A literature review demonstrated that intracerebroventricular route is an established and well-tolerated method for prolonged central nervous system drug delivery in pediatric and adult populations. Intracerebroventricular devices were present in patients from one to 7156 days. The number of punctures per device ranged from 2 to 280. Noninfectious complication rates per patient (range, 1.0% to 33.0%) were similar to infectious complication rates (0.0% to 27.0%). Clinician experience and training and the use of strict aseptic techniques have been shown to reduce the frequency of complications.

Thromboxane synthase (TXSA), an enzyme of the arachidonic acid metabolism, is upregulated in human glial tumors and is involved in glioma progression. Here, we analyzed the in vitro and in vivo effects of pharmacological inhibition of TXSA activity on human glioblastoma cells. Furegrelate, a specific inhibitor of TXSA, significantly inhibited tumor growth in an orthotopic glioblastoma model by inducing proapoptotic, antiproliferative, and antiangiogenic effects. Inhibition of TXSA induced a proapoptotic disposition of glioma cells and increased the sensitivity to the chemotherapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea, significantly prolonging the survival time of intracerebral glioma-bearing mice. Our data demonstrate that the targeted inhibition of TXSA activity improves the efficiency of conventional alkylation chemotherapy in vivo. Our study supports the role of TXSA activity for the progression of malignant glioma and the potential utility of its therapeutic modulation for glioma treatment. peerReviewed

Intraoperative ultrasound (IOUS) was used in planning the operative resection of intradural spinal tumors, to define its diagnostic potential and limitations. Since 1997, 78 patients diagnosed with an ependymoma (n = 24), astrocytoma (n = 7), hemangioblastoma (n = 7), neurinoma (n = 15), meningioma (n = 17) and filum terminale ependymoma (n = 8) were examined using intraoperative transdural sonography. Intramedullary tumors turned out to show a heterogeneous image with occasional cystic alterations and an indistinct demarcation to the myelon of comparable echogenicity. Intramedullary tumors are easily distinguishable from their extramedullary counterparts, which display a homogeneous signal intensity and sharp demarcation on IOUS. In conclusion, IOUS allows a reliable diagnosis of intraspinal tumors, allowing the distinction between intra- and extramedullary tumors through their respective signal characteristics. Using IOUS, the extension of the neurosurgical approach can be adopted to the true extent of the tumor; thus, avoiding further bone work while the dura is already opened and the frequently edematous spinal cord protrudes through the opening. Our experiences have shown that IOUS may reduce the procedure-related morbidity and should, therefore, be used as a standard intraoperative tool in these high-risk surgical entities. (E-mail: ).

We report a rare case of a brain abscess which drained spontaneously in a temporomandibular joint damaged by osteoarthritis. The female patient presented to our hospital with a severe headache and pain in the temporomandibular joint. She showed elevated inflammatory parameters with unknown cause. Magnetic resonance imaging of her whole body revealed a large temporal brain abscess extending into the glenoid fossa of the temporomandibular joint. The brain abscess was incised and drained by neurosurgeons in our hospital and in the same operation we resected the articular disc and the affected part of the right temporomandibular joint. Histological examination confirmed a chronic arthrosis in the resected bone of the temporomandibular joint and an inflammatory abscess in the resected brain tissue. The patient recovered well and the inflammation resolved as seen in postoperative investigations. Magnetic resonance imaging a month later confirmed local consolidation in the brain with no sign of residual inflammation.

Vascular endothelial growth factor (VEGF) is an important mediator of the intense angiogenesis which is characteristic of glioblastoma. While genetic manipulation of VEGF/VEGF receptor expression has previously been shown to inhibit glioblastoma growth, to date, no study has examined the efficacy of pharmacologic blockade of VEGF activity as a means to inhibit intracranial growth of human glioblastoma. Using intraperitoneal administration of a neutralizing anti-VEGF antibody, we demonstrate that inhibition of VEGF significantly prolongs survival in athymic rats inoculated in the basal ganglia with G55 human glioblastoma cells. Systemic anti-VEGF inhibition causes decreased tumor vascularity as well as a marked increase in tumor cell apoptosis in intracranial tumors. Although intracranial glioblastoma tumors grow more slowly as a consequence of anti-VEGF treatment, the histologic pattern of growth suggests that these tumors adapt to inhibition of angiogenesis by increased infiltration and cooption of the host vasculature.

A number of genes, including IGF2 and H19, are normally imprinted with preferential expression of the paternal or maternal allele, respectively. Loss of imprinting (LOI) of IGF2 and H19 is found in a number of tumours, suggesting that LOI of IGF2 and/or H19 may play an important role in tumorigenesis. The IGF2 gene codes for a fetal growth factor and the H19 gene is likely to act as an RNA with an antitumour effect. We investigated the imprinting status of IGF2 and H19 in human meningiomas. The normally imprinted IGF2 gene lacks imprint in the leptomeninges and choroid plexus of the brain. To examine the imprinting status of IGF2 and H19 in human meningiomas we used the ApaI polymorphism in exon 9 for the IGF2 gene and the AluI polymorphism in exon 5 for the H19 gene. In total, 24 meningiomas of WHO grade I, II and III were analysed. 15 meningiomas (63%) were informative for the ApaI polymorphism in the IGF2 gene. Monoallelic expression (MAE) for IGF2 was found in 11 out of 15 tumours (73%) which is in contrast to the lack of imprinting status of IGF2 in leptomeninges. Ten cases (42%) were heterozygous for the H19 gene and biallelic expression was found in 3 out of 10 meningiomas (30%). These results indicate that modulation of the imprinting status of IGF2 and H19 may play an important role for the development of meningiomas.

Meningiomas are usually benign tumors; however, they can recur after surgical resection and occasionally show histological progression to a higher malignancy grade. Five such rare cases of aggressively recurring meningiomas were present in our departmental cohort of 923 primary meningeal neoplasms operated over a 17-year period. Four other aggressively recurring meningeal tumors with a very similar clinical and histomorphological appearance (three undifferentiated meningeal sarcomas, one hemangiopericytoma) were also included in this study. We investigated whether disease progression can be traced by genetic alterations and whether a pattern of genetic alterations is specific for meningiomas. A total of 40 specimens from primary tumors and multiple recurrences of the nine patients were analyzed with 26 polymorphic allelic markers for deletions on 1p, 1q, 9q, 10q, 14q, and 22q. Loss of heterozygosity (LOH) at 22q was observed in all meningiomas cases at the earliest time point analyzed. Allelic loss at 1p was seen in the original tumor in two cases and upon meningioma recurrence in two others. Deletion on 10q occurred during tumor progression in two cases, and on 9q and 14q in one case. While allelic loss at 22q appears to be an early event in aggressive meningioma disease, there is a clear correlation of further deletions on chromosome arms 1p, 9q, 10q, and 14q with histopathological and clinical progression, as shown in these intraindividual trackings. None of these genetic findings were present in the non-meningiomatous meningeal tumors, indicating that meningothelial cells have their own lineage-specific genetic pathways towards clinical malignancy.

We report on a group of 76 patients who had been treated during a period in which preoperative embolization using interventional neuroradiologic technique was standard procedure. During this time, 20 consecutive patients were operated on without embolization, eight patients were treated with embolization only, and 48 patients were operated on after embolization. In 35 cases surgery immediately followed the last embolization procedure. All arteriovenous malformations (AVMs) were classified and the outcome analyzed according to Spetzler [J Neurosurg 1986; 65: 476-83]. Those lesions treated with a combination of embolization and surgery had higher Spetzler grading than those that had been operated without previous embolization. The overall recovery rate was 82.9%. In 7.9% of the cases the AVMs were not totally extirpated. The overall complication rate was 9.2%. It is concluded that preoperative embolization facilitates surgery and reduces the risk of severe morbidity and mortality, especially in high-grade lesions. In addition to the clinical results, the application and usefulness of Ethibloc as an embolizing agent is reported.

Dermorphin and a camel beta-endorphin ( β c -EP) analog in which residues 1–7 correspond to the dermorphin sequence ([Dermorphin 1–7 ]- β c -EP) have been investigated with respect to their receptor binding characteristics using human and camel β-EP as reference peptides. Tritiated dihydromorphine, [D-Ala 2 , D-Leu 5 ]-enkephalin, ethylketocyclazocine and human β-endorphin were used as primary ligands in the rat brain membrane preparation for radioreceptor assay. Camel β-endorphin was the most potent peptide in all experiments. [Dermorphin 1–7 ]- β c -EP is significantly less potent towards 3 H-ethylketocyclazocine and 3 H-[D-Ala 2 , D-Leu 5 ]-enkephalin but is as potent towards 3 H-dihydromorphine and 3 H-human β-endorphin. Dermorphin itself weakly displaces tritiated dihydromorphine, [D-Ala 2 , D-Leu 5 ]-enkephalin and ethylketocyclazocine (potency relative to camel β-EP, 1–4%) but it is more potent (9%) in competition with tritiated human β-endorphin. Dermorphin and the [Dermorphin 1–7 ]- β c -EP appear to interact preferentially with μ opiate receptors.

Primary cell cultures were initiated from surgically obtained specimens from human gliomas. After 4–10 passages in vitro the cells from 18 individual cases were seeded onto cluster dishes and left to attach for 24 h in medium containing fetal calf serum. Thereafter the medium was changed to serumfree, defined conditions and the following growth factors were added: EGF 1.5 × 10 − 8 M, PDGF 35 ng/ml, FGF 80 pg/ml. The growth factors were added fresh every 2 days. After 9 or 11 days in culture, the cells on one multiwell-plate were counted. In 8 cases another set which was cultured also in a multiwell-plate but on glass cover slides was immunostained for glial fibrillary acidic protein (GFAP), fibronectin (FN), A2B5 and galactocerebroside (galC). The proliferative response pattern in consequence to the growth factor addition varied greatly between different cases. In all cases a pronounced proliferative response was accompanied by marked changes on the culture morphology. Usually the best proliferative response was obtained with PDGF (10 cases) or FGF (8 cases) whereas EGF was most effective only in one case. Two cases showed only minimal response, one of which was an oligodendroglioma D according to Ludwig and another a gliosarcoma which was re-evaluated after 1 year in culture. It could be noted, however, that FGF had a tendency to be less effective in the group of malignant astrocytomas. The staining pattern of the cultures with the afore mentioned markers was not affected by the growth factor treatment. The proliferative response usually resulted in increased staining for fibronectin and never an induction of GFAP. A2B5 staining was positive only in one case of gliosarcoma and galC staining was regularly negative.

An antiserum against bovine pancreatic trypsin inhibitor (bPTI) has been raised in rabbits. The antiserum does not cross-react with known pituitary hormones and other proteins. A specific radioimmunoassay for bPTI has been developed. The ED50 is about 250 fmol per assay tube and the sensitivity is reliable to 15 fmol per tube. Immunoreactivity could be detected in bovine and sheep pituitaries, bovine brain, and adrenal medulla, but not in human, pig, and rat pituitaries. In the bovine pituitary the immunoreactivity is restricted to the posterior lobe.