Publications by authors named "Roland Goldbrunner"

141 Publications

Improving the efficacy and reliability of rTMS language mapping by increasing the stimulation frequency.

Hum Brain Mapp 2021 Nov 13;42(16):5309-5321. Epub 2021 Aug 13.

Faculty of Medicine and University Hospital, Center for Neurosurgery, Department of General Neurosurgery, University of Cologne, Cologne, Germany.

Repetitive TMS (rTMS) with a frequency of 5-10 Hz is widely used for language mapping. However, it may be accompanied by discomfort and is limited in the number and reliability of evoked language errors. We, here, systematically tested the influence of different stimulation frequencies (i.e., 10, 30, and 50 Hz) on tolerability, number, reliability, and cortical distribution of language errors aiming at improved language mapping. 15 right-handed, healthy subjects (m = 8, median age: 29 yrs) were investigated in two sessions, separated by 2-5 days. In each session, 10, 30, and 50 Hz rTMS were applied over the left hemisphere in a randomized order during a picture naming task. Overall, 30 Hz rTMS evoked significantly more errors (20 ± 12%) compared to 50 Hz (12 ± 8%; p <.01), whereas error rates were comparable between 30/50 and 10 Hz (18 ± 11%). Across all conditions, a significantly higher error rate was found in Session 1 (19 ± 13%) compared to Session 2 (13 ± 7%, p <.05). The error rate was poorly reliable between sessions for 10 (intraclass correlation coefficient, ICC = .315) and 30 Hz (ICC = .427), whereas 50 Hz showed a moderate reliability (ICC = .597). Spatial reliability of language errors was low to moderate with a tendency toward increased reliability for higher frequencies, for example, within frontal regions. Compared to 10 Hz, both, 30 and 50 Hz were rated as less painful. Taken together, our data favor the use of rTMS-protocols employing higher frequencies for evoking language errors reliably and with reduced discomfort, depending on the region of interest.
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http://dx.doi.org/10.1002/hbm.25619DOI Listing
November 2021

Clinical Characteristics and Magnetic Resonance Imaging-Based Prediction of the KLF4 Mutation in Meningioma.

World Neurosurg 2021 Oct 31;154:e665-e670. Epub 2021 Jul 31.

Department of Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.

Background: Meningioma is the most common primary brain tumor in adults. In recent years, several non-neurofibromin 2 mutations, i.e., AKT1, SMO, TRAF7, and KLF4 mutations, specific for meningioma have been identified. This study aims to analyze the clinical impact and imaging characteristics of the KLF4 mutation in meningioma.

Methods: Clinical, neuropathologic, and imaging data of 170 patients who underwent meningioma resection between 2013 and 2018 were retrospectively collected and tumors were analyzed for the presence of the KLF4 mutation. We collected imaging characteristics, performed volumetric analysis of tumor size and peritumoral edema (PTBE), and calculated the edema index (EI, i.e., ratio of PTBE to tumor volume). Receiver operating characteristic curve analysis was performed to identify cut-off EI values to predict the mutational status of KLF4.

Results: Eighteen (10.6%) of the meningiomas carried the KLF4 mutation; these were significantly associated with a secretory subtype (P < 0.001) and sphenoid wing location (P = 0.029). Smaller tumor size (P = 0.007), an increased PTBE (P = 0.012), and an increased EI (P = 0.001) proved to be significantly associated with the KLF4 mutation. In receiver operating characteristic curve analysis, EI predicted the KLF4 mutation with an area under the curve of 0.728 (P = 0.0016).

Conclusions: The KLF4 mutation is associated with a distinct small tumor subtype, prone to substantial PTBE. EI is a reliable parameter to predict the KLF4 mutation in meningioma, thus providing a tool for improvement of pre- and perioperative medical management.
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http://dx.doi.org/10.1016/j.wneu.2021.07.119DOI Listing
October 2021

TERT and its binding protein: overexpression of GABPA/B in high grade gliomas.

Oncotarget 2021 Jun 22;12(13):1271-1280. Epub 2021 Jun 22.

Laboratory of Neurooncology and Experimental Neurosurgery, Department of General Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.

Enhanced expression of TERT in gliomas is a result of two hotspot mutations, C228T and C250T, at the promoter region. GA-binding proteins selectively bind at these positions, respectively, causing an activation of the promoter and overexpression of TERT. GABP is a multimeric protein consisting of GABPA and GABPB with its isoforms GABPB1, GABPB1-L, GABPB1-S, GABPB2. In this study, we investigated the mRNA expression and association between TERT and GABPA/B isoforms in tumor samples of different glioma grades. The expression was determined by quantitative real-time PCR and the results were statistically analyzed. We present that TERT is mainly expressed in primary glioblastomas. All GA-binding proteins progress through the glioma grades and have the highest expression levels in secondary glioblastomas. In secondary glioblastomas after chemotherapy, GABPB1 and GABPB1-L are expressed on a lower level than without treatment. In high grades, TERT and GABPA, GAPB1, GABPB1-L, GABPB1-S are upregulated compared to low grades. Between primary and secondary glioblastomas with and without chemotherapy, TERT is elevated in the former while GABPB1 is increased in the secondary glioblastomas. GABPA and GABPB1, GABPB1-L and GABPB1-S positive correlate in primary glioblastomas. The present study confirms the upregulation of TERT in primary glioblastomas while all GABP proteins rise with the malignancy of the gliomas. Further investigations must be made to elucidate the relation between TERT and all GABP proteins as it may play a key role in the gliomagenesis.
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http://dx.doi.org/10.18632/oncotarget.27985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238242PMC
June 2021

EANO guideline on the diagnosis and management of meningiomas.

Neuro Oncol 2021 Jun 28. Epub 2021 Jun 28.

Department of Neurology, University Hospital and University of Zurich, Clinical Neuroscience Center, Zurich, Switzerland.

Meningiomas are the most common intracranial tumors. Yet, only few controlled clinical trials have been conducted to guide clinical decision making, resulting in variations of management approaches across countries and centers. However, recent advances in molecular genetics and clinical trial results help to refine the diagnostic and therapeutic approach to meningioma. Accordingly, the European Association of Neuro-Oncology (EANO) updated its recommendations for the diagnosis and treatment of meningiomas. A provisional diagnosis of meningioma is typically made by neuroimaging, mostly magnetic resonance imaging. Such provisional diagnoses may be made incidentally. Accordingly, a significant proportion of meningiomas, notably in patients that are asymptomatic or elderly or both, may be managed by a watch-and-scan strategy. A surgical intervention with tissue, commonly with the goal of gross total resection, is required for the definitive diagnosis according to the WHO classification. A role for molecular profiling including gene panel sequencing and genomic methylation profiling is emerging. A gross total surgical resection including the involved dura is often curative. Inoperable or recurrent tumors requiring treatment can be treated with radiosurgery, if size or the vicinity of critical structures allow that, or with fractionated radiotherapy (RT). Treatment concepts combining surgery and radiosurgery or fractionated RT are increasingly used, although there remain controversies regard timing, type and dosing of the various RT approaches. Radionuclide therapy targeting somatostatin receptors is an experimental approach, as are all approaches of systemic pharmacotherapy. The best albeit modest results with pharmacotherapy have been obtained with bevacizumab or multikinase inhibitors targeting vascular endothelial growth factor receptor, but no standard of care systemic treatment has been yet defined.
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http://dx.doi.org/10.1093/neuonc/noab150DOI Listing
June 2021

Impact of aneurysm morphology on aneurysmal subarachnoid hemorrhage severity, cerebral infarction and functional outcome.

J Clin Neurosci 2021 Jul 2;89:343-348. Epub 2021 Jun 2.

Center for Neurosurgery, Medical Faculty and University Hospital, University of Cologne, Kerpener Strasse 62, 50937 Cologne, Germany; Department of Neurosurgery, Hôpitaux Robert Schuman, 9 Rue Edward Steichen, 2540, Luxembourg.

Objective: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity. The objective was to evaluate, whether specific morphological aneurysm characteristics could serve as predictive values for aSAH severity, disease-related complications and clinical outcome.

Methods: A total of 453 aSAH patients (mean age: 54.9 ± 13.8 years, mean aneurysm size: 7.5 ± 3.6 mm) treated at a single center were retrospectively included. A morphometric analysis was performed based on angiographic image sets, determining aneurysm location, aneurysm size, neck width, aneurysm size ratios, aneurysm morphology and vessel size. The following outcome measures were defined: World Federation of Neurosurgical Societies (WFNS) grade 4 and 5, Fisher grade 4, vasospasm, cerebral infarction and unfavorable functional outcome.

Results: Regarding morphology parameters, aneurysm neck width was an independent predictor for Fisher 4 hemorrhage (OR: 1.1, 95%CI: 1.0-1.3, p = 0.048), while dome width (OR: 0.92, 95%CI: 0.86-0.97, p = 0.005) and internal carotid artery location (OR: 2.1, 95%CI: 1.1-4.2, p = 0.028) predicted vasospasm. None of the analyzed morphological characteristics prognosticated functional outcome. Patient age (OR: 0.95, 95%CI: 0.93-0.96, p < 0.001), WFNS score (OR: 4.8, 95%CI: 2.9-8.0, p < 0.001), Fisher score (OR: 2.3, 95%CI: 1.4-3.7, p < 0.001) and cerebral infarction (OR: 4.5, 95%CI: 2.7-7.8, p < 0.001) were independently associated with unfavorable outcome.

Conclusions: The findings indicate a correlation between aneurysm morphology, Fisher grade and vasospasm. Further studies will be required to reveal an independent association of aneurysm morphology with cerebral infarction and functional outcome.
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http://dx.doi.org/10.1016/j.jocn.2021.04.029DOI Listing
July 2021

Lesion-Function Analysis from Multimodal Imaging and Normative Brain Atlases for Prediction of Cognitive Deficits in Glioma Patients.

Cancers (Basel) 2021 May 14;13(10). Epub 2021 May 14.

Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, 52428 Juelich, Germany.

Cognitive deficits are common in glioma patients following multimodality therapy, but the relative impact of different types and locations of treatment-related brain damage and recurrent tumors on cognition is not well understood. In 121 WHO Grade III/IV glioma patients, structural MRI, -(2-[18F]fluoroethyl)-L-tyrosine FET-PET, and neuropsychological testing were performed at a median interval of 14 months (range, 1-214 months) after therapy initiation. Resection cavities, T1-enhancing lesions, T2/FLAIR hyperintensities, and FET-PET positive tumor sites were semi-automatically segmented and elastically registered to a normative, resting state (RS) fMRI-based functional cortical network atlas and to the JHU atlas of white matter (WM) tracts, and their influence on cognitive test scores relative to a cohort of matched healthy subjects was assessed. T2/FLAIR hyperintensities presumably caused by radiation therapy covered more extensive brain areas than the other lesion types and significantly impaired cognitive performance in many domains when affecting left-hemispheric RS-nodes and WM-tracts as opposed to brain tissue damage caused by resection or recurrent tumors. Verbal episodic memory proved to be especially vulnerable to T2/FLAIR abnormalities affecting the nodes and tracts of the left temporal lobe. In order to improve radiotherapy planning, publicly available brain atlases, in conjunction with elastic registration techniques, should be used, similar to neuronavigation in neurosurgery.
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http://dx.doi.org/10.3390/cancers13102373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156090PMC
May 2021

The Debatable Benefit of Gross-Total Resection of Brain Metastases in a Comprehensive Treatment Setting.

Cancers (Basel) 2021 Mar 21;13(6). Epub 2021 Mar 21.

Centre for Neurosurgery, Department of General Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50923 Cologne, Germany.

The value of gross-total surgical resection remains debatable in patients with brain metastases (BMs) as most patients succumb to systemic disease progression. In this study, we evaluated the impact of the extent of resection of singular/solitary BM on in-brain recurrence (iBR), focusing on local recurrence (LR) and overall survival (OS) in an interdisciplinary adjuvant treatment setting. In this monocentric retrospective analysis, we included patients receiving surgery of one BM and subsequent adjuvant treatment. A radiologist and a neurosurgeon determined in consensus the extent of resection based on magnetic resonance imaging. The OS was calculated using Kaplan-Meier estimates; prognostic factors for LR and OS were analysed by Log rank test and Cox proportional hazards. We analyzed 197 patients. Gross-total resection was achieved in 123 (62.4%) patients. All patients were treated with adjuvant radiotherapy, and 130 (66.0%) received systemic treatment. Ninety-six (48.7%) patients showed iBR with an LR rate of 23.4%. LR was not significantly influenced by the extent of resection ( = 0.139) or any other parameter. The median OS after surgery was 18 (95%CI 12.5-23.5) months. In univariate analysis, the extent of resection did not influence OS ( = 0.6759), as opposed to adjuvant systemic treatment ( < 0.0001) and controlled systemic disease ( = 0.039). Systemic treatment and controlled disease status remained independent factors for OS ( < 0.0001 and = 0.009, respectively). In this study, the extent of resection of BMs neither influenced the LR nor the OS of patients receiving interdisciplinary adjuvant treatment.
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http://dx.doi.org/10.3390/cancers13061435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004079PMC
March 2021

The Cologne Picture Naming Test for Language Mapping and Monitoring (CoNaT): An Open Set of 100 Black and White Object Drawings.

Front Neurol 2021 3;12:633068. Epub 2021 Mar 3.

Department of Special Education and Rehabilitation, Faculty of Human Sciences, University of Cologne, Cologne, Germany.

Language assessment using a picture naming task crucially relies on the interpretation of the given verbal response by the rater. To avoid misinterpretations, a language-specific and linguistically controlled set of unambiguous, clearly identifiable and common object-word pairs is mandatory. We, here, set out to provide an open-source set of black and white object drawings, particularly suited for language mapping and monitoring, e.g., during awake brain tumour surgery or transcranial magnetic stimulation, in German language. A refined set of 100 black and white drawings was tested in two consecutive runs of randomised picture order and was analysed in respect of correct, prompt, and reliable object recognition and naming in a series of 132 healthy subjects between 18 and 84 years (median 25 years, 64% females) and a clinical pilot cohort of 10 brain tumour patients (median age 47 years, 80% males). The influence of important word- and subject-related factors on task performance and reliability was investigated. Overall, across both healthy subjects and patients, excellent correct object naming rates (97 vs. 96%) as well as high reliability coefficients (Goodman-Kruskal's gamma = 0.95 vs. 0.86) were found. However, the analysis of variance revealed a significant, overall negative effect of low word frequency ( < 0.05) and high age ( < 0.0001) on task performance whereas the effect of a low educational level was only evident for the subgroup of 72 or more years of age ( < 0.05). Moreover, a small learning effect was observed across the two runs of the test ( < 0.001). In summary, this study provides an overall robust and reliable picture naming tool, optimised for the clinical use to map and monitor language functions in patients. However, individual familiarisation before the clinical use remains advisable, especially for subjects that are comparatively prone to spontaneous picture naming errors such as older subjects of low educational level and patients with clinically apparent word finding difficulties.
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http://dx.doi.org/10.3389/fneur.2021.633068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966504PMC
March 2021

Cyberknife hypofractionated stereotactic radiosurgery (CK-hSRS) as salvage treatment for brain metastases.

J Cancer Res Clin Oncol 2021 Sep 26;147(9):2765-2773. Epub 2021 Feb 26.

Department of Stereotaxy and Functional Neurosurgery, Centre of Neurosurgery, Faculty of Medicine and University Hospital, University of Cologne, Cologne, 50937, Germany.

Purpose: The introduction of hypofractionated stereotactic radiosurgery (hSRS) extended the treatment modalities beyond the well-established single-fraction stereotactic radiosurgery and fractionated radiotherapy. Here, we report the efficacy and side effects of hSRS using Cyberknife (CK-hSRS) for the treatment of patients with critical brain metastases (BM) and a very poor prognosis. We discuss our experience in light of current literature.

Methods: All patients who underwent CK-hSRS over 3 years were retrospectively included. We applied a surface dose of 27 Gy in 3 fractions. Rates of local control (LC), systemic progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier method. Treatment-related complications were rated using the Common Terminology Criteria for Adverse Events (CTCAE).

Results: We analyzed 34 patients with 75 BM. 53% of the patients had a large tumor, tumor location was eloquent in 32%, and deep seated in 15%. 36% of tumors were recurrent after previous irradiation. The median Karnofsky Performance Status was 65%. The actuarial rates of LC at 3, 6, and 12 months were 98%, 98%, and 78.6%, respectively. Three, 6, and 12 months PFS was 38%, 32%, and 15%, and OS was 65%, 47%, and 28%, respectively. Median OS was significantly associated with higher KPS, which was the only significant factor for survival. Complications CTCAE grade 1-3 were observed in 12%.

Conclusion: Our radiation schedule showed a reasonable treatment effectiveness and tolerance. Representing an optimal salvage treatment for critical BM in patients with a very poor prognosis and clinical performance state, CK-hSRS may close the gap between surgery, stereotactic radiosurgery, conventional radiotherapy, and palliative care.
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http://dx.doi.org/10.1007/s00432-021-03564-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310836PMC
September 2021

Microsurgical Clipping versus Advanced Endovascular Treatment of Unruptured Middle Cerebral Artery Bifurcation Aneurysms After a "Coil-First" Policy.

World Neurosurg 2021 05 17;149:e336-e344. Epub 2021 Feb 17.

Center for Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Department of Neuroradiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. Electronic address:

Objective: Although intracranial aneurysms are increasingly treated endovascularly, microsurgical clipping has been the standard approach for middle cerebral artery (MCA) aneurysms. We compared microsurgical clipping and state-of-the-art endovascular treatment of unruptured MCA bifurcation aneurysms treated at a neurovascular center following a "coil-first" policy.

Methods: This single-center study included 148 patients treated for 160 unruptured MCA bifurcation aneurysms. Technical success, complications, clinical outcome, and angiographic results were retrospectively compared.

Results: Microsurgical clipping was performed for 120 MCA aneurysms (75%) and endovascular treatment for 40 (25%; conventional coiling: 8, stent-assisted coiling: 16, balloon-assisted coiling: 3, and flow-disruption: 13). Technical treatment success was higher in the clipping group (100%) than in the endovascular group (92.5%, P = 0.015). Overall, complications occurred in 16.7% for clipping and in 20.0% for endovascular treatment (P = 0.631). Major ischemic stroke rates were 4.2% in the clipping group and 7.5% in the endovascular group (P = 0.414). At 6 months, a favorable outcome was obtained by 99.2% after clipping and 95.0% after endovascular treatment (P = 0.154). The 6-month complete aneurysm occlusion rates were by trend higher in the clipping group (89.2%) than in the endovascular group (75.9%, P = 0.078).

Conclusions: Microsurgical clipping was associated with a higher technical success rate and tendentially higher complete occlusion than endovascular treatment, with no additional morbidity and similar clinical outcome. On the basis of these results, clipping proves to be the standard treatment option for MCA bifurcation aneurysms. However, endovascular treatment represents a safe and efficient alternative treatment option for patients.
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http://dx.doi.org/10.1016/j.wneu.2021.02.027DOI Listing
May 2021

Brain Metastases in Elderly Patients-The Role of Surgery in the Context of Systemic Treatment.

Brain Sci 2021 Jan 18;11(1). Epub 2021 Jan 18.

Department of General Neurosurgery, University Hospital Cologne, Kerpener Straße 62, 50937 Cologne, Germany.

In patients with brain metastases (BM), advanced age is considered a negative prognostic factor. To address the potential reasons for that, we assessed 807 patients who had undergone BM resection; 315 patients aged at least 65 years (group A) were compared with 492 younger patients (group B). We analyzed the impact of the pre- and postoperative Karnofsky performance status (KPS), postoperative treatment structure and post-treatment survival. BM resection significantly improved KPS scores in both groups ( = 0.0001). Median survival after BM resection differed significantly between the groups (A: 5.81 . B: 8.12 months; = 0.0015). In both groups, patients who received postoperative systemic treatment showed significantly longer overall survival ( = 0.00001). However, elderly patients less frequently received systemic treatment ( = 0.0001) and the subgroup of elderly patients receiving such therapies had a significantly higher postsurgical KPS score ( = 0.0007). In all patients receiving systemic treatment, age was no longer a negative prognostic factor. Resection of BM improves the functional status of elderly patients, thus enhancing the likeliness to receive systemic treatment, which, in turn, leads to longer overall survival. In the context of such a treatment structure, age alone is no longer a prognostic factor for survival.
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http://dx.doi.org/10.3390/brainsci11010123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831306PMC
January 2021

MGMT-Positive vs MGMT-Negative Patients With Glioblastoma: Identification of Prognostic Factors and Resection Threshold.

Neurosurgery 2021 03;88(4):E323-E329

Center for Neurosurgery, Department of General Neurosurgery, University Hospital Cologne, Cologne, Germany.

Background: The importance of the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status as a predictive factor for the response to chemotherapy with temozolomide is well established. Its significance though at stratifying glioblastoma (GBM) patients in regard to their prognostic factors and the impact of surgical approach on them has not been identified.

Objective: To reveal possible differences in the prognostic factors and the impact of surgery between GBM patients stratified according to their MGMT status.

Methods: The authors retrospectively analyzed 186 patients with a newly diagnosed primary supratentorial GBM treated with surgical resection followed by standard radiation and chemotherapy. A prospective quantitative volumetric analysis of tumor characteristics identified on magnetic resonance imaging was performed.

Results: For the 109 patients with unmethylated MGMT promoter, extent of resection (EOR) represented independent predictor of survival, whereas residual tumor volume (RTV), Karnofsky Performance Score, and age were found to be independent prognostic factors of survival for the 77 patients with methylated MGMT promoter. For the group of patients with unmethylated and the group with methylated MGMT promoter, an EOR threshold of 70% and 98% and an RTV threshold of 1.5 and 1 cm3 were identified, respectively.

Conclusion: The selection of patients according to the MGMT promoter methylation status resulted in different prognostic factors and different resection thresholds for each patient population. A survival benefit seen from 70% EOR threshold in patients with MGMT unmethylated GBM supports the doctrine of maximum safe resection rather than the "all-or-nothing" approach.
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http://dx.doi.org/10.1093/neuros/nyaa562DOI Listing
March 2021

Impact of the weekend effect on outcome after microsurgical clipping of ruptured intracranial aneurysms.

Acta Neurochir (Wien) 2021 03 5;163(3):783-791. Epub 2021 Jan 5.

Center for Neurosurgery, Medical Faculty and University Hospital, University of Cologne, Kerpener Strasse 62, 50937, Cologne, Germany.

Background: The "weekend effect" describes the assumption that weekend and/or on-call duty admission of emergency patients is associated with increased morbidity and mortality rates. For aneurysmal subarachnoid hemorrhage, we investigated, whether presentation out of regular working hours and microsurgical clipping at nighttime correlates with worse patient outcome.

Methods: This is a retrospective review of consecutive patients that underwent microsurgical clipping of an acutely ruptured aneurysm at our institution between 2010 and 2019. Patients admitted during (1) regular working hours (Monday-Friday, 08:00-17:59) and (2) on-call duty and microsurgical clipping performed during (a) daytime (Monday-Sunday, 08:00-17:59) and (b) nighttime were compared regarding the following outcome parameters: operation time, treatment-related complications, vasospasm, functional outcome, and angiographic results.

Results: Among 157 enrolled patients, 104 patients (66.2%) were admitted during on-call duty and 48 operations (30.6%) were performed at nighttime. Admission out of regular hours did not affect cerebral infarction (p = 0.545), mortality (p = 0.343), functional outcome (p = 0.178), and aneurysm occlusion (p = 0.689). Microsurgical clipping at nighttime carried higher odds of unfavorable outcome at discharge (OR: 2.3, 95%CI: 1.0-5.1, p = 0.039); however, there were no significant differences regarding the remaining outcome parameters. After multivariable adjustment, clipping at nighttime did not remain as independent prognosticator of short-term outcome (OR: 2.1, 95%CI: 0.7-6.2, p = 0.169).

Conclusions: Admission out of regular working hours and clipping at nighttime were not independently associated with poor outcome. The adherence to standardized treatment protocols might mitigate the "weekend effect."
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http://dx.doi.org/10.1007/s00701-020-04689-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886827PMC
March 2021

Woven Endobridge Embolization Versus Microsurgical Clipping for Unruptured Anterior Circulation Aneurysms: A Propensity Score Analysis.

Neurosurgery 2021 03;88(4):779-784

Department of Radiology and Neuroradiology, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.

Background: Intrasaccular flow-disruption represents a new paradigm in endovascular treatment of wide-necked bifurcation aneurysms.

Objective: To retrospectively compare Woven Endobridge (WEB) embolization with microsurgical clipping for unruptured anterior circulation aneurysms using propensity score adjustment.

Methods: A total of 63 patients treated with WEB and 103 patients treated with clipping were compared based on the intention-to-treat principle. The primary outcome measures were immediate technical treatment success, major adverse events, and 6-mo complete aneurysm occlusion.

Results: The technical success rates were 83% for WEB and 100% for clipping. Procedure-related complications occurred more often in the clipping group (13%) than the WEB group (6%, adjusted P < .01). However, the rates of major adverse events were comparable in both groups (WEB: 3%, clip: 4%, adjusted P = .53). At the 6-mo follow-up, favorable functional outcomes were achieved in 98% of the WEB embolization group and 99% of the clipping group (adjusted P = .19). Six-month complete aneurysm occlusion was obtained in 75% of the WEB group and 94% of the clipping group (adjusted P < .01).

Conclusion: Microsurgical clipping was associated with higher technical success and complete occlusion rates, whereas WEB had a lower complication rate. Favorable functional outcomes were achieved in ≥98% of both groups. The decision to use a specific treatment modality should be made on an individual basis and in accordance with the patient's preferences.
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http://dx.doi.org/10.1093/neuros/nyaa539DOI Listing
March 2021

Impact of Obesity on Complication Rates, Clinical Outcomes, and Quality of Life after Minimally Invasive Transforaminal Lumbar Interbody Fusion.

J Neurol Surg A Cent Eur Neurosurg 2021 Mar 22;82(2):147-153. Epub 2020 Dec 22.

Center for Neurosurgery, University Hospital Cologne, Cologne, Nordrhein-Westfalen, Germany.

Background:  Percutaneous pedicle screw fixation in obese patients remains a surgical challenge. We aimed to compare patient-reported outcomes and complication rates between obese and nonobese patients who were treated by minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF).

Methods:  The authors retrospectively reviewed patients who underwent MIS-TLIF at a single institution between 2011 and 2014. Patients were classified as obese (body mass index [BMI] ≥30 kg/m) or nonobese (BMI < 30 kg/m), according to their BMI. Outcomes assessed were complications, numerical rating scale (NRS) scores for back and leg pain, Oswestry Disability Index (ODI), and 36-Item Short-Form Survey (SF-36) scores.

Results:  The final study group consisted of 71 patients, 24 obese (33.8%, 34.8 ± 3.8 kg/m) and 47 nonobese (66.2%, 25.4 ± 2.9 kg/m). Instrumentation failures (13.6 vs. 17.0%), dural tears (17.2 vs. 4.0%), and revision rates (16.7 vs. 19.1%) were similar between both groups ( > 0.05). Perioperative improvements in back pain (4.3 vs. 5.4,  = 0.07), leg pain (3.8 vs. 4.2,  = 0.6), and ODI (13.3 vs. 22.5,  = 0.5) were comparable among the groups and persisted at long-term follow-up. Obese patients had worse postoperative physical component SF-36 scores than nonobese patients (36.4 vs. 42.7,  = 0.03), while the mental component scores were not statistically different ( = 0.09).

Conclusion:  Obese patients can achieve similar improvement of the pain intensity and functional status even at long-term follow-up. In patients with appropriate surgical indications, obesity should not be considered a contraindication for MIS-TLIF surgery.
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http://dx.doi.org/10.1055/s-0040-1718758DOI Listing
March 2021

Timing of Development of Symptomatic Brain Metastases from Non-Small Cell Lung Cancer: Impact on Symptoms, Treatment, and Survival in the Era of Molecular Treatments.

Cancers (Basel) 2020 Dec 3;12(12). Epub 2020 Dec 3.

Department of Neurosurgery, University Medical Centre Regensburg, 93053 Regensburg, Germany.

Objective: We attempted to analyze whether early presentation with brain metastases (BM) represents a poor prognostic factor in patients with non-small cell lung cancer (NSCLC), which should guide the treatment team towards less intensified therapy.

Patients And Methods: In a retrospective bi-centric analysis, we identified patients receiving surgical treatment for NSCLC BM. We collected demographic-, tumor-, and treatment-related parameters and analyzed their influence on further survival.

Results: We included 377 patients. Development of BM was precocious in 99 (26.3%), synchronous in 152 (40.3%), and metachronous in 126 (33.4%) patients. The groups were comparable in terms of age ( = 0.76) and number of metastases ( = 0.11), and histology ( = 0.1); however, mutational status significantly differed ( = 0.002). The precocious group showed the worst clinical status as assessed by Karnofsky performance score (KPS) upon presentation ( < 0.0001). Resection followed by postoperative radiotherapy was the predominant treatment modality for precocious BM, while in syn- and metachronous BM surgical and radio-surgical treatment was balanced. Overall survival (OS) did not differ between the groups ( = 0.76). A good postoperative clinical status (KPS ≥ 70) and the application of any kind of adjuvant systemic therapy were independent predictive factors for OS.

Conclusion: Early BM presentation was not associated with worse OS in NSCLC BM patients.
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http://dx.doi.org/10.3390/cancers12123618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761690PMC
December 2020

MGMT promoter methylation analysis for allocating combined CCNU/TMZ chemotherapy: Lessons learned from the CeTeG/NOA-09 trial.

Int J Cancer 2021 04 10;148(7):1695-1707. Epub 2020 Nov 10.

Institute of Neuropathology and DGNN Brain Tumor Reference Center, Medical Faculty, Heinrich Heine University and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, Düsseldorf, Germany.

The CeTeG/NOA-09 trial showed a survival benefit for combined CCNU/TMZ therapy in MGMT-promoter-methylated glioblastoma patients (quantitative methylation-specific PCR [qMSP] ratio > 2). Here, we report on the prognostic value of the MGMT promoter methylation ratio determined by qMSP and evaluate the concordance of MGMT methylation results obtained by qMSP, pyrosequencing (PSQ) or DNA methylation arrays (MGMT-STP27). A potential association of qMSP ratio with survival was analyzed in the CeTeG/NOA-09 trial population (n = 129; log-rank tests, Cox regression analyses). The concordance of MGMT methylation assays (qMSP, PSQ and MGMT-STP27) was evaluated in 76 screened patients. Patients with tumors of qMSP ratio > 4 showed superior survival compared to those with ratios 2-4 (P = .0251, log-rank test). In multivariate analysis, the qMSP ratio was not prognostic across the study cohort (hazard ratio [HR] = 0.88; 95% CI: 0.72-1.08). With different cutoffs for qMSP ratio (4, 9, 12 or 25), the CCNU/TMZ benefit tended to be larger in subgroups with lower ratios (eg, for cutoff 9: HR 0.32 for lower subgroup, 0.73 for higher subgroup). The concordance rates with qMSP were 94.4% (PSQ) and 90.2% (MGMT-STP27). Discordant results were restricted to tumors with qMSP ratios ≤4 and PSQ mean methylation rate ≤25%. Despite a shorter survival in MGMT-promoter-methylated patients with lower methylation according to qMSP, these patients had a benefit from combined CCNU/TMZ therapy, which even tended to be stronger than in patients with higher methylation rates. With acceptable concordance rates, decisions on CCNU/TMZ therapy may also be based on PSQ or MGMT-STP27.
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http://dx.doi.org/10.1002/ijc.33363DOI Listing
April 2021

Surgical resection of symptomatic brain metastases improves the clinical status and facilitates further treatment.

Cancer Med 2020 10 28;9(20):7503-7510. Epub 2020 Aug 28.

Faculty of Medicine and University Hospital, Center for Neurosurgery, Dept of Neurosurgery, University of Cologne, Cologne, Germany.

Background: Brain metastases (BM) frequently cause focal neurological deficits leading to a reduced Karnofsky performance score (KPS). Since KPS is routinely used to guide the choice of adjuvant therapy, we hypothesized that improving KPS by surgical resection may improve the chance for adjuvant treatment and ultimately result in better survival. We therefore analyzed the course of a large cohort undergoing resection of symptomatic brain metastases in the context of further treatment and clinical outcome.

Patients And Methods: In a bi-centric retrospective analysis we retrieved baseline, clinical, and treatment-related parameters of patients operated on BM between 2010 and 2019. Survival was calculated using Kaplan-Meier estimates; prognostic factors for survival were analyzed by Log-rank test and Cox proportional hazards.

Results: We included 750 patients with a median age of 61 (19-87) years. The functional status was significantly improved by surgical resection, with a median preoperative (KPS) of 80 (10-100) increasing to 90 (0-100) after surgery (P < .0001). Moreover, surgery improved the RTOG recursive partitioning analysis (RPA) class from III to I/II in 82 patients. Postoperative local radiotherapy and systemic treatment were associated with significantly longer survival (P < .0001 for each). Systemic treatment was provided significantly more frequently in patients with a fair postoperative clinical status (KPS ≥ 70; P < .0001). The postoperative clinical status, postoperative radiotherapy, systemic treatment, controlled systemic disease and < 4 BM were independent predictors for survival.

Conclusion: The resection of symptomatic BM may restore clinical status, so enhancing the likelihood of receiving adjuvant treatment, and therefore leading to improved overall survival.
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http://dx.doi.org/10.1002/cam4.3402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571801PMC
October 2020

Invasive versus non-invasive mapping of the motor cortex.

Hum Brain Mapp 2020 10 26;41(14):3970-3983. Epub 2020 Jun 26.

Research Centre Jülich, Institute of Neuroscience and Medicine, Jülich, Germany.

Precise and comprehensive mapping of somatotopic representations in the motor cortex is clinically essential to achieve maximum resection of brain tumours whilst preserving motor function, especially since the current gold standard, that is, intraoperative direct cortical stimulation (DCS), holds limitations linked to the intraoperative setting such as time constraints or anatomical restrictions. Non-invasive techniques are increasingly relevant with regard to pre-operative risk-assessment. Here, we assessed the congruency of neuronavigated transcranial magnetic stimulation (nTMS) and functional magnetic resonance imaging (fMRI) with DCS. The motor representations of the hand, the foot and the tongue regions of 36 patients with intracranial tumours were mapped pre-operatively using nTMS and fMRI and by intraoperative DCS. Euclidean distances (ED) between hotspots/centres of gravity and (relative) overlaps of the maps were compared. We found significantly smaller EDs (11.4 ± 8.3 vs. 16.8 ± 7.0 mm) and better spatial overlaps (64 ± 38% vs. 37 ± 37%) between DCS and nTMS compared with DCS and fMRI. In contrast to DCS, fMRI and nTMS mappings were feasible for all regions and patients without complications. In summary, nTMS seems to be the more promising non-invasive motor cortex mapping technique to approximate the gold standard DCS results.
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http://dx.doi.org/10.1002/hbm.25101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469817PMC
October 2020

Delayed hospital admission of patients with aneurysmal subarachnoid hemorrhage: clinical presentation, treatment strategies, and outcome.

J Neurosurg 2020 Apr 17;134(3):1182-1189. Epub 2020 Apr 17.

1University of Cologne, Medical Faculty and University Hospital, Center for Neurosurgery, and.

Objective: Timely aneurysm occlusion and neurointensive care treatment are key principles in the management of aneurysmal subarachnoid hemorrhage (aSAH) to prevent secondary brain injury. Patients with early (EHA) and delayed hospital admission (DHA) were compared in terms of clinical presentation, treatment strategies, aSAH-related complications, and outcome.

Methods: In this retrospective study, consecutive aSAH patients were treated at a single neurovascular center between 2009 and 2019. Propensity score matching was performed to account for divergent baseline characteristics.

Results: Among 509 included patients, 55 were admitted more than 48 hours after ictus (DHA group). DHA patients were significantly younger (52 ± 11 vs 56 ± 14 years, p = 0.03) and had lower World Federation of Neurosurgical Societies scores (p < 0.01) than EHA patients. In 54.5% of the cases, DHA patients presented with neurological deterioration or aggravated symptoms. Propensity score matching revealed a higher vasospastic infarction rate in the DHA group (41.5%) than in the EHA group (22.6%) (p = 0.04). A similar portion of patients in both groups achieved favorable outcome at midterm follow-up (77.3% vs 73.6%, p = 0.87). DHA patients (62.3%) received conventional coiling more often than EHA patients (41.5%) (p = 0.03).

Conclusions: DHA patients are at an increased risk of cerebral infarction. Nevertheless, state-of-the-art neurointensive care treatment can result in a good clinical outcome.
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http://dx.doi.org/10.3171/2020.2.JNS20148DOI Listing
April 2020

KLF4-mutated meningiomas show enhanced hypoxia signaling and respond to mTORC1 inhibitor treatment.

Acta Neuropathol Commun 2020 04 3;8(1):41. Epub 2020 Apr 3.

Department of Neuropathology, Otto-von-Guericke University, Magdeburg, Germany.

Meningioma represents the most common primary brain tumor in adults. Recently several non-NF2 mutations in meningioma have been identified and correlated with certain pathological subtypes, locations and clinical observations. Alterations of cellular pathways due to these mutations, however, have largely remained elusive. Here we report that the Krueppel like factor 4 (KLF4)-K409Q mutation in skull base meningiomas triggers a distinct tumor phenotype. Transcriptomic analysis of 17 meningioma samples revealed that KLF4 mutated tumors harbor an upregulation of hypoxia dependent pathways. Detailed in vitro investigation further showed that the KLF4 mutation induces HIF-1α through the reduction of prolyl hydroxylase activity and causes an upregulation of downstream HIF-1α targets. Finally, we demonstrate that KLF4 mutated tumors are susceptible to mTOR inhibition by Temsirolimus. Taken together, our data link the KLF4 mediated upregulation of HIF pathways to the clinical and biological characteristics of these skull base meningiomas possibly opening new therapeutic avenues for this distinct meningioma subtype.
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http://dx.doi.org/10.1186/s40478-020-00912-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118946PMC
April 2020

Single-Step Resection of Sphenoorbital Meningiomas and Orbital Reconstruction Using Customized CAD/CAM Implants.

J Neurol Surg B Skull Base 2020 Apr 1;81(2):142-148. Epub 2019 Mar 1.

Center for Neurosurgery, University Hospital of Cologne, Cologne, Germany.

 Computer-aided design and manufacturing (CAD/CAM) implants are fabricated based on volumetric analysis of computed tomography (CT) scans and are routinely used for the reconstruction of orbital fractures. We present three cases of patients with sphenoorbital meningiomas that underwent tumor resection, orbital decompression, and orbital reconstruction with patient specific porous titanium or acrylic implants in a single procedure.  The extent of bone resection of the sphenoorbital meningiomas was planned in a virtual three-dimensional (3D) environment using preoperative thin-layer CT data. The anatomy of the orbital wall in the resection area was reconstructed by superimposing the contralateral unaffected orbit and by using the information of the neighboring bony structures. The customized implants and a corresponding craniotomy template were designed in the desired size and shape by the manufacturer.  All patients presented with a sphenoorbital meningioma and exophthalmos. After osteoclastic craniotomy with the drilling template, orbital decompression was performed. Implant fitting was tight in two cases and could be easily fixated with miniplates and screws. In the third patient, a reoperation was necessary for additional bone resection, as well as drilling and repositioning of the implant. The postoperative CT scans showed an accurate reconstruction of the orbital wall. After surgery, exophthalmos was substantially reduced and a satisfying cosmetic result could be finally achieved in all patients.  The concept of preoperative 3D virtual treatment planning and single-step orbital reconstruction with CAD/CAM implants after tumor resection involving the orbit is well feasible and can lead to good cosmetic results.
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http://dx.doi.org/10.1055/s-0039-1681044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082166PMC
April 2020

Penumbral Salvage by Delayed Clip Reposition 19 Hours After Cerebral Aneurysm Clipping-Induced Ischemia Results in Neurologic Restitution-Correlation with Indocyanine Green Videoangiography and FLOW 800 Measurements.

World Neurosurg 2020 06 3;138:61-67. Epub 2020 Mar 3.

University of Cologne, Faculty of Medicine and University Hospital, Center for Neurosurgery, Department of General Neurosurgery, Cologne, Germany.

Background: Cerebral infarction because of parent artery stenosis represents a potential complication of microsurgical aneurysm clipping.

Case Description: We report a case of a 60-year-old woman that developed left-sided hemiparesis and aphasia 9 hours after clipping of an unruptured middle cerebral artery aneurysm with heavy calcification of the aneurysm neck. Angiographic workup revealed a marked parent artery stenosis, which occurred presumably because of thrombus generation at the reconstructed aneurysm neck. Revision surgery with relocation of the aneurysm clip was ultimately performed 19 hours after symptom onset. Although follow-up computed tomography scan showed a small cerebral infarction, the patient recovered fully from surgery.

Conclusions: This case shows that relocation of the aneurysm clip in case of vessel stenosis can lead to penumbral salvage, even when performed more than 6 hours after symptom onset.
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http://dx.doi.org/10.1016/j.wneu.2020.02.122DOI Listing
June 2020

Flare Phenomenon in -(2-F-Fluoroethyl)-l-Tyrosine PET After Resection of Gliomas.

J Nucl Med 2020 09 31;61(9):1294-1299. Epub 2020 Jan 31.

Institute of Neuroscience and Medicine (INM-3, INM-4, and INM-5), Forschungszentrum Jülich, Jülich, Germany

PET using -(2-F-fluoroethyl)-l-tyrosine (F-FET) is useful to detect residual tumor tissue after glioma resection. Recent animal experiments detected reactive changes in F-FET uptake at the rim of the resection cavity within the first 2 wk after resection of gliomas. In the present study, we evaluated pre- and postoperative F-FET PET scans of glioma patients with particular emphasis on the identification of reactive changes after surgery. Forty-three patients with cerebral gliomas (9 low-grade, 34 high-grade; 9 primary tumors, 34 recurrent tumors) who had preoperative (time before surgery: median, 23 d; range, 6-44 d) and postoperative F-FET PET (time after surgery: median, 14 d; range, 5-28 d) were included. PET scans (20-40 min after injection) were evaluated visually for complete or incomplete resection and compared with MRI. Changes in F-FET uptake were evaluated by tumor-to-brain ratios in residual tumor and by maximum lesion-to-brain ratios near the resection cavity. Visual analysis of F-FET PET scans revealed complete resection in 16 of 43 patients and incomplete resection in the remaining patients. PET results were concordant with MRI in 69% of the patients. The maximum lesion-to-brain ratio for F-FET uptake near the resection cavity was significantly higher than preoperative values (1.59 ± 0.36 vs. 1.14 ± 0.17; = 43; < 0.001). In 11 patients (26%), a flare phenomenon was observed, with a considerable increase in F-FET uptake compared with preoperative values in either the residual tumor ( = 5) or areas remote from the tumor on the preoperative PET scan ( = 6) (2.92 ± 1.24 vs. 1.62 ± 0.75; < 0.001). Further follow-up in 5 patients showed decreasing F-FET uptake in the flare areas in 4 patients and progress in 1 patient. Our study confirmed that F-FET PET provides valuable information for assessing the success of glioma resection. Postoperative reactive changes at the rim of the resection cavity appear to be mild. However, in 23% of the patients, a postoperative flare phenomenon was observed that warrants further investigation.
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http://dx.doi.org/10.2967/jnumed.119.238568DOI Listing
September 2020

Effect of early palliative care for patients with glioblastoma (EPCOG): a randomised phase III clinical trial protocol.

BMJ Open 2020 01 7;10(1):e034378. Epub 2020 Jan 7.

Department of General Neurosurgery, Faculty of Medicine and University Hospital, Center for Neurosurgery, University of Cologne, Cologne, Germany.

​INTRODUCTION: Randomised controlled trials (RCTs) have shown a positive effect of early integration of palliative care (EIPC) in various advanced cancer entities regarding patients' quality of life (QoL), survival, mood, caregiver burden and reduction of aggressiveness of treatment near the end of life. However, RCTs investigating the positive effect of EIPC for patients suffering from glioblastoma multiforme (GBM) are lacking. After modelling work identifying the specific needs of GBM patients and their caregivers, the aim of this study is to investigate the impact of EIPC in this particular patient group. ​METHODS AND ANALYSIS: The recruitment period of this multicenter RCT started in May 2019. GBM patients (n=214) and their caregivers will be randomly assigned to either the intervention group (receiving proactive EIPC on a monthly basis) or the control group (receiving treatment according to international standards and additional, regular assessment of QoL ('optimised' standard care)).The primary outcome is QoL assessed by subscales of the Functional Assessment of Cancer Therapy for brain tumour (FACT-Br) from baseline to 6 months of treatment. Secondary outcomes are changes in QoL after 12 (end of intervention), 18 and 24 months (end of follow-up), the full FACT-Br scale, patients' palliative care needs, depression/anxiety, cognitive impairment, caregiver burden, healthcare use, cost-effectiveness and overall survival. ​ETHICS AND DISSEMINATION: The study will be conducted in accordance with the Declaration of Helsinki and has been approved by the local ethics committees of the University Clinics of Cologne, Aachen, Bonn, Freiburg and Munich (LMU). Results of the trial will be submitted for publication in a peer-reviewed, open access journal and disseminated through presentations at conferences. TRIAL REGISTRATION NUMBER: German Register for Clinical Studies (DRKS) (DRKS00016066); Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2019-034378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955518PMC
January 2020

Identifying Predictors for Aneurysm Remnants After Clipping by Morphometric Analysis and Proposal of a Novel Risk Score.

World Neurosurg 2020 Apr 31;136:e300-e309. Epub 2019 Dec 31.

University of Cologne, Medical Faculty and University Hospital, Center for Neurosurgery, Cologne, Germany.

Objective: Although the risk of aneurysm remnants after microsurgical clipping is generally low, complete aneurysm occlusion is not always guaranteed. We performed a morphometric analysis of intracranial aneurysms to identify predictors for aneurysm remnants and to propose a novel risk score.

Methods: This is a retrospective, single-center analysis of consecutive patients with ruptured and unruptured aneurysms who underwent microsurgical clipping and postoperative digital subtraction angiography between 2010 and 2018. Based on preoperative rotational angiography, distinct morphologic aneurysm characteristics were determined and correlated with postoperative angiographic results. Factors predictive in the univariate and multivariate analyses were determined to establish a risk score for postoperative remnants after aneurysm clipping.

Results: Among 140 patients with 166 clipped aneurysms, aneurysm remnants were present in 19.9%. In the multivariate analysis, ruptured aneurysm status (odds ratio [OR], 7.8; 95% confidence interval [CI], 1.7-36; P < 0.01) and increased aspect ratio (OR, 1.9; 95% CI, 1.0-4.0; P = 0.07) were associated with postoperative aneurysm remnants. Anterior communicating artery location (P = 0.02), internal carotid artery location (P = 0.06), increased aneurysm inclination angle (P < 0.01), and irregular aneurysm shape (P = 0.07) were further predictors for aneurysm remnants in the univariate analysis. These factors were weighted and included into a risk sum score for postoperative aneurysm remnants (range, 0-8 points), which performed with good accuracy (area under the curve = 0.807).

Conclusions: After external validation of the proposed risk score, it could help identify cases requiring angiographic control after aneurysm surgery.
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http://dx.doi.org/10.1016/j.wneu.2019.12.158DOI Listing
April 2020

Flow-regulated versus differential pressure valves for idiopathic normal pressure hydrocephalus: comparison of overdrainage rates and neurological outcome.

Acta Neurochir (Wien) 2020 01 12;162(1):15-21. Epub 2019 Nov 12.

Faculty of Medicine and University Hospital, Center for Neurosurgery, University of Cologne, Kerpener Strasse 62, 50937, Cologne, Germany.

Background: To compare flow-regulated (FR) and differential pressure (DP) valves for treatment of patients with idiopathic normal hydrocephalus (iNPH) focusing on overdrainage and neurological outcome.

Methods: This is a retrospective study of patients with iNPH treated with FR and DP valves at a single institution between 2008 and 2018. The neurological status was evaluated retrospectively with the Kiefer scale at baseline, after shunt placement and at the 6-month follow-up. Groups were compared using inverse probability of treatment weighting based on propensity scores.

Results: The study cohort consisted of 38 patients treated with FR valves and 49 with DP valves. The mean patient age was 72.0 ± 7.6 years. Based on the Kiefer scale score, neurological improvement at the 6-month follow-up was recorded in 79.6% in the DP group and 89.5% in the FR group (p = 0.252). The overdrainage rates were higher among DP valves (10.2%) than among FR valves (2.6%, adjusted p = 0.002). Valve malfunction occurred in 2.0% in the DP group and 5.3% in the FR group (adjusted p = 0.667).

Conclusions: The current study demonstrates a comparable neurological improvement between DP and FR valves, with potentially lower overdrainage rates among FR valves. Long-term studies will be necessary to draw a definite conclusion on FR valves for treatment of iNPH patients.
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http://dx.doi.org/10.1007/s00701-019-04088-9DOI Listing
January 2020

Accelerated Clustered Sparse Acquisition to Improve Functional MRI for Mapping Language Functions.

J Neurol Surg A Cent Eur Neurosurg 2020 Mar 28;81(2):95-104. Epub 2019 Oct 28.

Center of Neurosurgery, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Background:  Functional magnetic resonance imaging (fMRI) is a useful method for noninvasive presurgical functional mapping. However, the scanner environment is inherently unsuitable for the examination of auditory and language functions, due to the loud acoustic noise produced by the scanner. Interleaved acquisition methods alleviate this problem by providing a silent period for stimulus presentation and/or response control (sparse sampling) but at the expense of a diminished amount of data collected. There are possible improvements to these sparse acquisition methods that increase the amount of data by acquiring several images per event (clustered sampling). We tested accelerated clustered fMRI acquisition in comparison with conventional sparse sampling in a pilot study.

Methods:  The clustered and sparse acquisition techniques (7.4 minutes scanning time per protocol) were directly compared in 15 healthy subjects (8 men; mean age: 24 ± 3 years) using both a motor (tongue movement) and a language (overt picture-naming) task. Functional imaging data were analyzed using Statistical Parametric Mapping software (SPM12 Wellcome Department of Imaging Neuroscience, London, UK). For both tasks, activation levels were compared and Euclidean distances (EDs) between cluster centers (i.e., local activation maxima and centers of gravity) were calculated. Overlaps and laterality indices were computed for the picture-naming task. In addition, the feasibility of the clustered acquisition protocol in a clinical setting was assessed in one pilot patient.

Results:  For both tasks, activation levels were higher using the clustered acquisition protocol, reflected by bigger cluster sizes ( < 0.05). Mean ED between cluster centers ranged between 9.9 ± 5.4 mm (left superior temporal gyrus; centers of gravity) and 16.6 ± 13.2 mm (left inferior frontal gyrus; local activation maxima) for the picture-naming task. Overlaps between sparse and clustered acquisition reached 88% (Simpson overlap coefficient). A similar activation pattern for both acquisition methods was also confirmed in the clinical case.

Conclusion:  Despite some drawbacks inherent to the acquisition technique, the clustered sparse sampling protocol showed increased sensitivity for activation in language-related cortical regions with short scanning times. Such scanning techniques may be particularly advantageous for investigating patients with contraindications for long scans (e.g., reduced attention span).
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http://dx.doi.org/10.1055/s-0039-1691821DOI Listing
March 2020

Correlations between genomic subgroup and clinical features in a cohort of more than 3000 meningiomas.

J Neurosurg 2019 Oct 25:1-10. Epub 2019 Oct 25.

19Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Objective: Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts.

Methods: Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher's exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features.

Results: Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among "mutation unknown" samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor's underlying driver mutation.

Conclusions: Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.
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http://dx.doi.org/10.3171/2019.8.JNS191266DOI Listing
October 2019

Does Meningioma Volume Correlate With Clinical Disease Manifestation Irrespective of Histopathologic Tumor Grade?

J Craniofac Surg 2019 Nov-Dec;30(8):e799-e802

Department of General Neurosurgery, Center for Neurosurgery, University Hospital Cologne, Cologne, Germany.

Objectives: The aim of the study was to investigate the association between meningioma volume and the occurrence of clinic-radiologic signs of tumor aggressiveness. For volumetric approximation, the authors evaluated the method of semiautomatic image segmentation at hand of high-resolution MRI-image sequences.

Methods: ITK-SNAP was utilized for semiautomatic image segmentation of 58 gadolinium-contrast enhanced T1-weighted thin-slice MRI datasets for volumetric analysis. Furthermore, multimodal imaging datasets (including T2, FLAIR, T1) were evaluated for radiological biomarkers of aggressiveness and growth potential. Thereby generated data was checked for association with retrospectively collected data points.

Results: Location (P = 0.001), clinical disease manifestation (P = 0.033), peritumoral edema (P = 0.038), tumor intrinsic cystic degeneration (P = 0.007), three-dimensional complexity (P = 0.022), and the presence of meningioma mass effect (P = 0.001) were statistically associated with higher tumor volumes. There was no association between higher tumor volumes and histopathological tumor grade.

Conclusion: The size of a meningioma does not seem to reliably predict tumor grade. Growth potential seems to be influenced by tumor location. Higher tumor volumes were significantly associated with the occurrence of clinical symptoms.
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http://dx.doi.org/10.1097/SCS.0000000000005845DOI Listing
January 2020
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