Publications by authors named "Daniela Pierscianek"

57 Publications

Case Report: Pseudomeningeosis and Demyelinating Metastasis-Like Lesions From Checkpoint Inhibitor Therapy in Malignant Melanoma.

Front Oncol 2021 15;11:637185. Epub 2021 Apr 15.

Department of Neurology, Division of Clinical Neurooncology, University Hospital Essen, Essen, Germany.

Immune checkpoint inhibitors (ICIs) have considerably expanded the effective treatment options for malignant melanoma. ICIs revert tumor-associated immunosuppression and potentiate T-cell mediated tumor clearance. Immune-related neurologic adverse events (irNAEs) manifest in the central (CNS) or peripheral nervous system (PNS) and most frequently present as encephalitis or myasthenia gravis respectively. We report on a 47-year old male patient with metastatic melanoma who developed signs of cerebellar disease five weeks after the start of ICI treatment (ipilimumab and nivolumab). Magnetic resonance imaging (MRI) of the brain and spine revealed multiple new contrast enhancements suggestive of parenchymal and leptomeningeal metastasis. Cerebral spinal fluid (CSF) evaluation showed a lymphomononuclear pleocytosis in the absence of tumor cells. Subsequent stereotactic brain biopsy confirmed demyelinating disease. High-dose corticosteroid treatment resulted in immediate improvement of the clinical symptoms. MRI scans and CSF re-evaluation were conducted six weeks later and showed a near-complete remission. The strong resemblance to neoplastic CNS dissemination and irNAEs is a particularly difficult diagnostic challenge. Treating physicians should be aware of irNAEs as those can be effectively treated with high-dose steroids.
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http://dx.doi.org/10.3389/fonc.2021.637185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081911PMC
April 2021

Lipomas as an Extremely Rare Cause for Brachial Plexus Compression: A Case Series and Systematic Review.

J Brachial Plex Peripher Nerve Inj 2021 Jan 13;16(1):e10-e16. Epub 2021 Apr 13.

Department of Neurosurgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

 Brachial plexus lipomas are extremely rare benign tumors that may cause slow progression of neurological deficits leading to thoracic outlet syndrome. Up to now, surgery remains challenging. The aim of this study is to present our surgical treatment regime and long-term neurological outcome in three cases of giant brachial plexus lipomas and to show results of systematic review.  Retrospective analysis of our database "peripheral nerve lesion" to identify patients suffering from brachial plexus lipomas between January 1, 2012, and December 31, 2019. Systematic review was performed for literature published until March 31, 2020, analyzing PubMed, Google Scholar, Scopus, and the Cochrane Collaboration Library independently by two authors.  Over the past years, three patients suffering from giant brachial plexus lipomas attended to our neurosurgical department. All patients underwent preoperative magnetic resonance imaging (MRI), ultrasound examinations, and electrophysiological testing. Tumors were removed microsurgically via anterior/posterior, supraclavicular/infraclavicular, and combined approaches. The patients were accessed postoperatively by MRI and clinical follow-up. Systematic review of the literature revealed 22 cases, which were analyzed in regard to demographics, surgical treatment, and neurological outcome.  Brachial plexus lipomas are an extremely rare cause for brachial plexus compression. Total microsurgical removal with intraoperative electrophysiological monitoring is the treatment of choice with excellent long-term MRI and clinical outcome.
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http://dx.doi.org/10.1055/s-0041-1726087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043811PMC
January 2021

The 2016 Edition of the WHO Classification of Primary Brain Tumors: Applicable to Assess Individual Risk of Recurrence in Atypical Meningioma? A Single-Center Experience.

J Neurol Surg A Cent Eur Neurosurg 2021 Apr 12. Epub 2021 Apr 12.

Department of Neurosurgery, University Hospital of Essen, Essen, Germany.

Background And Study Aims/object:  Despite the relevance of molecular criteria for brain tumor diagnosis and prognosis, meningioma grading is still solely based on histologic features. Atypical meningiomas (AMs; WHO grade II) display a great histologic heterogeneity and individual courses of disease can differ significantly. This study aimed to identify clinically aggressive AMs that are prone to early recurrence after gross total resection (GTR) by assessing a specific histologic score.

Patients And Methods:  A retrospective analysis of 28 consecutive patients (17 females and 11 males; mean age of 62 years [range: 35-88 years]) treated in our institution between January 2006 and December 2015 was performed. Basic demographic and clinical characteristics were assessed. A scoring scale was designed to address the histologic diversity by summing up the individual histologic features in every tumor sample. According to that, points were awarded as follows: major AM defining criterion (3 points) and minor criterion (1 point).

Results:  The subclassification based on our specific histologic score revealed no significant difference in frequency of one (46.4%) or two (42.9%) AM defining features; three criteria were less frequently seen (10.7%). Mean follow-up was 61.89 ± 9.03 months. Local recurrence occurred in 35.7% after a mean time of 37.4 ± 22.6 months after primary surgery. Age > 60 years was significantly associated with a shorter progression-free survival (PFS). There was a trend toward shorter PFS with increasing scores, tantamount with the presence of several AM defining histologic criteria in one sample. No tumor relapse was seen when diagnosis was based only on minor criteria.

Conclusion:  AMs display a histologic diversity. There is a trend toward shorter PFS with increasing numbers of AM defining histologic features. The inclusion of this score in the decision algorithm regarding further treatment for patients >60 years after GTR might be helpful and should be evaluated in further studies.
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http://dx.doi.org/10.1055/s-0040-1720987DOI Listing
April 2021

Size does matter: The role of decompressive craniectomy extent for outcome after aneurysmal subarachnoid hemorrhage.

Eur J Neurol 2021 Mar 24. Epub 2021 Mar 24.

Department of Neurosurgery and Spine Surgery, University Hospital of Essen, Essen, Germany.

Background And Purpose: In previous studies in patients with traumatic brain injury and ischemic stroke, the size of decompressive craniectomy (DC) was reported to be paramount with regard to patient outcomes. We aimed to identify the impact of DC size on treatment results in individuals with aneurysmal subarachnoid hemorrhage (SAH).

Methods: The extent of DC in 232 patients with SAH who underwent bifrontal or hemicraniectomy between January 2003 and December 2015 was analyzed using semi-automated surface measurements. The study endpoints were course of intracranial pressure (ICP) treatment after DC, occurrence of cerebral infarcts, in-hospital mortality, and unfavorable outcome at 6 months (defined as modified Rankin scale score >3). The associations of DC size with the study endpoints were adjusted for DC timing, patient age, clinical and radiographic severity of SAH, aneurysm location, and treatment modality.

Results: The mean DC surface area was 100.9 (±45.8) cm . In multivariate analysis, a large DC (>105 cm ) was independently associated with a lower risk of cerebral infarcts (adjusted odds ratio [aOR] 0.30, 95% confidence interval [CI] 0.16-0.56), in-hospital mortality (aOR 0.28, 95% CI 0.14-0.56) and unfavorable outcome (aOR 0.51, 95% CI 0.27-0.98). Moreover, SAH patients with a small DC size (<75 cm ) were more likely to require prolonged (>3 days, aOR 3.60, 95% CI 1.37-9.42) and enhanced (aOR 2.31, 95% CI 1.12-4.74) postoperative ICP treatment.

Conclusion: This is the first study showing the impact of DC size on postoperative ICP control and patient outcome in the context of SAH; specifically, a large craniectomy flap (>105 cm ) might lead to better outcomes in SAH patients requiring decompressive surgery.
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http://dx.doi.org/10.1111/ene.14835DOI Listing
March 2021

Preoperative and early postoperative seizures in patients with glioblastoma-two sides of the same coin?

Neurooncol Adv 2021 Jan-Dec;3(1):vdaa158. Epub 2020 Nov 18.

Department of Neurosurgery and Spine Surgery, University Hospital Essen, Essen, Germany.

Background: Symptomatic epilepsy is a common symptom of glioblastoma, which may occur in different stages of disease. There are discrepant reports on association between early seizures and glioblastoma survival, even less is known about the background of these seizures. We aimed at analyzing the risk factors and clinical impact of perioperative seizures in glioblastoma.

Methods: All consecutive cases with de-novo glioblastoma treated at our institution between 01/2006 and 12/2018 were eligible for this study. Perioperative seizures were stratified into seizures at onset (SAO) and early postoperative seizures (EPS, ≤21days after surgery). Associations between patients characteristics and overall survival (OS) with SAO and EPS were addressed.

Results: In the final cohort ( = 867), SAO and EPS occurred in 236 (27.2%) and 67 (7.7%) patients, respectively. SAO were independently predicted by younger age ( = .009), higher KPS score ( = .002), tumor location (parietal lobe, = .001), GFAP expression (≥35%, = .045), and serum chloride at admission (>102 mmol/L, = .004). In turn, EPS were independently associated with tumor location (frontal or temporal lobe, = .013) and pathologic laboratory values at admission (hemoglobin < 12 g/dL, [ = .044], CRP > 1.0 mg/dL [ = 0.036], and GGT > 55 U/L [ = 0.025]). Finally, SAO were associated with gross-total resection ( = .006) and longer OS ( = .030), whereas EPS were related to incomplete resection ( = .005) and poorer OS ( = .009).

Conclusions: In glioblastoma patients, SAO and EPS seem to have quite different triggers and contrary impact on treatment success and OS. The clinical characteristics of SAO and EPS patients might contribute to the observed survival differences.
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http://dx.doi.org/10.1093/noajnl/vdaa158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813191PMC
November 2020

Machine learning-based differentiation between multiple sclerosis and glioma WHO II°-IV° using O-(2-[18F] fluoroethyl)-L-tyrosine positron emission tomography.

J Neurooncol 2021 Apr 27;152(2):325-332. Epub 2021 Jan 27.

Division of Clinical Neurooncology, Department of Neurology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany.

Introduction: This study aimed to test the diagnostic significance of FET-PET imaging combined with machine learning for the differentiation between multiple sclerosis (MS) and glioma II°-IV°.

Methods: Our database was screened for patients in whom FET-PET imaging was performed for the diagnostic workup of newly diagnosed lesions evident on MRI and suggestive of glioma. Among those, we identified patients with histologically confirmed glioma II°-IV°, and those who later turned out to have MS. For each group, tumor-to-brain ratio (TBR) derived features of FET were determined. A support vector machine (SVM) based machine learning algorithm was constructed to enhance classification ability, and Receiver Operating Characteristic (ROC) analysis with area under the curve (AUC) metric served to ascertain model performance.

Results: A total of 41 patients met selection criteria, including seven patients with MS and 34 patients with glioma. TBR values were significantly higher in the glioma group (TBRmax glioma vs. MS: p = 0.002; TBRmean glioma vs. MS: p = 0.014). In a subgroup analysis, TBR values significantly differentiated between MS and glioblastoma (TBRmax glioblastoma vs. MS: p = 0.0003, TBRmean glioblastoma vs. MS: p = 0.0003) and between MS and oligodendroglioma (ODG) (TBRmax ODG vs. MS: p = 0.003; TBRmean ODG vs. MS: p = 0.01). The ability to differentiate between MS and glioma II°-IV° increased from 0.79 using standard TBR analysis to 0.94 using a SVM based machine learning algorithm.

Conclusions: FET-PET imaging may help differentiate MS from glioma II°-IV° and SVM based machine learning approaches can enhance classification performance.
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http://dx.doi.org/10.1007/s11060-021-03701-1DOI Listing
April 2021

Dosimetric impact of the positioning variation of tumor treating field electrodes in the PriCoTTF-phase I/II trial.

J Appl Clin Med Phys 2021 Jan 3;22(1):242-250. Epub 2021 Jan 3.

Department of Radiotherapy, West German Cancer Center, University Hospital Essen, University of Duisburg, Essen, Germany.

Purpose: The aim of the present study based on the PriCoTTF-phase I/II trial is the quantification of skin-normal tissue complication probabilities of patients with newly diagnosed glioblastoma multiforme treated with Tumor Treating Field (TTField) electrodes, concurrent radiotherapy, and temozolomide. Furthermore, the skin-sparing effect by the clinically applied strategy of repetitive transducer array fixation around their center position shall be examined.

Material And Methods: Low-dose cone-beam computed tomography (CBCT) scans of all fractions of the first seven patients of the PriCoTTF-phase I/II trial, used for image guidance, were applied for the dosimetric analysis, for precise TTField transducer array positioning and contour delineation. Within this trial, array positioning was varied from fixation-to-fixation period with a standard deviation of 1.1 cm in the direction of the largest variation of positioning and 0.7 cm in the perpendicular direction. Physical TTField electrode composition was examined and a respective Hounsfield Unit attributed to the TTField electrodes. Dose distributions in the planning CT with TTField electrodes in place, as derived from prefraction CBCTs, were calculated and accumulated with the algorithm Acuros XB. Dose-volume histograms were obtained for the first and second 2 mm scalp layer with and without migrating electrodes and compared with those with fixed electrodes in an average position. Skin toxicity was quantified according to Lyman's model. Minimum doses in hot-spots of 0.05 cm and 25 cm ( D , D ) size in the superficial skin layers were analyzed.

Results: Normal tissue complication probabilities (NTCPs) for skin necrosis ranged from 0.005% to 1.474% (median 0.111%) for the different patients without electrodes. NTCP logarithms were significantly dependent on patient (P < 0.0001) and scenario (P < 0.0001) as classification variables. Fixed positioning of TTField arrays increased skin-NTCP by a factor of 5.50 (95%, CI: 3.66-8.27). The variation of array positioning increased skin-NTCP by a factor of only 3.54 (95%, CI: 2.36-5.32) (P < 0.0001, comparison to irradiation without electrodes; P = 0.036, comparison to irradiation with fixed electrodes). NTCP showed a significant rank correlation with D25cm over all patients and scenarios (r  = 0.76; P < 0.0001).

Conclusion: Skin-NTCP calculation uncovers significant interpatient heterogeneity and may be used to stratify patients into high- and low-risk groups of skin toxicity. Array position variation may mitigate about one-third of the increase in surface dose and skin-NTCP by the TTField electrodes.
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http://dx.doi.org/10.1002/acm2.13144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856507PMC
January 2021

The PRESSURE score to predict decompressive craniectomy after aneurysmal subarachnoid haemorrhage.

Brain Commun 2020 17;2(2):fcaa134. Epub 2020 Sep 17.

Department of Neurosurgery, University Hospital of Essen, D-45147 Essen, Germany.

The prognosis of patients with aneurysmal subarachnoid haemorrhage requiring decompressive craniectomy is usually poor. Proper selection and early performing of decompressive craniectomy might improve the patients' outcome. We aimed at developing a risk score for prediction of decompressive craniectomy after aneurysmal subarachnoid haemorrhage. All consecutive aneurysmal subarachnoid haemorrhage cases treated at the University Hospital of Essen between January 2003 and June 2016 (test cohort) and the University Medical Center Freiburg between January 2005 and December 2012 (validation cohort) were eligible for this study. Various parameters collected within 72 h after aneurysmal subarachnoid haemorrhage were evaluated through univariate and multivariate analyses to predict separately primary (PrimDC) and secondary decompressive craniectomy (SecDC). The final analysis included 1376 patients. The constructed risk score included the following parameters: intracerebral ('arenchymal') haemorrhage (1 point), 'apid' vasospasm on angiography (1 point), arly cerebral infarction (1 point), aneurysm ac > 5 mm (1 point), clipping (' urgery', 1 point), age nder 55 years (2 points), Hunt and Hess grade ≥ 4 ('educed consciousness', 1 point) and xternal ventricular drain (1 point). The score (0-9 points) showed high diagnostic accuracy for the prediction of PrimDC and SecDC in the test (area under the curve = 0.842/0.818) and validation cohorts (area under the curve = 0.903/0.823), respectively. 63.7% of the patients scoring ≥6 points required decompressive craniectomy (versus 12% for the PRESSURE < 6 points,  < 0.0001). In the subgroup of the patients with the PRESSURE ≥6 points and absence of dilated/fixed pupils, PrimDC within 24 h after aneurysmal subarachnoid haemorrhage was independently associated with lower risk of unfavourable outcome (modified Rankin Scale >3 at 6 months) than in individuals with later or no decompressive craniectomy ( < 0.0001). Our risk score was successfully validated as reliable predictor of decompressive craniectomy after aneurysmal subarachnoid haemorrhage. The PRESSURE score might present a background for a prospective randomized clinical trial addressing the utility of early prophylactic decompressive craniectomy in aneurysmal subarachnoid haemorrhage.
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http://dx.doi.org/10.1093/braincomms/fcaa134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660044PMC
September 2020

Demographic, radiographic, molecular and clinical characteristics of primary gliosarcoma and differences to glioblastoma.

Clin Neurol Neurosurg 2021 01 1;200:106348. Epub 2020 Nov 1.

Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium, Partner Site University Hospital Essen, Essen, Germany.

Objective: Gliosarcoma (GSC) is a rare histological variant of glioblastoma (GBM). Due to limited evidence regarding clinical, genetic and radiographic characteristics of GSC, this study aimed to analyze independent outcome predictors of GSC, and to address the differences between GSC and GBM concerning the baseline characteristics and patients' survival.

Methods: Patients treated between 2001 and 2018 for the diagnosis of GBM and GSC were included in this study. Patients' records were reviewed for demographic, clinical, genetic and radiographic characteristics. Univariate, multivariate and propensity score matched analyses were performed.

Results: In the GSC sub-cohort (N = 56), patients' age, preoperative clinical status, midline tumor location and tumor size were found to be independently associated with overall survival. As compared to GBM individuals (N = 1249), a temporal location (p = 0.002), presence of eccentric tumor cysts (p < 0.001), a higher ratio of TP53 staining (p = 0.002) and a lower ratio of GFAP staining (p = 0.005) were characteristic for GSC. The diagnosis of GSC was associated with a poorer survival (p = 0.002) independently of the patients' age, sex, clinical status and extent of resection, However, this association was no more significant, when enhancing the multivariate analysis with molecular-genetic characteristics (IDH1 mutation and MGMT promotor methylation status).

Discussion: Certain radiographic and molecular-genetic patterns present the distinct characteristics of GSC. There is an association between the diagnosis of GSC and a poorer outcome. This difference might be linked to different genetic alterations in GBM and GSC. Prospective studies are needed to further elucidate the characteristics of GSC and develop targeted treatment approaches for this rare variant.
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http://dx.doi.org/10.1016/j.clineuro.2020.106348DOI Listing
January 2021

DNA promoter methylation of CCM genes in human cerebral cavernous malformations: Importance of confirming MSP data through sequencing.

Eur J Med Genet 2020 Dec 22;63(12):104090. Epub 2020 Oct 22.

Department of Neurosurgery, University Hospital Essen, Hufelandstrasse 55, 45122, Essen, Germany. Electronic address:

Background: Cerebral cavernous malformations (CCMs) is the second most common cerebrovascular disease and is classified as familial (20%) and sporadic (80%) forms. Loss of function mutation of three CCM genes results in the familial CCM. Considering the similar clinic presentation of familial and sporadic CCMs, and based on enriched CpG islands in the DNA promoter region of three CCM genes, we hypothesized that DNA methylation of the CpG islands of the CCM genes is involved in human CCM, thereby leading to loss of CCM genes.

Material And Methods: 69 human CCMs including sporadic (n = 40), multiple (n = 15) and familial (n = 14) cases. DNA was extracted from the surgical specimens of CCMs followed by bisulfite conversion. The methylation status of the promoter regions of three CCM genes was detected by methylation specific PCR (MSP). To confirm the results of MSP, four MSP-positive probes showing CCM3 methylation underwent deep bisulfite sequencing (DBS).

Results: MSP mostly excluded methylation of CCM1 and CCM2 promotor regions (data not shown). In the case of CCM3, 12 out of 55 sporadic cases showed positivity for MSP (21.8%). Deep bisulfite sequencing revealed that four CCM3 MSP positive cases were all negative for DNA methylation.

Conclusion: The present study suggests that DNA promotor methylation of CCM1-3 genes is not involved in human family CCMs and that it is important to confirm MSP data with DBS. Further study with higher number of sporadic CCM patients is required for better understanding whether this epigenetic mechanism is involved in the pathology of CCM.
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http://dx.doi.org/10.1016/j.ejmg.2020.104090DOI Listing
December 2020

Drug repositioning of antiretroviral ritonavir for combinatorial therapy in glioblastoma.

Eur J Cancer 2020 11 19;140:130-139. Epub 2020 Oct 19.

Institute of Reconstructive Neurobiology, Division of Stem Cell Pathologies, Life and Brain Centre, University of Bonn Medical Faculty and University Hospital Bonn, Germany; DKFZ Division Translational Neurooncology at the West German Cancer Center (WTZ), DKTK Partner Site, University Hospital Essen, Germany; German Cancer Consortium (DKTK), Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.

Background: The protease inhibitor ritonavir (RTV) is a clinical-stage inhibitor of the human immunodeficiency virus. In a drug repositioning approach, we here exhibit the additional potential of RTV to augment current treatment of glioblastoma, the most aggressive primary brain tumour of adulthood.

Methods: We explored the antitumour activity of RTV and mechanisms of action in a broad spectrum of short-term expanded clinical cell samples from primary and recurrent glioblastoma and in a cohort of conventional cell lines and non-tumour human neural controls in vitro. To validate RTV efficacy in monotherapeutic and in combinatorial settings, we used patient-derived xenograft models in a series of in vivo studies.

Results: RTV monotherapy induced a selective antineoplastic response and demonstrated cytostatic and anti-migratory activity at clinical plasma peak levels. Additional exposure to temozolomide or irradiation further enhanced the effects synergistically, fostered by mechanisms of autophagy and increased endoplasmic reticulum stress. In xenograft models, we consequently observed increasing overall survival under the combinatorial effect of RTV and temozolomide.

Conclusions: Our data establish RTV as a valuable repositioning candidate for further exploration as an adjunct therapeutic in the clinical care of glioblastoma.
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http://dx.doi.org/10.1016/j.ejca.2020.09.017DOI Listing
November 2020

Predictors of catheter-associated meningitis in pediatric patients after brain tumor surgery: A 10-year single center experience.

J Neurol Sci 2020 Nov 18;418:117100. Epub 2020 Aug 18.

Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Objective: To evaluate the incidence of catheter-associated meningitis (CAM) in a pediatric population receiving brain tumor surgery, and to identify the major risk factors involved.

Methods: We retrospectively analyzed the medical and radiological records of 205 pediatric patients who received 251 external ventricular drains (EVDs) between January 2008 and December 2017. All patients less than 18 years old who underwent cerebrospinal fluid (CSF) diversion in the course of brain tumor surgery were included. Patients with central nervous system infection (CNS) at the time of EVD insertion were excluded.

Results: A total of 99 patients receiving 107 EVDs met the study selection criteria. Among this population, the incidence of CAM was 19.2%. Median time-to-infection was 5 days. CAM prolonged the period of drainage in 57.9% of the cases. An extended ICU stay (>3 days) was statistically significantly associated with the occurrence of CAM. In the multivariate analysis, the presence of a high-grade CNS tumor was a predictor of an extended intensive care unit (ICU) stay. Furthermore, CSF leakage along the catheter tunnel was an independent predictor of CAM.

Conclusion: Our data confirms CAM as a significant complication in the acute treatment of hydrocephalus associated with pediatric brain tumors. To limit the incidence of CAM, measures must be taken to prevent CSF leakage, particularly among patients with high-grade CNS tumors that are likely to stay longer in the ICU and need prompt postoperative radiotherapy and oncological treatment.
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http://dx.doi.org/10.1016/j.jns.2020.117100DOI Listing
November 2020

Seizures at the onset of aneurysmal SAH: epiphenomenon or valuable predictor?

J Neurol 2021 Feb 27;268(2):493-501. Epub 2020 Aug 27.

Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany.

Objective: Seizures at the onset (SAO) of aneurysmal subarachnoid hemorrhage (aSAH) occur in up to one of every five cases. To date, there is no consensus on causal background and clinical value of these early bleeding-related seizures. This study aimed to analyze the predictors and the impact of SAO in aSAH.

Methods: All aSAH patients from the institutional observational cohort (01/2003-06/2016) were retrospectively reviewed. Patients' charts and emergency protocols from first responders were screened for the occurrence of seizures in the first 24 h after aSAH. Patients' baseline characteristics and occurrence of post-hemorrhagic complications were analyzed. Outcome endpoints included in-hospital mortality and poor outcome at 6-month follow-up (modified Rankin Scale > 3).

Results: Of 984 patients included in the final analysis, SAO occurred in 93 cases (9.5%) and were independently associated with younger age (< 51 years, p < 0.001), WFNS grade ≥ 4 (p < 0.001), aneurysm characteristics (location at the proximal branch of the anterior cerebral artery [p = 0.037] and irregular sac [p = 0.019]) and admission body temperature > 38.3 ℃ (p = 0.008). There was an association between SAO and early complications (early infarcts [p = 0.004] and primary decompressive craniectomy [p = 0.024]). Only in the subgroup analysis restricted to the younger individuals, SAO independently predicted poor outcome of aSAH (p = 0.002).

Significance: Onset seizures following aSAH are rare and most likely related to the severity of early brain injury. Particularly, younger individuals are not only at higher risk for SAO, but are also prone to poor outcome in case of aSAH accompanied with SAO.

Trial Registration Number: German clinical trial registry (DRKS, unique identifier: DRKS00008749, 06/09/2015).
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http://dx.doi.org/10.1007/s00415-020-10173-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880934PMC
February 2021

Adjustable pressure valves for chronic hydrocephalus following subarachnoid hemorrhage: Is it worthwhile?

Clin Neurol Neurosurg 2020 11 5;198:106133. Epub 2020 Aug 5.

Department of Neurosurgery and Spine Surgery, University Hospital, University of Duisburg-Essen, Essen, Germany.

Objective: Compared to fixed pressure valves (FPV), adjustable pressure valves (APV) might reduce the rates of over/underdrainage necessitating revision surgery after shunt placement. But due to higher implant costs and valve vulnerability, the use APV in neurosurgery is still limited. The aim of this study was to evaluate the clinical utility of APV in patients with aneurysmal subarachnoid hemorrhage (aSAH).

Material And Methods: All consecutive aSAH patients undergoing ventriculoperitoneal shunt (VPS) placement at our institution between 2003 and 2016 were eligible. Rates and the risk factors for shunt valve dysfunction and over/underdrainage were evaluated.

Results: A total of 189 patients were included in the final analysis. FPV were implanted in the majority of patients (173/91.5 %). Revision surgery due to over/underdrainage was performed in 8 (4.6 %) cases with FPV and in no case with APV. Higher patients' age (>65 years, p = 0.011; aOR 10.36) and bone flap reimplantation following decompressive craniectomy (p = 0.044; aOR 6.53) independently predicted the need for revision surgery for over/underdrainage. There was no difference in the occurrence of valve dysfunction between the two valve types (1 [6.3 %] APV, 12 [6.9 %] FPV), p > 0.99). Patients requiring revision surgery for over/underdrainage had a higher risk for unfavorable outcome at 6 months follow-up (mRS>3, p = 0.009; aOR = 8.0).

Conclusion: APV is a valuable option for aSAH individuals undergoing VPS implantation to reduce the need for revision surgery for over/underdrainage. Particularly, elderly patients and those requiring bone flap reimplantation might benefit from APV.
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http://dx.doi.org/10.1016/j.clineuro.2020.106133DOI Listing
November 2020

The predominant expression of cancer stem cell marker ALDH1A3 in tumor infiltrative area is associated with shorter overall survival of human glioblastoma.

BMC Cancer 2020 Jul 17;20(1):672. Epub 2020 Jul 17.

Department of Neurosurgery and Spine Surgery, University hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany.

Background: ALDH1A3 is a cancer stem cell marker in neoplasms including glioblastoma (GBM). However, the comprehensive role of ALDH1A3 in GBM remains unclear. This study attempted to investigate the expression of ALDH1A3 in human GBM tissues and its association with clinical parameters.

Methods: Thirty primary GBM and 9 control were enrolled in this study. ALDH1A3 mRNA and protein expression levels were detected by RT-PCR and western blot, respectively. Immunohistochemistry and immunofluorescence staining were performed to evaluate the regional and cellular expression manner of ALDH1A3. The association of ALDH1A3 expression with multiple clinical parameters was analyzed.

Results: ALDH1A3 protein level, but not mRNA level, in a subgroup of GBM was significantly higher than that in the control group. ALDH1A3 immunoreactivity was detected heterogeneously in individual GBMs. Fifteen of 30 cases showed a positive of ALDH1A3 immunoreactivity which was predominantly observed in the tumor infiltrative area (TI). Double immunofluorescence staining revealed a co-localization of ALDH1A3 with GFAP in glial-shaped cells and in tumor cells. ALDH1A3 immunoreactivity was often merged with CD44, but not with CD68. Moreover, ALDH1A3 expression was positively associated with the tumor edema grade and inversely with overall survival (OS) (median OS: 16 months vs 10 months), but with neither MGMT promoter methylation status nor Ki67 index in GBM. An upregulation of ALDH1A3 was accompanied by a reduced expression of STAT3β and p-STAT3β.

Conclusions: Inter- and intra-tumoral heterogeneous expression of ALDH1A3 was exhibited in GBMs. A high immunoreactivity of ALDH1A3 in tumor infiltrative area was associated with shorter OS, especially in patients with MGMT promoter methylation. Our findings propose ALDH1A3 not only as a predictive biomarker but also as a potential target for personalized therapy of GBM.
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http://dx.doi.org/10.1186/s12885-020-07153-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368792PMC
July 2020

Pathophysiology of Intracranial Aneurysms: COX-2 Expression, Iron Deposition in Aneurysm Wall, and Correlation With Magnetic Resonance Imaging.

Stroke 2020 08 10;51(8):2505-2513. Epub 2020 Jul 10.

Department of Neurosurgery (J.R., B.C., D.P., P.D., M.D.O., Y.Z., R.J., U.S., K.H.W.), University Hospital Essen, Germany.

Background And Purpose: The pathophysiology of development, growth, and rupture of intracranial aneurysms (IAs) is only partly understood. Cyclooxygenase 2 (COX-2) converts arachidonic acid to prostaglandin H, which, in turn, is isomerized to prostaglandin E. In the human body, COX-2 plays an essential role in inflammatory pathways. This explorative study aimed to investigate COX-2 expression in the wall of IAs and its correlation to image features in clinical (1.0T, 1.5T, and 3.0T) magnetic resonance imaging (MRI) and ultra-high-field 7T MRI.

Methods: The study group comprised 40 patients with partly thrombosed saccular IAs. The cohort included 17 ruptured- and 24 unruptured IAs, which had all been treated microsurgically. Formaldehyde-fixed paraffin-embedded samples were immunohistochemically stained with a monoclonal antibody against COX-2 (Dako, Santa Clara, CA; Clone: CX-294). We correlated Perls Prussian blue staining, MRI, and clinical data with immunohistochemistry, analyzed using the Trainable Weka Segmentation algorithm.

Results: Aneurysm dome size ranged between 2 and 67 mm. The proportion of COX-2 positive cells ranged between 3.54% to 85.09%. An upregulated COX-2 expression correlated with increasing IA dome size (=0.047). Furthermore, there was a tendency of higher COX-2 expression in most ruptured IAs (=0.064). At all field strengths, MRI shows wall hypointensities due to iron deposition correlating with COX-2 expression (=0.022).

Conclusions: Iron deposition and COX-2 expression in IAs walls correlate with signal hypointensity in MRI, which might, therefore, serve as a biomarker for IA instability. Furthermore, as COX-2 was also expressed in small unruptured IAs, it could be a potential target for specific medical treatment.
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http://dx.doi.org/10.1161/STROKEAHA.120.030590DOI Listing
August 2020

The SHORT Score for Preoperative Assessment of the Risk for Short-Term Survival in Glioblastoma.

World Neurosurg 2020 06 4;138:e370-e380. Epub 2020 Mar 4.

Department of Neurosurgery, University Hospital Essen, Essen, Germany; German Cancer Consortium, Partner Site University Hospital Essen, Essen, Germany.

Background: Despite recent improvements in treatment of glioblastoma (GBM), some patients still have a short survival. We sought to develop a new risk score for preoperative assessment of short-term survival (STS) (<6 months) in patients with GBM.

Methods: All adult patients who underwent surgical resection of GBM between 2004 and 2014 were included (N = 379). Demographic and clinical parameters, which were available at admission, were assessed. Variables were evaluated in univariate and multivariate analyses. The score was validated in a separate cohort of patients with GBM who underwent surgical resection between 2015 and 2018.

Results: The following independent predictors of STS were integrated into a new score: body height (<169 cm, 1 point), arterial hypertension (1 point), age (≤54 years, 0 points; 55-74 years, 1 points; ≥75 years, 2 points), and poor clinical status (Karnofsky performance scale [KPS] score: ≤60%, 2 points; 70%-80%, 1 point; ≥90%, 0 points). The new risk score, SHORT (Small body height, Hypertension, Older age, Reduced KPS score, short-Term survival), ranged from 0 to 6 points and showed good accuracy of risk estimation for STS in GBM (area under the curve: 0.715). STS rates were 9.7%, 23.1%, and 70% in patients with GBM scoring <2 points, 2-4 points, and >4 points (P < 0.0001). The score was successfully validated (area under the curve: 0.770).

Conclusions: This study presents the SHORT score for preoperative assessment of STS risk in patients with GBM. This risk score needs external validation in larger patient cohorts from other institutions. Our score might be a tool to facilitate treatment decisions in patients with GBM before surgery.
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http://dx.doi.org/10.1016/j.wneu.2020.02.131DOI Listing
June 2020

Macrophages/Microglia Represent the Major Source of Indolamine 2,3-Dioxygenase Expression in Melanoma Metastases of the Brain.

Front Immunol 2020 5;11:120. Epub 2020 Feb 5.

Skin Cancer Unit of the Dermatology Department, Medical Faculty, West German Cancer Center, University Duisburg-Essen, Essen, Germany.

The manifestation of brain metastases in patients with advanced melanoma is a common event that limits patient's survival and quality of life. The immunosuppressive properties of the brain parenchyma are very different compared to the rest of the body, making it plausible that the current success of cancer immunotherapies is specifically limited here. In melanoma brain metastases, the reciprocal interplay between immunosuppressive mediators such as indoleamine 2, 3-dioxygenase (IDO) or programmed cell death-ligand 1 (PD-L1) in the context of neoplastic transformation are far from being understood. Therefore, we analyzed the immunoreactive infiltrate (CD45, CD3, CD8, Forkhead box P3 [FoxP3], CD11c, CD23, CD123, CD68, Allograft Inflammatory factor 1[AIF-1]) and PD-L1 with respect to IDO expression and localization in melanoma brain metastases but also in matched metastases at extracranial sites to correlate intra- and interpatient data with therapy response and survival. Comparative tissue analysis identified macrophages/microglia as the major source of IDO expression in melanoma brain metastases. In contrast to the tumor infiltrating lymphocytes, melanoma cells exhibited low IDO expression levels paralleled by cell surface presentation of PD-L1 in intracranial metastases. Absolute numbers and pattern of IDO-expressing cells in metastases of the brain correlated with recruitment and localization of CD8 T cells, implicating dynamic impact on the regulation of T cell function in the brain parenchyma. However, paired analysis of matched intra- and extracranial metastases identified significantly lower fractions of cytotoxic CD8 T cells in intracranial metastases while all other immune cell populations remain unchanged. In line with the already established clinical benefit for PD-L1 expression in extracranial melanoma metastases, Kaplan-Meier analyses correlated PD-L1 expression in brain metastases with favorable outcome in advanced melanoma patients undergoing immune checkpoint therapy. In summary, our data provide new insights into the landscape of immunosuppressive factors in melanoma brain metastases that may be useful in the implication of novel therapeutic strategies for patients undergoing cancer immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2020.00120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013086PMC
March 2021

In the wall lies the truth: a systematic review of diagnostic markers in intracranial aneurysms.

Brain Pathol 2020 05 27;30(3):437-445. Epub 2020 Feb 27.

Department of Neurosurgery, University Hospital of Essen, Essen, Germany.

Objective: Despite recent advances in molecular biology and genetics, the development of intracranial aneurysms (IA) is still poorly understood. Elucidation of the processes occurring in the IA wall is essential for a better understanding of IA pathophysiology. We sought to analyze the current evidence from histological, molecular and genetic studies of IA.

Methods: We systematically searched PubMed, Scopus, Web of Science and Cochrane Library for articles published before Mar 1, 2019 reporting on different diagnostic markers in human IA specimens. Expression of the markers in IA wall (vs. healthy arterial wall) and association with the rupture status were analyzed. The quality of the included studies and the level of the evidence for the markers were incorporated into the final data assessment.

Results: We included 123 studies reporting on analyses of 3476 IA (median 19 IA/study) published between 1966 and 2018. Based on microscopic, biochemical, genetic and biomechanical analyses, data on 358 diagnostic targets in the IA wall were collected. We developed a scale to distribute the diagnostic markers according to their specificity for IA or healthy arterial wall, as well as for ruptured or unruptured IA. We identified different functional pathways, which might reflect the intrinsic and extrinsic processes underlying IA pathophysiology.

Conclusions: Multiple histological and molecular markers and the related functional pathways contributing to the development of IA might present promising targets for future therapeutic interventions. Because of small numbers of IA samples in each study, 89% of the analyzed diagnostic markers presented with the lowest level of evidence. This underlines the need for the initiation of a multi-centric prospective histological IA register for pooled data analysis.
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http://dx.doi.org/10.1111/bpa.12828DOI Listing
May 2020

Preoperative Survival Prediction in Patients With Glioblastoma by Routine Inflammatory Laboratory Parameters.

Anticancer Res 2020 02;40(2):1161-1166

Department of Neurosurgery, University Hospital Essen, Essen, Germany.

Background: Glioblastoma (GBM) is the most common malignant brain tumor in adults and still carries a dismal prognosis. As several studies detected a connection between inflammation and GBM prognosis, we sought to explore possible associations between routinely investigated inflammatory parameters and GBM outcome.

Patients And Methods: Patients treated for GBM at our Institution between 2004 and 2014 were included. White blood cell count (WBC), C-reactive protein (CRP) and the ratio of platelets and WBC (Plt/WBC) were evaluated preoperatively. Medical records were reviewed for clinical parameters (age, sex, preoperative clinical condition, genetic alterations). Study endpoints were overall (OS) and 1- and 2-year survival.

Results: In the final cohort consisting of 565 individuals with GBM, univariate analysis showed significant associations for WBC, CRP and Plt/WBC ratio with OS. Kaplan-Meier survival plot confirmed significantly poorer OS in patients with WBC>12/nl and with CRP≥2.9 mg/dl. In multivariate analysis, a WBC of >12/nl was an independent prognostic factor for all three outcome parameters and CRP≥2.9 mg/dl for OS and 1-year survival.

Conclusion: Preoperative WBC and CRP values were confirmed as independent predictors of GBM outcome. This emphasizes the need for further evaluation of the role of inflammation in the prognosis of GBM.
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http://dx.doi.org/10.21873/anticanres.14058DOI Listing
February 2020

Tumour Treating Fields (TTFields) in combination with lomustine and temozolomide in patients with newly diagnosed glioblastoma.

J Cancer Res Clin Oncol 2020 Mar 11;146(3):787-792. Epub 2019 Dec 11.

Division of Clinical Neurooncology, Department of Neurology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.

Purpose: In the EF-14 trial for newly diagnosed glioblastoma (ndGBM) patients addition of Tumour Treating Fields (TTFields) to temozolomide treatment resulted in a significantly improved overall survival (OS). In the NOA-09/CeTeG trial, combination of lomustine and temozolomide was superior to temozolomide monotherapy in patients with O6-methylguanine DNA methyltransferase (MGMT) promoter methylated (MGMTm) ndGBM. We evaluated combination of these two treatment modalities in patients with MGMTm ndGBM. There have been so far no data on the combination of these two efficient regimens.

Methods: This bicentric retrospective analysis investigated 16 patients. Parameters evaluated included safety outcome as measured by Common Toxicity Criteria for Adverse Events (CTCAE), clinical outcomes, and compliance to treatment.

Results: Hematologic adverse events CTCAE ≥ 3 were observed in seven, hepatotoxic adverse events of CTCAE ≥ 3 in four patients. Mild to moderate skin toxicity was detected in six patients. At data cutoff, patients demonstrated a median progression-free survival (PFS) of 20 months. The usage rate of TTFields showed a high median adherence (83%) to the therapy.

Conclusions: This analysis provides first indication that the combination of TTFields/lomustine/temozolomide is safe and feasible. The observed survival outcomes might suggest potential beneficial effects.
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http://dx.doi.org/10.1007/s00432-019-03106-8DOI Listing
March 2020

TET2 promotor methylation and TET2 protein expression in pediatric posterior fossa ependymoma.

Neuropathology 2020 Apr 28;40(2):138-143. Epub 2019 Nov 28.

Department of Neurosurgery, University Hospital of Essen, Essen, Germany.

Pediatric posterior fossa ependymoma (PF) is one of the most common brain tumors in children. Recently, two subtypes of PF were identified. PF-A has a dismal prognosis and shows a hypermethylation phenotype, whereas PF-B shows a great genomic instability. The ten-eleven translocation methylcytosine dioxygenase 2 (TET2) gene (TET2) has been linked to the regulation of DNA methylation. We analyzed TET2 promotor methylation and protein expression to assess the role of TET2 in PF. Medical records of all PF cases treated in our institution between 1993 and 2015 were evaluated regarding tumor histology, grade, tumor location, gender, age, tumor recurrence, distant metastasis, survival and time to progression. Subsequently, we analyzed TET2 promotor methylation using methylation-specific polymerase chain reaction. TET2 protein expression was assessed using immunohistochemistry. Low TET2 expression was detected in seven of 17 cases. There was an association between low TET2 expression and tumor recurrence (P = 0.049). A TET2 promotor methylation was detected in five of 10 cases. There was no association between the TET2 promotor methylation with recurrence, tumor grade or gender. TET2 promotor methylation and low TET2 expression was detected in a subgroup of PF. Our data show an association between low TET2 expression and tumor recurrence in PF.
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http://dx.doi.org/10.1111/neup.12615DOI Listing
April 2020

A rare case of a completely thrombosed bilobed giant intracranial aneurysm of the anterior cerebral artery with spontaneous parent vessel thrombosis: case report.

BMC Neurol 2019 Nov 23;19(1):297. Epub 2019 Nov 23.

Department of Neurosurgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Background: A huge spherical intracranial mass can sometimes be misdiagnosed, due to the lack of typical radiographic features. Thrombosed giant intracranial aneurysms (GIAs) are an uncommon but still a possible differential diagnosis that must be kept in mind to guarantee the best surgical approach and resection of the lesion. We describe an extremely rare case of a huge bifrontal mass mimicking a cystic echinococcosis, in which the surgery unveiled a completely thrombosed GIA of the left anterior cerebral artery (ACA).

Case Presentation: A 61-year-old patient complained about intermittent weakness of the right leg, mild holocephalic headache, beginning cognitive deficits and lethargy. Magnetic resonance imaging (MRI) showed a huge partially calcified and bilobed frontal mass with peripheral edema. Based on a time-resolved angiography with interleaved Stochastic trajectories MRI (TWIST-MRI), a vascular origin of the lesion was considered unlikely. Therefore, the surgery was performed under the suspicion of a cystic echinococcosis but revealed a bilobed GIA of the left ACA with a parent vessel thrombosis. Although only a limited left frontal craniotomy was performed, a proximal control of the parent vessel could be ensured, and the aneurysm was successfully clipped. The patient showed postoperatively no new neurological deficits.

Conclusions: Completely thrombosed GIAs with parent vessel thrombosis are rare lesions that might be misdiagnosed if typical radiographic features are missing. Thus, in case of an intracranial spherical mass with signs of intralesional hemorrhage and mural calcifications, presence of a completely thrombosed GIA should be considered as a possible differential diagnosis.
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http://dx.doi.org/10.1186/s12883-019-1529-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875162PMC
November 2019

To resect or not to resect? Risks and benefits of surgery in older patients with glioblastoma.

J Geriatr Oncol 2020 05 28;11(4):688-693. Epub 2019 Oct 28.

Department of Neurosurgery, University Hospital Essen, Essen, Germany; German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany.

Introduction: Glioblastoma multiforme (GBM) has a peak incidence in patients older than 65 years. The aim of the present study is to evaluate the impact of surgical strategy on short- and long-term outcomes of older GBM patients.

Methods: A total of 273 older patients (65-84 years) from 2006 to 2014 were operated in our neurosurgical center. The study endpoints were postoperative change of the Karnofsky performance status scale (KPS) and overall survival (OS). The extent of resection (EOR) was categorized into gross total resection (GTR, >95% by volume), subtotal resection (STR, ≤95%) and stereotactic biopsy (SB). The subgroup analyses were performed in two age groups dichotomized at 75 years.

Results: EOR was associated with the risk of postoperative decline of KPS only in patients aged ≥75 years (p = 0.0002/p = 0.0014 for SB vs. GTR and STR respectively), but not in the age group 65-74 years (p = 0.1511/p = 0.2701). The mean OS in the whole cohort was 8.4 months (±9.6). GTR was superior to SB with regards to OS (p < 0.0001/p = 0.0017). STR revealed a more favorable OS than SB only in patients aged 65-74 years (p = 0.0077). Multivariate analysis confirmed that only GTR was independently associated with OS (p < 0.0001/p = 0.013).

Conclusions: GTR may provide a better OS even in GBM patients with advanced age. STR still shows a benefit over SB for OS in older patients <75 years. For older individuals, SB presents a safer option with regards to the risk of postoperative morbidity and should be favored in cases, when the surgical alternative is limited to STR.
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http://dx.doi.org/10.1016/j.jgo.2019.10.013DOI Listing
May 2020

Simultaneous primary cancer occurrence of melanoma and pulmonary adenocarcinoma in leptomeningeal metastases: a case report.

BMC Cancer 2019 Oct 23;19(1):995. Epub 2019 Oct 23.

Division of Clinical Neurooncology, Department of Neurology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.

Background: Leptomeningeal metastasis (LM) is a predominantly late stage, devastating complication of a variety of malignant solid tumors. Diagnosis relies predominantly on neurological, radiographic, and cerebrospinal fluid (CSF) assessments. Recently, liquid biopsy tests derived from CSF has shown to be a feasible, noninvasive promising approach to tumor molecular profiling for proper brain cancer diagnostic treatment, thereby providing an opportunity for CSF-based personalized medicine. However, LM is typically misleadingly assumed to originate from only one primary tumor type.

Case Presentation: In this case report, we provide first evidence of the co-occurrence of LM originating from more than one primary tumor types.

Discussion And Conclusions: Based on this patient case profile, the co-occurrence of LM from two or more primary tumor types should be accounted for when deriving diagnostic conclusions from liquid biopsy tests.
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http://dx.doi.org/10.1186/s12885-019-6183-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813083PMC
October 2019

Treatment allocation of ruptured anterior communicating artery aneurysms: The influence of aneurysm morphology.

Clin Neurol Neurosurg 2019 Nov 30;186:105506. Epub 2019 Aug 30.

Department of Neurosurgery, University Hospital, University of Duisburg-Essen, Essen, Germany.

Objectives: Since publication of the ISAT study, the majority of neurovascular centers adhere to "coil first" policy for patients with subarachnoid hemorrhage (SAH). However, final allocation in favor of coiling or clipping is based on anatomic features of ruptured intracranial aneurysms with respect to clinical characteristics of SAH. In this study, we analyzed the parameters relevant for treatment allocation of ruptured anterior communicating artery aneurysms (AComAA).

Patients And Methods: From our institutional SAH database, all cases with ruptured AComAA, which underwent diagnostic subtraction angiography (DSA) with subsequent treatment allocation, were included. The radiographic features of AComAA were collected from pre-treatment DSA. In addition, demographic, clinical and radiographic parameters of SAH were recorded. The variables selected through univariate analyses were subsequently evaluated using multivariate regression analysis.

Results: Of 300 SAH patients in the final analysis, the majority of the cases underwent endovascular coiling (n = 221, 73.7%). The following aneurysm features were associated with treatment modality in the univariate analysis: maximal sack size (p = 0.034), perpendicular height (p = 0.007), aspect ratio (p < 0.001) and sack/neck-ratio (p = 0.001). Accordingly, the following cutoffs for these variables were defined upon the receiver operating characteristics curves: 5 mm for sack size, 6 mm for perpendicular height, 1.6 for aspect ratio and sack/neck-ratio. In the multivariate analysis, aspect ratio of 1.6 was the only independent predictor of treatment allocation (p = 0.005; aOR = 2.57; 95% CI 1.33-4.96), which remained significant (p = 0.003; aOR = 2.77; 95% CI 1.41-5.45) after adjusting for patients' age, WFNS & Fisher grades, as well as intracerebral hematoma volume.

Conclusion: Although not-routinely assessed during initial allocation treatment, our retrospective analysis proved that aspect ratio is a reliable predictor of treatment allocation of ruptured AComAA. Except for large space-occupying ICH commonly obligating the microsurgical treatment, other clinical and radiographic characteristics of SAH do not seem to be of clinical relevance for the selection of treatment modality.
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http://dx.doi.org/10.1016/j.clineuro.2019.105506DOI Listing
November 2019

Endovascular treatment of cerebral vasospasm after subarachnoid hemorrhage: More is more.

Neurology 2019 07 5;93(5):e458-e466. Epub 2019 Jul 5.

From the Department of Neurosurgery (R.J., D.P., M.D.O., U.S.) and Institute for Diagnostic and Interventional Radiology (C.M., M.F.), University Hospital of Essen; Department of Neurosurgery (R.J., R.R., M.S., J.B.), Medical Center, University of Freiburg; and Institute for Medical Biometry and Medical Informatics (K.K.) and Department of Neuroradiology (C.T., H.U.), University Medical Center Freiburg, Germany.

Objective: Delayed cerebral ischemia (DCI) is strongly associated with poor outcome after subarachnoid hemorrhage (SAH). Cerebral vasospasm is a major contributor to DCI and requires special attention. To evaluate the effect of vasospasm management on SAH outcome, we performed a pooled analysis of 2 observational SAH cohorts.

Materials: Data from 2 institutional databases with consecutive patients with SAH treated between 2005 and 2012 were pooled. The effect of 2 institutional standards of conservative and endovascular vasospasm treatment (EVT) on the rates of DCI (new cerebral infarcts not visible on the post-treatment imaging) and unfavorable outcome (modified Rankin Scale score >2) at 6 months follow-up was analyzed.

Results: The final analysis included 1,057 patients with SAH. There was no difference regarding demographic (age and sex), clinical (Hunt & Hess grades, acute hydrocephalus, treatment modality, and infections), and radiographic (Fisher grades and aneurysm location) characteristics of the populations. However, there was a significant difference in the rate (24.4% [121/495] vs 14.4% [81/562], < 0.0001) and timing (first treatment on day 6 vs 8.9 after SAH, < 0.0001) of EVT. The rates of DCI (20.8% vs 29%, = 0.0001) and unfavorable outcome (44% vs 50.6%, = 0.04) were lower in the cohort with more frequent and early EVT. Multivariate analysis confirmed independent effect of EVT standard on DCI risk and outcome.

Conclusions: A preventive strategy utilizing frequent and early EVT seems to reduce the risk of DCI in patients with SAH and improve their functional outcome. We recommend prospective evaluation of the value of preventive EVT strategy on SAH.

Classification Of Evidence: This study provides Class III evidence that for patients with SAH, a frequent and early EVT to treat vasospasm reduces the risk of DCI and improves functional outcome.
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http://dx.doi.org/10.1212/WNL.0000000000007862DOI Listing
July 2019

Intracranial aneurysms in patients with tuberous sclerosis complex: a systematic review.

J Neurosurg Pediatr 2019 May 10;24(2):174-183. Epub 2019 May 10.

Objective: Tuberous sclerosis complex (TSC) is a rare multisystem genetic disease. Arterial wall developmental disorders, such as aneurysms, in association with TSC have been well described for extracranial vasculature. The characteristics of intracranial aneurysms (IAs) in TSC have not previously been addressed in the literature. This systematic review was performed to identify and assess the distinct characteristics of IAs in patients with TSC.

Methods: The authors searched PubMed, Scopus, and Web of Science for publications describing cases of TSC and IA reported before August 7, 2018. They also report 2 cases of IAs in TSC patients treated at their own institution.

Results: Thirty-three TSC patients with a total of 42 IAs were included in this review. Three individuals presented with subarachnoid hemorrhage. The IAs were large or giant in 57.1% and fusiform in 45.2% of the cases. Most of the IAs (61.9%, 26 of 42) originated from the internal carotid artery. There was a higher prevalence of pediatric cases (66.7%) and male patients (63.6%, 21 of 32 individuals with known sex) among the collected series.

Conclusions: TSC patients with IAs are characterized with a higher proportion of large/giant and fusiform IAs and young age, suggesting rapid aneurysmal growth. Furthermore, there is a distinct location pattern of IAs and an inverse sex ratio than in the healthy population. Large population-based patient registers are required to improve the understanding of epidemiology and pathophysiology of IA formation in TSC.
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http://dx.doi.org/10.3171/2019.2.PEDS18661DOI Listing
May 2019

Comparison of L-Methyl-11C-Methionine PET With Magnetic Resonance Spectroscopy in Detecting Newly Diagnosed Glioma.

Clin Nucl Med 2019 Jun;44(6):e375-e381

Nuclear Medicine Unit, Department of Imaging and Clinical Pathology, Rovigo, Italy.

Aims: Amino acid PET and magnetic resonance spectroscopy (MRS) are at the forefront of noninvasive imaging techniques used for detection and subtyping of glioma-suspicious lesions. In this pilot study, we compare L-methyl-C-methionine PET and MRS for their ability to predict glioma subtypes.

Methods: Nineteen patients with histologically, confirmed newly diagnosed glioma underwent preoperative L-methyl-C-methionine PET and MRS in 1 diagnostic session. According to the molecular portfolio and histopathologic diagnosis, patients were subdivided in isocitrate dehydrogenase (IDH) wild-type glioblastoma, IDH wild-type grade II/III glioma, IDH-mutant grade II/III glioma without 1p/19q codeletion, and with 1p/19q codeletion subgroups. Maximum tumor-to-brain ratio (TBRmax), creatine, choline, and N-acetyl aspartate peaks were correlated with postoperative histopathologic tumor diagnoses.

Results: Maximum tumor-to-brain ratio was highest in glioblastoma patients (4.18) followed by patients with IDH wild-type grade II and III glioma (3.41). The latter TBRmax values were higher compared with those in patients with IDH-mutant grade II/III glioma without 1p/19q codeletion (1.95) and in patients with IDH-mutant 1p/19q codeleted grade II and III glioma (2.79). Magnetic resonance spectroscopy marker distribution showed no clear trend. Receiver operating characteristic analysis revealed TBRmax to be the best performing parameter in identifying IDH status (area under the curve, 0.67) and all spectroscopy markers combined in identifying glioma subgroups (area under the curve, 0.68), respectively.

Conclusions: L-Methyl-C-methionine PET and MRS bear limited potential in glioma subgrouping. L-Methyl-C-methionine PET appears to be superior in differentiating IDH status, whereas MRS is more helpful in glioma subgrouping.
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http://dx.doi.org/10.1097/RLU.0000000000002577DOI Listing
June 2019

Association of Surgical Resection, Disability, and Survival in Patients with Glioblastoma.

J Neurol Surg A Cent Eur Neurosurg 2019 Jul 9;80(4):262-268. Epub 2019 Apr 9.

Department of Neurosurgery, University Hospital Essen, Essen, Germany.

Objective:  Extent of resection (EOR) and Karnofsky Performance Status (KPS) are at odds in glioblastoma (GBM) surgery, that is, the anticipated postoperative disability limits the EOR. This study analyzes the correlation of different surgical modalities with the resulting physical status and survival of patients with GBM.

Methods:  A total of 565 patients with primary GBM were operated on in a single institution between 2006 and 2014. Possible surgical modalities comprised supratotal resection (SLR), gross total resection (GTR; ≥ 95% by volume), tumor debulking (TDB; ≤ 95% by volume), and stereotactic biopsy (SB). Pre- and postoperative KPS before and up to 4 weeks after surgery as well as overall survival (OS) rate were determined retrospectively. Hazard ratio (HR) and 95% confidence intervals were calculated using a Cox proportional hazards model.

Results:  Median postoperative KPS was ≥ 70, irrespective of surgical modality. Mean OS was 12.5 months. Multivariate analysis revealed age ≥ 70 years (HR: 1.93), preoperative KPS < 70 (HR: 2.15), and unmethylation in promoter (HR: 1.27) as independent factors for worse OS. Regarding surgical modality, SB was associated with the worst survival (HR: 2.3) followed by TDB (HR: 1.36). SLR was inferior to GTR (HR: 1.27).

Conclusion:  Higher EOR in patients with GBM does not seem inevitably correlated with increasing functional impairment, but better survival, provided there is a balanced preoperative indication. Nevertheless, SLR does not seem to be superior to GTR. Whenever possible, maximal safe resection should be considered in patients with GBM, even if an EOR ≥ 95% is not possible.
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http://dx.doi.org/10.1055/s-0039-1685170DOI Listing
July 2019