Search Results (26)

Objective: Central neurocytomas (CNs), classified as CNS (central nervous system) grade 2 tumors, are exceptionally rare tumors, accounting for approximately 0.1–0.5% of all intracranial neoplasms, and are typically characterized by a benign clinical course and frequent association with hydrocephalus. This study aims to present a comprehensive analysis of surgical and adjuvant therapies for CN. Methods: The study comprised all patients who underwent microsurgical tumor removal in our center over the past decade (2013–2023). Clinical manifestations, surgical and adjuvant therapy approaches, MRI and histological findings, clinical outcomes, and recurrence-free survival were evaluated. Results: A total of eleven patients (six men, mean age of 28.0 years; five women, mean age of 53.6 years) underwent surgical treatment. Intraventricular tumors were the most common (72.7%, n = 8). The predominant presenting symptoms were headache and visual disturbances. All tumors exhibited contrast enhancement on MRI. Hydrocephalus was present in five patients. The Ki67 proliferation index ranged from 2% to 10%, with nine patients exhibiting Ki67 > 3%. The median recurrence-free survival was 38.0 months (IQR: 25.0–53.0). The most severe postoperative complications included aphasia, hemiparesis, and memory impairment, resulting in a postoperative Karnofsky Performance Status (KPS) below 70% in five patients. Follow-up assessments showed significant symptomatic improvement in all affected patients. Conclusions: Gross total resection is the recommended first-line therapy with favorable neurological outcomes and for atypical CN as well. Adjuvant radiotherapy should be reserved for tumor progression and recurrence. The role of adjuvant chemotherapy remains unclear, but it may be an option for CN with a high proliferation index. Full article

Background and Objectives: Development of acute coronary syndrome (ACS) after aneurysmal subarachnoid hemorrhage (aSAH) strongly affects further neuro-intensive care management. We aimed to analyze the incidence, risk factors and clinical impact of ACS in aSAH patients. Materials and Methods: This retrospective analysis included 855 aSAH cases treated between 01/2003 and 06/2016. The occurrence of ACS during 3 weeks of aSAH was documented. Patients’ demographic, clinical, radiographic and laboratory characteristics at admission were collected as potential ACS predictors. The association between ACS and the aSAH outcome was analyzed as the occurrence of cerebral infarcts in the computed tomography scans and unfavorable outcome (modified Rankin scale > 3) at 6 months after aSAH. Univariable and multivariable analyses were performed. Results: ACS was documented in 28 cases (3.3%) in the final cohort (mean age: 54.9 years; 67.8% females). In the multivariable analysis, there was a significant association between ACS, an unfavorable outcome (adjusted odds ratio [aOR] = 3.43, p = 0.027) and a borderline significance with cerebral infarcts (aOR = 2.5, p = 0.066). The final prediction model for ACS occurrence included five independent predictors (age > 55 years [1 point], serum sodium < 142 mmol/L [3 points], blood sugar ≥ 170 mg/dL [2 points], serum creatine kinase ≥ 255 U/L [3 points] and gamma-glutamyl transferase ≥ 36 U/L [1 point]) and showed high diagnostic accuracy for ACS prediction (AUC = 0.879). Depending on the cumulative score value, the risk of ACS in the cohort varied between 0% (0 points) and 66.7% (10 points). Conclusions: ACS is a rare, but clinically very relevant, complication of aSAH. The development of ACS can reliably be predicted by the presented prediction model, which enables the early identification of aSAH individuals at high risk for ACS. External validation of the prediction model is mandatory. Full article

Overcoming temozolomide (TMZ)-resistance is a major challenge in glioblastoma therapy. Therefore, identifying the key molecular player in chemo-resistance becomes urgent. We previously reported the downregulation of PDCD10 in primary glioblastoma patients and its tumor suppressor-like function in glioblastoma cells. Here, we demonstrate that the loss of PDCD10 causes a significant TMZ-resistance during treatment and promotes a rapid regrowth of tumor cells after treatment. PDCD10 knockdown upregulated MGMT, a key enzyme mediating chemo-resistance in glioblastoma, accompanied by increased expression of DNA mismatch repair genes, and enabled tumor cells to evade TMZ-induced cell-cycle arrest. These findings were confirmed in independent models of PDCD10 overexpressing cells. Furthermore, PDCD10 downregulation led to the dedifferentiation of glioblastoma cells, as evidenced by increased clonogenic growth, the upregulation of glioblastoma stem cell (GSC) markers, and enhanced neurosphere formation capacity. GSCs derived from PDCD10 knockdown cells displayed stronger TMZ-resistance and regrowth potency, compared to their parental counterparts, indicating that PDCD10-induced stemness may independently contribute to tumor malignancy. These data provide evidence for a dual role of PDCD10 in tumor suppression by controlling both chemo-resistance and dedifferentiation, and highlight PDCD10 as a potential prognostic marker and target for combination therapy with TMZ in glioblastoma. Full article

(1) Background: Although the incidence of glioblastoma (GB) has a peak in patients aged 75–84 years, no standard treatment regimen for elderly patients has been established so far. The goal of this study was to analyze the outcome of GB patients ≥ 65 years to detect predictors with relevant impacts on overall survival (OS) and progression-free survival (PFS). (2) Methods: Medical records referred to our institution from 2006 to 2020 were analyzed. Adult GB patients with clinical data, postoperative MRI data, and ≥1 follow-up investigation after surgical resection were included. The complete cohort was divided into a younger (<65) and an elderly group (≥65 years). Multiple factors regarding OS and PFS were scanned using univariate and multivariable regression with p < 0.05. (3) Results: 1004 patients were included with 322 (61.0%) male individuals in the younger and 267 (56.1%) males in the older cohort. The most common tumor localization was frontal in both groups. Gross total resection (GTR) was the most common surgical procedure in both groups, followed by subtotal resection (STR) (145; 27.5%) in the younger group, and biopsy (156; 32.8%) in the elderly group. Multivariate analyses detected that in the younger cohort, MGMT promoter methylation and GTR were predictors for a longer OS, while MGMT methylation, GTR, and hypofractionated radiation were significantly associated with a longer OS in the elderly group. (4) Conclusions: Elderly patients benefit from surgical resection of GB when they show MGMT promoter methylation, undergo GTR, and receive hypofractionated radiation. Furthermore, MGMT methylation seems to be associated with a longer PFS in elderly patients. Further investigations are required to confirm these findings, especially within prospective radiation therapy studies and molecular examinations. Full article

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessments is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p = 0.049), it was only necessary in less than 10% of the cases with preoperative (but discontinued) corticosteroid treatment. Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p = 0.015). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p = 0.02). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for early surgical intervention. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after the discontinuation of CS remains a case-by-case decision. The effect of anticoagulation and dual antiplatelet therapy on diagnostic accuracy might have been underestimated and should be examined closely in future investigations. Full article

Background: Stroke mimics are common in the emergency department (ED) and early detection is important to initiate appropriate treatment and withhold unnecessary procedures. We aimed to compare the frequency, clinical characteristics and predictors of non-neurological and neurological stroke mimics transferred to our ED for suspected stroke. Methods: This was a cross-sectional study of consecutive patients with suspected stroke transported to the ED of the University Hospital Essen between January 2017 and December 2021 by the city’s Emergency Medical Service. We investigated patient characteristics, preclinical data, symptoms and final diagnoses in patients with non-neurological and neurological stroke mimics. Multinominal logistic regression analysis was performed to assess predictors of both etiologic groups. Results: Of 2167 patients with suspected stroke, 762 (35.2%) were diagnosed with a stroke mimic. Etiology was non-neurological in 369 (48.4%) and neurological in 393 (51.6%) cases. The most common diagnoses were seizures (23.2%) and infections (14.7%). Patients with non-neurological mimics were older (78.0 vs. 72.0 y, p < 0.001) and more likely to have chronic kidney disease (17.3% vs. 9.2%, p < 0.001) or heart failure (12.5% vs. 7.1%, p = 0.014). Prevalence of malignancy (8.7% vs. 13.7%, p = 0.031) and focal symptoms (38.8 vs. 57.3%, p < 0.001) was lower in this group. More than two-fifths required hospitalization (39.3 vs. 47.1%, p = 0.034). Adjusted multinominal logistic regression revealed chronic kidney and liver disease as independent positive predictors of stroke mimics regardless of etiology, while atrial fibrillation and hypertension were negative predictors in both groups. Prehospital vital signs were independently associated with non-neurological stroke mimics only, while age was exclusively associated with neurological mimics. Conclusions: Up to half of stroke mimics in the neurological ED are of non-neurological origin. Preclinical identification is challenging and a high proportion requires hospitalization. Awareness of underlying etiologies and differences in clinical characteristics is important to provide optimal care. Full article

Hyper-angiogenesis is a typical feature of glioblastoma (GBM), the most aggressive brain tumor. We have reported the expression of aldehyde dehydrogenase 1A3 (ALDH1A3) in proliferating vasculature in GBM patients. We hypothesized that ALDH1A3 may act as an angiogenesis promoter in GBM. Two GBM cell lines were lentivirally transduced with either ALDH1A3 (ox) or an empty vector (ev). The angiogenesis phenotype was studied in indirect and direct co-culture of endothelial cells (ECs) with oxGBM cells (oxGBMs) and in an angiogenesis model in vivo. Angiogenesis array was performed in oxGBMs. RT²-PCR, Western blot, and double-immunofluorescence staining were performed to confirm the expression of targets identified from the array. A significantly activated angiogenesis phenotype was observed in ECs indirectly and directly co-cultured with oxGBMs and in vivo. Overexpression of ALDH1A3 (oxALDH1A3) led to a marked upregulation of PAI-1 and IL-8 mRNA and protein and a consequential increased release of both proteins. Moreover, oxALDH1A3-induced angiogenesis was abolished by the treatment of the specific inhibitors, respectively, of PAI-1 and IL-8 receptors, CXCR1/2. This study defined ALDH1A3 as a novel angiogenesis promoter. oxALDH1A3 in GBM cells stimulated EC angiogenesis via paracrine upregulation of PAI-1 and IL-8, suggesting ALDH1A3-PAI-1/IL-8 as a novel signaling for future anti-angiogenesis therapy in GBM. Full article

In order to minimize the risk of infections during the COVID-19 pandemic, remote video consultations (VC) experienced an upswing in most medical fields. However, telemedicine in neuro-oncology comprises unique challenges and opportunities. So far, evidence-based insights to evaluate and potentially customize current concepts are scarce. To fill this gap, we analyzed >3700 neuro-oncological consultations, of which >300 were conducted as VC per patients’ preference, in order to detect how both patient collectives distinguished from one another. Additionally, we examined patients’ reasons, suitable/less suitable encounters, VC’s benefits and disadvantages and future opportunities with an anonymized survey. Patients that participated in VC had a worse clinical condition, higher grade of malignancy, were more often diagnosed with glioblastoma and had a longer travel distance (all p < 0.01). VC were considered a fully adequate alternative to face-to-face consultations for almost all encounters that patients chose to participate in (>70%) except initial consultations. Most participants preferred to alternate between both modalities rather than participate in one alone but preferred VC over telephone consultation. VC made patients feel safer, and participants expressed interest in implementing other telemedicine modalities (e.g., apps) into neuro-oncology. VC are a promising addition to patient care in neuro-oncology. However, patients and encounters should be selected individually. Full article

Background: While prognosis of glioblastoma after trimodality treatment is well examined, recurrence pattern with respect to the delivered dose distribution is less well described. Therefore, here we examine the gain of additional margins around the resection cavity and gross-residual-tumor. Methods: All recurrent glioblastomas initially treated with radiochemotherapy after neurosurgery were included. The percentage overlap of the recurrence with the gross tumor volume (GTV) expanded by varying margins (10 mm to 20 mm) and with the 95% and 90% isodose was measured. Competing-risks analysis was performed in dependence on recurrence pattern. Results: Expanding the margins from 10 mm to 15 mm, to 20 mm, to the 95%- and 90% isodose of the delivered dose distribution with a median margin of 27 mm did moderately increase the proportion of relative in-field recurrence volume from 64% to 68%, 70%, 88% and 88% (p < 0.0001). Overall survival of patients with in-and out-field recurrence was similar (p = 0.7053). The only prognostic factor significantly associated with out-field recurrence was multifocality of recurrence (p = 0.0037). Cumulative incidences of in-field recurrences at 24 months were 60%, 22% and 11% for recurrences located within a 10 mm margin, outside a 10 mm margin but within the 95% isodose, or outside the 95% isodose (p < 0.0001). Survival from recurrence was improved after complete resection (p = 0.0069). Integrating these data into a concurrent-risk model shows that extending margins beyond 10 mm has only small effects on survival hardly detectable by clinical trials. Conclusions: Two-thirds of recurrences were observed within a 10 mm margin around the GTV. Smaller margins reduce normal brain radiation exposure allowing for more extensive salvage radiation therapy options in case of recurrence. Prospective trials using margins smaller than 20 mm around the GTV are warranted. Full article

Objective: Acute hydrocephalus is a common complication in patients with aneurysmal subarachnoid hemorrhage (SAH). Several ventricular indices have been introduced to enable measurements of ventricular morphology. Previously, researchers have showed their diagnostic value for various neurological disorders. In this study, we evaluated the association between ventricular indices and the clinical course, occurrence of complications and outcome of SAH. Methods: A total of 745 SAH patients with available early admission computed tomography scans were included in the analyses. Six ventricular indices (bifrontal, bicaudate, ventricular and third ventricle ratios and Evans’ and Huckman’s indices) were measured. Primary endpoints included the occurrence of cerebral infarctions, in-hospital mortality and a poor outcome at 6 months. Secondary endpoints included different adverse events in the course of SAH. Clinically relevant cut-offs for the indices were determined using receiver operating curves. Univariate analyses were performed. Multivariate analyses were conducted on significant findings in a stepwise backward regression model. Results: The higher the values of the ventricular indices were and the older the patient was, the higher the WFNS and Fisher’s scores were, and the lower the SEBES score was at admission. Patients with larger ventricles showed a shorter duration of intracranial pressure increase > 20 mmHg and required decompressive craniectomy less frequently. Ventricular indices were independently associated with the parameters of inflammatory response after SAH (C-reactive protein in serum and interleukin-6 in cerebrospinal fluid and fever). Finally, there were independent correlations between larger ventricles and all the primary endpoints. Conclusions: The lower risk of intracranial pressure increase and absence of an association with vasospasm or systemic infections during SAH, and the poorer outcome in individuals with larger ventricles might be related to a more pronounced neuroinflammatory response after aneurysmal bleeding. These observations might be helpful in the development of specific medical and surgical treatment strategies for SAH patients depending on the initial ventricle measurements. Full article

Objectives: The transphenoidal bi-nostril endoscopic resection of pituitary adenomas is regarded as a minimally invasive treatment nowadays. However, sino-nasal outcome and health-related quality of life (HRQoL) might still be impaired after the adenomectomy, depending on patients’ prior medical history and health status. A systematic postoperative comparison is required to assess differences in perceived sino-nasal outcome and HRQoL. Methods: In this single-center observational study, we collected data from 81 patients, operated between August 2016 and August 2021, at a 3–6-month follow-up after adenomectomy. We employed the sino-nasal outcome test for neurosurgery (SNOT-NC) and the HRQoL inventory Short Form (SF)-36 to compare sino-nasal and HRQoL outcome in patients with or without allergies, previous nose surgeries, presence of pain, snoring, sleep apnea, usage of continuous positive airway pressure (cpap), and nose drop usage. Results: At the 3–6-month follow-up, patients with previous nasal surgery showed overall reduced subjective sino-nasal health, increased nasal and ear/head discomfort, increased visual impairment, and decreased psychological HRQoL (all p ≤ 0.026) after pituitary adenomectomy. Patients with pain before surgery showed a trend-level aggravated physical HRQoL (p = 0.084). Conclusion: Our data show that patients with previous nasal surgery have an increased risk of an aggravated sino-nasal and HRQoL outcome after pituitary adenomectomy. These patients should be thoroughly informed about potential consequences to induce realistic patient expectations. Moreover, the study shows that patients with moderately severe allergies, snoring, and sleep apnea (± cpap) usually do not have to expect a worsened sino-nasal health and HRQoL outcome. Full article

Background and Objectives: Spinal meningiomas, which are well characterized and are most frequently intradural extramedullary tumors, represent 25% of all intradural spinal tumors. The goal of this study was to compare the outcomes of surgically treated patients with spinal meningiomas in two time intervals with special emphasis on postoperative functional outcomes. Methods: Patients with spinal meningiomas admitted to our department between 1990 and 2020 were enrolled and divided into a historic cohort (HC; treated 1990–2007) and a current cohort (CC; treated 2008–2020). Patients’ clinical data and surgical and radiological reports were retrospectively analyzed up to 5 years. Preoperative and postoperative neurological function were assessed using the modified McCormick Scale (mMCS). The Charlson Comorbidity Index (CCI) was used to evaluate the effect of comorbidities on the preoperative status and postoperative outcome. Results: We included 300 patients. Participants in the CC (n = 144) were significantly younger compared to those in the HC (n = 156), with twice as many patients <50 years of age (p < 0.001). The most common tumor location was the thoracic spine (n = 204). The median follow-up was 38.1 months (±30.3 standard deviation). A symptom duration until surgery <12 months was significantly associated with an earlier improvement in the mMCS (p = 0.045). In the CC, this duration was shorter and patients’ neurological function at the first and last follow-ups was significantly better than for those in the HC (p < 0.001 for both). Conclusions: Our study results suggested that the impact of surgical management and postoperative rehabilitation on spinal meningioma patients’ long-term neurological outcome has reached important milestones over the last decades. An earlier diagnosis led to earlier surgical treatment and improved patients’ postoperative neurological recovery. Our results exposed that surgical therapy for spinal meningioma should be performed within 12 months after appearance of symptoms to achieve a better recovery. Full article

Objective: Previous reports indicate a negative impact of anemia on the outcome of an aneurysmal subarachnoid hemorrhage (SAH). We aimed to identify the outcome-relevant severity of post-SAH anemia. Methods: SAH cases treated at our institution between 01/2005 and 06/2016 were included (n = 640). The onset, duration, and severity (nadir hemoglobin (nHB) level) of anemia during the initial hospital stay were recorded. Study endpoints were new cerebral infarctions, a poor outcome six months post-SAH (modified Rankin scale > 3), and in-hospital mortality. To assess independent associations with the study endpoints, different multivariable regression models were performed, adjusted for relevant patient and baseline SAH characteristics as well as anemia-associated clinical events during the SAH. Results: The rates of anemia were 83.3%, 67.7%, 40.0%, 15.9%, and 4.5% for an nHB < 11 g/dL, < 10 g/dL, < 9 g/dL, < 8 g/dL, and < 7 g/dL, respectively. The higher the anemia severity, the later was the onset (post-SAH days 2, 4, 5.4, 7.6 and 8, p < 0.0001) and the shorter the duration (8 days, 6 days, 4 days, 3 days, and 2 days, p < 0.0001) of anemia. In the final multivariable analysis, only an nHB < 9 g/dL was independently associated with all study endpoints: adjusted odds ratio 1.7/3.22/2.44 for cerebral infarctions/in-hospital mortality/poor outcome. The timing (post-SAH day 3.9 vs. 6, p = 0.001) and duration (3 vs. 5 days, p = 0.041) of anemia with an nHB < 9 g/dL showed inverse associations with the risk of in-hospital mortality, but not with other study endpoints. Conclusions: Anemia is very common in SAH patients affecting four of five individuals during their hospital stay. An nHB decline to < 9 g/dL was strongly associated with all study endpoints, independent of baseline characteristics and SAH-related clinical events. Our data encourage further prospective evaluations of the value of different transfusion strategies in the functional outcomes of SAH patients. Full article

Background: Rosette-forming glioneuronal tumor (RGNT) is an extremely rare entity described for the first time in the WHO classification of tumors of the central nervous system in 2007. Predominantly, single case reports of RGNT in the pineal region have been published, and specific therapy concepts are pending. Methods: The study group comprised all patients with the RGNT (CNS WHO grade 1) in the pineal region that underwent microsurgical tumor removal in our center (August 2018–June 2021). Surgical strategy, histological findings, and clinical outcome are presented, and the results are evaluated and compared to published case reports. Results: Four male patients aged under 50 years (range between 20 and 48 years) and one female patient, 51 years old, were included in this study. Chronic headaches and generalized epileptic seizures were the main symptoms. Supra-cerebellar infratentorial gross total tumor resection (GTR) was performed in two cases, two patients underwent subtotal tumor resection, and an endoscopic biopsy was performed in case five. Conclusion: In cases where surgical resection seems feasible with a reasonable surgical risk, we advocate GTR. Regular and long-term MRI follow-up is essential to detect a slow tumor progression. The role of additional chemotherapy or radiotherapy remains unclear. Full article

Temozolomide (TMZ) is the first line of standard therapy in glioblastoma (GBM). However, relapse occurs due to TMZ resistance. We attempted to establish an acquired TMZ resistance model that recapitulates the TMZ resistance phenotype and the relevant gene signature. Two GBM cell lines received two cycles of TMZ (150 µM) treatment for 72 h each. Regrown cells (RG2) were defined as TMZ resistant cells. MTT assay revealed significantly less susceptibility and sustained growth of RG2 compared with parental cells after TMZ challenge. TMZ-induced DNA damage significantly decreased in 53BP1-foci reporter transduced-RG2 cells compared with parental cells, associated with downregulation of MSH2 and MSH6. Flow cytometry revealed reduced G2/M arrest, increased EdU incorporation and suppressed apoptosis in RG2 cells after TMZ treatment. Colony formation and neurosphere assay demonstrated enhanced clonogenicity and neurosphere formation capacity in RG2 cells, accompanied by upregulation of stem markers. Collectively, we established an acute TMZ resistance model that recapitulated key features of TMZ resistance involving impaired mismatch repair, redistribution of cell cycle phases, increased DNA replication, reduced apoptosis and enhanced self-renewal. Therefore, this model may serve as a promising research tool for studying mechanisms of TMZ resistance and for defining therapeutic approaches to GBM in the future. Full article