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Background The incidence of cervical myelopathy due to spinal stenosis is constantly growing in an aging population. Especially in multisegmental disease, dorsal laminectomy is the intervention of choice. Intraoperative imaging with ultrasound might provide additional information about extent and sufficiency of spinal cord decompression. Methods In this prospective study, the width of the subarachnoid space was systematically measured by intraoperative ultrasound at predefined sites at the cranial and caudal edge of decompression in axial and sagittal reconstruction. These data were compared with corresponding sites on postoperative T2-weighted MRI imaging. In addition, the functional outcome was assessed by modified Japanese Orthopaedic Association (mJOA) score. A historical patient cohort treated without ultrasound-guided laminectomy served as control group. Results Altogether, 29 patients were included. According to mJOA score at last follow-up, 7/29 patients reported stable symptoms and 21/29 patients showed a substantial benefit with no or minor residual neurological deficits. One patient suffered from a new C5 palsy. Intraoperative ultrasound-guided posterior decompression provided excellent overview in all cases. Measurement of the width of the subarachnoid space acquired by intraoperative ultrasound and postoperative MRI images showed a very high correlation, especially at the cranial level (p r = 0.880). Bland–Altman analysis showed that most patients were within the 1.96 × SD limits of agreement throughout all measurements. No ultrasound procedure-related complications were observed. Compared to a historical cohort of 27 patients, no significant differences were found regarding functional outcome (p = 0.711). Conclusion Intraoperative sonography visualises the surgically achieved restoration of the subarachnoid space in good correlation with postoperative MRI and might serve as a fast, precise and reliable tool for intraoperative imaging in cervical laminectomy. However, we could not demonstrate a clinical benefit with regard to functional outcome.

Background The aim of our study was to evaluate the additional benefit of intraoperative computed tomography (iCT), intraoperative computed tomography angiography (iCTA), and intraoperative computed tomography perfusion (iCTP) in the intraoperative detection of impending ischemia to established methods (indocyanine green videoangiography (ICGVA), microDoppler, intraoperative neuromonitoring (IONM)) for initiating timely therapeutic measures. Methods Patients with primary aneurysms of the anterior circulation between October 2016 and December 2019 were included. Data of iCT modalities compared to other techniques (ICGVA, microDoppler, IONM) was recorded with emphasis on resulting operative conclusions leading to inspection of clip position, repositioning, or immediate initiation of conservative treatment strategies. Additional variables analyzed included patient demographics, aneurysm-specific characteristics, and clinical outcome. Results Of 194 consecutive patients, 93 patients with 100 aneurysms received iCT imaging. While IONM and ICGVA were normal, an altered vessel patency in iCTA was detected in 5 (5.4%) and a mismatch in iCTP in 7 patients (7.5%). Repositioning was considered appropriate in 2 patients (2.2%), where immediate improvement in iCTP could be documented. In a further 5 cases (5.4%), intensified conservative therapy was immediately initiated treating the reduced CBP as clip repositioning was not considered causal. In terms of clinical outcome at last FU, mRS0 was achieved in 85 (91.4%) and mRS1-2 in 7 (7.5%) and remained mRS4 in one patient with SAH (1.1%). Conclusions Especially iCTP can reveal signs of impending ischemia in selected cases and enable the surgeon to promptly initiate therapeutic measures such as clip repositioning or intraoperative onset of maximum conservative treatment, while established tools might fail to detect those intraoperative pathologic changes.

Penetrating traumas of the head are generally life-threatening injuries, whose management poses a substantial challenge for emergency department teams. These injuries are characteristically violence-associated and frequently accompanied by damage of essential organs including brain, meninges, large vessels, cranial nerves, eyes, viscerocranium, internal ear, and/or labyrinth. Here, we present an exceptional case of head trauma caused by a knife blade, which was stuck deep inside in the petrous bone. After the extraction of the knife, the patient had very few immediate and no long-term post-traumatic complications. In conclusion, high-end technical equipment as well as an interdisciplinary team of specialized physicians is recommended for the management of penetrating head trauma to optimize the outcome.

OBJECTIVE The transsphenoidal approach is the standard for most pituitary tumors. Despite low morbidity, postoperative CSF fistulas and meningitis are specific complications. Various surgical closure techniques for intraoperative CSF (iCSF) leak and sellar reconstruction have been described. For many years the authors have applied synthetic materials for iCSF leak repair and sellar closure in a standardized fashion in their department. Here they analyze the surgical outcome as well as risk factors for iCSF leak and meningitis. METHODS All patients with transsphenoidal resection of a pituitary adenoma performed by the same surgeon between January 2013 and December 2019 were screened retrospectively. A small amount of iCSF flow without a diaphragmatic defect was classified as a minor leak, and obvious CSF flow with or without a diaphragmatic defect was classified as a major leak. In case of iCSF leak, a fibrin- and thrombin-coated sponge was used to cover the diaphragmatic defect and another one was used for the sellar opening. A gelatin sponge was placed in the sphenoid sinus as an abutment. The primary and secondary outcomes were the number of postoperative CSF (pCSF) leaks and meningitis, respectively. Clinical, histological, and perioperative data from medical records were collected to identify risk factors for CSF leak and meningitis. RESULTS Of 417 transsphenoidal surgeries, 359 procedures in 348 patients with a median age of 54 years were included. There were 96 iCSF leaks (26.7%; 37.5% major, 62.5% minor). In 3 of 359 cases (0.8%) a pCSF fistula occurred, requiring revision surgery in 2 patients and a lumbar drain in 1 patient. Meningitis occurred in 3 of 359 cases (0.8%). All 3 patients recovered without sequelae after antibiotic therapy. According to univariate analysis, risk factors for iCSF leak were macroadenoma (p = 0.006) and recurrent adenoma (p = 0.032). An iCSF leak was found less often in functioning adenomas (p = 0.025). In multivariate analysis recurrent tumors remained as a risk factor (p = 0.021) for iCSF leak. Patients with iCSF leak were at increased risk for a pCSF leak (p = 0.005). A pCSF leak in turn represented the key risk factor for meningitis (p = 0.033). CONCLUSIONS Patients with macroadenomas and recurrent adenomas are especially at risk for iCSF leak. An iCSF leak in turn increases the risk for a pCSF leak, which carries the risk for meningitis. The authors’ surgical technique leads to a very low rate of pCSF leaks and meningitis without using autologous graft materials. Hence, this technique is safe and improves patient comfort by avoiding the disadvantages of autologous graft harvesting.

BackgroundTERT gene alterations (TERT-alt) have been linked to increased risk of recurrence in meningiomas, whereas the association to mortality largely remain incompletely investigated. As incongruence between clinical course and WHO grade exists, reliable biomarkers have been sought.MethodsWe applied the Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data Statement. We compiled data from eight studies and allocated patients to TERT-alt (n=59) or TERT promoter wild-type (TERTp-wt; n=618). We compared the two groups stratified for WHO grades as: incidence rates, survival probabilities and cumulative recurrences. We estimated the effects of WHO grade, age at diagnosis and sex as HRs.ResultsTERT-alt occurred in 4.7%, 7.9% and 15.4% of WHO-I/WHO-II/WHO-III meningiomas, respectively. The median recurrence-free survival was 14 months for all TERT-alt patients versus 101 months for all TERTp-wt patients. The HR for TERT-alt was 3.74 in reference to TERTp-wt. For all TERT-alt patients versus all TERTp-wt patients, the median overall survival was 58 months and 160 months, respectively. The HR for TERT-alt was 2.77 compared with TERTp-wt. TERT-alt affected prognosis independent of WHO grades. Particularly, the recurrence rate was 4.8 times higher in WHO-I/-II TERT-alt patients compared with WHO-III TERTp-wt patients. The mortality rate was 2.7 times higher in the WHO-I and WHO-II TERT-alt patients compared with WHO-III TERTp-wt patients.ConclusionsTERT-alt is an important biomarker for significantly higher risk of recurrence and death in meningiomas. TERT-alt should be managed and surveilled aggressively. We propose that TERT-alt analysis should be implemented as a routine diagnostic test in meningioma and integrated into the WHO classification.Trial registration numberPROSPERO: CRD42018110566.

For meningiomas, the 2016 revision of the WHO classification introduced brain invasion per se as a sufficient condition to classify as grade II. We analyzed whether meningiomas previously graded as WHO grade I differ in prognosis depending on the presence of microscopic brain invasion. A consecutive series of patients with intracranial meningioma WHO grade I (± brain invasion) at two neurosurgical departments was analyzed retrospectively. Cox regression models on progression-free survival (PFS) and Kaplan–Meier survival estimates were performed. 875 adult patients were included. Histological diagnosis of brain invasion was confirmed in 28 patients. Median follow-up was 73 months. In univariate and multivariate models, gross total resection gained favorable prognostic influence for PFS (p

Background Functional preservation in patients with WHO grade I meningioma involving the cavernous sinus (CSM) is crucial for long-term tumor control. Concise data on the functional outcome of an interdisciplinary, multimodal treatment are scarce. We analyzed functional outcome and tumor control in CSM patients following maximal safe resection (MSR), fractionated stereotactic radiotherapy (FSRT), or combination of them, retrospectively. Methods Patients with WHO grade I CSM treated between 2003 and 2017 were included. Prior to FSRT, a 68Ga-DOTATATE PET/CT was performed for radiation planning. Progression-free survival (PFS) was analyzed using Kaplan–Meier method and log-rank test was performed to test differences between groups. Visual function was analyzed at baseline and follow-up. Results Eighty-five patients were included. MSR alone was performed in 48 patients (group A), MSR followed by FSRT in 25 patients (group B), and FSRT alone in 12 patients (group C). Intracranial tumor volumes were higher in A and B compared to C (median 9.2/10.8/4.3 ccm for A/B/C, P = .023). Median follow-up was 47/46/45 months and PFS at 5 years 55.7%, 100%, and 100% in A/B/C, respectively (P < .001). Optic nerve compression was more common in A (91.7%) and B (84.0%) than C (16.7%), P < .001. Post-therapeutic new onset or deterioration of double vision was observed in 29% (A), 17% (B), and 0% (C). Conclusion Personalized treatment strategies for CSM are essential to control space-occupying or functionally compromising lesions. The additional potential side effect of radiotherapy seems to be justified under the aspect of longer tumor control with low functional risk. Without space-occupying effect of CSM, FSRT alone is reasonably possible.

TERT promoter mutations have been associated with increased risk of recurrence in meningioma cohorts, thus a potential biomarker for aggressive phenotypes. A main purpose of refining tumour classification is better predictions on the patient level. We compiled data from previous published cohorts to investigate patient-level predictions of recurrence based on TERTp-mut status. Implementation of TERTp-mut into the WHO grading led to better patient prognostication by improved prediction of recurrence. Our results support implementation of TERTp-mut into diagnostics and classification of meningiomas.

Background Functional preservation in patients with WHO grade I meningioma involving the cavernous sinus (CSM) is crucial for long-term tumor control. Concise data on the functional outcome of an interdisciplinary, multimodal treatment are scarce. We analyzed functional outcome and tumor control in CSM patients following maximal safe resection (MSR), fractionated stereotactic radiotherapy (FSRT), or combination of them, retrospectively. Methods Patients with WHO grade I CSM treated between 2003 and 2017 were included. Prior to FSRT, a 68Ga-DOTATATE PET/CT was performed for radiation planning. Progression-free survival (PFS) was analyzed using Kaplan–Meier method and log-rank test was performed to test differences between groups. Visual function was analyzed at baseline and follow-up. Results Eighty-five patients were included. MSR alone was performed in 48 patients (group A), MSR followed by FSRT in 25 patients (group B), and FSRT alone in 12 patients (group C). Intracranial tumor volumes were higher in A and B compared to C (median 9.2/10.8/4.3 ccm for A/B/C, P = .023). Median follow-up was 47/46/45 months and PFS at 5 years 55.7%, 100%, and 100% in A/B/C, respectively (P < .001). Optic nerve compression was more common in A (91.7%) and B (84.0%) than C (16.7%), P < .001. Post-therapeutic new onset or deterioration of double vision was observed in 29% (A), 17% (B), and 0% (C). Conclusion Personalized treatment strategies for CSM are essential to control space-occupying or functionally compromising lesions. The additional potential side effect of radiotherapy seems to be justified under the aspect of longer tumor control with low functional risk. Without space-occupying effect of CSM, FSRT alone is reasonably possible.

Background Prognostic markers for meningioma recurrence are needed to guide patient management. Apart from rare hereditary syndromes, the impact of a previous unrelated tumor disease on meningioma recurrence has not been described before. Methods We retrospectively searched our database for patients with meningioma WHO grade I and complete resection provided between 2002 and 2016. Demographical, clinical, pathological, and outcome data were recorded. The following covariates were included in the statistical model: age, sex, clinical history of unrelated tumor disease, and localization (skull base vs. convexity). Particular interest was paid to the patients’ past medical history. The study endpoint was date of tumor recurrence on imaging. Prognostic factors were obtained from multivariate proportional hazards models. Results Out of 976 meningioma patients diagnosed with a meningioma WHO grade I, 416 patients fulfilled our inclusion criteria. We encountered 305 women and 111 men with a median age of 57 years (range: 21–89 years). Forty-six patients suffered from a tumor other than meningioma, and no TERT mutation was detected in these patients. There were no differences between patients with and without a positive oncological history in terms of age, tumor localization, or mitotic cell count. Clinical history of prior tumors other than meningioma showed the strongest association with meningioma recurrence (p = 0.004, HR = 3.113, CI = 1.431–6.771) both on uni- and multivariate analysis. Conclusion Past medical history of tumors other than meningioma might be associated with an increased risk of meningioma recurrence. A detailed pre-surgical history might help to identify patients at risk for early recurrence.

Aim The aim of the current study was to enlighten the evolution of prostate-specific membrane antigen (PSMA) expression in glioblastoma between initial diagnosis and recurrence in order to provide preliminary insight for further clinical investigations into innovative PSMA-directed treatment concepts in neuro-oncology. Methods Patients who underwent resection for de-novo glioblastoma (GBM) and had a re-resection in case of a recurrent tumor following radiochemotherapy and subsequent chemotherapy were included (n = 16). Histological and immunohistochemical stainings were performed at initial diagnosis and at recurrence (n = 96 tissue specimens). Levels of PSMA expression both in endothelial and non-endothelial cells as well as vascular density (CD34) were quantified via immunohistochemistry and changes between initial diagnosis and recurrence were determined. Immunohistochemical findings were correlated with survival and established clinical parameters. Results PSMA expression was found to be present in all GBM tissue samples at initial diagnosis as well as in all but one case of recurrent tumor samples. The level of PSMA expression in glioblastoma varied inter-individually both in endothelial and non-endothelial cells. Likewise, the temporal evolution of PSMA expression highly varied in between patients. The level of vascular PSMA expression at recurrence and its change between initial diagnosis and recurrence was associated with post recurrence survival time: Patients with high vascular PSMA expression at recurrence as well as patients with increasing PSMA expression throughout the disease course survived shorter than patients with low vascular PSMA expression or decreasing vascular PSMA expression. There was no significant correlation of PSMA expression with MGMT promoter methylation status or Ki-67 labelling index. Conclusion PSMA is expressed in glioblastoma both at initial diagnosis and at recurrence. High vascular PSMA expression at recurrence seems to be a negative prognostic marker. Thus, PSMA expression in GBM might present a promising target for theranostic approaches in recurrent glioblastoma. Especially PSMA PET imaging and PSMA-directed radioligand therapy warrant further studies in brain tumor patients.

BACKGROUND Magnetic resonance imaging (MRI) based characterization has previously shown heterogeneity in tumor appearance according to IDH mutation status. We have recently investigated the relevance of contrast enhancement to be dependent on IDH mutation status in glioma WHO II and III. Here, we aimed at further characterizing tumor growth patterns and their prognostic value in these tumors. METHODS MRI and clinical data of patients with newly diagnosed glioma WHO II and III from two different centers were retrospectively reviewed. Radiological data such as localization, presence of contrast enhancement, T2-volume as well as tumor growth pattern (“diffuse” vs. “circumscript”) were obtained. Progression-free (PFS) and overall survival (OS) were determined and correlated with clinical, radiological and molecular characteristics using univariate and multivariate regression analyses. RESULTS 390 patients were included, 69% thereof having an IDH mutation. The median T2-volume was 46.0 ml, IDH mutant tumors being larger (50.7 ml) than IDH wildtype tumors (36.0 ml), p = 0.01. A total of 172 tumors were classified as “circumscript” and 218 as “diffuse”; the majority of IDH wildtype tumors (71%) were well delineated compared to 51% in the IDH mutant group (p< 0.0001). Apart from clinical parameters such as younger age, lower KPS, complete resection and delayed treatment, “circumscript” tumor growth pattern was associated with improved survival in the entire group (p = 0.016). When analyzed according to IDH mutation status, “circumscript” tumor growth pattern was significantly associated with OS and PFS (p = 0.006 and p = 0.002) in the IDH wildtype, but not in the IDH mutant group (p = 0.34 and p = 0.81). CONCLUSION IDH wildtype tumors present more often with a ”circumscript” growth pattern on initial T2 MRI. However, this “circumscript” growth pattern was associated with improved survival only in the IDH wiltdtype but not in the IDH mutant group.

Monitoring treatment response after chemotherapy of gadolinium-(Gd)-negative gliomas is challenging as conventional MRI often indicates no radiological changes. We hypothesize that 18F-FET-PET can be used as a biomarker for response assessment in Gd-negative gliomas undergoing chemotherapy. Sixty-one patients harboring Gd-negative WHO grade II or III glioma receiving alkylating agents (temozolomide or CCNU/procarbacine) were included. All patients underwent MRI and 18F-FET-PET before chemotherapy and 6 months later. We calculated T2-volume, 18F-FET-PET based biological tumour volume (BTV) and maximal tumour-to-brain ratio (TBRmax). Moreover, dynamic PET acquisition was performed using time-activity-curves (TACs) analysis. For MRI-based response assessment, RANO criteria for low-grade glioma were used. For 18F-FET-PET, following classification scheme was tested: responsive disease (RD) when a decrease in either BTV ≥ 25% and/or TBRmax ≥ 10% occurred, an increase in BTV ≥ 25% and/or TBRmax increase > 10% characterized progressive disease (PD), minor changes ± 25% for BTV and ± 10% for TBRmax were regarded as stable disease (SD). Post-chemotherapy survival (PCS) and time-to-treatment failure (TTF) were calculated using the Kaplan–Meier method. 18F-FET-PET based response has shown patients with RD to have the longest TTF time (78.5 vs 24.6 vs 24.1 months, p = 0.001), while there was no significant difference between patients with a SD and PD. A comparable pattern was observed for PCS (p

Transcriptional activating mutations in the promoter region of the telomerase reverse transcriptase (TERT) gene occur at high frequency in various types of solid tumors and have also been reported for meningiomas. Especially for atypical and anaplastic meningiomas, the prognostic relevance of TERT promoter mutation is yet unclear. The present study aimed to analyze the frequency of TERT promoter mutation and define its long-term prognostic significance beyond clinical and histological factors in a cohort of meningiomas WHO grade II and III. Patients undergoing surgical resection of aggressive meningiomas were included. Analysis for C228T and C250T mutation in the TERT promoter region was performed using PCR method. Patients were stratified into two groups (TERT mutated vs. TERT wild type). Univariate analysis was conducted using molecular and histological factors. 87 patients with atypical (N = 72) and anaplastic meningiomas (N = 15) were included in the study. TERT promoter region was found to be mutated in 4 WHO grade II and 2 WHO grade III meningiomas. TERT promoter mutation was associated with shorter progression free survival than TERT wild type meningiomas (median PFS 12.5 vs. 26 months, p = .004). In the univariate analysis, TERT promoter mutation had a strong prognostic value on overall survival (p = .009) and progression free survival. Presence of TERT promoter mutation is associated with shorter progression free survival and overall survival in meningiomas WHO grade II and III. In these tumors, TERT promoter mutation should be considered as a clinically relevant prognostic factor to identify high risk patients.

Stratification of glioma according to isocitrate dehydrogenase 1/2 (IDH1/2) mutation and 1p/19q codeletion status has gained major importance in the new World Health Organization (WHO) classification. Parameters derived from uptake dynamics of 18F-fluoro-ethyl-tyrosine PET (18F-FET-PET) such as minimal time-to-peak (TTPmin) allow discrimination between different prognostic glioma subgroups, too. The present study is aimed at exploring whether TTPmin analysis provides prognostic information beyond the WHO classification.Three hundred patients with newly diagnosed WHO 2007 grades II-IV gliomas with 18F-FET-PET imaging at diagnosis were grouped into 4 subgroups (IDH1/2 mut-1p/19q codel; IDH1/2 mut-1p/19q non-codel; IDH1/2 wildtype WHO grade II and III tumors; and glioblastoma). Clinical and imaging factors such as age, Karnofsky performance score, treatment, TTPmin, and maximal tumor-to-brain ratio (TBRmax) were analyzed with regard to progression-free and overall survival (PFS and OS) via univariate and multivariate regression analysis.PFS and OS were longest in the IDH1/2 mut-1p/19q codel subgroup, followed by IDH1/2 mut-1p/19q non-codel, IDH1/2 wildtype, and GBM (P0.001). Further, outcome stratified by TTPmin with a cutoff of 17.5 minutes revealed significantly longer PFS and OS in patients with TTPmin17.5 minutes (P0.001 for PFS and OS). Lower TBRmax values or the absence of 18F-FET uptake was also associated with favorable outcome in the entire group. In the subgroup analyses, longer median TTPmin was associated with improved outcome specifically in the IDH1/2 mut-1p/19q non-codel group.18F-FET-PET-derived dynamic analysis defines prognostically distinct subgroups of IDH1/2 mutant-1p/19q non-codel gliomas which cannot be distinguished as yet by molecular marker analysis.

Background Surgeon's intraoperative estimation of meningioma extent of resection (Simpson Grade, SG) is widely used as a prognostic factor for recurrence. However, the validity of SG is still a matter of debate. In preoperative imaging, 68Ga-DOTATATE/PET-CT has been shown to detect meningioma tissue even more sensitively than magnetic resonance imaging (MRI). Objective To evaluate the Simpson grading within the framework of modern postoperative imaging techniques (MRI; PET-CT). Methods At first, patients with WHO grade I meningioma, surgical resection, and postoperative 68Ga-DOTATATE/PET-CT within 6 mo after surgery were retrospectively analyzed. Second, an analogous prospective cohort of patients with WHO grade I meningioma was investigated by comparing SG after meningioma removal with postoperative MRI and 68Ga-DOTATATE/PET-CT within 6 mo after surgery. Results A total of 37 patients were retrospectively analyzed. In total, 5/8 patients with SG-I and II resections showed tumor remnants according to postoperative PET-CT (SG 62.5% false negative). In the prospective cohort of 52 tumors, PET-CT displayed tracer uptake in 15/37 SG-I or II resections indicating unexpected tumor remnants (SG 40.5% false negative). MRI was false negative in 7 of these 15 cases (MRI 18.9% false negative) (P = .037). Discordant results according to PET-CT were more often found in convexity (40%) and falcine (46.7%) meningiomas than in skull base meningiomas (18.2%). Conclusion Intraoperative Simpson grading is at risk to underestimate tumor remnants, predominantly in grade I and II resections. Postoperative PET-CT improves detection rates compared to MRI. Prognostic impact of postoperative meningioma remnants according to PET-CT needs to be investigated prospectively.

ObjectiveThe aim of this study was to investigate the diagnostic potential of the inflammatory markers interleukin-6 (IL-6), total leukocyte count (TLC), and protein in the CSF and IL-6, C-reactive protein, and white blood cell count in the serum for the early diagnosis of ventriculitis in patients with traumatic brain injury (TBI) and an external ventricular drain compared with patients without ventriculitis.MethodsRetrospective data from 40 consecutive patients with TBI and an external ventricular drain treated in the authors’ intensive care unit between 2013 and 2017 were analyzed. For all markers, arithmetical means and standard deviations, area under the curve (AUC), cutoff values, sensitivity, specificity, positive likelihood ratio (LR), and negative LR were calculated and correlated with presence or absence of ventriculitis.ResultsThere were 35 patients without ventriculitis and 5 patients with ventriculitis. The mean ± SD IL-6 concentration in CSF was significantly increased, with 6519 ± 4268 pg/mL at onset of ventriculitis compared with 1065 ± 1705 pg/mL in patients without ventriculitis (p = 0.04). Regarding inflammatory markers in CSF, IL-6 showed the highest diagnostic potential for differentiation between the presence and absence of ventriculitis (AUC 0.938, cutoff 4064 pg/mL, sensitivity 100%, specificity 92.3%, positive LR 13, and negative LR 0), followed by TLC (AUC 0.900, cutoff 64.5 /µL, sensitivity 100%, specificity 80%, positive LR 5.0, and negative LR 0) and protein (AUC 0.876, cutoff 31.5 mg/dL, sensitivity 100%, specificity 62.5%, positive LR 2.7, and negative LR 0).ConclusionsThe level of IL-6 in CSF has the highest diagnostic value of all investigated inflammatory markers for detecting ventriculitis in TBI patients at an early stage. In particular, CSF IL-6 levels higher than the threshold of 4064 pg/mL were significantly associated with the probability of ventriculitis.

INTRODUCTION: The revised version of the WHO classification system (2016) introduced molecular markers being of prognostic importance in gliomas. Primary spinal cord astrocytomas are very rare. Aggressive surgical resection is believed to be critical for extending progression free and overall survival. However, the prognostic significance of molecular variables remains unclear for these tumors. Herein we investigate molecular chances of spinal gliomas, which may allow more accurate risk stratification. METHODS: We performed genome sequencing in 10 spinal astrocytomas undergoing surgical resection between 2000 and 2017. These spinal astrocytomas include glioblastomas (WHO grade IV), anaplastic astrocytomas (WHO grade III), diffuse astrocytomas (WHO grade II) and pilocytic astrocytoma (WHO grade I). RESULTS: We identified 5 spinal glioblastomas, 1 anaplastic astrocytoma, 2 diffuse astrocytomas and 2 pilocytic astrocytomas. Median overall survival (OS) was 6 months (range: 2–14 months) for grade IV tumors, 33 months (range: 30–136 months) for grade II and III tumors and 95 months (range: 49–141 months) for grade I tumors, respectively. One grade II and one grade I tumor were carrying the IDH1 and IDH2 mutation, all other tumors were IDH wild type (OS: 93 vs. 10 months). Gross total resection was not achieved in any patient. 9 patients received adjuvant radiotherapy. The most current findings in spinal GBM were H3F3A mutations (5/5) and ATRX mutation (3/5). H3F3A mutation was observed in 1 WHO grade II tumor with a OS of 33 months. Mutation in H3F3A and WHO grade was associated with shortened OS in univariate analysis. WHO grade II tumors were found to have mutations in CCND2, DDX3X, EGFR, HIST1H3B, KIT, MYC, PDGFRA, PTCH2, SMARCA4 and TSC2. CONCLUSION: Genomic analysis of spinal astrocytomas provides an opportunity to identify potential clinically relevant information. These data indicate an association between H3F3A mutation and a shortened overall survival in spinal astrocytomas.

Treatment of symptomatic intracranial cysts remains a controversial issue. We present a risk/benefit profile of a minimally invasive, not yet described, stereotactic internal shunt implantation technique. The provided data might serve as a reference against which other treatment modalities could be compared.From our prospective database, we identified a consecutive series of patients with symptomatic, untreated cysts who had undergone internal shunting from 2009 to 2017. We estimated the rates of clinical symptom improvement (RCSI), cyst reduction, total complications, and long-term complications. A minimal follow-up of 6 months was required. The prognostic factors were obtained from logistic regression models. Cyst recurrence-free survival was calculated using the Kaplan-Meier method. The outcomes data were compared with those from reported alternative treatment strategies using χWe included 38 patients. The cyst locations differed greatly and included the cerebellum (n = 2), brainstem (n = 5), and pineal area (n = 4). Cyst-associated hydrocephalus (n = 6) resolved after treatment. The 2-year cyst recurrence-free survival rate was 97%. The RCSI and rate of cyst reduction, total complications, and long-term complications was 91%, 97%, 11%, and 2.6%, respectively. We did not find any risk factors associated with the rate of total complications. The RCSI and rate of total and long-term complications compared favorably (P0.01) with the corresponding estimates of alternative treatments (P0.01).The described stereotactic internal shunt implantation technique is safe and can be successfully applied for treatment of cystic formations in any location in the brain.

BACKGROUND: For meningiomas, the 2016 revision of the WHO classification of tumors of the central nervous system introduced brain invasion per se as a sufficient condition to classify as grade II. We analyzed whether meningiomas previously graded as WHO grade I differ in prognosis according to the feature of brain invasion. MATERIAL AND METHODS: All consecutive patients having been operated between 1/2009 and 03/2016 upon a meningioma being diagnosed as WHO grade I according to the previous (2007) WHO classification system were included. The reference point of the study was the date of surgery. Date of last follow up was 11/2017. Study endpoint was the date of tumor progression. Prognostic factors were obtained from multivariate proportional hazards models. RESULTS: 949 adult patients were included. The median follow-up was 43 months (range: 3–78 months). Gross total resection (GTR) was achieved in 719 (75.8%) patients, adjuvant radiotherapy was applied in 91 (9.9%) patients. Brain invasion was diagnosed by histology in 24 (2.5%) patients. Patients with/without brain invasion did not differ in terms of age and extent of resection. Patients with histologically proven brain invasion received more often adjuvant radiotherapy (p=0.008). 88 patients experienced tumor recurrence/ progression, overall survival was not reached in the majority of patients. The overall median PFS for patients with (without) brain invasion was 22 (23) months (p=0.48). In univariate and multivariate models subtotal resection and history of malignancy gained unfavorable prognostic influence for PFS (p

Objective We sought to identify potential risk factors for the development of shunt-dependent chronic hydrocephalus after aneurysmal subarachnoid hemorrhage (SAH) and external ventricular drain (EVD) insertion. In particular, the role of inflammatory markers within the cerebrospinal fluid (CSF) was assessed. Methods For this single-center analysis, data were generated from consecutive patients with SAH and the need for EVD implantation treated on our neurosurgical intensive care unit between 2013 and 2015. Parameters were patient characteristics (age, sex, comorbidity), severity of SAH (according to the World Federation of Neurological Society score), imaging findings (intraventricular hemorrhage, diameter of the third ventricle, location of the ruptured aneurysm), and acute course of disease (cerebral infarction, vasospasm). Moreover, the impact of EVD drainage volume and CSF markers (total protein [CSFTP], red blood cell count [CSFRBC], interleukin-6 [CSFIL-6], and glucose [CSFGlc]) was assessed. Statistics including receiver-operating-curve with corresponding area-under-the-curve (AUC) analysis were calculated using SPSS. Results Overall, 63 patients (21 males, mean age 55.2 years) were included. Twenty-one patients (30%) developed a shunt-dependent hydrocephalus. Significant risk factors for shunt dependency were the World Federation of Neurological Society score, cerebral infarction, and diameter of the third ventricle (P Conclusions The time course of selected inflammatory markers in CSF may support management considerations in the early phase after SAH and critical impairment of CSF circulation.

Background Mutation of the isocitrate dehydrogenase (IDH) gene and co-deletion on chromosome 1p/19q is becoming increasingly relevant for the evaluation of clinical outcome in glioma. Among the imaging parameters, contrast enhancement (CE) in WHO II/III glioma has been reported to indicate poor outcome in the past. We aimed at reassessing the prognostic value of CE in these tumours within the framework of molecular markers using a machine learning approach (random survival forests [RSF]) as well as conventional Cox regression modelling. Methods 301 patients with WHO grade II (n = 181) or grade III glioma (n = 120) were stratified according to their molecular profile. Pre-operative magnetic resonance imaging (MRI) was reviewed and volumetric analyses of CE and T2 volumes were performed followed by conventional univariate and multivariate Cox analyses. Furthermore, the dataset was split into discovery and validation datasets, and RSFs were trained on the discovery dataset to predict the individual risk of each patient. Concordance indices for Cox and RSF models were determined and the variable importance of explanatory variables was assessed using the minimal-depth concept. Results In IDH mut tumours only, both conventional Cox regression modelling and RSF analyses showed that CE on initial MRI is a prognostic factor for survival with dependence on volume (p Conclusions In patients with diffuse IDH wt gliomas WHO grade II/III, CE is not associated with survival, whereas in tumours with an IDH mutation, presence of CE on initial MRI is linked to inferior survival.

Background:Contrast enhancement (CE) and anaplasia have been reported to indicate poor outcome in diffuse glioma. Recently, mutational status of the IDH1/2 gene and loss of heterozygosity on chromosome 1p/19q (LOH1p/19q) have gained relevance for the evaluation of clinical outcome. Currently, a three-way classification based on IDH1/2 mutation and LOH 1p/19q has gained further importance and will eventually supersede the current WHO grading system in terms of risk stratification and treatment planning. Thus, we aimed in the present study to re-evaluate CE and histopathological WHO grading as risk factors for survival within the framework of these molecular markers.Methods:332 patients with diffuse glioma WHO grade II (n=189) or grade III (n=143) were stratified into 3 groups: IDH1/2 wild type (n=118), IDH1/2 mutated with (n=123) and without (n=91) LOH1p/19q. Preoperative magnetic resonance (MR) imaging was reviewed for presence of CE. Univariate and multivariate analyses were conducted taking into account CE, WHO grading, molecular as well as age, Karnofsky performance status, surgical procedure and adjuvant therapy.Results:In multivariate analysis, CE was not associated with OS in IDH1/2 wild type tumors whereas histopathological WHO grading had a strong independent prognostic value on OS in (p=0.001). In gliomas with IDH1/2 mutation, CE independently predicts shorter survival (p=0.04) and this effect seems to be especially pronounced in the IDH1/2 mutated group without LOH 1p/19q.Conclusions:In patients with diffuse gliomas WHO grade II/III and IDH1/2 wildtype, CE is not associated with survival in contrast to WHO grading. In patients with an IDH1/2 mutation, presence of CE on initial MRI is linked to inferior survival while grading is not.

2029Background: Mutational status of the IDH1/2 gene and co-deletion of on chromosome 1p/19q (co-del 1p/19q) is gaining further relevance for the evaluation of clinical outcome in lower grade gliom...

2058Background: Stratification of glial tumors according to IDH mutation and 1p/19q co-deletion status will gain further importance for tumor classification and treatment in the near future. In analogy, factors derived from 18FET-PET uptake dynamics such as time-to-peak (TTP) analysis allow discrimination between different prognostic groups. The present study aims at correlating molecular tumor characteristics and TTP analysis and to analyze associations with clinical outcome. Methods: 300 patients with de novo WHO grade II-IV gliomas with 18FET-PET imaging at diagnosis were grouped according to IDH mutation and 1p/19q co-deletion status into 3 subgroups (IDH wildtype, IDH mut/non co-del 1p/19q and IDH mut/co-del 1p/19q). Clinical and imaging factors such as age, Karnofsky performance status, treatment and 18FET-PET derived TTP analysis were analyzed with regard to progression-free and overall survival (PFS and OS) via univariate and multivariate regression analysis. Results: PFS and OS was longest in the...