Perifocal edema is a risk factor for preoperative seizures in patients with meningioma WHO grade 2 and 3.

BACKGROUND: Patients with intracranial meningiomas frequently suffer from tumor-related seizures prior to resection, impacting patients' quality of life. We aimed to elaborate on incidence and predictors for seizures in a patient cohort with meningiomas WHO grade 2 and 3. METHODS: We retrospectively searched for patients with meningioma WHO grade 2 and 3 according to the 2021 WHO classification undergoing tumor resection. Clinical, histopathological and imaging findings were collected and correlated with preoperative seizure development. Tumor and edema volumes were quantified. RESULTS: Ninety-five patients with a mean age of 59.5 ± 16.0 years were included. Most tumors (86/95, 90.5%) were classified as atypical meningioma WHO grade 2. Nine of 95 tumors (9.5%) corresponded to anaplastic meningiomas WHO grade 3, including six patients harboring TERT promoter mutations. Meningiomas were most frequently located at the convexity in 38/95 patients (40.0%). Twenty-eight of 95 patients (29.5%) experienced preoperative seizures. Peritumoral edema was detected in 62/95 patients (65.3%) with a median volume of 9 cm3 (IR: 0-54 cm3). Presence of peritumoral edema but not age, tumor localization, TERT promoter mutation, brain invasion or WHO grading was associated with incidence of preoperative seizures, as confirmed in multivariate analysis (OR: 6.61, 95% CI: 1.18, 58.12, p = *0.049). Postoperative freedom of seizures was achieved in 91/95 patients (95.8%). CONCLUSIONS: Preoperative seizures were frequently encountered in about every third patient with meningioma WHO grade 2 or 3. Patients presenting with peritumoral edema on preoperative imaging are at particular risk for developing tumor-related seizures. Tumor resection was highly effective in achieving seizure freedom.

Postoperative [68Ga]Ga-DOTA-TATE PET/CT imaging is prognostic for progression-free survival in meningioma WHO grade 1.

PURPOSE: Tumor resection represents the first-line treatment for symptomatic meningiomas, and the extent of resection has been shown to be of prognostic importance. Assessment of tumor remnants with somatostatin receptor PET proves to be superior to intraoperative estimation with Simpson grading or MRI. In this preliminary study, we evaluate the prognostic relevance of postoperative PET for progression-free survival in meningiomas. METHODS: We conducted a post hoc analysis on a prospective patient cohort with resected meningioma WHO grade 1. Patients received postoperative MRI and [68Ga]Ga-DOTA-TATE PET/CT and were followed regularly with MRI surveillance scans for detection of tumor recurrence/progression. RESULTS: We included 46 patients with 49 tumors. The mean age at diagnosis was 57.8 ± 1.7 years with a male-to-female ratio of 1:1.7. Local tumor progression occurred in 7/49 patients (14%) after a median follow-up of 52 months. Positive PET was associated with an increased risk for progression (*p = 0.015) and a lower progression-free survival (*p = 0.029), whereas MRI was not. 20 out of 20 patients (100%) with negative PET findings remained recurrence-free. The location of recurrence/progression on MRI was adjacent to regions where postoperative PET indicated tumor remnants in all cases. Gross tumor volumes were higher on PET compared to MRI (*p = 0.032). CONCLUSION: Our data show that [68Ga]Ga-DOTA-TATE PET/CT is highly sensitive in revealing tumor remnants in patients with meningioma WHO grade 1. Negative PET findings were associated with a higher progression-free survival, thus improving surveillance. In patients with tumor remnants, additional PET can optimize adjuvant radiotherapy target planning of surgically resected meningiomas.

Implementation of TERT promoter mutations improve prognostication of the WHO classification in meningioma.

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.

A simple surgical technique for sellar closure after transsphenoidal resection of pituitary adenomas in the context of risk factors for cerebrospinal fluid leaks and meningitis.

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.

Intraoperative ultrasonography in laminectomy for degenerative cervical spondylotic myelopathy: a clinical and radiological evaluation.

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 < 0.001, 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.

Detection of impending perfusion deficits by intraoperative computed tomography (iCT) in aneurysm surgery of the anterior circulation.

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.

Past medical history of tumors other than meningioma is a negative prognostic factor for tumor recurrence in meningiomas WHO grade I.

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.

Poor prognosis associated with TERT gene alterations in meningioma is independent of the WHO classification: an individual patient data meta-analysis.

BACKGROUND: TERT 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. METHODS: We 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. RESULTS: TERT-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. CONCLUSIONS: TERT-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 NUMBER: PROSPERO: CRD42018110566.

Microscopic brain invasion in meningiomas previously classified as WHO grade I is not associated with patient outcome.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.001, HR: 0.237, CI 0.170-0.382). 170 patients with the brain/meningioma interface present in histopathological specimen were separately analyzed as a subgroup. Importantly, presence of brain invasion did not reach significance for PFS, even in the subgroup with available specimen of brain/meningioma interface (p = 0.787, HR: 0.852, CI 0.268-2.710 and p = 0.811, HR: 0.848, CI 0.222-3.246, respectively). Patients with and without brain invasion did not differ in terms of age, tumor location and extent of resection, but were more likely to receive radiotherapy (p = 0.03) of tumor remnants. However, subgroup analysis of non-irradiated tumors revealed no prognostic influence of brain invasion (p = 0.749, HR: 0.772, CI 0.158-3.767). CONCLUSIONS: In this bi-institutional series, brain invasion was frequent among meningiomas WHO grade I when brain/meningioma interface was available for histology (16.5%). However, brain invasion did not impact early recurrence.

Significance of cerebrospinal fluid inflammatory markers for diagnosing external ventricular drain-associated ventriculitis in patients with severe traumatic brain injury.

Objective: The 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. Methods: Retrospective 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. Results: There 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). Conclusions: The 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.

TERT promoter mutation is associated with worse prognosis in WHO grade II and III meningiomas.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

18F-FET-PET as a biomarker for therapy response in non-contrast enhancing glioma following chemotherapy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.001). T2-volume based assessment was not associated with outcome. CONCLUSION: 18F-FET-PET is a promising biomarker for early response assessment in Gd-negative gliomas undergoing chemotherapy. It might be helpful for a timely adjustment of potentially ineffective treatment concepts and overcomes limitations of conventional structural imaging.

Spinal Tuberculosis within the Vertebral Arch Mimicking a Malignant Tumor: Case Report.

BACKGROUND: Spinal tuberculosis is a manifestation of extrapulmonary tuberculosis. The incidence of tuberculosis is low in high-income countries; however, globally, it still remains one of the most frequent fatal infectious diseases. Because of its rarity in developed countries, spinal tuberculosis can be mistaken for malignant tumors of the spine, especially in case of an atypical radiologic manifestation and without pulmonary affection. METHODS: We present the case of a 39-year-old man from South India with quickly progressing gait disturbance and hypesthesia below the Th10 level. Magnetic resonance imaging revealed an osteolytic lesion of the vertebral arch Th2 with central necrosis and compression of the spinal cord altogether highly suspicious for spinal metastasis. RESULTS: After surgical removal of the mass by laminectomy, the patient regained normal neurologic function. Histology revealed a severe granulomatous inflammation and DNAhybridization of polymerase chain reaction (PCR) products detected Mycobacterium tuberculosis-specific DNA in the sample. Biopsy of an enlarged hilar lymphnode allowed us to obtain material to successfully perform a drug resistance test to start specific antimicrobial therapy. CONCLUSION: Spinal tuberculosis, even with atypical radiologic appearance, has to be considered a differential diagnosis in patients with provenance from endemic countries. A multidisciplinary diagnostic approach helps perform antimicrobial susceptibility testing to avoid delaying the start of antibiotic therapy.

Stab Injury of the Petrosal Bone: Case Report and Literature Review.

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.

Multimodal therapy of cavernous sinus meningioma: Impact of surgery and 68Ga-DOTATATE PET-guided radiation therapy on tumor control and functional outcome.

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.

PSMA Expression in Glioblastoma as a Basis for Theranostic Approaches: A Retrospective, Correlational Panel Study Including Immunohistochemistry, Clinical Parameters and PET Imaging.

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.

Molecular diagnostics helps to identify distinct subgroups of spinal astrocytomas.

Primary spinal cord astrocytomas are rare, hence few data exist about the prognostic significance of molecular markers. Here we analyze a panel of molecular alterations in association with the clinical course. Histology and genome sequencing was performed in 26 spinal astrocytomas operated upon between 2000 and 2020. Next-generation DNA/RNA sequencing (NGS) and methylome analysis were performed to determine molecular alterations. Histology and NGS allowed the distinction of 5 tumor subgroups: glioblastoma IDH wildtype (GBM); diffuse midline glioma H3 K27M mutated (DMG-H3); high-grade astrocytoma with piloid features (HAP); diffuse astrocytoma IDH mutated (DA), diffuse leptomeningeal glioneural tumors (DGLN) and pilocytic astrocytoma (PA). Within all tumor entities GBM (median OS: 5.5 months), DMG-H3 (median OS: 13 months) and HAP (median OS: 8 months) showed a fatal prognosis. DMG-H3 tend to emerge in adolescence whereas GBM and HAP develop in the elderly. HAP are characterized by CDKN2A/B deletion and ATRX mutation. 50% of PA tumors carried a mutation in the PIK3CA gene which is seemingly associated with better outcome (median OS: PIK3CA mutated 107.5 vs 45.5 months in wildtype PA). This exploratory molecular profiling of spinal cord astrocytomas allows to identify distinct subgroups by combining molecular markers and histomorphology. DMG-H3 tend to develop in adolescence with a similar dismal prognosis like GBM and HAP in the elderly. We here describe spinal HAP with a distinct molecular profile for the first time.

Simpson Grade Revisited - Intraoperative Estimation of the Extent of Resection in Meningiomas Versus Postoperative Somatostatin Receptor Positron Emission Tomography/Computed Tomography and Magnetic Resonance Imaging.

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.

Stereotactic Internal Shunt Placement in Congenital Intracranial Cysts.

INTRODUCTION: 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. METHODS: 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 χ2 statistics. RESULTS: We 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 (P < 0.01) with the corresponding estimates of alternative treatments (P < 0.01). CONCLUSIONS: 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.