The importance of additional intracranial injuries in epidural hematomas: detailed clinical analysis, long-term outcome, and literature review in surgically managed epidural hematomas.

Objective: Epidural hematomas (EDH) occur in up to 8.2% of all traumatic brain injury patients, with more than half needing surgical treatment. In most patients suffering from this perilous disease, good recovery with an excellent clinical course is possible. However, the clinical course is mainly dependent on the presence of additional intracerebral injuries. Few studies comparing isolated and combined EDH in detail exist. Methods: We performed a retrospective single-center study from April 2002 to December 2014. The mean follow-up time was more than 6 years. In addition to analyzing diverse clinicoradiological data, we performed a systematic literature review dealing with a detailed comparison of patients with (combined) and without (isolated) additional intracerebral injuries. Results: We included 72 patients in the study. With increasing age, combined EDH had a higher incidence than isolated EDH. The mortality rate of the patients in the cohort was 10%, of which 0% had isolated EDH and 10% had combined EDH. Good recovery was achieved in 69% of patients, of which 91% had isolated EDH and 50% had combined EDH. A subgroup analysis of the different additional intracerebral injuries in combined EDH demonstrated no significant difference in outcome. A systematic literature review only identified six studies. Patients with isolated EDH had a statistically significantly lower mortality risk [relative risk (RR): 0.22; 95% CI: 0.12-0.39] and a statistically significantly lower risk of unfavorable Glasgow outcome scale score (RR: 0.21; 95% CI: 0.14-0.31) than patients with combined EDH. Conclusions: An excellent outcome in patients with surgically treated isolated EDH is possible. Furthermore, patients with combined EDH or isolated EDH with a low Glasgow coma scale (GCS) score may have favorable outcomes in 50% of the cases. Therefore, every possible effort for treatment should be made for this potentially lethal injury.

Heme Biosynthesis Factors and 5-ALA Induced Fluorescence: Analysis of mRNA and Protein Expression in Fluorescing and Non-fluorescing Gliomas.

Objective: The intraoperative visualization of adult-type diffuse gliomas with 5-aminolevulinic acid (5-ALA) induced fluorescence is widely used in the neurosurgical field. While visible 5-ALA induced fluorescence is found in the majority of high-grade gliomas, most low-grade gliomas lack visible fluorescence during surgery. Recently, the heme biosynthesis pathway was identified as crucial influencing factor for presence of visible fluorescence since it metabolizes 5-ALA to fluorescing Protoporphyrin IX (PpIX). However, the exact alterations within the heme biosynthesis pathway resulting in visible 5-ALA induced fluorescence in gliomas are still unclear. The aim of the present study was thus to compare the mRNA and protein expression of promising intramitochondrial heme biosynthesis enzymes/transporters in glioma tissue samples of different fluorescence behavior. Methods: A total of 19 strongly fluorescing and 21 non-fluorescing tissue samples from neurosurgical adult-type diffuse gliomas (WHO grades II-IV) were included in the current analysis. In these samples, we investigated the mRNA expression by quantitative real time PCR and protein expression using immunohistochemistry of the intramitochondrial heme biosynthesis enzymes Coproporphyrinogen Oxidase (CPOX), Protoporphyrinogen Oxidase (PPOX), Ferrochelatase (FECH), and the transporter ATP-binding Cassette Subfamily B Member 2 (ABCG2). Results: Regarding mRNA expression analysis, we found a significantly decreased ABCG2 expression in fluorescing specimens compared to non-fluorescing samples (p = 0.001), whereas no difference in CPOX, PPOX and FECH was present. With respect to protein expression, significantly higher levels of CPOX (p = 0.005), PPOX (p < 0.01) and FECH (p = 0.003) were detected in fluorescing samples. Similar to mRNA expression analysis, the protein expression of ABCG2 (p = 0.001) was significantly lower in fluorescing samples. Conclusion: Distinct alterations of the analyzed heme biosynthesis factors were found primarily on protein level. Our data indicate that heme biosynthesis pathway activity in general is enhanced in fluorescing gliomas with upregulation of PpIX generating enzymes and decreased ABCG2 mediated PpIX efflux outweighing the also increased further metabolization of PpIX to heme. Intramitochondrial heme biosynthesis factors thus constitute promising pharmacological targets to optimize intraoperative 5-ALA fluorescence visualization of usually non-fluorescing tumors such as low-grade gliomas.

Does pigmentation, hemosiderin and blood effect visible 5-ALA fluorescence in cerebral melanoma metastasis?

INTRODUCTION: The clinical impact of 5-aminolevulinic acid (5-ALA) fluorescence during resection of brain metastases is not yet clear.. Recent data demonstrated significantly lower incidence of visible fluorescence in cerebral melanoma metastases (CMM) compared to other brain metastases (BM). The aim of this study was to investigate if characteristic melanoma features such as pigmentation, intratumoural hemosiderin and bleeding have an influence on visible fluorescence in CMM. MATERIALS AND METHODS: A retrospective study of two neurosurgical centers was performed including adult patients with resection of CMM after preoperative administration of 5-ALA. Data on the fluorescence status (visible or no fluorescence), the fluorescence quality (strong, vague, none) and fluorescence homogeneity (homogeneous or heterogeneous) of each CMM were collected. The amount of melanin, hemosiderin and intratumoural bleeding was semi-quantitatively determined and automated computer-based calculation of the relative pigmented area was performed in fluorescing and non-fluorescing CMM samples. RESULTS: Altogether, 29 CMM were surgically removed after 5-ALA administration. Visible fluorescence was detected in 8 CMM (28%), whereas no fluorescence was detected in 21 CMM (72%). In detail, 3 tumors (10%) showed strong fluorescence, 5 tumors (17%) revealed vague fluorescence and in 21 tumors (72%) no fluorescence was found. In total, 8 fluorescing and 25 non-fluorescing CMM samples were investigated. According to the semi-quantitatively calculated fluorescence status, no statistically significant difference in the median amount of melanin (p = 0.242), hemosiderin (p = 0.603) and bleeding (p = 0.762) between CMM samples with and without visible fluorescence was found. Moreover, the automatically assessed relative pigmented area did not show a statistically significant difference between samples with visible and no fluorescence (p = 0.966). CONCLUSION: Our data indicate that 5-ALA fluorescence is not dependent on the amount of pigmentation, intratumoural hemosiderin and bleeding in CMM. We thus assume that other factors are responsible for the low rate of visible fluorescence in CMM.

The Digital Brain Tumour Atlas, an open histopathology resource.

Currently, approximately 150 different brain tumour types are defined by the WHO. Recent endeavours to exploit machine learning and deep learning methods for supporting more precise diagnostics based on the histological tumour appearance have been hampered by the relative paucity of accessible digital histopathological datasets. While freely available datasets are relatively common in many medical specialties such as radiology and genomic medicine, there is still an unmet need regarding histopathological data. Thus, we digitized a significant portion of a large dedicated brain tumour bank based at the Division of Neuropathology and Neurochemistry of the Medical University of Vienna, covering brain tumour cases from 1995-2019. A total of 3,115 slides of 126 brain tumour types (including 47 control tissue slides) have been scanned. Additionally, complementary clinical annotations have been collected for each case. In the present manuscript, we thoroughly discuss this unique dataset and make it publicly available for potential use cases in machine learning and digital image analysis, teaching and as a reference for external validation.

Prognostic Value of 5-ALA Fluorescence, Tumor Cell Infiltration and Angiogenesis in the Peritumoral Brain Tissue of Brain Metastases.

Complete resection is an indispensable treatment option in the management of brain metastases (BM). 5-aminolevulinic acid (5-ALA) fluorescence is used for improved intraoperative visualization of tumor tissue in gliomas and was recently observed in BM. We investigated the potential of 5-ALA fluorescence to visualize the infiltrative growth of BM in the peritumoral brain tissue and its histopathological correlate. Patients with BM resection after 5-ALA administration and collection of tissue samples from peritumoral brain tissue were included. Each tissue sample was histopathologically investigated for tumor cell infiltration and angiogenesis. Altogether, 88 samples were collected from the peritumoral brain tissue in 58 BM of 55 patients. Visible 5-ALA fluorescence was found in 61 (69%) of the samples, tumor infiltration in 19 (22%) and angiogenesis in 13 (15%) of samples. Angiogenesis showed a significant correlation with presence of fluorescence (p = 0.008). Moreover, angiogenesis was related to visible 5-ALA fluorescence and showed an association with patient prognosis since it was significantly correlated to shorter time to local progression/recurrence (p = 0.001) and lower one-year survival (p = 0.031). Consequently, angiogenesis in the peritumoral brain tissue of BM might be a novel prognostic marker for individualized perioperative treatment concepts in the future.

Postoperative Magnetic Resonance Imaging After Surgery of Brain Metastases: Analysis of Extent of Resection and Potential Risk Factors for Incomplete Resection.

BACKGROUND: Extent of resection (EOR) constitutes a crucial factor for patient prognosis in surgery of brain metastases (BMs). According to early studies using postoperative magnetic resonance imaging (MRI), an unexpected residual tumor was not uncommon. Knowledge of potential risk factors for incomplete BM resection would be of major importance to optimize surgical strategies. The aim of this study was to evaluate EOR in a large cohort and analyze potential risk factors for incomplete BM resection. METHODS: Patients with BM resection and available postoperative MRI were included. Intraoperative estimation of EOR by the neurosurgeon was noted. Additionally, EOR was determined by postoperative MRI. Potential risk factors for incomplete resection were investigated. RESULTS: There were 145 patients with 163 BMs included. According to postoperative MRI, complete resection was achieved in 103 (63%) BMs, and resection was incomplete in 44 (27%) BMs. Postoperative MRI detected unexpected residual tumor in 32 (25%) BMs, and a misjudgment of the EOR by the neurosurgeon was found in 29% of cases. Regarding risk factors for incomplete resection, preoperative tumor volume was significantly larger in incompletely resected BMs compared with completely resected BMs (P = 0.011). All other analyzed risk factors had no significant influence on EOR. CONCLUSIONS: Our data indicate that postoperative MRI is able to detect a high portion of unexpected residual tumors after surgery of BMs. Preoperative tumor volume in particular represents an important risk factor for incomplete resection, and hence neurosurgeons should pay special attention to avoid residual tumor tissue.