European survey on neurosurgical management of primary central nervous system lymphomas and preoperative corticosteroid therapy.

Introduction: Preoperative corticosteroid therapy (CST) is common in primary central nervous system lymphoma (PCNSL) and may complicate histopathological diagnosis. There is an ongoing debate on the best management after preoperative CST. Research question: We aimed to survey how different European neurosurgical units treat PCNSL patients after preoperative CST. Methods: An English-language survey consisting of 21 questions addressing the management of patients with suspected PCNSL and preoperative CST was sent to European hospitals. The survey also included three clinical cases to assess the decision-making process in a clinical setting. Results: The survey was completed by 74 European hospitals. There was no clear consensus on how to treat a patient with PCNSL after CST. Accordingly, 24.3% responded that they would generally defer surgery regardless of a possible radiological response, 47.3% would defer surgery only if there is regression in preoperative MRI and the remaining 28.4% would defer surgery only if the tumor had completely vanished. Furthermore, there were distinct discrepancies in responses of neurosurgical units regarding their general management approach and their case-based decision in the three example cases. The results of our survey also showed regional differences and differences in treatment decisions between high-, intermediate- and low-volume centers. Discussion and conclusion: There was no clear consensus on how to treat patients with suspected PCNSL and preoperative CST. Furthermore, most centers also showed inconsistencies in their responses regarding their general approach as well as individual patient treatment. More high-quality evidence-based recommendations are needed to improve consensus and thus patient care.

Radiomic features define risk and are linked to DNA methylation attributes in primary CNS lymphoma.

Background: The prognostic roles of clinical and laboratory markers have been exploited to model risk in patients with primary CNS lymphoma, but these approaches do not fully explain the observed variation in outcome. To date, neuroimaging or molecular information is not used. The aim of this study was to determine the utility of radiomic features to capture clinically relevant phenotypes, and to link those to molecular profiles for enhanced risk stratification. Methods: In this retrospective study, we investigated 133 patients across 9 sites in Austria (2005-2018) and an external validation site in South Korea (44 patients, 2013-2016). We used T1-weighted contrast-enhanced MRI and an L1-norm regularized Cox proportional hazard model to derive a radiomic risk score. We integrated radiomic features with DNA methylation profiles using machine learning-based prediction, and validated the most relevant biological associations in tissues and cell lines. Results: The radiomic risk score, consisting of 20 mostly textural features, was a strong and independent predictor of survival (multivariate hazard ratio = 6.56 [3.64-11.81]) that remained valid in the external validation cohort. Radiomic features captured gene regulatory differences such as in BCL6 binding activity, which was put forth as testable treatment target for a subset of patients. Conclusions: The radiomic risk score was a robust and complementary predictor of survival and reflected characteristics in underlying DNA methylation patterns. Leveraging imaging phenotypes to assess risk and inform epigenetic treatment targets provides a concept on which to advance prognostic modeling and precision therapy for this aggressive cancer.

Microsurgical Creation of Giant Bifurcation Aneurysms in Rabbits for the Evaluation of Endovascular Devices.

Giant aneurysms are dangerous lesions requiring endovascular treatment, with high rates of aneurysm recanalization and re-rupture. Reliable in vivo models are rare but are required for testing new endovascular devices. We demonstrate the technical aspects of the creation of giant bifurcation aneurysms in New Zealand white rabbits (2.5-5.5 kg). A 25-30 mm long venous pouch is taken from the external jugular vein, and a bifurcation between both carotid arteries is created microsurgically. The pouch is sutured in the bifurcation to mimic a giant aneurysm. This protocol summarizes our previously published standard technique for venous pouch true arterial bifurcation aneurysms and highlights its essential modification steps for giant aneurysms. Using this modified technique, we were able to create an animal model for giant aneurysms with high comparability to humans regarding the hemodynamics and coagulation systems. Furthermore, low morbidity and high aneurysm patency rates were achieved. The proposed giant aneurysm model offers an excellent possibility for testing new endovascular devices.

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.

Perioperative levetiracetam for seizure prophylaxis in seizure-naive brain tumor patients with focus on neurocognitive functioning.

INTRODUCTION: In seizure-naive brain tumor patients, the efficacy of perioperative prophylactic antiepileptic drug treatment remains controversial. In case of administration, the common preferred drug is levetiracetam (LEV) because of its favorable pharmacological profile. Research to date has not sufficiently determined how LEV affects cognition in the short term, as is the case in the perioperative period. The objective of this prospective study was to examine the neurocognitive functioning of seizure-naive brain tumor patients after receiving LEV perioperatively. METHODS: Fortythree patients with supratentorial brain tumor scheduled for surgery received LEV three days before until six days after surgery as seizure prophylaxis. Cognitive functioning (NeuroCogFX), LEV plasma-levels, hematotoxicity, side-effects, as well as health-related quality of life (HRQoL, Qolie31), were recorded preoperatively before (Baseline) and after onset of LEV (Pre-Op), 4-6 days postoperatively (Post-Op) and 21 days postoperatively (Follow-Up). RESULTS: No significant changes in cognitive functioning and HRQoL were seen after onset of preoperative LEV. There was a significant improvement of NeuroCogFX total-score at Follow-Up (p = 0.004) compared to Baseline. The overall-score Qolie31 showed simultaneous improvement patterns as cognitive functioning (p < 0.001). The most frequent side effect related to study drug was somnolence (in 28.6% of patients). CONCLUSIONS: A significant improvement of cognitive functioning, as well as an improvement in HRQoL, were detected postoperatively. This is presumably due to the debulking effect of the surgery. Nevertheless, LEV has no detrimental effect on cognitive functioning in the perioperative phase in seizure-naive brain tumor patients. TRIAL REGISTRATION: This study was registered prospectively (Date: 25/11/2015; EudraCT: 2015-003,916-19).

Surviving the Scene in Civilian Penetrating Brain Injury: Injury Type, Cause and Outcome in a Consecutive Patient Series in Austria.

Background: Penetrating brain injury (PBI) is a heterogeneous condition with many variables. Few data exist on civilian PBI. In some publications, PBI differentiation between low-velocity injury (LVI) and high-velocity injury (HVI) is made, but exact definitions are not given yet. The incidence of PBI depends heavily on the country of origin. Furthermore, captive bolt pistol (CBP) injuries represent a rare type of LVI and almost no reports exist in the human medical literature. Treatment of PBI has been controversially discussed due to high morbidity and mortality with results varying considerably between series. Prognostic factors are of utmost importance to identify patients who presumably benefit from treatment. Methods: A retrospective, single-center analysis of a consecutive patient series was performed from September 2005 to May 2018. We included all patients with PBI who reached our hospital alive and received any neurosurgical operative procedure. Results: Of 24 patients, 38% died, 17% had an unfavourable outcome, and 46% had a favourable outcome. In total, 58% of patients with PBI were self-inflicted. Leading causes of injury were firearms, while captive bolt pistols were responsible for 21% of injuries. LVI represented 54%, and HVI represented 46%. The outcome in HVI was significantly worse than that in LVI. A favourable outcome was achieved in 69% of LVI and 18% of HVI. Low GCS and pathological pupillary status at admission correlated significantly with an unfavourable outcome and death. Conclusions: PBI is a heterogeneous injury with many variables and major geographical and etiological differences. Differentiation between LVI and HVI is crucial for decision-making and predicting outcomes. In patients presenting with object trajectories crossing the midline, no favourable outcome could be achieved. Nevertheless, in total, a favourable outcome was possible in almost half of the patients who succeeded in surgery.

An Update on Neurosurgical Management of Primary CNS Lymphoma in Immunocompetent Patients.

Primary central nervous system lymphomas (PCNSL) are rare CNS tumors that harbor a conspicuously longer diagnostic delay compared to other malignant brain tumors. The gold standard for diagnosis is stereotactic biopsy to acquire tissue for histopathological analysis and therefore neurosurgery plays a central role when reducing the diagnostic period is mandated. However, histopathological diagnosis could be complicated if the patient was preoperatively exposed to corticosteroids. Besides the histopathological result, diagnosis of a PCNSL also requires full diagnostic workup to exclude cerebral metastatic disease of a systemic lymphoma. Most reviews of PCNSL discuss recent advancements in systemic treatment options from an (neuro-)oncologic viewpoint, whereas our intention was to discuss the optimization of the diagnostic period and therefore describe current standards of imaging, summarizing the diagnostic workup, discussing the surgical workup and future diagnostic prospects as well as the influence of preoperative corticosteroid therapy to reduce the diagnostic delay of PCNSL patients.

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 meningioma surface factor: a novel approach to quantify shape irregularity on preoperative imaging and its correlation with WHO grade.

OBJECTIVE: Atypical and anaplastic meningiomas account for 20% of all meningiomas. An irregular tumor shape on preoperative MRI has been associated with WHO grade II-III histology. However, this subjective allocation does not allow quantification or comparison. An objective parameter of irregularity could substantially influence resection strategy toward a more aggressive approach. Therefore, the aim of this study was to objectively quantify the level of irregularity on preoperative MRI and predict histology based on WHO grade using this novel approach. METHODS: A retrospective study on meningiomas resected between January 2010 and December 2018 was conducted at two neurosurgical centers. This novel approach relies on the theory that a regularly shaped tumor has a smaller surface area than an irregularly shaped tumor with the same volume. A factor was generated using the surface area of a corresponding sphere as a reference, because for a given volume a sphere represents the shape with the smallest surface area possible. Consequently, the surface factor (SF) was calculated by dividing the surface area of a sphere with the same volume as the tumor with the surface area of the tumor. The resulting value of the SF ranges from > 0 to 1. Finally, the SF of each meningioma was then correlated with the corresponding histopathological grading. RESULTS: A total of 126 patients were included in this study; 60.3% had a WHO grade I, 34.9% a WHO grade II, and 4.8% a WHO grade III meningioma. Calculation of the SF demonstrated a significant difference in SFs between WHO grade I (SF 0.851) and WHO grade II-III meningiomas (SF 0.788) (p < 0.001). Multivariate analysis identified SF as an independent prognostic factor for WHO grade (OR 0.000009, 95% CI 0.000-0.159; p = 0.020). CONCLUSIONS: The SF is a proposed mathematical model for a quantitative and objective measurement of meningioma shape, instead of the present subjective assessment. This study revealed significant differences between the SFs of WHO grade I and WHO grade II-III meningiomas and demonstrated that SF is an independent prognostic factor for WHO grade.

Extent of spinal canal obliteration as prognostic factor for functional outcome in patients with spontaneous spinal epidural hematoma: a retrospective study.

BACKGROUND: Spontaneous spinal epidural hematoma (SSEDH) is a rare condition with potentially devastating consequences. Known prognostic factors are short time to surgery, preoperative neurologic condition, and age. The aim of this study was to investigate the impact of the transversal hematoma extent with its subsequent spinal canal obliteration on outcome in patients with SSEDH. METHODS: A retrospective study including all patients that underwent surgery due to SSEDH at the University Hospital of St. Poelten between 1/7/2005 and 30/6/2020 was conducted. The percentage of spinal canal obliteration at the level where the hematoma was most prominent was calculated and correlated to functional outcome. RESULTS: A total of 17 patients could be included in this study. Preoperative ASIA impairment scale showed positive correlation with postoperative outcome (p = 0.005). Patients with a favorable outcome (ASIA D and E) showed a statistically significant lower mean obliteration of the spinal canal by the hematoma with 46.4% (± 8%) in comparison to patients with an unfavorable outcome with 62.1% (± 6%, p = 0.001). A cut-off of 51% yielded a sensitivity and specificity for favorable outcome of 100% and 70% respectively (area under the ROC 0.93, p < 0.001). CONCLUSION: Preoperative percentage of spinal canal obliteration is statistically significant lower in patients with favorable outcome in surgically treated patients with spontaneous spinal epidural hematoma.

Nerve root herniation with entrapment in the facet joint gap after lumbar decompression surgery: a case presentation.

BACKGROUND: An incidental dural tear is a well-known complication during spine surgery. A rare consequence is a postoperative nerve root herniation. The purpose of this report is to describe a case of such a herniation with entrapment in the facet gap joint and to present the first MR images of this rare surgical complication. CASE PRESENTATION: We report a case of a patient who underwent lumbar decompression surgery and afterwards suffered a sudden intractable sciatica. Postoperative MRI showed a new facet joint gap effusion. During revision surgery an entrapped nerve root was found in the facet joint gap. In retrospective, the herniated nerve root is visible on postoperative MRI. CONCLUSION: This case report highlights a rare complication during spine surgery. This finding is important as signs suggestive for nerve root herniation can easily be overlooked on MRI. Furthermore, this represents the first MRI documentation of this complication.

Influence of preoperative corticosteroid treatment on rate of diagnostic surgeries in primary central nervous system lymphoma: a multicenter retrospective study.

BACKGROUND: Corticosteroid therapy (CST) prior to biopsy may hinder histopathological diagnosis in primary central nervous system lymphoma (PCNSL). Therefore, preoperative CST in patients with suspected PCNSL should be avoided if clinically possible. The aim of this study was thus to analyze the difference in the rate of diagnostic surgeries in PCNSL patients with and without preoperative CST. METHODS: A multicenter retrospective study including all immunocompetent patients diagnosed with PCNSL between 1/2004 and 9/2018 at four neurosurgical centers in Austria was conducted and the results were compared to literature. RESULTS: A total of 143 patients were included in this study. All patients showed visible contrast enhancement on preoperative MRI. There was no statistically significant difference in the rate of diagnostic surgeries with and without preoperative CST with 97.1% (68/70) and 97.3% (71/73), respectively (p = 1.0). Tapering and pause of CST did not influence the diagnostic rate. Including our study, there are 788 PCNSL patients described in literature with an odds ratio for inconclusive surgeries after CST of 3.3 (CI 1.7-6.4). CONCLUSIONS: Preoperative CST should be avoided as it seems to diminish the diagnostic rate of biopsy in PCNSL patients. Yet, if CST has been administered preoperatively and there is still a contrast enhancing lesion to target for biopsy, surgeons should try to keep the diagnostic delay to a minimum as the likelihood for acquiring diagnostic tissue seems sufficiently high.

Fluorescence-guided resection in bone and soft tissue infiltrating meningiomas.

BACKGROUND: Bone infiltration of the tumour is common in meningioma surgery. This may also affect patients without indicative signs of bone infiltration on preoperative imaging. Unrecognized bone invasion may lead to higher recurrence rates. 5-ALA fluorescence-guided resection (5-ALA-fg) could be a promising tool to help recognize possible bone invasion and/or tumour remnants. However, there is still little data about 5-ALA-fg resection in bone and soft tissue infiltrating meningiomas. METHODS: We performed a retrospective study of 11 patients who were operated with the aid of 5-ALA due to bone and soft tissue infiltrating meningiomas at the University Hospital of St. Poelten between 2013 and 2019. RESULTS: Strong and homogeneous fluorescence of the meningioma was observed in 9 cases (81.8%) and vague and heterogeneous fluorescence in 2 cases (18.2%). Hyperostosis on computerized tomography was evident in 3 of 6 cases (50%) and bone infiltration was visible in preoperative magnetic resonance imaging in 7 of 11 patients (63.6%). All eleven patients showed positive fluorescence of the bone infiltrating part. In all 7 cases where tissue could be collected, histopathological testing verified tumour infiltration (100%). There was also fluorescence of the periosteum in 3 cases and histopathological testing verified tumour infiltration in 100%. CONCLUSION: There is growing evidence that 5-ALA-fg resection can help to identify bone infiltration in meningioma surgery. Therefore, it may help to improve extent of resection. However, further studies are necessary to investigate the rate of false-negative fluorescence and its effect on progression free survival. If 5-ALA-fg resection of meningioma is performed, the attending surgeon should also consider investigating the adjacent periosteum under blue light for detection of possible fluorescence.

Detailed analysis of 5-aminolevulinic acid induced fluorescence in different brain metastases at two specialized neurosurgical centers: experience in 157 cases.

OBJECTIVE: Incomplete neurosurgical resection of brain metastases (BM) due to insufficient intraoperative visualization of tumor tissue is a major clinical challenge and might result in local recurrence. Recently, visible 5-aminolevulinic acid (5-ALA) induced fluorescence was first reported in patients with BM. The aim of this study was thus to investigate, for the first time systematically, the value of 5-ALA fluorescence for intraoperative visualization of BM in a large patient cohort. METHODS: Adult patients (≥ 18 years) with resection of suspected BM after preoperative 5-ALA administration were prospectively recruited at two specialized neurosurgical centers. During surgery, the fluorescence status (visible or no fluorescence); fluorescence quality (strong, vague, or none); and fluorescence homogeneity (homogeneous or heterogeneous) of each BM was investigated. Additionally, these specific fluorescence characteristics of BM were correlated with the primary tumor type and the histopathological subtype. Tumor diagnosis was established according to the current WHO 2016 criteria. RESULTS: Altogether, 157 BM were surgically treated in 154 patients. Visible fluorescence was observed in 104 BM (66%), whereas fluorescence was absent in the remaining 53 cases (34%). In detail, 53 tumors (34%) showed strong fluorescence, 51 tumors (32%) showed vague fluorescence, and 53 tumors (34%) had no fluorescence. The majority of BM (84% of cases) demonstrated a heterogeneous fluorescence pattern. According to primary tumor, visible fluorescence was less frequent in BM of melanomas compared to all other tumors (p = 0.037). According to histopathological subtype, visible fluorescence was more common in BM of ductal breast cancer than all other subtypes (p = 0.008). It is of note that visible fluorescence was observed in the surrounding brain tissue after the resection of BM in 74 (67%) of 111 investigated cases as well. CONCLUSIONS: In this largest series to date, visible 5-ALA fluorescence was detected in two-thirds of BM. However, the characteristic heterogeneous fluorescence pattern and frequent lack of strong fluorescence limits the use of 5-ALA in BM and thus this technique needs further improvements.

Contralateral progression after unilateral evacuation of bilateral chronic subdural hematomas: the volume relation ratio as prognostic factor?

OBJECTIVEUnilateral evacuation of bilateral chronic subdural hematomas (bcSDHs) is associated with higher retreatment rates than an initial bilateral intervention. One reason for that is a possible progression in the size of the contralateral side after unilateral treatment. Thus, the authors focused their study on finding predictors of the need for contralateral retreatment.METHODSAll patients who had undergone unilateral or bilateral evacuation of bcSDHs in the Department of Neurosurgery at the University Hospital of St. Poelten during a 5-year period (7/2012 to 6/2017) were retrospectively identified. The preoperative hematoma volume was calculated using the XYZ/2 method.RESULTSOf a total of 103 patients with bcSDHs, 61 patients underwent bilateral evacuation and 42 patients underwent unilateral evacuation. The retreatment rate after bilateral evacuation was significantly lower than that after unilateral evacuation (14.8% vs 31%, respectively; p = 0.049). Contralateral retreatment after unilateral evacuation was necessary in 9 patients (21.4%). The preoperative contralateral hematoma volume was significantly higher in those patients who needed contralateral retreatment after initial unilateral evacuation (68.4 cm3 vs 27.4 cm3, respectively; p < 0.001). Furthermore, the so-called volume relation ratio created by dividing the smaller by the larger hematoma volume was significantly higher when contralateral retreatment became necessary (0.56 vs 0.21, respectively; p < 0.001).CONCLUSIONSPatients needing evacuation of bcSDHs should be considered for primary bilateral evacuation if the hematoma volume on the smaller side is greater than 40 cm3 and the subsequent volume relation ratio is greater than 0.4.

Fluorescence-guided resection of extracranial soft tissue tumour infiltration in atypical meningioma.

The exact role of 5-aminolevulinic acid (5-ALA) fluorescence-guided meningioma resection is as yet unclear. Although most of the meningiomas show positive fluorescence, the influence on outcome, fluorescence heterogeneity within the tumour, the correlation between fluorescence and the proliferation rate, as well as different quantitative measurements are a matter of debate. Positive fluorescence in bone infiltrative meningiomas is well described, whereas little data exist about 5-ALA fluorescence within soft tissue infiltration. We add a case of histologically confirmed fluorescent tumour infiltration into soft tissue. A 78-year-old woman underwent resection of an atypical meningioma at the University Hospital of St. Poelten. Preoperative imaging showed tumour infiltration throughout the calvaria. 5-ALA fluorescence of the tumour as well as bone, periost and temporal muscle helped to perform a gross total resection. Histological examination showed an atypical meningioma (WHO Grade II) and gave proof of tumour infiltration of the bone and temporal muscle. With the aid of 5-ALA fluorescence, a gross total resection could be performed.