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Purpose: Sodium fluorescein is a dye that, intravenously injected, selectively accumulates in high-grade glioma (HGG) tissue through a damaged blood–brain barrier. In this article, the final results of a multicentric prospective phase II trial (FLUOGLIO) on fluorescein-guided HGG resection through a dedicated filter on the surgical microscope were reported.Methods: Patients with suspected HGGs considered suitable for removal were eligible to participate in this trial. Fluorescein was intravenously injected at a dose of 5 to 10 mg/kg. The primary endpoint was the percentage of patients with histologically confirmed HGGs, without contrast-enhancing tumor at the immediate postoperative MRI. Secondary endpoints were PFS, residual tumor on postoperative MRI, overall survival, neurologic deficits, and fluorescein-related toxicity. The sensitivity and specificity of fluorescein in identifying tumor tissue were estimated by fluorescent and nonfluorescent biopsies at the tumor margin. The study was registered on the European Regulatory Authorities website (EudraCT 2011-002527-18).Results: Fifty-seven patients aged 45 to 75 years were screened for participation, and 46 were considered for primary and secondary endpoints. Mean preoperative tumor volume was 28.75 cm3 (range, 1.3–87.8 cm3). Thirty-eight patients (82.6%) underwent a complete tumor removal. Median follow-up was 11 months. PFS-6 and PFS-12 were 56.6% and 15.2%. Median survival was 12 months. No adverse reaction related to SF administration was recorded. The sensitivity and specificity of fluorescein in identifying tumor tissue were respectively 80.8% and 79.1%.Conclusions: Fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and enables a high percentage of contrast-enhancing tumor in patients with HGGs. Clin Cancer Res; 24(1); 52–61. ©2017 AACR.

Supplementary Material. Serious Adverse Events reported for the 56 initially enrolled patients in the FLUOGLIO study.

Supplementary Figure 2 from CD133+ and CD133− Glioblastoma-Derived Cancer Stem Cells Show Differential Growth Characteristics and Molecular Profiles

Supplementary Data 3 from CD133+ and CD133− Glioblastoma-Derived Cancer Stem Cells Show Differential Growth Characteristics and Molecular Profiles

Supplementary Figure 1 from CD133+ and CD133− Glioblastoma-Derived Cancer Stem Cells Show Differential Growth Characteristics and Molecular Profiles

Supplementary Data 2 from CD133+ and CD133− Glioblastoma-Derived Cancer Stem Cells Show Differential Growth Characteristics and Molecular Profiles

Supplementary Figure 1 from Temozolomide Preferentially Depletes Cancer Stem Cells in Glioblastoma

Although glioblastomas show the same histologic phenotype, biological hallmarks such as growth and differentiation properties vary considerably between individual cases. To investigate whether different subtypes of glioblastomas might originate from different cells of origin, we cultured tumor cells from 22 glioblastomas under medium conditions favoring the growth of neural and cancer stem cells (CSC). Secondary glioblastoma (n = 7)–derived cells did not show any growth in the medium used, suggesting the absence of neural stem cell–like tumor cells. In contrast, 11/15 primary glioblastomas contained a significant CD133+ subpopulation that displayed neurosphere-like, nonadherent growth and asymmetrical cell divisions yielding cells expressing markers characteristic for all three neural lineages. Four of 15 cell lines derived from primary glioblastomas grew adherently in vitro and were driven by CD133− tumor cells that fulfilled stem cell criteria. Both subtypes were similarly tumorigenic in nude mice in vivo. Clinically, CD133− glioblastomas were characterized by a lower proliferation index, whereas glial fibrillary acidic protein staining was similar. GeneArray analysis revealed 117 genes to be differentially expressed by these two subtypes. Together, our data provide first evidence that CD133+ CSC maintain only a subset of primary glioblastomas. The remainder stems from previously unknown CD133− tumor cells with apparent stem cell–like properties but distinct molecular profiles and growth characteristics in vitro and in vivo. [Cancer Res 2007;67(9):4010–5]

Supplementary Data 1 from CD133+ and CD133− Glioblastoma-Derived Cancer Stem Cells Show Differential Growth Characteristics and Molecular Profiles

The prognosis of patients suffering from glioblastoma (GBM) is dismal despite multimodal therapy. Although chemotherapy with temozolomide may contain tumor growth for some months, invariable tumor recurrence suggests that cancer stem cells (CSC) maintaining these tumors persist. We have therefore investigated the effect of temozolomide on CD133+ and CD133− GBM CSC lines. Although differentiated tumor cells constituting the bulk of all tumor cells were resistant to the cytotoxic effects of the substance, temozolomide induced a dose- and time-dependent decline of the stem cell subpopulation. Incubation with sublethal concentrations of temozolomide for 2 days completely depleted clonogenic tumor cells in vitro and substantially reduced tumorigenicity in vivo. In O6-methylguanine-DNA-methyltransferase (MGMT)–expressing CSC lines, this effect occurred at 10-fold higher doses compared with MGMT-negative CSC lines. Thus, temozolomide concentrations that are reached in patients were only sufficient to completely eliminate CSC in vitro from MGMT-negative but not from MGMT-positive tumors. Accordingly, our data strongly suggest that optimized temozolomide-based chemotherapeutic protocols might substantially improve the elimination of GBM stem cells and consequently prolong the survival of patients. [Cancer Res 2008;68(14):5706–15]

Supplementary Table 1 from Temozolomide Preferentially Depletes Cancer Stem Cells in Glioblastoma

The vasodilatory calcitonin gene-related peptide (CGRP) is excessively released after spontaneous subarachnoid hemorrhage (sSAH) and modulates psycho-behavioral function. In this pilot study, we prospectively analyzed the treatment-specific differences in the secretion of endogenous CGRP into cerebrospinal fluid (CSF) during the acute stage after good-grade sSAH and its impact on self-reported health-related quality of life (hrQoL). Twenty-six consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out 19% (n = 5)): 35% (n = 9) underwent endovascular aneurysm occlusion, 23% (n = 6) microsurgery, and 23% (n = 6) of the patients with perimesencephalic SAH received standardized intensive medical care. An external ventricular drain was inserted within 72 h after the onset of bleeding. CSF was drawn daily from day 1–10. CGRP levels were determined via competitive enzyme immunoassay and calculated as “area under the curve” (AUC). All patients underwent a hrQoL self-report assessment (36-Item Short Form Health Survey (SF-36), ICD-10-Symptom-Rating questionnaire (ISR)) after the onset of sSAH (t1: day 11–35) and at the 6-month follow-up (t2). AUC CGRP (total mean ± SD, 5.7 ± 1.8 ng/ml/24 h) was excessively released into CSF after sSAH. AUC CGRP levels did not differ significantly when dichotomizing the aSAH (5.63 ± 1.77) and pSAH group (5.68 ± 2.08). aSAH patients revealed a higher symptom burden in the ISR supplementary item score (p = 0.021). Multiple logistic regression analyses corroborated increased mean levels of AUC CGRP in CSF at t1 as an independent prognostic factor for a significantly higher symptom burden in most ISR scores (compulsive-obsessive syndrome (OR 5.741, p = 0.018), anxiety (OR 7.748, p = 0.021), depression (OR 2.740, p = 0.005), the supplementary items (OR 2.392, p = 0.004)) and for a poorer performance in the SF-36 physical component summary score (OR 0.177, p = 0.001). In contrast, at t2, CSF AUC CGRP concentrations no longer correlated with hrQoL. To the best of our knowledge, this study is the first to correlate the levels of endogenous CSF CGRP with hrQoL outcome in good-grade sSAH patients. Excessive CGRP release into CSF may have a negative short-term impact on hrQoL and emotional health like anxiety and depression. While subacutely after sSAH, higher CSF levels of the vasodilator CGRP are supposed to be protective against vasospasm-associated cerebral ischemia, from a psychopathological point of view, our results suggest an involvement of CSF CGRP in the dysregulation of higher integrated behavior.

Objective Postoperative spinal epidural hematoma (pSEH) with symptomatic compression of nervous structures after spinal decompression surgery is a rare complication. Delayed evacuation may result in severe neurologic impairment. We present a large single-center analysis of the prevalence, potential risk factors, and functional recovery after pSEH. Methods A retrospective review of our institutional database of spinal decompression surgery over 15 years yielded 6,024 consecutive patients. A total of 42 patients who had undergone surgical revision due to postoperative neurologic deterioration or intractable radiating pain and radiographically confirmed pSEH were allocated to the pSEH group. A matched 3:1 control group was formed (126 patients with the same surgical procedure, same year, same sex, and similar age). Charts, surgical reports, and radiographic data were reviewed for demographics, duration of symptoms, history of medical treatment, medication, comorbidities, radiographic extension, surgical strategy, and pre- and postoperative neurologic performance. Median follow-up was 3 months. Risk factors for pSEH, complete recovery, and recovery of neurologic symptoms were analyzed with univariable and multivariable logistic regression models. Results The prevalence of pSEH in this population was 0.69% (n = 42) with these locations: 7 of 1,284 (0.54%) cervical, 1 of 774 (0.12%) thoracic, and 34 of 3,966 (0.85%) lumbar. Use of anticoagulants (p = 0.003), pathologic coagulation values in the preoperative blood test (p = 0.034), and cigarette smoking (p = 0.003) were identified as independent risk factors of pSEH. Surgery in more than one level showed a trend toward an increased risk of pSEH. Pain as the only symptom (p = 0.0001) was a significant predictor of complete recovery. Patients symptomatic with paraplegia (p = 0.026) had a significantly higher risk of a poor neurologic outcome without full recovery of neurologic symptoms. Conclusion The prevalence of pSEH was lower than previously reported incidences. Use of anticoagulants, pathologic coagulation values, and cigarette smoking were identified as independent risk factors of pSEH. Functional outcome was related to the duration between hematoma evacuation and the clinical presentation of symptomatic pSEH.

Cerebral aneurysms are pouch-like focal dilatations of intracranial arteries, which usually occurred at their branching points. Most of these aneurysms remain asymptomatic and never ruptures. When an aneurysm ruptures, it may bleed into the brain parenchyma resulting in a parenchymal hemorrhage, or more often, it will bleed into the subarachnoid space, resulting in a subarachnoid hemorrhage (SAH). Cerebral aneurysms are not a disease unique to the modern society and a lot of improvements have been achieved especially in its treatment in the second half of the 20th century, especially after the adoption of microsurgical techniques and FDA approval for detachable coils as Endovascular techniques to treat cerebral aneurysms in 1995. The aim of the current study is to review basic knowledge about the cerebral aneurysms, with brief telescopic view on areas of conflicts, to know the current state of research regarding the cerebral aneurysms to conclude what the future research trends should be.

Neuropsychological dysfunction after treatment of spontaneous subarachnoid haemorrhage (sSAH) is common but underreported. The vasoconstrictor neuropeptide Y (NPY) is excessively released after sSAH and in psychiatric disorders. We prospectively analysed the treatment-specific differences in the secretion of endogenous cerebrospinal fluid (CSF) NPY during the acute stage after sSAH and its impact on cognitive processing.A total of 26 consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out n = 5): n = 9 underwent endovascular aneurysm occlusion, n = 6 microsurgery, and n = 6 patients with perimesencephalic SAH received standardized intensive medical care. Ventricular CSF was drawn daily from day 1-10. CSF NPY levels were determined with competitive enzyme immunoassay. All patients underwent neuropsychological self-report assessment [36-Item Short Form Health Survey (SF-36) and ICD-10-Symptom-Rating questionnaire (ISR)] after the onset of sSAH (day 11-35; tAt tTo the best of our knowledge, this study is the first to correlate the levels of endogenous NPY in supratentorial CSF with cognitive outcome in good-grade sSAH patients. Excessive NPY release into CSF may have a short-term influence on the pathogenesis of neuropsychological deficits. The impact of cerebrovascular manipulation on NPY release has to be further elucidated.ANOVA: analysis of variance; aSAH: aneurysmal subarachnoid haemorrhage; AUC: area under the curve; CBF: cerebral blood flow; CSF: cerebrospinal fluid; CT (scan): computed tomography (scan); CV: cerebral vasospasm; DIND: delayed ischemic neurological deficit; DSA: digital subtraction angiography; EIA: enzyme immunoassay; EV: endovascular aneurysm occlusion; EVD: external ventricular drainage; FU: 6-month follow-up; GCS: Glasgow Coma Scale; Ghp: general health perceptions; GOS: Glasgow Outcome Scale; h: hour/s; HH: Hunt and Hess; ICU: intensive care unit; ISR: ICD-10-Symptom-Rating questionnaire; MCS: mental component summary; Mhi: general mental health; min: minute/s; min-max: minimum - maximum; ml: millilitre; mRS: modified Ranking Scale; MS: microsurgical clipping, microsurgical aneurysm occlusion; ng: nanograms; no. [n]: number; NPY: Neuropeptide Y; p: p value; Pain: bodily pain; PCS: physical component summary; Pfi: physical functioning; pSAH: perimesencephalic subarachnoid haemorrhage; PTSD: posttraumatic stress disorder; QoL: quality of life; Rawhtran: health transition item; Rolem: role limitations because of emotional problems; Rolph: role limitations due to physical health problems; SAH: subarachnoid haemorrhage; SD: standard deviation; SF-36: 36-Item Short Form Health Survey; Social: social functioning; sSAH: spontaneous subarachnoid haemorrhage; TCD: trans-cranial Doppler ultrasound; (test) t

Advanced morphology analysis and image-based hemodynamic simulations are increasingly used to assess the rupture risk of intracranial aneurysms (IAs). However, the accuracy of those results strongly depends on the quality of the vessel wall segmentation. To evaluate state-of-the-art segmentation approaches, the Multiple Aneurysms AnaTomy CHallenge (MATCH) was announced. Participants carried out segmentation in three anonymized 3D DSA datasets (left and right anterior, posterior circulation) of a patient harboring five IAs. Qualitative and quantitative inter-group comparisons were carried out with respect to aneurysm volumes and ostia. Further, over- and undersegmentation were evaluated based on highly resolved 2D images. Finally, clinically relevant morphological parameters were calculated. Based on the contributions of 26 participating groups, the findings reveal that no consensus regarding segmentation software or underlying algorithms exists. Qualitative similarity of the aneurysm representations was obtained. However, inter-group differences occurred regarding the luminal surface quality, number of vessel branches considered, aneurysm volumes (up to 20%) and ostium surface areas (up to 30%). Further, a systematic oversegmentation of the 3D surfaces was observed with a difference of approximately 10% to the highly resolved 2D reference image. Particularly, the neck of the ruptured aneurysm was overrepresented by all groups except for one. Finally, morphology parameters (e.g., undulation and non-sphericity) varied up to 25%. MATCH provides an overview of segmentation methodologies for IAs and highlights the variability of surface reconstruction. Further, the study emphasizes the need for careful processing of initial segmentation results for a realistic assessment of clinically relevant morphological parameters.

Objectives We report on five patients with gadolinium-negative (non-enhancing magnetic resonance imaging–MRI) but 18F-fluoroethyl tyrosine positron-emission tomography (FET-PET) positive glioma (NEG) undergoing surgery under fluorescence-guidance with fluorescein sodium 10% (FL, Alkon, Germany) in combination with a dedicated light filter (YELLOW 560 nm, Carl Zeiss Meditec, Germany). Patients and method Since 2017, five patients (3 female, 2 male; mean age 45.4 years) underwent fluorescence-guided surgery for supratentorial, intracerebral lesions which showed no contrast-enhancement in the preoperative MRI but were, however, strongly suspicious for gliomas. Accordingly, all patients received a preoperative FET-PET scan and detailed histopathological workup was performed. After giving written informed consent, all patients received 5 mg/kg of FL at the induction of anesthesia. Surgery was conducted under white light and under the YELLOW 560 nm filter. We reviewed the surgical protocols, navigational storage and the image databases of our surgical microscopes for evidence of intraoperative fluorescence that corresponded to the FET-PET positive area. Results In all patients we found distinct accordances between the FET-PET positive areas and the fluorescing regions within the targeted lesions. Histopathological workup of the fluorescent tissue revealed anaplastic oligodendroglioma, IDH-mutant and 1p/19-codeleted (WHO grade III) (n = 2), anaplastic astrocytoma, IDH-mutant (WHO grade III) (n = 1), oligodendroglioma, IDH-mutant and 1p/19q-codeleted (WHO grade II) (n = 1) and pilocytic astrocytoma (WHO grade I) (n = 1). No adverse events were noted. Discussion and conclusion Despite the lack of gadolinium-enhancement in the preoperative MRI, all patients intravenously received FL to guide resection. Irrespective of the final grading, FL was extremely helpful in detecting the lesions and in identifying their border zones. In selected patients with NEG, but strong metabolic activity according to the FET-PET, FL may significantly increase the accuracy of surgery.

Space-occupying spinal metastases (SM), commonly diagnosed because of acute neurological deterioration, consequently lead to immediate decompression with tumor removal or debulking. In this study, we analyzed a series of patients with surgically treated spinal metastases and explicitly sought to determine individual predictors of functional outcome.94 patients (26 women, 68 men; mean age 64.0 years) with spinal metastases, who had been surgically treated at our department, were included retrospectively. We reviewed the pre- and postoperative charts, surgical reports, radiographic data for demographics, duration of symptoms, histopathology, stage of systemic disease, co-morbidities, radiographic extension, surgical strategy, neurological performance (Frankel Grade Classification), and the Karnofsky Performance Index (KPI).Emergency surgery within24 h after discharge had been conducted in 33% of patients. Prostate carcinoma (29.5%) and breast carcinoma (11.6%) were the most common histopathologies. Median KPI was 60% at admission that had significantly improved at discharge (KPI 70%; p = 0.01). The rate of complications without revision was 4.3%, the revision rate 4.2%. From admission to discharge, pain had been significantly reduced (p = 0.019) and motor deficits significantly improved (p = 0.003). KPI had been significantly improved during in-hospital treatment (median 60 vs 70, p = 0.010). In the multivariable analysis, predictors of poor outcome (KPI 70) were male sex, multiple metastases, and pre-existing bowel and bladder dysfunction. Median follow up was 2 months.In our series, surgery for spinal metastases (laminectomy, tumor removal, and mass reduction) significantly reduced pain as well as sensory and motor deficits. We identified male sex, multiple metastases, and pre-existing bowel and bladder dysfunction as predictors of negative outcome.

Purpose: Sodium fluorescein is a dye that, intravenously injected, selectively accumulates in high-grade glioma (HGG) tissue through a damaged blood–brain barrier. In this article, the final results of a multicentric prospective phase II trial (FLUOGLIO) on fluorescein-guided HGG resection through a dedicated filter on the surgical microscope were reported. Methods: Patients with suspected HGGs considered suitable for removal were eligible to participate in this trial. Fluorescein was intravenously injected at a dose of 5 to 10 mg/kg. The primary endpoint was the percentage of patients with histologically confirmed HGGs, without contrast-enhancing tumor at the immediate postoperative MRI. Secondary endpoints were PFS, residual tumor on postoperative MRI, overall survival, neurologic deficits, and fluorescein-related toxicity. The sensitivity and specificity of fluorescein in identifying tumor tissue were estimated by fluorescent and nonfluorescent biopsies at the tumor margin. The study was registered on the European Regulatory Authorities website (EudraCT 2011-002527-18). Results: Fifty-seven patients aged 45 to 75 years were screened for participation, and 46 were considered for primary and secondary endpoints. Mean preoperative tumor volume was 28.75 cm3 (range, 1.3–87.8 cm3). Thirty-eight patients (82.6%) underwent a complete tumor removal. Median follow-up was 11 months. PFS-6 and PFS-12 were 56.6% and 15.2%. Median survival was 12 months. No adverse reaction related to SF administration was recorded. The sensitivity and specificity of fluorescein in identifying tumor tissue were respectively 80.8% and 79.1%. Conclusions: Fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and enables a high percentage of contrast-enhancing tumor in patients with HGGs. Clin Cancer Res; 24(1); 52–61. ©2017 AACR.

Objective Cranioplasty reshapes the neurocranium and viscerocranium after craniectomy. Different materials have been used for cranioplasty. However, no consistent data are yet available comparing these different materials regarding indications, complications, and outcome. We report our experience with preformed titanium implants and freehand molded polymethylmethacrylate (PMMA) implants for cranioplasty. Methods This retrospective single-center analysis included 120 consecutive cranioplasty patients who had been operated between 2006 and 2013. A total of 60 patients (27 women, 33 men; mean age: 54 years) had received a preformed titanium implant and 60 patients (22 women, 38 men; mean age: 46 years) a freehand molded PMMA implant. We evaluated all demographic and procedure-related data, indications, and outcome. The longest follow-up was 5.5 years. Results The most frequent indications for cranioplasty were trauma (n = 48 [40%]), malignant infarction (n = 27 [23%]), tumor (n = 22 [18%]), spontaneous intracerebral or aneurysmal subarachnoid hemorrhage (n = 16 [13%]), revision surgery (n = 5 [4%]), and empyema (n = 2 [2%]). PMMA implants were more often associated with wound-healing disorders (p Conclusion Cranioplasty with preformed titanium implants seems to be superior to freehand molded PMMA implants regarding surgical morbidity, revision rate, and aesthetic results.

Background Surgical treatment of meningiomas next to venous sinuses is difficult because of their irregular growth patterns and infiltration into the venous sinuses, making gross total resection impossible in some patients. We evaluated the postoperative clinical and neurologic course of this tumor subgroup. Methods This study included 141 consecutive patients with meningioma located within 20 mm of a major venous sinus. Complete data sets were available for all patients. We reviewed patient charts and surgical reports for demographics, histology, and clinical and neurologic performance preoperatively and postoperatively and during follow-up. Radiographic images were screened for tumor extension, infiltration into the skull, sinus infiltration (Sindou grade), extent of resection (Simpson grade), and tumor recurrence. Results Immediate postoperative neurologic improvement was found in 53.7% ( n = 36) of patients with preoperative neurologic deficits ( n = 67). Follow-up was up to 13.5 years. Medical Research Council Neurological Performance Scale and Karnofsky performance scale postoperatively improved in 24.1% and 55.3% of patients, respectively. Local tumor recurrence was detected in 10.6% (n = 15) of patients. Higher World Health Organization grade ( P = 0.03), tumor size ( P = 0.001), and bone invasion ( P = 0.002) were predictors of local tumor recurrence. The median MIB-1 labeling index in patients with tumor recurrence was twice as high as in patients without recurrence. Conclusions Surgical removal of meningiomas adjacent to venous sinuses reduces neurologic impairment and enables local tumor control in most patients. Tumor size, bone infiltration, and higher World Health Organization grade are important predictors of tumor recurrence.

Objectives White Matter lesions (WML) are a risk factor for cognitive impairment in Parkinson’s disease. There is no clear evidence of reduced general cognitive function after DBS. However, a subgroup of patients develops dementia rapidly after DBS despite careful patient selection processes. The aim of this study was to evaluate the load of WML as a possible risk factor for cognitive decline following STN DBS. Patients and methods 40 PD-patients receiving bilateral STN-DBS were followed at least three years after surgery to detect dementia. All patients underwent comprehensive neuropsychological assessment and MRI before surgery. The extent of WML was assessed using an automated approach. WML volume was correlated to the onset of dementia and the decline of a cognitive composite score retrospectively. Results Patients with a rapid onset of dementia within one, respective three following DBS showed significant higher WML volumes compared to cognitive normal and MCI patients (55.8 cm3 ± 18.836 vs. 9.3 cm3 ± 12.2; p = 0.002). The same significant association was found in a multivariable model, including the covariables age, gender and PD disease duration (p = 0.01). WML volume was associated to the rate of decline in cognitive composite score within three years after DBS surgery (p = 0.006; R2 = 0.40) after correction for age. Conclusions Damaged white matter may lead to a reduced compensation of disconnections in cognitive circuits caused by the implantation of the DBS electrodes or by chronic stimulation. The role of WML as a prognostic factor for the cognitive outcome after DBS may be underestimated. The WML burden should be taken seriously in preoperative risk stratification.

Objectives Fluorescein Sodium (FL) enhances areas in the brain with a disrupted blood brain barrier (BBB). Solitary brain abscesses (BA) are characterized by the pathognomonic finding of BBB disruption. Consequently, FL may have the potential to improve the intra-operative visualization of BA. Here, we report a series of patients with BA that where treated surgically after application of FL in combination with a dedicated light filter integrated in the surgical microscope. Methods 7 patients (4 female, 3 male; mean age 53.8 years) with BA were included, all of them gave written informed consent. 5 mg/kg bodyweight of FL was administered via the central venous line at induction of anesthesia, approximately 30–45 min prior to surgery. We screened the surgical reports for any statement concerning the intensity of fluorescent staining. Results Fluorescent staining was bright in all patients. Surgical removal of all parts of the BA, aspiration of pus and dissection of the capsule, were performed in the fluorescence-mode under the filtered light. We encountered no adverse events. Conclusion The accumulation of FL resulted in brilliant visualization of the infected area under the YELLOW 560 nm filter. This small clinical study adds to the rapidly emerging clinical experiences of the use of fluorescein in neurosurgery, even for non-neoplastic lesions. However, prospective and randomized clinical trials are still necessary to establish the beneficial use of FL.

Cerebral metastasis (CM) is the most common malignancy affecting the brain. In patients eligible for surgery, complete tumor removal is the most important predictor of overall survival and neurological outcome. The emergence of surgical microscopes fitted with a fluorescein-specific filter have facilitated fluorescein-guided microsurgery and identification of tumor tissue. In 2012, we started evaluating fluorescein (FL) with the dedicated microscope filter in cerebral metastases (CM). After describing the treatment results of our first 30 patients, we now retrospectively report on 95 patients. Ninety-five patients with CM of different primary cancers were included (47 women, 48 men, mean age, 60 years, range, 25–85 years); 5 mg/kg bodyweight of FL was intravenously injected at induction of anesthesia. A YELLOW 560-nm filter (Pentero 900, ZEISS Meditec, Germany) was used for microsurgical tumor resection and resection control. The extent of resection (EOR) was assessed by means of early postoperative contrast-enhanced MRI and the grade of fluorescent staining as described in the surgical reports. Furthermore, we evaluated information on neurological outcome and surgical complications as well as any adverse events. Ninety patients (95%) showed bright fluorescent staining that markedly enhanced tumor visibility. Five patients (5%); three with adenocarcinoma of the lung, one with melanoma of the skin, and one with renal cell carcinoma) showed insufficient FL staining. Thirteen patients (14%) showed residual tumor tissue on the postoperative MRI. Additionally, the MRI of three patients did not confirm complete resection beyond doubt. Thus, gross-total resection had been achieved in 83% (n = 79) of patients. No adverse events were registered during the postoperative course. FL and the YELLOW 560-nm filter are safe and feasible tools for increasing the EOR in patients with CM. Further prospective evaluation of the FL-guided technique in CM-surgery is in planning.

BACKGROUND Incidental durotomy (ID) during spinal surgery is a risk factor for the development of cerebrospinal fluid (CSF) fistula. The rates of ID with or without consecutive CSF fistula vary according to the extent of the surgical procedure. Revision surgery has the highest rates of dural tears. However, not every case of ID leads to CSF fistula requiring revision surgery. The objective of this study was to analyze the predictors for the development of CSF fistula after ID. METHODS This retrospective study included 6024 consecutive patients who had been surgically treated for degenerative spinal disease at our clinic over the past 15 years. Patients who had undergone surgical revision for CSF fistula were assigned to the CSF fistula group. A matched 3:1 control group (ID group) was formed of patients with ID but without CSF fistula. Charts, surgical reports, and radiographic data were reviewed and statistically analyzed for demographics, duration of symptoms, co-morbidities, surgical strategy, and pre- and postoperative neurological performance. RESULTS The 15-year incidence of CSF fistula in the overall population was 0.36% (n=22). The following locations were affected: n=18 lumbar (81.8%), n=2 cervical (9.1%), and n=2 thoracic (9.1%). The extent of ID was similar in both groups. The two groups did not significantly differ with regard to the intraoperative management of dural repair with primary suturing (p=0.345), dural patches, sealant, or collagen matrix (p=0.228; p=0.081; p=0.081). In the postoperative period, bed rest in supine position for 48 hours (p=0.037) and laxative therapy (p=0.034) were the most beneficial treatment modalities for preventing CSF fistula. Patients with CSF fistula were hospitalized significantly longer (21 days vs. 10 days in the control group; p

BACKGROUND Recently, tumor treating fields (TTFields) were established for the treatment of newly diagnosed GBM. One of the most crucial parameters defining the treatment efficacy of TTFields is the electric field intensity. The dielectric properties of the normal intracranial compartments are well established, allowing the prediction of the electric field distribution. In contrast, there is no data available about the dielectric properties of brain tumor tissue. In this study we determined the dielectric properties of brain tumors by analyzing resected tissue following a fast acquisition protocol. To account for the intratumoral heterogeneity, different regions of the tumor were analyzed separately. MATERIAL AND METHODS A cohort of 84 patients with tumors of different histology and malignancy grade have been recruited (meningioma: n=26; brain metastases n=18; low grade glioma n=6; glioblastoma n=34). Tissue probes were acquired whenever possible from the vital tumor area, and perinecrotic compartment identified intraoperatively using neuronavigation, intraoperative ultrasound and fluorescence guidance. After acquisition, the tissue was measured immediately to avoid artifacts induced by temperature change, differences of fluid composition as well as post resection ischemia. A fragment was dissected from each tissue sample and was placed into a cylindrical cell with a known diameter. Two parallel electrodes were placed on both sides of the sample and the thickness of the tissue was measured using a micrometer. The impedance was recorded at frequencies 20Hz-1MHz using a software specifically developed for this study, which controls the LCR meter (Keysight Technologies, Santa Rosa, USA). The measured impedance was translated into dielectric properties of the sample (conductivity and relative permittivity) based on the parallel plate model, the recorded complex impedance and the geometry of the samples. Each tissue probe was fixed, H&E stained and histologically analyzed. RESULTS We found significant differences between the conductivity of different types of tumors with meningiomas showing the lowest conductivity (mean conductivity [S/m]: 0.193; range: 0.327 - 0.113) and GBM tissue exhibiting the highest conductivity values (mean conductivity [S/m]: 0.402; range: 0.893 - 0.157). Consistently, the perinecrotic areas of tumors displayed lower conductivity values compared to the solid tumor compartments. Also, we found a significant intratumoral heterogeneity in tumors of one specific histological diagnosis. CONCLUSION The dielectric properties of intracranial tumors appear to be depending on histological class and malignancy grade and show significant intratumoral heterogeneity. These results may allow a more precise modelling of electric field intensity distribution within the tumor.

Goal: Cerebral amyloid angiopathy (CAA) is the second-most common cause of nontraumatic intracerebral hemorrhages (ICH), surpassed only by uncontrolled hypertension. We characterized the percentage, risk factors, and comorbidities of patients suffering from CAA-related ICH in relation to long-term outcomes. Material and Methods: We performed retrospective analyses and clinical follow-ups of individuals suffering from ICH who were directly admitted to neurosurgery between 2002 and 2016. Findings: Seventy-four of 174 (42%) spontaneous nontraumatic lobar ICH cases leastwise satisfied the modified Boston criteria definition for at least “possible CAA.” Females suffered a higher risk of CAA-caused ICH (42 of 74, 56.8%, P= .035). Atrial fibrillation as a major comorbidity was observed in 19 patients (25.7%). Recovery (decrease of modified Rankin scale [mRS]) was highest during hospitalization in the acute clinic. One-year mortality was as follows: 14 of 25 patients (56%) with probable CAA without supporting pathology, 6 of 18, and 8 of 31 patients with supporting pathology and possible CAA, respectively. Only 10 of 74 (13.6%) had favorable long-term outcomes (mRS ≤2). Increasing numbers of lobar hemorrhages, low initial Glasgow Coma Scale, and subarachnoid hemorrhage were significantly associated with poor survivability, whereas statins, antithrombotic agents, an intraventricular hemorrhage, and midline shift played seemingly minor roles. Conclusions: Symptomatic ICH is a serious stage in CAA progression with high mortality. The high incidence of concurrent atrial fibrillation in these patients may support data on more widespread vascular pathology in CAA.

Background: Herein, we report our clinical experience with the novel polyethylene glycol-covered matrix dural onlay, Hemopatch® (Baxter Deutschland GmbH, Unterschleißheim, Germany) for the prevention of postoperative cerebrospinal fluid (CSF) fistulas. Methods: Retrospectively, 22 consecutive patients (11 females, 11 males, mean age: 49.8 years, range: 15–77 years) with oncological and vascular intracranial lesions were included in this study. In all patients, the Hemopatch was applied as the dural onlay. The accuracy of the primary dural sutures was distinguished into 1) no visible gaps, 2) small gaps < 3 mm, and 3) large gaps > 3 mm. We evaluated the patient charts, surgical reports, and postoperative images. The median follow-up was three months. We recorded any wound healing disorder, such as infection or CSF fistula, and postoperative hemorrhage resulting in surgical revision. Results: Supratentorial, infratentorial, and transsphenoidal approaches were conducted in 17, four, and one patient, respectively. Accurate sutures without visible gaps, small gaps, and large gaps were covered with the Hemopatch in 11, eight, and three patients. One patient developed a CSF fistula (4.5%), one patient had a wound infection (4.5%), and in one patient, a remote cerebellar hemorrhage occurred (unrelated to the dural closure) (4.5%). Thus, the surgical revision rate due to wound healing disorders was 9% (2/22). Conclusion: It is safe and feasible to use the Hemopatch as a dural sealant. The rate of postoperative wound healing disorders in our population was in the lower range of reported surgical revision rates after supra-/infratentorial craniotomies. However, prospective and controlled clinical trials are still warranted.

Background Few studies have addressed the effect of treatment of unruptured intracranial aneurysm (UIA) on cognitive function. Objective Neuropsychological assessment after UIA treatment is underreported, and prospective trials have repeatedly been demanded. In 2014, we conducted a prospective controlled study to evaluate the differences in cognitive processing caused by the treatment of anterior circulation UIAs. Patients and Methods Thirty patients were enrolled until September 2015. Ten patients received endovascular aneurysm occlusion (EV), 10 patients were treated microsurgically (MS), and 10 patients with surgically treated degenerative lumbar spine disease (LD) served as control. All patients underwent extended standardized neuropsychological assessment before (t 1 ) and 6 weeks after treatment (t 2 ). Tests included verbal, visual, and visuospatial memory, psychomotor functioning, executive functioning, and its subdomains verbal fluency and cognitive flexibility. We statistically evaluated intragroup and intergroup changes. Results Intragroup comparisons and group-rate analysis showed no significant impairment in overall neuropsychological performance, either postinterventionally or postoperatively. However, the postoperative performance in cognitive processing speed, cognitive flexibility, and executive functioning was significantly worse in the MS group than in the EV ( P = 0.038) and LD group ( P = 0.02). Compared with the EV group, patients with MS showed significant postoperative impairment in a subtest for auditory-verbal memory (Wechsler Memory Scale, Fourth Edition, Logical Memory II; MS vs. EV P = 0.011). The MS group trended toward posttreatment impairment in subtests for verbal fluency and semantic memory (Regensburg Word Fluency Test; MS vs. EV P = 0.083) and in auditory-verbal memory (Wechsler Memory Scale, Fourth Edition, Logical Memory II; MS vs. LD P = 0.06). Conclusions Our preliminary data showed no effect of anterior circulation UIA treatment on overall neuropsychological function but impaired short-term executive processing in surgically treated patients.

Medical complications severely impair recovery of neurosurgical patients after craniotomy. The purpose of this study was to identify patients at risk of peri- and postoperative medical complications. Therefore, we present a large population of patients with different medical complications after elective craniotomy.We retrospectively screened all patients who had been consecutively treated at our department between June 2009 and June 2014. Patients with any postoperative thromboembolic complication or pulmonary or systemic infection were compared with a control group without any medical complication. Peri- and postoperative complications were statistically analyzed with regard to their association with age, sex, comorbidity, indication for craniotomy, duration of surgery, surgical position, type of anesthesia, and previous craniotomy by means of logistic regression models.Of 1800 patients screened, 133 patients (67 women and 66 men aged between 14 and 85 years) had developed medical complications (overall morbidity, 7.4%). We found statistically significant correlations between thromboembolic events and meningioma, previous craniotomy, duration of surgery, and hypertension (P = 0.002, P = 0.032, P0.001, and P0.001, respectively). Severe infection was associated with age, duration of surgery, and craniopharyngioma and pituitary adenoma (P = 0.012, P = 0.004, and P = 0.029, respectively). Prolonged stay in the intensive care unit was associated with increased duration of surgery and hypertension (P = 0.002 and P0.001).In this study, we identified predictors that help characterize patients at risk of medical complications after elective neurosurgical procedures. These correlations should be taken into account when advising patients on craniotomy.

BACKGROUND: Recently, tumor treating fields (TTFields) have been established as an effective new approach for the treatment of newly diagnosed GBM. One of the most crucial parameters defining the treatment efficacy of TTFields is the electric field intensity. Essentially, the higher the electric field intensity, the higher the tumor cell killing that can be achieved by TTFields. The electric properties of the normal intracranial compartments (cerebrospinal fluid, blood, white and grey mater) are well established, allowing the prediction of the electric field distribution by finite element mesh modelling. In contrast, there is no data available about the electric properties of tumor tissue, which leads to a lack of information regarding the electric field intensity within the tumor. In this study we will determine the dieclectric properties of malignant glioma by analyzing resected tissue following a fast acquisition protocol. To account for the intratumoral heterogeneity, different regions of the tumor will be sampled and analyzed separately. MATERIAL AND METHODS: Twenty patients with high grade glioma currently being recruited. Tissue probes are acquired from the infiltration zone, vital tumor area, and perinecrotic compartment identified intraoperatively using neuronavigation, intraoperative ultrasound and fluorescence guidance. From each region, five tissue probes are sampled. Immediately after acquisition, the tissue is immediately to avoid artifacts by temperature change, change of fluid composition as well as post resection ischemia. A cylindrical fragment is dissected from each tissue sample and is placed into a cylindrical cell with a known diameter. Two parallel electrodes are placed on both sides of the sample and the thickness of the tissue is measured using a micrometer. The impedance is recorded at frequencies 20Hz-1MHz using a software specificly developed for this study, which controls the LCR meter (Keysight Technologies, Santa Rosa, USA). The measured impedance is then translated into dielectric properties of the sample (conductivity and relative permittivity) based on the parallel plate model, the recorded complex impedance and the geometry of the samples. Each tissue probe will be fixed, H&E stained and histologically analyzed for tumor cell count and specific tissue features (infiltration into normal brain, vital tumor area, necrosis). RESULTS: The study has received a positive vote from the Ethical Board of the University Regensburg Medical Center. The first patients are being recruited, the actual results will be evaluated and presented during the meeting.