Opportunities and Alternatives of Modern Radiation Oncology and Surgery for the Management of Resectable Brain Metastases.

Postsurgical radiotherapy (RT) has been early proven to prevent local tumor recurrence, initially performed with whole brain RT (WBRT). Subsequent to disadvantageous cognitive sequalae for the patient and the broad distribution of modern linear accelerators, focal irradiation of the tumor has omitted WBRT in most cases. In many studies, the effectiveness of local RT of the resection cavity, either as single-fraction stereotactic radiosurgery (SRS) or hypo-fractionated stereotactic RT (hFSRT), has been demonstrated to be effective and safe. However, whereas prospective high-level incidence is still lacking on which dose and fractionation scheme is the best choice for the patient, further ablative techniques have come into play. Neoadjuvant SRS (N-SRS) prior to resection combines straightforward target delineation with an accelerated post-surgical phase, allowing an earlier start of systemic treatment or rehabilitation as indicated. In addition, low-energy intraoperative RT (IORT) on the surgical bed has been introduced as another alternative to external beam RT, offering sterilization of the cavity surface with steep dose gradients towards the healthy brain. This consensus paper summarizes current local treatment strategies for resectable brain metastases regarding available data and patient-centered decision-making

Impact of Levetiracetam Treatment on 5-Aminolevulinic Acid Fluorescence Expression in IDH1 Wild-Type Glioblastoma

The amino acid 5-aminolevulinic acid (5-ALA) is the most established neurosurgical fluorescent dye and facilitates the achievement of gross total resection. In vitro studies raised concerns that antiepileptic drugs (AED) reduce the quality of fluorescence. Between 2013 and 2018, 175 IDH1 wild-type glioblastoma (GB) patients underwent 5-ALA guided surgery. Patients’ data were retrospectively reviewed regarding demographics, comorbidities, medications, tumor morphology, neuropathological characteristics, and their association with intraoperative 5-ALA fluorescence. The fluorescence of 5-ALA was graded in a three point scaling system (grade 0 = no; grade 1 = weak; grade 2 = strong). Univariable analysis shows that the intake of dexamethasone or levetiracetam, and larger preoperative tumor area significantly reduce the intraoperative fluorescence activity (fluorescence grade: 0 + 1). Multivariable binary logistic regression analysis demonstrates the preoperative intake of levetiracetam (adjusted odds ratio: 12.05, 95% confidence interval: 3.91–37.16, p = 0.001) as the only independent and significant risk factor for reduced fluorescence quality. Preoperative levetiracetam intake significantly reduced intraoperative fluorescence. The indication for levetiracetam in suspected GB should be carefully reviewed and prophylactic treatment avoided for this tumor entity. Future comparative trials of neurosurgical fluorescent dyes need a special focus on the influence of levetiracetam on fluorescence intensity. Further trials must validate our findings

Postoperative Hematoma Expansion in Patients Undergoing Decompressive Hemicraniectomy for Spontaneous Intracerebral Hemorrhage

Introduction: The aim of the study was to analyze risk factors for hematoma expansion (HE) in patients undergoing decompressive hemicraniectomy (DC) in patients with elevated intracranial pressure due to spontaneous intracerebral hematoma (ICH). Methods: We retrospectively evaluated 72 patients with spontaneous ICH who underwent DC at our institution. We compared the pre- and postoperative volumes of ICH and divided the patients into two groups: first, patients with postoperative HE > 6 cm3 (group 1), and second, patients without HE (group 2). Additionally, we screened the medical history for anticoagulant and antiplatelet medication (AC/AP), bleeding-related comorbidities, age, admission Glasgow coma scale and laboratory parameters. Results: The rate of AC/AP medication was higher in group 1 versus group 2 (15/16 vs. 5/38, p < 0.00001), and patients were significantly older in group 1 versus group 2 (65.1 ± 16.2 years vs. 54.4 ± 14.3 years, p = 0.02). Furthermore, preoperative laboratory tests showed lower rates of hematocrit (34.1 ± 5.4% vs. 38.1 ± 5.1%, p = 0.01) and hemoglobin (11.5 ± 1.6 g/dL vs. 13.13 ± 1.8 g/dL, p = 0.0028) in group 1 versus group 2. In multivariate analysis, the history of AC/AP medication was the only independent predictor of HE (p < 0.0001, OR 0.015, CI 95% 0.001–0.153). Conclusion: We presented a comprehensive evaluation of risk factors for hematoma epansion by patients undergoing DC due to ICH

Dehydration Status at Admission Predicts Recurrence in Patients with Traumatic Chronic Subdural Hematoma

Objective: There remains a significant risk of chronic subdural hematoma (CSDH) recurring after treatment. Patient-related predictors and surgical procedures have been investigated in many studies. In contrast, the literature remains scant on reports of the potential impact of dehydration on the admission of affected patients and on the CSDH recurrence rate. Methods: All consecutively admitted patients with CSDH and surgical treatment at the authors’ institution between 2015 and 2019 were retrospectively identified. Dehydration was assessed as a blood urea/creatinine (U/Cr) ratio > 80. The association between dehydration on admission and postoperative complication rates, in-hospital mortality, and recurrence of CSDH, with the need for additional surgical treatment, was further analyzed. Results: A total of 265 patients with CSDH requiring surgery were identified. In 32 patients (12%), further surgery was necessary due to the recurrence of CSDH. It was found that 9 of the 265 patients with CSDH (3%) suffered from dehydration at the time of admission. Multivariate analysis revealed diabetes mellitus (p = 0.02, OR 2.7, 95% CI 1.2–6.5), a preoperative midline shift > 5 mm (p = 0.003, OR 3.3, 95% CI 1.5–7.5) and dehydration on admission (p = 0.002, OR 10.3, 95% CI 2.4–44.1) as significant and independent predictors for the development of CSDH recurrence that requires surgery. Conclusion: the present findings indicate that dehydration on admission appears to be an independent predictor for CSDH recurrence that requires surgery

Using CRISPR/Cas9 genome editing in human iPSCs for deciphering the pathogenicity of a novel CCM1 transcription start site deletion

Cerebral cavernous malformations are clusters of aberrant vessels that can lead to severe neurological complications. Pathogenic loss-of-function variants in the CCM1, CCM2, or CCM3 gene are associated with the autosomal dominant form of the disease. While interpretation of variants in protein-coding regions of the genes is relatively straightforward, functional analyses are often required to evaluate the impact of non-coding variants. Because of multiple alternatively spliced transcripts and different transcription start points, interpretation of variants in the 5′ untranslated and upstream regions of CCM1 is particularly challenging. Here, we identified a novel deletion of the non-coding exon 1 of CCM1 in a proband with multiple CCMs which was initially classified as a variant of unknown clinical significance. Using CRISPR/Cas9 genome editing in human iPSCs, we show that the deletion leads to loss of CCM1 protein and deregulation of KLF2, THBS1, NOS3, and HEY2 expression in iPSC-derived endothelial cells. Based on these results, the variant could be reclassified as likely pathogenic. Taken together, variants in regulatory regions need to be considered in genetic CCM analyses. Our study also demonstrates that modeling variants of unknown clinical significance in an iPSC-based system can help to come to a final diagnosis

Pain management with epidural catheter and epidural analgesia after spinal dorsal instrumentation of lumbar spine.

Spinal dorsal instrumentation (SDI) is an established treatment for degenerative spinal diseases. Adequate and immediate postoperative pain control is important for patient recovery and may be compromised by uncertainty about its efficacy and concern about early postoperative surgical complications or adverse events. The aim of the current study was to compare the use of epidural analgesia (EA) with systemic analgesia (SA) as regards pain reduction and early postoperative complications after SDI. Pain management with epidural or systemic analgesia in patients undergoing SDI by posterior approach between January 2019 and July 2020 was evaluated by clinical functional testing, measuring total opioid amounts used, and evaluating numerical rating scale values 24 and 96 hours postoperatively. The following were also monitored: demographic data, number of affected segments, length of hospital stay, inflammatory markers (leukocytes and serum C-reactive protein), early postoperative surgical complication rates, and adverse events. In total 79 patients were included (33 in the EA and 46 in the SA group). The SA group had significantly lower numerical rating scale values at days 1 to 4 after surgery (P ≤ .001) and lower cumulative opioid use than the EA group (P < .001). We found no difference in infection parameters, length of hospital stay or surgery-related complication rates. Our data demonstrate that epidural anesthesia was inferior to an opioid-based SA regime in reducing postoperative pain in patients undergoing spinal surgery. There is no benefit to the use of epidural catheters

Patient Safety Comparison of Frameless and Frame-Based Stereotactic Navigation for Brain Biopsy&mdash;A Single Center Cohort Study

Leksell stereotactic system-based aspiration biopsy is a common procedure in the neurosurgical treatment of deep-seated or multiple brain lesions. This study aimed to evaluate the benefit of frameless biopsy using VarioGuide compared to frame-based biopsy using the Leksell stereotactic system (LSS). We analyzed all brain biopsies using VarioGuide or LSS at our neurooncological Department of Neurosurgery in the University Hospital of Bonn between January 2018 and August 2020. We analyzed demographic data, duration of surgery, size of lesion, localization, and early complications. Uni-variable analyses were carried out on data from both groups. In total, 109 biopsies were compared (40 VarioGuide vs. 69 LSS). Patients with VarioGuide were significant older (74 (62&ndash;80) years vs. 67 (57&ndash;76) years; p = 0.03) and had a shorter duration of general anesthesia (163 (138&ndash;194) min vs. 193 (167&ndash;215) min, p &lt; 0.001). We found no significant differences in surgery duration (VarioGuide median 28 min (IQR 20&ndash;38); LSS: median 30 min (IQR 25&ndash;39); p = 0.1352) or in early complication rates (5% vs. 7%; p = 0.644). A slightly higher false negative biopsy rate was registered in the LSS group (3 vs. 1; p = 0.1347). The size of the lesions also did not differ significantly between the two groups (18.31 &plusmn; 26.35 cm3 vs. 12.63 &plusmn; 14.62; p = 0.15). Our data showed that biopsies performed using VarioGuide took significantly less time than LSS biopsies and did not differ in complication rates. Both systems offered a high degree of patient safety

Safety metric profiling in surgery for temporal glioblastoma: lobectomy as a supra-total resection regime preserves perioperative standard quality rates

Introduction!#!Supra-total resection in terms of anterior temporal lobectomy (ATL) has gained growing attention with regard to superior long-term disease control for temporal-located glioblastoma. However, aggressive onco-surgical approaches-geared beyond conventional gross total resections (GTR)-may be associated with peri- and postoperative unfavorable events which significantly worsen initial favorable postoperative outcome. In the current study we analyzed our institutional database with regard to patient safety indicators (PSIs), hospital-acquired conditions (HACs) and specific cranial surgery-related complications (CSC) as high standard quality metric profiles in patients that had undergone surgery for temporal glioblastoma.!##!Methods!#!Between 2012 and 2018, 61 patients with temporal glioblastoma underwent GTR or temporal lobectomy at the authors' institution. Both groups of differing resection modalities were analyzed with regard to the incidence of PSIs, HACs and CSCs.!##!Results!#!Overall, we found 6 PSI and 2 HAC events. Postoperative hemorrhage (3 out of 61 patients; 5%) and catheter-associated urinary tract infection (2 out 61 patients; 3%) were identified as the most frequent PSIs and HACs. PSIs were present in 1 out of 41 patients (5%) for the temporal GTR and 2 out of 20 patients for the lobectomy group (p = 1.0). Respective rates for PSIs were 5 of 41 (12%) and 1 of 20 (5%) (p = 0.7). Further, CSCs did not yield significant differences between these two resection modalities (p = 1.0).!##!Conclusion!#!With regard to ATL and GTR as differing onco-surgical approaches these data suggest ATL in terms of an aggressive supra-total resection strategy to preserve perioperative standard safety metric profiles

Seizure outcome in temporal glioblastoma surgery: lobectomy as a supratotal resection regime outclasses conventional gross-total resection

Introduction!#!The postoperative seizure freedom represents an important secondary outcome measure in glioblastoma surgery. Recently, supra-total glioblastoma resection in terms of anterior temporal lobectomy (ATL) has gained growing attention with regard to superior long-term disease control for temporal-located glioblastoma compared to conventional gross-total resections (GTR). However, the impact of ATL on seizure outcome in these patients is unknown. We therefore analyzed ATL and GTR as differing extents of resection in regard of postoperative seizure control in patients with temporal glioblastoma and preoperative symptomatic seizures.!##!Methods!#!Between 2012 and 2018, 33 patients with preoperative seizures underwent GTR or ATL for temporal glioblastoma at the authors' institution. Seizure outcome was assessed postoperatively and 6 months after tumor resection according to the International League Against Epilepsy (ILAE) classification and stratified into favorable (ILAE class 1) versus unfavorable (ILAE class 2-6).!##!Results!#!Overall, 23 out of 33 patients (70%) with preoperative seizures achieved favorable seizure outcome following resection of temporal located glioblastoma. For the ATL group, postoperative seizure freedom was present in 13 out of 13 patients (100%). In comparison, respective rates for the GTR group were 10 out of 20 patients (50%) (p = 0.002; OR 27; 95% CI 1.4-515.9).!##!Conclusions!#!ATL in terms of a supra-total resection strategy was associated with superior favorable seizure outcome following temporal glioblastoma resection compared to GTR. Regarding above mentioned survival benefit following ATL compared to GTR, ATL as an aggressive supra-total resection regime might constitute the surgical modality of choice for temporal-located glioblastoma