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Background Glioblastoma is the most aggressive primary brain tumor in adults. The prognosis is still very poor with a median survival time less than a year. A growing body of data supports the role for fatty acid oxidation (FAO) in the aggressive behavior of glioblastoma. We have previously shown that meldonium, an orally active compound that impairs FAO, caused significant growth reduction of glioblastoma in mice. Here, we report three cases of experimental meldonium-containing therapy in end-stage recurrent glioblastoma patients. Methods Three end-stage glioblastoma patients, who had second relapse tumor progression after standard of care therapy, received 500 mg meldonium twice a day on the top of the existing therapy regimen. Tolerability and treatment outcomes were monitored. Results Meldonium was well tolerated by all three patients. One patient experienced long-term growth arrest and maintained clinically stable disease status, currently 24 months into treatment with meldonium. In contrast, the other two patients passed away. Conclusions The case reports presented here suggest good tolerability and the potential for meldonium to improve outcome in glioblastoma patients. Controlled clinical trials need to follow to evaluate systematically possible benefits from the integration of meldonium into standard glioblastoma treatment protocols.

Introduction Endoscopy was first employed in the surgical treatment of neurosurgical diseases early in the twentieth century, but did not become an established practice for a long time, mainly because of poor technology and clinical results. After a slow re-appearance in the 1980s, the 1990s saw an explosion of techniques and instrumentation. Continuing technological improvement has led to further expansion of surgical techniques and indications for use of neuroendoscopy. Discussion The expansion of ventricular endoscopy has led to significant understanding of CSF disorders. Aqueduct stenosis as cause of hydrocephalus and arachnoid cysts are an example of pathologies, the concept and understanding of which now is considerably enhanced, due to the application of neuroendoscopy in their treatment. Management of loculated hydrocephalus has been facilitated considerably with the use of the endoscope. The concepts of aqueductoplasty, septostomy, and foraminoplasty of the foramina of Monro and Magendie emerged, which were previously unknown. Skull base surgery, especially surgery for craniopharyngioma, has seen dramatic improvement in results with the use of the endoscope. Coupling of the endoscope with neuronavigation has expanded technical capabilities even further. Overall, we can do a lot more with the endoscope now in comparison to 30 years ago. Conclusion We should always remember that the endoscope is only a tool. Its use has indications and limitations related to its design and our ability to extract the maximum, in the context of its shortcomings. Further technological advances will push surgical frontiers even more in years to come.

Purpose Endoscopic transaqueductal stenting has become a well-accepted treatment option for a selected small subset of aqueductal stenosis-related obstructive hydrocephalus. However, transaqueductal stenting poses unique challenges and risks which requires critical consideration. This report discusses the clinical experiences with transaqueductal stenting for periaqueductal tumor-related aqueductal stenosis focusing on pediatric patients. Methods A retrospective analysis of all patients undergoing endoscopic TAS from 01/1993 to 01/2022 in the author’s departments was performed. Demographic, clinical, radiological, and intraoperative endoscopic data were evaluated. All patients with AS-related occlusive hydrocephalus that was treated with TAS were analyzed and prospectively followed. Special attention has been given to providing insights into indications, surgical technique, and limitations. Results Out of 28 endoscopic transaqueductal endoscopis stenting procedures, five procedures were performed on periaqueductal tumor-related obstructive hydrocephalus, two children and three adult patients. CSF pathway was obstructed by tumor located in the aqueduct in 2, by tumor in the thalamus/mesencephalon in 1, by a tumor within the third ventricle in 1, and by a tumor of the lamina tecti in 1. Simultaneously with transaqueductal stenting, 2 endoscopic third ventriculostomies (ETV), 3 tumor biopsies, and 1 tumor resection were performed. Postoperative complications included the following: CSF fistula (1 case), and asymptomatic fornix contusion (1 case). A working aqueductal stent was achieved in all cases based on clinical follow-up evaluation. Postoperatively, all patients showed improvement or resolution of their symptoms. The mean follow-up period was 25.2 months (range, 1–108 months). One patient died due to tumor progression during early follow-up. No stent migration was seen. Conclusion Endoscopic third ventriculostomy remains the gold standard for treatment of CSF circulation obstructions with lesions in the posterior third ventricle and aqueduct. Transaqueductal stenting for periaqueductal tumor-related aqueductal compression is technically feasible. However, because of the potential high risks and subtle advantages compared with ETV transaqueductal stenting, it might be indicated in a small subset of well-selected patients if alternative treatment options are not at hand.

Surgical treatment of arachnoid cysts remains under debate. Although many authors favor endoscopic techniques, others attribute a higher recurrence rate to the endoscope. The authors report their experience with endoscopic procedures for arachnoid cyst. All pure endoscopic procedures for arachnoid cysts performed by the authors were analyzed. Particular reference was given to surgical complications and patient outcome in relation to cyst location and endoscopic technique. Sixty-six endoscopic procedures were performed in 61 patients (mean age, 28 years; range, 23 days to 74 years; 35 males, 26 females). The main presenting symptoms were cephalgia (61%), hemisymptoms (18%), and macrocephalus (18%). Cyst location was temporobasal (34%), suprasellar (21%), at the cisterna quadrigemina (18%), paraxial supratentorial (16%), and various (10%). Thirty cystocisternostomies, 14 ventriculocystostomies, 12 cystoventriculostomies, and 10 ventriculocystocisternostomies were performed. The overall clinical success rate was 90%. The endoscopic technique was abandoned in 4 cases (7%). Postoperative complications were found in 16%; there was only one permanent deficit (2%). Five recurrences (8%) occurred up to 7 years after the first procedure. Of the various locations, the temporobasal cysts were the most difficult to treat with lowest clinical success (81%), highest recurrence (19%), and highest complication rate (24%). Of the various endoscopic techniques, ventriculocystostomy and ventriculocystocisternostomy reached the highest success rates with 100%. Endoscopic techniques provide very good results in arachnoid cyst treatment. The most frequent cyst location is the most difficult to treat. A long-term follow-up is recommended since recurrences can occur many years after the procedure.

PurposeDespite being rarely reported, ischemic insults resulting from compromising small brainstem perforators following microvascular decompression (MVD) remain a potential devastating complication. To avoid this complication, we have been using indocyanine green (ICG) angiography intraoperatively to check the flow within the small brainstem perforators. We aim to evaluate the safety and usefulness of ICG videoangiography in MVD.MethodsWe extracted retrospective data of patients who received ICG videoangiography from our prospectively maintained database for microvascular decompression. We noted relevant data including demographics, offending vessels, operative technique, outcome, and complications.ResultsOut of the 438 patients, 15 patients with a mean age (SD) of 53 ± 10.5 years underwent intraoperative ICG angiography. Male:female was 1:1.14. The mean disease duration prior to surgery was 7.7 ± 5.3 years. The mean follow-up (SD) was 50.7 ± 42.0 months. In 14 patients, the offending vessel was an artery, and in one patient, a vein. Intraoperative readjustment of the Teflon pledget or sling was required in 20% (3/15) of the cases. No patient had any sort of brainstem ischemia. Eighty percent of the patients (12/15) experienced complete resolution of the spasms. 86.7% (13/15) of the patients reported a satisfactory outcome with marked improvement of the spasms. Three patients experienced slight hearing affection after surgery, which improved in two patients later. There was no facial or lower cranial nerve affection.ConclusionIntraoperative ICG is a safe tool for evaluating the flow within the brain stem perforators and avoiding brainstem ischemia in MVD for hemifacial spasm.

Advances in spine surgery enable technically safe interventions in older patients with disabling spine disease, yet postoperative delirium (POD) poses a serious risk for postoperative recovery. This study investigates biomarkers of pro-neuroinflammatory states that may help objectively define the pre-operative risk for POD. This study enrolled patients aged ≥60 scheduled for elective spine surgery under general anesthesia. Biomarkers for a pro-neuroinflammatory state included S100 calcium-binding protein β (S100β), brain-derived neurotrophic factor (BDNF), Gasdermin D, and the soluble ectodomain of the triggering receptor expressed on myeloid cells 2 (sTREM2). Postoperative changes of Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and C-reactive protein (CRP) were assessed as markers of systemic inflammation preoperatively, intraoperatively, and early postoperatively (up to 48 h). Patients with POD (n = 19, 75.7 ± 5.8 years) had higher pre-operative levels of sTREM2 (128.2 ± 69.4 pg/mL vs. 97.2 ± 52.0 pg/mL, p = 0.049) and Gasdermin D (2.9 ± 1.6 pg/mL vs. 2.1 ± 1.4 pg/mL, p = 0.29) than those without POD (n = 25, 75.6 ± 5.1 years). STREM2 was additionally a predictor for POD (OR = 1.01/(pg/mL) [1.00–1.03], p = 0.05), moderated by IL-6 (Wald-χ2 = 4.06, p = 0.04). Patients with POD additionally showed a significant increase in IL-6, IL-1β, and S100β levels on the first postoperative day. This study identified higher levels of sTREM2 and Gasdermin D as potential markers of a pro-neuroinflammatory state that predisposes to the development of POD. Future studies should confirm these results in a larger cohort and determine their potential as an objective biomarker to inform delirium prevention strategies.

The development of brain metastases hallmarks disease progression in 20–40% of melanoma patients and is a serious obstacle to therapy. Understanding the processes involved in the development and maintenance of melanoma brain metastases (MBM) is critical for the discovery of novel therapeutic strategies. Here, we generated transcriptome and methylome profiles of MBM showing high or low abundance of infiltrated Iba1 high tumor-associated microglia and macrophages (TAMs). Our survey identified potential prognostic markers of favorable disease course and response to immune checkpoint inhibitor (ICi) therapy, among them APBB1IP and the interferon-responsive gene ITGB7 . In MBM with high ITGB7/APBB1IP levels, the accumulation of TAMs correlated significantly with the immune score. Signature-based deconvolution of MBM via single sample GSEA revealed enrichment of interferon-response and immune signatures and revealed inflammation, stress and MET receptor signaling. MET receptor phosphorylation/activation maybe elicited by inflammatory processes in brain metastatic melanoma cells via stroma cell-released HGF. We found phospho-MET Y1234/1235 in a subset of MBM and observed a marked response of brain metastasis-derived cell lines (BMCs) that lacked druggable BRAF mutations or developed resistance to BRAF inhibitors (BRAFi) in vivo to MET inhibitors PHA-665752 and ARQ197 (tivantinib). In summary, the activation of MET receptor in brain colonizing melanoma cells by stromal cell-released HGF may promote tumor self-maintenance and expansion and might counteract ICi therapy. Therefore, therapeutic targeting of MET possibly serves as a promising strategy to control intracranial progressive disease and improve patient survival.

Purpose Endoscopic third ventriculostomy (ETV) is an effective treatment for obstructive hydrocephalus. Secondary stoma closure may be life threatening and is the most common reason for late ETV failure, mostly secondary to local scarring. Local stents intended to maintain patency are rarely used. In this study, we summarize our experience using stented ETV (sETV), efficacy, and safety. Material and methods Data was retrospectively collected from all consecutive patients who underwent ETV with stenting at four centers. Collected data included indications for using sETV, hydrocephalic history, surgical technique, outcomes, and complications. Results Sixty-seven cases were included. Forty had a primary sETV, and 27 had a secondary sETV (following a prior shunt, ETV, or both). The average age during surgery was 22 years. Main indications for sETV included an adjacent tumor ( n  = 15), thick or redundant tuber cinereum ( n  = 24), and prior ETV failure ( n  = 16). Fifty-nine patients (88%) had a successful sETV. Eight patients failed 11 ± 8 months following surgery. Reasons for failure included obstruction of the stent, reabsorption insufficiency, and CSF leak ( n  = 2 each), and massive hygroma and tumor spread ( n  = 1 each). Complications included subdural hygroma ( n  = 4), CSF leak ( n  = 2), and stent malposition ( n  = 1). There were no complications associated with two stent removals. Conclusion Stented ETV appears to be feasible and safe. It may be indicated in selected cases such as patients with prior ETV failure, or as a primary treatment in cases with anatomical alterations caused by tumors or thickened tuber cinereum. Future investigations are needed to further elucidate its role in non-communicating hydrocephalus.