The role of surgical management for prolactin-secreting tumors in the era of dopaminergic agonists: An international multicenter report.

OBJECTIVE: First-line prolactin-secreting tumor (PST) management typically involves treatment with dopamine agonists and the role of surgery remains to be further explored. We examined the international experience of 12 neurosurgical centers to assess the patient characteristics, safety profile, and effectiveness of surgery for PST management. METHODS: Patients surgically treated for PST from January 2017 through December 2020 were evaluated for surgical characteristics, outcomes, and safety. RESULTS: Among 272 patients identified (65.1% female), the mean age was 38.0 ± 14.3 years. Overall, 54.4% of PST were macroadenomas. Minor complications were seen in 39.3% of patients and major complications were in 4.4%. The most common major complications were epistaxis and worsened vision. Most minor complications involved electrolyte/sodium dysregulation. At 3-6 months, local control on imaging was achieved in 94.8% of cases and residual/recurrent tumor was seen in 19.3%. Reoperations were required for 2.9% of cases. On multivariate analysis, previous surgery was significantly predictive of intraoperative complications (6.14 OR, p < 0.01) and major complications (14.12 OR, p < 0.01). Previous pharmacotherapy (0.27 OR, p = 0.02) and cavernous sinus invasion (0.19 OR, p = 0.03) were significantly protective against early endocrinological cure. Knosp classification was highly predictive of residual tumor or PST recurrence on 6-month follow-up imaging (4.60 OR, p < 0.01). There was noted institutional variation in clinical factors and outcomes. CONCLUSION: Our results evaluate a modern, multicenter, global series of PST. These data can serve as a benchmark to compare with DA therapy and other surgical series. Further study and longer term outcomes could provide insight into how patients benefit from surgical treatment.

Changes in frailty among patients hospitalized for spine pathologies during the COVID-19 pandemic in Germany-a nationwide observational study.

PURPOSE: In spine care, frailty is associated with poor outcomes. The aim of this study was to describe changes in frailty in spine care during the coronavirus disease 2019 (COVID-19) pandemic and their relation to surgical management and outcomes. METHODS: Patients hospitalized for spine pathologies between January 1, 2019, and May 17, 2022, within a nationwide network of 76 hospitals in Germany were retrospectively included. Patient frailty, types of surgery, and in-hospital mortality rates were compared between pandemic and pre-pandemic periods. RESULTS: Of the 223,418 included patients with spine pathologies, 151,766 were admitted during the pandemic and 71,652 during corresponding pre-pandemic periods in 2019. During the pandemic, the proportion of high-frailty patients increased from a range of 5.1-6.1% to 6.5-8.8% (p < 0.01), while the proportion of low frailty patients decreased from a range of 70.5-71.4% to 65.5-70.1% (p < 0.01). In most phases of the pandemic, the Elixhauser comorbidity index (ECI) showed larger increases among high compared to low frailty patients (by 0.2-1.8 vs. 0.2-0.8 [p < 0.01]). Changes in rates of spine surgery were associated with frailty, most clearly in rates of spine fusion, showing consistent increases among low frailty patients (by 2.2-2.5%) versus decreases (by 0.3-0.8%) among high-frailty patients (p < 0.02). Changes in rates of in-hospital mortality were not associated with frailty. CONCLUSIONS: During the COVID-19 pandemic, the proportion of high-frailty patients increased among those hospitalized for spine pathologies in Germany. Low frailty was associated with a rise in rates of spine surgery and high frailty with comparably larger increases in rates of comorbidities.

Trends in frailty in brain tumor care during the COVID-19 pandemic in a nationwide hospital network in Germany.

PURPOSE: Among brain tumor patients, frailty is associated with poor outcomes. The COVID-19 pandemic has led to increased frailty in the general population. To date, evidence on changes in frailty among brain tumor patients during the pandemic is lacking. We aimed to compare frailty among brain tumor patients in Germany during the COVID-19 pandemic to the pre-pandemic era and to assess potential effects on brain tumor care. METHODS: In this retrospective observational study, we compared frailty among brain tumor patients hospitalized during the COVID-19 pandemic in years 2020 through 2022 to pre-pandemic years 2016 through 2019 based on administrative data from a nationwide network of 78 hospitals in Germany. Using the Hospital Frailty Risk Score (HFRS), frailty was categorized as low, intermediate, or high. We examined changes in frailty, patient demographics, the burden of comorbidity, rates of surgery, and mortality rates for different frailty groups during the pandemic and compared them to pre-pandemic levels. RESULTS: Of the 20,005 included hospitalizations for brain tumors, 7979 were during the pandemic (mean age 60.0 years (± 18.4); females: 49.8%), and 12,026 in the pre-pandemic period (mean age: 59.0 years [± 18.4]; females: 49.2%). Average daily admissions decreased from 8.2 (± 5.1) during pre-pandemic years to 7.3 (± 4.5) during the pandemic (p < 0.01). The overall median HFRS decreased from 3.1 (IQR: 0.9-7.3) during the pre-pandemic years to 2.6 (IQR: 0.3-6.8) during the pandemic (p < 0.01). At the same time, the Elixhauser Comorbidity Index (ECI) decreased from 17.0 (± 12.4) to 16.1 (± 12.0; p < 0.01), but to a larger degree among high compared to low frailty cases (by 1.8 vs. 0.3 points; p = 0.04). In the entire cohort, the mean length of stay was significantly shorter in the pandemic period (9.5 days [± 10.7]) compared with pre-pandemic levels (10.2 days [± 11.8]; p < 0.01) with similar differences in the three frailty groups. Rates of brain tumor resection increased from 29.9% in pre-pandemic years to 36.6% during the pandemic (p < 0.001) without differences between frailty levels. Rates of in-hospital mortality did not change during the pandemic (6.1% vs. 6.7%, p = 0.07), and there was no interaction with frailty. CONCLUSION: Even though our findings are limited in that the HFRS is validated only for patients ≥ 75 years of age, our study among patients of all ages hospitalized for brain tumors in Germany suggests a marked decrease in levels of frailty and in the burden of comorbidities during the COVID-19 pandemic.

Crooke Cell Adenoma Confers Poorer Endocrinological Outcomes Compared with Corticotroph Adenoma: Results of a Multicenter, International Analysis.

BACKGROUND: Crooke cell adenomas (CCAs) are a rare, aggressive subset of secretory pituitary corticotroph adenomas (sCTAs) found in 5%-10% of patients with Cushing disease. Multiple studies support worse outcomes in CCAs but are limited by small sample size and single-institution databases. We compared outcomes in CCA and sCTA using a multicenter, international retrospective database of high-volume skull base centers. METHODS: Patients surgically treated for pituitary adenoma from January 2017 through December 2020 were included. RESULTS: Among 2826 patients from 12 international centers, 20 patients with CCA and 480 patients with sCTA were identified. No difference in baseline demographics, tumor characteristics, or postoperative complications was seen. Microsurgical approaches (60% CCA vs. 62.3% sCTA) were most common. Gross total resection was higher in CCA patients (100% vs. 83%, P = 0.05). Among patients with gross total resection according to intraoperative findings, fewer CCA patients had postoperative hormone normalization of pituitary function (50% vs. 77.8%, P < 0.01) and remission of hypersecretion by 3-6 months (75% vs. 84.3%, P < 0.01). This was the case despite CCA having better local control rates (100% vs. 96%, P < 0.01) and fewer patients with remnant on magnetic resonance imaging (0% vs. 7.2%, P < 0.01). A systematic literature review of 35 studies reporting on various treatment strategies reiterated the high rate of residual tumor, persistent hypercortisolism, and tumor-related mortality in CCA patients. CONCLUSIONS: This modern, multicenter series of patients with CCA reflects their poor prognosis and reduced postsurgical hormonal normalization. Further work is necessary to better understand the pathophysiology of CCA to devise more targeted treatment approaches.

Defining benchmark outcomes for transsphenoidal surgery of pituitary adenomas: a multicenter analysis.

IMPORTANCE: Benchmarks aid in improve outcomes for surgical procedures. However, best achievable results that have been validated internationally for transsphenoidal surgery (TS) are not available. OBJECTIVE: We aimed to establish standardized outcome benchmarks for TS of pituitary adenomas. DESIGN: A total of 2685 transsphenoidal tumor resections from 9 expert centers in 3 continents were analyzed. SETTING: Patients were risk stratified, and the median values of each center's outcomes were established. The benchmark was defined as the 75th percentile of all median values for a particular outcome. The postoperative benchmark outcomes included surgical factors, endocrinology-specific values, and neurology-specific values. RESULTS: Of 2685 patients, 1149 (42.8%) defined the low-risk benchmark cohort. Within these benchmark cases, 831 (72.3%) patients underwent microscopic TS, and 308 (26.8%) patients underwent endoscopic endonasal resection. Of all tumors, 799 (29.8%) cases invaded the cavernous sinus. The postoperative complication rate was 19.6% with mortality between 0.0% and 0.8%. Benchmark cutoffs were ≤2.9% for reoperation rate, ≤1.9% for cerebrospinal fluid leak requiring intervention, and ≤15.5% for transient diabetes insipidus. At 6 months, benchmark cutoffs were calculated as follows: readmission rate: ≤6.9%, new hypopituitarism ≤6.0%, and tumor remnant ≤19.2%. CONCLUSIONS: This analysis defines benchmark values for TS targeting morbidity and mortality and represents the best outcomes in the best patients in expert centers. These cutoffs can be used to assess different centers, patient populations, and novel surgical techniques. It should be noted that the benchmark values may influence each other and must be evaluated in their own context.

Decompressive Surgery in the Treatment of Acute Ischemic Stroke during the First Four Waves of the COVID-19 Pandemic in Germany: A Nationwide Observational Cohort Study.

BACKGROUND: The COVID-19 pandemic has significantly affected acute ischemic stroke (AIS) care. In this study, we examined the effects of the pandemic on neurosurgical AIS care by means of decompressive surgery (DS). METHODS: In this retrospective observational study, we compared the characteristics, in-hospital processes, and in-hospital mortality rates among patients hospitalized for AIS during the first four waves of the pandemic (between January 1, 2020 and October 26, 2021) versus the corresponding periods in 2019 (prepandemic). We used administrative data from a nationwide hospital network in Germany. RESULTS: Of the 177 included AIS cases with DS, 60 were from 2019 and 117 from the first four pandemic waves. Compared with the prepandemic levels, there were no changes in weekly admissions for DS during the pandemic. The same was true for patient age (range: 51.7-60.4 years), the number of female patients (range: 33.3-57.1%), and the prevalence of comorbidity, as measured by the Elixhauser Comorbidity Index (range: 13.2-20.0 points). Also, no alterations were observed in transfer to the intensive care unit (range: 87.0-100%), duration of in-hospital stay (range: 14.6-22.7 days), and in-hospital mortality rates (range: 11.8-55.6%). CONCLUSION: In Germany, compared with the prepandemic levels, AIS patients undergoing DS during the first four waves of the pandemic showed no changes in demographics, rates of comorbidity, and in-hospital mortality rates. This is in contrast to previous evidence on patients with less critical types of AIS not requiring DS and underlines the uniqueness of the subgroup of AIS patients requiring DS. Our findings suggests that these patients, in contrast to AIS patients in general, were unable to forgo hospitalization during the COVID-19 pandemic. Maintaining the delivery of DS is an essential aspect of AIS care during a pandemic.

[Prehospital care of pediatric traumatic brain injury]. / Präklinische Versorgung von Schädel-Hirn-Traumen bei Kindern.

BACKGROUND: Traumatic brain injury (TBI) in children and adolescents is associated with significant morbidity and, in severe TBI, mortality. The aim of this article is to provide an overview of the spectrum of TBI, its pathophysiology, and current treatment recommendations for prehospital management of children and adolescents with TBI. MATERIALS AND METHODS: The current literature was reviewed for studies on the management of TBI in children and adolescents. RESULTS: In recent years, a large number of scientific studies have been published that have resulted in evidence-based guidelines for primary care of children with TBI. The primary aim is to minimize secondary brain damage following TBI, for which immediate assessment of the severity of TBI at the scene based on clinical findings and the accident mechanism and initiation of specific treatment measures to prevent hypoxia, hypotension, and hypothermia are critical. Not only prehospital management, but also the rapid transfer of children with severe TBI to centers with high neurosurgical, pediatric surgical, and pediatric intensive care expertise is of particular importance to improve survival and neurological outcome after severe TBI. CONCLUSION: Structured prehospital management may help reduce secondary brain injury after TBI and lead to improved clinical outcomes.

Intraoperative MRI-Guided Resection Is Not Superior to 5-Aminolevulinic Acid Guidance in Newly Diagnosed Glioblastoma: A Prospective Controlled Multicenter Clinical Trial.

PURPOSE: Prospective data suggested a superiority of intraoperative MRI (iMRI) over 5-aminolevulinic acid (5-ALA) for achieving complete resections of contrast enhancement in glioblastoma surgery. We investigated this hypothesis in a prospective clinical trial and correlated residual disease volumes with clinical outcome in newly diagnosed glioblastoma. METHODS: This is a prospective controlled multicenter parallel-group trial with two center-specific treatment arms (5-ALA and iMRI) and blinded evaluation. The primary end point was complete resection of contrast enhancement on early postoperative MRI. We assessed resectability and extent of resection by an independent blinded centralized review of preoperative and postoperative MRI with 1-mm slices. Secondary end points included progression-free survival (PFS) and overall survival (OS), patient-reported quality of life, and clinical parameters. RESULTS: We recruited 314 patients with newly diagnosed glioblastomas at 11 German centers. A total of 127 patients in the 5-ALA and 150 in the iMRI arm were analyzed in the as-treated analysis. Complete resections, defined as a residual tumor ≤0.175 cm³, were achieved in 90 patients (78%) in the 5-ALA and 115 (81%) in the iMRI arm (P = .79). Incision-suture times (P < .001) were significantly longer in the iMRI arm (316 v 215 [5-ALA] minutes). Median PFS and OS were comparable in both arms. The lack of any residual contrast enhancing tumor (0 cm³) was a significant favorable prognostic factor for PFS (P < .001) and OS (P = .048), especially in methylguanine-DNA-methyltransferase unmethylated tumors (P = .006). CONCLUSION: We could not confirm superiority of iMRI over 5-ALA for achieving complete resections. Neurosurgical interventions in newly diagnosed glioblastoma shall aim for safe complete resections with 0 cm³ contrast-enhancing residual disease, as any other residual tumor volume is a negative predictor for PFS and OS.

A Multicenter, Propensity Score-Matched Assessment of Endoscopic Versus Microscopic Approaches in the Management of Pituitary Adenomas.

BACKGROUND AND OBJECTIVES: There is considerable controversy as to which of the 2 operating modalities (microsurgical or endoscopic transnasal surgery) currently used to resect pituitary adenomas (PAs) is the safest and most effective intervention. We compared rates of clinical outcomes of patients with PAs who underwent resection by either microsurgical or endoscopic transnasal surgery. METHODS: To independently assess the outcomes of each modality type, we sought to isolate endoscopic and microscopic PA surgeries with a 1:1 tight-caliper (0.01) propensity score-matched analysis using a multicenter, neurosurgery-specific database. Surgeries were performed between 2017 and 2020, with data collected retrospectively from 12 international institutions on 4 continents. Matching was based on age, previous neurological deficit, American Society of Anesthesiologists (ASA) score, tumor functionality, tumor size, and Knosp score. Univariate and multivariate analyses were performed. RESULTS: Among a pool of 2826 patients, propensity score matching resulted in 600 patients from 9 surgery centers being analyzed. Multivariate analysis showed that microscopic surgery had a 1.91 odds ratio (OR) ( P = .03) of gross total resection (GTR) and shorter operative duration ( P < .01). However, microscopic surgery also had a 7.82 OR ( P < .01) for intensive care unit stay, 2.08 OR ( P < .01) for intraoperative cerebrospinal fluid (CSF) leak, 2.47 OR ( P = .02) for postoperative syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was an independent predictor for longer postoperative stay (ß = 2.01, P < .01). Overall, no differences in postoperative complications or 3- to 6-month outcomes were seen by surgical approach. CONCLUSION: Our international, multicenter matched analysis suggests microscopic approaches for pituitary tumor resection may offer better GTR rates, albeit with increased intensive care unit stay, CSF leak, SIADH, and hospital utilization. Better prospective studies can further validate these findings as matching patients for outcome analysis remains challenging. These results may provide insight into surgical benchmarks at different centers, offer room for further registry studies, and identify best practices.

Structure of Neurosurgical Care in Germany in Comparison to Countries Organized in the European Association of Neurosurgical Societies: A Need to Reorganize Neurosurgical Training and Care in Germany.

BACKGROUND: Although the world is experiencing a deficit in the neurosurgical workforce, the number of neurosurgeons in Germany has increased within the last two decades. The aim of the present study was to assess the neurosurgical workforce in Germany, compare it to European countries, and assess structures in neurosurgical departments in Germany. METHODS: Data regarding the number of neurosurgeons in Germany as well as the number of departments, beds, cases, and neurosurgical procedures were gathered. A survey among German neurosurgical departments was performed to assess the structure of neurosurgical care. Furthermore, another survey among European countries was performed to acquire information regarding the number of surgeons and the regulation of training. RESULTS: From 2000 to 2019, the number of board-certified neurosurgeons in Germany increased by 151% from 973 to 2,446. During the same period, the German population increased by only 1% from 82.26 million to 83.17 million. Thus, the number of neurosurgeons per 100,000 inhabitants increased from 1.18 to 2.94. The increase of neurosurgeons is not paralleled by an increase in departments or an increase in neurosurgical procedures within the active neurosurgical departments. In comparison to the participating European countries, where the number of neurosurgeons per 100,000 inhabitants ranged from 0.45 to 2.94, with Germany shows the highest number. CONCLUSIONS: German institutions of medical administration urgently need to consider regulation of neurosurgical specialist training to prevent a further uncontrolled increase in neurosurgeons in a manner that is not adapted to the needs of neurosurgical care for the German population. Actions might include a regulation of entry to the training and of the number of training sites. Furthermore, an integration of non-physician assistant health care professionals and delegation of non-surgical workload from neurosurgeons is necessary. A further increase in neurosurgeons would be associated with a decrease in the surgical caseload per surgeons during training and after board certification, which might compromise the quality of neurosurgical care.

Effects of the COVID-19 Pandemic on Spinal Fusion Procedures for Spinal Infections in a Nationwide Hospital Network in Germany.

BACKGROUND: The full impact of the COVID-19 pandemic on surgical spine care is difficult to assess due to a lack in nationwide evidence from more recent phases of the pandemic. We aimed to describe changes in in-hospital processes associated with spinal fusion procedures in the treatment of spinal infections (SI) during different phases of the pandemic. METHODS: In this retrospective observational study, we examined the in-hospital prevalence and outcomes of spinal fusion procedures for SI (along with patient characteristics, rates of transfer to intensive care units, and mortality rates) during the first four waves of the pandemic compared with the corresponding prepandemic periods in 2019. We used administrative data from a nationwide network of 76 hospitals managing 7% of all in-hospital cases in Germany. RESULTS: We observed no significant change in the prevalence of SI fusion procedures during the pandemic, neither in total numbers (349 vs. 373) nor for each wave separately. On a patient level, we found no differences in age, sex, and the prevalence of paresis, and no relevant differences in associated comorbidities. The rate of mechanical ventilation did not change during any of the examined pandemic waves: it ranged between 9.5 and 18.6% during the pandemic and 3.1 and 16.0% during the corresponding prepandemic control periods. The rate of transfer to intensive care changed only during wave 4 (from 70.4 to 54.8%; p = 0.046) but not in any other pandemic phases. We observed no changes in in-hospital mortality rates (range: 2.9-9.7% vs. 6.2-11.3%) or in duration of hospital stay (range: 26.2-30.8 days vs. 20.8-29.2 days). CONCLUSIONS: The main finding of our study is that within this nationwide network of spine care centers in Germany, the delivery of surgical treatment of SI by means of spinal fusion procedures was maintained throughout the first four waves of the pandemic. Furthermore, there were no relevant changes in patient demographics, in-hospital processes, and mortality rates.

Resilience in Lower Grade Glioma Patients.

Current data show that resilience is an important factor in cancer patients' well-being. We aim to explore the resilience of patients with lower grade glioma (LGG) and the potentially influencing factors. We performed a cross-sectional assessment of adult patients with LGG who were enrolled in the LoG-Glio registry. By phone interview, we administered the following measures: Resilience Scale (RS-13), distress thermometer, Montreal Cognitive Assessment Test for visually impaired patients (MoCA-Blind), internalized stigmatization by brain tumor (ISBI), Eastern Cooperative Oncological Group performance status (ECOG), patients' perspective questionnaire (PPQ) and typical clinical parameters. We calculated correlations and multivariate regression models. Of 74 patients who were assessed, 38% of those showed a low level of resilience. Our results revealed significant correlations of resilience with distress (p < 0.001, −0.49), MOCA (p = 0.003, 0.342), ECOG (p < 0.001, −0.602), stigmatization (p < 0.001, −0.558), pain (p < 0.001, −0.524), and occupation (p = 0.007, 0.329). In multivariate analyses, resilience was negatively associated with elevated ECOG (p = 0.020, ß = −0.383) and stigmatization levels (p = 0.008, ß = −0.350). Occupation showed a tendency towards a significant association with resilience (p = 0.088, ß = −0.254). Overall, low resilience affected more than one third of our cohort. Low functional status is a specific risk factor for low resilience. The relevant influence of stigmatization on resilience is a novel finding for patients suffering from a glioma and should be routinely identified and targeted in clinical routine.

Eloquent Lower Grade Gliomas, a Highly Vulnerable Cohort: Assessment of Patients' Functional Outcome After Surgery Based on the LoG-Glio Registry.

Majority of lower grade glioma (LGG) are located eloquently rendering surgical resection challenging. Aim of our study was to assess rate of permanent deficits and its predisposing risk factors. We retrieved 83 patients harboring an eloquently located LGGs from the prospective LoG-Glio Database. Patients without surgery or incomplete postoperative data were excluded. Sign rank test, explorative correlations by Spearman ρ and multivariable regression for new postoperative deficits were calculated. Eloquent region involved predominantly motor (45%) and language (40%). At first follow up after 3 months permanent neuro-logical deficits (NDs) were noted in 39%. Mild deficits remained in 29% and severe deficits in 10%. Complete tumor removal (CTR) was successfully in 62% of intended cases. Postoperative and 3-month follow up National Institute of Health Stroke Score (NIHSS) showed significantly lower values than preoperatively (p<0.001). 38% cases showed a decreased NIHSS at 3-month, while occurrence was only 14% at 9-12-month follow up. 6/7 patients with mild aphasia recovered after 9-12 months, while motor deficits present at 3-month follow up were persistent in majority of patients. Eastern oncology group functional status (ECOG) significantly decreased by surgery (p < 0.001) in 31% of cases. Between 3-month and 9-12-months follow up no significant improvement was seen. In the multivariable model CTR (p=0.019, OR 31.9), and ECOG>0 (p=0.021, OR 8.5) were independent predictors for permanent postoperative deficit according to NIHSS at 3-month according to multivariable regression model. Patients harboring eloquently located LGG are highly vulnerable for permanent deficits. Almost one third of patients have a permanent reduction of their functional status based on ECOG. Risk of an extended resection has to be balanced with the respective oncological benefit. Especially, patients with impaired pre-operative status are at risk for new permanent deficits. There is a relevant improvement of neurological symptoms in the first year after surgery, especially for patients with slight aphasia.

First German Guideline on Diagnostics and Therapy of Clinically Non-Functioning Pituitary Tumors.

Although non-functioning pituitary tumors are frequent, diagnostic and therapeutic concepts are not well standardized. We here present the first German multidisciplinary guideline on this topic. The single most important message is to manage the patients by a multidisciplinary team (consisting at least of an endocrinologist, a neurosurgeon, and a (neuro-) radiologist). The initial diagnostic work-up comprises a detailed characterization of both biochemical (focusing on hormonal excess or deficiency states) and morphological aspects (with magnetic resonance imaging of the sellar region). An ophthalmological examination is only needed in presence of symptoms or large tumors affecting the visual system. Asymptomatic, hormonally inactive tumors allow for a 'wait and scan' strategy. In contrast, surgical treatment by an experienced pituitary surgeon is standard of care in case of (impending) visual impairment. Therapeutic options for incompletely resected or recurrent tumors include re-operation, radiotherapy, and observation; the individual treatment plan should be developed multidisciplinary. Irrespective of the therapeutic approach applied, patients require long-term follow-up. Patient with larger pituitary tumors or former surgery/radiotherapy should be regularly counseled regarding potential symptoms of hormonal deficiency states.

Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany-Updated series of 120 cases.

BACKGROUND: Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran reversing its anticoagulant effects within minutes. Thereby, patients with acute ischemic stroke who are on dabigatran treatment may become eligible for thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). In patients on dabigatran with intracerebral hemorrhage idarucizumab could prevent lesion growth. AIMS: To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of acute ischemic stroke or intracranial hemorrhage. METHODS: Retrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch from January 2016 to August 2018 were used. RESULTS: One-hundred and twenty stroke patients received idarucizumab in 61 stroke centers. Eighty patients treated with dabigatran presented with ischemic stroke and 40 patients suffered intracranial bleeding (intracerebral hemorrhage (ICH) in n = 27). In patients receiving intravenous thrombolysis with rt-PA following idarucizumab, 78% showed a median improvement of 7 points in National Institutes of Health Stroke Scale. No bleeding complications were reported. Hematoma growth was observed in 3 out of 27 patients with ICH. Outcome was favorable with a median National Institutes of Health Stroke Scale improvement of 4 points and modified Rankin score 0-3 in 61%. Six out of 40 individuals (15%) with intracranial bleeding died during hospital stay. CONCLUSION: Administration of rt-PA after reversal of dabigatran activity with idarucizumab in case of acute ischemic stroke seems feasible, effective, and safe. In dabigatran-associated intracranial hemorrhage, idarucizumab appears to prevent hematoma growth and to improve outcome.

Baseline T1 hyperintense and diffusion-restricted lesions are not linked to prolonged survival in bevacizumab-treated glioblastoma patients of the GLARIUS trial.

PURPOSE: The phase II GLARIUS trial assigned patients with newly diagnosed, O-6-methylguanine-DNA methyltransferase promoter non-methylated glioblastoma to experimental bevacizumab/irinotecan (BEV/IRI) or standard temozolomide (TMZ). To identify subpopulations with a particularly favorable course, we assessed the prognostic potential of magnetic resonance imaging (MRI) markers before treatment onset. METHODS: MRIs at baseline (before treatment onset) were analyzed for T1-hyperintense and diffusion-restricted lesions; as well as the presence of both hyperintense and diffusion-restricted (double positive) lesions. The MRI findings were correlated with overall and progression-free survival. RESULTS: MRI scans were evaluable in 71% of the GLARIUS modified intention-to-treat population (n = 121 of 170; 88 patients in the BEV/IRI arm, and 33 patients in the TMZ control arm). Diffusion-restricted and T1 hyperintense lesions were present in 60% and 65% of patients in BEV/IRI arm, while 57% and 63% were found in the TMZ arm, respectively. Double positive lesions were found in 37% of BEV/IRI patients and in 39% of TMZ patients. Neither the presence of T1-hyperintense, diffusion-restricted lesions, nor double positive lesions were associated with improved survival. CONCLUSIONS: Baseline T1-hyperintense and diffusion-restricted lesions are not suitable to predict progression-free or overall survival of patients treated with bevacizumab/irinotecan or temozolomide.

Consensus on Postoperative Recommendations After Transsphenoidal Surgery.

BACKGROUND: Guidelines for patient behavior following transsphenoidal surgery do not exist. To gain generally recommendations, the German pituitary working group conducted a study among pituitary surgeons to elucidate their opinions and customs of patients' counselling. METHODS: Questions concerning daily activities, exertion of sports and work life were addressed. It was asked to provide the postoperative time interval after which specific activities can be resumed both after a routine or an extended approach. RESULTS: Fourteen pituitary surgeons returned the completed questionnaire. Following routine operations, washing the hair was allowed within one week, blowing the nose after 3, flying on an airplane and driving a car after one, lifting heavy weights after 4, playing wind instruments after 6, use of CPAP (continuous positive airway pressure) device after 3, permit leisure sports after 2 to 4 weeks (except for scuba diving). Competitive sports can be resumed after 6 weeks. Occupation with mental demands was considered feasible after 2 weeks, with physical labor after 4 weeks. After extended transsphenoidal surgery, the recommended time interval was roughly twice as long compared to the routine approach. Driving a car was allowed within the first 4 weeks after surgery by some pituitary surgeons, while others allow driving only after 3 months analogous to the regulations after craniotomy. The risk of scuba diving was considered high. CONCLUSIONS: The data of our study and the literature, and expert opinions from related scientific fields resulted in a consensus on recommendations for patients' conduct to minimize risks after transsphenoidal surgery.

Unilateral Tuberothalamic Artery Ischemia Caused by Pituitary Apoplexy.

BACKGROUND AND IMPORTANCE: Pituitary apoplexy (PA) occasionally occurs in patients with pituitary adenoma and may cause severe functional deficits. Headache, pituitary insufficiency, visual impairment, and cranial nerve palsies are the most frequent symptoms in patients with PA. Secondary cerebral ischemia develops in only a limited number of PA patients. Two pathogenic mechanisms were previously proposed. One states that ischemia may be due to major vessel encasement or to vessel compression, as a result of extended tumor growth. The second states that cerebral vasospasm following PA may cause ischemia. We present another mechanism. After PA, a sudden increase in suprasellar tumor volume can lead to compression of perforating arteries causing hypoperfusion and subsequent focal ischemia of the thalamus, basal ganglia, and internal capsule. CLINICAL PRESENTATION: We present the case of a 75-year-old woman who, after having PA, developed cerebral ischemia in the territory of the left anterior thalamus and internal capsule that is primarily supplied by the tuberothalamic artery. Computed tomography and magnetic resonance imaging are used to describe how mechanical compression of the tuberothalamic artery caused this rare phenomenon. The recent literature, vascular anatomy, and pathophysiologic aspects of PA are discussed. CONCLUSION: PA can lead to compression of perforating arteries, for example, the tuberothalamic artery supplying the thalamus or lenticulostriate region, and thus cause hypoperfusion and subsequent focal cerebral ischemia. This may occur when perforating cerebral arteries are affected and compressed by the sudden increase in tumor volume due to hemorrhage or tumor swelling.

Calvian Endo-pen: New Coagulation Forceps for Endoscopic Endonasal Transsphenoidal Surgery.

OBJECTIVE: Over the past few years bipolar electrocoagulation techniques in neurosurgery have been continually improving. However, limited access during endoscopic endonasal transsphenoidal surgery (EETS) for central skull base pathologies and the requirement of very precise coagulation in that dedicated anatomical area requires further refinement of bipolar coagulation instruments. We describe our experience (effectiveness of coagulation, intraoperative handling, and the use as a dissecting tool) with a new type of coagulation forceps, the Calvian endo-pen (Sutter Medizintechnik, Freiburg, Germany) during EETS. METHOD: From June to August 2015, 12 patients with central skull base lesions (9 with a pituitary adenoma and 1 each with epidermoid, hemangioma, and juvenile angiofibroma) were operated on with the Calvian endo-pen. RESULTS: The application of the Calvian endo-pen was feasible in all cases. The angled thin tips proved to be very effective and precise for soft tissue coagulation to achieve hemostasis. Even very small vessels could be occluded selectively. It was also helpful for outward dissection in separating normal from tumor tissue. CONCLUSION: The use of the Calvian endo-pen is safe and effective during EETS for central skull base pathologies. Its ease in intraoperative handling (maneuverability, cleaning) and precise coagulation makes it a promising instrument for EETS.

Tumor growth patterns of MGMT-non-methylated glioblastoma in the randomized GLARIUS trial.

BACKGROUND: We evaluated patterns of tumor growth in patients with newly diagnosed MGMT-non-methylated glioblastoma who were assigned to undergo radiotherapy in conjunction with bevacizumab/irinotecan (BEV/IRI) or standard temozolomide (TMZ) within the randomized phase II GLARIUS trial. METHODS: In 142 patients (94 BEV/IRI, 48 TMZ), we reviewed magnetic resonance imaging scans at baseline and first tumor recurrence. Based on contrast-enhanced T1-weighted and fluid-attenuated inversion recovery images, we assessed tumor growth patterns and tumor invasiveness. Tumor growth patterns were classified as either multifocal or local at baseline and recurrence; at first recurrence, we additionally assessed whether distant lesions appeared. Invasiveness was determined as either diffuse or non-diffuse. Associations with treatment arms were calculated using Fisher's exact test. RESULTS: At baseline, 115 of 142 evaluable patients (81%) had a locally confined tumor. Between treatment arms, there was no significant difference in the fraction of tumors that changed from an initially local tumor growth pattern to a multifocal pattern (12 and 13%, p = 0.55). Distant lesions appeared in 17% (BEV/IRI) and 13% (TMZ) of patients (p = 0.69). 15% of patients in the BEV/IRI arm and 8% in the TMZ arm developed a diffuse growth pattern from an initially non-diffuse pattern (p = 0.42). CONCLUSIONS: The tumor growth and invasiveness patterns do not differ between BEV/IRI and TMZ-treated MGMT-non-methylated glioblastoma patients in the GLARIUS trial. BEV/IRI was not associated with an increased rate of multifocal, distant, or highly invasive tumors at the time of recurrence.