Spontaneous intracerebral hemorrhage - patients retrospectively consent to fibrinolytic surgery despite poor neurological outcome and reduced health-related quality of life.

Spontaneous intracerebral hemorrhage (ICH) might lead to devastating consequences. Nonetheless, subjective interpretation of life circumstances might vary. Recent data from ischemic stroke patients show that there might be a paradox between clinically rated neurological outcome and self-reported satisfaction with quality of life. Our hypothesis was that minimally invasive surgically treated ICH patients would still give their consent to stereotactic fibrinolysis despite experiencing relatively poor neurological outcome. In order to better understand the patients' perspective and to enhance insight beyond functional outcome, this is the first study assessing disease-specific health-related quality of life (hrQoL) in ICH after fibrinolytic therapy. We conducted a retrospective analysis of patients with spontaneous ICH treated minimally invasive by stereotactic fibrinolysis. Subsequently, using standardized telephone interviews, we evaluated functional outcome with the modified Rankin Scale (mRS), health-related Quality of Life with the Quality of life after Brain Injury Overall scale (QOLIBRI-OS), and assessed retrospectively if the patients would have given their consent to the treatment. To verify the primary hypothesis that fibrinolytic treated ICH patients would still retrospectively consent to fibrinolytic therapy despite a relatively poor neurological outcome, we conducted a chi-square test to compare good versus poor outcome (mRS) between consenters and non-consenters. To investigate the association between hrQoL (QOLIBRI-OS) and consent, we conducted a Mann-Whitney U-test. Moreover, we did a Spearman correlation to investigate the correlation between functional outcome (mRS) and hrQoL (QOLIBRI-OS). The analysis comprised 63 data sets (35 men, mean age: 66.9 ± 11.8 years, median Hemphill score: 3 [2-3]). Good neurological outcome (mRS 0-3) was achieved in 52% (33/63) of the patients. Patients would have given their consent to surgery retrospectively in 89.7% (52/58). These 52 consenting patients comprised all 33 patients (100%) who achieved good functional outcome and 19 of the 25 patients (76%) who achieved poor neurological outcome (mRS 4-6). The mean QOLIBRI-OS value was 49.55 ± 27.75. A significant association between hrQoL and retrospective consent was found (p = 0.004). This study supports fibrinolytic treatment of ICH even in cases when poor neurological outcome would have to be assumed since subjective perception of deficits could be in contrast with the objectively measured neurological outcome. HrQoL serves as a criterion for success of rtPa lysis therapy in ICH.

Influence of cerebrospinal fluid drainage in the first days after aneurysm rupture on the severity of early brain injury following aneurysmal subarachnoid hemorrhage.

PURPOSE: Progressive cerebral edema with refractory intracranial hypertension (ICP) requiring decompressive hemicraniectomy (DHC) is a severe manifestation of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH). The purpose of the study was to investigate whether a more pronounced cerebrospinal fluid (CSF) drainage has an influence on cerebral perfusion pressure (CPP) and the extent of EBI after aSAH. METHODS: Patients with aSAH and indication for ICP-monitoring admitted to our center between 2012 and 2020 were retrospectively included. EBI was categorized based on intracranial blood burden, persistent loss of consciousness, and SEBES (Subarachnoid Hemorrhage Early Brain Edema Score) score on the third day after ictus. The draining CSF and vital signs such as ICP and CPP were documented daily. RESULTS: 90 out of 324 eligible aSAH patients (28%) were included. The mean age was 54.2 ± 11.9 years. DHC was performed in 24% (22/90) of patients. Mean CSF drainage within 72 h after ictus was 168.5 ± 78.5 ml. A higher CSF drainage within 72 h after ictus correlated with a less severe EBI and a less frequent need for DHC (r=-0.33, p = 0.001) and with a higher mean CPP on day 3 after ictus (r = 0.2351, p = 0.02). CONCLUSION: A more pronounced CSF drainage in the first 3 days of aSAH was associated with higher CPP and a less severe course of EBI and required less frequently a DHC. These results support the hypothesis that an early and pronounced CSF drainage may facilitate blood clearance and positively influence the course of EBI.

Early localization of tissue at risk for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: blood distribution on initial imaging vs early CT perfusion.

OBJECTIVE: Delayed cerebral ischemia (DCI) is a potentially reversible adverse event after aneurysmal subarachnoid hemorrhage (aSAH), when early detected and treated. Computer tomography perfusion (CTP) is used to identify the tissue at risk for DCI. In this study, the predictive power of early CTP was compared with that of blood distribution on initial CT for localization of tissue at risk for DCI. METHODS: A consecutive patient cohort with aSAH treated between 2012 and 2020 was retrospectively analyzed. Blood distribution on CT was semi-quantitatively assessed with the Hijdra-score. The vessel territory with the most surrounding blood and the one with perfusion deficits on CTP performed on day 3 after ictus were considered to be at risk for DCI, respectively. RESULTS: A total of 324 patients were included. Delayed infarction occurred in 17% (56/324) of patients. Early perfusion deficits were detected in 82% (46/56) of patients, 85% (39/46) of them developed infarction within the predicted vessel territory at risk. In 46% (25/56) a vessel territory at risk was reliably determined by the blood distribution. For the prediction of DCI, blood amount/distribution was inferior to CTP. Concerning the identification of "tissue at risk" for DCI, a combination of both methods resulted in an increase of sensitivity to 64%, positive predictive value to 58%, and negative predictive value to 92%. CONCLUSIONS: Regarding the DCI-prediction, early CTP was superior to blood amount/distribution, while a consideration of subarachnoid blood distribution may help identify the vessel territories at risk for DCI in patients without early perfusion deficits.

Optimal cerebral perfusion pressure in aneurysmal subarachnoid hemorrhage and its relation to perfusion deficits on CT-perfusion.

Preservation of optimal cerebral perfusion is a crucial part of the acute management after aneurysmal subarachnoid hemorrhage (aSAH). A few studies indicated possible benefits of maintaining a cerebral perfusion pressure (CPP) near the calculated optimal CPP (CPPopt), representing an individually optimal condition at which cerebral autoregulation functions at its best. This retrospective observational monocenter study was conducted to investigate, whether "suboptimal" perfusion with actual CPP deviating from CPPopt correlates with perfusion deficits detected by CT-perfusion (CTP). A consecutive cohort of aSAH-patients was reviewed and patients with available parameters for CPPopt-calculation, who simultaneously received CTP, were analyzed. By plotting the pressure reactivity index (PRx) versus CPP, CPP correlating the lowest PRx value was identified as CPPopt. Perfusion deficits on CTP were documented. In 86 out of 324 patients, the inclusion criteria were met. Perfusion deficits were detected in 47% (40/86) of patients. In 43% of patients, CPP was lower than CPPopt, which correlated with detected perfusion deficits (r = 0.23, p = 0.03). Perfusion deficits were found in 62% of patients with CPPCPPopt (OR 3, p = 0.01). These findings support the hypothesis, that a deviation of CPP from CPPopt is an indicator of suboptimal cerebral perfusion.

Establishing reliable selection criteria for performing fibrinolytic therapy in patients with intracerebral haemorrhage based on prognostic tools.

OBJECTIVES: Minimally invasive surgery combined with fibrinolytic therapy is a promising treatment option for patients with intracerebral haemorrhage (ICH), but a meticulous patient selection is required, because not every patient benefits from it. The ICH score facilitates a reliable patient selection for fibrinolytic therapy except for ICH-4. This study evaluated whether an additional use of other prognostic tools can overcome this limitation. MATERIALS AND METHODS: A consecutive ICH patient cohort treated with fibrinolytic therapy between 2010 and 2020 was retrospectively analysed. The following prognostic tools were calculated: APACHE II, ICH-GS, ICH-FUNC, and ICH score. The discrimination power of every score was determined by ROC-analysis. Primary outcome parameters regarding the benefit of fibrinolytic therapy were the in-hospital mortality and a poor outcome defined as modified Rankin scale (mRS) > 4. RESULTS: A total of 280 patients with a median age of 72 years were included. The mortality rates according to the ICH score were ICH-0 = 0 % (0/0), ICH-1 = 0 % (0/22), ICH-2 = 7.1 % (5/70), ICH-3 = 17.3 % (19/110), ICH-4 = 67.2 % (45/67), ICH-5 = 100 % (11/11). The APACHE II showed the best discrimination power for in-hospital mortality (AUC = 0.87, p < 0.0001) and for poor outcome (AUC = 0.79, p < 0.0001). In the subgroup with ICH-4, APACHE II with a cut-off of 24.5 showed a good discriminating power for in-hospital mortality (AUC = 0.83, p < 0.001) and for poor outcome (AUC = 0.87, p < 0.001). CONCLUSIONS: An additional application of APACHE II score increases the discriminating power of ICH score 4 enabling a more precise appraisal of in-hospital mortality and of functional outcome, which could support the patient selection for fibrinolytic therapy.

Personalized prognosis stratification of newly diagnosed glioblastoma applying a statistical decision tree model.

PURPOSE: Glioblastoma (GBM) is the most frequent glioma in adults with a high treatment resistance resulting into limited survival. The individual prognosis varies depending on individual prognostic factors, that must be considered while counseling patients with newly diagnosed GBM. The aim of this study was to elaborate a risk stratification algorithm based on reliable prognostic factors to facilitate a personalized prognosis estimation early on after diagnosis. METHODS: A consecutive patient cohort with confirmed GBM treated between 2010 and 2021 was retrospectively analyzed. Clinical, radiological, and molecular parameters were assessed and included in the analysis. Overall survival (OS) was the primary outcome parameter. After identifying the strongest prognostic factors, a risk stratification algorithm was elaborated with estimated odds of survival. RESULTS: A total of 462 GBM patients were analyzed. The strongest prognostic factors were Charlson Comorbidity Index (CCI), extent of tumor resection, and adjuvant treatment. Patients with CCI ≤ 1 receiving tumor resection had the highest survival odds (88% for 10 months). On the contrary, patients with CCI > 3 receiving no adjuvant treatment had the lowest survival odds (0% for 10 months). The 10-months survival rate in patients with CCI > 3 receiving adjuvant treatment was 56% for patients younger than 70 years and 22% for patients older than 70 years. CONCLUSION: A risk stratification algorithm based on significant prognostic factors allowed a personalized early prognosis estimation at the time of GBM diagnosis, that can contribute to a more personalized patient counseling.

Radiofrequency thermocoagulation under neuromonitoring guidance and general anesthesia for treatment of refractory trigeminal neuralgia.

OBJECTIVE: Radiofrequency thermocoagulation (RFT) for refractory trigeminal neuralgia is usually performed in awake patients to localize the involved trigeminal branches. It is often a painful experience. Here, we present RFT under neuromonitoring guidance and general anesthesia. METHOD: Stimulation of trigeminal branches at the foramen ovale with the tip of the RFT cannula is performed under short general anesthesia. Antidromic sensory-evoked potentials (aSEP) are recorded from the 3 trigeminal branches. The cannula is repositioned until the desired branch can be stimulated and lesioned. CONCLUSION: aSEP enable accurate localization of involved trigeminal branches during RFT and allow performing the procedure under general anesthesia.

Differentiation of multiple brain metastases and glioblastoma with multiple foci using MRI criteria.

OBJECTIVE: Glioblastoma with multiple foci (mGBM) and multiple brain metastases share several common features on magnetic resonance imaging (MRI). A reliable preoperative diagnosis would be of clinical relevance. The aim of this study was to explore the differences and similarities between mGBM and multiple brain metastases on MRI. METHODS: We performed a retrospective analysis of 50 patients with mGBM and compared them with a cohort of 50 patients with multiple brain metastases (2-10 lesions) histologically confirmed and treated at our department between 2015 and 2020. The following imaging characteristics were analyzed: lesion location, distribution, morphology, (T2-/FLAIR-weighted) connections between the lesions, patterns of contrast agent uptake, apparent diffusion coefficient (ADC)-values within the lesion, the surrounding T2-hyperintensity, and edema distribution. RESULTS: A total of 210 brain metastases and 181 mGBM lesions were analyzed. An infratentorial localization was found significantly more often in patients with multiple brain metastases compared to mGBM patients (28 vs. 1.5%, p < 0.001). A T2-connection between the lesions was detected in 63% of mGBM lesions compared to 1% of brain metastases. Cortical edema was only present in mGBM. Perifocal edema with larger areas of diffusion restriction was detected in 31% of mGBM patients, but not in patients with metastases. CONCLUSION: We identified a set of imaging features which improve preoperative diagnosis. The presence of T2-weighted imaging hyperintensity connection between the lesions and cortical edema with varying ADC-values was typical for mGBM.

Positioning of epidural electrode for motor cortex stimulation in general anesthesia based on intraoperative electrophysiological monitoring to treat refractory trigeminal neuropathic pain.

BACKGROUND: Motor cortex stimulation (MCS) represents a treatment option for refractory trigeminal neuralgia (TGN). Usually, patients need to be awake during surgery to confirm a correct position of the epidural electrode above the motor cortex, reducing patient's comfort. METHOD: Epidural cortical mapping (ECM) and motor evoked potentials (MEPs) were intraoperatively performed for correct localization of motor cortex under general anesthesia that provided comparable results to test stimulation after letting the patient to be awake during the operation. CONCLUSION: Intraoperative ECM and MEPs facilitate a confirmation of correct MCS-electrode position above the motor cortex allowing the MCS-procedure to be performed under general anesthesia.

Interaction of Optimal Cerebral Perfusion Pressure with Early Brain Injury and its Impact on Ischemic Complications and Outcome Following Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Cerebral autoregulation is impaired early on after aneurysmal subarachnoid hemorrhage (aSAH). The study objective was to explore the pressure reactivity index (PRx) and cerebral perfusion pressure (CPP) in the earliest phase after aneurysm rupture and to address the question of whether an optimal CPP (CPPopt)-targeted management is associated with less severe early brain injury (EBI). METHODS: Patients with aSAH admitted between 2012 and 2020 were retrospectively included in this observational cohort study. The PRx was calculated as a correlation coefficient between intracranial pressure and mean arterial pressure. By plotting the PRx versus CPP, CPP correlating the lowest PRx value was identified as CPPopt. EBI was assessed by applying the Subarachnoid Hemorrhage Early Brain Edema Score (SEBES) on day 3 after ictus. An SEBES ≥ 3 was considered severe EBI. RESULTS: In 90 of 324 consecutive patients with aSAH, intracranial pressure monitoring was performed ≥ 7 days, allowing for PRx calculation and CPPopt determination. Severe EBI was associated with larger mean deviation of CPP from CPPopt 72 h after ictus (r = 0.22, p = 0.03). Progressive edema requiring decompressive hemicraniectomy was associated with larger deviation of CPP from CPPopt on day 2 (r = 0.23, p = 0.02). The higher the difference of CPP from CPPopt on day 3 the higher the mortality rate (r = 0.31, p = 0.04). CONCLUSIONS: Patients with CPP near to the calculated CPPopt in the early phase after aSAH experienced less severe EBI, less frequently received decompressive hemicraniectomy, and exhibited a lower mortality rate. A prospective evaluation of CPPopt-guided management starting in the first days after ictus is needed to confirm the clinical validity of this concept.

Effectiveness of Lumbar Cerebrospinal Fluid Drain Among Patients With Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial.

Importance: After aneurysmal subarachnoid hemorrhage, the use of lumbar drains has been suggested to decrease the incidence of delayed cerebral ischemia and improve long-term outcome. Objective: To determine the effectiveness of early lumbar cerebrospinal fluid drainage added to standard of care in patients after aneurysmal subarachnoid hemorrhage. Design, Setting, and Participants: The EARLYDRAIN trial was a pragmatic, multicenter, parallel-group, open-label randomized clinical trial with blinded end point evaluation conducted at 19 centers in Germany, Switzerland, and Canada. The first patient entered January 31, 2011, and the last on January 24, 2016, after 307 randomizations. Follow-up was completed July 2016. Query and retrieval of data on missing items in the case report forms was completed in September 2020. A total of 20 randomizations were invalid, the main reason being lack of informed consent. No participants meeting all inclusion and exclusion criteria were excluded from the intention-to-treat analysis. Exclusion of patients was only performed in per-protocol sensitivity analysis. A total of 287 adult patients with acute aneurysmal subarachnoid hemorrhage of all clinical grades were analyzable. Aneurysm treatment with clipping or coiling was performed within 48 hours. Intervention: A total of 144 patients were randomized to receive an additional lumbar drain after aneurysm treatment and 143 patients to standard of care only. Early lumbar drainage with 5 mL per hour was started within 72 hours of the subarachnoid hemorrhage. Main Outcomes and Measures: Primary outcome was the rate of unfavorable outcome, defined as modified Rankin Scale score of 3 to 6 (range, 0 to 6), obtained by masked assessors 6 months after hemorrhage. Results: Of 287 included patients, 197 (68.6%) were female, and the median (IQR) age was 55 (48-63) years. Lumbar drainage started at a median (IQR) of day 2 (1-2) after aneurysmal subarachnoid hemorrhage. At 6 months, 47 patients (32.6%) in the lumbar drain group and 64 patients (44.8%) in the standard of care group had an unfavorable neurological outcome (risk ratio, 0.73; 95% CI, 0.52 to 0.98; absolute risk difference, -0.12; 95% CI, -0.23 to -0.01; P = .04). Patients treated with a lumbar drain had fewer secondary infarctions at discharge (41 patients [28.5%] vs 57 patients [39.9%]; risk ratio, 0.71; 95% CI, 0.49 to 0.99; absolute risk difference, -0.11; 95% CI, -0.22 to 0; P = .04). Conclusion and Relevance: In this trial, prophylactic lumbar drainage after aneurysmal subarachnoid hemorrhage lessened the burden of secondary infarction and decreased the rate of unfavorable outcome at 6 months. These findings support the use of lumbar drains after aneurysmal subarachnoid hemorrhage. Trial Registration: ClinicalTrials.gov Identifier: NCT01258257.

Optimizing the structure of interdisciplinary tumor boards for effective cancer care.

Introduction: Multi-professional interdisciplinary tumor boards (ITB) are essential institutions to discuss all newly diagnosed, relapsed or complex cancer patients in a team of specialists to find an optimal cancer care plan for each individual patient with regard to national and international clinical practice guidelines, patient´s preference and comorbidities. In a high-volume cancer center, entity-specific ITBs take place at least once a week discussing a large number of patients. To a high level of expertise and dedication, this also requires an enormous amount of time for physicians, cancer specialists and administrative support colleagues, especially for radiologists, pathologists, medical oncologists and radiation oncologists, who must attend all cancer-specific boards according to certification requirements. Methods: In this 15-month prospective German single-center analysis, we examined the established structures of 12 different cancer-specific ITBs at the certified Oncology Center and demonstrate tools helping to optimize processes before, during and after the boards for optimal, time-saving procedures. Results: By changing pathways, introducing revised registration protocols and new digital supports we could show that the workload of preparation by radiologists and pathologists could be reduced significantly by 22.9% (p=<0.0001) and 52.7% (p=<0.0001), respectively. Furthermore, two questions were added to all registration forms about the patient´s need for specialized palliative care support that should lead to more awareness and early integration of specialized help. Discussion: There are several ways to reduce the workload of all ITB team members while maintaining high quality recommendations and adherence to national and international guidelines.

Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial: Study protocol for a randomized controlled trial.

RATIONALE: Aneurysmal subarachnoid hemorrhage (SAH) has high morbidity and mortality. While the primary injury results from the initial bleeding cannot currently be influenced, secondary injury through vasospasm and delayed cerebral ischemia worsens outcome and might be a target for interventions to improve outcome. To date, beside the aneurysm treatment to prevent re-bleeding and the administration of oral nimodipine, there is no therapy available, so novel treatment concepts are needed. Evidence suggests that inflammation contributes to delayed cerebral ischemia and poor outcome in SAH. Some studies suggest a beneficial effect of anti-inflammatory glucocorticoids, but there are no data from randomized controlled trials examining the efficacy of glucocorticoids. Therefore, current guidelines do not recommend the use of glucocorticoids in SAH. AIM: The Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial aims to determine whether dexamethasone improves outcome in a clinically relevant endpoint in SAH patients. METHODS AND DESIGN: FINISHER is a multicenter, prospective, randomized, double-blinded, placebo-controlled clinical phase III trial which is testing the outcome and safety of anti-inflammatory treatment with dexamethasone in SAH patients. SAMPLE SIZE ESTIMATES: In all, 334 patients will be randomized to either dexamethasone or placebo within 48 h after SAH. The dexamethasone dose is 8 mg tds for days 1-7 and then 8 mg od for days 8-21. STUDY OUTCOME: The primary outcome is the modified Rankin Scale (mRS) at 6 months, which is dichotomized to favorable (mRS 0-3) versus unfavorable (mRS 4-6). DISCUSSION: The results of this study will provide the first phase III evidence as to whether dexamethasone improves outcome in SAH.

The value of comorbidities and illness severity scores as prognostic tools for early outcome estimation in patients with aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe cerebrovascular disease not only causing brain injury but also frequently inducing a significant systemic reaction affecting multiple organ systems. In addition to hemorrhage severity, comorbidities and acute extracerebral organ dysfunction may impact the prognosis after aSAH as well. The study objective was to assess the value of illness severity scores for early outcome estimation after aSAH. A retrospective analysis of consecutive aSAH patients treated from 2012 to 2020 was performed. Comorbidities were evaluated applying the Charlson comorbidity index (CCI) and the American Society of Anesthesiologists (ASA) classification. Organ dysfunction was assessed by calculating the simplified acute physiology score (SAPS II) 24 h after admission. Modified Rankin scale (mRS) at 3 months was documented. The outcome discrimination power was evaluated. A total of 315 patients were analyzed. Significant comorbidities (CCI > 3) and physical performance impairment (ASA > 3) were found in 15% and 12% of all patients, respectively. The best outcome discrimination power showed SAPS II (AUC 0.76), whereas ASA (AUC 0.65) and CCI (AUC 0.64) exhibited lower discrimination power. A SAPS II cutoff of 40 could reliably discriminate patients with good (mRS ≤ 3) from those with poor outcome (p < 0.0001). Calculation of SAPS II allowed a comprehensive depiction of acute organ dysfunctions and facilitated a reliable early prognosis estimation in our study. In direct comparison to CCI and ASA, SAPS II demonstrated the highest discrimination power and deserves a consideration as a prognostic tool after aSAH.

Prognostic differences and implications on treatment strategies between butterfly glioblastoma and glioblastoma with unilateral corpus callosum infiltration.

Approximately 25% of glioblastomas show at diagnosis a corpus callosum infiltration, which is associated with poor prognosis. The extent of corpus callosum involvement, however, ranges from partial unilateral to complete bilateral infiltration. The role of surgery in glioblastoma with corpus callosum involvement is controversial. In this study, we aimed to examine prognostic differences between glioblastoma with unilateral and glioblastoma with bilateral corpus callosum infiltration, and to evaluate possible treatment strategy implications. Patients with newly diagnosed glioblastoma from 2010 to 2019 were included. Corpus callosum infiltration was assessed in contrast-enhanced T1-weighted preoperative magnetic resonance imaging. Extent of resection, adjuvant treatments and overall survival were evaluated. Corpus callosum involvement was found in 96 (26.4%) out of 363 patients with newly diagnosed glioblastoma. Bilateral corpus callosum infiltration was found in 27 out of 96 patients (28%), and 69 patients had unilateral corpus callosum infiltration. Glioblastoma with corpus callosum affection had significantly lower median overall survival compared to glioblastoma without corpus callosum involvement (9 vs. 11 months, p = 0.02). A subgroup analysis of glioblastoma with unilateral corpus callosum infiltration revealed a significant difference in median overall survival dependent on extent of resection (6.5 without gross total resection vs. 11 months with gross total resection, Log-rank test p = 0.02). Our data confirms a shorter overall survival in glioblastoma subpopulation with corpus callosum involvement, especially for glioblastoma with bilateral corpus callosum infiltration. However, patients with partial corpus callosum infiltration undergoing gross total resection exhibited a significant survival benefit compared to their counterparts without gross total resection. Whenever reasonably achievable gross total resection should be considered as an integral part of the treatment strategy in glioblastoma with partial corpus callosum infiltration.

Regorafenib for recurrent high-grade glioma: a unicentric retrospective analysis of feasibility, efficacy, and toxicity.

We describe here 11 consecutive patients with recurrence of high-grade glioma treated with regorafenib at our university medical center. The majority of patients had MGMT promoter methylation (9/11 cases). Regorafenib was given as 2nd line systemic treatment in 6/11 patients and 3rd or higher line treatment in 5/11 patients. The median number of applied cycles was 2 with dosage reductions in 5/11. Response to treatment was observed in 4/11 (PR in 1/11, and SD in 3/11). Median overall survival for the cohort was 16.1 months, median progression-free survival 9.0 months, and median time to treatment failure 3.3 months. Side effects of any CTCAE grade were noted in all patients, hereby 6/11 with CTCAE °III-IV reactions. High-grade side effects were of dermatologic, cardiovascular, and hematologic nature. A mean treatment delay of 57.5 days (range 23-119) was noted between tumor board recommendation and treatment initiation due to the application process for off-label use in this indication. In conclusion, treatment with regorafenib in relapsed high-grade glioma is a feasible treatment option but has to be considered carefully due to the significant side effect profile.

Infratentorial ganglioglioma mimicking a cerebellar metastasis.

We report a case of an infratentorial ganglioglioma in a 56-year-old male, who underwent magnetic resonance imaging (MRI) during the diagnostic workup for a suspected lung cancer. The MRI scan revealed a space-occupying lesion of the left lobulus semilunaris superior cerebelli, which was assumed being a metastasis. The asymptomatic lesion was resected to establish the diagnosis. Histologic and immunohistochemical studies showed a ganglioglioma with World Health Organization grade I characteristics. Although ganglioglioma typically exhibits a supratentorial predilection, it should be included in the differential diagnosis of lesions occurring in the cerebellum.

The Impact of Endovascular Rescue Therapy on the Clinical and Radiological Outcome After Aneurysmal Subarachnoid Hemorrhage: A Safe and Effective Treatment Option for Hemodynamically Relevant Vasospasm?

Objective: Cerebral vasospasm (CVS) represents one of the multiple contributors to delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH). Especially the management of CVS, refractory to medical treatment, is a challenging task during the acute phase after aSAH. Endovascular rescue therapies (ERT), such as medical and mechanical dilation, are possible treatment options on an individual basis. However, data about the influence on the patients' functional outcomes are limited. This study aims to assess the impact of ERT on the long-term functional outcome in aSAH-patients with refractory CVS. Methods: We performed a retrospective analysis of aSAH patients treated between 2012 and 2018. CVS was considered refractory, if it persisted despite oral/intravenous nimodipine application and induced hypertension. The decision to perform ETR was made on an individual basis, according to the detection of "tissue at risk" on computed tomography perfusion (CTP) scans and CVS on computed tomography angiography (CTA) or digital subtraction angiography (DSA). The functional outcome was assessed according to the modified Rankin scale (mRS) 3 months after the ictus, whereas an mRS ≤ 2 was considered as a good outcome. Results: A total of 268 patients were included. Out of these, 205 patients (76.5%) were treated without ERT (group 1) and 63 patients (23.5%) with ERT (group 2). In 20 patients (31.8%) balloon dilatation was performed, in 23 patients (36.5%) intra-arterial nimodipine injection alone, and in 20 patients (31.8%) both procedures were combined. Considering only the patient group with DCI, the patients who were treated with ERT had a significantly better outcome compared to the patients without ERT (Mann-Whitney test, p = 0.02). Conclusion: Endovascular rescue therapies resulted in a significantly better functional outcome in patients with DCI compared to the patient group treated without ETR. CTP and CTA-based identification of "tissue at risk" might be a reliable tool for patient selection for performing ERT.

Defining the impact of adjuvant treatment on the prognosis of patients with inoperable glioblastoma undergoing biopsy only: does the survival benefit outweigh the treatment effort?

Patients with inoperable glioblastoma (GBM) usually experience worse prognosis compared to those in whom gross total resection (GTR) is achievable. Considering the treatment duration and its side effects identification of patients with survival benefit from treatment is essential to guarantee the best achievable quality of life. The aim of this study was to evaluate the survival benefit from radio-chemotherapy and to identify clinical, molecular, and imaging parameters associated with better outcome in patients with biopsied GBMs. Consecutive patients with inoperable GBM who underwent tumor biopsy at our department from 2005 to 2019 were retrospectively analyzed. All patients had histologically confirmed GBM and were followed up until death. The overall survival (OS) was calculated from date of diagnosis to date of death. Clinical, radiological, and molecular predictors of OS were evaluated. A total of 95 patients with biopsied primary GBM were enrolled in the study. The mean age was 64.3 ± 13.2 years; 56.8% (54/95) were male, and 43.2% (41/95) female. Median OS in the entire cohort was 5.5 months. After stratification for adjuvant treatment, a higher median OS was found in the group with adjuvant treatment (7 months, range 2-88) compared to the group without treatment (1 month, range 1-5) log-rank test, p < 0.0001. Patients with inoperable GBM undergoing biopsy indeed experience a very limited OS. Adjuvant treatment is associated with significantly longer OS compared to patients not receiving treatment and should be considered, especially in younger patients with good clinical condition at presentation.

In Vivo Vasospasm Induction by Ultrasound Application in the Chicken Chorioallantoic Membrane Model.

Cerebral vasospasm is a highly investigated phenomenon in neurovascular research. Experimental vasospasm models are irreplaceable for the evaluation of new antivasospastic drugs. In this study, we assessed the reliability of in vivo vasospasm induction by ultrasound application in the chicken chorioallantoic membrane (CAM) model. After incubation of fertilized chicken eggs for four days, a fenestration was performed to enable examination of the CAM vessels. On the thirteenth day, continuous-wave ultrasound (3 MHz, 1 W/cm2) was applied on the CAM vessels for 60 s. The ultrasound effect on the vessels was recorded by life imaging (5-MP HD-microscope camera, Leica®). The induced vessel diameter changes were evaluated in a defined time interval of 20 min using a Fiji macro. The vessel diameter before and after sonication was measured and the relative diameter reduction was determined. A first reduction of vessel diameter was observed after three minutes with an average vessel-diameter decrease to 77%. The maximum reduction in vessel diameter was reached eight minutes after sonication with an average vessel diameter decrease to 57% (mean relative diameter reduction of 43%, range 44-61%), ANOVA, p = 0.0002. The vasospasm persisted for all 20 recorded minutes post induction. Vasospasm can be reliably induced by short application of 3 MHz-ultrasound to the CAM vessels. This might be a suitable in vivo model for the evaluation of drug effects on vasospasm in an experimental setting as intermediary in the transition process from in vitro to in vivo assessment using animal models.