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

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

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10143-022-01826-z

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

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/cm(2)) 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

Ultrasound-induced release of nimodipine from drug-loaded block copolymer micelles: in vivo analysis

Nimodipine prevents cerebral vasospasm and improves functional outcome after aneurysmal subarachnoid hemorrhage (aSAH). The beneficial effect is limited by low oral bioavailability of nimodipine, which resulted in an increasing use of nanocarriers with sustained intrathecal drug release in order to overcome this limitation. However, this approach facilitates only a continuous and not an on-demand nimodipine release during the peak time of vasospasm development. In this study, we aimed to assess the concept of controlled drug release from nimodipine-loaded copolymers by ultrasound application in the chicken chorioallantoic membrane (CAM) model. Nimodipine-loaded copolymers were produced with the direct dissolution method. Vasospasm of the CAM vessels was induced by means of ultrasound (Physiomed, continuous wave, 3 MHz, 1.0 W/cm(2)). The ultrasound-mediated nimodipine release (Physiomed, continuous wave, 1 MHz, 1.7 W/cm(2)) and its effect on the CAM vessels were evaluated. Measurements of vessel diameter before and after ultrasound-induced nimodipine release were performed using ImageJ. The CAM model could be successfully carried out in all 25 eggs. After vasospasm induction and before drug release, the mean vessel diameter was at 57% (range 44–61%) compared to the baseline diameter (set at 100%). After ultrasound-induced drug release, the mean vessel diameter of spastic vessels increased again to 89% (range 83–91%) of their baseline diameter, which was significant (p = 0.0002). We were able to provide a proof of concept for in vivo vasospasm induction by ultrasound application in the CAM model and subsequent resolution by ultrasound-mediated nimodipine release from nanocarriers. This concept merits further evaluation in a rat SAH model. GRAPHICAL ABSTRACT: [Image: see text