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.

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.

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.

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.

New-onset seizures after cranioplasty-a different view on a putatively frequently observed phenomenon.

BACKGROUND: New-onset seizures after cranioplasty (NOSAC) are reported to be a frequent complication of cranioplasty (CP) after decompressive hemicraniectomy (DHC). There are considerable differences in the incidence of NOSAC and contradictory data about presumed risk factors in the literature. We suggest NOSAC to be a consequence of patients' initial condition which led to DHC, rather than a complication of subsequent CP. We conducted a retrospective analysis to verify our hypothesis. METHODS: The medical records of all patients ≥ 18 years who underwent CP between 2002 and 2017 at our institution were evaluated including incidence of seizures, time of seizure onset, and presumed risk factors. Indication for DHC, type of implant used, timing of CP, patient age, presence of a ventriculoperitoneal shunt (VP shunt), and postoperative complications were compared between patients with and without NOSAC. RESULTS: A total of 302 patients underwent CP between 2002 and 2017, 276 of whom were included in the outcome analysis and the incidence of NOSAC was 23.2%. Although time between DHC and CP differed significantly between DHC indication groups, time between DHC and seizure onset did not differ, suggesting the occurrence of seizures to be independent of the procedure of CP. Time of follow-up was the only factor associated with the occurrence of NOSAC. CONCLUSION: New-onset seizures may be a consequence of the initial condition leading to DHC rather than of CP itself. Time of follow-up seems to play a major role in detection of new-onset seizures.

Cranioplasty following ventriculoperitoneal shunting: lessons learned.

OBJECTIVE: Cranioplasty (CP) is considered as a straightforward and technically unchallenging operation; however, complication rates are high reaching up to 56%. Presence of a ventriculoperitoneal shunt (VPS) and timing of CP are reported risk factors for complications. Pressure gradients and scarring at the site of the cranial defect seem to be critical in this context. The authors present their experiences and lessons learned. METHODS: A consecutive series of all patients who underwent CP at the authors' institution between 2002 and 2017 were included in this retrospective analysis. Complications were defined as all events that required reoperation. Logistic regression analysis and chi-squared test were conducted to evaluate the complication rates according to suspected risk factors. RESULTS: A total of 302 patients underwent cranioplasty between 2002 and 2017. The overall complication rate was 17.5%. Complications included epi-/subdural fluid collection (7.3%) including hemorrhage (4.6%) and hygroma (2.6%), bone graft resorption (5.3%), bone graft infection (2.0%), and hydrocephalus (5.7%). Overall, 57 patients (18.9%) had undergone shunt implantation prior to CP. The incidence of epi-/subdural fluid collection was 19.3% in patients with VPS and 4.5% in patients without VPS, OR 5.1 (95% CI 2.1-12.4). Incidence of hygroma was higher in patients who underwent early CP. Patients with temporary shunt ligation for CP did not suffer from complications. CONCLUSION: CP in patients with a VPS remains a high-risk procedure. Any effort to understand the pressure dynamics and to reduce factors that may trigger the formation of a large epidural space must be undertaken.

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.

Radiosurgery as a Stand-Alone Treatment Option for Cerebral Dural Arteriovenous Fistulas: the Vienna Series.

BACKGROUND: Gamma Knife radiosurgery (GKRS) has been demonstrated to be an effective and safe treatment method for dural arteriovenous fistulas (DAVFs). However, only few studies, mostly with limited patient numbers, have evaluated radiosurgery as a sole and upfront treatment option for DAVFs. METHODS: Thirty-three DAVF patients treated with GKRS as a stand-alone management at our institution between January 1992 and January 2020 were included in this study. Obliteration rates, time to obliteration, neurologic outcome, and complications were evaluated retrospectively. RESULTS: Complete overall obliteration was achieved in 20/28 (71%) patients. The postradiosurgery actuarial rates of obliteration at 2, 5, and 10 years were 53, 71, and 85%, respectively. No difference in time to obliteration between carotid-cavernous fistulas (CCFs; 14/28, 50%, 17 months; 95% confidence interval [CI]: 7.4-27.2) and non-CCFs (NCCFs; 14/28, 50%, 37 months; 95% CI: 34.7-38.5; p = 0.111) were found. Overall, the neurologic outcome in our series was highly favorable at the time of the last follow-up. A complete resolution of symptoms was seen in two-thirds (20/30, 67%) of patients. One patient with multiple DAVFs suffered from an intracranial hemorrhage of the untreated lesion and died during the follow-up period, resulting in a yearly bleeding risk of 0.5%. No complications after radiosurgery were observed in our series. CONCLUSION: Our results show that GKRS is a safe and effective stand-alone management option for selected DAVF patients.

Outcome of 107 conservatively managed unruptured brain arteriovenous malformations: a single center's 30-year experience.

OBJECTIVE: Since the publication of A Randomized Trial of Unruptured Brain AVMs (ARUBA), the management of unruptured brain arteriovenous malformations (bAVMs) has been controversially discussed. Long-term follow-up data on the exclusively conservative management of unruptured bAVMs are scarce. The authors evaluated the long-term outcomes of patients with unruptured untreated bAVMs in a real-life cohort. METHODS: A retrospective observational cohort of 107 patients (of 897 bAVM patients referred to the authors' institution) with a diagnosis of unruptured and conservatively managed bAVMs is presented. AVMs of all Spetzler-Martin grades were observed. The mean follow-up period was 84 months. In 44% of patients, a follow-up period of 5 years or longer was observed. A national death register comparison completed the outcome analysis. RESULTS: The median age at diagnosis, sex distribution, neurological presentation, and modified Rankin Scale score were comparable to the patients in the medical management arm of the ARUBA study. Patients were mainly young, predominantly male, and in good clinical condition. Similar to the ARUBA cohort, 77% of this study's cohort presented in an excellent clinical status at the time of last follow-up. However, 17% of patients had at least one hemorrhage, resulting in an overall annual hemorrhage risk of 2.7% in the observation period. Moreover, the cumulative 1-, 5-, and 10-year overall hemorrhage rates were 3.0%, 11.3%, and 15.3%, respectively. Consequently, the long-term follow-up AVM-related mortality rate amounted to 8%. The estimated median overall survival after AVM diagnosis was 19.3 years (95% CI 14.0-24.6 years). A multivariate Cox regression model revealed temporal and deep-seated localization as an independent risk factor for AVM hemorrhage, while the presence of seizures reached borderline significance as a risk factor. CONCLUSIONS: The authors' results represent the long-term course of unruptured untreated bAVMs. Their data support the conclusion that even in the post-ARUBA era, tailored active treatment options may be offered to patients with unruptured bAVMs. For patient counseling, individual risk factors should be weighed against the center's treatment-specific risks.

Concomitant radiosurgical and targeted oncological treatment improves the outcome of patients with brain metastases from gastrointestinal cancer.

BACKGROUND: So far, only limited studies exist that evaluate patients with brain metastases (BM) from GI cancer and associated primary cancers who were treated by Gamma Knife Radiosurgery (GKRS) and concomitant immunotherapy (IT) or targeted therapy (TT). METHODS: Survival after GKRS was compared to the general and specific Graded Prognostic Assessment (GPA) and Score Index for Radiosurgery (SIR). Further, the influence of age, sex, Karnofsky Performance Status Scale (KPS), extracranial metastases (ECM) status at BM diagnosis, number of BM, the Recursive Partitioning Analysis (RPA) classes, GKRS1 treatment mode and concomitant treatment with IT or TT on the survival after GKRS was analyzed. Moreover, complication rates after concomitant GKRS and mainly TT treatment are reported. RESULTS: Multivariate Cox regression analysis revealed IT or TT at or after the first Gamma Knife Radiosurgery (GKRS1) treatment as the only significant predictor for overall survival after GKRS1, even after adjusting for sex, KPS group, age group, number of BM at GKRS1, RPA class, ECM status at BM diagnosis and GKRS treatment mode. Concomitant treatment with IT or TT did not increase the rate of adverse radiation effects. There was no significant difference in local BM progression after GKRS between patients who received IT or TT and patients without IT or TT. CONCLUSION: Good local tumor control rates and low rates of side effects demonstrate the safety and efficacy of GKRS in patients with BM from GI cancers. The concomitant radiosurgical and targeted oncological treatment significantly improves the survival after GKRS without increasing the rate of adverse radiation effects. To provide local tumor control, radiosurgery remains of utmost importance in modern GI BM management.

How to dose-stage large or high-risk brain metastases: an alternative two-fraction radiosurgical treatment approach.

OBJECTIVE: The authors sought to evaluate clinical outcome in patients with large, high-risk brain metastases (BMs) treated with different dose strategies by use of two-fraction dose-staged Gamma Knife radiosurgery (GKRS). METHODS: A retrospective analysis was performed with data from 142 patients from two centers who had been treated with two-fraction dose-staged GKRS between June 2015 and January 2020. Depending on the changes in marginal dose between the first (GKRS1) and second (GKRS2) GKRS treatments, the study population was divided into three treatment groups: dose escalation, dose maintenance, and dose de-escalation. RESULTS: The 142 study patients underwent two-fraction dose-staged GKRS treatments for 166 large, high-risk BMs. The median tumor volume of 7.4 cm3 decreased significantly from GKRS1 to GKRS2 (4.4 cm3; p < 0.001), and to the last follow-up (1.8 cm3; p < 0.001). These significant differences in BM volume reduction were achieved in all three treatment groups. However, differences according to the primary tumor histology were apparent: while dose maintenance seemed to be the most effective treatment strategy for BMs from lung cancer or melanoma, dose escalation was the most beneficial treatment option for BMs from breast, gastrointestinal, or genitourinary cancer. Of note, the vast majority of patients who underwent dose-staged BM treatment did not show any significant postradiosurgical complications. CONCLUSIONS: In patients with large, high-risk BMs, dose-staged GKRS treatment represents an effective local treatment method with acceptable complication risks. Different dose-strategy options are available that may be chosen according to the primary tumor histology and treatment volume but may also be tailored to the findings at GKRS2.

Neutrophil-to-Lymphocyte Ratio Is Superior to Other Leukocyte-Based Ratios as a Prognostic Predictor in Non-Small Cell Lung Cancer Patients with Radiosurgically Treated Brain Metastases Under Immunotherapy or Targeted Therapy.

OBJECTIVE: To investigate predictive value of preradiosurgery leukocyte-based prognostic ratios in a selected cohort of non-small cell lung cancer (NSCLC) patients with radiosurgery-treated brain metastases (BM) and concomitant immunotherapy (IT) or targeted therapy (TT). METHODS: We performed a retrospective analysis of 166 patients with NSCLC BM treated with Gamma Knife radiosurgery. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio were assessed within 14 days before radiosurgery. RESULTS: In radiosurgically treated patients with NSCLC BM with concomitant IT or TT, estimated median survival after first Gamma Knife radiosurgery treatment was significantly longer in patients with NLR cutoff value <5 (P = 0.038). Consequently, the Cox regression model for NLR cutoff value groups revealed a significant hazard ratio of 1.519 (95% confidence interval 1.020-2.265, P = 0.040). In addition, each increase in NLR of 1 equaled an increase of 5.4% in risk of death (hazard ratio 1.054, 95% confidence interval 1.024-1.085, P < 0.001). After adjusting for sex, age, Karnofsky performance scale, and presence of extracranial metastases, NLR remained a significant and independent predictor for survival (hazard ratio 1.047, 95% confidence interval 1.017-1.078, P = 0.002). In contrast, platelet-to-lymphocyte ratio and lymphocyte-to-monocyte ratio did not exhibit the same predictive value among patients with radiosurgery-treated BM with concomitant IT or TT. CONCLUSIONS: In patients with NSCLC BM treated with radiosurgery with concomitant IT or TT, preradiosurgery NLR represents a simple prognostic predictor for survival and is superior to other leukocyte-based ratios. NLR may be relevant for clinical decision making, therapeutic evaluation, patient counseling, and appropriate stratification of future clinical trials among patients with radiosurgery-treated BM.