Proposed Definition of Experimental Secondary Ischemia for Mouse Subarachnoid Hemorrhage.

Inconsistency in outcome parameters for delayed cerebral ischemia (DCI) makes it difficult to compare results between mouse studies, in the same way inconsistency in outcome parameters in human studies has for long obstructed adequate comparison. The absence of an established definition may in part be responsible for the failed translational results. The present article proposes a standardized definition for DCI in experimental mouse models, which can be used as outcome measure in future animal studies. We used a consensus-building approach to propose a definition for "experimental secondary ischemia" (ESI) in experimental mouse subarachnoid hemorrhage that can be used as an outcome measure in preclinical studies. We propose that the outcome measure should be as follows: occurrence of focal neurological impairment or a general neurological impairment compared with a control group and that neurological impairment should occur secondarily following subarachnoid hemorrhage (SAH) induction compared with an initial assessment following SAH induction. ESI should not be used if the condition can be explained by general anesthesia or if other means of assessments sufficiently explain function impairment. If neurological impairment cannot reliably be evaluated, due to scientific setup. Verification of a significant secondary impairment of the cerebral perfusion compared with a control group is mandatory. This requires longitudinal examination in the same animal. The primary aim is that ESI should be distinguished from intervention-related ischemia or neurological deficits, in order establish a uniform definition for experimental SAH in mice that is in alignment with outcome measures in human studies

Defining activities in neurovascular microsurgery training : entrustable professional activities for vascular neurosurgery

Background Entrustable professional activities (EPAs) represent an assessment framework with an increased focus on competency-based assessment. Originally developed and adopted for undergraduate medical education, concerns over resident ability to practice effectively after graduation have led to its implementation in residency training but yet not in vascular neurosurgery. Subjective assessment of resident or fellow performance can be problematic, and thus, we aim to define core EPAs for neurosurgical vascular training. Methods We used a nominal group technique in a multistep interaction between a team of experienced neurovascular specialists and a medical educator to identify relevant EPAs. Panel members provided feedback on the EPAs until they reached consent. Results The process produced seven core procedural EPAs for vascular residency and fellowship training, non-complex aneurysm surgery, complex aneurysm surgery, bypass surgery, arteriovenous malformation resection, spinal dural fistula surgery, perioperative management, and clinical decision-making. Conclusion These seven EPAs for vascular neurosurgical training may support and guide the neurosurgical society in the development and implementation of EPAs as an evaluation tool and incorporate entrustment decisions in their training programs.Peer reviewe

Intensive blood pressure control affects cerebral blood flow in type 2 diabetes mellitus patients

Type 2 diabetes mellitus is associated with microvascular complications, hypertension, and impaired dynamic cerebral autoregulation. Intensive blood pressure (BP) control in hypertensive type 2 diabetic patients reduces their risk of stroke but may affect cerebral perfusion. Systemic hemodynamic variables and transcranial Doppler-determined cerebral blood flow velocity (CBFV), cerebral CO2 responsiveness, and cognitive function were determined after 3 and 6 months of intensive BP control in 17 type 2 diabetic patients with microvascular complications (T2DM+), in 18 diabetic patients without (T2DM-) microvascular complications, and in 16 nondiabetic hypertensive patients. Cerebrovascular reserve capacity was lower in T2DM+ versus T2DM- and nondiabetic hypertensive patients (4.6±1.1 versus 6.0±1.6 [P<0.05] and 6.6±1.7 [P<0.01], Δ%mean CBFV/mm Hg). After 6 months, the attained BP was comparable among the 3 groups. However, in contrast to nondiabetic hypertensive patients, intensive BP control reduced CBFV in T2DM- (58±9 to 54±12 cm·s(-1)) and T2DM+ (57±13 to 52±11 cm·s(-1)) at 3 months, but CBFV returned to baseline at 6 months only in T2DM-, whereas the reduction in CBFV progressed in T2DM+ (to 48±8 cm·s(-1)). Cognitive function did not change during the 6 months. Static cerebrovascular autoregulation appears to be impaired in type 2 diabetes mellitus, with a transient reduction in CBFV in uncomplicated diabetic patients on tight BP control, but with a progressive reduction in CBFV in diabetic patients with microvascular complications, indicating that maintenance of cerebral perfusion during BP treatment depends on the progression of microvascular disease. We suggest that BP treatment should be individualized, aiming at a balance between BP reduction and maintenance of CBFV

A Systematic and Meta-Analysis of Mortality in Experimental Mouse Models Analyzing Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

Animal models are established to display the pathophysiological changes following subarachnoid hemorrhage (SAH). The aim of the present study was to determine case fatality in mouse delayed cerebral ischemia (DCI) models, to compare mortality in mouse DCI models to case fatality in human SAH patients, and to identify factors influencing mouse mortality. A systematic search of the PubMed database was performed to identify all studies that assessed mouse DCI models. Mortality rates and predictor variables were extracted and compared to the human case fatality after SAH as previously reported. Predictors for mouse mortality were identified through multivariate analysis. Forty-eight studies were included in the quantitative analysis. The mean overall mortality rate was 21% in mouse DCI models. However, the time period between induction of SAH and evaluation of mortality rates is a significant variable influencing the mortality rate in mouse SAH models. The experimental SAH model was the only significant predictor for mouse mortality after 48 h. In contrast, neither the genetic background nor the anesthetic changed the case fatality rate. Mouse mortality at 24, 48, and 72 h after experimental SAH in DCI models was significantly lower than human case fatality following aneurysmal SAH. The mean overall mortality rate in mouse DCI models is significantly lower than human case fatality following aneurysmal SAH. However, time between SAH induction and evaluation is a significant variable influencing the mortality rate in mouse SAH models. Further analyses will be required to establish whether and to which extent different DCI models affect mortality and reflect human pathophysiology

An introduction to the pathophysiology of aneurysmal subarachnoid hemorrhage

Pathophysiological processes following subarachnoid hemorrhage (SAH) present survivors of the initial bleeding with a high risk of morbidity and mortality during the course of the disease. As angiographic vasospasm is strongly associated with delayed cerebral ischemia (DCI) and clinical outcome, clinical trials in the last few decades focused on prevention of these angiographic spasms. Despite all efforts, no new pharmacological agents have shown to improve patient outcome. As such, it has become clear that our understanding of the pathophysiology of SAH is incomplete and we need to reevaluate our concepts on the complex pathophysiological process following SAH. Angiographic vasospasm is probably important. However, a unifying theory for the pathophysiological changes following SAH has yet not been described. Some of these changes may be causally connected or present themselves as an epiphenomenon of an associated process. A causal connection between DCI and early brain injury (EBI) would mean that future therapies should address EBI more specifically. If the mechanisms following SAH display no causal pathophysiological connection but are rather evoked by the subarachnoid blood and its degradation production, multiple treatment strategies addressing the different pathophysiological mechanisms are required. The discrepancy between experimental and clinical SAH could be one reason for unsuccessful translational results

Endovascular aneurysm closure during out of office hours is not related to complications or outcome

Purpose: A possible disadvantage of endovascular occlusion outside work hours is that complex procedures might expose patients to additional risk when performed in a suboptimal setting. In this prospective cohort study, we evaluated whether treatment during out of office hours is a risk factor for per-procedural complications and clinical outcome. Methods: We included 471 endovascular-treated, consecutive aneurysmal subarachnoid hemorrhage patients (56.6 ± 13.1, 69% female), from two prospective observational databases which were retrospectively analyzed. Primary outcome was the occurrence of per-procedural complications. Secondary outcomes were good clinical outcome (modified ranking scale ≤ 2) and death at 6-month follow-up. We determined odds ratios (OR) with 95% confidence intervals (CI) by ordered polytomous logistic regression analysis and adjusted odds ratios (aOR) for age, World Federation of Neurosurgical Societies grade, and time to treatment. Results: Most patients were treated during office hours (363/471; 77.1%). Treatment during out of office hours did not result in an increased risk of per-procedural complications (OR 0.85 (95% CI 0.53–1.37; p = 0.51). Patients treated during out of office hours displayed similar odds of good clinical outcome and death after 6 months (OR 1.14, 95% CI 0.68–1.97 and 1.16 95% CI 0.56–2.29, respectively) compared to patients treated during office hours. Conclusion: In our study, endovascular coil embolization during out of office hours did not expose patients to an increased risk of procedural complications or affect functional outcome after 6 months

Blood pressure reduction after gastric bypass surgery is explained by a decrease in cardiac output

Blood pressure (BP) decreases in the first weeks after Roux-and-Y gastric bypass surgery. Yet the pathophysiology of the BP-lowering effects observed after gastric bypass surgery is incompletely understood. We evaluated BP, systemic hemodynamics, and baroreflex sensitivity in 15 obese women[mean age 42 +/- 7 standard deviation (SD) yr, body mass index 45 +/- 6 kg/m2] 2 wk before and 6 wk following Roux-and-Y gastric bypass surgery. Six weeks after gastric bypass surgery, mean body weight decreased by 13 +/- 5 kg (10%, P < 0.001). Office BP decreased from 137 +/- 10/86 +/- 6 to 128 +/- 12/81 +/- 9 mmHg (P < 0.001, P < 0.01), while daytime ambulatory BP decreased from 128 +/- 14/80 +/- 9 to 114 +/- 10/73 +/- 6 mmHg (P = 0.01, P = 0.05), whereas nighttime BP decreased from 111 +/- 13/66 +/- 7 to 102 +/- 9/62 +/- 7 mmHg (P = 0.04, P < 0.01). The decrease in BP was associated with a 1.6 +/- 1.2 l/min (20%, P < 0.01) decrease in cardiac output (CO), while systemic vascular resistance increased (153 +/- 189 dyn s cm-5, 15%, P < 0.01). The maximal ascending slope in systolic blood pressure decreased (192 mmHg/s, 19%, P = 0.01), suggesting a reduction in left ventricular contractility. Baroreflex sensitivity increased from 9.0 [6.4-14.3] to 13.8 [8.5-19.0] ms/mmHg (median [interquartile range]; P < 0.01) and was inversely correlated with the reductions in heart rate (R = -0.64, P = 0.02) and CO (R = -0.61, P = 0.03). In contrast, changes in body weight were not correlated with changes in either BP or CO. The BP reduction following Roux-and-Y gastric bypass surgery is correlated with a decrease in CO independent of changes in body weight. The contribution of heart rate to the reduction in CO together with enhanced baroreflex sensitivity suggests a shift toward increased parasympathetic cardiovascular control. The reason for the decrease in blood pressure (BP) in the first weeks after gastric bypass surgery remains to be elucidated. We show that the reduction in BP following surgery is caused by a decrease in cardiac output. In addition, the maximal ascending slope in systolic blood pressure decreased suggesting a reduction in left ventricular contractility and cardiac workload. These findings help to understand the physiological changes following gastric bypass surgery and are relevant in light of the increased risk of heart failure in these patient