Rescue therapy for vasospasm following aneurysmal subarachnoid hemorrhage:a propensity score-matched analysis with machine learning

OBJECTIVE Rescue therapies have been recommended for patients with angiographic vasospasm (aVSP) and delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). However, there is little evidence from randomized clinical trials that these therapies are safe and effective. The primary aim of this study was to apply game theory-based methods in explainable machine learning (ML) and propensity score matching to determine if rescue therapy was associated with better 3-month outcomes following post-SAH aVSP and DCI. The authors also sought to use these explainable ML methods to identify patient populations that were more likely to receive rescue therapy and factors associated with better outcomes after rescue therapy. METHODS Data for patients with aVSP or DCI after SAH were obtained from 8 clinical trials and 1 observational study in the Subarachnoid Hemorrhage International Trialists repository. Gradient boosting ML models were constructed for each patient to predict the probability of receiving rescue therapy and the 3-month Glasgow Outcome Scale (GOS) score. Favorable outcome was defined as a 3-month GOS score of 4 or 5. Shapley Additive Explanation (SNAP) values were calculated for each patient-derived model to quantify feature importance and interaction effects. Variables with high S HAP importance in predicting rescue therapy administration were used in a propensity score-matched analysis of rescue therapy and 3-month GOS scores. RESULTS The authors identified 1532 patients with aVSP or DCI. Predictive, explainable ML models revealed that aneurysm characteristics and neurological complications, but not admission neurological scores, carried the highest relative importance rankings in predicting whether rescue therapy was administered. Younger age and absence of cerebral ischemia/ infarction were invariably linked to better rescue outcomes, whereas the other important predictors of outcome varied by rescue type (interventional or noninterventional). In a propensity score-matched analysis guided by SHAP-based variable selection, rescue therapy was associated with higher odds of 3-month GOS scores of 4-5 (OR 1.63, 95% CI 1.22-2.17). CONCLUSIONS Rescue therapy may increase the odds of good outcome in patients with aVSP or DCI after SAH. Given the strong association between cerebral ischemia/infarction and poor outcome, trials focusing on preventative or therapeutic interventions in these patients may be most able to demonstrate improvements in clinical outcomes. Insights developed from these models may be helpful for improving patient selection and trial design

Development and validation of outcome prediction models for aneurysmal subarachnoid haemorrhage:the SAHIT multinational cohort study

Objective To develop and validate a set of practical prediction tools that reliably estimate the outcome of subarachnoid haemorrhage from ruptured intracranial aneurysms (SAH). Design Cohort study with logistic regression analysis to combine predictors and treatment modality. Setting Subarachnoid Haemorrhage International Trialists' (SAHIT) data repository, including randomised clinical trials, prospective observational studies, and hospital registries. Participants Researchers collaborated to pool datasets of prospective observational studies, hospital registries, and randomised clinical trials of SAH from multiple geographical regions to develop and validate clinical predicti

Development and validation of outcome prediction models for aneurysmal subarachnoid haemorrhage: the SAHIT multinational cohort study

Objective To develop and validate a set of practical prediction tools that reliably estimate the outcome of subarachnoid haemorrhage from ruptured intracranial aneurysms (SAH). Design Cohort study with logistic regression analysis to combine predictors and treatment modality. Setting Subarachnoid Haemorrhage International Trialists’ (SAHIT) data repository, including randomised clinical trials, prospective observational studies, and hospital registries. Participants Researchers collaborated to pool datasets of prospective observational studies, hospital registries, and randomised clinical trials of SAH from multiple geographical regions to develop and validate clinical prediction models. Main outcome measure Predicted risk of mortality or functional outcome at three months according to score on the Glasgow outcome scale. Results Clinical prediction models were developed with individual patient data from 10 936 patients and validated with data from 3355 patients after development of the model. In the validation cohort, a core model including patient age, premorbid hypertension, and neurological grade on admission to predict risk of functional outcome had good discrimination, with an area under the receiver operator characteristics curve (AUC) of 0.80 (95% confidence interval 0.78 to 0.82). When the core model was extended to a “neuroimaging model,” with inclusion of clot volume, aneurysm size, and location, the AUC improved to 0.81 (0.79 to 0.84). A full model that extended the neuroimaging model by including treatment modality had AUC of 0.81 (0.79 to 0.83). Discrimination was lower for a similar set of models to predict risk of mortality (AUC for full model 0.76, 0.69 to 0.82). All models showed satisfactory calibration in the validation cohort. Conclusion The prediction models reliably estimate the outcome of patients who were managed in various settings for ruptured intracranial aneurysms that caused subarachnoid haemorrhage. The predictor items are readily derived at hospital admission. The web based SAHIT prognostic calculator (http://sahitscore.com) and the related app could be adjunctive tools to support management of patients

Clinical characteristics and outcome of aneurysmal subarachnoid hemorrhage with intracerebral hematoma

OBJECTIVE Intracerebral hematoma (ICH) with subarachnoid hemorrhage (SAH) indicates a unique feature of intracranial aneurysm rupture since the aneurysm is in the subarachnoid space and separated from the brain by pia mater. Broad consensus is lacking regarding the concept that ultra-early treatment improves outcome. The aim of this study is to determine the associative factors for ICH, ascertain the prognostic value of ICH, and investigate how the timing of treatment relates to the outcome of SAH with concurrent ICH. METHODS The study data were pooled from the SAH International Trialists repository. Logistic regression was applied to study the associations of clinical and aneurysm characteristics with ICH. Proportional odds models and dominance analysis were applied to study the effect of ICH on 3-month outcome (Glasgow Outcome Scale) and investigate the effect of time from ictus to treatment on outcome. RESULTS Of the 5362 SAH patients analyzed, 1120 (21%) had concurrent ICH. In order of importance, neurological status, aneurysm location, aneurysm size, and patient ethnicity were significantly associated with ICH. Patients with ICH experienced poorer outcome than those without ICH (OR 1.58; 95% CI 1.37-1.82). Treatment within 6 hours of SAH was associated with poorer outcome than treatment thereafter (adjusted OR 1.67; 95% CI 1.04-2.69). Subgroup analysis with adjustment for ICH volume, location, and midline shift resulted in no association between time from ictus to treatment and outcome (OR 0.99; 95% CI 0.94-1.07). CONCLUSIONS The most important associative factor for ICH is neurological status on admission. The finding regarding the value of ultra-early treatment suggests the need to more robustly reevaluate the concept that hematoma evacuation of an ICH and repair of a ruptured aneurysm within 6 hours of ictus is the most optimal treatment path

Emotional expressions associated with therapeutic inertia in multiple sclerosis care

Background Emotions play a critical role in our daily decisions. However, it remains unclear how and what sort of emotional expressions are associated with therapeutic decisions in multiple sclerosis (MS) care. Our goal was to evaluate the relationship between emotions and affective states (as captured by muscle facial activity and emotional expressions) and TI amongst neurologists caring for MS patients when making therapeutic decisions. Methods 38 neurologists with expertise in MS were invited to participate in a face-to-face study across Canada. Participants answered questions regarding their clinical practice, aversion to ambiguity, and the management of 10 simulated case-scenarios. TI was defined as lack of treatment initiation or escalation when there was clear evidence of clinical and radiological disease activity. We recorded facial muscle activations and their associated emotional expressions during the study, while participants made therapeutic choices. We used a validated machine learning algorithm of the AFFDEX software to code for facial muscle activations and a predefined mapping to emotional expressions (disgust, fear, surprise, etc.). Mixed effects models and mediation analyses were used to evaluate the relationship between ambiguity aversion, facial muscle activity/emotional expressions and TI measured as a binary variable and a continuous score. Results 34 (89.4%) neurologists completed the study. The mean age [standard deviation (SD)] was 44.6 (11.5) years; 38.3% were female and 58.8% self-identified as MS specialists. Overall, 17 (50%) participants showed TI in at least one case-scenario and the mean (SD) TI score was 0.74 (0.90). Nineteen (55.9%) participants had aversion to ambiguity in the financial domain. The multivariate analysis adjusted for age, sex and MS expertise showed that aversion to ambiguity in the financial domain (OR 1.56, 95%CI 1.32–1.86) was associated with TI. Most common muscle activations included mouth open (23.4%), brow furrow (20.9%), brow raise (17.6%), and eye widening (13.1%). Most common emotional expressions included fear (5.1%), disgust (3.2%), sadness (2.9%), and surprise (2.8%). After adjustment for age, sex, and physicians’ expertise, the multivariate analysis revealed that brow furrow (OR 1.04; 95%CI 1.003–1.09) and lip suck (OR 1.06; 95%CI 1.01–1.11) were associated with an increase in TI prevalence, whereas upper lip raise (OR 0.30; 95%CI 0.15–0.59), and chin raise (OR 0.90; 95%CI 0.83–0.98) were associated with lower likelihood of TI. Disgust and surprise were associated with a lower TI score (disgust: p < 0.001; surprise: p = 0.008) and lower prevalence of TI (ORdisgust: 0.14, 95%CI 0.03–0.65; ORsurprise: 0.66, 94%CI 0.47–0.92) after adjusting for covariates. The mediation analysis showed that brow furrow was a partial mediator explaining 21.2% (95%CI 14.9%-38.9%) of the association between aversion to ambiguity and TI score, followed by nose wrinkle 12.8% (95%CI 8.9%-23.4%). Similarly, disgust was the single emotional expression (partial mediator) that attenuated (-13.2%, 95%CI -9.2% to -24.3%) the effect of aversion to ambiguity on TI. Conclusions TI was observed in half of participants in at least one case-scenario. Our data suggest that facial metrics (e.g. brow furrow, nose wrinkle) and emotional expressions (e.g. disgust) are associated with physicians’ choices and partially mediate the effect of aversion to ambiguity on TI

Sex differences in delayed cerebral ischemia after subarachnoid hemorrhage

OBJECTIVE In this study the authors sought to investigate the sex differences in the risk of delayed cerebral ischemia (DCI), delayed cerebral infarction, and the role of hormonal status. METHODS Ten studies included in the SAHIT (SAH International Trialists) repository were analyzed using a fitting logistic regression model. Heterogeneity between the studies was tested using I(2) statistics, and the results were pooled using a random-effects model. Multivariable analysis was adjusted for the effects of neurological status and fixed effect of study. An additional model was examined in which women and men were split into groups according to an age cut point of 55 years, as a surrogate to define hormonal status. RESULTS A pooled cohort of 6713 patients was analyzed. The risk of DCI was statistically significantly higher in women than in men (OR 1.29, 95% CI 1.12-1.48); no difference was found with respect to cerebral infarction (OR 1.17, 95% CI 0.98-1.40). No difference was found in the risk of DCI when comparing women ≤ 55 and > 55 years (OR 0.87, 95% CI 0.74-1.02; p = 0.08) or when comparing men ≤ 55 and > 55 years (p = 0.38). Independent predictors of DCI were World Federation of Neurosurgical Societies (WFNS) grade, Fisher grade, age, and sex. Independent predictors of infarction included WFNS grade, Fisher grade, and aneurysm size. CONCLUSIONS Female sex is associated with a higher risk of DCI. Sex differences may play a role in the pathogenesis of DCI but are not associated with menopausal status. The predictors of DCI and cerebral infarction were identified in a very large cohort and reflect experience from multiple institutions

Predictors of Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage with Asymptomatic Angiographic Vasospasm on Admission

Risk of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) with asymptomatic angiographic vasospasm on admission is unclear in the literature. The goal of this study is to identify predictors of clinical DCI in this group of patients

The SAFARI Score to Assess the Risk of Convulsive Seizure During Admission for Aneurysmal Subarachnoid Hemorrhage

BACKGROUND Seizure is a significant complication in patients under acute admission for aneurysmal SAH and could result in poor outcomes. Treatment strategies to optimize management will benefit from methods to better identify at-risk patients. OBJECTIVE To develop and validate a risk score for convulsive seizure during acute admission for SAH. METHODS A risk score was developed in 1500 patients from a single tertiary hospital and externally validated in 852 patients. Candidate predictors were identified by systematic review of the literature and were included in a backward stepwise logistic regression model with in-hospital seizure as a dependent variable. The risk score was assessed for discrimination using the area under the receiver operator characteristics curve (AUC) and for calibration using a goodness-of-fit test. RESULTS The SAFARI score, based on 4 items (age ≥ 60 yr, seizure occurrence before hospitalization, ruptured aneurysm in the anterior circulation, and hydrocephalus requiring cerebrospinal fluid diversion), had AUC = 0.77, 95% confidence interval (CI): 0.73-0.82 in the development cohort. The validation cohort had AUC = 0.65, 95% CI 0.56-0.73. A calibrated increase in the risk of seizure was noted with increasing SAFARI score points. CONCLUSION The SAFARI score is a simple tool that adequately stratified SAH patients according to their risk for seizure using a few readily derived predictor items. It may contribute to a more individualized management of seizure following SAH

Assessment of the incremental prognostic value from the modified frailty index-5 in complete traumatic cervical spinal cord injury

Abstract Frailty, as measured by the modified frailty index-5 (mFI-5), and older age are associated with increased mortality in the setting of spinal cord injury (SCI). However, there is limited evidence demonstrating an incremental prognostic value derived from patient mFI-5. We conducted a retrospective cohort study to evaluate in-hospital mortality among adult complete cervical SCI patients at participating centers of the Trauma Quality Improvement Program from 2010 to 2018. Logistic regression was used to model in-hospital mortality, and the area under the receiver operating characteristic curve (AUROC) of regression models with age, mFI-5, or age with mFI-5 was used to compare the prognostic value of each model. 4733 patients were eligible. We found that both age (80 y versus 60 y: OR 3.59 95% CI [2.82 4.56], P < 0.001) and mFI-5 (score ≥ 2 versus < 2: OR 1.53 95% CI [1.19 1.97], P < 0.001) had statistically significant associations with in-hospital mortality. There was no significant difference in the AUROC of a model including age and mFI-5 when compared to a model including age without mFI-5 (95% CI Δ AUROC [− 8.72 × 10–4 0.82], P = 0.199). Both models were superior to a model including mFI-5 without age (95% CI Δ AUROC [0.06 0.09], P < 0.001). Our findings suggest that mFI-5 provides minimal incremental prognostic value over age with respect to in-hospital mortality for patients complete cervical SCI

Functional outcome after poor-grade subarachnoid hemorrhage: a single-center study and systematic literature review

BACKGROUND AND PURPOSE Poor-grade subarachnoid hemorrhage (SAH) (World Federation of Neurosurgical Societies grade 4 and 5) is associated with high mortality rates and unfavorable functional outcomes. We report a single-center cohort of poor-grade SAH patients, combined with a systematic review of studies reporting functional outcome in the poor-grade SAH population. METHODS Data on a cohort of poor-grade SAH patients treated between 2009 and 2013 were retrospectively collected and combined with a systematic review (from inception to November 2015; PubMed, Embase). Two reviewers assessed the studies independently based on predefined inclusion criteria: consecutive poor-grade SAH, functional outcome measured at least 3 months after hemorrhage, and the report of patients who died before aneurysm treatment. RESULTS The search yielded 329 publications, and 23 met our inclusion criteria with 2713 subjects enrolled from 1977 to 2014 in 10 countries (including 179 poor-grade patients from our cohort). Mortality rate was 60 % (1683 patients), of which 806 (29 %) died before and 877 (31 %) died after aneurysm treatment, respectively. Treatment was undertaken in 1775 patients (1775/2826-63 %): 1347 by surgical clipping (1347/1775-76 %) and 428 (428/1775-24 %) by endovascular methods. Outcome was favorable in 794 patients (28 %) and unfavorable in 1867 (66 %). When the studies were grouped into decades, favorable outcome increased from 13 % in the late 1970s to early 1980s to 35 % in the late 1980s to early 1990s, and remained unchanged thereafter. CONCLUSION Although mortality remains high in poor-grade SAH patients, a favorable functional outcome can be achieved in approximately one-third of patients. The development of new diagnostic methods and implementation of therapeutic approaches were probably responsible for the decrease in mortality and improvement in the functional outcome from 1970 to the 1990s. The plateau in functional outcome seen thereafter might be explained by the treatment of sicker and older patients and by the lack of new therapeutic interventions specific for SAH