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Background Context: Existing degenerative cervical myelopathy (DCM) severity scales have significant shortcomings, creating a strong impetus for the development of a practical measurement tool with sound psychometric properties., Purpose: This work reports the item generation and reduction of the Cervical Myelopathy Severity Index (CMSI), a new DCM patient-reported outcome measure of symptoms and functional limitations., Design: Prospective observational study., Patient Sample: Adult DCM patients belonging to one of three distinct treatment groups: (1) observation cohort, (2) preoperative surgical cohort, (3) 6 to 12 months postoperative cohort., Outcome Measures: Patient-reported outcome measure of symptoms and functional limitations., Methods: Item generation was performed using semi-structured patient focus groups emphasizing symptoms experienced and functional limitations. Readability was assessed through think-aloud patient interviews. Item reduction involved surveys of DCM patients with a spectrum of disease severity and board-certified spine surgeons experienced in the treatment of DCM. A priori criteria for item removal included: patient median importance/severity <2 (of 4), 30% or more no severity (response of zero), item severity correlations ≤ 0.80 (Spearman), item severity reliability (weighted kappa <0.60) based on a 2-week interval and clinician median importance <2 with retention of items with very high clinical importance., Results: There were 42 items generated from a combination of specialist input and patient focus groups. Items captured sensorimotor symptoms and limitations related to upper and lower extremities as well as sphincter dysfunction. Ninety-eight patients (43, 30, 25 observation, pre- and postsurgery respectively) and 51 surgeons completed the assessment. Twenty-three items remained after application of median importance and severity thresholds and weighted kappa cutoffs. After elimination of highly correlated (>0.80) items and combining two similar items, the final CMSI questionnaire list included 14 items., Conclusions: The CMSI is a new DCM patient-reported clinical measurement tool developed using patient and clinician input to inform item generation and reduction. Future work will evaluate the reliability, validity, and responsiveness of the CMSI in relation to existing myelopathy measurement indices., Competing Interests: Declaration of Competing Interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: A paucity of treatments to prevent delayed cerebral ischemia (DCI) has stymied recovery after aneurysmal subarachnoid hemorrhage (aSAH). Nicardipine has long been recognized as a potent cerebrovascular vasodilator with a history off-label use to prevent vasospasm and DCI. Multiple centers have developed nicardipine prolonged release implants (NPRI) that are directly applied during clip ligation to locally deliver nicardipine throughout the vasospasm window. Here we perform a systematic review and meta-analysis to assess whether NPRI confers protection against DCI and improves functional outcomes after aSAH., Materials and Methods: A systematic search of PubMed, Ovid Embase, and Cochrane databases was performed for studies reporting the use of NPRI after aSAH published after January 1, 1980. We included all studies assessing the association of NPRI with DCI and or functional outcomes. Findings from studies with control arms were analyzed using a random effects model. A separate network meta-analysis was performed, including controlled NPRI studies, single-arm NPRI reports, and the control-arms of modern aSAH randomized clinical trials as additional comparators., Results: The search identified 214 unique citations. Three studies with 284 patients met criteria for the random effects model. The pooled summary odds ratio for the association of NPRI and DCI was 0.21 (95% CI 0.09-0.49, p = 0.0002) with no difference in functional outcomes (OR 1.80, 95% CI 0.63 - 5.16, p = 0.28). 10 studies of 866 patients met criteria for the network meta-analysis. The pooled summary odds ratio for the association of NPRI and DCI was 0.30 (95% CI 0.13-0.89,p = 0.017) with a trend towards improved functional outcomes (OR 1.68, 0.63 - 4.13 95% CI, p = 0.101)., Conclusions: In these meta-analyses, NPRI decreases the incidence of DCI with a non-significant trend towards improvement in functional outcomes. Randomized trials on the role of intrathecal calcium channel blockers are warranted to evaluate these observations in a prospective manner., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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 (SHAP) values were calculated for each patient-derived model to quantify feature importance and interaction effects. Variables with high SHAP 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.

Objective: Cerebral vasospasm and delayed cerebral ischemia (DCI) contribute to poor outcome following subarachnoid hemorrhage (SAH). With the paucity of effective treatments, the authors describe their experience with intrathecal (IT) nicardipine for this indication., Methods: Patients admitted to the Emory University Hospital neuroscience ICU between 2012 and 2017 with nontraumatic SAH, either aneurysmal or idiopathic, were included in the analysis. Using a propensity-score model, this patient cohort was compared to patients in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository who did not receive IT nicardipine. The primary outcome was DCI. Secondary outcomes were long-term functional outcome and adverse events., Results: The analysis included 1351 patients, 422 of whom were diagnosed with cerebral vasospasm and treated with IT nicardipine. When compared with patients with no vasospasm (n = 859), the treated group was significantly younger (mean age 51.1 ± 12.4 years vs 56.7 ± 14.1 years, p < 0.001), had a higher World Federation of Neurosurgical Societies score and modified Fisher grade, and were more likely to undergo clipping of the ruptured aneurysm as compared to endovascular treatment (30.3% vs 11.3%, p < 0.001). Treatment with IT nicardipine decreased the daily mean transcranial Doppler velocities in 77.3% of the treated patients. When compared to patients not receiving IT nicardipine, treatment was not associated with an increased rate of bacterial ventriculitis (3.1% vs 2.7%, p > 0.1), yet higher rates of ventriculoperitoneal shunting were noted (19.9% vs 8.8%, p < 0.01). In a propensity score comparison to the SAHIT database, the odds ratio (OR) to develop DCI with IT nicardipine treatment was 0.61 (95% confidence interval [CI] 0.44-0.84), and the OR to have a favorable functional outcome (modified Rankin Scale score ≤ 2) was 2.17 (95% CI 1.61-2.91)., Conclusions: IT nicardipine was associated with improved outcome and reduced DCI compared with propensity-matched controls. There was an increased need for permanent CSF diversion but no other safety issues. These data should be considered when selecting medications and treatments to study in future randomized controlled clinical trials for SAH.

Pneumonia, wound infections, and sepsis (PWS) are the leading causes of acute mortality after traumatic spinal cord injury (SCI). However, the impact of PWS on neurological and functional outcomes is largely unknown. The present study analyzed participants from the prospective North American Clinical Trials Network (NACTN) registry and the Surgical Timing in Acute SCI Study (STASCIS) for the association between PWS and functional outcome (assessed as Spinal Cord Independence Measure subscores for respiration and indoor ambulation) at 6 months post-injury. Neurological outcome was analyzed as a secondary end-point. Among 1299 participants studied, 180 (14%) developed PWS during the acute admission. Compared with those without PWS, participants with PWS were mostly male (76% vs. 86%; p  = 0.007), or presented with mostly American Spinal Injury Association Impairment Scale (AIS) grade A injury (36% vs. 61%; p  < 0.001). There were no statistical differences between participants with or without PWS with respect to time from injury to surgery, and administration of steroids. Dominance analysis showed injury level, baseline AIS grade, and subject pre-morbid medical status collectively accounted for 77.7% of the predicted variance of PWS. Regression analysis indicated subjects with PWS demonstrated higher odds for respiratory (odds ratio [OR] 3.91, 95% confidence interval [CI]: 1.42-10.79) and ambulatory (OR 3.94, 95% CI: 1.50-10.38) support at 6 month follow-up in adjusted analysis. This study has shown an association between PWS occurring during acute admission and poorer functional outcomes following SCI.

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 (OR disgust : 0.14, 95%CI 0.03-0.65; OR surprise : 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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Differences in clinical outcomes between centers and countries may reflect variation in patient characteristics, diagnostic and therapeutic policies, or quality of care. The purpose of this study was to investigate the presence and magnitude of between-center and between-country differences in outcome after aneurysmal subarachnoid hemorrhage (aSAH)., Methods: The authors analyzed data from 5972 aSAH patients enrolled in randomized clinical trials of 3 different treatments from the Subarachnoid Hemorrhage International Trialists (SAHIT) repository, including data from 179 centers and 20 countries. They used random effects logistic regression adjusted for patient characteristics and timing of aneurysm treatment to estimate between-center and between-country differences in unfavorable outcome, defined as a Glasgow Outcome Scale score of 1-3 (severe disability, vegetative state, or death) or modified Rankin Scale score of 4-6 (moderately severe disability, severe disability, or death) at 3 months. Between-center and between-country differences were quantified with the median odds ratio (MOR), which can be interpreted as the ratio of odds of unfavorable outcome between a typical high-risk and a typical low-risk center or country., Results: The proportion of patients with unfavorable outcome was 27% (n = 1599). The authors found substantial between-center differences (MOR 1.26, 95% CI 1.16-1.52), which could not be explained by patient characteristics and timing of aneurysm treatment (adjusted MOR 1.21, 95% CI 1.11-1.44). They observed no between-country differences (adjusted MOR 1.13, 95% CI 1.00-1.40)., Conclusions: Clinical outcomes after aSAH differ between centers. These differences could not be explained by patient characteristics or timing of aneurysm treatment. Further research is needed to confirm the presence of differences in outcome after aSAH between hospitals in more recent data and to investigate potential causes.

Background Context: Predictors of outcome after surgery for degenerative cervical myelopathy (DCM) have been determined previously through hypothesis-driven multivariate statistical models that rely on a priori knowledge of potential confounders, exclude potentially important variables because of restrictions in model building, cannot include highly collinear variables in the same model, and ignore intrinsic correlations among variables., Purpose: The present study aimed to apply a data-driven approach to identify patient phenotypes that may predict outcomes after surgery for mild DCM., Study Design: This is a principal component analysis of data from two related prospective, multicenter cohort studies., Patient Sample: The study included patients with mild DCM, defined by a modified Japanese Orthopaedic Association score of 15-17, undergoing surgical decompression as part of the AOSpine CSM-NA or CSM-I trials., Outcome Measures: Patient outcomes were evaluated preoperatively at baseline and at 6 months, 1 year, and 2 years after surgery. Quality of life (QOL) was evaluated by the Neck Disability Index (NDI) and Short Form-36 version 2 (SF-36v2). These are both patient self-reported measures that evaluate health-related QOL, with NDI being specific to neck conditions and SF-36v2 being a generic instrument., Materials and Methods: The analysis included 154 patients. A heterogeneous correlation matrix was created using a combination of Pearson, polyserial, and polychoric regressions among 67 variables, which then underwent eigen decomposition. Scores of significant principal components (PCs) (with eigenvalues>1) were included in multivariate logistic regression analyses for three dichotomous outcomes of interest: achievement of the minimum clinically important difference [MCID] in (1) NDI (≤-7.5), (2) SF-36v2 Physical Component Summary (PCS) score (≥5), and (3) SF-36v2 Mental Component Summary (MCS) score (≥5)., Results: Twenty-four significant PCs accounting for 75% of the variance in the data were identified. Two PCs were associated with achievement of the MCID in NDI. The first (PC 1) was dominated by variables related to surgical approach and number of operated levels; the second (PC 21) consisted of variables related to patient demographics, severity and etiology of DCM, comorbid status, and surgical approach. Both PC 1 and PC 21 also correlated with SF-36v2 PCS score, in addition to PC 4, which described patients' physical profile, including gender, height, and weight, as well as comorbid renal disease; PC 6, which received large loadings from variables related to cardiac disease, impaired mobility, and length of surgery and recovery; and PC 9, which harbored large contributions from features of upper limb dysfunction, cardiorespiratory disease, surgical approach, and region. In addition to PC 21, a component profiling patients' socioeconomic status and support systems and degree of physical disability (PC 24) was associated with achievement of the MCID in SF-36 MCS score., Conclusions: Through a data-driven approach, we identified several phenotypes associated with disability and physical and mental health-related QOL. Such data reduction methods may separate patient-, disease-, and treatment-related variables more accurately into clinically meaningful phenotypes that may inform patient care and recruitment into clinical trials., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The course, treatment response, and recovery potential after acute traumatic spinal cord injury (SCI) have been shown to differ depending on the neurological level of injury. There are limited data focused on thoracic-level injuries, however. A cohort of 86 patients from the prospectively maintained North American Clinical Trials Network SCI registry were identified and studied to characterize the patterns of neurological recovery and to determine rates of acute hospital death and pulmonary complications. Regression analyses were used to examine the relationship between timing of surgery and administration of methylprednisolone on neurologic and clinical outcomes. Neurological conversion (≥1 American Spinal Injury Association Impairment Scale [AIS] grade improvement) was poorest for AIS grade A patients; 14.3% converted at last available follow-up (mean eight months). While rates of conversion were more optimistic for AIS-B patients (54.5%) and AIS C injuries (77.8%) at the same time point, none of the AIS grade D patients converted to AIS E. At last available follow-up (mean eight months), the magnitudes of lower motor extremity score (LEMS) change were highest for AIS C injuries (21.9 points), then AIS B (17.7 points), AIS D (16.4 points), and finally AIS A (2.5 points) (p < 0.05). Early surgical intervention (<24 h post-injury) was independently associated with an additional seven points in motor recovery and a 60% decreased incidence of pulmonary events (p < 0.05). Methylprednisolone administration was not an independent predictor of neurological outcome or pulmonary complications. Evaluation of this cohort obtained from a modern multi-center SCI registry provides an update on the natural history, acute death, and incidence of pulmonary complications after traumatic thoracic SCI. Although small sample size limited the extent of analyses possible, early surgical treatment was associated with significantly larger motor recovery and lower rates of pulmonary complications.

Background: 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., Methods: An exploratory subgroup analysis was conducted in the SAHIT (Subarachnoid Hemorrhage International Trialists) data repository to identify predictors of clinical DCI in patients with good-grade aSAH (World Federation of Neurological Surgeons grade I and II) with angiographic vasospasm on admission. Predictors considered include age, sex, systolic blood pressure at presentation, World Federation of Neurological Surgeon grade, Fisher grade, aneurysm size and location, treatment modality, hydrocephalus requiring external ventricular drain insertion, and severity of vasospasm. The predictors were ranked based on dominance analysis with R 2 as fit statistics and assessed in a set of logistic regression analysis models., Results: Four data sets out of 16 studies in the SAHIT database were analyzed, with a total of 4125 patients. One hundred and ninety-one patients (4.6%) had asymptomatic angiographic vasospasm at admission. Of those, 78 patients (40.8%) developed clinical DCI. Univariate analysis showed significant associations between severe vasospasm on admission and development of clinical DCI (odds ratio, 9.5, 95% confidence interval, 2.07-43.50; P = 0.004). None of the studied predictors was associated with the development of clinical DCI on multivariate analysis., Conclusions: Asymptomatic angiographic vasospasm in patients with good-grade aSAH on admission is uncommon. Further studies are needed to identify high-risk patients for the development of DCI in the context of asymptomatic early vasospasm., (Copyright © 2016 Elsevier Inc. All rights reserved.)