Publications by authors named "Adam de Havenon"

96 Publications

Evaluation of Systolic Blood Pressure, Use of Aspirin and Clopidogrel, and Stroke Recurrence in the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial.

JAMA Netw Open 2021 Jun 1;4(6):e2112551. Epub 2021 Jun 1.

Department of Neurology, New York University, New York.

Importance: Elevated systolic blood pressure (SBP) after acute ischemic stroke and transient ischemic attack (TIA) is associated with future stroke risk.

Objective: To explore the association of dual antiplatelet therapy (DAPT) with stroke recurrence among patients with acute ischemic stroke and TIA with or without elevated baseline SBP.

Design, Setting, And Participants: This cohort study performed a post hoc subgroup analysis of the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which was a multicenter trial conducted from 2010 to 2018 at 269 sites in 10 countries in North America, Europe, Australia, and New Zealand. Patients enrolled in POINT with available blood pressure and outcome data were included in this cohort. Statistical analysis was performed from November 2020 to January 2021.

Exposures: Baseline SBP less than 140 mm Hg vs greater than or equal to 140 mm Hg and the interaction term of SBP (<140 mm Hg vs ≥140 mm Hg) × treatment group (aspirin vs DAPT).

Main Outcomes And Measures: The primary outcome was ischemic stroke during 90 days of follow-up. The statistical analysis fit Cox proportional hazards models adjusted for patient age, race, premorbid hypertension, diabetes, and final diagnosis of the qualifying event (stroke vs TIA).

Results: Among 4781 patients in the cohort, the mean (SD) age was 64.6 (13.1) years; 2142 (44.8%) were male individuals, 3487 (72.9%) were White individuals, and 266 (5.6%) had a primary outcome of ischemic stroke during follow-up. There were 946 patients (19.8%) with baseline SBP less than 140 mm Hg and 3835 (80.2%) with SBP greater than or equal to 140 mm Hg. The interaction term (SBP × treatment) was significant (P for interaction = .03). In the subgroup of patients with SBP less than 140 mm Hg, the hazard ratio (HR) of DAPT vs aspirin alone for ischemic stroke was 0.36 (95% CI, 0.18-0.72; P = .004), whereas the HR in the subgroup with SBP greater than or equal to 140 mm Hg was 0.79 (95% CI, 0.60-1.02; P = .08). When evaluating the outcome of ischemic stroke within 7 days of randomization, the interaction term was significant (P for interaction = .02), and the HR for patients with DAPT with SBP less than 140 mm Hg was 0.19 (95% CI, 0.07-0.55; P = .002).

Conclusions And Relevance: In the POINT trial, patients with SBP less than 140 mm Hg at presentation received a greater benefit from 90 days of DAPT than those with higher baseline SBP, particularly for reduction of early ischemic stroke recurrence. Additional research is needed to replicate these findings and potentially test whether mild SBP reduction and DAPT within 12 hours of stroke onset lowers early risk of stroke recurrence.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.12551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178708PMC
June 2021

Lacunar stroke: mechanisms and therapeutic implications.

J Neurol Neurosurg Psychiatry 2021 May 26. Epub 2021 May 26.

Department of Neurology, University of Utah Hospital, Salt Lake City, Utah, USA.

Lacunar stroke is a marker of cerebral small vessel disease and accounts for up to 25% of ischaemic stroke. In this narrative review, we provide an overview of potential lacunar stroke mechanisms and discuss therapeutic implications based on the underlying mechanism. For this paper, we reviewed the literature from important studies (randomised trials, exploratory comparative studies and case series) on lacunar stroke patients with a focus on more recent studies highlighting mechanisms and stroke prevention strategies in patients with lacunar stroke. These studies suggest that lacunar stroke is a heterogeneous disease with various mechanisms, including most commonly lipohyalinosis and less commonly atheromatous disease and cardioembolism, highlighting the importance of a careful review of brain and neurovascular imaging, a cardiac and systemic evaluation. A better understanding of pathomechanisms of neurological deterioration may lead to investigating the utility of novel treatment strategies and optimisation of short-term antithrombotic treatment strategies to reduce the risk of neurological deterioration and prevent long-term disability in patients with lacunar stroke.
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http://dx.doi.org/10.1136/jnnp-2021-326308DOI Listing
May 2021

Blood Pressure Management After Endovascular Therapy: An Ongoing Debate.

Stroke 2021 Jun 18;52(6):e263-e265. Epub 2021 May 18.

The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia (C.S.A.).

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http://dx.doi.org/10.1161/STROKEAHA.121.034995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191365PMC
June 2021

Predicting 90-Day Outcome After Thrombectomy: Baseline-Adjusted 24-Hour NIHSS Is More Powerful Than NIHSS Score Change.

Stroke 2021 May 18:STROKEAHA120032487. Epub 2021 May 18.

Department of Neurology and Rehabilitation Medicine, University of Cincinnati, OH (P.K.).

Background And Purpose: The National Institutes of Health Stroke Scale (NIHSS) measured at an early time point is an appealing surrogate marker for long-term functional outcome of stroke patients treated with endovascular therapy. However, definitions and analytical methods for an early NIHSS-based outcome measure that optimize power and precision in clinical studies are not well-established.

Methods: In this post-hoc analysis of our prospective observational study that enrolled endovascular therapy-treated patients at 12 comprehensive stroke centers across the US, we compared the ability of 24-hour NIHSS, ΔNIHSS (baseline minus 24-hour NIHSS), and percentage change (NIHSS×100/baseline NIHSS), analyzed as continuous and dichotomous measures, to predict 90-day modified Rankin Scale (mRS) using logistic regression (adjusted for age, baseline NIHSS, glucose, hypertension, Alberta Stroke Program Early CT Score, time to recanalization, recanalization status, and intravenous thrombolysis) and Spearman ρ.

Results: Of 485 patients in the BEST (Blood Pressure After Endovascular Stroke Therapy) cohort, 446 (92%) with 90-day follow-up data were included. An absolute 24-hour NIHSS, adjusted for baseline in multivariable modeling, had the highest predictive power of all definitions evaluated (aR 0.368 and adjusted odds ratio 0.79 [0.75-0.84], <0.001 for mRS score 0-2; aR 0.444 and adjusted odds ratio 0.84 [0.8-0.86] for ordinal mRS). For predicting mRS score of 0-2 with a cut point, the second most efficient approach, the optimal threshold for 24-hour NIHSS score was ≤7 (sensitivity 80.1%, specificity 80.4%; adjusted odds ratio 12.5 [7.14-20], <0.001), followed by percent change in NIHSS (sensitivity 79%, specificity 58.5%; adjusted odds ratio 4.55 [2.85-7.69], <0.001).

Conclusions: Twenty-four-hour NIHSS, adjusted for baseline, was the strongest predictor of both dichotomous and ordinal 90-day mRS outcomes for endovascular therapy-treated patients. A dichotomous 24-hour NIHSS score of ≤7 was the second-best predictor. Although ΔNIHSS, continuous and dichotomized at ≥4, predicted 90-day outcomes, absolute 24-hour NIHSS definitions performed better.
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http://dx.doi.org/10.1161/STROKEAHA.120.032487DOI Listing
May 2021

Characteristics and Outcomes Among US Patients Hospitalized for Ischemic Stroke Before vs During the COVID-19 Pandemic.

JAMA Netw Open 2021 05 3;4(5):e2110314. Epub 2021 May 3.

Department of Neurology, University of Utah, Salt Lake City.

Importance: After the emergence of COVID-19, studies reported a decrease in hospitalizations of patients with ischemic stroke (IS), but there are little to no data regarding hospitalizations for the remainder of 2020, including outcome data from a large cohort of patients with IS and comorbid COVID-19.

Objective: To assess hospital discharge rates, demographic factors, and outcomes of hospitalization associated with the COVID-19 pandemic among US patients with IS before vs during the COVID-19 pandemic.

Design, Setting, And Participants: This retrospective cohort study used data from the Vizient Clinical Data Base on 324 013 patients with IS at 478 nonfederal hospitals in 43 US states between January 1, 2019, and December 31, 2020. Patients were eligible if they were admitted to the hospital on a nonelective basis and were not receiving hospice care at the time of admission. A total of 41 166 discharged between January and March 2020 were excluded from the analysis because they had unreliable data on COVID-19 status, leaving 282 847 patients for the study.

Exposure: Ischemic stroke and laboratory-confirmed COVID-19.

Main Outcomes And Measures: Monthly counts of discharges among patients with IS in 2020. Demographic characteristics and outcomes, including in-hospital death, among patients with IS who were discharged in 2019 (control group) were compared with those of patients with IS with or without comorbid COVID-19 (COVID-19 and non-COVID-19 groups, respectively) who were discharged between April and December 2020.

Results: Of the 282 847 patients included in the study, 165 912 (50.7% male; 63.4% White; 26.3% aged ≥80 years) were allocated to the control group; 111 418 of 116 935 patients (95.3%; 51.9% male; 62.8% White; 24.6% aged ≥80 years) were allocated to the non-COVID-19 group and 5517 of 116 935 patients (4.7%; 58.0% male; 42.5% White; 21.3% aged ≥80 years) to the COVID-19 group. A mean (SD) of 13 846 (553) discharges per month among patients with IS was reported in 2019. Discharges began decreasing in February 2020, reaching a low of 10 846 patients in April 2020 before returning to a prepandemic level of 13 639 patients by July 2020. A mean (SD) of 13 492 (554) discharges per month was recorded for the remainder of 2020. Black and Hispanic patients accounted for 21.4% and 7.0% of IS discharges in 2019, respectively, but accounted for 27.5% and 16.0% of those discharged with IS and comorbid COVID-19 in 2020. Compared with patients in the control and non-COVID-19 groups, those in the COVID-19 group were less likely to smoke (16.0% vs 17.2% vs 6.4%, respectively) and to have hypertension (73.0% vs 73.1% vs 68.2%) or dyslipidemia (61.2% vs 63.2% vs 56.6%) but were more likely to have diabetes (39.8% vs 40.5% vs 53.0%), obesity (16.2% vs 18.4% vs 24.5%), acute coronary syndrome (8.0% vs 9.2% vs 15.8%), or pulmonary embolus (1.9% vs 2.4% vs 6.8%) and to require intubation (11.3% vs 12.3% vs 37.6%). After adjusting for baseline factors, patients with IS and COVID-19 were more likely to die in the hospital than were patients with IS in 2019 (adjusted odds ratio, 5.17; 95% CI, 4.83-5.53; National Institutes of Health Stroke Scale adjusted odds ratio, 3.57; 95% CI, 3.15-4.05).

Conclusions And Relevance: In this cohort study, after the emergence of COVID-19, hospital discharges of patients with IS decreased in the US but returned to prepandemic levels by July 2020. Among patients with IS between April and December 2020, comorbid COVID-19 was relatively common, particularly among Black and Hispanic populations, and morbidity was high.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.10314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129817PMC
May 2021

The association between transthoracic echocardiogram parameters and white matter hyperintensities.

Clin Neurol Neurosurg 2021 Jul 4;206:106672. Epub 2021 May 4.

Department of Neurology, University of Utah, Salt Lake City, UT 84132, USA. Electronic address:

Objective: Identify abnormal cardiac chamber size and hemodynamic parameters on transthoracic echocardiogram (TTE) as predictors of advancing cerebral small vessel disease (CSVD) on brain magnetic resonance imaging (MRI).

Materials And Methods: A retrospective chart review of adults with a brain MRI and a 2-dimensional TTE was performed. WMH measured by the Fazekas score served as the primary outcome. We fit multivariate ordinal logistic regression models to the Fazekas score with the individual predictors of the TTE measurements and adjusted for potential confounders.

Results: 132 individuals were included. Cardiac functional markers were not significant, including tricuspid annular plane systolic excursion (p = 0.818), right ventricular ejection fraction (p = 0.818) and left ventricular ejection fraction (p = 0.673). Cardiac structural markers included right atrial area (p = 0.247), right ventricular internal diameter (RVID, p = 0.020) and left atrial area (LAA, p = 0.041). RVID and LAA were identified as being predictors, although the direction of the association suggested that normal values resulted in more WMH. Analysis of isolated DWM or PVWM Fazekas scores were not associated with cardiac structure or function.

Conclusions: In our study, we found that normal LAA and RVID values were associated with an increased degree of WMH on MRI. This finding may represent earlier identification of WMH prior to TTE cardiac changes. Future studies are needed for more robust quantitative comparison as well as evaluation prospectively of the association between cardiac chamber sizes and development of WMH.
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http://dx.doi.org/10.1016/j.clineuro.2021.106672DOI Listing
July 2021

Carotid Stenosis and Recurrent Ischemic Stroke: A Post-Hoc Analysis of the POINT Trial.

Stroke 2021 May 4:STROKEAHA121034089. Epub 2021 May 4.

Department of Neurology and Department of Psychiatry, University of Massachusetts Medical Center, Worcester (N.H.).

Background And Purpose: Randomized trials demonstrated the benefit of dual antiplatelet therapy in patients with minor ischemic stroke or high-risk transient ischemic attack. We sought to determine whether the presence of carotid stenosis was associated with increased risk of ischemic stroke and whether the addition of clopidogrel to aspirin was associated with more benefit in patients with versus without carotid stenosis.

Methods: This is a post-hoc analysis of the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) that randomized patients with minor ischemic stroke or high-risk transient ischemic attack within 12 hours from last known normal to receive either clopidogrel plus aspirin or aspirin alone. The primary predictor was the presence of ≥50% stenosis in either cervical internal carotid artery. The primary outcome was ischemic stroke. We built Cox regression models to determine the association between carotid stenosis and ischemic stroke and whether the effect of clopidogrel was modified by ≥50% carotid stenosis.

Results: Among 4881 patients enrolled POINT, 3941 patients met the inclusion criteria. In adjusted models, ≥50% carotid stenosis was associated with ischemic stroke risk (hazard ratio, 2.45 [95% CI, 1.68-3.57], <0.001). The effect of clopidogrel (versus placebo) on ischemic stroke risk was not significantly different in patients with <50% carotid stenosis (adjusted hazard ratio, 0.68 [95% CI, 0.50-0.93], =0.014) versus those with ≥50% carotid stenosis (adjusted hazard ratio, 0.88 [95% CI, 0.45-1.72], =0.703), value for interaction=0.573.

Conclusions: The presence of carotid stenosis was associated with increased risk of ischemic stroke during follow-up. The effect of added clopidogrel was not significantly different in patients with versus without carotid stenosis.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03354429.
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http://dx.doi.org/10.1161/STROKEAHA.121.034089DOI Listing
May 2021

Endovascular therapy with or without intravenous thrombolysis in acute stroke with tandem occlusion.

J Neurointerv Surg 2021 Apr 28. Epub 2021 Apr 28.

Department of Diagnostic and Therapeutic Neuroradiology, Université de Lorraine, CHRU-Nancy, Nancy, France

Background: Endovascular therapy (EVT) is effective and safe in patients with tandem occlusion. The benefit of intravenous thrombolysis (IVT) prior to EVT in acute tandem occlusion is debatable.

Objective: To compare EVT alone with EVT plus IVT in patients with acute ischemic stroke due to anterior circulation tandem occlusions.

Methods: This is an individual patient pooled analysis of the Thrombectomy In TANdem lesions (TITAN) and Endovascular Treatment in Ischemic Stroke (ETIS) Registries. Patients were divided into two groups based on prior IVT treatment: (1) IVT+ group, which included patients who received IVT prior to EVT, (2) IVT- group, which included patients who did not receive IVT prior to EVT. Propensity score (inverse probability of treatment weighting (IPTW)) was used to reduce baseline between-group differences. The primary outcome was favorable outcome-that is, modified Rankin Scale (mRS) score 0 to 2 at 90 days.

Results: Overall, 602 consecutive patients with an acute stroke with tandem occlusion were included (380 and 222 in the bridging therapy and EVT alone groups, respectively). Onset to imaging time was shorter in the IVT+ group (median 103 vs 140 min). In contrast, imaging to puncture time was longer in the IVT+ group (median 107 vs 91 min). In IPTW analysis, the IVT+ group had higher odds of favorable outcome, excellent outcome (90-day mRS score 0-1), and successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b/3 at the end of EVT). There was no difference in the risk of significant hemorrhagic complications between groups. In secondary analysis of patients treated with acute cervical internal carotid artery stenting, bridging therapy was associated with higher odds of favorable outcome and lower odds of mortality at 90 days.

Conclusions: Our results suggest that bridging therapy in patients with acute ischemic stroke due to anterior tandem occlusion is safe and may improve functional outcome, even in the setting of acute cervical internal carotid artery stenting during EVT.
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http://dx.doi.org/10.1136/neurintsurg-2020-017202DOI Listing
April 2021

Ischaemic stroke on anticoagulation therapy and early recurrence in acute cardioembolic stroke: the IAC study.

J Neurol Neurosurg Psychiatry 2021 Apr 26. Epub 2021 Apr 26.

Neuroscience Institute, Spectrum Health, Grand Rapids, Michigan, USA.

Background And Purpose: A subset of ischaemic stroke patients with atrial fibrillation (AF) have ischaemic stroke despite anticoagulation. We sought to determine the association between prestroke anticoagulant therapy and recurrent ischaemic events and symptomatic intracranial haemorrhage (sICH).

Methods: We included consecutive patients with acute ischaemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study from eight comprehensive stroke centres in the USA. We compared recurrent ischaemic events and delayed sICH risk using adjusted Cox regression analyses between patients who were prescribed anticoagulation (ACp) versus patients who were naïve to anticoagulation therapy prior to the ischaemic stroke (anticoagulation naïve).

Results: Among 2084 patients in IAC, 1518 had prior anticoagulation status recorded and were followed for 90 days. In adjusted Cox hazard models, ACp was associated with some evidence of a higher risk higher risk of 90-day recurrent ischaemic events only in the fully adjusted model (adjusted HR 1.50, 95% CI 0.99 to 2.28, p=0.058) but not increased risk of 90-day sICH (adjusted HR 1.08, 95% CI 0.46 to 2.51, p=0.862). In addition, switching anticoagulation class was not associated with reduced risk of recurrent ischaemic events (adjusted HR 0.41, 95% CI 0.12 to 1.33, p=0.136) nor sICH (adjusted HR 1.47, 95% CI 0.29 to 7.50, p=0.641).

Conclusion: AF patients with ischaemic stroke despite anticoagulation may have higher recurrent ischaemic event risk compared with anticoagulation-naïve patients. This suggests differing underlying pathomechanisms requiring different stroke prevention measures and identifying these mechanisms may improve secondary prevention strategies.
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http://dx.doi.org/10.1136/jnnp-2021-326166DOI Listing
April 2021

Association of Preeclampsia With Incident Stroke in Later Life Among Women in the Framingham Heart Study.

JAMA Netw Open 2021 Apr 1;4(4):e215077. Epub 2021 Apr 1.

Department of Obstetrics and Gynecology, University of Utah, Salt Lake City.

Importance: Contemporary research suggests an association between preeclampsia and later-life stroke among women. To our knowledge, no research to date has accounted for the time-varying nature of shared risk factors for preeclampsia and later-life stroke incidence.

Objective: To assess the relative risk of incident stroke in later life among women with and without a history of preeclampsia after accounting for time-varying covariates.

Design, Setting, And Participants: This population-based cohort study was a secondary analysis of data from the Framingham Heart Study, which was conducted from 1948 to 2016. Women were included in the analysis if they were stroke free at enrollment and had a minimum of 3 study visits and 1 pregnancy before menopause, hysterectomy, or age 45 years. Data on vascular risk factors, history of preeclampsia, and stroke incidence were collected biannually. Participants were followed up until incident stroke or censorship from the study. Marginal structural models were used to evaluate the relative risk of incident stroke among participants with and without a history of preeclampsia after accounting for time-varying covariates. Data were analyzed from May 2019 to December 2020.

Exposures: Presence or absence of preeclampsia among women with 1 or more pregnancies.

Main Outcomes And Measures: Incident stroke in later life.

Results: A total of 1435 women (mean [SD] age, 44.4 [7.7] years at the beginning of the study; 100% White) with 41 422 person-years of follow-up were included in the analytic sample. Of those, 169 women had a history of preeclampsia, and 231 women experienced strokes during follow-up. At baseline, women with preeclampsia were more likely to be younger, to be receiving cholesterol-lowering medications, to have lower cholesterol and higher diastolic blood pressure, and to currently smoke. The association between preeclampsia and stroke in the marginal structural model was only evident when adjustment was made for all vascular risk factors over the life course, which indicated that women with a history of preeclampsia had a higher risk of stroke in later life compared with women without a history of preeclampsia (relative risk, 3.79; 95% CI, 1.24-11.60).

Conclusions And Relevance: The findings of this cohort study suggest that preeclampsia may be a risk factor for later-life stroke among women after adjustment for time-varying vascular and demographic factors. Future research is warranted to fully explore the mediation of this association by midlife vascular risk factors.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.5077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076961PMC
April 2021

Impact of COVID-19 on the hospitalization, treatment, and outcomes of intracerebral and subarachnoid hemorrhage in the United States.

PLoS One 2021 14;16(4):e0248728. Epub 2021 Apr 14.

Department of Neurology, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah, United States of America.

Objective: To examine the outcomes of adult patients with spontaneous intracranial and subarachnoid hemorrhage diagnosed with comorbid COVID-19 infection in a large, geographically diverse cohort.

Methods: We performed a retrospective analysis using the Vizient Clinical Data Base. We separately compared two cohorts of patients with COVID-19 admitted April 1-October 31, 2020-patients with intracerebral hemorrhage (ICH) and those with subarachnoid hemorrhage (SAH)-with control patients with ICH or SAH who did not have COVID-19 admitted at the same hospitals in 2019. The primary outcome was in-hospital death. Favorable discharge and length of hospital and intensive-care stay were the secondary outcomes. We fit multivariate mixed-effects logistic regression models to our outcomes.

Results: There were 559 ICH-COVID patients and 23,378 ICH controls from 194 hospitals. In the ICH-COVID cohort versus controls, there was a significantly higher proportion of Hispanic patients (24.5% vs. 8.9%), Black patients (23.3% vs. 20.9%), nonsmokers (11.5% vs. 3.2%), obesity (31.3% vs. 13.5%), and diabetes (43.4% vs. 28.5%), and patients had a longer hospital stay (21.6 vs. 10.5 days), a longer intensive-care stay (16.5 vs. 6.0 days), and a higher in-hospital death rate (46.5% vs. 18.0%). Patients with ICH-COVID had an adjusted odds ratio (aOR) of 2.43 [1.96-3.00] for the outcome of death and an aOR of 0.55 [0.44-0.68] for favorable discharge. There were 212 SAH-COVID patients and 5,029 controls from 119 hospitals. The hospital (26.9 vs. 13.4 days) and intensive-care (21.9 vs. 9.6 days) length of stays and in-hospital death rate (42.9% vs. 14.8%) were higher in the SAH-COVID cohort compared with controls. Patients with SAH-COVID had an aOR of 1.81 [1.26-2.59] for an outcome of death and an aOR of 0.54 [0.37-0.78] for favorable discharge.

Conclusions: Patients with spontaneous ICH or SAH and comorbid COVID infection were more likely to be a racial or ethnic minority, diabetic, and obese and to have higher rates of death and longer hospital length of stay when compared with controls.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248728PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046225PMC
May 2021

White Matter Hyperintensity and Cardiovascular Disease Outcomes in the SPRINT MIND Trial.

J Stroke Cerebrovasc Dis 2021 Jun 3;30(6):105764. Epub 2021 Apr 3.

Departments of Neurology: University of Utah, MUSC, Johns Hopkins University, University of Chicago, MGH, 175 N. Medical Dr, Salt Lake City, UT 84132, USA. Electronic address:

Background: The Systolic Blood Pressure Intervention Trial (SPRINT) randomized patients to a goal systolic blood pressure (SBP) <120 mm Hg vs. <140 mm Hg. In a subset of participants, the SPRINT MIND ancillary study performed a baseline MRI and measured white matter hyperintensity volume (WMHv). In this secondary analysis, we evaluated the association between baseline WMHv and cardiovascular events during follow-up in the overall sample.

Methods: The primary outcome was the same as SPRINT, a composite of stroke, myocardial infarction, acute coronary syndrome, decompensated congestive heart failure, or cardiovascular death. We fit Cox models to the primary outcome and report adjusted hazard ratios (HR) for log-transformed WMHv and quartiles of WMHv.

Results: Among 717 participants, the median (IQR) baseline WMHv was 1.62 (0.66-3.98) mL. The primary outcome occurred in 51/719 (7.1%). The median WMHv was higher in patients with the primary outcome (3.40 mL versus 1.56 mL, p < 0.001). In adjusted models, WMHv as a log-transformed continuous variable was associated with the primary outcome (HR 1.44, 95% CI 1.15-1.80). The highest quartile of WMHv, compared to the lowest, was also independently associated with the primary outcome (HR 3.21, 95% CI 1.27-8.13).

Conclusions: We found that the baseline volume of WMH was associated with future CVD risk in SPRINT MIND. Prospective clinical trials with larger sample sizes than the current study are needed to determine whether intensive BP lowering can reduce the high cardiovascular risk in patients with WMH.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107132PMC
June 2021

Toxic Metabolic Encephalopathy in Hospitalized Patients with COVID-19.

Neurocrit Care 2021 Mar 16. Epub 2021 Mar 16.

Department of Neurology, New York University Grossman School of Medicine, New York, NY, USA.

Background: Toxic metabolic encephalopathy (TME) has been reported in 7-31% of hospitalized patients with coronavirus disease 2019 (COVID-19); however, some reports include sedation-related delirium and few data exist on the etiology of TME. We aimed to identify the prevalence, etiologies, and mortality rates associated with TME in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients.

Methods: We conducted a retrospective, multicenter, observational cohort study among patients with reverse transcriptase-polymerase chain reaction-confirmed SARS-CoV-2 infection hospitalized at four New York City hospitals in the same health network between March 1, 2020, and May 20, 2020. TME was diagnosed in patients with altered mental status off sedation or after an adequate sedation washout. Patients with structural brain disease, seizures, or primary neurological diagnoses were excluded. The coprimary outcomes were the prevalence of TME stratified by etiology and in-hospital mortality (excluding comfort care only patients) assessed by using a multivariable time-dependent Cox proportional hazards models with adjustment for age, race, sex, intubation, intensive care unit requirement, Sequential Organ Failure Assessment scores, hospital location, and date of admission.

Results: Among 4491 patients with COVID-19, 559 (12%) were diagnosed with TME, of whom 435 of 559 (78%) developed encephalopathy immediately prior to hospital admission. The most common etiologies were septic encephalopathy (n = 247 of 559 [62%]), hypoxic-ischemic encephalopathy (HIE) (n = 331 of 559 [59%]), and uremia (n = 156 of 559 [28%]). Multiple etiologies were present in 435 (78%) patients. Compared with those without TME (n = 3932), patients with TME were older (76 vs. 62 years), had dementia (27% vs. 3%) or psychiatric history (20% vs. 10%), were more often intubated (37% vs. 20%), had a longer hospital length of stay (7.9 vs. 6.0 days), and were less often discharged home (25% vs. 66% [all P < 0.001]). Excluding comfort care patients (n = 267 of 4491 [6%]) and after adjustment for confounders, TME remained associated with increased risk of in-hospital death (n = 128 of 425 [30%] patients with TME died, compared with n = 600 of 3799 [16%] patients without TME; adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.02-1.52, P = 0.031), and TME due to hypoxemia conferred the highest risk (n = 97 of 233 [42%] patients with HIE died, compared with n = 631 of 3991 [16%] patients without HIE; aHR 1.56, 95% CI 1.21-2.00, P = 0.001).

Conclusions: TME occurred in one in eight hospitalized patients with COVID-19, was typically multifactorial, and was most often due to hypoxemia, sepsis, and uremia. After we adjustment for confounding factors, TME was associated with a 24% increased risk of in-hospital mortality.
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http://dx.doi.org/10.1007/s12028-021-01220-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962078PMC
March 2021

Endothelial Shear Stress and Platelet FcγRIIa Expression in Intracranial Atherosclerotic Disease.

Front Neurol 2021 25;12:646309. Epub 2021 Feb 25.

Department of Medicine, Cardiovascular Research Institute, University of Vermont, Burlington, VT, United States.

Intracranial atherosclerotic disease (ICAD) has been characterized by the degree of arterial stenosis and downstream hypoperfusion, yet microscopic derangements of endothelial shear stress at the luminal wall may be key determinants of plaque growth, vascular remodeling and thrombosis that culminate in recurrent stroke. Platelet interactions have similarly been a principal focus of treatment, however, the mechanistic basis of anti-platelet strategies is largely extrapolated rather than directly investigated in ICAD. Platelet FcγRIIa expression has been identified as a potent risk factor in cardiovascular disease, as elevated expression markedly increases the risk of recurrent events. Differential activation of the platelet FcγRIIa receptor may also explain the variable response of individual patients to anti-platelet medications. We review existing data on endothelial shear stress and potential interactions with the platelet FcγRIIa receptor that may alter the evolving impact of ICAD, based on local pathophysiology at the site of arterial stenosis. Current methods for quantification of endothelial shear stress and platelet activation are described, including tools that may be readily adapted to the clinical realm for further understanding of ICAD.
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http://dx.doi.org/10.3389/fneur.2021.646309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947292PMC
February 2021

Five-Year Trends in Payments for Neurologist-Prescribed Drugs in Medicare Part D.

Neurology 2021 04 10;96(16):e2132-e2137. Epub 2021 Mar 10.

From the University of Utah (A.d.H., A.D., S.D., P.W., N.S.), Salt Lake City; University of Michigan (B.C.), Ann Arbor; Boston University (J.N.), MA; Emory University (G.J.E.), Atlanta, GA; American Academy of Neurology (B.M.), Minneapolis, MN; and University of Colorado (K.V.N.), Denver.

Objective: To determine whether there was an increase in payments for neurologist-prescribed drugs, we performed a retrospective analysis of prescription claims in the Medicare Part D Prescriber Public Use Files from 2013 to 2017.

Methods: We included claims prescribed by providers with the taxonomy "neurology" and included drugs present in all 5 years. Drugs were designated in 2013 as generic (GEN), brand name only (BNO), and brand name prescribed even though a generic equivalent is available (BNGE). To observe payment trends, the percentage change in the per claim payment was compared between drug classes.

Results: We included 520 drugs, of which 322 were GEN, 61 were BNO, and 137 were BNGE, representing 90,716,536 claims and generating payments of $26,654,750,720. While the number of claims from 2013 to 2017 increased only 7.6%, the total payment increased 50.4%. Adjusted for inflation, claim payments for GEN drug increased 0.6%, compared to significant increases in BNO and BNGE drugs of 42.4% and 45.0% ( < 0.001). The percentage of overall GEN claims increased from 81.9% to 88.0%, BNO increased from 4.9% to 6.2%, and BNGE decreased from 13.3% to 5.8%. Neuroimmunology/multiple sclerosis drugs represented >50% of the total payments despite being only 4.3% of claims.

Conclusions: Payments for neurologist-prescribed brand name, but not generic, drugs in Medicare Part D increased consistently and well above inflation from 2013 to 2017. Unless the overall trend stabilizes or is reversed or high cost-to-claim drugs are addressed, this trend will place an increasing burden on the neurologic Medicare budget.
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http://dx.doi.org/10.1212/WNL.0000000000011712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166447PMC
April 2021

Magnitude of blood pressure change and clinical outcomes after thrombectomy in stroke caused by large artery occlusion.

Eur J Neurol 2021 Jun 19;28(6):1922-1930. Epub 2021 Mar 19.

Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Background: Extremes of both high and low systolic blood pressure (SBP) after mechanical thrombectomy (MT) in large artery occlusion stroke are known predictors of unfavorable outcome. However, the effect of SBP change (∆SBP) during the first 24 h on thrombectomy outcomes remains unclear. We aimed to investigate the association between ∆SBP at different time intervals and thrombectomy outcomes.

Methods: We analyzed MT-treated patients registered in the SITS International Stroke Thrombectomy Registry from January 1, 2014 to September 3, 2019. Primary outcome was 3-month unfavorable outcome (modified Rankin scale scores 3-6). We defined ∆SBP as the mean SBP of a given time interval after MT (0-2, 2-4, 4-12, 12-24 h) minus admission SBP. Multivariable mixed logistic regression models were used to adjust for known confounders and center as random effect. Subgroup analyses were included to contrast specific subpopulations. Restricted cubic splines were used to model the associations.

Results: The study population consisted of 5835 patients (mean age 70 years, 51% male, median NIHSS 16). Mean ∆SBP was -12.3, -15.7, -17.2, and -16.9 mmHg for the time intervals 0-2, 2-4, 4-12 h, and 12-24 h, respectively. Higher ∆SBP was associated with unfavorable outcome at 0-2 h (odds ratio 1.065, 95% confidence interval 1.014-1.118), 2-4 h (1.140, 1.081-1.203), 4-12 h (1.145, 1.087-1.203), and 12-24 h (1.145, 1.089-1.203), for every increase of 10 mmHg. Restricted cubic spline models suggested that increasing ∆SBP was associated with unfavorable outcome, with higher values showing increased risk of unfavorable outcome.

Conclusion: SBP increase after thrombectomy in large artery occlusion stroke is associated with poor functional outcome.
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http://dx.doi.org/10.1111/ene.14807DOI Listing
June 2021

Predicting neuroimaging eligibility for extended-window endovascular thrombectomy.

J Neurosurg 2021 Feb 26:1-5. Epub 2021 Feb 26.

5Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah.

Objective: Endovascular thrombectomy (EVT) and tissue plasminogen activator (tPA) are effective ischemic stroke treatments in the initial treatment window. In the extended treatment window, these treatments may offer benefit, but CT and MR perfusion may be necessary to determine patient eligibility. Many hospitals do not have access to advanced imaging tools or EVT capability, and further patient care would require transfer to a facility with these capabilities. To assist transfer decisions, the authors developed risk indices that could identify patients eligible for extended-window EVT or tPA.

Methods: The authors retrospectively identified stroke patients who had concurrent CTA and perfusion and evaluated three potential outcomes that would suggest a benefit from patient transfer. The first outcome was large-vessel occlusion (LVO) and target mismatch (TM) in patients 5-23 hours from last known normal (LKN). The second outcome was TM in patients 5-15 hours from LKN with known LVO. The third outcome was TM in patients 4.5-12 hours from LKN. The authors created multivariable models using backward stepping with an α-error criterion of 0.05 and assessed them using C statistics.

Results: The final predictors included the National Institutes of Health Stroke Scale (NIHSS), the Alberta Stroke Program Early CT Score (ASPECTS), and age. The prediction of the first outcome had a C statistic of 0.71 (n = 145), the second outcome had a C statistic of 0.85 (n = 56), and the third outcome had a C statistic of 0.86 (n = 54). With 1 point given for each predictor at different cutoffs, a score of 3 points had probabilities of true positive of 80%, 90%, and 94% for the first, second, and third outcomes, respectively.

Conclusions: Despite the limited sample size, compared with perfusion-based examinations, the clinical variables identified in this study accurately predicted which stroke patients would have salvageable penumbra (C statistic 71%-86%) in a range of clinical scenarios and treatment cutoffs. This prediction improved (C statistic 85%-86%) when utilized in patients with confirmed LVO or a less stringent tissue mismatch (TM < 1.2) cutoff. Larger patient registries should be used to validate and improve the predictive ability of these models.
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http://dx.doi.org/10.3171/2020.8.JNS20386DOI Listing
February 2021

Using Ultrasound and Inflammation to Improve Prediction of Ischemic Stroke: A Secondary Analysis of the Multi-Ethnic Study of Atherosclerosis.

Cerebrovasc Dis Extra 2021 18;11(1):37-43. Epub 2021 Feb 18.

Department of Neurology, University of Utah, Salt Lake City, Utah, USA.

Introduction: Current ischemic stroke risk prediction is primarily based on clinical factors, rather than imaging or laboratory markers. We examined the relationship between baseline ultrasound and inflammation measurements and subsequent primary ischemic stroke risk.

Methods: In this secondary analysis of the Multi-Ethnic Study of Atherosclerosis (MESA), the primary outcome is the incident ischemic stroke during follow-up. The predictor variables are 9 carotid ultrasound-derived measurements and 6 serum inflammation measurements from the baseline study visit. We fit Cox regression models to the outcome of ischemic stroke. The baseline model included patient age, hypertension, diabetes, total cholesterol, smoking, and systolic blood pressure. Goodness-of-fit statistics were assessed to compare the baseline model to a model with ultrasound and inflammation predictor variables that remained significant when added to the baseline model.

Results: We included 5,918 participants. The primary outcome of ischemic stroke was seen in 105 patients with a mean follow-up time of 7.7 years. In the Cox models, we found that carotid distensibility (CD), carotid stenosis (CS), and serum interleukin-6 (IL-6) were associated with incident stroke. Adding tertiles of CD, IL-6, and categories of CS to a baseline model that included traditional clinical vascular risk factors resulted in a better model fit than traditional risk factors alone as indicated by goodness-of-fit statistics.

Conclusions: In a multiethnic cohort of patients without cerebrovascular disease at baseline, we found that CD, CS, and IL-6 helped predict the occurrence of primary ischemic stroke. Future research could evaluate if these basic ultrasound and serum measurements have implications for primary prevention efforts or clinical trial inclusion criteria.
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http://dx.doi.org/10.1159/000514373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989729PMC
June 2021

Optimal Carotid Plaque Features on Computed Tomography Angiography Associated With Ischemic Stroke.

J Am Heart Assoc 2021 Feb 15;10(5):e019462. Epub 2021 Feb 15.

Department of RadiologyUtah Center for Advanced Imaging Research Salt Lake City UT.

Background Stenosis has historically been the major factor used to determine carotid stroke sources. Recent evidence suggests that specific plaque features detected on imaging may be more highly associated with ischemic stroke than stenosis. We sought to determine computed tomography angiography (CTA) imaging features of carotid plaque that optimally discriminate ipsilateral stroke sources. Methods and Results In this institutional review board-approved retrospective cross-sectional study, 494 ipsilateral carotid CTA-brain magnetic resonance imaging pairs were available for analysis after excluding patients with alternative stroke sources. Carotid CTA and clinical markers were recorded, a multivariable Poisson regression model was fitted, and backward elimination was performed with a 2-sided threshold of <0.10. Discriminatory value was determined using receiver operating characteristic analysis, area under the curve, and bootstrap validation. The final CTA carotid-source stroke prediction model included intraluminal thrombus (prevalence ratio, 2.8 [<0.001]; 95% CI, 1.6-4.9), maximum soft plaque thickness (prevalence ratio, 1.2 [<0.001]; 95% CI, 1.1-1.4), and the rim sign (prevalence ratio, 2.0 [=0.007]; 95% CI, 1.2-3.3). The final discriminatory value (area under the curve=78.3%) was higher than intraluminal thrombus (56.4%, <0.001), maximum soft plaque thickness (76.4%, =0.007), or rim sign alone (69.9%, =0.001). Furthermore, NASCET (North American Symptomatic Carotid Endarterectomy Trial) stenosis categories (cutoffs of 50% and 70%) had lower stroke discrimination (area under the curve=67.4%, <0.001). Conclusions Optimal discrimination of ipsilateral carotid sources of stroke requires information on intraluminal thrombus, maximum soft plaque thickness, and the rim sign. These results argue against the sole use of carotid stenosis to determine stroke sources on CTA, and instead suggest these alternative markers may better diagnose vulnerable carotid plaque and guide treatment decisions.
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http://dx.doi.org/10.1161/JAHA.120.019462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174260PMC
February 2021

Impaired Distal Perfusion Predicts Length of Hospital Stay in Patients with Symptomatic Middle Cerebral Artery Stenosis.

J Neuroimaging 2021 05 10;31(3):475-479. Epub 2021 Feb 10.

Department of Neurology, University of California at Los Angeles, Los Angeles, CA.

Background And Purpose: Perfusion imaging can risk stratify patients with symptomatic intracranial stenosis. We aim to determine the association between perfusion delay and length of hospital stay (LOS) in symptomatic middle cerebral artery (MCA) stenosis patients.

Methods: This is a retrospective study of consecutive patients admitted to a comprehensive stroke center over 5 years with ischemic stroke or transient ischemic attack (TIA) within 7 days of symptom onset due to MCA stenosis (50-99%) and underwent perfusion imaging. Patients were divided into three groups: mismatch volume ≥ 15 cc based on T max > 6 second delay, T max 4-6 second delay, and <4 second delay. The outcome was LOS, both as a continuous variable and categorical (≥7 days [prolonged LOS] vs. <7 days). We used adjusted regression analyses to determine the association between perfusion categories and LOS.

Results: One hundred and seventy eight of 194 patients met the inclusion criteria. After adjusting for age and NIHSS, T max >6 second mismatch was associated with prolonged LOS (OR 2.94 95% CI 1.06-8.18; P = .039), but T max 4-6 second was not (OR 1.45 95% CI .46-4.58, P = .528). We found similar associations when LOS was a continuous variable for T max > 6 second (β coefficient = 2.01, 95% CI .05-3.97, P = .044) and T max 4-6 second (β coefficient = 1.24, 95% CI -.85 to 3.34, P = .244).

Conclusion: In patients with symptomatic MCA stenosis, T max > 6 second perfusion delay is associated with prolonged LOS. Prospective studies are needed to validate our findings.
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http://dx.doi.org/10.1111/jon.12839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119309PMC
May 2021

Duration of symptomatic stroke and successful reperfusion with endovascular thrombectomy for anterior circulation large vessel occlusive stroke.

J Neurointerv Surg 2021 Feb 1. Epub 2021 Feb 1.

Neuroscience, Mercy Health Saint Vincent Medical Center, Toledo, Ohio, USA

Background: It has been reported that longer time intervals from stroke onset to endovascular therapy are associated with lower rates of successful reperfusion in acute ischemic stroke patients with large vessel occlusion. However, procedural variables and potential mechanisms of this association have not been fully elucidated.

Methods: We performed a secondary analysis of individual patient data from the North American Solitaire Stent Retriever Acute Stroke (NASA) and Trevo Stent-Retriever Acute Stroke (TRACK) registries. We included patients with occlusion of the internal carotid artery or middle cerebral artery (M1 and M2 segments) who were treated by mechanical thrombectomy within 24 hours of last known normal. The primary outcome was reperfusion, defined as a Thrombolysis In Cerebral Infarction (TICI) score ≥2b. The secondary outcome was reperfusion on the first pass. The primary predictor was duration of symptomatic stroke, defined as time from last known normal to time of final pass. Adjusted logistic regression models were utilized to determine associations between variables and outcome.

Results: We included 506 patients, of which 401 (79.3%) achieved successful reperfusion (TICI 2b/3). The mean (SD) duration of symptomatic stroke was 6.8 (3.5) hours and in the adjusted logistic regression model the duration of symptomatic stroke was associated with reperfusion (OR 0.90, 95% CI 0.84 to 0.96) and reperfusion on the first pass (OR 0.89, 95% CI 0.83 to 0.95). In that model, the predicted probability of reperfusion was 88% (95% CI 0.83 to 0.92) at 1 hour, 81% (95% CI 0.78 to 0.84) at 6 hours, 70% (95% CI 0.63 to 0.77) at 12 hours, and 42% (95% CI 0.17 to 0.67) at 24 hours (p=0.001). Reperfused patients were significantly younger, more likely to be male, and to have had a balloon guide catheter used during the procedure.

Conclusion: In a real-world cohort of acute ischemic stroke patients with anterior circulation occlusion treated with endovascular therapy, longer duration of symptomatic stroke is associated with lower rates of successful reperfusion and reperfusion on the first pass.
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http://dx.doi.org/10.1136/neurintsurg-2020-016961DOI Listing
February 2021

Blood Pressure Management Before, During, and After Endovascular Thrombectomy for Acute Ischemic Stroke.

Semin Neurol 2021 Feb 20;41(1):46-53. Epub 2021 Jan 20.

Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee.

There is an absence of specific evidence or guideline recommendations on blood pressure management for large vessel occlusion stroke patients. Until randomized data are available, the periprocedural blood pressure management of patients undergoing endovascular thrombectomy can be viewed in two phases relative to the achievement of recanalization. In the hyperacute phase, prior to recanalization, hypotension should be avoided to maintain adequate penumbral perfusion. The American Heart Association guidelines should be followed for the upper end of prethrombectomy blood pressure: ≤185/110 mm Hg, unless post-tissue plasminogen activator administration when the goal is <180/105 mm Hg. After successful recanalization (thrombolysis in cerebral infarction [TICI]: 2b-3), we recommend a target of a maximum systolic blood pressure of < 160 mm Hg, while the persistently occluded patients (TICI < 2b) may require more permissive goals up to <180/105 mm Hg. Future research should focus on generating randomized data on optimal blood pressure management both before and after endovascular thrombectomy, to optimize patient outcomes for these divergent clinical scenarios.
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http://dx.doi.org/10.1055/s-0040-1722721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063274PMC
February 2021

Effect of Premorbid Anxiolytic Medications on Ischemic Stroke Functional Outcome.

Stroke 2021 Jan 7;52(2):e51-e52. Epub 2021 Jan 7.

Department of Neurology, University of Utah (C.P., K.-H.W., E.L.S., K.T., A.H.d.H.).

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http://dx.doi.org/10.1161/STROKEAHA.120.032812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855749PMC
January 2021

Impact of Intracranial Pressure Monitor-Guided Therapy on Neurologic Outcome After Spontaneous Nontraumatic Intracranial Hemorrhage.

J Stroke Cerebrovasc Dis 2021 Mar 22;30(3):105540. Epub 2020 Dec 22.

Neurology, Clinical Neurosciences Center, University of Utah, Salt Lake City, UT, USA.

Objectives: Intracranial pressure (ICP) monitors have been used in some patients with spontaneous intracranial hemorrhage (ICH) to provide information to guide treatment without clear evidence for its use in this population. We assessed the impact of ICP monitor placement, including external ventricular drains and intraparenchymal monitors, on neurologic outcome in this population.

Materials And Methods: In this secondary analysis of the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation III trial, the primary outcome was poor outcome (modified Rankin Scale score 4-6) and the secondary outcome was death, at 1 year from onset. We compared outcomes in patients with or without an ICP monitor using unadjusted and adjusted logistic regression models. The analyses were repeated in a balanced cohort created with propensity score matching.

Results: Seventy patients underwent ICP monitor placement and 424 did not. Poor outcome was seen in 77.1% of patients in the ICP-monitor subgroup compared with 53.8% in the no-monitor subgroup (p<0.001). Of patients in the ICP-monitor subgroup, 31.4% died, compared with 21.0% in the no-monitor subgroup (p=0.053). In multivariate models, ICP monitor placement was associated with a >2-fold greater risk of poor outcome (odds ratio 2.76, 95% CI 1.30-5.85, p=0.008), but not with death (p=0.652). Our findings remained consistent in the propensity score-matched cohort.

Conclusion: These results question whether ICP monitor-guided therapy in patients with spontaneous nontraumatic ICH improves outcome. Further work is required to define the causal pathway and improve identification of patients that might benefit from invasive ICP monitoring.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080544PMC
March 2021

Rabbit models of intracranial atherosclerotic disease for pathological validation of vessel wall MRI.

Neuroradiol J 2021 Jun 16;34(3):193-199. Epub 2020 Dec 16.

Department of Neurology, University of Utah, USA.

Introduction: Vessel wall magnetic resonance imaging can improve the evaluation of intracranial atherosclerotic disease. However, pathological validation is needed to improve vessel wall magnetic resonance imaging techniques. Human pathology samples are not practical for such analysis, so an animal model is therefore needed.

Materials And Methods: Watanabe heritable hyperlipidemic rabbits and apolipoprotein E knockout rabbits were evaluated against New Zealand white wild-type rabbits. Evaluation of intracranial arteries was performed with vessel wall magnetic resonance imaging and pathological analysis, rating the presence and severity of disease in each segment. Two-tailed -tests were performed to compare disease occurrence and severity prevalence among rabbit subtypes. Sensitivity and specificity were calculated to assess the diagnostic accuracy of vessel wall magnetic resonance imaging.

Results: Seventeen rabbits (five Watanabe heritable hyperlipidemic, four apolipoprotein E knockout and eight New Zealand white) were analysed for a total of 51 artery segments. Eleven segments (five Watanabe heritable hyperlipidemic and six apolipoprotein E knockout) demonstrated intracranial atherosclerotic disease on pathology. Disease model animals had lesions more frequently than New Zealand white animals (<0.001). The sensitivity and specificity of vessel wall magnetic resonance imaging for the detection of intracranial atherosclerotic disease were 68.8% and 95.2%, respectively. When excluding mild cases to assess vessel wall magnetic resonance imaging accuracy for detecting moderate to severe intracranial atherosclerotic disease lesions, sensitivity improved to 100% with unchanged specificity.

Conclusion: Intracranial atherosclerotic disease can be reliably produced and detected using 3T vessel wall magnetic resonance imaging-compatible Watanabe heritable hyperlipidemic and ApoE rabbit models. Further analysis is needed to characterize better the development and progression of the disease to correlate tissue-validated animal findings with those in human vessel wall magnetic resonance imaging studies.
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http://dx.doi.org/10.1177/1971400920980153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165905PMC
June 2021

Impact of COVID-19 on Outcomes in Ischemic Stroke Patients in the United States.

J Stroke Cerebrovasc Dis 2021 Feb 9;30(2):105535. Epub 2020 Dec 9.

Department of Neurology, University of Utah, 175 N. Medical Dr, Salt Lake City, UT 84132, United States. Electronic address:

Background: Studies have shown worse outcomes in patients with comorbid ischemic stroke (IS) and coronavirus disease 2019 (COVID-19), but have had small sample sizes.

Methods: We retrospectively identified patients in the Vizient Clinical Data Base® with IS as a discharge diagnosis. The study outcomes were in-hospital death and favorable discharge (home or acute rehabilitation). In the primary analysis, we compared IS patients with laboratory-confirmed COVID-19 (IS-COVID) discharged April 1-July 31, 2020 to pre-COVID IS patients discharged in 2019 (IS controls). In a secondary analysis, we compared a matched cohort of IS-COVID patients to patients within the IS controls who had pneumonia (IS-PNA), created with inverse-probability-weighting (IPW).

Results: In the primary analysis, we included 166,586 IS controls and 2086 IS-COVID from 312 hospitals in 46 states. Compared to IS controls, IS-COVID were less likely to have hypertension, dyslipidemia, or be smokers, but more likely to be male, younger, have diabetes, obesity, acute renal failure, acute coronary syndrome, venous thromboembolism, intubation, and comorbid intracerebral or subarachnoid hemorrhage (all p<0.05). Black and Hispanic patients accounted for 21.7% and 7.4% of IS controls, respectively, but 33.7% and 18.5% of IS-COVID (p<0.001). IS-COVID, versus IS controls, were less likely to receive alteplase (1.8% vs 5.6%, p<0.001), mechanical thrombectomy (4.4% vs. 6.7%, p<0.001), to have favorable discharge (33.9% vs. 66.4%, p<0.001), but more likely to die (30.4% vs. 6.5%, p<0.001). In the matched cohort of patients with IS-COVID and IS-PNA, IS-COVID had a higher risk of death (IPW-weighted OR 1.56, 95% CI 1.33-1.82) and lower odds of favorable discharge (IPW-weighted OR 0.63, 95% CI 0.54-0.73).

Conclusions: Ischemic stroke patients with COVID-19 are more likely to be male, younger, and Black or Hispanic, with significant increases in morbidity and mortality compared to both ischemic stroke controls from 2019 and to patients with ischemic stroke and pneumonia.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832426PMC
February 2021

Benefit of endovascular thrombectomy for M2 middle cerebral artery occlusion in the ARISE II study.

J Neurointerv Surg 2020 Nov 20. Epub 2020 Nov 20.

Mercy Health St Vincent Medical Center, Toledo, Ohio, USA

Background: The benefit of endovascular thrombectomy for acute ischemic stroke with M2 segment middle cerebral artery occlusion remains controversial, with uncertainty and paucity of data specific to this population.

Objective: To compare outcomes between M1 and M2 occlusions in the Analysis of Revascularization in Ischemic Stroke with EmboTrap (ARISE II) trial.

Methods: We performed a prespecified analysis of the ARISE II trial with the primary outcome of 90-day modified Rankin Scale score of 0-2, which we termed good outcome. Secondary outcomes included reperfusion rates and major adverse events. The primary predictor was M2 occlusion, which we compared with M1 occlusion.

Results: We included 183 patients, of whom 126 (69%) had M1 occlusion and 57 (31%) had M2 occlusion. There was no difference in the reperfusion rates or adverse events between M2 and M1 occlusions. The rate of good outcome was not different in M2 versus M1 occlusions (70.2% vs 69.7%, p=0.946). In a logistic regression model adjusted for age, sex, and baseline National Institutes of Health Stroke Scale score, M2 occlusions did not have a significantly different odds of good outcome compared with M1 occlusions (OR 0.94, 95% CI 0.47 to 1.88, p=0.87).

Conclusion: In ARISE II, M2 occlusions achieved a 70.2% rate of good outcome at 90 days, which is above published rates for untreated M2 occlusions and superior to prior reports of M2 occlusions treated with endovascular thrombectomy. We also report similar rates of good outcome, successful reperfusion, death, and other adverse events when comparing the M1 and M2 occlusions.
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http://dx.doi.org/10.1136/neurintsurg-2020-016427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134506PMC
November 2020

Cerebral Venous Sinus Thrombosis in the COVID-19 Pandemic.

J Neuroophthalmol 2020 12 28;40(4):457-462. Epub 2020 Oct 28.

Department of Neurology (CM, RAP, SY, KI, JT), New York University Langone Medical Center, New York, New York; and Department of Neurology (AdH), University of Utah School of Medicine, Salt Lake City, Utah.

Background: Recent studies have noted concern for increased thromboembolic events in the setting of Coronavirus Disease 2019 (COVID-19). Cerebral venous sinus thrombosis (CVST) is a form of thromboembolism that has been observed as a neuro-ophthalmologic complication of COVID-19.

Methods: Review of the scientific literature.

Results: In this article, we report an overview of CVST epidemiology, clinical presentation, diagnostics, disease pathophysiology, and management in the setting of COVID-19.

Conclusion: CVST is an uncommon thromboembolic event with variable phenotypes and multiple etiologies. Neurologic complications can be severe, including significant visual deficits and death. Current observations suggest that the risk of CVST may be profoundly impacted by this novel COVID-19 pandemic, thus prompting increased attention to disease presentation, pathogenesis, and management.
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http://dx.doi.org/10.1097/WNO.0000000000001122DOI Listing
December 2020

The Effect of Hyperglycemia on Infarct Growth after Reperfusion: An Analysis of the DEFUSE 3 trial.

J Stroke Cerebrovasc Dis 2021 Jan 6;30(1):105380. Epub 2020 Nov 6.

Department of Neurology, University of Utah Medical Center, Salt Lake City, UT, United States. Electronic address:

Background And Purpose: Brain infarct growth, despite successful reperfusion, decreases the likelihood of good functional outcome after ischemic stroke. In patients undergoing reperfusion, admission glucose is associated with poor outcome but the effect of glucose level on infarct growth is not well studied.

Materials And Methods: This is a secondary analysis of the DEFUSE 3 trial. The primary predictor was baseline glucose level and the primary outcome is the change of the ischemic core volume from the baseline to 24-hour follow-up imaging (∆core), transformed as a cube root to reduce right skew. We included DEFUSE 3 patients who were randomized to endovascular therapy, had perfusion imaging data at baseline, an MRI at 24 hours, and who achieved TICI 2b or 3. Linear regression models, both unadjusted and adjusted, were fit to the primary outcome and all models included the baseline core volume as a covariate to normalize ∆core.

Results: We identified 62 patients who met our inclusion criteria. The mean age was 68.1±13.1 (years), 48.4% (30/62) were men, and the median (IQR) cube root of ∆core was 2.8 (2.0-3.8) mL. There was an association between baseline glucose level and normalized ∆core in unadjusted analysis (beta coefficient 0.010, p = 0.01) and after adjusting for potential confounders (beta coefficient 0.008, p = 0.03).

Conclusion: In acute ischemic stroke patients with large vessel occlusion undergoing successful endovascular reperfusion, baseline hyperglycemia is associated with infarction growth. Further study is needed to establish potential neuroprotective benefits of aggressive glycemic control prior to and after reperfusion.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736545PMC
January 2021