Characteristics of a Diverse Cohort of Stroke Patients with SARS-CoV-2 and Outcome by Sex.

BACKGROUND AND PURPOSE: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with stroke. The role of sex on stroke outcome has not been investigated. To objective of this paper is to describe the characteristics of a diverse cohort of acute stroke patients with COVID-19 disease and determine the role of sex on outcome. METHODS: This is a retrospective study of patients with acute stroke and SARS-CoV-2 infection admitted between March 15 to May 15, 2020 to one of the six participating comprehensive stroke centers. Baseline characteristics, stroke subtype, workup, treatment and outcome are presented as total number and percentage or median and interquartile range. Outcome at discharge was determined by the modified Rankin Scale Score (mRS). Variables and outcomes were compared for males and females using univariate and multivariate analysis. RESULTS: The study included 83 patients, 47% of which were Black, 28% Hispanics/Latinos, and 16% whites. Median age was 64 years. Approximately 89% had at least one preexisting vascular risk factor (VRF). The most common complications were respiratory failure (59%) and septic shock (34%). Compared with females, a higher proportion of males experienced severe SARS-CoV-2 symptoms requiring ICU hospitalization (73% vs. 49%; p = 0.04). When divided by stroke subtype, there were 77% ischemic, 19% intracerebral hemorrhage and 3% subarachnoid hemorrhage. The most common ischemic stroke etiologies were cryptogenic (39%) and cardioembolic (27%). Compared with females, males had higher mortality (38% vs. 13%; p = 0.02) and were less likely to be discharged home (12% vs. 33%; p = 0.04). After adjustment for age, race/ethnicity, and number of VRFs, mRS was higher in males than in females (OR = 1.47, 95% CI = 1.03-2.09). CONCLUSION: In this cohort of SARS-CoV-2 stroke patients, most had clinical evidence of coronavirus infection on admission and preexisting VRFs. Severe in-hospital complications and worse outcomes after ischemic strokes were higher in males, than females.

The effects of cerebral white matter changes on cardiovascular responses to cognitive and physical activity in a stroke population.

Autonomic nervous system (ANS) control may be disrupted by cerebrovascular disease. We investigated the relationship between alterations in white matter integrity and regulation of the ANS in 23 participants who sustained a stroke within 5 years. These participants underwent diffusion tensor imaging, and fractional anisotropy values were calculated (DTI-FA) for each hemisphere and lobe. Cognitive and physical exertion tasks were performed while recording an electrocardiogram. Respiratory sinus arrhythmia (RSA) decreased more during a verbal fluency task with lower left hemisphere DTI-FA. Further, the physical stressor yielded decreases in RSA with lower frontal DTI-FA and higher temporal lobe DTI-FA, p < .05 (perhaps a release effect on the central autonomic network). Decrements in ANS regulation may have functional consequences that alter behavior, as well as potentially increasing the risk for further vascular disease.

Is asymptomatic hemorrhagic transformation really innocuous?

OBJECTIVES: Asymptomatic hemorrhagic transformation (HT) is not associated with immediate deterioration of patients with acute ischemic stroke. However, it is unclear whether it is clinically innocuous with respect to long-term outcome. The aim of this study was to determine the impact of asymptomatic HT on 3-month outcome. METHODS: A consecutive series of 1,618 patients, hospitalized between January 2004 and August 2007 for ischemic stroke within 7 days from symptom onset were identified in a prospective stroke registry database. Those who had no evidence of acute cerebral ischemia on diffusion-weighted MRI, who did not undergo T2-weighted gradient echo MRI, whose modified Rankin Scale (mRS) score at 3 months after stroke onset was not available, or who had symptomatic HT were excluded. The odds ratio (OR) of asymptomatic HT was calculated for the full distribution of mRS score and adjusted for variables with p < 0.25 with respect to their associations with asymptomatic HT or functional outcome. RESULTS: Of 1,412 patients eligible for the study, 100 (7.1%) had asymptomatic HT. Patients who experienced asymptomatic HT were more likely to have cardioembolic stroke, to receive thrombolytic therapy, to receive anticoagulation with heparin, and to have a higher initial NIH Stroke Scale score. The crude and adjusted ORs of asymptomatic HT for an increment of mRS score at 3 months were 2.94 (95% confidence interval 2.05-4.24) and 1.90 (1.27-2.82), respectively. CONCLUSIONS: Our study shows that the odds of a worse outcome are increased by a factor of 2 in patients with asymptomatic HT compared with those without HT after acute ischemic stroke.

Thalamic integrity underlies executive dysfunction in traumatic brain injury.

OBJECTIVE: To quantify the effects of traumatic brain injury on integrity of thalamocortical projection fibers and to evaluate whether damage to these fibers accounts for impairments in executive function in chronic traumatic brain injury. METHODS: High-resolution (voxel size: 0.78 mm x 0.78 mm x 3 mm(3)) diffusion tensor MRI of the thalamus was conducted on 24 patients with a history of single, closed-head traumatic brain injury (TBI) (12 each of mild TBI and moderate to severe TBI) and 12 age- and education-matched controls. Detailed neuropsychological testing with an emphasis on executive function was also conducted. Fractional anisotropy was extracted from 12 regions of interest in cortical and corpus callosum structures and 7 subcortical regions of interest (anterior, ventral anterior, ventral lateral, dorsomedial, ventral posterior lateral, ventral posterior medial, and pulvinar thalamic nuclei). RESULTS: Relative to controls, patients with a history of brain injury showed reductions in fractional anisotropy in both the anterior and posterior corona radiata, forceps major, the body of the corpus callosum, and fibers identified from seed voxels in the anterior and ventral anterior thalamic nuclei. Fractional anisotropy from cortico-cortico and corpus callosum regions of interest did not account for significant variance in neuropsychological function. However, fractional anisotropy from the thalamic seed voxels did account for variance in executive function, attention, and memory. CONCLUSIONS: The data provide preliminary evidence that traumatic brain injury and resulting diffuse axonal injury results in damage to the thalamic projection fibers and is of clinical relevance to cognition.

Predictors of recurrent stroke in African Americans.

BACKGROUND: Stroke incidence and mortality are disproportionately higher among African Americans than among whites. OBJECTIVE: To describe the recurrent stroke characteristics and determine the predictability of known vascular risk factors for stroke recurrence in African Americans. METHODS: The authors followed 1,809 African Americans in the African-American Antiplatelet Stroke Prevention Study with recent noncardioembolic ischemic stroke for recurrent stroke, recurrent stroke subtype, and disability. RESULTS: Of the subjects, 10.6% experienced a recurrent stroke during follow-up. The mean interval between eligibility and recurrent stroke was 325 days (median 287 days, SD = 224 days). Stroke recurrence resulted in an average 1.5-point increase in the National Institute of Health Stroke Scale (p < 0.001) and a 3.5-point decrease in modified Barthel Index (p < 0.001). Of previously nondisabled subjects, 48% became disabled or died after stroke recurrence (p < 0.0001). Longitudinal analysis resulted in a hazard for recurrent stroke for each 10-mm Hg increase in systolic blood pressure of 1.103 (95% CI: 1.031 to 1.179, p = 0.004), pulse pressure 1.123 (95% CI: 1.041 to 1.213, p = 0.003), and mean arterial pressure 1.123 (95% CI: 1.001 to 1.260, p = 0.048). Multivariate analysis revealed increases in the recurrent stroke hazard for increases in baseline Glasgow Outcome Score (1.449, 95% CI: 1.071 to 1.961, p = 0.016) and increases in longitudinal pulse pressure (1.009, 95% CI: 1.001 to 1.017, p = 0.029). CONCLUSION: Recurrent stroke leads to disability and disability predicts recurrent stroke. Hypertension is the most predictive modifiable stroke risk factor.

Vascular and Alzheimer-type pathology in an autopsy study of African-Americans.

The authors studied 13 autopsy brains from a larger cohort of 270 African-Americans with a clinical diagnosis of Alzheimer disease (AD), vascular dementia (VaD), or stroke without dementia. Two subjects exhibited changes of pure VaD, 5 had pure AD, and 6 showed a mixture of AD pathology and strokes. Overall, there was good agreement between the pathologic diagnoses and the clinical diagnoses.

Acetaminophen in the treatment of headaches associated with dipyridamole-aspirin combination.

The authors assessed the prevalence of headaches following extended-release dipyridamole/aspirin combination (DAC), and the efficacy of acetaminophen in the treatment of these headaches. Following DAC, 38.7% of the participants developed headaches. The headaches were self-limited (69.4% placebo efficacy in 2 hours) and the incidence markedly declined over time. Acetaminophen was no more effective than placebo in the acute and preemptive treatment of these headaches.

Prevalence and knowledge of transient ischemic attack among US adults.

BACKGROUND: Little information is available about public knowledge of TIA and prevalence of a TIA diagnosis. METHODS: The National Stroke Association sponsored a telephone survey by single-stage random-digit dialing of noninstitutionalized US residents > or =18 years old, which was conducted in 1999. Demographic characteristics of participants were compared to the US population to produce weights for projections. Independent predictors of knowledge and diagnosis of TIA were determined by including all demographic characteristics in logistic regression models. RESULTS: Among 10,112 participants, 2.3% reported having been told by a physician that they had a TIA. Older age, lower income, and fewer years of education were independently associated with a diagnosis of TIA. Of those with TIA, only 64% saw a physician within 24 hours of the event. A physician diagnosis of stroke was reported by 2.3% of participants, of whom 19% recalled having had a TIA before the stroke. An additional 3.2% of participants recalled symptoms consistent with TIA but did not seek medical attention. Only 8.2% correctly related the definition of TIA and 8.6% could identify a typical symptom. Men, nonwhites, and those with lower income and fewer years of education were less likely to be knowledgeable about TIA. CONCLUSIONS: An estimated 4.9 million people in the US report a diagnosis of TIA, and many more recall symptoms consistent with TIA but do not seek medical attention. Reducing stroke risk after TIA could have substantial impact on public health but will require public education about the importance of having stroke symptoms evaluated, even if they resolve.

Awareness, treatment, and control of vascular risk factors in African Americans with stroke.

OBJECTIVE: To investigate control of risk factors in African American patients with previous stroke. METHODS: The baseline history, physical examination, and laboratory data for 1,086 subjects enrolled in the African American Antiplatelet Stroke Prevention Study from 1995 to 1999 were studied. The level of awareness, pharmacologic treatment, and control of diabetes mellitus (casual plasma glucose level > or =200 mg/dL), hypertension (blood pressure > or =140/90 mm Hg), and hypercholesterolemia (serum total cholesterol level > or =240 mg/dL) were determined. RESULTS: Forty percent of subjects reported a history of diabetes mellitus or use of diabetic medication, and 2% of the remaining subjects had a serum glucose level of > or =200 mg/dL. Of those subjects known to be diabetic, 33% had a serum glucose level of > or =200 mg/dL. A history of hypertension or use of antihypertensive medication was reported in 87% of subjects, and 48% of the remaining subjects were found to have a blood pressure of > or =140/90 mm Hg on exam. Of those subjects known to be hypertensive by history, 73% were on antihypertensive medication, but only 30% of the treated subjects had a blood pressure under 140/90 mm Hg. A history of hypercholesterolemia or use of a lipid-lowering agent was reported in 40% of subjects, and 24% of the remaining subjects had a cholesterol level of > or =240 mg/dL. Use of a lipid-lowering agent was reported in 43% of subjects known to be hypercholesterolemic, and 38% of the hypercholesterolemic subjects had a cholesterol level of > or =240 mg/dL. CONCLUSION: Inadequate rates of awareness and control of cardiovascular disease and stroke risk factors are seen in a clinical trial of African American stroke patients and are comparable with those of previously published reports.

Ischemic stroke outcome: racial differences in the trial of danaparoid in acute stroke (TOAST).

OBJECTIVE: To determine racial differences in baseline stroke risk factors and other measures in the Trial of ORG 10172 in Acute Stroke Therapy (TOAST). Differences in these factors could influence response to acute stroke therapy and overall stroke outcome. METHODS: The authors compared baseline demographic, medical, stroke, physical examination, CT, laboratory, and neurologic factors among 292 African-American and 801 white patients who enrolled in the TOAST study. TOAST compared danaparoid (ORG 10172) with placebo among acute ischemic stroke patients who were treated within 24 hours of stroke onset. RESULTS: African-Americans were younger and more frequently had hypertension, diabetes mellitus, congestive heart failure, and prior strokes. In addition, African-Americans had higher mean diastolic blood pressure, more lacunar strokes, and more severe prestroke disability. There were no significant differences between African-Americans and white patients in outcomes at 7 days, overall number of adverse experiences, or occurrence of serious bleeds or hemorrhagic transformations. However, there was a trend toward a higher rate of favorable outcomes in white patients at 7 days. There was no significant difference in very favorable outcome at 3 months between African-American and white patients, but significantly more white patients had favorable outcome at 3 months. CONCLUSION: Although African-Americans possess a number of factors that should predict higher rates of poor stroke outcome after acute therapy, they have the capacity to respond similarly to white patients after acute stroke therapy. Perhaps younger age and presence of lacunar infarction are stronger predictors of good outcomes than was appreciated previously.

A comparison of stroke risk factors in patients enrolled in stroke prevention trials.

The high prevalence of stroke risk factors may explain, in part, the high incidence of stroke in African Americans. To further investigate the role of stroke risk factors, we compared stroke risk factor profiles of patients in the African-American Antiplatelet Stroke Prevention Study (AAASPS) with those in other stroke prevention studies in which the enrollees were predominately white. The baseline characteristics of the AAASPS enrollees obtained from an interim AAASPS database of 1,087 patients from 65 centers in the U.S. between December 1995 and June 1999 was compared to the baseline characteristics of 53,293 predominantly non-African American patients enrolled in 23 other stroke prevention studies (pNAA). Percentages were reported for qualitative characteristics, and means and standard deviations (SDs) for quantitative characteristics. For selected qualitative characteristics, 95% confidence intervals were given for population percentages in each study. The comparison of baseline characteristics showed that hypertension was more prevalent in AAASPS (84% [95% CI 82.2, 86.61) compared to pNAA trial patients (range of 27% to 67%). Diabetes mellitus was more common in AAASPS (39.1%) compared to pNAA trial patients (17.1%). Cardiac disease, however, was less common in AAASPS than in pNAA trials. The frequency of baseline characteristics of AAASPS patients is different from those of pNAA studies. Risk factor profiles are important as they may help to predict stroke subtype and outcome. Furthermore, the differences in baseline characteristics may portend differences in response to treatment and incidence of adverse events.

A pilot survey of African-American physician perceptions about clinical trials.

African Americans have been underrepresented in clinical trials. However, African-American physician attitudes about clinical trials may influence patient recruitment. We identified the perceptions of African-American physician members of the Cook County Physicians Association (CCPA) about clinical trials in the Chicago Metropolitan area using a self-administered questionnaire. An 18-item, 2-page survey that included information about physician demographics, practice type, and specialty, and perceptions regarding clinical research was sent to each of the 609 active or inactive members of the CCPA, a predominantly African-American physician organization. Each survey was accompanied by a letter of explanation and a self-addressed, return envelope. Data from the surveys were stored and analyzed in a database. A total of 166 members (27%) completed the survey. Fifty percent of the respondents were men and 50% were women. The mean age of the group was 45 years, and almost half had participated previously as a local investigator, or assisted on a clinical or laboratory study. Factors identified by the members as possibly being disadvantages to participation in a clinical trial, or factors influencing African-American recruitment included: (a) lack of patient awareness of clinical trials (93%); (b) patient mistrust of the medical community (92%); (c) additional administrative tasks in conjunction with a patient enrolled in a study (56%); (d) blind drug assignment (41.6%). African-American physicians perceive inherent disadvantages from participation in clinical trials and have pinpointed factors that may influence patient recruitment. These factors may be addressed by focused physician and community education.

Stroke in African Americans.

There is an excess burden of cerebrovascular disease in African Americans. This article will define possible reasons for excess stroke risk, review racial differences in stroke subtype and stroke prevention programs in the African American Community, and delineate sequelae of stroke. The authors provide insights about stroke prevention in African Americans and highlight challenges to reduce the burden of cerebrovascular disease in this high-risk group.

Autopsy recruitment program for African Americans.

A specialized brain autopsy recruitment program was implemented within the context of advance medical directives and end-of-life treatment decisions. The program was implemented within the framework of a larger study. The purpose of the program was to (1) improve the rate of consent for brain autopsy among African Americans diagnosed with stroke and dementia, and (2) obtain more empirical information on the underlying reasons for the low response rate (4%) in this minority group. A convenience sample of 133 patient and family caregiver pairs was selected for participation. Face-to-face, open-ended interviews were conducted to ascertain reasons for autopsy preferences and to identify respondents interested in the postmortem procedure. Preferences for brain autopsy were ascertained and individuals interested in the procedure were subsequently followed through death or over the 2 1/2 year course of the study. Brain necropsies were conducted on patients requesting the examination. Thirty-six (36) patient and family pairs consented to the procedure, 16 were indecisive and 81 refused. Factors influencing decisions included existing attitudes toward autopsy, family agreement regarding the procedure, and assurance that funeral arrangements would not be delayed. Ninety deaths and two autopsies were conducted before implementation of the specialized recruitment program, yielding a 2.22% completion rate, and 34 deaths with 10 postmortems conducted within the time frame of the recruitment study, yielding a 29% autopsy completion rate. Fisher exact test (p < 0.0001) revealed a significant difference in the proportion of autopsies completed before and after implementation of the specialized recruitment program. Findings strongly suggest that culturally sensitive recruitment programs may increase the rate of autopsy request made by African American caregivers for relatives diagnosed with dementia and stroke. To obtain a higher rate of consent than that obtained in the general population, the program must contain ethnically sensitive recruitment strategies.

Prevention of vascular dementia.

Stroke is an important public health problem worldwide. Those at high risk of stroke may be at high risk of cognitive impairment and dementia after stroke. Modifiable cardiovascular risk factors in midlife including hypertension, alcohol use, cigarette smoking, and certain dietary factors may be important targets for prevention of vascular causes of cognitive impairment. These same types of factors may also be associated with Alzheimer disease. Better control of cardiovascular disease risk factors might lead to delay or prevention of vascular dementia and Alzheimer disease.