Telestroke Training: Considerations for Expansion of Vascular Neurology Program Requirements.

Telemedicine for stroke (Telestroke) has been a key component to efficient, widespread acute stroke care for many years. The expansion of reimbursement through the Furthering Access to Stroke Telemedicine Act and rapid deployment of telemedicine resources during the COVID-19 public health emergency have further expanded remote care, with practitioners of varying educational backgrounds, and experience providing acute stroke care via telemedicine (Telestroke). Some Telestroke practitioners have not had fellowship-level vascular neurology training and many are without training specific to virtual modalities. While many vascular neurology fellowship programs incorporate Telestroke training into the curriculum, components of this curriculum are not consistent, extent of involvement is variable, and not all fellows receive hands-on training in remote care. Furthermore, the extent of training and evaluation of Telestroke in American Board of Psychiatry and Neurology training requirements and Accreditation Council for Graduate Medical Education assessments for vascular neurology fellowship are not standardized. We suggest that Telestroke be formally incorporated into vascular neurology fellowship curricula and provide considerations for key components of this training and metrics for evaluation.

Telestroke Across the Continuum of Care: Lessons from the COVID-19 Pandemic.

While use of telemedicine to guide emergent treatment of ischemic stroke is well established, the COVID-19 pandemic motivated the rapid expansion of care via telemedicine to provide consistent care while reducing patient and provider exposure and preserving personal protective equipment. Temporary changes in re-imbursement, inclusion of home office and patient home environments, and increased access to telehealth technologies by patients, health care staff and health care facilities were key to provide an environment for creative and consistent high-quality stroke care. The continuum of care via telestroke has broadened to include prehospital, inter-facility and intra-facility hospital-based services, stroke telerehabilitation, and ambulatory telestroke. However, disparities in technology access remain a challenge. Preservation of reimbursement and the reduction of regulatory burden that was initiated during the public health emergency will be necessary to maintain expanded patient access to the full complement of telestroke services. Here we outline many of these initiatives and discuss potential opportunities for optimal use of technology in stroke care through and beyond the pandemic.

A Systematic Review of Practice Guidelines and Recommendations for Discontinuation of Cholinesterase Inhibitors in Dementia.

Cholinesterase inhibitors (ChEIs) are the primary pharmacological treatment for symptom management of Alzheimer disease (AD), but they carry known risks during long-term use, and do not guarantee clinical effects over time. The balance of risks and benefits may warrant discontinuation at different points during the disease course. Indeed, although there is limited scientific study of deprescribing ChEIs, clinicians routinely face practical decisions about whether to continue or stop medications. This review examined published practice recommendations for discontinuation of ChEIs in AD. To characterize the scientific basis for recommendations, we first summarized randomized controlled trials of ChEI discontinuation. We then identified practice guidelines by professional societies and in textbooks and classified them according to 1) whether they made a recommendation about discontinuation, 2) what the recommendation was, and 3) the proposed grounds for discontinuation. There was no consensus in guidelines and textbooks about discontinuation. Most recommended individualized discontinuation decisions, but there was essentially no agreement about what findings or situations would warrant discontinuation, or even about what domains to consider in this process. The only relevant domain identified by most guidelines and textbooks was a lack of response or a loss of effectiveness, both of which can be difficult to ascertain in the course of a progressive condition. Well-designed, long-term studies of discontinuation have not been conducted; such evidence is needed to provide a scientific basis for practice guidelines. It seems reasonable to apply an individualized approach to discontinuation while engaging patients and families in treatment decisions. .

Meta-analysis of genome-wide association studies identifies 1q22 as a susceptibility locus for intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar or nonlobar based on the location of ruptured blood vessels within the brain. These different locations also signal different underlying vascular pathologies. Heritability estimates indicate a substantial genetic contribution to risk of ICH in both locations. We report a genome-wide association study of this condition that meta-analyzed data from six studies that enrolled individuals of European ancestry. Case subjects were ascertained by neurologists blinded to genotype data and classified as lobar or nonlobar based on brain computed tomography. ICH-free control subjects were sampled from ambulatory clinics or random digit dialing. Replication of signals identified in the discovery cohort with p < 1 × 10(-6) was pursued in an independent multiethnic sample utilizing both direct and genome-wide genotyping. The discovery phase included a case cohort of 1,545 individuals (664 lobar and 881 nonlobar cases) and a control cohort of 1,481 individuals and identified two susceptibility loci: for lobar ICH, chromosomal region 12q21.1 (rs11179580, odds ratio [OR] = 1.56, p = 7.0 × 10(-8)); and for nonlobar ICH, chromosomal region 1q22 (rs2984613, OR = 1.44, p = 1.6 × 10(-8)). The replication included a case cohort of 1,681 individuals (484 lobar and 1,194 nonlobar cases) and a control cohort of 2,261 individuals and corroborated the association for 1q22 (p = 6.5 × 10(-4); meta-analysis p = 2.2 × 10(-10)) but not for 12q21.1 (p = 0.55; meta-analysis p = 2.6 × 10(-5)). These results demonstrate biological heterogeneity across ICH subtypes and highlight the importance of ascertaining ICH cases accordingly.

Variability in the Use of Platelet Transfusion in Patients with Intracerebral Hemorrhage: Observations from the Ethnic/Racial Variations of Intracerebral Hemorrhage Study.

BACKGROUND: We examined platelet transfusion (PTx) in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, hypothesizing that rates of PTx would vary among hospitals and depend on whether patients were on an antiplatelet therapy or underwent intracerebral hemorrhage (ICH) surgical treatment. METHODS: The ERICH study is a prospective observational study evaluating risk factors for ICH among whites, blacks, and Hispanics. We identified factors associated with PTx, examined practice patterns of PTx across the United States, and explored the association of PTx with mortality and poor outcome (modified Rankin Scale score 4-6). RESULTS: Nineteen centers enrolled 2572 ICH cases; 11.7% received PTx. Factors significantly associated with PTx were antiplatelet use before onset (odds ratio [OR], 5.02; 95% confidence interval [CI], 3.81-6.61, P < .0001), thrombocytopenia (OR, 13.53; 95% CI, 8.43-21.72, P < .0001), and ventriculostomy placement (OR, 1.85; 95% CI, 1.36-2.52, P < .0001). Blacks were less likely (OR, .57; 95% CI, .41-0.80) to receive PTx. Among patients who received PTx, 42.4% were not on an antiplatelet therapy before onset. Twenty-three percent of patients on antiplatelet therapy received PTx, but percentages varied from 0% to 71% across centers. There was no difference in mortality or poor outcome at 3 months between patients receiving PTx and those who did not. CONCLUSIONS: The frequency of PTx for ICH varies across academic centers. Thrombocytopenia, antiplatelet use, vascular risk factors, and ventriculostomy placement were associated with PTx. PTx was not associated with improved outcomes. We anticipate reduced PTx use over time given recent clinical trial data suggesting its use could be harmful; however, the issue of whether surgical management warrants PTx remains.

Prophylactic Antiepileptic Drug Use and Outcome in the Ethnic/Racial Variations of Intracerebral Hemorrhage Study.

BACKGROUND AND PURPOSE: The role of antiepileptic drug (AED) prophylaxis after intracerebral hemorrhage (ICH) remains unclear. This analysis describes prevalence of prophylactic AED use, as directed by treating clinicians, in a prospective ICH cohort and tests the hypothesis that it is associated with poor outcome. METHODS: Analysis included 744 patients with ICH enrolled in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study before November 2012. Baseline clinical characteristics and AED use were recorded in standardized fashion. ICH location and volume were recorded from baseline neuroimaging. We analyzed differences in patient characteristics by AED prophylaxis, and we used logistic regression to test whether AED prophylaxis was associated with poor outcome. The primary outcome was 3-month modified Rankin Scale score, with 4 to 6 considered poor outcome. RESULTS: AEDs were used for prophylaxis in 289 (39%) of the 744 subjects; of these, levetiracetam was used in 89%. Patients with lobar ICH, craniotomy, or larger hematomas were more likely to receive prophlyaxis. Although prophylactic AED use was associated with poor outcome in an unadjusted model (odds ratio, 1.40; 95% confidence interval, 1.04-1.88; P=0.03), this association was no longer significant after adjusting for clinical and demographic characteristics (odds ratio, 1.11; 95% confidence interval, 0.74-1.65; P=0.62). CONCLUSIONS: We found no evidence that AED use (predominantly levetiracetam) is independently associated with poor outcome. A prospective study is required to assess for a more modest effect of AED use on outcome after ICH.

Epilepsy surgery perceptions among general neurologists and epilepsy specialists: A survey.

OBJECTIVE: Surgical intervention for drug-resistant epilepsy (DRE) is a safe and efficacious evidence-based treatment. Yet, neurologists have historically revealed hesitance in referring patients for surgical evaluations. The present study surveyed general neurologists and epilepsy specialists to assess their views and process in referring patients for specialized epilepsy care and epilepsy surgery. METHODS: A 14-item survey assessing epilepsy referrals and views of epilepsy surgery was distributed to all neurologists currently practicing in a large national integrated health system using REDCap. Responses were qualitatively analyzed and differences between general neurologists and epileptologists were assessed using chi-squared tests. RESULTS: In total, 100 responses were received from 67 general neurologists and 33 epileptologists with several similarities and differences emerging between the two groups. Both groups endorsed surgery and neuromodulation as treatment options in DRE, felt that seizure frequency rather than duration was relevant in considering epilepsy surgery, and indicated patient preference as the largest barrier limiting epilepsy surgery. General neurologists were more likely to require ≥ 3 ASMs to fail to diagnose DRE compared to epileptologists (45% vs. 15%, p < 0.01) who more often required ≥ 2 ASMs to fail. Epileptologists were also more likely than neurologists to try a new ASM (75.8% vs. 53.7%, p < 0.05) or optimize the current ASM (75.8% vs. 49.3%, p < 0.05) in DRE. General neurologists were more likely to consider epilepsy surgery to be less efficacious (p = 0.001) or less safe (p < 0.05). SIGNIFICANCE: Overall, neurologists appear to have generally positive opinions of epilepsy surgery, which is a change from prior literature and represents a changing landscape of views toward this intervention. Furthermore, epileptologists and general neurologists endorsed more similarities than differences in their opinions of surgery and steps to referral, which is another encouraging finding. Those gaps that remain between epileptologists and general neurologists, particularly in standards of ASM prescription, may be addressed by more consistent education about DRE and streamlining of surgical referral procedures.

Open Burn Pit Exposure in Headache Disorder and Migraine.

Importance: Open burn pits have commonly been used for waste disposal by the US military but have not been systematically investigated as an independent risk factor for headache disorders. Objective: To evaluate the association between exposure to open burn pits and incidence of headache and migraine. Design, Setting, and Participants: This retrospective cohort study used data from the Veterans Health Administration Headache Cohort along with data from the US Department of Defense and the Airborne Hazards and Open Burn Pit (AH&OBP) Registry to assess registry participants with potential exposure to open burn pits in the Veterans Health Administration from April 1, 2014, through October 31, 2022. Participants were included by linking data from the AH&OBP Registry to their US Department of Defense and Veterans Health Administration electronic health records. Those with preexisting headache were removed from the analytic sample. The analysis was conducted between November 1, 2022, and January 31, 2024. Exposure: Open burn pit exposure composite variables based on the registry questionnaire were examined, specifically being near open burn pits, days near open burn pits, and having open burn pit duties. Main Outcomes and Measures: Primary incident outcomes included medically diagnosed headache disorders and medically diagnosed migraine. Results: The analytic sample included 247 583 veterans (mean [SD] age, 27.9 [7.7] years; 222 498 [89.9%] male). After covariates were controlled for at baseline, participants who were near an open burn pit with open burn pit duties had the highest adjusted odds of medically diagnosed headache disorders (adjusted odds ratio [AOR], 1.59; 95% CI, 1.46-1.74), migraine (AOR, 1.60; 95% CI, 1.43-1.79), and self-reported disabling migraine (AOR, 1.93; 95% CI, 1.69-2.20) compared with those without exposure. The 2 highest quartiles of cumulative burn pit exposure (290-448 days and >448 days) had significantly higher adjusted odds of medically diagnosed headache (290-448 days: AOR, 1.20; 95% CI, 1.09-1.31; >448 days: AOR, 1.55; 95% CI, 1.41-1.70) and migraine (290-448 days: AOR, 1.19; 95% CI, 1.07-1.34; >448 days: AOR, 1.48; 95% CI, 1.32-1.65). Conclusions and Relevance: In this cohort study, a dose-dependent association existed between open burn pit exposure and medically diagnosed headache and migraine. These new data identify potentially important associations between open burn bit exposure and new-onset headache among service personnel as well as a possible health condition that may be encountered more frequently in Veterans Health Administration facilities during mandatory screening for military exposures.

Temporal Trends and Racial Disparities in Long-Term Survival After Stroke.

BACKGROUND AND OBJECTIVES: Few studies have examined trends and disparities in long-term outcome after stroke in a representative US population. We used a population-based stroke study in the Greater Cincinnati Northern Kentucky region to examine trends and racial disparities in poststroke 5-year mortality. METHODS: All patients with acute ischemic strokes (AISs) and intracerebral hemorrhages (ICHs) among residents ≥20 years old were ascertained using ICD codes and physician-adjudicated using a consistent case definition during 5 periods: July 1993-June 1994 and calendar years 1999, 2005, 2010, and 2015. Race was obtained from the medical record; only those identified as White or Black were included. Premorbid functional status was assessed using the modified Rankin Scale, with a score of 0-1 being considered "good." Mortality was assessed with the National Death Index. Trends and racial disparities for each subtype were analyzed with logistic regression. RESULTS: We identified 8,428 AIS cases (19.3% Black, 56.3% female, median age 72) and 1,501 ICH cases (23.5% Black, 54.8% female, median age 72). Among patients with AIS, 5-year mortality improved after adjustment for age, race, and sex (53% in 1993/94 to 48.3% in 2015, overall effect of study year p = 0.009). The absolute decline in 5-year mortality in patients with AIS was larger than what would be expected in the general population (5.1% vs 2.8%). Black individuals were at a higher risk of death after AIS (odds ratio [OR] 1.23, 95% CI 1.08-1.39) even after adjustment for age and sex, and this effect was consistent across study years. When premorbid functional status and comorbidities were included in the model, the primary effect of Black race was attenuated but race interacted with sex and premorbid functional status. Among male patients with a good baseline functional status, Black race remained associated with 5-year mortality (OR 1.4, 95% CI 1.1-1.7, p = 0.002). There were no changes in 5-year mortality after ICH over time (64.4% in 1993/94 to 69.2% in 2015, overall effect of study year p = 0.32). DISCUSSION: Long-term survival improved after AIS but not after ICH. Black individuals, particularly Black male patients with good premorbid function, have a higher mortality after AIS, and this disparity did not change over time.

Trends Over Time in Stroke Incidence by Race in the Greater Cincinnati Northern Kentucky Stroke Study.

BACKGROUND AND OBJECTIVES: Understanding the current status of and temporal trends of stroke epidemiology by age, race, and stroke subtype is critical to evaluate past prevention efforts and to plan future interventions to eliminate existing inequities. We investigated trends in stroke incidence and case fatality over a 22-year time period. METHODS: In this population-based stroke surveillance study, all cases of stroke in acute care hospitals within a 5-county population of southern Ohio/northern Kentucky in adults aged ≥20 years were ascertained during a full year every 5 years from 1993 to 2015. Temporal trends in stroke epidemiology were evaluated by age, race (Black or White), and subtype (ischemic stroke [IS], intracranial hemorrhage [ICH], or subarachnoid hemorrhage [SAH]). Stroke incidence rates per 100,000 individuals from 1993 to 2015 were calculated using US Census data and age-standardized, race-standardized, and sex-standardized as appropriate. Thirty-day case fatality rates were also reported. RESULTS: Incidence rates for stroke of any type and IS decreased in the combined population and among White individuals (any type, per 100,000, 215 [95% CI 204-226] in 1993/4 to 170 [95% CI 161-179] in 2015, p = 0.015). Among Black individuals, incidence rates for stroke of any type decreased over the study period (per 100,000, 349 [95% CI 311-386] in 1993/4 to 311 [95% CI 282-340] in 2015, p = 0.015). Incidence of ICH was stable over time in the combined population and in race-specific subgroups, and SAH decreased in the combined groups and in White adults. Incidence rates among Black adults were higher than those of White adults in all time periods, and Black:White risk ratios were highest in adults in young and middle age groups. Case fatality rates were similar by race and by time period with the exception of SAH in which 30-day case fatality rates decreased in the combined population and White adults over time. DISCUSSION: Stroke incidence is decreasing over time in both Black and White adults, an encouraging trend in the burden of cerebrovascular disease in the US population. Unfortunately, however, Black:White disparities have not decreased over a 22-year period, especially among younger and middle-aged adults, suggesting the need for more effective interventions to eliminate inequities by race.

Racial Disparities in Blood Pressure at Time of Acute Ischemic Stroke Presentation: A Population Study.

BACKGROUND: Hypertension is a stroke risk factor with known disparities in prevalence and management between Black and White patients. We sought to identify if racial differences in presenting blood pressure (BP) during acute ischemic stroke exist. METHODS AND RESULTS: Adults with acute ischemic stroke presenting to an emergency department within 24 hours of last known normal during study epochs 2005, 2010, and 2015 within the Greater Cincinnati/Northern Kentucky Stroke Study were included. Demographics, histories, arrival BP, National Institutes of Health Stroke Scale score, and time from last known normal were collected. Multivariable linear regression was used to determine differences in mean BP between Black and White patients, adjusting for age, sex, National Institutes of Health Stroke Scale score, history of hypertension, hyperlipidemia, smoking, stroke, body mass index, and study epoch. Of 4048 patients, 853 Black and 3195 White patients were included. In adjusted analysis, Black patients had higher presenting systolic BP (161 mm Hg [95% CI, 159-164] versus 158 mm Hg [95% CI, 157-159], P<0.01), diastolic BP (86 mm Hg [95% CI, 85-88] versus 83 mm Hg [95% CI, 82-84], P<0.01), and mean arterial pressure (111 mm Hg [95% CI, 110-113] versus 108 mm Hg [95% CI, 107-109], P<0.01) compared with White patients. In adjusted subanalysis of patients <4.5 hours from last known normal, diastolic BP (88 mm Hg [95% CI, 86-90] versus 83 mm Hg [95% CI, 82-84], P<0.01) and mean arterial pressure (112 mm Hg [95% CI, 110-114] versus 108 mm Hg [95% CI, 107-109], P<0.01) were also higher in Black patients. CONCLUSIONS: This population-based study suggests differences in presenting BP between Black and White patients during acute ischemic stroke. Further study is needed to determine whether these differences influence clinical decision-making, outcome, or clinical trial eligibility.

Impact of Poverty on Stroke Recurrence: A Population-Based Study.

BACKGROUND AND OBJECTIVES: Poverty is associated with greater stroke incidence. The relationship between poverty and stroke recurrence is less clear. METHODS: In this population-based study, incident strokes within the Greater Cincinnati/Northern Kentucky region were ascertained during the 2015 study period and followed up for recurrence until December 31, 2018. The primary exposure was neighborhood socioeconomic status (nSES), defined by the percentage of households below the federal poverty line in each census tract in 4 categories (≤5%, >5%-10%, >10%-25%, >25%). Poisson regression models provided recurrence rate estimates per 100,000 residents using population data from the 2015 5-year American Community Survey, adjusting for age, sex, and race. In a secondary analysis, Cox models allowed for the inclusion of vascular risk factors in the assessment of recurrence risk by nSES among those with incident stroke. RESULTS: Of 2,125 patients with incident stroke, 245 had a recurrent stroke during the study period. Poorer nSES was associated with increased stroke recurrence, with rates of 12.5, 17.5, 25.4, and 29.9 per 100,000 in census tracts with ≤5%, >5%-10%, >10%-25%, and >25% below the poverty line, respectively (p < 0.01). The relative risk (95% CI) for recurrent stroke among Black vs White individuals was 2.54 (1.91-3.37) before adjusting for nSES, and 2.00 (1.47-2.74) after adjusting for nSES, a 35.1% decrease. In the secondary analysis, poorer nSES (HR 1.74, 95% CI 1.10-2.76 for lowest vs highest category) and Black race (HR 1.31, 95% CI 1.01-1.70) were both independently associated with recurrence risk, though neither retained significance after full adjustment. Age, diabetes, and left ventricular hypertrophy were associated with increased recurrence risk in fully adjusted models. DISCUSSION: Residents of poorer neighborhoods had a dose-dependent increase in stroke recurrence risk, and neighborhood poverty accounted for approximately one-third of the excess risk among Black individuals. These results highlight the importance of poverty, race, and the intersection of the 2 as potent drivers of stroke recurrence.

Apolipoprotein E, statins, and risk of intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Apolipoprotein E (ApoE) genotypes have been associated with lobar intracerebral hemorrhage (ICH). Although statins have been associated with an increased risk of ICH, meta-analyses have not consistently shown a statin-induced risk of ICH. Here, we test whether hypercholesterolemia (HC) and ApoE polymorphisms affect the risk of ICH by statin use. METHODS: The Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS) study is a prospective, demographically matched case-control study of ICH. A similar study of ICH, Genetic Risks for Medication-Related Hemorrhagic Stroke (GOCHA), was used as a replication cohort. Subjects were classified as normocholesterolemia, HC without statin use, and HC with statin use. Statistical comparisons were performed using Fisher exact test, χ2 tests, and the Breslow-Day test. RESULTS: The discovery cohort consisted of 558 ICH cases and 1444 controls, and the replication cohort consisted of 1020 ICH cases and 382 controls. The association of lower risk for HC was not attenuated by statin use. Statin use was observed to confer a higher risk for lobar ICH in those carrying ApoE4/E4 and ApoE2/E4 genotypes in both discovery and replication cohorts, and a test for interaction showed a trend towards significance (P=0.11 for statin and ApoE4/E4). CONCLUSIONS: Statin use does not seem to attenuate the association of HC with decreased risk for nonlobar ICH. Our data support a gene-by-drug effect for lobar ICH, but larger sample sizes are needed to confirm the association before any clinical change is warranted. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov. Unique identifier: NCT00930280.

Hyperglycemia in acute ischemic stroke: a vascular perspective.

Admission hyperglycemia complicates approximately one-third of acute ischemic strokes and is associated with a worse clinical outcome. Both human and animal studies have showed that hyperglycemia is particularly detrimental in ischemia/reperfusion. Decreased reperfusion blood flow has been observed after middle cerebral artery occlusion in acutely hyperglycemic animals, suggesting the vasculature as an important site of hyperglycemic reperfusion injury. This paper reviews biochemical and molecular pathways in the vasculature that are rapidly affected by hyperglycemia and concludes that these changes result in a pro-vasoconstrictive, pro-thrombotic and pro-inflammatory phenotype that renders the vasculature vulnerable to reperfusion injury. Understanding these pathways should lead to the development of rational therapies that reduce hyperglycemic reperfusion injury and thus improve outcome in this large subset of acute ischemic stroke patients.

Assessment of the interaction of age and sex on 90-day outcome after intracerebral hemorrhage.

OBJECTIVE: Because age affects hormonal production differently in women compared with men, we sought to define sex and age interactions across a multiracial/ethnic population after intracerebral hemorrhage (ICH) to uncover evidence that loss of gonadal hormone production would result in loss of the known neuroprotective effects of gonadal hormones. METHODS: Clinical and radiographic data from participants in the Ethnic/Racial Variations of Intracerebral Hemorrhage study and the Genetic and Environmental Risk Factors for Hemorrhagic Stroke study prior to December 2013 were used. Relationships among sex, age, and outcome after ICH in 616 non-Hispanic black, 590 Hispanic, and 868 non-Hispanic white participants were evaluated using multivariable logistic regression analysis. Poor outcome was defined as modified Rankin Scale score ≥3 at 90 days after ICH. RESULTS: Sex differences were found in multiple variables among the racial/ethnic groups, including age at onset, premorbid neurologic status, and neurologic outcome after ICH. Overall, no sex-age interaction effect was found for mortality (p = 0.183) or modified Rankin Scale score (p = 0.378) at 90 days after ICH. In racial/ethnic subgroups, only the non-Hispanic black cohort provided possible evidence of a sex-age interaction on 90-day modified Rankin Scale score (p = 0.003). CONCLUSION: Unlike in ischemic stroke, there was no evidence that patient sex modified the effect of age on 90-day outcomes after ICH in a large multiracial/ethnic population. Future studies should evaluate biological reasons for these differences between stroke subtypes. CLINICALTRIALSGOV IDENTIFIER: NCT01202864.

Pathological effects of obstructive apneas during the sleep cycle in an animal model of cerebral small vessel disease.

We tested the hypothesis that apneas during the sleep cycle exacerbate hypertension and accelerate changes that occur with cerebral small vessel disease. Obstructive sleep apnea was modeled by intermittent inflations of a chronically implanted tracheal balloon to occlude the airway during the sleep cycle (termed OSA) in spontaneously hypertensive stroke-prone (SHRSP) rats, a model of cerebral small vessel disease. SHRSP rats and their parent strain, Wistar Kyoto (WKY) rats, were exposed to OSA for 2 weeks (from 9 to 11 or from 18 to 20 weeks). At 9 weeks, hypertension was developing in the SHRSP rats and was firmly established by 18 weeks. OSA exposure increased systolic blood pressure in SHRSP rats by ≈30 mm Hg in both age groups compared with shams that were surgically prepared but not exposed to OSA (P<0.05). OSA exposure also increased systolic blood pressure in WKY rats by 20 and 37 mm Hg at 11 and 20 weeks, respectively (P<0.05). OSA exposure in SHRSP rats compromised blood-brain barrier integrity in white matter at both 11 and 20 weeks of age when compared with SHRSP sham rats (P<0.05). Microglia were activated in SHRSP rats exposed to OSA but not in sham rats at 11 weeks (P<0.05). At 20 weeks, microglia were activated in sham SHRSP rats (P<0.05) compared with WKY sham rats and were not further activated by OSA. Neither was blood-brain barrier integrity altered nor microglia activated in any of the WKY groups. We conclude that OSA accelerates the onset of the cerebral pathologies associated with cerebral small vessel disease in SHRSP, but not WKY, rats.

Hyperglycemia worsens outcome after rt-PA primarily in the large-vessel occlusive stroke subtype.

Hyperglycemia at the time of ischemic stroke has been associated with poorer outcomes. Preclinical literature suggests that hyperglycemia is an independent prognostic factor and the vasculature is more vulnerable to reperfusion injury. We applied a method to match subjects on important baseline factors to test whether, independent of stroke severity, stroke subtype influences the effect of hyperglycemia on outcome after recombinant tissue plasminogen activator (rt-PA). We reanalyzed the NINDS rt-PA dataset with respect to matching variables baseline NIHSS, age, and investigator-determined stroke subtypes small-vessel occlusive stroke (SVS), large-vessel occlusive stroke (LVS), and cardioembolic stroke (CES), above and below a glucose threshold of 150 mg/dl. Ninety-day outcomes were compared. Post hoc baseline matching was excellent in most cases. Hyperglycemia was associated with worsened functional outcome mostly in the LVS subtype with increased mortality in the placebo arm (15.3% mortality normoglycemia vs. 30.6% hyperglycemia; p = .046), worse functional outcome in the rt-PA arm (modified Rankin Score (mRS) 0-1; 46.3 vs. 22.0%; p = .034), and no improvement in functional outcome with rt-PA compared to placebo (mRS 0-1; 25% in both groups). Among hyperglycemic subjects, CES subjects showed significant improvement following rt-PA (p = .027). After matching for baseline severity, the influence of hyperglycemia on outcome was primarily in the LVS subtype, especially after rt-PA. This finding is consistent with a deleterious effect of hyperglycemia on ischemia/reperfusion of symptomatic large arteries. If confirmed, the particular vulnerability of the LVS subtype is important in understanding the role of stroke subtype in the mechanism of worsening and potential treatment of hyperglycemic stroke patients.

APOE ε variants increase risk of warfarin-related intracerebral hemorrhage.

OBJECTIVE: We aimed to assess the effect of APOE ε variants on warfarin-related intracerebral hemorrhage (wICH), evaluated their predictive power, and tested for interaction with warfarin in causing wICH. METHODS: This was a prospective, 2-stage (discovery and replication), case-control study. wICH was classified as lobar or nonlobar based on the location of the hematoma. Controls were sampled from ambulatory clinics (discovery) and random digit dialing (replication). APOE ε variants were directly genotyped. A case-control design and logistic regression analysis were utilized to test for association between APOE ε and wICH. A case-only design and logistic regression analysis were utilized to test for interaction between APOE ε and warfarin. Receiver operating characteristic curves were implemented to evaluate predictive power. RESULTS: The discovery stage included 319 wICHs (44% lobar) and 355 controls. APOE ε2 was associated with lobar (odds ratio [OR] 2.46; p < 0.001) and nonlobar wICH (OR 1.67; p = 0.04), whereas ε4 was associated with lobar (OR 2.09; p < 0.001) but not nonlobar wICH (p = 0.35). The replication stage (63 wICHs and 1,030 controls) confirmed the association with ε2 (p = 0.03) and ε4 (p = 0.003) for lobar but not for nonlobar wICH (p > 0.20). Genotyping information on APOE ε variants significantly improved case/control discrimination of lobar wICH (C statistic 0.80). No statistical interaction between warfarin and APOE was found (p > 0.20). CONCLUSIONS: APOE ε variants constitute strong risk factors for lobar wICH. APOE exerts its effect independently of warfarin, although power limitations render this absence of interaction preliminary. Evaluation of the predictive ability of APOE in cohort studies is warranted.

The Impact of Left Ventricular Hypertrophy and Diastolic Dysfunction on Outcome in Intracerebral Hemorrhage Patients.

BACKGROUND: The objective of this study was to determine the prevalence of LVH and DD in patients presenting with supratentorial deep ICH and to determine if the presence of LVH or DD was an independent predictor of initial ICH volume, hematoma expansion, or poor outcome. METHODS: A cross-sectional study was performed on ICH patients who presented from 7/2008 to 12/2010. Cases were excluded if ICH was traumatic, lobar, infratentorial, secondary to elevated international normalized ratio, suspicious for underlying structural malformation, or where surgical evacuation was performed. Logistic and linear regressions were used to assess the ability of LVH to predict ICH imaging characteristics and patient outcomes. RESULTS: After adjusting for use of hemostatic agents, LVH was not a significant independent predictor of initial ICH volume (P = 0.344) or 33% volume expansion (P = 0.378). After adjusting for age, infectious complications, and use of hemostatic agents, LVH was not a significant independent predictor of poor functional outcome (P = 0.778). Similar results were seen for DD. CONCLUSION: In our sample, patients with deep ICH and LVH were more likely to develop IVH, but LVH was not a significant independent predictor of initial ICH volume, hematoma expansion, or poor short-term outcome.