Stroke, infections, and New Mechanisms: a Narrative Review.

The global and regional burden of stroke.

Intracerebral hemorrhage (ICH) is the second most common cause of stroke and accounts for 8% to 15% of strokes in Western societies with an estimated incidence of 10 to 25 per 100 000 persons.1–3 Despite advances in the field of stroke and neurocritical care,4 the 30-day mortality has not changed significantly over the past 20 years.3 Indeed, ICH has the highest rates of dependence or death among stroke types and proven treatments are lacking. Clinical trials aimed at limiting hemorrhage growth, procoagulant agents for hemostasis,5 and surgical evacuation6 have not translated into improved clinical outcomes. Antihypertensive therapy for the purpose of reducing hematoma growth has been a mainstay of acute management. Guidelines recommend maintaining mean arterial pressure <130 mm Hg during the acute phase7; however, controversies exist given the lack of randomized clinical trial data and uncertainties about the rapidity and target level of blood pressure (BP)-lowering. Recent Phase 2 clinical trials evaluating acute BP control have shown promise in reducing hematoma expansion with an adequate safety profile and Phase 3 trials are underway.8,9 Besides hematoma growth, other pathophysiological processes occur in the setting of ICH and may serve as potential therapeutic targets. In the acute period after ICH, a rapid rise in intracranial pressure (ICP) from an expanding hematoma may reduce cerebral perfusion pressure. In this setting, interventions aimed at BP-lowering and hemostasis may theoretically induce thrombosis or exacerbate brain ischemia, particularly in patients with pre-existing cerebrovascular disease. A recent publication suggests that aggressive BP-lowering may actually cause acute brain ischemia and worsen outcomes after ICH.10 In this review, we outline the data on secondary acute ischemic injury after ICH, review the prevalence of remote ischemic lesions and risk factors associated with their occurrence, explore potential …

Background: In this study, we aimed to determine the global prevalence, chronological order of symptom appearance, and mortality rates with regard to hemorrhagic and ischemic stroke in patients with coronavirus disease 2019 (COVID-19) and to discuss possible pathogeneses of hemorrhagic and ischemic stroke in individuals with the disease. Methods: We searched the PubMed, Scopus, and Web of Science databases for relevant articles published up to November 8, 2020. Data regarding study characteristics, hemorrhagic stroke, ischemic stroke, and COVID-19 were retrieved in accordance with the PRISMA guidelines. The Newcastle-Ottawa scale was used to assess the quality of the eligible studies. The pooled prevalence and mortality rate of hemorrhagic and ischemic stroke were calculated. Results: The pooled estimate of prevalence of hemorrhagic stroke was 0.46% (95% CI 0.40%-0.53%; I 2 =89.81%) among 67,155 COVID-19 patients and that of ischemic stroke was 1.11% (95% CI 1.03%-1.22%; I 2 =94.07%) among 58,104 COVID-19 patients. Ischemic stroke was more predominant (incidence: 71.58%) than hemorrhagic stroke (incidence: 28.42%) in COVID-19 patients who experienced a stroke. In COVID-19 patients who experienced a stroke, hospital admission with respiratory symptoms was more commonly reported than that with neurological symptoms (20.83% for hemorrhagic stroke and 5.51% for ischemic stroke versus 6.94% for hemorrhagic stroke and 5.33% for ischemic stroke, respectively). The pooled mortality rate of COVID-19 patients who experienced a hemorrhagic and ischemic stroke was 44.72% (95% CI 36.73%-52.98%) and 36.23% (95% CI 30.63%-42.24%), respectively. Conclusions: Although the occurrence of hemorrhagic and ischemic stroke is low, the mortality rates of both stroke types in patients with COVID-19 are concerning, and therefore, despite several potential pathogeneses that have been proposed, studies aimed at definitively elucidating the mechanisms of hemorrhagic and ischemic stroke in individuals with COVID-19 are warranted. PROSPERO registration: CRD42020224470 (04/12/20).

Background: In this study, we aimed to determine the global prevalence, chronological order of symptom appearance, and mortality rates with regard to hemorrhagic and ischemic stroke in patients with coronavirus disease 2019 (COVID-19) and to discuss possible pathogeneses of hemorrhagic and ischemic stroke in individuals with the disease. Methods: We searched the PubMed, Scopus, and Web of Science databases for relevant articles published up to November 8, 2020. Data regarding study characteristics, hemorrhagic stroke, ischemic stroke, and COVID-19 were retrieved in accordance with the PRISMA guidelines. The Newcastle-Ottawa scale was used to assess the quality of the eligible studies. The pooled prevalence and mortality rate of hemorrhagic and ischemic stroke were calculated. Results: The pooled estimate of prevalence of hemorrhagic stroke was 0.46% (95% CI 0.40%–0.53%; I 2=89.81%) among 67,155 COVID-19 patients and that of ischemic stroke was 1.11% (95% CI 1.03%–1.22%; I 2=94.07%) among 58,104 COVID-19 patients. Ischemic stroke was more predominant (incidence: 71.58%) than hemorrhagic stroke (incidence: 28.42%) in COVID-19 patients who experienced a stroke. In COVID-19 patients who experienced a stroke, hospital admission with respiratory symptoms was more commonly reported than that with neurological symptoms (20.83% for hemorrhagic stroke and 5.51% for ischemic stroke versus 6.94% for hemorrhagic stroke and 5.33% for ischemic stroke, respectively). The pooled mortality rate of COVID-19 patients who experienced a hemorrhagic and ischemic stroke was 44.72% (95% CI 36.73%–52.98%) and 36.23% (95% CI 30.63%–42.24%), respectively. Conclusions: Although the occurrence of hemorrhagic and ischemic stroke is low, the mortality rates of both stroke types in patients with COVID-19 are concerning, and therefore, despite several potential pathogeneses that have been proposed, studies aimed at definitively elucidating the mechanisms of hemorrhagic and ischemic stroke in individuals with COVID-19 are warranted. PROSPERO registration: CRD42020224470 (04/12/20)

Introduction: The time course and risk of hemorrhagic and ischemic stroke following left ventricular assist device (LVAD) placement is not well described. Hypothesis: Ischemic and hemorrhagic stroke are major causes of mortality following LVAD placement. Methods: Prospectively collected data of Heartmate II (N=335) and Heartware (N=70) LVAD patients from a single center were reviewed from 10/21/2004-5/19/2015. Patients were followed until transplant or death. Predictors of ischemic and hemorrhagic stroke (ICH, SAH, SDH) occurring during hospitalization for LVAD placement (early stroke) or in follow-up (late stroke) were assessed using Chi-squared or Mann-Whitney U tests. The association of stroke and mortality was assessed using multivariable logistic regression analysis. Results: Of 405 patients, stroke occurred in 69 (17%). Early ischemic and hemorrhagic stroke occurred in 18 (4.4%) and 11 (2.7%) patients, respectively. Late ischemic and hemorrhagic stroke occurred in 25 (6.2%) and 29 (7.2%) patients, respectively and 11 (3%) had more than one stroke. ICH was the most common type of hemorrhagic stroke (N=23). History of implanted cardioverter defibrillator, tobacco use, poor NYHA class and hypertension post-LVAD significantly predicted ischemic stroke, while history of hypertension and arrhythmia predicted hemorrhagic stroke (all P&lt;0.05). Stroke was the leading primary cause of death in 17% of LVAD patients (second only to multi-system organ failure [21%]). Most deaths were related to late ischemic stroke (N=9/150, 6%), or late hemorrhagic stroke (N=15/150, 10%), while only 2 (1%) died from early stroke. After adjusting for age, NYHA class, and LVAD type, late ischemic stroke (adjusted odds ratio [aOR] 8.8, 95% CI 3.3-23.5, P&lt;0.0001) and late hemorrhagic stroke (aOR 9.7, 95% CI 4.0-23.4, P&lt;0.0001) predicted death, while early ischemic or hemorrhagic stroke did not. Conclusions: Stroke is a leading cause of death in LVAD patients. Late ischemic and hemorrhagic stroke have a greater impact on mortality than early stroke. Management of risk factors, such as hypertension post LVAD, may reduce stroke and mortality rates.

Background: Atherosclerotic stroke risk factors are prevalent among young adults with stroke. However, it is not certain if these risk factors are contributors to the majority of index mechanisms of stroke in young adults. Methods: This retrospective cohort study included young adults age 18-50 with a primary stroke diagnosis (ischemic stroke, IS, transient ischemic attack, TIA, intracerebral hemorrhage, ICH, subarachnoid hemorrhage, SAH) evaluated in inpatient or outpatient settings at a tertiary care academic medical center between 1/2016-12/2017. Covariates included demographics, medical history, stroke subtype, and stroke mechanism. Comparisons were made using the Chi-square, Fisher exact, and t tests. Results: This study included 263 patients (128 women, 135 men). Atherosclerotic risk factors were common among young adults: hypertension (38%), hyperlipidemia (25%), diabetes (20%), tobacco use (47%). Women were more likely to have migraine (34% vs 16%, p=0.001), and men were more likely to be tobacco users (39% vs 54%, p=0.01). Women had more aneurysmal SAH (62% vs 23% hemorrhagic strokes, p&lt;0.001). Men had more hypertensive ICH (3% vs 23% hemorrhagic strokes, p=0.02). When comparing the frequency of atherosclerotic risk factors between young adults with stroke mechanisms commonly implicated with atherosclerosis (e.g. large artery atherosclerosis, LAA, small vessel occlusions, SVO) and unrelated stroke mechanisms, these risk factors were not more frequent in patients with LAA and SVO. Conclusion: Despite a high prevalence of atherosclerotic risk factors among young adults with stroke in this cohort, only a small proportion of young adults had stroke mechanisms pathogenically related to these risk factors. This observation should prompt further research on risk factors related to non-atherosclerotic mechanisms of stroke in young adults and modification of patient counseling about the role of atherosclerotic risk factors to their index strokes.

Response: We are delighted to notice the growing interest on stroke in young adults. In their study involving 250 patients, Spengos and Vemmos report astonishing similarities between young Finnish1 and Greek2 ischemic stroke patients regarding demographics, risk factor profile, and etiology. Strong evidence supports the protecting effects of Mediterranean diet on cardiovascular diseases,3 but in young adults, with only few having stroke attributable to atherosclerosis, the diet may apparently not play a major role. With regards to those with stroke of other determined etiology, we would, however, expect clear differences between their patients and ours due to genetic and geographic …

Objective We examined the association between initiation of antidepressants within the first year after ischaemic stroke (IS) in young adults and long-term fatal and non-fatal cardiovascular events, as well as all-cause mortality. Patients and methods The Helsinki Young Stroke Registry (HYSR) includes patients aged 15–49 years with their first-ever IS occurring 1994–2007. From nationwide registers, we obtained data on prescriptions (1993–2011) and outcomes of interest (1994–2011). Time of initiating post-stroke antidepressants (PSADs) was defined as time of the first filled prescription for antidepressants within the first year from IS. To account for non-random assignment of PSADs, we performed propensity score matching and studied the relationship between PSAD initiation and outcomes using Cox regression models with time-varying coefficients. Results Of all patients (n = 888), 206 (23.2%) initiated PSADs within the first year, of which 203 (98.5%) could be matched to 406 non-initiators. In this matched sample of 609 patients, the median follow-up time was 8.1 (interquartile range [IQR] 5.0–12.6) years and 169 (28.9%) patients had any cardiovascular events, 95 (15.8%) had recurrent ischaemic or haemorrhagic strokes and 106 (17.4%) died. Adjusted for sociodemographics and cardiovascular comorbidities, PSAD initiation was associated with recurrent ischaemic or haemorrhagic stroke 5–10 years after IS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 1.32–7.12). No association emerged between PSAD initiation and other outcomes. Conclusions In young adults, PSAD initiation within the first year after IS was associated with a heightened hazard of recurrent ischaemic or haemorrhagic stroke in the long term. Future studies are needed to verify the results and to further study the nature of this finding. KEY MESSAGES Initiation of post-stroke antidepressants (PSADs) within the first year after ischaemic stroke (IS) was associated with a heightened hazard of recurrent ischaemic or haemorrhagic stroke in the long term. Patients starting antidepressants after IS should be followed up more closely in case of recurrent events. Future studies are needed to verify the results and to further study the nature of this finding.

IntroductionWe evaluated trends in hospitalization incidence and mortality due to hemorrhagic and ischemic stroke in young adults, according to gender and developed regions in Brazil.MethodsBetween 2008–2018, we performed a population-based time-series study using official hospitalization and death data due to stroke, in individuals aged 10–49 years, from Southeast and South, Brazil. Data were based on reports from the Unified Health System of Hospital Information System and Mortality Information System. Stroke was defined by the International Classification of Diseases, 10th revision (I60–I63). A Prais-Winsten regression model was performed and the Annual Percentage Change was calculated.ResultsIn total, 78,123 hospitalizations of individuals aged 10–49 years were recorded, of which 59,448 (76%) resulted from hemorrhagic stroke (HS). The hospitalizations for HS was significantly decreased (- 4.37%) among men and women in both regions. The hospitalizations for ischemic stroke (IS) was flat, except between 2011 and 2018, when IS hospitalization rates increased. In the analysis by states, HS hospitalizations declined across all states, except for Espírito Santo, where it remained unchanged (p > 0.05). IS flat hospitalizations were observed in all states, except Espírito Santo, where it increased by 24.93%. In terms of mortality, 28,625 deaths were recorded, of which 26,548 (92.7%) resulted from HS. HS mortality decreased significantly by -3.48%and IS mortality by -3.84%. Decreases also occurred in all Southeast and South states (p < 0.05). IS remained unchanged across all states, except Minas Gerais, where it decreased by -14.95%.ConclusionsWe identified a decline in the hospitalizations and mortality of HS and a flat trend for IS in developed regions of Brazil. The recent period (2011–2018) demonstrated increasing rates in the hospitalizations of IS in both regions and genders. The mortality rates for HS and IS decreased between 2008–2018 in Southeast and South Brazil for both genders.

Background: Recent evidence suggests that stroke is increasing as a cause of morbidity and mortality in younger adults, where it carries particular significance for working individuals. Accurate and up-to-date estimates of stroke burden are important for planning stroke prevention and management in younger adults. Objectives: This study aims to estimate prevalence, mortality and disability-adjusted life years (DALYs) and their trends for total, ischemic stroke (IS) and hemorrhagic stroke (HS) in the world for 1990-2013 in adults aged 20-64 years. Methodology: Stroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease (GBD) 2013 methods. All available data on rates of stroke incidence, excess mortality, prevalence and death were collected. Statistical models were used along with country-level covariates to estimate country-specific stroke burden. Stroke-specific disability weights were used to compute years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013. Results: In 2013, in younger adults aged 20-64 years, the global prevalence of HS was 3,725,085 cases (95% UI 3,548,098-3,871,018) and IS was 7,258,216 cases (95% UI 6,996,272-7,569,403). Globally, between 1990 and 2013, there were significant increases in absolute numbers and prevalence rates of both HS and IS for younger adults. There were 1,483,707 (95% UI 1,340,579-1,658,929) stroke deaths globally among younger adults but the number of deaths from HS (1,047,735 (95% UI 945,087-1,184,192)) was significantly higher than the number of deaths from IS (435,972 (95% UI 354,018-504,656)). There was a 20.1% (95% UI -23.6 to -10.3) decline in the number of total stroke deaths among younger adults in developed countries but a 36.7% (95% UI 26.3-48.5) increase in developing countries. Death rates for all strokes among younger adults declined significantly in developing countries from 47 (95% UI 42.6-51.7) in 1990 to 39 (95% UI 35.0-43.8) in 2013. Death rates for all strokes among younger adults also declined significantly in developed countries from 33.3 (95% UI 29.8-37.0) in 1990 to 23.5 (95% UI 21.1-26.9) in 2013. A significant decrease in HS death rates for younger adults was seen only in developed countries between 1990 and 2013 (19.8 (95% UI 16.9-22.6) and 13.7 (95% UI 12.1-15.9)) per 100,000). No significant change was detected in IS death rates among younger adults. The total DALYs from all strokes in those aged 20-64 years was 51,429,440 (95% UI 46,561,382-57,320,085). Globally, there was a 24.4% (95% UI 16.6-33.8) increase in total DALY numbers for this age group, with a 20% (95% UI 11.7-31.1) and 37.3% (95% UI 23.4-52.2) increase in HS and IS numbers, respectively. Conclusions: Between 1990 and 2013, there were significant increases in prevalent cases, total deaths and DALYs due to HS and IS in younger adults aged 20-64 years. Death and DALY rates declined in both developed and developing countries but a significant increase in absolute numbers of stroke deaths among younger adults was detected in developing countries. Most of the burden of stroke was in developing countries. In 2013, the greatest burden of stroke among younger adults was due to HS. While the trends in declining death and DALY rates in developing countries are encouraging, these regions still fall far behind those of developed regions of the world. A more aggressive approach toward primary prevention and increased access to adequate healthcare services for stroke is required to substantially narrow these disparities.

Establishing new approaches for the prevention and treatment of stroke relies on identifying modifiable risk factors that contribute to the development of this complex disease. Mendelian randomization (MR) studies, analogous to naturally occurring randomized trials, can assess causality of potentially modifiable biomarkers and offer new insights into biological pathways. Stroke is the second leading cause of death worldwide and the chief determinant of long-term disability. Stroke is a heterogeneous disease arising from several distinct underlying pathologies and is typically classified as ischemic or hemorrhagic, and further subclassified using imaging data. Ischemic stroke (IS), including its 3 main subtypes: small vessel disease, large vessel disease, and cardioembolic stroke, accounts for ≈80% of stroke and is the result of an interrupted blood supply, leading to localized areas of ischemia in the brain. Small vessel disease may be a consequence of nonatherosclerotic, as well as atherosclerotic, mechanisms that result in an occlusion of the small perforating arteries, whereas large vessel disease results from occlusions or emboli from plaque rupture in larger vessels, such as a carotid artery. Cardioembolic stroke arises typically from emboli from the heart. By contrast, hemorrhagic stroke is a consequence of intracerebral hemorrhage (bleeding into the brain) or subarachnoid hemorrhage (bleeding into the subarachnoid space). These diverse stroke subtypes have distinct underlying pathologies reflecting different risk factor distributions. MR studies, using genetic variants as instrumental variables, afford a powerful approach to assessing causality of risk factors and avoid biases inherent in observational studies, including confounding and reverse causation. This review considers the contribution of MR studies to stroke epidemiology and their relevance to understanding risk factors and new therapeutic targets for stroke. Meta-analyses of large prospective studies have enhanced our knowledge of classical and emerging risk factors for stroke.1–4 Classical risk factors for stroke include nonmodifiable characteristics, …

Background: Neonatal stroke occurs in an estimated 1 in 3000 live births and is the most common cause of hemiplegic cerebral palsy in term infants. Most population based studies on neonatal stroke in the past have been single center or regional, focused only on ischemic stroke, and with less than 100 cases. Large administrative datasets can provide information on comorbid perinatal conditions in neonatal stroke. Methods: Data for patients aged 0-28 days with a diagnosis of either ischemic or hemorrhagic stroke (either subarachnoid or intracerebral hemorrhage) were extracted from the Cerner Health Facts EMR database from 2000-2018. Incidence of birth demographics, perinatal complications, anti-epileptic use, and aspirin use was assessed. Odds ratios were calculated against a cohort of neonates without stroke. Results: Among 1,591,104 neonates in the Cerner EMR database, 452 (59%) neonates were identified with ischemic stroke and 311 (41%) with hemorrhagic stroke. The most common comorbidities for ischemic stroke were neonatal sepsis (16%, OR=13.1), head and scalp birth injury (13%, OR=7.1) and hypoxic injury (12%, OR=38.7). The most common comorbidities for hemorrhagic stroke were head and scalp birth injury (30%, OR=19.5), prematurity (26%, OR=4.2) and neonatal sepsis (23%, OR=13.1). Procedure codes for intubation, neonatal resuscitation, and epinephrine use were prominent in both hemorrhagic (15.1%, OR=35) and ischemic stroke (8.9%, OR=19.1). The proportion of hemorrhagic and ischemic stroke patients receiving antiepileptics was 23% and 27%, respectively. The proportion of ischemic stroke patients who received aspirin was 16.4%. Conclusion: This population based study of neonatal stroke, the largest of its kind, demonstrated a wide variety of comorbid conditions with ischemic and hemorrhagic stroke. Antiepileptic use is common in neonatal ischemic stroke, though in our population-based study of both academic and non-academic centers the prevalence is less than prior estimates. Sepsis, head and scalp injuries, prematurity, and hypoxic injury are associated with neonatal hemorrhagic and ischemic stroke, though prevalence varies between types. More study is needed on specific risk factors and pathogenesis in neonatal stroke.

BackgroundMethamphetamine use and stroke are significant public health problems. Strokes among people aged below 45 years are much less common than in older age groups but have significant mortality and...

Enrollment in the stenting and aggressive medical management for the prevention of stroke in intracranial stenosis (SAMMPRIS) trial was halted owing to higher-than-expected 30-day stroke rates in the stenting arm. Improvement in periprocedural stroke rates from angioplasty and stenting for intracranial atherosclerotic disease (ICAD) requires an understanding of the mechanisms of these events. To identify the types and mechanisms of periprocedural stroke after angioplasty and stenting for ICAD. Patients who experienced a hemorrhagic or ischemic stroke or a cerebral infarct with temporary signs within 30 days of attempted angioplasty and stenting in SAMMPRIS were identified. Study records, including case report forms, procedure notes, and imaging were reviewed. Strokes were categorized as ischemic or hemorrhagic. Ischemic strokes were categorized as perforator territory, distal embolic, or delayed stent thrombosis. Hemorrhagic strokes were categorized as subarachnoid or intraparenchymal. Causes of hemorrhage (wire perforation, vessel rupture) were recorded. Three patients had an ischemic stroke after diagnostic angiography. Two of these strokes were unrelated to the procedure. Twenty-one patients had an ischemic stroke (n = 19) or cerebral infarct with temporary signs (n = 2) within 30 days of angioplasty and stenting. Most (n = 15) were perforator territory and many of these occurred after angiographically successful angioplasty and stenting of the basilar artery (n = 8). Six patients experienced a subarachnoid hemorrhage (3 from wire perforation) and 7 had a delayed intraparenchymal hemorrhage. Efforts at reducing complications from angioplasty and stenting for ICAD must focus on reducing the risks of regional perforator infarction, delayed intraparenchymal hemorrhage, and wire perforation.

Although acute brain injury is common in patients receiving extracorporeal membrane oxygenation, little is known regarding the mechanism and predictors of ischemic and hemorrhagic stroke. We aimed to determine the risk factors and outcomes of each ischemic and hemorrhagic stroke in patients with venoarterial extracorporeal membrane oxygenation support. Retrospective analysis. Data reported to the Extracorporeal Life Support Organization by 310 extracorporeal membrane oxygenation centers from 2013 to 2017. Patients more than 18 years old supported with a single run of venoarterial extracorporeal membrane oxygenation. None. Of 10,342 venoarterial extracorporeal membrane oxygenation patients, 401 (3.9%) experienced ischemic stroke and 229 (2.2%) experienced hemorrhagic stroke. Reported acute brain injury during venoarterial extracorporeal membrane oxygenation decreased from 10% to 6% in 5 years. Overall in-hospital mortality was 56%, but rates were higher when ischemic stroke and hemorrhagic stroke were present (76% and 86%, respectively). In multivariable analysis, lower pre-extracorporeal membrane oxygenation pH (adjusted odds ratio, 0.21; 95% CI, 0.09-0.49; p < 0.001), higher PO2 on first day of extracorporeal membrane oxygenation (adjusted odds ratio, 1.01; 95% CI, 1.00-1.02; p = 0.009), higher rates of extracorporeal membrane oxygenation circuit mechanical failure (adjusted odds ratio, 1.33; 95% CI, 1.02-1.74; p = 0.03), and renal replacement therapy (adjusted odds ratio, 1.49; 95% CI, 1.14-1.94; p = 0.004) were independently associated with ischemic stroke. Female sex (adjusted odds ratio, 1.61; 95% CI, 1.16-2.22; p = 0.004), extracorporeal membrane oxygenation duration (adjusted odds ratio, 1.01; 95% CI, 1.00-1.03; p = 0.02), renal replacement therapy (adjusted odds ratio, 1.81; 95% CI, 1.30-2.52; p < 0.001), and hemolysis (adjusted odds ratio, 1.87; 95% CI, 1.11-3.16; p = 0.02) were independently associated with hemorrhagic stroke. Despite a decrease in the prevalence of acute brain injury in recent years, mortality rates remain high when ischemic and hemorrhagic strokes are present. Future research is necessary on understanding the timing of associated risk factors to promote prevention and management strategy.