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Patent Foramen Ovale Closure Reduces Clinical but Not Silent Brain Infarcts

Mona Al Banna, MB BCh, Msc(Res)

Messé SR, Erus G, Bilello M, Davatzikos C, Andersen G, Iversen HK, Roine RO, Sjöstrand C, Rhodes JF, Søndergaard L, Kasner SE, and on behalf of the Gore REDUCE Study Investigators. Patent Foramen Ovale Closure Decreases the Incidence but Not the Size of New Brain Infarction on Magnetic Resonance Imaging: An Analysis of the REDUCE Trial. Stroke. 2021;52:3419–3426.

Patent foramen ovale (PFO) is found in one quarter of the population. However, in cryptogenic strokes, PFOs have been found in approximately one half of patients. (1) The association is even stronger in younger patients with a stroke, as a four-fold greater incidence of PFO has been detected compared to a stroke-free age- and sex-matched control group. (2) The pathophysiology of PFO-related stroke involves the paradoxical embolism of a clot from the venous circulation to the arterial circulation through a right-to-left shunt. Therefore, PFO closure to eradicate the right-to-left shunt has been proposed as an intervention to reduce PFO-related stroke. Percutaneous PFO closure devices have been in use for many years. However, up until recently, clinical trials did not show significantly lower rates of recurrent stroke with PFO closure compared to standard medical therapy alone. (3-5) A sub-group analysis of the RESPECT (Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment) trial showed significant reduction of stroke recurrence in patients with larger sized PFOs and atrial septal aneurysm. (6) The latest randomized controlled trials investigating the benefit of PFO closure utilized stricter inclusion criteria, in which patients were only eligible for closure if they had PFOs with an associated large interatrial shunt or atrial septal aneurysm, cortical stroke, and were <60 years old. (7-9) These trials concluded that the rate of recurrent stroke was significantly lower with closure, with one stroke avoided at 2 years for every 24 treated patients. (7)However, due to feasibility, these trials used an open label design where the patients and the treating clinicals were aware of the treatment assignment, increasing the risk of bias.

Real-World Experience of Mechanical Thrombectomy in Patients With Pre-Stroke Disability

Ammad Mahmood, MBChB

Millán M, Ramos-Pachón A, Dorado L, Bustamante A, Hernández-Pérez M, Rodríg uez-Esparragoza L, Gomis M, Remollo S, Castaño C, Werner M, et al., and on behalf of the Cat-SCR Consortium. Predictors of Functional Outcome After Thrombectomy in Patients With Prestroke Disability in Clinical Practice. Stroke. 2021.

Major clinical trials generally exclude patients with pre-stroke disability, generally defined as pre-stroke modified Rankin scale (mRS) of ≥2 or 3. Accordingly, thrombectomy guidelines [1, 2] state the benefit of mechanical thrombectomy (MT) for patients with pre-stroke disability is less clear, particularly for those aged >80. Patients with pre-stroke disability are routinely considered for MT particularly when other clinical and radiological factors are favorable, such as early presentation or good ASPECTS score. In this registry-based study, patients with mRS of 2 or 3 who underwent MT in the Catalonia stroke network were examined to assess any association between pre-stroke disability and outcomes, as well as aiming to identify factors predictive of favorable outcome for patients with pre-stroke disability. A favorable outcome in this context was defined as a return to baseline mRS at 90 days.

The Relationship Between Cerebrovascular Disease Profiles and Neurodegenerative Disease

Mona Al Banna, MB BCh, Msc(Res)

Lamar M, Leurgans S, Kapasi A, Barnes LL, Boyle PA, Bennett DA, Arfanakis K, Schneider JA. Complex Profiles of Cerebrovascular Disease Pathologies in the Aging Brain and Their Relationship With Cognitive Decline. Stroke. 2021.

Neurodegenerative disease with concurrent cerebrovascular disease (CVD) is associated with poorer long-term outcomes and increased functional dependency. Studies suggest that the co-existence of neurodegenerative pathologies and cerebrovascular pathologies ranges from 33-75%. However, little is known about the most common frequencies of cerebrovascular disease pathology types and the combinations of cerebrovascular pathologies that are encountered with dementia. The authors of this study set out to identify CVD frequencies and combinations in neurodegenerative disease and their association with cognitive domains affected.

By |December 15th, 2021|clinical|0 Comments

Article Commentary: “Smoking Cessation in Stroke Survivors in the United States”

Nurose Karim, MD

Parikh NS, Parasram M, White H, Merkler AE, Navi BB, Kamel H. Smoking Cessation in Stroke Survivors in the United States: A Nationwide Analysis. Stroke. 2021.

Smoking is one of the leading and preventable causes of stroke. After a primary stroke, there is an increased risk for future strokes, and recurrent strokes are usually more disabling. This article is highlighting two major topics: rate of smoking cessation in stroke survivors and comparing it with cancer survivors. The hypothesis is that smoker cessation rate is higher in cancer survivors as compared to stroke survivors.

This is a retrospective study of prospective data from 2013-2019 from the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System (BRFSS), which includes patients above age 18. Pregnant patients and those with incomplete information regarding their stroke, cancer or smoking status were excluded. A total of 3,029,122 respondents were identified, and their information was validated. Smoking status was self-reported and was validated as well. Quit ratio is defined as the proportion of ever smokers who quit. “Ever smokers,” by definition, smoked at least 100 cigarettes in a person’s lifetime. Inverse of the quit ratio is the proportion of ever smokers who continue to smoke.

By |December 13th, 2021|clinical|0 Comments

A New Independent Risk Factor for Stroke? A Brief Review of “Cumulative Concussion and Odds of Stroke in Former National Football League Players”

Yasmin Aziz, MD

Brett BL, Kerr ZY, Aggarwal NT, Chandran A, Mannix R, Walton S, DeFreese JD, Echemendia RJ, Guskiewicz KM, McCrea MA, Meehan III WP. Cumulative Concussion and Odds of Stroke in Former National Football League Players. Stroke. 2021.

In the last 20 years, the discovery of chronic traumatic encephalopathy has captured the attention of both the scientific and athletic communities, sparking a renewed interest in sports safety and concussion protocols. Inspired by preclinical studies, the authors for this article sought to examine if another feared neurologic complication, stroke, is associated with lifetime concussion exposure. In this cross-sectional study, nearly 979 men 50 years or older with at least one year’s experience in the National Football League (NFL) were sent a questionnaire asking about demographics, current functioning, as well as medical, football, concussion, and stroke history. Concussion was specifically defined using standard definition (i.e., not restricted to only episodes of being “knocked out”), and stroke history was defined by a personal history of obtaining this diagnosis from a healthcare provider. Concussion number was subgrouped into 5 categories: 0, 1-2, 3-5, 6-9, and 10 or more events. Traditional demographic risk factors were collected and placed in a multivariate logistic model to estimate adjusted odds ratio (aOR) for stroke.

By |December 10th, 2021|clinical|0 Comments

Ischemic Stroke in Hospitalized COVID-19 Patients: Incidence, Risk Factors, and Outcomes

Melissa Bailey, MD

Sluis WM, Linschoten M, Buijs JE, Biesbroek JM, den Hertog HM, Ribers T, Nieuwkamp DJ, van Houwelingen RC, Dias A, van Uden IWM, et al. Risk, Clinical Course, and Outcome of Ischemic Stroke in Patients Hospitalized With COVID-19: A Multicenter Cohort Study. Stroke. 2021;52:3978–3986.

Stroke occurrence in COVID-19 patients has been widely observed, but our understanding of the incidence and outcomes associated with stroke in those with COVID-19 is still under investigation. The association between COVID-19 and thromboembolic events has been well established, and studies have reported varying incidences of ischemic stroke associated with this disease. However, few studies have analyzed the association between ischemic stroke and other cardiovascular risk factors in those with COVID-19. Sluis and colleagues investigated the incidence, associated risk factors, and outcomes in hospitalized patients in order to add to the growing body of literature regarding stroke and COVID-19.

By |December 8th, 2021|clinical|0 Comments

Article Commentary: “Increased COVID-19 Mortality in People With Previous Cerebrovascular Disease”

Ericka Samantha Teleg, MD

Lazcano U, Cuadrado-Godia E, Grau M, Subirana I, Martinez-Carbonell E, Boher-Massaguer M, Rodríguez-Campello A, Giralt-Steinhauer E, Fernández-Pérez I, Jiménez-Conde J, et al. Increased COVID-19 Mortality in People With Previous Cerebrovascular Disease: A Population-Based Cohort Study. Stroke. 2021.

The COVID-19 pandemic has shaped and changed the diagnostic, treatment, and management landscape in stroke healthcare throughout the world. The authors of this study emphasized several important points in the beginning in defining their research question: Is previous stroke an independent risk factor for mortality after COVID-19?

At the start, COVID-19 had stroke specialists and other health care specialists analyze mortality and risk of cerebrovascular disease in a population-based cohort in a prospective methodology. This is the strength of this article; using a prospective methodology to answer a research question such as theirs is a challenge since the pandemic landscape is continuously evolving. Several other studies utilized hospital cohorts.

By |December 7th, 2021|clinical|0 Comments

World Stroke Congress: RAISE Session on New Frontiers in Neurocardiology in the 2020s

Sishir Mannava, MD

World Stroke Congress
October 28–29, 2021

Neurocardiology: The Neurologist’s Perspective – Dr. Edip Gurol

Dr. Gurol started by discussing the importance of the neurologist classifying stroke etiologies, and ultimately concern for cardioembolic infarct, and the importance of long-term cardiac monitoring in these patients as highlighted by the findings in the CRYSTAL-AF and REVEAL-AF studies. Another important role of neurologists in these patients is stratifying ICH risk if they require anticoagulation (AC). The FDA approved AC for stroke prevention, include warfarin, direct oral antiocoagulants (DOACs), and left atrial appendage closure (LAAC) with WATCHMAN/Amulet devices. Importantly, AC increased intracranial hemorrhage (ICH) risks, and outcomes of AC-associated ICH are extremely poor. High-risk categories include prior brain bleed (of many types), brain microbleeds on MRI (as highlighted in the CROMIS-2 study), white matter disease on MRI, and cognitive/gait problems. AC has been associated with between 5-7x the risk of ICH as compared to antiplatelets (AP). In a recent trial from the UK, which randomized patients to AC vs AP after spontaneous ICH, 8% (AC) as opposed to 4% (AP) had recurrent ICH. Mortality of AC-related ICH is very high, ~50%. Having a prior history of ICH related to hypertension < mixed-ICH < cerebral amyloid angiopathy ICH significantly increases recurrent ICH risk as well. This concept also applies to patients who have independent evidence of lobar microbleeds. Interestingly, Dr. Gurol highlighted a 2019 study from Neurology that showed moderate/severe white matter hyperintensities were associated with ~6% increased risk of ICH if given AC (Marti-Fabregas et al). Regarding LAAC in nonvalvular atrial fibrillation, the PRAGUE-17 trial showed that stroke prevention and bleeding risks were similar when comparing closure to DOACs. Dr. Gurol closed with discussion of patent foramen ovale (PFO) closure for stroke prevention, highlighting that hypercoagulable states and other causes should be evaluated prior to PFO closure. Ultimately, all decision-making regarding AC or device placement (LAAC, PFO) should be shared with the patient.

Declining Treatment Gaps in the United States

Sohei Yoshimura, MD, PhD

Otite FO, Saini V, Sur NB, Patel S, Sharma R, Akano EO, Anikpezie N, Albright K, Schmidt E, Hoffman H, et al. Ten-Year Trend in Age, Sex, and Racial Disparity in tPA (Alteplase) and Thrombectomy Use Following Stroke in the United States. Stroke. 2021;52:2562-2570. 

Stroke is a common disease, but there have been reports of common stroke treatment disparities related to several factors, such as age, gender, and race. This study evaluated national trends in age-, sex-, and race-specific use of IV tPA and mechanical thrombectomy (MT), the most important quality indicators for standardized stroke treatment. The data was obtained from National Inpatients Samples (NIS), the largest publicly available inpatient healthcare database in the United States.  The authors used ICD-9-CM and ICD-10-MC/procedure coding system to identify exposures and outcomes. This study revealed that the overall frequency of IV tPA and MT utilization in the U.S. increased in all age, sex, and race groups over the last decade. The pace of the increase was more pronounced in ≥80 year old patients and in Black and Hispanic patients, leading to a decline in age- and race-associated treatment gaps over time. The faster increase of IV rPA usage in women also led to narrowing of sex-related treatment gaps.

By |November 29th, 2021|clinical|0 Comments

Article Commentary: “Demographic Disparities in Proximity to Certified Stroke Care in the United States”

Parth Upadhyaya, DO

Yu CY, Blaine T, Panagos PD, Kansagra AP. Demographic Disparities in Proximity to Certified Stroke Care in the United States. Stroke. 2021;52:2571–2579.

In recent years, the widened net for time-dependent interventions of acute stroke finds a counterpoint with irregular geographic distribution of capable certified stroke centers. With this comes unequal access for varied demographics. The authors aim to identify these gaps to better focus resources on disparities as stroke care continues to evolve.

By using United States Census Bureau data, the authors first determined the location of population density centroids of each census tract (U.S. Census Bureau) and the three nearest certified stroke centers by linear distance. The shortest road distance designated the nearest stroke center to each given census tract. Age, race, ethnicity, insurance status and income for each census tract, in addition to urban versus nonurban location, were identified in relation to stroke centers. Urban was defined by population density of 1000 people per square mile with a minimum of 2,500 people. By creating a hypothetical urban and nonurban reference tract, confounding factors were controlled, and before-mentioned characteristics elucidated.

By |November 24th, 2021|clinical|0 Comments