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Role of Adolescent Body Mass Index in Stroke in Young Adults

Setareh Salehi Omran, MD

Bardugo A, Fishman B, Libruder C, Tanne D, Ram A, Hershkovitz Y, Zucker I, Furer A, Gilon R, Chodick G, et al. Body Mass Index in 1.9 Million Adolescents and Stroke in Young Adulthood. Stroke. 2021.

Despite a decline in stroke hospitalizations among older adults within the United States, there is an increasing incidence of stroke in young adults. Multiple factors are thought to play a role, including a possible increase in atherosclerotic risk factors such as obesity among young adults. Adolescent obesity is an ongoing epidemic that can lead to several complications, including diabetes, metabolic syndrome, and cardiovascular disease. Several studies have shown an association between adolescent obesity and subsequent risk of stroke in older age. It is unclear whether adolescent obesity is associated with the development of stroke in young adults.

Using data from the Israeli National Stroke Registry, Bardugo et al. examined the incidence and association between adolescent obesity and stroke in the young in Israel. Their study included all adolescents who underwent a medical evaluation prior to their mandatory military service between 1985 and 2013. The medical evaluation included information on demographics, vascular risk factors, and body mass index (BMI). BMI values were grouped according to percentiles for age and sex established by the U.S. CDC: underweight (less than 5th percentile), low-normal BMI (5th to 49th percentile), high-normal BMI (50th to 84th percentile), overweight (85th to 94th percentile), or obese (>95th percentile). The primary outcome was a first stroke event as recorded in the national registry between 2014 and 2018. Importantly, data was unavailable for patients who developed a stroke before 2014. Cox proportional hazard models were used to estimate the hazard ratios (HRs) for incidence stroke using the low-normal BMI as the reference group. In addition to a crude HR, the authors also performed three additional analyses adjusted for: 1) sex and age; 2) sex, age, and socio-demographic values; 3) sex, age, socio-demographic values, and diabetes status at beginning of follow-up. The authors also performed several sensitivity and subgroup analyses, including analyses restricted by diabetes status and optimal blood pressure at adolescence.

Using Available Imaging to Effectively Estimate Core Volumes

Lauren Peruski, DO

Voleti S, Vidovich J, Corcoran B, Zhang B, Khandwala V, Mistry E, Khatri P, Tomsick T, Vagal A. Correlation of Alberta Stroke Program Early Computed Tomography Score With Computed Tomography Perfusion Core in Large Vessel Occlusion in Delayed Time Windows. Stroke. 2021;52;498-504.

Patients presenting with an acute ischemic stroke usually undergo non-contrasted CT (NCCT) scan of the brain, followed by a CT angiogram (CTA) of the head and neck if applicable. These studies, along with physical examination, would guide recommendations regarding thrombolysis and endovascular thrombectomy. In 2000, the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was introduced as a way to assess early ischemic changes on NCCT, providing a prediction of functional outcome and ischemic core volume.  In 2018, the DAWN and DEFUSE 3 trials were published, showing an added benefit of CT perfusion (CTP) imaging in the assessment of certain acute ischemic strokes. Unfortunately, countless hospitals worldwide do not yet have CT perfusion technology available and continue to rely on standard CT scanning alone. We previously did not have data applying the ASPECTS model to cases beyond 6 hours from last known normal time. The authors of this paper hypothesized that NCCT ASPECTS and CTA-source image (CTA-SI) ASPECTS would correlate with automated CTP core volume estimates beyond 6 hours.

Article Commentary: “Unequal Local Progress Towards Healthy People 2020 Objectives for Stroke and Coronary Heart Disease Mortality”

Yasmin Aziz, MD

Woodruff RC, Casper M, Loustalot, Vaughan AS. Unequal Local Progress Towards Healthy People 2020 Objectives for Stroke and Coronary Heart Disease Mortality. Stroke. 2021.

Healthy People is a national initiative that sets prevention-based goals for the United States in ten-year increments. Healthy People 2020 (HP2020) had a goal to decrease the mortality of stroke and coronary heart disease (CHD) by at least 20% or more, bringing death rates down to 34.8 per 100,000 in stroke and to 103.4 per 100,000 in CHD. The goal of this study was to see which geographic areas were able to meet the HP2020 death rate goal or decrease their own regional mortality from stroke or CHD by at least 20%. In order to accomplish this, investigators queried the National Vital Statistics System and the National Center for Health Statistics for all counties in the United States in which people died from stroke or CHD, as defined by the International Classification of Diseases codes. Death rates for 2017 were then compared to rates from 2007 and were mapped via a Bayesian spatiotemporal model to assess progress. 

Is There a Magic Number for Thrombectomy Retrieval Attempts?

Melanie R. F. Greenway, MD

Flottmann F, Brekenfeld C, Broocks G, Leischner H, McDonough R, Faizy T, Deb-Chatterji M, Alegiani A, Thomalla G, Mpotsaris A, et al. Good Clinical Outcome Decreases With Number of Retrieval Attempts in Stroke Thrombectomy: Beyond the First-Pass Effect. Stroke. 2021;52:482-490.

Between discussion of the “First Pass Effect”1,2 and wondering “When to Stop,”3 finding a magic number of retrieval attempts that optimizes potential good outcome and minimizes risk of adverse events continues to be an important clinical question. 

Utilizing the German Stroke Registry-Endovascular Treatment section, the authors focused on reviewing number of retrieval attempts as it correlates with final TICI score and modified Rankin Score (mRS) at 90 days.  They analyzed 2611 patients from 2015-2018, 1225 of which met inclusion and exclusion criteria. All patients included were 18 years of age or older, underwent endovascular therapy of the intracranial anterior circulation, and had a complete set of data needed for the study. A successful reperfusion was defined as TICI 2b or 3, and a “good clinical outcome” was defined as mRS 0-2.

Should We Blame the Heart? Recurrent Ischemic Stroke in Patients With Atrial Fibrillation and Small Vessel Disease

Alejandro Rodríguez-Vázquez, MD

Du H, Wilson D, Ambler G , Banerjee G, Shakeshaft C, Cohen H, Yousry T, Al-Shahi Salman R, Lip GYH, Houlden H, et al. Small Vessel Disease and Ischemic Stroke Risk During Anticoagulation for Atrial Fibrillation After Cerebral Ischemia. Stroke. 2021;52:91–99.

Atrial fibrillation (AF) is one of the most important risk factors associated with ischemic stroke, with a 4.7 to 7.7%/year risk of cerebrovascular events despite anticoagulation. These recurrences could be explained because of an inadequate anticoagulation or alternative stroke mechanisms such as small vessel disease (SVD).

The authors analyzed data from the CROMIS-2 study, a multicenter prospective inception cohort study of patients anticoagulated for AF after an ischemic stroke or transient ischemic attack. They included 1419 patients with MR imaging and a total follow-up of 24 months after the first cerebrovascular event. SVD was present in 768 (54.1%) patients, defined as the presence of ≥11 basal ganglia perivascular spaces (BGPV), ≥11 centrum semiovale perivascular spaces, cerebral microbleeds, lacunes and/or moderate to severe white matter hyperintensities (which included periventricular Fazekas grade 3 or deep white matter Fazekas grade ≥2).

Expanding Access to Mechanical Thrombectomy

Kevin O’Connor, MD

Lopez-Rivera V, Salazar-Marioni S, Abdelkhaleq R, Savitz SI, Czap AL, Alderazi YJ, Chen PR, Grotta JC, Blackburn SL, Jones W, et al. Integrated Stroke System Model Expands Availability of Endovascular Therapy While Maintaining Quality Outcomes. Stroke. 2021;52:1022–1029.

Models of acute stroke care delivery, including for endovascular therapy (EVT), continue to evolve. Lopez-Rivera et al. piloted an integrated stroke system (ISS) in a large urban area that expanded EVT capabilities from an initial site to four EVT-capable hospitals. The ISS comprised a shared provider group, as well as a standardized management protocol. The primary endpoint was time from symptom onset to hospital arrival before and after implementation of the ISS. They also considered safety (postprocedural hemorrhage rate) and functional outcomes (good outcome defined as an mRS 0-2 at 90 days).

A total of 513 patients underwent EVT both pre- and post-ISS. Of these, primary endpoint evaluable data was available for the 352 patients (68.6%) who had a known time of symptom onset. There was a 40-minute decrease in time from known onset to hospital arrival compared to before the establishment of the ISS after adjusting for age and NIHSS (95% CI, 16–65, P<0.01). Among the 513 patients, there were decreases in both door to recanalization (153 versus 129 minutes, pre-ISS versus post-ISS, P<0.0001) and onset to groin puncture (229 versus 202 minutes, pre-ISS to post-ISS, P<0.05). Rates of procedural complications and good outcomes were comparable between the original EVT hospital and the three new sites included in the ISS. The reason that time of symptom onset was not known for 31% of the cohort was not explained and could be a source of bias.

Fibromuscular Dysplasia in Spontaneous Cervical Artery Dissection: A Hypothetical Question

Lukas Mayer, MD

Bonacina S, Grassi M, Zedde M, Zini A, Bersano A, Gandolfo C, Silvestrelli G, Baracchini C, Cerrato P, Lodigiani C, et al. Clinical Features of Patients With Cervical Artery Dissection and Fibromuscular Dysplasia. Stroke. 2021;52:821–829.

The search for characteristic features of underlying vasculopathy and/or connective tissue disease in patients with spontaneous cervical artery dissection has been going on for quite some time now, more recently yielding progress on multiple levels. Especially in vascular imaging, the coexistence of radiological hallmarks supposedly attributed to fibromuscular dysplasia (FMD) has been of interest in these subjects.

Through their recently published study, Bonacina et al. add to this interesting and highly relevant topic. The authors reviewed case files and imaging data of 1283 subjects enrolled in the multicenter Italian Project of Stroke in Young Adults Cervical Artery Dissection (IPSYS CeAD) study with the inclusion criterion being first-ever spontaneous cervical artery dissection (sCeAD) between January 2000 and June 2019. Through their work-up, they generated a cohort clinically consistent with most previously described sCeAD studies, as patients were in their mid 40s at sCeAD onset, males predominated, coexistent cerebrovascular risk factors were infrequent at baseline and cerebral ischemia was evident in more than 80% of sCeAD cases. Solely, the 60 to 40% split of internal carotid to vertebral artery affection might suggest an older sample of patients as more recent sCeAD-cohorts support an equal distribution of anterior and posterior circulation dissection. The latter has predominantly been attributed to the increased availability of advanced cerebrovascular imaging (e.g., 3T MRI – fat saturated T1 imaging). In 8% of subjects, according to the most recent expert consensus guidelines, vascular imaging was consistent with cerebrovascular FMD. Acute management and clinical manifestation did not differ in those with or without these signs. Subjects did, however, differ in some demographics and clinical characteristics, as those with imaging findings suggestive of FMD were more frequently women, more likely to have intracranial aneurysms and first-degree relatives with sCeAD. Upon follow-up, they also were more likely to have pseudoaneurysms, multivessel involvement of sCeAD and sCeAD recurrence. Bonacina et al. further describe pathophysiological mechanisms possibly linking migraine with aura, cerebrovascular FMD and sCeAD.

Brain’s Resident Immune Cells Gone Rogue: Impacts on Thalamic Degeneration After Stroke

Lin Kooi Ong, PhD

Cao Z, Harvey SS, Chiang T, Foltz AG, Lee AG, Cheng MY, Steinberg GK. Unique Subtype of Microglia in Degenerative Thalamus After Cortical Stroke. Stroke. 2021;52:687–698.

In my previous Blogging Stroke post, it is apparent that brain damage is not only confined to the primary infarction site after ischemic stroke, but also in remote regions of the brain. Indeed, secondary thalamic degeneration has been constantly observed in neuroimaging studies among stroke patients with cortical stroke as well as in experimental stroke models. While the mechanisms involved in the development of secondary thalamic degeneration have not been fully elucidated, studies suggest that neuroinflammation is most likely involved. Microglia are thought to be the primary resident immune cells of the brain mediating neuroinflammatory responses after stroke.

In this study, Cao and colleagues investigated the spatiotemporal changes of neurodegeneration, neuroinflammatory responses, and microglial activation for up to 84 days after experimental cortical stroke. They found that microglial activation occurred rapidly and preceded the progressive neuronal loss in the thalamus after stroke. Results from transcriptome analysis of the thalamus showed robust increase in the expression of neuroinflammation and microglia related genes. Excitingly, using a cell sorting technique, the team discovered a unique subtype of CD11c-positive microglia with disease-associated molecular profiles in the thalamus. These disease-associated microglia include reduced expression of Tmem119 and CX3CR1, and increased expression of ApoE, Axl, LpL, CSF1, and Cst7.

Expanding Knowledge of Pediatric ICH

Kevin O’Connor, MD

Boulouis G, Hak JF, Kerleroux B, Benichi S, Stricker S, Gariel F, Alias Q, Bourgeois M, Meyer P, Kossorotoff M, et al. Hemorrhage Expansion After Pediatric Intracerebral Hemorrhage. Stroke. 2021;52:588-594.

Intracerebral hemorrhage (ICH), similar to most aspects of pediatric stroke, is not as well-studied as it is in adults, in part due to its lower incidence in children. Boulouis et al. retrospectively assessed a cohort of pediatric ICH patients at a single center in Paris, France (2000-2019). Various exclusion criteria reduced their patient population from 243 to 52. Of these children, 18 had hemorrhage expansion (HE; 34.6%) and 8 of these had significant hemorrhage expansion (sHE; 15.4%). Children with sHE were more likely to have coagulation disorders (50.0% versus 2.3%; P=0.022) and tended to more frequently have focal deficits on presentation, although the difference was not significant (75.0% versus 43.2%; P=0.08). Underlying coagulation disorders were independently associated with any HE (adjusted OR, 14.4 [95% CI, 1.04–217]; P=0.048).

Outcomes were assessed using the King’s Outcome Scale for Childhood Head Injury (KOSCHI) score at 12 months. Scores <5 were poor, with scores of 2-3 reflecting severe disabilities, and score of 1 representing death. Just under half of the 52 children had a poor outcome (n=21, 40.4%) with 8 being severely disabled or dying (15.4%). Significant HE was associated with poor outcome in general (adjusted OR, 6.01 [95% CI, 0.91–39.82]; P=0.048) and with severe disability or death in particular (adjusted OR 21.71 [95% CI, 3.35–140.64]; P=0.001).

By |April 30th, 2021|clinical|0 Comments

Endovascular Stroke Therapy in the Extended Time Window: Beneficial Even in the Absence of Perfusion Imaging?

Tolga Daniel Dittrich, MD

Nogueira RG, Haussen DC, Liebeskind D, Jovin TG, Gupta R, Jadhav A, Budzik RF, Baxter B, Krajina A, Bonafe A, et al. Stroke Imaging Selection Modality and Endovascular Therapy Outcomes in the Early and Extended Time Windows. Stroke. 2021;52:491-497.

Perfusion imaging currently represents a key selection tool for endovascular therapy (EVT) in stroke patients with large vessel occlusions in the extended time window. However, the extent to which imaging modality influences clinical outcome in EVTs remains unclear in this context.

Nogueira et al. tackled this question by comparing the functional outcome of patients with intracranial carotid, M1-, or M2-occlusions of the middle cerebral artery with modified Rankin Scale score from 0 to 2 and time to treatment between early (i.e., 0-6 hours) and extended time windows (i.e., 6-24 hours) depending on the imaging modality received. These were either non-contrast computed tomography (NCCT)±CT angiography (CTA) or NCCT±CTA with CT perfusion (CTP).