American Heart Association

Monthly Archives: April 2021

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).

Optimal Timing of Anticoagulation After Ischemic Stroke in Patients With Atrial Fibrillation?

Walter Valesky, MD

Labovitz AJ, Rose DZ, Fradley MG, Meriwether J, Renati S, Martin R, Kasprowicz T, Murtagh R, Kip K, Beck T, et al. Early Apixaban Use Following Stroke in Patients With Atrial Fibrillation: Results of the AREST Trial. Stroke. 2021;52:1164-1171.

In the era of direct oral anticoagulant (DOAC) therapy, a paucity of clinical trials exist guiding anticoagulation for atrial fibrillation (AF) after acute ischemic stroke (AIS). European Heart Rhythm Association guidelines promoted (by expert panel) a 1-3-6-12 day approach with anticoagulation started after 1 day in patients with a transient ischemic attack (TIA), after 3 days in those with small strokes, after 6 days in those patients with moderate strokes and approximately 2 weeks in those with large arterial distribution strokes.­1 Guidelines from the American Heart Association are extremely broad and recommend starting anticoagulation after 4-14 days in patients with ischemic stroke.2 Additionally, these recommendations are based on data that do not adequately reflect the current management of AF using DOACs.3 Labovitz et al. attempt to give clarity to this topic with an open-label, randomized trial to evaluate the safety of early use of apixaban in patients with recent stroke compared to warfarin. 

In the AREST trial, the authors enrolled patients with onset of symptoms of AIS or TIA within 3-5 days or within 3 days, respectively. These patients also had a history of AF or newly diagnosed AF confirmed using usual methods by an electrophysiologist. Once randomized, patients in the apixaban group were started on day 0-3 for TIA, day 3-5 for small-sized AIS (<1.5cm in largest dimension), and day 7-9 for medium-sized AIS (>1.5cm but less than a full vascular territory). Patients randomized to receive warfarin were started at 1-week post-TIA or 2 weeks post-stroke. Patients with large-sized AIS (entire vascular territory) and brainstem strokes were excluded. In addition, patients with obvious contraindications to anticoagulation use such as intracranial hemorrhage (ICH), hemorrhagic transformation, as well as those with AIS believed to be from non-embolic etiologies were excluded.

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

The Role of Time and Collateral Status on Ischemic Core Overestimation on CT Perfusion

Tolga Daniel Dittrich, MD

García-Tornel Á, Campos D, Rubiera M, Boned S, Olivé-Gadea M, Requena M, Ciolli L, Muchada M, Pagola J, Rodriguez-Luna D, et al. Ischemic Core Overestimation on Computed Tomography Perfusion. Stroke. 2021.

Computed tomography perfusion (CTP) has become widely accepted as the imaging modality for the estimation of the infarct core and subsequent selection for endovascular treatment (EVT) in ischemic stroke due to large vessel occlusion (LVO), especially in the late time window. The radiological correlate for the core in CTP is usually the volume of tissue with a (compared with the contralateral hemisphere) reduction in cerebral blood flow (CBF) <30%. Overestimation of the core in CTP is thought to be time-dependent and may be a concern, especially with rapid imaging after symptom onset and fast reperfusion after imaging.

García-Tornel et al. addressed the question of the influence of time and collateral status on ischemic core overestimation. They retrospectively evaluated patients with anterior circulation LVO strokes with successful reperfusion after EVT. The core was considered to be the tissue with CBF <30% in CTP. Collateral status was assessed by the hypoperfusion intensity ratio (time to maximum of tissue residue function >6 seconds/time to maximum of tissue residue function >10 seconds). The reference for the final infarct volume was the non-contrast CT after 24 to 48 hours.

How Old is Too Old for a Statin?

Kevin O’Connor, MD

Lefeber GJ, Knol W, Souverein PC, Bouvy ML, de Boer A, Koek HL. Statins After Ischemic Stroke in the Oldest: A Cohort Study Using the Clinical Practice Research Datalink Database. Stroke. 2021;52:1244–1252.

Statins are a component of usual care following ischemic stroke, but evidence for their initiation in patients age >80-years is limited. Lefeber et al. conducted an observational cohort study to examine the effect of statin initiation on recurrence of cardiovascular events and mortality in those age >80-years following a first stroke. They performed the same analyses on patients aged 65-80 for comparison.

Patients ≥80 and 65-80 had reductions in cardiovascular events when prescribed statins for > 2 years (≥80 adjusted HR, 0.70 [95% CI, 0.52–0.92]; 65-80 adjusted HR, 0.67 [95% CI, 0.49–0.91]) compared to no statin use. There was no significant difference in event rates for either cohort when treated for 1-2 years compared to untreated patients (≥80 adjusted HR, 0.79 [95% CI, 0.59–1.07]; 65-80 adjusted HR, 1.00 [95% CI, 0.69–1.46]). Using a statin for less than one year was associated with reductions in both groups (≥80 adjusted HR, 0.43 [95% CI, 0.29–0.41]; 65-80 adjusted HR, 0.43 [95% CI, 0.34–0.54]). Compared to < 2 years of statin use (or no use), there was a nonsignificant trend toward lower risk for the ≥80 cohort (adjusted HR, 0.80 [95% CI, 0.62–1.02]) and a significant reduction in the 65-80 group (adjusted HR, 0.74 [95% CI, 0.57–0.96]) with use >2 years. Adjusted for mortality, the NNT to reduce cardiovascular events in the ≥80 group and the 65-80 group were 48.8 and 68, respectively.

By |April 28th, 2021|clinical|0 Comments

Article Commentary: “Intracerebral Hemorrhage Incidence, Mortality, and Association With Oral Anticoagulation Use”

Wern Yew Ding, MBChB

Fernando SM, Qureshi D, Talarico R, Tanuseputro P, Dowlatshahi D, Sood MM, Smith EE, Hill MD, McCredie VA, Scales DC, et al. Intracerebral Hemorrhage Incidence, Mortality, and Association With Oral Anticoagulation Use: A Population Study. Stroke. 2021.

Intracranial hemorrhage (ICH) is the second most common form of stroke and is associated with significant morbidity and mortality. A small proportion of this is related to the use of oral anticoagulation. Given the increased adoption of specialized stroke units, the outcome of these patients may have improved. In this study of adult patients with a diagnosis of ICH in Ontario between April 2009 and March 2019, Fernando and colleagues sought to investigate the incidence, trends, and short- and long-term outcomes following ICH at a population level. For this purpose, the authors utilized the health administrative database from the entire population of Ontario, Canada. Patients with spontaneous, non-traumatic ICH were identified using ICD-10 codes that were specifically chosen to avoid misclassification bias such as those with hemorrhagic transformation from ischemic stroke.

By |April 27th, 2021|clinical|0 Comments

Minor Stroke With High Risk: A New Neurological Deterioration Score

Elena Zapata-Arriaza, MD

Seners P, Ben Hassen W, Lapergue B, Arquizan C, Heldner, MR, Henon H, Perrin C, Strambo, D, Cottier J-P, Sablot D, et al; for the MINOR-STROKE Collaborators. Prediction of Early Neurological Deterioration in Individuals With Minor Stroke and Large Vessel Occlusion Intended for Intravenous Thrombolysis Alone. JAMA Neurol. 2021;78:321-328.

The conjunction of minor stroke and large vessel occlusion (LVO) occurs in a considerable frequency of patients. The question in the acute phase is always the same: Should we perform mechanical thrombectomy when symptoms are presented? Should we use bridging therapy? We do not have valid clinical trials that answer this question, but Seners and colleagues have performed a multicenter retrospective analysis to identify incidence and predictors of early neurological deterioration due to ischemia (ENDi) and thus develop and validate an easily applicable predictive score of ENDi following IVT in patients with minor stroke (NIHSS ≤ 5) and LVO (ICA T/L, Tandem lesion, M1, M2 and Basilar arteries). ENDi was defined as 4 or more points’ deterioration on NIHSS score within the first 24 hours without parenchymal hemorrhage on follow-up imaging or another identified cause.

By |April 27th, 2021|clinical|0 Comments

The Value of Simulation-Based Education in Stroke Training

Tolga D. Dittrich, MD

Evans NR, Minhas JS, Mehdi Z, Mistri AK. Incorporating Simulation-Based Education Into Stroke Training. Stroke. 2021;52:e6–e9.

Simulation-based education (SBE) is an emerging field in medical education. Several techniques are available, such as role-playing, realistic mannequins, or virtual reality, which can be used alone or in combination with one another. The fields of application in the training of stroke physicians are manifold. They range from learning clinical treatment pathways for junior clinicians to highly specific manual skills for advanced physicians.

Evans and co-authors identified three essential components for the development of successful SBE programs: (1) fidelity (i.e., creating an authentic learning experience); (2) feedback (i.e., consolidating the simulation experience); and (3) transfer of knowledge (i.e., transferring what has been learned into clinical practice).

By |April 26th, 2021|clinical|0 Comments

What Happens to Busted Clots After Using the Clot Buster?

Kevin O’Connor, MD

Ohara T, Menon BK, Al-Ajlan FS, Horn M, Najm M, Al-Sultan A, Puig J, Dowlatshahi D, Calleja Sanz AI, Sohn SI, et al.; for INTERRSeCT Study Investigators. Thrombus Migration and Fragmentation After Intravenous Alteplase Treatment: The INTERRSeCT Study. Stroke. 2021;52:203–212.

Ohara et al. conducted a post hoc analysis of data collected in the INTERRSeCT study (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) to study thrombus changes in ICA or MCA occlusions following IV t-PA and whether this affected clinical outcomes. The 427 INTERRSeCT study patients underwent baseline CTA as well as repeat CTA or conventional angiogram following IV t-PA administration. The investigators compared the proximal position of the clot on baseline and repeat imaging, and if it migrated, they graded the degree of movement on a 0-3 scale with higher grades indicating more distal movement. If there was no change in proximal position, they assessed thrombus fragmentation determined by the presence of a new thrombus in a distal artery. A 90-day modified Rankin Scale score ≤2 was considered a good outcome.