American Heart Association

Are NIHSS Score and Age More Than Just Numbers?

Meghana Srinivas, MD

Bres-Bullrich M, Fridman S, Sposato LA. Relative Effect of Stroke Severity and Age on Outcomes of Mechanical Thrombectomy in Acute Ischemic Stroke. Stroke. 2021;52:2846–2848.

In this article by Maria Bres-Bullrich et al., the authors discuss the utilization of prognostic tools in determining functional outcomes in patients with acute ischemic due to an anterior circulation large vessel occlusion (LVO) with or without mechanical thrombectomy (MT). Mechanical thrombectomy (MT) is the standard of care for patients presenting with anterior circulation LVO. However, not all patients who receive MT benefit in a similar way. Stroke severity and age, which are readily available, are strong determinants of outcomes in patients receiving MT in clinical trials, and they heavily influence the decision to perform MT. However, there is a possible discrepancy between observational studies and clinical trials, with the former showing older age group (≥80 years) is associated with lower likelihood of shift to better outcomes and higher rates of death. In real-world practice, the interplay between stroke severity and age, as well as the relative weight of each variable on outcomes, are poorly understood.

CHIP and Stroke: Risk for Cerebrovascular Diseases Dwells in the Bone Marrow

Aurora Semerano, MD

Bhattacharya R, Zekavat SM, Haessler J, Fornage M, Raffield L, Uddin MM, Bick AG, Niroula A, Yu B, Gibson C, et al. Clonal Hematopoiesis Is Associated With Higher Risk of Stroke. Stroke. 2021.

Clonal hematopoiesis of indeterminate potential (CHIP) consists of a clonal expansion of circulating blood cells that arises from somatic mutations in hematopoietic stem cells. This condition usually does not entail abnormal blood cell counts and is common in older individuals, since it has been detected by DNA sequencing in >10% of people aged 70+ years. While carrying a relatively modest risk of developing hematological malignancy, from 2014 onwards CHIP has been unexpectedly and increasingly recognized as an independent, non-traditional risk factor for cardiovascular diseases and atherosclerosis, underlying the important interplay between aging, inflammation, and cardiovascular health. Interestingly, CHIP is determined by mutations in a handful of genes, which are currently under active investigations in experimental models. For example, accelerated atherosclerosis and increased release of inflammatory cytokines have been found in mice that bear TET2-deficient leukocytes. The relationship between CHIP and stroke risk was first reported in 2014 by Jaiswal et al.1 Indeed, by analyzing two cohorts of ~3000 patients, the presence of a somatic mutation was associated with an increased risk of ischemic stroke with a hazard ratio of 2.6 (95% CI, 1.4 to 4.8).

In the article by Bhattacharya et al. recently published in Stroke, the authors aimed at expanding the knowledge about the association between CHIP and risk of cerebrovascular events, taking into account both ischemic and hemorrhagic strokes, as well as stroke etiology. A total of 86,178 individuals from 8 prospective cohorts or biobanks were included. The overall prevalence of CHIP at baseline was 6%. CHIP was associated with an increased risk of total stroke (hazard ratio, 1.14; 95% CI, 1.03–1.27). Unexpectedly, this relationship was primarily driven by a 24% increased odds of hemorrhagic stroke, particularly subarachnoid hemorrhage. Though CHIP was not found to be associated with ischemic stroke overall, in exploratory analyses from one female patient cohort, CHIP was more strongly associated with small vessel disease than with large artery atherosclerosis or cardioembolic etiologies. When analyzing mutations in specific CHIP genes, TET2 showed the strongest association with total stroke and ischemic stroke, whereas DMNT3A and TET2 were each associated with increased risk of hemorrhagic stroke.

To TEE or Not to TEE?

Kevin O’Connor, MD

Thomalla G, Upneja M, Camen S, Jensen M, Schröder J, Barow E, Boskamp S, Ostermeier B, Kissling S, Leinisch E, et al. Treatment-Relevant Findings in Transesophageal Echocardiography After Stroke: A Prospective Multicenter Cohort Study. Stroke. 2021.

About one fifth of acute ischemic strokes and transient ischemic attacks stem from cardioembolism. Although cardiac ultrasound is generally recommended as a reasonable diagnostic study, there is ongoing debate on the utility of transthoracic echocardiography (TTE) versus transesophageal echocardiography (TEE). In practice, TTE may be preferred as it is less invasive and easier to obtain but at the expense of decreased sensitivity when evaluating for some pathologies involving the aorta and left atrium. Thomalla et al. designed the Comparative Effectiveness Study of Transthoracic and Transesophageal Echocardiography in Stroke (CONTEST) study to compare the diagnostic yield of treatment-relevant findings (i.e., findings sufficient to justify a change in medication, intervention, or surgery) of TTE and TEE in patients with acute ischemic stroke, transient ischemic attack, or retinal ischemia of undetermined cause. Despite early study termination due to funding cessation, 494 patients were enrolled with 454 undergoing both TTE and TEE.  

The Tissue Clock: “Prediction of Stroke Infarct Growth Rates by Baseline Perfusion Imaging”

Tolga D. Dittrich, MD

Wouters A, Robben D, Christensen S, Marquering HA, Roos YBWEM, van Oostenbrugge RJ, van Zwam WH, Dippel DWJ, Majoie CBLM, Schonewille WJ, et al. Prediction of Stroke Infarct Growth Rates by Baseline Perfusion Imaging. Stroke. 2021.

For the acute treatment of ischemic stroke with endovascular therapy (EVT), the time between symptom onset and therapy initiation is considered crucial so far. However, the trend has shifted in recent years from rigid time windows to more individualized, advanced imaging-based, patient selection for EVT.

CT-based perfusion imaging (CTP) has gained importance in identifying individuals with potentially salvageable brain tissue. Automated perfusion assessments using specialized software (e.g., RAPID) are frequently employed in clinical practice to calculate mismatch volume. For the analysis, two key parameters are defined: the relative cerebral blood flow (rCBF) below 30% as a reflection of the ischemic core volume and the delay to the maximum of the residue function (Tmax) of more than 6 seconds, which defines critically hypoperfused brain tissue. The final infarct volume often corresponds with the ischemic core volume determined at baseline in cases of successful reperfusion. In patients without reperfusion, the size of the hypoperfused brain tissue can be used to predict the final infarct size. However, accurate prediction of final infarct size, especially as a function of reperfusion status, is not possible using these conventional CTP analyses as they only represent snapshots at the time of examination.

Article Commentary: “SLEAP SMART (Sleep Apnea Screening Using Mobile Ambulatory Recorders After TIA/Stroke)”

Dixon Yang, MD

Boulos MI, Kamra M, Colelli DR, Kirolos N, Gladstone DJ, Boyle K, Sundaram A, Hopyan JJ, Swartz RH, Mamdani M, et al. SLEAP SMART (Sleep Apnea Screening Using Mobile Ambulatory Recorders After TIA/Stroke): A Randomized Controlled Trial. Stroke. 2021.

Obstructive sleep apnea (OSA) is common in stroke/transient ischemic attack (TIA) survivors. Untreated OSA can increase risk of cardiovascular disease, including recurrent stroke, and lead to worse functional outcomes. Yet, OSA remains underdiagnosed after stroke. Barriers to diagnosis may include patient inconvenience and cost of an in-laboratory polysomnography (iPSG); therefore, Boulos et al. sought to compare the diagnostic performance of a home sleep apnea test (HSAT) in SLEAP SMART.

The primary objective of SLEAP SMART was to determine the proportion of OSA diagnosed at 6 months after stroke/TIA using HSAT as compared to iPSG. Secondarily, the trial sought to evaluate if screening for OSA with HSAT when compared to iPSG led to increased CPAP prescription, reduced daytime sleepiness, improved sleep-related quality of life, improved functional outcomes, improved patient experience with the sleep test, and cost-effectiveness for the diagnosis of OSA. Participants were recruited from 2015-2017 at a single Canadian center who had imaging-confirmed stroke or stroke-physician diagnosed TIA within the last 6 months. Exclusion criteria were a prior diagnosis of OSA, current CPAP use, comorbidities or use of medical devices that could compromise HSAT accuracy, barriers to complying with CPAP therapy, and significant physical or cognitive impairment. Eligible patients were randomized 1:1 to iPSG or HSAT. OSA was defined as apnea-hyponea index ≥15 or apnea-hyponea index ≥5 with a lowest oxygen desaturation ≤88%. Primary outcomes were compared using intention-to-treat analysis.

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

Using Post-Thrombectomy CT Perfusion to Improve Tissue Reperfusion Assessments

Vignan Yogendrakumar, MD, MSc

Tan Z, Parsons M, Bivard A, Sharma G, Mitchell P, Dowling R, Bush S, Xu A, Yan B. Optimal Tissue Reperfusion Estimation by Computed Tomography Perfusion Post-Thrombectomy in Acute Ischemic Stroke. Stroke. 2021.

In the thrombectomy era of acute stroke care, it is commonplace to utilize mTICI scores as one of the primary measures of assessing reperfusion status immediately post-procedure. In many studies, it is common to see a measure of mTICI scores 2b-3 as a representation of a good study outcome. However, registry data shows us that mTICI 2b scores are associated with an independent functional state in only 40% of patients. While the surrogate use of mTICI status to represent tissue reperfusion status is certainly a reasonable approach, the association between mTICI score and actual tissue status remains unclear.

In this study by Tan and colleagues, acute stroke patients treated at the Royal Melbourne Hospital with endovascular clot retrieval underwent CT or MRI perfusion at 24-36 hours post procedure. Comparing the baseline and follow-up perfusion scans, the authors defined optimal tissue reperfusion (TOR) as a >90% reduction of penumbra (using TMax>6s) volume. In 82 patients, those who had higher mTICI scores were more likely to achieve TOR at follow-up. Notably, achieving mTICI scores of 2c or 3 were more likely to be associated with TOR compared to mTICI 2b. Clinically, TOR was associated with improved clinical outcomes in multivariable logistic regression models.

By |November 9th, 2021|clinical|0 Comments

World Stroke Congress: “Stroke in Low to Middle Income Countries”

Ericka Samantha Teleg, MD

World Stroke Congress
October 28–29, 2021

Plenary Session: “Stroke in Low to Middle Income Countries”

While the landscape of stroke changes in terms of innovations, pathways and technology, there is a continuing increase of stroke burden in the low to middle income countries (LMICs). This session was moderated by Dr. Norlinah Ibrahim and Dr. Mayowa Owolabi.

Dr. Owolabi opened the discussion by giving an overview of the Lancet Commission in giving evidence-based recommendations that are pragmatic in nature extending to primary, secondary, and tertiary prevention, keeping in mind that these regions bear a burden due to limited resources. He emphasized the Stroke Quadrangle that includes epidemiological surveillance, acute care, rehabilitation, palliative care, health promotion, and disease prevention. He set the stage by reiterating that there is scarcity of funding for primary stroke prevention, particularly in LMICs. There is indeed an absence of an integrative approach. Regional and national differences in policymaking are also a variable. 

ASPECTS Score as a Biomarker to Predict Clinical Outcome

Arooshi Kumar, MD

Liebeskind DS, Saber H, Bhuva P, Xiang B, Yoo AJ, Jadhav AP, Haussen DC, Budzik RF, Bonafe A, Yavagal DR, et al. Serial ASPECTS in the DAWN Trial: Infarct Evolution and Clinical Impact. Stroke. 2021;52:3318–3324.

With the rapid adoption of endovascular therapy (EVT) for selected ischemic stroke patients, there remains a need to identify practical biomarkers to help predict treatment efficacy and clinical outcomes. The Alberta Stroke Program Early CT Score (ASPECTS) grading system is a well-accepted method to capture the degree of brain injury following stroke in the anterior circulation.1,2 While it has emerged as one standard method to quantify degree of ischemia and select candidates for endovascular treatment (EVT), the utility of post-intervention ASPECTS scores remains unclear.

To that end, a secondary SWIFT analysis demonstrated that post-treatment ASPECTS score was a reliable predictor of 90-day clinical function after stroke for presenting in the early intervention window (< 6hours).3 This study aimed at investigating the relevance of post-treatment ASPECTS score for later presenting window (6-24 hours) patients with ischemic stroke using the DAWN trial results. In this study, the ASPECTS score, initial and after 24 hours, was tabulated from 81 CT-CT pairs, 56 CT-MRI pairs, and 66 MRI-MRI pairs.

Article Commentary: “d-dimer Level as a Predictor of Recurrent Stroke in Patients With Embolic Stroke of Undetermined Source”

Meghana Srinivas, MD

Choi KH, Kim JH, Kim JM, Kang KW, Lee C, Kim JT, Choi SM, Park MS, Cho KH. d-dimer Level as a Predictor of Recurrent Stroke in Patients With Embolic Stroke of Undetermined Source. Stroke. 2021;52:2292–2301.

Embolic stroke of underdetermined source is used to identify patients with nonlacunar embolic cryptogenic strokes with a more restrictive inclusion criteria for strokes of cryptogenic origin and complete diagnostic workup in comparison to classic cryptogenic strokes.

Patients with a diagnosis of ESUS at the time of their index stroke carry a high risk of recurrent strokes, which is approximately twice as compared to cryptogenic stroke other than ESUS. Given this incidence, it is important to identify the underlying mechanism and cause of strokes for secondary stroke prevention. Although the most common mechanism in ESUS is embolism with covert atrial fibrillation being the most common cause, recent randomized control trials have shown that non-vitamin antagonist oral anticoagulants (OACs) are not superior to aspirin in preventing recurrence of strokes in patients with ESUS. This can be explained by the heterogeneity among the potential causes of ESUS, which can be covert AF and hidden malignancy to patients with ipsilateral carotid stenosis of less than 50% and aortic arch atherosclerosis. As in the name, it is unknown at least at the time of initial presentation. It is important to identify factors which can predict the risk of recurrent stroke in patients with ESUS and use the right secondary preventative measures.

Post-Stroke Epilepsy in Children

Kevin O’Connor, M.D.

Sundelin HEK, Tomson T, Zelano J, Söderling J, Bang P, Ludvigsson JF. Pediatric Ischemic Stroke and Epilepsy: A Nationwide Cohort Study. Stroke. 2021.

Post-stroke epilepsy is a well-known entity, particularly in adults. To explore post-stroke epilepsy in children, Sundelin et al. used the Swedish National Registers to identify 1220 children with ischemic stroke (including cerebral venous sinus thrombosis, which could not be differentiated in the Register) and 12155 comparators between 1969-2016; they excluded patients with previously known epilepsy.

Of the 1220 children with ischemic stroke, 219 (18%) developed post-stroke epilepsy compared to 91 comparators (0.7%). The epilepsy risk was highest in the six months following stroke (HR, 119.4 [95% CI, 48.0–297.4]) and remained elevated even at 20 years post-stroke (HR, 7.9 [95% CI, 3.3–19.0]). The cumulative incidence of post-stroke epilepsy increased with longer follow-up periods: 11.9% at 5 years (95% CI, 10.1%–14.0%), 21.6% (95% CI, 19.0%–24.6%), and 26.4% at 30 years (95% CI, 23.0%–30.1%).