The authors utilize a unique approach to weigh-in on a brewing controversy in acute ischemic stroke management: Is intravenous thrombolysis (IVT) beneficial in large vessel occlusion (LVO) in patients receiving endovascular therapy (EVT)? Rather than reporting on symptomatic intracranial hemorrhage, as is typical in studies evaluating IVT, these authors evaluated distal migration of clot that was subsequently not amenable to retrieval with EVT in patients treated with and without thrombolytics. The hypothesis being that IVT will reduce clot size to a point that it may be dislodged from a larger, more proximal vessel to embolize into a smaller caliber, more distal vessel and not be amenable to EVT.
For their evaluation, the authors utilized a retrospective record review of patients evaluated at the Kaiser Permanente healthcare system in Northern California undergoing EVT after presenting with symptoms of acute ischemic stroke. EVT was performed at one of two comprehensive stroke centers (CSC) in the area functioning as a receiving hospital for 19 other primary stroke centers (PSC). Patients were included whether they initially presented to the PSC and were transferred or if they presented directly to the CSC. Successful recanalization was defined as a modified thrombolysis in cerebral infarction (mTICI) scale of 2b/3.
Endovascular therapies (EVT) are a cornerstone of acute ischemic stroke therapy. CT- based perfusion imaging (CT-P), in addition to native CT and CT angiography, has become established in many clinics for the identification of patients with large vessel occlusions (LVO) who are eligible for EVT. But how does the choice of initial imaging protocol affect the probability of conducting EVT in patients with LVO?
A recent retrospective cohort study with four stroke centers has addressed this question. All four centers routinely performed native CT and CT angiography as part of the initial radiological assessment. The capacity to perform CT-P and EVT was present at all centers at all times. One participating center routinely performed additional CT-P with a high rate of usage (CTP-H), whereas the other three centers performed CT-P at a lower rate of usage (CTP-L) only at clinical discretion.
The guidelines of the American Heart Association/American Stroke Association recommend MRI to identify diffusion-positive FLAIR-negative lesions (DWI-FLAIR mismatch) for selecting patients who can benefit from IV alteplase in acute ischemic stroke (AIS) patients who awake with stroke symptoms or have unclear time of onset > 4.5 hours from last known well.1 The efficacy and safety of IV alteplase for these patients was revealed by the WAKE-UP trial.2
In the WAKE-UP trial, a favorable outcome defined by mRS 0 to 1 at 90 days was achieved in 53.3% in the alteplase group and 41.8% in the placebo group (adjusted odds ratio, 1.61; 95% confidence interval [CI], 1.09 to 2.36; P = 0.02). The trial was stopped early for lack of funding, and there was numerically more death (4.1% vs 1.2%, P=0.07) and significantly more symptomatic intracranial hemorrhage (sICH) (2.0% vs. 0.4%, P= 0.15). So, there still have been some concerns about safety of the therapy.
Intravenous tissue-type plasminogen activator (IV tPA) and endovascular stroke treatment (EST) are considered standard-of-care for acute ischemic stroke. However, it is unclear whether there is a benefit to administrating IV tPA before EST in patients with large vessel occlusion who are eligible for both treatments. The need for IV tPA prior to EST has been further questioned by the results of the randomized DIRECT-MT trial, where EST alone was shown to be noninferior to IV tPA followed by EST.
Although IV tPA may improve early recanalization and reperfusion, there is concern for distal thrombus migration prior to EST, which may make the thrombus less accessible for endovascular retrieval. Data is scarce on how often this occurs. To address this issue, Flint et al performed a retrospective chart review of stroke cases in Kaiser Permanente Northern California’s Stroke EXPRESS program and examined the impact of IV tPA before EST on the rate of distal embolization, recanalization, and outcomes. The healthcare system comprises of 21 hospitals, two of which are comprehensive stroke centers, and is managed by a telemedicine program. All patients treated fully within the Kaiser Permanente Northern California system for both IV tPA and EST were included. Primary outcome was distal embolization, and secondary outcomes were angiographic (complete recanalization) and short- and long-term clinical improvements. Multivariable logistic regression was used to determine whether IV tPA with EST was associated with an increased risk of distal embolization compared to EST alone.
Large vessel occlusion of the posterior circulation has devastating effects and carries high morbidity and mortality. One of the main causes for this stroke subtype is vertebral atherosclerosis. The optimal treatment for the non-acute intracranial vertebral artery occlusion (NA-ICVAO) in patients at high risk of stroke despite the best medical treatment remains unclear. Some case-report studies showed that endovascular recanalization (ER) is feasible. However, a large heterogeneity of perioperative outcomes and a high incidence of complications makes critical to identify which patients would benefit from intervention.
In this study, the authors aimed to define an angiographic classification to explore the feasibility and safety of endovascular recanalization for symptomatic atherosclerotic NA-ICVAO that might become a reference for patient selection and risk stratification in future trials. They retrospectively analyzed 50 patients with atherosclerotic NA-ICVAO that were treated with angioplasty and stenting. Patients were divided into 4 groups according to the following angiographic classification: type I (Figure 1A), the occlusion length is ≤15 mm; type II (Figure 1B), the occlusion length is >15 mm; type III (Figure 1C and 2), the occlusion length is >15 mm, and the tortuosity angle of the occluded segment is ≥45°; and type IV (Figure 1D), the occlusion extends to the epidural segment.
Figure 1. Illustration of the angiographic classification of nonacute intracranial vertebral artery occlusion. A, Type I, the occlusion length is ≤15 mm. B, Type II, the occlusion length is >15 mm. C, Type III, the occlusion length is >15 mm, and the tortuosity angle of the occluded segment is ≥45°. D, Type IV, the occlusion extends to the epidural segment.
The median duration of occlusion was 45 days, and the median time from last symptom onset to endovascular treatment was 15 days. The overall technical success rate was 76%. The perioperative complication rate was 16% (8/50); vascular dissection occurred in 5 cases (4 asymptomatic and 1 mild stroke). One patient died of vascular perforation. Stroke or death beyond 30 days was 10.2% (5/49), 2 patients died (one for cerebral hemorrhage and another from ischemic stroke), 1 patient experienced severe ischemic stroke, and 2 patients had mild ischemic stroke. In angiographic follow-up, 4 patients developed in-stent restenosis and 3 developed reclusions.
The battle against the COVID-19 pandemic continues worldwide. As our understanding of COVID-19 evolves, so does our understanding of its neurological complications. Available evidence shows COVID-19 induces a hypercoagulable state and increases risk of thrombosis, especially in severe disease.
Early data has suggested a higher rate of ischemic stroke in severe COVID-19 infection. Majidi et al. have reported on the clinical and paraclinical findings in emergent large vessel occlusion (ELVO) stroke during New York’s COVID-19 outbreak. This retrospective observational study included data from all patients presenting with an ELVO during the peak 3-week period of hospitalizations and deaths from COVID-19. Data was collected from eight New York hospitals from March 21 to April 12, 2020. Data regarding demographics, comorbidities, risk factors, clinical presentation, treatment received, clinical outcome, and COVID-19 disease status were collected.
Due to the rapid worldwide spread of SARS-CoV-2, the World Health Organization declared COVID-19 as a public health emergency on January 30, 2020. Measures to contain the pandemic have not only halted day-to-day living, but have shifted key health and societal priorities, as the pandemic posed an unprecedented situation.
Some recent evidence suggests a decrease in ischemic stroke incidence with some European stroke centers reporting a reduction in acute stroke admissions by as much as 50-80% during the initial phase of the COVID-19 crisis. Furthermore, stroke centers in China highlighted a drop in thrombectomy rates by about 25-50% in large cities and that a majority of stroke patients did not find access to dedicated stroke units. It is important to scrutinize whether these changes are indeed true.
In the September 2020 issue of Stroke, Jasne and co-authors present important data on stroke incidence, interventions, and outcomes before and during the COVID-19 crisis. The authors recorded stroke code calls in 3 major hospitals in Connecticut during the initial peak of SARS-CoV-2 infections from January to April 2020 and compared the stroke code activity with corresponding dates of previous years. Additionally, differences in patient characteristics (i.e., demographics, clinical presentation, pre-existing conditions, socioeconomic status, age), acute stroke management (door-to-needle/door-to-reperfusion time), and outcome were assessed to identify changes during the pandemic.
Premature infants are already at high risk of neurodevelopmental delay from prematurity alone, but additional injury from intraventricular hemorrhage (IVH) is all too common, occurring in up to a fifth of premature infants.1 Infants with IVH clearly cannot afford further brain injury, so providers have to remain vigilant for the delayed co-morbidity of post-hemorrhagic hydrocephalus (PHH), which can occur in a quarter of those with severe IVH.2 Red blood cell breakdown and the release of hemoglobin is proinflammatory and damages the choroid plexus and periventricular white matter. The products of cellular destruction are thought to clog cerebrospinal fluid (CSF) reabsorption and lead to hydrocephalus.1
Understanding the detailed pathophysiology of PHH could help neonatal providers determine which infants are most at risk and could also suggest future therapeutic strategies. A study by Mahaney et al. in the June 2020 issue of Stroke3 sets out to shed light on the relationship between the clearance of blood products from the CSF after IVH and the development of PHH.
Endovascular therapy has become an invaluable tool in the treatment of acute ischemic stroke as it can provide significant improvement in the functional outcome of selected patients. Since its reception, studies have broadened the time window for endovascular therapy by using perfusion imaging during acute ischemic strokes to determine how much cerebral tissue is, or close to be, infarcted (i.e., the core) and comparing it to tissue which has reduced blood flow but is likely salvageable with reperfusion (i.e., the penumbra). The volume of the core, as well as ratio between core and penumbra, ultimately determines which patients are appropriate for endovascular therapy. Studies have shown that cerebral collateral circulation can be a major determinant of final infarct volume and can thus impact who would be deemed appropriate for thrombectomy. However, data on whether the status of collateral circulation impacts final clinical outcome in those undergoing thrombectomy remains discrepant.
In this retrospective study, Al-Dasuqi et al. investigated how collateral status impacts final infarct size, as well as functional outcomes, in those with successful and unsuccessful recanalization following endovascular therapy with either mechanical thrombectomy or intra-arterial thrombolytic drug delivery. The authors selected patients who: had evidence of large vessel occlusion on CTA in the ICA or MCA at the M1 or proximal M2 segment; underwent mechanical thrombectomy or intraarterial thrombolysis, with or without IV-tPA before intervention; had follow up MRI obtained within 24 hours to 7 days post endovascular treatment. The collateral status of patients was defined using a grading system designed by Miteff et al.1 There are 3 grades which include: “good,” where the entire MCA distal to the occluded segment reconstitutes with contrast; “moderate,” where some MCA branches distal to the occluded segment reconstituted in the sylvian fissure; and “poor,” where only distal superficial MCA branches reconstituted distal to the occlusion. Though many different grading systems for collateralization have been created, Al-Dasuqi et al. used the grading system by Miteff et al. because this grading system showed to be reliable in predicting favorable and poor outcomes in patients treated with IV-tPA while other collateral grading systems were of limited value. Successful recanalization was defined by mTICI score of 2b-3. A summation map of all infarct lesions detected on MRI was created to identify regions of infarct associated with mTICI scores and collateral grading. Early functional outcome was measured using the modified Rankin Scale (mRS) at discharge with a favorable outcome defined as mRS score of 0 to 2.
Dr. Das: Dr. Ihara, on behalf of the Blogging Stroke team, it is my pleasure to welcome you to this author interview about your publication in Stroke regarding the association between CNM gene-positive Streptococcus mutans and increased incidence of cerebral microbleeds. Given Streptococcus mutans is a common pathogen associated with dental caries, it is a potential treatment target to prevent increase in cerebral microbleeds.
Many of our readers come from a stroke background and may not be as familiar with oral pathology. It will be of interest to start by discussing some common oral pathogens implicated in cerebrovascular disease. Also, what is specific about Streptococcus mutans, and particularly the ones positive for CNM gene?
Dr. Ihara: More than 500 bacterial species have been estimated to exist in the oral cavity, and many remain to be identified and characterized. Of all the known pathogenic oral bacteria, a few have been linked to cerebrovascular diseases. Our co-investigator Prof. Nakano reported that certain strains of Streptococcus mutans (S. mutans) are potential risk factors for intracerebral hemorrhage in stroke-prone spontaneously hypertensive rats and mice with photochemically induced middle cerebral artery occlusion.1 This corresponds with findings showing periodontal infections to be risk factors for stroke, and that S. mutans is detected in 100% of samples of atherosclerotic plaques. S. mutans is a major pathogen in dental caries that can cause bacteremia by dental procedures, such as tooth extraction and periodontal surgery, or even tooth brushing in daily life. S. mutans is well known to be responsible for infective endocarditis. The hemorrhage-causing S. mutans strains express collagen-binding protein Cnm on their cell surface, enabling them to attach to exposed collagen fibers on the surface of damaged blood vessels and prevent platelet activation, thereby, leading to hemorrhages. Another dental bacterium, Porphyromonas gingivalis (P. gingivalis), is also found in atherosclerotic plaques and has been linked to the increased risk of ischemic stroke. P. gingivalis adheres to and infects endothelial cells not only to increase the expression of endothelial adhesion molecules and promote monocyte/macrophage infiltration, but also to produce cysteine proteinase gingipains, which activate protease-activated receptors-1 and -4 on platelets to induce platelet aggregation. Thus, infection from P. gingivalis could cause small vessel disease pathology through thrombotic occlusion and BBB disruption through inflammation.
