Preprocedural Imaging : A Review of Different Radiological Factors Affecting the Outcome of Thrombectomy.

BACKGROUND: Endovascular treatment (EVT) has strong evidence for its effectiveness in treatment of acute ischemic stroke (AIS); however, up to half of the patients who undergo EVT still do not have good functional outcomes. Various prethrombectomy radiological factors have been shown to be associated with good clinical outcomes and may be the key to better functional outcomes, reduced complications, and reduced mortality. In this paper, we reviewed the current literature on these imaging parameters so they can be employed to better estimate the probability of procedural success, therefore allowing for more effective preprocedural planning of EVT strategies. We reviewed articles in the literature related to imaging factors which have been shown to be associated with EVT success. The factors which are reviewed in this paper included: anatomical factors such as 1) the type of aortic arch and its characteristics, 2) the characteristics of the thrombus such as length, clot burden, permeability, location, 3) the middle cerebral artery features including the tortuosity and underlying intracranial stenosis, 4) perfusion scans estimating the volume of infarct and the penumbra and 5) the effect of collaterals on the procedure. The prognostic effect of each factor on the successful outcome of EVT is described. The identification of preprocedural thrombectomy imaging factors can help to improve the chances of recanalization, functional outcomes, and mortality. It allows the interventionist to make time-sensitive decisions in the treatment of acute ischemic stroke.

Subclinical Cardiomyopathy in Miyoshi Myopathy Detected by Late Gadolinium Enhancement Cardiac Magnetic Resonance Imaging.

Dysferlin is a sarcolemmal protein present in muscle cells. It is responsible for muscle membrane repair. Dysferlin gene (DYSF) mutation, resulting in deficiency in this protein, is termed dysferlinopathy. Clinically, it manifests as early adulthood onset of muscle weakness with markedly elevated creatine kinase levels. The main phenotypes are limb-girdle muscular dystrophy type 2B (LGMD2B), affecting proximal muscles, and Miyoshi myopathy (MM), affecting distal muscles. Dysferlin is also present in cardiomyocytes, and case reports have emerged of cardiac abnormalities in dysferlinopathy. While routine methods of cardiac screening, namely, electrocardiography or echocardiography, are convenient and noninvasive, they often exhibit insufficient diagnostic sensitivity for detecting subclinical cardiac remodeling during early stages of cardiomyopathy. Cardiac magnetic resonance imaging though can provide accurate assessment of cardiac chamber sizes and function. With gadolinium administration, it can also detect areas of myocardial scarring and fibrosis. Early diagnosis of neuromuscular disease-related cardiomyopathy is of clinical significance, as appropriate treatment can retard myocardial fibrosis, delaying cardiomyopathy progression. We present a case of a patient with MM incidentally diagnosed with concomitant cardiomyopathy.

Impact of the COVID-19 pandemic on hyperacute stroke treatment: experience from a comprehensive stroke centre in Singapore.

The Coronavirus disease 2019 (COVID-19) pandemic is rapidly evolving and affecting healthcare systems across the world. Singapore has escalated its alert level to Disease Outbreak Response System Condition (DORSCON) Orange, signifying severe disease with community spread. We aimed to study the overall volume of AIS cases and the delivery of hyperacute stroke services during DORSCON Orange. This was a single-centre, observational cohort study performed at a comprehensive stroke centre responsible for AIS cases in the western region of Singapore, as well as providing care for COVID-19 patients. All AIS patients reviewed as an acute stroke activation in the Emergency Department (ED) from November 2019 to April 2020 were included. System processes timings, treatment and clinical outcome variables were collected. We studied 350 AIS activation patients admitted through the ED, 206 (58.9%) pre- and 144 during DORSCON Orange. Across the study period, number of stroke activations showed significant decline (p = 0.004, 95% CI 6.513 to - 2.287), as the number of COVID-19 cases increased exponentially, whilst proportion of activations receiving acute recanalization therapy remained stable (p = 0.519, 95% CI - 1.605 to 2.702). Amongst AIS patients that received acute recanalization therapy, early neurological outcomes in terms of change in median NIHSS at 24 h (-4 versus -4, p = 0.685) were largely similar between the pre- and during DORSCON orange periods. The number of stroke activations decreased while the proportion receiving acute recanalization therapy remained stable in the current COVID-19 pandemic in Singapore.

A multinational, multicentre study on the psychological outcomes and associated physical symptoms amongst healthcare workers during COVID-19 outbreak.

OBJECTIVE: Since the declaration of the coronavirus 2019 (COVID-19) outbreak as pandemic, there are reports on the increased prevalence of physical symptoms observed in the general population. We investigated the association between psychological outcomes and physical symptoms among healthcare workers. METHODS: Healthcare workers from 5 major hospitals, involved in the care for COVID-19 patients, in Singapore and India were invited to participate in a study by performing a self-administered questionnaire within the period of February 19 to April 17, 2020. Healthcare workers included doctors, nurses, allied healthcare workers, administrators, clerical staff and maintenance workers. This questionnaire collected information on demographics, medical history, symptom prevalence in the past month, Depression Anxiety Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) instrument. The prevalence of physical symptoms displayed by healthcare workers and the associations between physical symptoms and psychological outcomes of depression, anxiety, stress, and post-traumatic stress disorder (PTSD) were evaluated. RESULTS: Out of the 906 healthcare workers who participated in the survey, 48 (5.3%) screened positive for moderate to very-severe depression, 79 (8.7%) for moderate to extremely-severe anxiety, 20 (2.2%) for moderate to extremely-severe stress, and 34 (3.8%) for moderate to severe levels of psychological distress. The commonest reported symptom was headache (32.3%), with a large number of participants (33.4%) reporting more than four symptoms. Participants who had experienced symptoms in the preceding month were more likely to be older, have pre-existing comorbidities and a positive screen for depression, anxiety, stress, and PTSD. After adjusting for age, gender and comorbidities, it was found that depression (OR 2.79, 95% CI 1.54-5.07, p = 0.001), anxiety (OR 2.18, 95% CI 1.36-3.48, p = 0.001), stress (OR 3.06, 95% CI 1.27-7.41, p = 0.13), and PTSD (OR 2.20, 95% CI 1.12-4.35, p = 0.023) remained significantly associated with the presence of physical symptoms experienced in the preceding month. Linear regression revealed that the presence of physical symptoms was associated with higher mean scores in the IES-R, DASS Anxiety, Stress and Depression subscales. CONCLUSIONS: Our study demonstrates a significant association between the prevalence of physical symptoms and psychological outcomes among healthcare workers during the COVID-19 outbreak. We postulate that this association may be bi-directional, and that timely psychological interventions for healthcare workers with physical symptoms should be considered once an infection has been excluded.

Effect of erroneous body-weight estimation on outcome of thrombolyzed stroke patients.

Intravenously administered tissue plasminogen activator (IV-tPA), dose determined by patients' body-weight, remains the only approved drug treatment for acute ischemic stroke (AIS). Since a shorter onset-to-treatment time results in better functional outcome, treatment is often initiated according to the estimated or last-known body-weight of the patient. This approach may result in underdosing or overdosing of tPA. In this multicenter retrospective study, we evaluated the extent of error in tPA dosing in our AIS cohort and its impact on functional outcome and symptomatic intracranial hemorrhage (SICH). Consecutive AIS patients, receiving IV-tPA, dose determined by the estimated body-weight, at three tertiary centers between January and December 2017 were included. Collected data included information about demographics, cardiovascular risk factors, stroke subtype and National Institute of Health Stroke Scale (NIHSS) score. Estimated and measured body-weights were recorded. Modified Rankin scale (mRS) of 2 or more defined unfavorable outcome. The study included 150 patients. Median age was 64 -years (IQR 55-75) with male preponderance (67%) and median NIHSS score of 9 points (IQR 6-17). Mean measured weight of our study population was 58 (SD 13) kg. Median difference between actual and estimated body-weight was 3 kg (IQR 1.5-6). Difference was more than 10% in 35 (23.3%) patients. Good functional outcome (mRS 0-1) was achieved by 74 (49.3%) patients and 10 (6.8%) developed SICH. NIHSS (OR 1.288; 95% CI 1.157-1.435, p < 0.001) and large artery atherosclerosis (OR 5.878; 95% CI 1.929-17.910, p = 0.002) were independent predictors of unfavorable functional outcome. Our finding of the statistically insignificant 2.5-fold increase in poor outcomes among patients where the estimated and actual weight differed by more than 10% should be interpreted with caution due to the limited sample size. Significant difference occurs between estimated and actual body-weight in a considerable proportion of thrombolysed AIS patients. However, this discrepancy does not affect functional outcome or the risk of SICH.

Gut Microbiota and Stroke.

Ischemic stroke remains a significant health problem, which is expected to increase owing to an aging population. A considerable proportion of stroke patients suffer from gastrointestinal complications, including dysphagia, gastrointestinal hemorrhage, and constipation. Often, these complications adversely affect stroke outcomes. Recent research postulates the role of "brain-gut axis" in causing gut microbiota dysbiosis and various complications and outcomes. In this review, we present our current understanding about the interaction between commensal gut microbiome and brain in determining the course of stroke.

Low-dose versus standard-dose alteplase in acute ischemic stroke in Asian stroke registries: an individual patient data pooling study.

OBJECTIVE: To investigate the comparative efficacy and safety of the low-dose versus standard-dose alteplase using real-world acute stroke registry data from Asian countries. METHODS: Individual participant data were obtained from nine acute stroke registries from China, Japan, Philippines, Singapore, South Korea, and Taiwan between 2005 and 2018. Inverse probability of treatment weight was used to remove baseline imbalances between those receiving low-dose versus standard-dose alteplase. The primary outcome was death or disability defined by modified Rankin Scale scores of 2 to 6 at 90 days. Secondary outcomes were symptomatic intracerebral hemorrhage and death. Generalized linear mixed models with the individual registry as a random intercept were performed to determine associations of treatment with low-dose alteplase and outcomes. RESULTS: Of the 6250 patients (mean age 66 years, 36% women) included in these analyses, 1610 (24%) were treated with low-dose intravenous alteplase. Clinical outcomes for low-dose alteplase were not significantly different to those for standard-dose alteplase, adjusted odds ratios for death or disability: 1.00 (0.85-1.19) and symptomatic intracerebral hemorrhage 0.87 (0.63-1.19), except for lower death with borderline significance, 0.77 (0.59-1.01). CONCLUSIONS: The present analyses of real-world Asian acute stroke registry data suggest that low-dose intravenous alteplase has overall comparable efficacy for functional recovery and greater potential safety in terms of reduced mortality, to standard-dose alteplase for the treatment of acute ischemic stroke.

Rationale and design of a randomized trial of early intensive blood pressure lowering on cerebral perfusion parameters in thrombolysed acute ischemic stroke patients.

BACKGROUND AND RATIONALE: Uncertainty persists over the optimal management of blood pressure (BP) in the early phase of acute ischemic stroke (AIS). This study aims to determine the safety and effects of intensive BP lowering on cerebral blood flow (CBF) and functional in AIS patients treated with intravenous thrombolysis. METHODS: In a randomized controlled trial, 54 thrombolysed AIS patients with a systolic BP of 160 to 180 mm Hg will be randomized to early intensive BP lowering (systolic target range 140-160 mm Hg) or guideline-based BP management (systolic range 160-180 mm Hg) during first 72-hours using primarily intravenous labetalol. We hypothesize that early intensive BP lowering will not reduce CBF by 20% and/or increase the volume of hypoperfused tissue by >20% on computed tomographic perfusion. Clinical outcome will be assessed using a dichotomized modified Rankin scale (scores 0-1 as excellent outcome vs scores 2-6 as dead or dependent) at 90 days. Other outcome would be symptomatic intracerebral hemorrhage. The trial is registered at ClinicalTrials.gov, NCT03443596. CONCLUSION: This randomized study will provide important information about the physiological effects of BP reduction on cerebral perfusion after intravenous thrombolysis in AIS.

Improvement in Door-to-Needle Time in Patients with Acute Ischemic Stroke via a Simple Stroke Activation Protocol.

BACKGROUND: In acute ischemic stroke (AIS), treatment with intravenous tissue-type plasminogen activator (IV-tPA) is time-sensitive. All stroke centers make continual efforts to reduce door-to-needle time (DNT) with varying success. We present the impact of modifications to our stroke activation protocol on DNT. METHODS: We included 404 consecutive patients with AIS receiving IV-tPA between January 2014 and December 2016. First changes in stroke activation protocol were made in March 2015 in the form of prenotification by paramedics, direct transfer from ambulance to computed tomography (CT) scanner, and rapid en route neurological assessment by an emergency physician and neurologist. In March 2016, a second amendment was made where a stroke nurse accompanied the patient to expedite various steps in the treatment pathway, including endovascular treatment in eligible cases. RESULTS: Both protocol amendments resulted in improvement in DNT and door-to-CT time from 84 ± 47 minutes before intervention to 69 ± 33 minutes after protocol amendment 1 to 59 ± 37 minutes after protocol amendment 2. In particular, the second amendment (144 patients) showed significant shortening of DNT compared with the 137 patients before (59 ± 37 minutes versus 69 ± 33 minutes, P = .020), with a higher percentage achieving the target of 60 minutes (68.1% versus 48.2%, P < .001). This finding was attributed to a reduction in both door-to-CT time and CT-to-needle time. This improvement remained consistent over subsequent months. CONCLUSIONS: The application of a simple systems-based, multidisciplinary stroke activation protocol may help in significant reduction in DNT. Encouraging increased patient ownership by stroke nurses appeared to be a promising approach for timely administration of definitive acute therapies.

Eligibility for mechanical thrombectomy in acute ischemic stroke: A phase IV multi-center screening log registry.

No eligibility screening logs were kept in recent mechanical thrombectomy (MT) RCTs establishing safety and efficacy of endovascular reperfusion therapies for acute ischemic stroke (AIS). We sought to evaluate the potential eligibility for MT among consecutive AIS patients in a prospective international multicenter study. We prospectively evaluated consecutive AIS patients admitted in four tertiary-care stroke centers during a twelve-month period. Potential eligibility for MT was evaluated using inclusion criteria from MR CLEAN & REVASCAT. Our study population consisted of 1464 AIS patients (mean age 67±14years, 56% men, median admission NIHSS-score: 5, IQR: 3-10). A total of 123 (8%, 95% CI: 7%-10%) and 82 (6%, 95% CI: 5%-7%) patients fulfilled the inclusion criteria for MR CLEAN&REVASCAT respectively. No evidence of heterogeneity (p>0.100) was found in the eligibility for MT across the participating centers. Absence of proximal intracranial occlusion (69%) and hospital arrival outside the eligible time window (38% for MR CLEAN & 35% for REVASCAT) were the two most common reasons for ineligibility for MT. Our everyday clinical practice experience suggests that approximately one out of thirteen to seventeen consecutive AIS may be eligible for MT if inclusion criteria for MR CLEAN and REVASCAT are strictly adhered to.

Improvement in cerebral hemodynamic parameters and outcomes after superficial temporal artery-middle cerebral artery bypass in patients with severe stenoocclusive disease of the intracranial internal carotid or middle cerebral arteries.

OBJECT: Both the older and the recent extracranial-intracranial (EC-IC) bypass trials for symptomatic carotid occlusion failed to demonstrate a reduction in stroke recurrence. However, the role of superficial temporal artery (STA)-middle cerebral artery (MCA) bypass in patients with symptomatic intracranial stenoocclusive disease has been rarely evaluated. The authors evaluated serial changes in various cerebral hemodynamic parameters in patients with severe stenoocclusive disease of the intracranial internal carotid artery (ICA) or middle cerebral artery (MCA) and impaired cerebral vasodilatory reserve (CVR), treated by STA-MCA bypass surgery or medical treatment. METHODS: Patients with severe stenoocclusive disease of the intracranial ICA or MCA underwent transcranial Doppler (TCD) ultrasonography and CVR assessment using the breath-holding index (BHI). Patients with impaired BHI (< 0.69) were further evaluated with acetazolamide-challenge technitium-99m hexamethylpropyleneamine oxime ((99m)Tc HMPAO) SPECT. STA-MCA bypass surgery was offered to patients with impaired CVR on SPECT. All patients underwent TCD and SPECT at 4 ± 1 months and were followed up for cerebral ischemic events. RESULTS: A total of 112 patients were included. This total included 73 men, and the mean age of the entire study population was 56 years (range 23-78 years). (99m)Tc HMPAO SPECT demonstrated impaired CVR in 77 patients (69%). Of these 77 patients, 46 underwent STA-MCA bypass while 31 received best medical treatment. TCD and acetazolamide-challenge (99m)Tc HMPAO SPECT repeated at 4 ± 1 months showed significant improvement in the STA-MCA bypass group. During a mean follow-up of 34 months (range 18-39 months), only 6 (13%) of 46 patients in the bypass group developed cerebral ischemic events, as compared with 14 (45%) of 31 patients receiving medical therapy (absolute risk reduction 32%, p = 0.008). CONCLUSIONS: STA-MCA bypass surgery in carefully selected patients with symptomatic severe intracranial stenoocclusive disease of the intracranial ICA or MCA results in significant improvement in hemodynamic parameters and reduction in stroke recurrence.

Plaque Inflammation Imaging in Severe Carotid Stenosis and Recurrent Cerebral Ischemia.

A strong relationship exists between the severity of carotid stenosis and early stroke risk. Inflammation is believed to be an important event for atherosclerotic plaque destabilization and subsequent thromboembolism. (18)F-FDG can image atherosclerotic inflammation, providing information about plaque biology, which may serve as a useful biomarker for the assessment of early stroke risk.

External validation of the Boston Acute Stroke Imaging Scale and M1-BASIS in thrombolyzed patients.

BACKGROUND AND PURPOSE: Radiological findings play an essential role in therapeutic decision making and prognostication in acute ischemic stroke (AIS). The Boston Acute Stroke Imaging Scale (BASIS) and Middle Cerebral Artery-BASIS (M1-BASIS) methodologies are rapid purely radiological instruments and easily applicable for patients with AIS. We validated these methods in patients with AIS treated with intravenous tissue-type plasminogen activator. METHODS: For BASIS, patients were labeled as having major stroke if there was occlusion of distal internal carotid artery, proximal (both M1 and M2 segments) of middle cerebral artery or the basilar artery, or an Alberta Stroke Program Early CT Score≤7. M1-BASIS differs from BASIS by classifying AIS patients with M2 occlusion as a minor stroke. We evaluated these classification systems for predicting functional outcomes (modified Rankin Scale score 0-1) at 3 months. RESULTS: Two hundred sixty-five consecutive AIS patients treated with intravenous tissue-type plasminogen activator were included. On multivariate analysis, younger age (odds ratio, 1.039, 95% confidence interval, 1.009-1.070; P=0.011), lower National Institutes of Health Stroke Scale score (odds ratio, 1.140; 95% confidence interval, 1.073-1.210; P<0.001), and minor stroke by M1-BASIS (odds ratio, 2.376; 95% confidence interval, 1.047-5.393; P=0.039) were independent predictors of good functional outcome. When compared with National Institutes of Health Stroke Scale, the receiver operating characteristic curves for both BASIS (area under the curve, 0.721) and M1-BASIS (area under the curve, 0.795) correlated well with clinical severity scores. M1-BASIS has an additive effect with the National Institutes of Health Stroke Scale score to predict good outcomes. CONCLUSIONS: The purely radiological M1-BASIS correlates well with the clinical severity of stroke and can be a reliable prognostication tool in thrombolyzed AIS patients. This system might find an important place in the current era of telestroke.

Association between reversible cerebral vasoconstriction syndrome and thrombotic thrombocytopenic purpura.

BACKGROUND: Reversible cerebrovascular constriction syndrome (RCVS) presents with thunderclap headache and ischemic neurological deficits due to focal vasoconstrictions in major intracranial arteries. Reversibility of focal vasoconstrictions is the hallmark of RCVS. The commonest conditions associated with RCVS are a post-partum state and administration of vasoactive agents. METHODS: We describe a series of 3 cases of thrombotic thrombocytopenic purpura (TTP) who presented with thunderclap headache and focal neurological deficits. RESULTS: Vascular imaging revealed focal areas of constrictions in multiple intracranial arteries. All cases were treated with plasmapheresis and serial transcranial Doppler (TCD) and magnetic resonance angiography revealed resolution of cerebral vasoconstriction, accompanied by clinical recovery. CONCLUSION: RCVS should be considered in patients with TTP who presented with thunderclap headache. TCD is an important tool for monitoring the course of cerebral vasoconstriction in TTP.

Internal cerebral vein asymmetry on follow-up brain computed tomography after intravenous thrombolysis in acute anterior circulation ischemic stroke is associated with poor outcome.

BACKGROUND: Identifying early predictors of functional outcome after acute ischemic stroke (AIS) is important for planning rehabilitation strategies. Internal cerebral veins (ICV) drain deep parts of brain, run parallel to each other, and consistently seen on computed tomography angiography (CTA). Even minor asymmetry in their filling can be identified. We hypothesized that venous drainage would be impaired in patients with acute occlusion of internal carotid artery or middle cerebral artery. Because systemic thrombolysis can alter the vascular findings, we evaluated the relationship between ICV asymmetry on follow-up CTA and functional outcome. METHODS: Consecutive AIS patients treated with intravenous thrombolysis between 2007 and 2010 were included. ICV asymmetry was assessed by 2 independent blinded stroke neurologists/neuroradiologists. Functional outcome was assessed by the modified Rankin Scale (mRS) at 3 months, dichotomized as good (0-1) and poor (2-6). Data were analyzed for predictors of functional outcome. RESULTS: Of 2238 patients with AIS, 226 (10.1%) anterior circulation AIS patients received intravenous thrombolysis. The median age was 65 years (range 19-92), 44% were men, and median National Institutes of Health Stroke Scale (NIHSS) score was 16 points (range 4-32). Hypertension was the commonest risk factor in 173 (76.5%) patients, whereas 78 (34.5%) had atrial fibrillation. ICV asymmetry on follow-up CTA was assessed in 103 (45.5%) patients. Admission NIHSS score (odds ratio [OR] 1.07; 95% confidence interval [CI] 1.079-1.201, P = .046), change in NIHSS score during first 24 hours (OR .737; 95% CI .672-.807, P < .0001), and ICV asymmetry on follow-up CTA (OR 20.3; 95% CI 4.67-52.07, P < .0001) independently predicted poor outcome at 3 months. CONCLUSIONS: ICV asymmetry on follow-up CTA after intravenous thrombolysis is an early predictor of poor functional outcome.