Novel Autoantibodies in Idiopathic Small Fiber Neuropathy.

OBJECTIVE: Small fiber neuropathy (SFN) is clinically and etiologically heterogeneous. Although autoimmunity has been postulated to be pathophysiologically important in SFN, few autoantibodies have been described. We aimed to identify autoantibodies associated with idiopathic SFN (iSFN) by a novel high-throughput protein microarray platform that captures autoantibodies expressed in the native conformational state. METHODS: Sera from 58 SFN patients and 20 age- and gender-matched healthy controls (HCs) were screened against >1,600 immune-related antigens. Fluorescent unit readout and postassay imaging were performed, followed by composite data normalization and protein fold change (pFC) analysis. Analysis of an independent validation cohort of 33 SFN patients against the same 20 HCs was conducted to identify reproducible proteins in both cohorts. RESULTS: Nine autoantibodies were screened with statistical significance and pFC criteria in both cohorts, with at least 50% change in serum levels. Three proteins showed consistently high fold changes in main and validation cohorts: MX1 (FC = 2.99 and 3.07, respectively, p = 0.003, q = 0.076), DBNL (FC = 2.11 and 2.16, respectively, p = 0.009, q < 0.003), and KRT8 (FC = 1.65 and 1.70, respectively, p = 0.043, q < 0.003). Further subgroup analysis into iSFN and SFN by secondary causes (secondary SFN) in the main cohort showed that MX1 is higher in iSFN compared to secondary SFN (FC = 1.61 vs 0.106, p = 0.009). INTERPRETATION: Novel autoantibodies MX1, DBNL, and KRT8 are found in iSFN. MX1 may allow diagnostic subtyping of iSFN patients. ANN NEUROL 2022;91:66-77.

Detection of Atrial Fibrillation After Ischemic Stroke with an Insertable Cardiac Monitor: A Systematic Review and Individual Patient Data Meta-Analysis of Randomised Clinical Trials.

OBJECTIVE: In ischemic stroke patients, we compared the use of insertable cardiac monitor (ICM) versus non-ICM methods of cardiac monitoring on the incidence of atrial fibrillation (AF) detection and other clinical outcomes. BACKGROUND: Current guidelines recommend the routine use of 12-lead electrocardiography or Holter monitoring for AF detection after ischemic stroke. Recent randomised controlled trials have investigated the impact of ICM versus non-ICM methods of cardiac monitoring for AF detection in this population. However, precise recommendations for monitoring post-stroke AF are lacking; including the optimal timing, duration, and method of electrocardiography monitoring. METHODS: A systematic search was conducted on Embase and PubMed from database inception until 27 October 2022 to include randomised controlled trials that compared ICM with non-ICM methods of cardiac monitoring for post-stroke AF detection. This yielded 3 randomised controlled trials with a combined cohort of 1231 patients with a recent ischemic stroke. Individual patient data (IPD) was then reconstructed from Kaplan-Meier curves and analysed using the shared-frailty Cox model. An aggregate data meta-analysis was conducted for 1231 patients across all 3 studies for outcomes that could not be reconstructed using IPD. RESULTS: One-stage meta-analysis demonstrated an increase in the hazard ratio (HR 6.01, 95% CI 3.40-10.60; p<0.001) of AF detection in patients undergoing monitoring via ICM compared to standard care. Aggregate data meta analysis revealed a significant increase in initiation of anticoagulation (OR 3.09, 95% CI 2.05 - 4.66; p<0.00001) in the ICM group. However, no significant differences in the incidence of recurrent ischemic stroke, transient ischemic attack or death were found. CONCLUSIONS: In this meta-analysis, we found that the use of ICM increased the detection rate of post-stroke AF and the rate of anticoagulation initiation. However, this did not translate into a reduced incidence of recurrent ischemic stroke.

Safety and clinical outcomes in endovascular treatment for symptomatic cerebral venous thrombosis: a single-center experience with meta-analysis.

The role of mechanical thrombectomy (MT) in cerebral venous sinus thrombosis (CVT) is ambiguous. This study aims to share our experience with MT in CVT, supplemented by a meta-analysis on this treatment. All patients who had MT for CVT at our institution, between 2016 and 2021, were retrospectively reviewed for treatment indications, the technique used, success and complication rates, and clinical outcomes. A meta-analysis was performed for clinical and safety outcomes from published literature with > 10 patients. A total of 15 patients were included in this study. All had a venous hemorrhage or deteriorating despite anticoagulation. MT was performed using aspiration (with wide bore catheters) in 7 patients: aspiration with stent retriever in 5 and transjugular Fogarty-balloon thrombectomy in 3 patients. Adjunctive intra-sinus thrombolysis (IST) was used in 4 cases and venoplasty in 3. Technical success (restoring antegrade venous flow on arterial injection) was 100% with no procedure-related major complication. The direct transjugular approach was cheaper and faster. At 3-month follow-up, 86% of patients had good outcomes (MRS < 2). Meta-analysis of clinical and safety outcomes from 22 and 20 studies, respectively, demonstrated a positive association between MT and good outcomes as well as no significant association with hazardous periprocedural events. EVT via mechanical means for CVT is feasible in our series and meta-analysis. From our experience, trans-jugular Fogarty balloon embolectomy seems to be a potential cost-saving option, at least in a certain part of the world.

Etiologies, mechanisms, and risk factors of ischemic stroke in a young Asian adult cohort.

OBJECTIVES: Risk factors and causes of acute ischemic stroke (AIS) are more diverse in young adults, and traditional stroke classifications may be inadequate. Precise characterisation of AIS is important for guiding management and prognostication. We describe stroke subtypes, risk factors and etiologies for AIS in a young Asian adult population. MATERIALS AND METHODS: Young AIS patients aged 18-50 years admitted to two comprehensive stroke centres from 2020-2022 were included. Stroke etiologies and risk factors were adjudicated using Trial of Org 10172 in Acute Stroke Treatment (TOAST) and International Pediatric Stroke Study (IPSS) risk factors. Potential embolic sources (PES) were identified in a subgroup with embolic stroke of undetermined source (ESUS). These were compared across sex, ethnicities and age groups (18-39 years versus 40-50 years). RESULTS: A total of 276 AIS patients were included, with mean age 43±5.7 years and 70.3% male. Median duration of follow-up was 5 months (IQR: 3-10). The most common TOAST subtypes were small-vessel disease (32.6%) and undetermined etiology (24.6%). IPSS risk factors were identified in 95% of all patients and 90% with undetermined etiology. IPSS risk factors included atherosclerosis (59.5%), cardiac disorders (18.7%), prothrombotic states (12.4%) and arteriopathy (7.7%). In this cohort, 20.3% had ESUS, of which 73.2% had at least one PES, which increased to 84.2% in those <40 years old. CONCLUSIONS: Young adults have diverse risk factors and causes of AIS. IPSS risk factors and ESUS-PES construct are comprehensive classification systems that may better reflect heterogeneous risk factors and etiologies in young stroke patients.

Effect of Sex on Outcomes of Mechanical Thrombectomy in Basilar Artery Occlusion: A Multicentre Cohort Study.

INTRODUCTION: Identifying differences in outcome of basilar artery occlusion (BAO) between males and females may be useful in aiding clinical management. Recent studies have demonstrated widespread underrepresentation of women in acute stroke clinical trials. This international multicentre study aimed to determine sex differences in outcome after mechanical thrombectomy (MT) for patients with acute BAO. METHODS: We performed a retrospective analysis of consecutive patients with BAO who had undergone MT in seven stroke centres across five countries (Singapore, Taiwan, United Kingdom, Sweden, and Germany), between 2015 and 2020. Primary outcome was a favourable functional outcome measured by a modified Ranking Scale (mRS) of 0-3 at 90 days. Secondary outcomes were mRS 0-3 upon discharge, mortality, symptomatic intracranial haemorrhage (sICH) and subarachnoid haemorrhage (SAH). RESULTS: Among the 322 patients who underwent MT, 206 (64.0%) patients were male and 116 (36.0%) were female. Females were older than males (mean ± SD 70.9 ± 14.3 years vs. 65.6 ± 133.6 years; p = 0.001) and had higher rates of atrial fibrillation (38.9% vs. 24.2%; p = 0.012). Time from groin puncture to reperfusion was shorter in females than males (mean ± SD 57.2 ± 37.2 min vs. 71.1 ± 50.9 min; p = 0.021). Despite these differences, primary and secondary outcome measures were similar in females and males, with comparable rates of favourable 90-day mRS scores (mean ± SD 46 ± 39.7 vs. 71 ± 34.5; OR = 1.20; 95% confidence interval [CI] = 0.59-2.43; p = 0.611), favourable discharge mRS scores (mean ± SD 39 ± 31.6 vs. 43 ± 25.9; OR = 1.38; 95% CI = 0.69-2.78; p = 0.368) and in-hospital mortality (mean ± SD 30 ± 25.9 vs. 47 ± 22.8; OR = 1.15; 95% CI = 0.55-2.43; p = 0.710. Rates of complications such as sICH (mean ± SD 5 ± 4.3 vs. 9 ± 4.4; OR = 0.46; 95% CI = 0.08-2.66; p = 0.385) and SAH (mean ± SD 4 ± 3.4 vs. 5 ± 2.4; OR = 0.29; 95% CI = 0.03-3.09; p = 0.303) comparably low in both groups. CONCLUSION: Females achieved comparable functional outcomes compared with males after undergoing MT for BAO acute ischemic stroke.

Effect of frailty on outcomes of endovascular treatment for acute ischaemic stroke in older patients.

BACKGROUND: frailty has been shown to be a better predictor of clinical outcomes than age alone across many diseases. Few studies have examined the relationship between frailty, stroke and stroke interventions such as endovascular thrombectomy (EVT). OBJECTIVE: we aimed to investigate the impact of frailty measured by clinical frailty scale (CFS) on clinical outcomes after EVT for acute ischemic stroke (AIS) in older patients ≥70 years. METHODS: in this retrospective cohort study, we included all consecutive AIS patients age ≥ 70 years receiving EVT at a single comprehensive stroke centre. Patients with CFS of 1-3 were defined as not frail, and CFS > 3 was defined as frail. The primary outcome was modified Rankin Score (mRS) at 90 days. The secondary outcomes included duration of hospitalisation, in-hospital mortality, carer requirement, successful reperfusion, symptomatic intracranial haemorrhage and haemorrhagic transformation. RESULTS: a total of 198 patients were included. The mean age was 78.1 years and 52.0% were female. Frail patients were older, more likely to be female, had more co-morbidities. CFS was significantly associated with poor functional outcome after adjustment for age, NIHSS and time to intervention (adjusted odds ratio [aOR] 1.54, 95% confidence interval [CI] 1.04-2.28, P = 0.032). There was trend towards higher mortality rate in frail patients (frail: 18.3%; non-frail: 9.6%; P = 0.080). There were no significant differences in other secondary outcomes except increased carer requirement post discharge in frail patients (frail: 91.6%; non-frail: 72.8%; P = 0.002). CONCLUSIONS: frailty was associated with poorer functional outcome at 90 days post-EVT in patients ≥ 70 years.

Outcomes in young adults with acute ischemic stroke undergoing endovascular thrombectomy: A real-world multicenter experience.

Endovascular thrombectomy (EVT) is the standard of care for anterior circulation acute ischemic stroke (AIS) with large vessel occlusion (LVO). Young patients with AIS-LVO have distinctly different underlying stroke mechanisms and etiologies. Much is unknown about the safety and efficacy of EVT in this population of young AIS-LVO patients. All consecutive AIS-LVO patients aged 50 years and below were included in this multicenter cohort study. The primary outcome measured was functional recovery at 90 days, with modified Rankin Scale of 0-2 deemed as good functional outcome. A total of 275 AIS-LVO patients that underwent EVT from 10 tertiary centers in Germany, Sweden, Singapore, and Taiwan were included. Successful reperfusion was achieved in 85.1% (234/275). Good functional outcomes were achieved in 66.0% (182/275). Arterial dissection was the most prevalent stroke etiology (42/195, 21.5%). National Institutes of Health Stroke Scale (NIHSS) score at presentation was inversely related to good functional outcomes (aOR: 0.92, 95% CI: 0.88-0.96 per point increase, p < 0.001). Successful reperfusion (aOR: 3.22, 95% CI: 1.44-7.21, p = 0.005), higher ASPECTS (aOR: 1.21, 95% CI: 1.01-1.44, p = 0.036), and bridging intravenous thrombolysis (aOR: 2.37, 95% CI: 1.29-4.34, p = 0.005) independently predicted good functional outcomes. Successful reperfusion was inversely associated with in-hospital mortality (aOR: 0.14, 95% CI: 0.03-0.57, p = 0.006). History of hypertension strongly predicted in-hospital mortality (aOR: 4.59, 95% CI: 1.10-19.13, p = 0.036). While differences in functional outcomes exist across varying stroke aetiologies, high rates of successful reperfusion and good outcomes are generally achieved in young AIS-LVO patients undergoing EVT.

Association of Electrocardiographic P-Wave Markers and Atrial Fibrillation in Embolic Stroke of Undetermined Source.

BACKGROUND: Several P-wave indices are thought to represent underlying atrial remodeling and have been associated with ischaemic stroke even in the absence of atrial fibrillation (AF). However, the utility of these P-wave indices in predicting outcomes in patients with embolic stroke of undetermined source (ESUS) has not been studied. The aim of this study is to examine these different P-wave indices towards predicting new-onset AF and stroke recurrence in a cohort of patients with ESUS, thereby demonstrating the value of these electrocardiographic markers for stroke risk stratification. METHODS: Between October 2014 and October 2017, consecutive patients diagnosed with ESUS were followed for new-onset AF and ischaemic stroke recurrence. The various P-wave indices, namely, the P-terminal force in the precordial lead V1 (PTFV1), P-wave duration, P-wave dispersion, interatrial blocks, and P-wave axis, were assessed on the initial electrocardiogram on presentation and studied for their relation to eventual AF detection and recurrent stroke. RESULTS: 181 ischaemic stroke patients with ESUS were recruited and followed up for a median duration of 2.1 years. An abnormal PTFV1 was associated with occult AF detection but not with recurrent ischaemic strokes. No significant association was observed between the other P-wave indices with either occult AF or stroke recurrence. CONCLUSION: PTFV1 is associated with AF detection but not recurrent strokes in ESUS patients and can be a useful electrocardiographic marker for further risk stratification in ESUS patients.

Headache Related to PPE Use during the COVID-19 Pandemic.

PURPOSE OF REVIEW: Personal protection equipment (PPE)-associated headache is an unusual secondary headache disorder that predominantly occurs in healthcare workers as a consequence of the donning of protective respirators, face masks and/or eyewear. The appreciation of this entity is important given the significant ramifications upon the occupational health of healthcare workers and could additionally have an impact on persons living with pre-existing headache disorder(s). RECENT FINDINGS: There has been a renewed interest and recognition of PPE-associated headaches amongst healthcare professionals, largely brought about by the ongoing COVID-19 pandemic which has besieged healthcare systems worldwide. De novo PPE-associated headaches may present with migrainous or tension-type features and can be viewed as a subtype of external compression headache. The prognosis of the disorder is generally favourable, given that most headaches are short-lived without long-term sequalae. Several aetiologies have been postulated to account for the development of these headaches. Notably, these headaches can affect the occupational health and work performance of healthcare workers. In this review, we discuss the epidemiology, clinical characteristics, probable etiopathogenesis, management and prognosis of PPE-associated headaches in the context of the COVID-19 pandemic. Future directions for research and PPE development are proposed.

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.

Left Atrial Volume Index Predicts New-Onset Atrial Fibrillation and Stroke Recurrence in Patients with Embolic Stroke of Undetermined Source.

INTRODUCTION: It is unclear which surrogate of atrial cardiopathy best predicts the risk of developing a recurrent ischemic stroke in embolic stroke of undetermined source (ESUS). Left atrial diameter (LAD) and LAD index (LADi) are often used as markers of left atrial enlargement in current ESUS research, but left atrial volume index (LAVi) has been found to be a better predictor of cardiovascular outcomes in other patient populations. OBJECTIVE: We aim to compare the performance of LAVi, LAD, and LADi in predicting the development of new-onset atrial fibrillation (AF) and stroke recurrence in ESUS. METHODS: Between October 2014 and October 2017, consecutive patients diagnosed with ESUS were followed for new-onset AF, ischemic stroke recurrence, and a composite outcome of occult AF and stroke recurrence. LAVi and LADi were measured by transthoracic echocardiogram; "high" LAVi was defined as ≥35 mL/m2 in accordance with American Society of Echocardiography guidelines. RESULTS: 185 ischemic stroke patients with ESUS were recruited and followed for a median duration of 2.1 years. Increased LAVi was associated with new-onset AF detection (aOR 1.08; 95% CI 1.03-1.14; p = 0.003) and stroke recurrence (aOR 1.05; 95% CI 1.01-1.10; p = 0.026). Patients with "high" LAVi had a higher likelihood of developing a composite of AF detection and stroke recurrence (HR 3.45; 95% CI 1.55-7.67; p = 0.002). No significant association was observed between LADi and either occult AF or stroke recurrence. CONCLUSIONS: LAVi is associated with new-onset AF and stroke recurrence in ESUS patients and may be a better surrogate of atrial cardiopathy.

Headaches Associated With Personal Protective Equipment - A Cross-Sectional Study Among Frontline Healthcare Workers During COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease of pandemic proportions. Healthcare workers in Singapore working in high-risk areas were mandated to wear personal protective equipment (PPE) such as N95 face mask and protective eyewear while attending to patients. OBJECTIVES: We sought to determine the risk factors associated with the development of de novo PPE-associated headaches as well as the perceived impact of these headaches on their personal health and work performance. The impact of COVID-19 on pre-existing headache disorders was also investigated. METHODS: This is a cross-sectional study among healthcare workers at our tertiary institution who were working in high-risk hospital areas during COVID-19. All respondents completed a self-administered questionnaire. RESULTS: A total of 158 healthcare workers participated in the study. Majority [126/158 (77.8%)] were aged 21-35 years. Participants included nurses [102/158 (64.6%)], doctors [51/158 (32.3%)], and paramedical staff [5/158 (3.2%)]. Pre-existing primary headache diagnosis was present in about a third [46/158 (29.1%)] of respondents. Those based at the emergency department had higher average daily duration of combined PPE exposure compared to those working in isolation wards [7.0 (SD 2.2) vs 5.2 (SD 2.4) hours, P < .0001] or medical ICU [7.0 (SD 2.2) vs 2.2 (SD 0.41) hours, P < .0001]. Out of 158 respondents, 128 (81.0%) respondents developed de novo PPE-associated headaches. A pre-existing primary headache diagnosis (OR = 4.20, 95% CI 1.48-15.40; P = .030) and combined PPE usage for >4 hours per day (OR 3.91, 95% CI 1.35-11.31; P = .012) were independently associated with de novo PPE-associated headaches. Since COVID-19 outbreak, 42/46 (91.3%) of respondents with pre-existing headache diagnosis either "agreed" or "strongly agreed" that the increased PPE usage had affected the control of their background headaches, which affected their level of work performance. CONCLUSION: Most healthcare workers develop de novo PPE-associated headaches or exacerbation of their pre-existing headache disorders.

An unusual cause of acute ischemic stroke: Adult Onset Still's Disease.

Adult Onset Still's Disease (AOSD) is a systemic inflammatory disease of unknown aetiology. The usual manifestations of AOSD are spiking fevers, arthritis, and an evanescent salmon-pink rash, with neurological manifestations occasionally described. Stroke is a rare manifestation of AOSD and the exact mechanism for stroke in AOSD remains unknown, although it has been hypothesized to be secondary to thrombocytosis or vasculitis. We present a case where acute ischemic stroke secondary to a floating internal carotid artery thrombus was an early manifestation of AOSD. The patient also had prolonged high spiking fevers, significant leucocytosis, arthralgias and transaminitis. He responded well to a high dose of oral corticosteroids and was eventually started on anticoagulation for secondary stroke prevention. To our knowledge, this is the first described case of arterial thrombosis associated with AOSD. We postulate that thrombocytosis, vasculitis and hypercoagulability from the underlying inflammatory state may have contributed to the ischemic stroke.

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.

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.

Genotype-guided versus traditional clinical dosing of warfarin in patients of Asian ancestry: a randomized controlled trial.

BACKGROUND: Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry, yet its utility in Asian patients remains unresolved. METHODS: An open-label, non-inferiority, 1:1 randomized trial was conducted at three academic hospitals in South East Asia, involving 322 ethnically diverse patients newly indicated for warfarin (NCT00700895). Clinical follow-up was 90 days. The primary efficacy measure was the number of dose titrations within the first 2 weeks of therapy, with a mean non-inferiority margin of 0.5 over the first 14 days of therapy. RESULTS: Among 322 randomized patients, 269 were evaluable for the primary endpoint. Compared with traditional dosing, the genotype-guided group required fewer dose titrations during the first 2 weeks (1.77 vs. 2.93, difference -1.16, 90% CI -1.48 to -0.84, P < 0.001 for both non-inferiority and superiority). The percentage of time within the therapeutic range over 3 months and median time to stable international normalized ratio (INR) did not differ between the genotype-guided and traditional dosing groups. The frequency of dose titrations (incidence rate ratio 0.76, 95% CI 0.67 to 0.86, P = 0.001), but not frequency of INR measurements, was lower at 1, 2, and 3 months in the genotype-guided group. The proportions of patients who experienced minor or major bleeding, recurrent venous thromboembolism, or out-of-range INR did not differ between both arms. For predicting maintenance doses, the pharmacogenetic algorithm achieved an R2 = 42.4% (P < 0.001) and mean percentage error of -7.4%. CONCLUSIONS: Among Asian adults commencing warfarin therapy, a pharmacogenetic algorithm meets criteria for both non-inferiority and superiority in reducing dose titrations compared with a traditional dosing approach, and performs well in prediction of actual maintenance doses. These findings imply that clinicians may consider applying a pharmacogenetic algorithm to personalize initial warfarin dosages in Asian patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00700895 . Registered on June 19, 2008.

High Incidence of Occult Atrial Fibrillation in Asian Patients with Cryptogenic Stroke.

BACKGROUND: Occult atrial fibrillation (AF) is not uncommon in patients with stroke. In western cohorts, insertable loop recorders (ILRs) have been shown to be the gold-standard and are cost-effective for AF detection. Anticoagulation for secondary stroke prevention is indicated if AF is detected. The incidence of occult AF among Asian patients with cryptogenic stroke is unclear. METHODS: Patients with cryptogenic stroke referred between August 2014 and February 2017 had ILRs implanted. Episodes of AF >2 minutes duration were recorded using proprietary algorithms within the ILRs, whereupon clinicians and patients were alerted via remote monitoring. All AF episodes were adjudicated using recorded electrograms. Once AF was detected, patients were counseled for anticoagulation. RESULTS: Seventy-one patients with cryptogenic stroke, (age 61.9 ± 13.5 years, 77.5% male, mean CHA2DS2VASc score of 4.2 ± 1.3) had ILRs implanted. Time from stroke to the ILR implant was a median of 66 days. Duration of ILR monitoring was 345 ± 229 days. The primary endpoint of AF detection at 6 months was 12.9%; and at 12 months it was 15.2%. Median time to detection of AF was 50 days. The AF episodes were all asymptomatic and lasted a mean of 77 minutes (± 118.9). Anticoagulation was initiated in all but 1 patient found to have AF. CONCLUSIONS: The incidence of occult AF is high in Asian patients with cryptogenic stroke and comparable to western cohorts. The combination of ILR and remote monitoring is a highly automated, technologically driven, and clinically effective technique to screen for AF.

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.

Validation of Serial Alberta Stroke Program Early CT Score as an Outcome Predictor in Thrombolyzed Stroke Patients.

BACKGROUND: The Alberta Stroke Program Early CT Score (ASPECTS) on baseline imaging is an established predictor of functional outcome in anterior circulation acute ischemic stroke (AIS). We studied ASPECTS before intravenous thrombolysis (IVT) and at 24 hours to assess its prognostic value. METHODS: Data for consecutive anterior circulation AIS patients treated with IVT from 2006 to 2013 were extracted from a prospectively managed registry at our tertiary center. Pre-thrombolysis and 24-hour ASPECTS were evaluated by 2 independent neuroradiologists. Outcome measures included symptomatic intracranial hemorrhage (SICH), modified Rankin Scale (mRS) at 90 days, and mortality. Unfavorable functional outcome was defined by mRS >1. Dramatic ASPECTS progression (DAP) was defined as deterioration in ASPECTS by 6 points or more. RESULTS: Of 554 AIS patients thrombolyzed during the study period, 400 suffered from anterior circulation infarction. The median age was 65 years (interquartile range (IQR): 59-70) and the median National Institutes of Health Stroke Scale score was 18 points (IQR: 12-22). Compared with the pre-IVT ASPECTS (area under the curve [AUC] = .64, 95% confidence interval [CI]: .54-.65, P = .001), ASPECTS on the 24-hour CT scan (AUC = .78, 95% CI: .73-.82, P < .001), and change in ASPECTS (AUC = .69, 95% CI: .64-.74, P < .001) were better predictors of unfavorable functional outcome at 3 months. DAP, noted in 34 (14.4%) patients with good baseline ASPECTS (8-10 points), was significantly associated with unfavorable functional outcome (odds ratio [OR]: 9.91, 95% CI: 3.37-29.19, P ≤ .001), mortality (OR: 21.99, 95% CI: 7.98-60.58, P < .001), and SICH (OR: 8.57, 95% CI: 2.87-25.59, P < .001). CONCLUSION: Compared with the pre-thrombolysis score, ASPECTS measured at 24 hours as well as serial change in ASPECTS is a better predictor of 3-month functional outcome.

The Montreal Cognitive Assessment is superior to National Institute of Neurological Disease and Stroke-Canadian Stroke Network 5-minute protocol in predicting vascular cognitive impairment at 1 year.

BACKGROUND: The predictive ability of National Institute of Neurological Disease and Stroke-Canadian Stroke Network (NINDS-CSN) 5-minute protocol and Montreal Cognitive Assessment (MoCA) administered sub-acutely and at the convalescent phase after stroke for significant vascular cognitive impairment (VCI) at 1 year is unknown. We compared prognostic values of these tests. METHODS: Patients with ischemic stroke and transient ischemic attack (TIA) received MoCA sub-acutely (within 2 weeks) and 3-6 months after stroke followed by a formal neuropsychological evaluation at 1 year. The total score of NINDS-CSN 5-minutes protocol was derived from MoCA. Moderate-severe VCI was defined as neuropsychological impairment in ≥ 3 domains. Area under the receiver operating characteristic curve (AUC) analyses were conducted to establish the optimal cutoff points and discriminatory properties of the MoCA and NINDS-CSN 5-minute protocol in detecting moderate-severe VCI. RESULTS: Four hundre patients were recruited at baseline. Of these, 291 received a formal neuropsychological assessment 1 year after stroke. 19% patients had moderate-severe VCI. The MoCA was superior to the NINDS-CSN 5-minute protocol [sub-acute AUCs: 0.89 vs 0.80, p < 0.01; 3-6 months AUCs: 0.90 vs 0.83, p < 0.01] in predicting for moderate-severe VCI at 1 year. At respective cutoff points, MoCA had significantly higher sensitivity than the NINDS-CSN 5-minute protocol at baseline (p = 0.01) and 3-6 months (p = 0.04). CONCLUSIONS: MoCA administered sub-acutely and 3-6 months after stroke is superior to the NINDS-CSN 5-minute protocol in predicting moderate-severe VCI at 1 year.