Early versus Later Anticoagulation for Stroke with Atrial Fibrillation.

BACKGROUND: The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear. METHODS: We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days. RESULTS: Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days. CONCLUSIONS: In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.).

Early Versus Late Initiation of Direct Oral Anticoagulants After Ischemic Stroke in People With Atrial Fibrillation and Hemorrhagic Transformation: Prespecified Subanalysis of the Randomized Controlled ELAN Trial.

BACKGROUND: Whether hemorrhagic transformation (HT) modifies the treatment effect of early compared with late initiation of direct oral anticoagulation in people with ischemic stroke and atrial fibrillation is unknown. METHODS: This is a post hoc analysis of the ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation). The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, major extracranial bleeding, systemic embolism, or vascular death within 30 days. Secondary outcomes were the individual components, 30- and 90-day functional outcome. We estimated outcomes based on HT, subclassified as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) on prerandomization imaging (core laboratory rating) using adjusted risk differences between treatment arms. RESULTS: Overall, 247 of 1970 participants (12.5%) had HT (114 HI 1, 77 HI 2, 34 PH 1, 22 PH 2). For the primary outcome, the estimated adjusted risk difference (early versus late) was -2.2% (95% CI, -7.8% to 3.5%) in people with HT (HI: -4.7% [95% CI, -10.8% to 1.4%]; PH: 6.1% [95% CI, -8.5% to 20.6%]) and -0.9% (95% CI, -2.6% to 0.8%) in people without HT. Numbers of symptomatic intracranial hemorrhage were identical in people with and without HT. With early treatment, the estimated adjusted risk difference for poor 90-day functional outcome (modified Rankin Scale score, 3-6) was 11.5% (95% CI, -0.8% to 23.8%) in participants with HT (HI: 7.4% [95% CI, -6.4% to 21.2%]; PH: 25.1% [95% CI, 0.2% to 50.0%]) and -2.6% (95% CI, -7.1% to 1.8%) in people without HT. CONCLUSIONS: We found no evidence of major treatment effect heterogeneity or safety concerns with early compared with late direct oral anticoagulation initiation in people with and without HT. However, early direct oral anticoagulation initiation may worsen functional outcomes in people with PH. REGISTRATION: URL: http://www.clinicaltrials.gov; Unique identifier: NCT03148457.

Mechanical Thrombectomy Global Access For Stroke (MT-GLASS): A Mission Thrombectomy (MT-2020 Plus) Study.

BACKGROUND: Despite the well-established potent benefit of mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke, access to MT has not been studied globally. We conducted a worldwide survey of countries on 6 continents to define MT access (MTA), the disparities in MTA, and its determinants on a global scale. METHODS: Our survey was conducted in 75 countries through the Mission Thrombectomy 2020+ global network between November 22, 2020, and February 28, 2021. The primary end points were the current annual MTA, MT operator availability, and MT center availability. MTA was defined as the estimated proportion of patients with LVO receiving MT in a given region annually. The availability metrics were defined as ([current MT operators×50/current annual number of estimated thrombectomy-eligible LVOs]×100 = MT operator availability) and ([current MT centers×150/current annual number of estimated thrombectomy-eligible LVOs]×100= MT center availability). The metrics used optimal MT volume per operator as 50 and an optimal MT volume per center as 150. Multivariable-adjusted generalized linear models were used to evaluate factors associated with MTA. RESULTS: We received 887 responses from 67 countries. The median global MTA was 2.79% (interquartile range, 0.70-11.74). MTA was <1.0% for 18 (27%) countries and 0 for 7 (10%) countries. There was a 460-fold disparity between the highest and lowest nonzero MTA regions and low-income countries had 88% lower MTA compared with high-income countries. The global MT operator availability was 16.5% of optimal and the MT center availability was 20.8% of optimal. On multivariable regression, country income level (low or lower-middle versus high: odds ratio, 0.08 [95% CI, 0.04-0.12]), MT operator availability (odds ratio, 3.35 [95% CI, 2.07-5.42]), MT center availability (odds ratio, 2.86 [95% CI, 1.84-4.48]), and presence of prehospital acute stroke bypass protocol (odds ratio, 4.00 [95% CI, 1.70-9.42]) were significantly associated with increased odds of MTA. CONCLUSIONS: Access to MT on a global level is extremely low, with enormous disparities between countries by income level. The significant determinants of MT access are the country's per capita gross national income, prehospital LVO triage policy, and MT operator and center availability.

Development and effect of a coordinated Community Health Worker (CHW) Intervention (C-CHW-I) model for the stroke survivors in Kerala, South India.

INTRODUCTION: Structured models for secondary prevention of stroke in community settings are scarce. We aimed to develop and evaluate a model for improving medication adherence and enhanced risk factor monitoring. METHODS: We developed a multimodal C-CHW-I model for stroke survivors. Following training, all patients received a minimum of three CHW home visits, and once in 3-month telephone-call and health education for six months by CHWs. Seven blocks from 16 blocks of the study area were randomised to additionally receive an SMS alert for six months to reinforce CHW involvement. The primary outcomes were medication adherence and risk factor monitoring, and the secondary outcome was risk factor control. RESULTS: The mean age of the study population was 64+12 years, 765(85%) had ischaemic stroke. In the overall study cohort receiving the CHW intervention, mean medication adherence significantly improved from 3.56(0.88) at baseline to 3.78(0.61) at 6 months; p<0.001. Overall risk factor monitoring improved from 42.7% to 49.7%, and mean (standard deviation) systolic blood pressure (SBP) significantly reduced from 138(21) mmHg to 132(15) mmHg at 6-months; p<0.001. In patients additionally receiving SMS-based intervention, a statistically significant improvement in medication adherence was seen at 3 months (3.76+0.64 versus 3.61+0.81; p=0.008) however no difference persisted at 6 months. The proportion of smokers and alcohol users reduced in both groups with a trend to greater reduction in the intervention group (smokers:5.9% versus 2.8% (p=0.446) and alcohol users: 1.6% versus 1.4%(p=0.474)). At six months, the SBP did not differ (SBP (132.1(16.2) in the SMS group versus 133.2(15.8) mmHg in the control group, p=0.409). CONCLUSION: Our model improved medication adherence and risk factor monitoring of stroke survivors in community settings, and this can reduce stroke burden in the community.

Progressive lacunar strokes behave differently from stable ones even at one year-An observational study.

BACKGROUND AND AIMS: Small fraction of lacunar stroke patients have an early fluctuating course, described as progressive lacunar syndrome [PLS].We studied the predictors and short term outcome of progressive lacunar strokes in comparison with those with an early stable course. MATERIALS AND METHODS: Single centre retrospective study where patients with lacunar strokes from 2016 to 2020 were included in the study. Progression was defined as increase in stroke severity [NIHSS] by ≥2 points from baseline without imaging evidence of new infarcts or haemorrhagic transformation. We compared the clinical variables, risk factors, imaging, treatment received and 1 year outcome of subjects with PLS with those with a stable course, with modified Rankin score 0-2 taken as good outcome. RESULTS: Of the 216 patients with a mean age 63.17 years, progressive course was noted in 56 subjects [26 %].Majority of the fluctuations occurred within 24 h of onset of symptoms. Though stroke severity at admission was comparable between the 2 groups, discharge and 1 year outcome was poorer in those with an early progressive course. We found that presentation as pure motor syndrome, hypertriglyceridemia and thrombolytic therapy were predictors of poor outcome in progressive lacunar strokes, while age, risk factors, infarct location or leukoaraiosis failed to show an association. Thalamic infarcts and atypical lacunar syndromes were associated with a stable course. CONCLUSION: Progressive course is seen in a quarter of lacunar strokes and they have poorer outcome at 1 year. Our finding of thrombolysis being associated with worse outcome in PLS patients, should alert physicians regarding need for more definitive therapies for this condition.

Biomarkers predict hemorrhagic transformation and stroke severity after acute ischemic stroke.

OBJECTIVES: Hemorrhagic transformation (HT) is a complication occurring in patients with acute ischemic stroke (AIS) either spontaneously or post-thrombolysis leading to significant morbidity and mortality. We assessed circulating matrix metalloproteinase-9 (MMP-9), Claudin-5, and soluble serum stimulation-2 (sST2) in HT and stroke severity in AIS based on their temporal distribution. MATERIALS AND METHODS: We prospectively enrolled 111 AIS patients within 12 h from onset. Patient demographic, clinical, and imaging details were documented. Follow-up imaging was conducted 24-48 h after admission. Blood samples were taken at three time-points from stroke onset. HT was classified according to the European Co-operative Acute Stroke Study-III(ECASS-III). Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Multiple logistic regression and receiver operating characteristic curve were conducted to determine the discriminative capacity. RESULTS: Mean age was 62.3 ± 11.7 years and median baseline NIHSS was 12[IQR 8.0-18.0]. HT was detected in 30(27%) patients. Biomarker levels at 12 h were elevated with median MMP-9 concentration of 153.9 ng/mL[IQR 110.6-309 ng/mL] indicating a trend toward significant positive correlation with HT(P = 0.05). Claudin-5 levels at 12 h was elevated but was not statistically significant (43.1 pg/mL[IQR:26.7-72.6 pg/mL] vs 59.4 pg/mL[IQR:24.5-100.8 pg/mL];P = 0.4). Multiple logistic regression indicated Claudin-5 levels at 12 h (OR 9.46;95% CI:1.97-64.6;P = 0.010) and baseline low ASPECTS score(OR 20.3;95% CI:3.46-193; P = 0.003) independently predicted HT. MMP-9 at 12 h was significantly elevated in patients with moderate to severe strokes (P = 0.04). CONCLUSIONS: Claudin-5 and low ASPECTS independently predicted HT. MMP-9 was positively correlated with baseline stroke severity.

Biomarkers in the Prediction of Hemorrhagic Transformation in Acute Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Hemorrhagic transformation (HT) is a complication that occurs spontaneously or after thrombolysis in acute ischemic stroke (AIS) and can increase morbidity and mortality. The association of biomarkers with the risk of HT has been variably reported. We conducted a systematic review of the literature and meta-analysis and sought to compare blood biomarkers associated with HT and its subtypes by evaluating its predictability and correlation with outcome in AIS. METHODS: The study protocol was registered in the PROSPERO database (CRD42020201334) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Among 2,230 articles identified from Cochrane Library, PubMed, and Web of Science databases, 30 quality-appraised articles were found eligible. Meta-analysis was conducted for matrix metalloproteinase-9 (MMP-9), cellular fibronectin (c-Fn), ferritin, S100 calcium-binding protein B (S100B), and neutrophil-lymphocyte ratio (NLR). We also reviewed biomarkers for correlation with the functional outcome at 90 days from stroke onset (poor outcome modified Rankin scale >2). RESULTS: The pooled diagnostic odds ratio (DORpooled) was the highest for baseline c-Fn levels (299.253 [95% CI, 20.508-4,366.709]), followed by MMP-9 (DORpooled, 29.571 [95% CI 17.750-49.267]) and ferritin (DORpooled, 24.032 [95% CI 2.557-225.871]). However, wide confidence intervals for ferritin and c-Fn suggested lesser reliability of the markers. Patients with MMP-9 levels ≥140 ng/mL were 29.5 times at higher risk of developing symptomatic HT after AIS (area under the curve = 0.881). S100B (DORpooled, 6.286 [95% CI, 1.861-21.230]) and NLR (DORpooled, 5.036 [95% CI, 2.898-8.749]) had lower diagnostic accuracies. Among the markers not included for meta-analysis, caveolin-1, thrombin-activated fibrinolysis inhibitor, plasminogen activator inhibitor-1, and soluble ST2 were highly sensitive. Elevated levels of MMP-9, ferritin, and NLR were found to be associated with poor functional outcomes and mortality. CONCLUSION: Of the 5 biomarkers, there was enough evidence that MMP-9 has higher diagnostic accuracy for predicting the risk of HT before thrombolysis. MMP-9, ferritin, and NLR also predicted poor short-term outcomes.

MoCA in five Indian languages: A brief screening tool to diagnose dementia and MCI in a linguistically diverse setting.

INTRODUCTION AND OBJECTIVES: Early dementia diagnosis in low and middle-income countries (LMIC) is challenging due to limited availability of brief, culturally appropriate, and psychometrically validated tests. Montreal Cognitive Assessment (MoCA) is one of the most widely used cognitive screening tests in primary and secondary care globally. In the current study, we adapted and validated MoCA in five Indian languages (Hindi, Bengali, Telugu, Kannada, and Malayalam) and determined the optimal cut-off points that correspond to screening for clinical diagnosis of dementia and MCI. METHODS: A systematic process of adaptation and modifications of MoCA was fulfilled. A total of 446 participants: 214 controls, 102 dementia, and 130 MCI were recruited across six centers. RESULTS: Across five languages, the area under the curve for diagnosis of dementia varied from 0.89 to 0.98 and MCI varied from 0.73 to 0.96. The sensitivity, specificity and optimum cut-off scores were established separately for five Indian languages. CONCLUSIONS: The Indian adapted MoCA is standardized and validated in five Indian languages for early diagnosis of dementia and MCI in a linguistically and culturally diverse population.

High-resolution MR vessel wall imaging in determining the stroke aetiology and risk stratification in isolated middle cerebral artery disease.

PURPOSE: High-resolution MR vessel wall imaging (HRVWI) can characterise vessel wall pathology affecting intracranial circulation and helps in differentiating intracranial vasculopathies. The aim was to differentiate intracranial pathologies involving middle cerebral artery (MCA) in patients with ischemic stroke and characterise the high-risk plaques in intracranial atherosclerotic disease (ICAD) using HRVWI. METHODS: Patients with ischemic stroke with isolated MCA disease with ≥ 50% luminal narrowing by vascular imaging were enrolled within 2 weeks of onset and underwent high-resolution (3 T) intracranial vessel wall imaging (VWI). The pattern of vessel wall thickening, high signal on T1-weighted images, juxtaluminal hyperintensity, pattern and grade of enhancement were studied. The TOAST classification before and after HRVWI and the correlation of the recurrence of ischemic events at 3 months with imaging characteristics were analysed. RESULTS: Of the 36 patients, the mean age was 49.53 ± 15.61 years. After luminal imaging, by TOAST classification, 12 of 36 patients had stroke of undetermined aetiology. After vessel wall imaging, lesions in MCA were analysed. Of them, 23 patients had ICAD, 8 had vasculitis, and 2 had partially occlusive thrombus in MCA. The ability of HRVWI to bring a change in diagnosis was significant (p = 0.031). Of the 23 patients with ICAD, 12 patients had recurrent strokes within 3 months. The presence of grade 2 contrast enhancement (p = 0.02) and type 2 wall thickening (p = 0.03) showed a statistically significant association with recurrent ischemic events. CONCLUSION: High-resolution MRVWI can help in identifying the aetiology of stroke. The HRVWI characteristics in ICAD can help in risk stratification.

Picture-naming test for a linguistically diverse population with cognitive impairment and dementia.

BACKGROUND: Picture-naming tests (PNTs) evaluate linguistic impairment in dementia due to semantic memory impairment, impaired lexical retrieval or perceptual deficits. They also assess the decline in naming impairment at various stages of dementia and mild cognitive impairment (MCI) that occurs due to progressive cognitive impairment. With the increasing numbers of people with dementia globally, it is necessary to have validated naming tests and norms that are culturally and linguistically appropriate. AIMS: In this cross-sectional study we harmonized a set of 30 images applicable to the Indian context across five languages and investigated the picture-naming performance in patients with MCI and dementia. METHODS & PROCEDURES: A multidisciplinary expert group formed by the Indian Council of Medical Research (ICMR) collaborated towards developing and adapting a picture naming test (PNT) known as the ICMR-PNT in five Indian languages: Hindi, Bengali, Telugu, Kannada and Malayalam. Based on cross-cultural adaptation guidelines and item-wise factor analysis and correlations established separately across five languages, the final version of the ICMR-PNT test was developed. A total of 368 controls, 123 dementia and 128 MCI patients were recruited for the study. Psychometric properties of the adapted version of the ICMR-PNT were examined, and sensitivity and specificity were examined. OUTCOMES & RESULTS: The ICMR-PNT scores in all languages combined were higher in controls compared with patients with dementia and MCI (F2, 615 = 139.85; p < 0.001). Furthermore, PNT scores for MCI was higher in comparison with patients with dementia in all languages combined (p < 0.001). The area under the curve across the five languages ranged from 0.81 to 1.00 for detecting dementia. There was a negative correlation between Clinical Dementia Rating (CDR) and ICMR-PNT scores and a positive correlation between Addenbrooke's Cognitive Examination-III (ACE-III) and ICMR-PNT scores in control and patient groups. CONCLUSIONS & IMPLICATIONS: The ICMR-PNT was developed by following cross-cultural adaptation guidelines and establishing correlations using item-wise factor analysis across five languages. This adapted PNT was found to be a reliable tool when assessing naming abilities effectively in mild to moderate dementia in a linguistically diverse context. WHAT THIS PAPER ADDS: What is already known on this subject Picture-naming evaluates language impairment linked to naming difficulties due to semantic memory, lexical retrieval or perceptual disturbances. As a result, picture naming tests (PNTs) play an important role in the diagnosis of dementia. In a heterogeneous population such as India, there is a need for a common PNT that can be used across the wide range of languages. What this study adds to existing knowledge PNTs such as the Boston Naming Test (BNT) were developed for the educated, mostly English-speaking, Western populations and are not appropriate for use in an Indian context. To overcome this challenge, a PNT was harmonized in five Indian languages (Hindi, Bengali, Telugu, Kannada and Malayalam) and we report the patterns of naming difficulty in patients with MCI and dementia. The ICMR-PNT demonstrated good diagnostic accuracy when distinguishing patients with mild to moderate dementia from cognitively normal individuals. What are the potential or actual clinical implications of this work? With the growing number of persons suffering from Alzheimer's disease and other forms of dementia around the world, its critical to have culturally and linguistically relevant naming tests and diagnosis. This validated ICMR-PNT can be used widely as a clinical tool to diagnose dementia and harmonize research efforts across diverse populations.

Dysphagia Continues to Impact Recovery at One Year After Stroke-An Observational Study.

OBJECTIVES: Dysphagia is one of the most common medical complication after acute stroke, which can impact hospital stay and discharge outcome. Here we sought to study the predictors and 1 year outcome of patients with acute post stroke dysphagia. METHODS: Single centre hospital based observational study of all acute ischemic stroke patients who had undergone formal swallow assessment within 24 hours of admission with a 1 year completed follow-up were recruited by screening of medical records. Clinical, imaging and swallow assessment details were extracted as per proforma. 3 month and 1 year outcome were assessed using modified Rankin scale. Correlations were made with clinical and imaging findings, in hospital worsening and dysphagia at discharge with short and long term functional outcome. RESULTS: We had 469 patients included in our study, with a mean age 61. 04(±19. 09) years and median NIHSS 9. 52(IQR 4). 56. 75% of AIS patients had some degree of dysphagia at admission. We found that admission stroke severity and in-hospital worsening were independently predictive of severe swallow dysfunction at discharge. At 3-4 weeks after stroke, only 20.27% of the patients with moderate-severe dysphagia at baseline has persistent swallow deficits requiring modification of feeds. Dysphagia continued to have a significant association with outcome at 1 year, independent of admission stroke severity. CONCLUSIONS: Majority of patients with acute post stroke dysphagia recover well within 3-4 weeks after stroke. Patients with post stroke dysphagia had more in hospital neurological worsening. Post stroke dysphagia continued to have an impact on functional outcome up to 1 year after stroke.

Does thrombus imaging characteristics predict the degree of recanalisation after endovascular thrombectomy in acute ischaemic stroke?

BACKGROUND: Identification of computed tomography (CT) thrombus imaging characteristics can predict the degree of recanalization and outcome after endovascular thrombectomy (EVT) in patients with acute ischaemic stroke and large vessel occlusion. AIM: We analyzed the thrombus imaging characteristics and procedural factors and correlated with the degree of recanalization and functional outcome after EVT. METHODS: We evaluated the thrombus imaging characteristics (hyperdense MCA sign, thrombus location, length and thrombus permeability) from thin slice CT and CT angiogram. In addition, groin to recanalization time, number of passes, and EVT technique were documented. The primary outcome was degree of recanalization (mTICI score) and secondary outcome was modified Rankin scale (mRS) at 3 months. RESULTS: The mean age of 102 patients was 60.5±11.8 years. Patients with hyperdense MCA sign (90 % vs 75%, p=0.07) and permeable thrombus (86 % vs 70 %, p=0.09) had good recanalization (mTICI grade 2b,2c or 3). The requirement of <3 passes (90 % vs 62 %, p= 0.001) was associated with good recanalization. Multiple logistic regression analysis showed thrombus permeability (OR 5.9; 95% CI 1.3-26.6, p=0.02), use of stent retreiver alone (without aspiration) (OR 5.4; 95% CI 1.3-22.5, p=0.02) and a puncture to recanalization ≤60 minutes (OR 7.9; 95% CI 1.7-36.8; p=0.008) were associated with good recanalization. The requirement of ≥3 passes was associated with poor functional outcome (OR 3.4;95% CI 1.2-9.8; p=0.02). CONCLUSIONS: Thrombus permeability was a predictor of successful recanalization after EVT. The requirement of three or more passes during EVT was associated with poor recanalization and poor functional outcome.

INSTRuCT: Protocol, Infrastructure, and Governance.

Background and Purpose: Very few large scale multicentric stroke clinical trials have been done in India. The Indian Council of Medical Research funded INSTRuCT (Indian Stroke Clinical Trial Network) as a task force project with the objectives to establish a state-of-the-art stroke clinical trial network and to conduct pharmacological and nonpharmacological stroke clinical trials relevant to the nation and globally. The purpose of the article is to enumerate the structure of multicentric stroke network, with emphasis on its scope, challenges and expectations in India. Methods: Multiple expert group meetings were conducted by Indian Council of Medical Research to understand the scope of network to perform stroke clinical trials in the country. Established stroke centers with annual volume of 200 patients with stroke with prior experience of conducting clinical trials were included. Central coordinating center, standard operating procedures, data and safety monitoring board were formed. Discussion: In first phase, 2 trials were initiated namely, SPRINT (Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in India) and Ayurveda treatment in the rehabilitation of patients with ischemic stroke in India (RESTORE [Rehabilitation of Ischemic stroke Patients in India: A Randomized controlled trial]). In second phase, 4 trials have been approved. SPRINT trial was the first to be initiated. SPRINT trial randomized first patient on April 28, 2018; recruited 3048 patients with an average of 128.5 per month so far. The first follow-up was completed on May 27, 2019. RESTORE trial randomized first patient on May 22, 2019; recruited 49 patients with an average of 3.7 per month so far. The first follow-up was completed on August 30, 2019. Conclusions: In next 5 years, INSTRuCT will be able to complete high-quality large scale stroke trials which are relevant globally. REGISTRATION: URL: http://www.ctri.nic.in/; Unique Identifier: CTRI/2017/05/008507.

Life Style and Behavioural Factors are Associated with Stroke Recurrence Among Survivors of First Episode of Stroke: A Case Control Study.

BACKGROUND: Secondary stroke prevention treatment is associated with an 80% reduction in risk of recurrent stroke. But one out of every four strokes are recurrent. Adherence to pharmacological therapy and strict control of risk factors are essential for prevention of recurrent strokes. METHODS: Pair matched incident case control study was done to find out the factors associated with stroke recurrence after first ever stroke. Incident cases of recurrent strokes and age and post stroke period matched controls were recruited prospectively. The estimated sample size for the study was 70 matched pairs. Data collected from medical records and by visiting their homes. Analysis was done using R statistical software. RESULTS: Bivariate analysis showed cardio embolic stroke subtype, poor lipid control, unhealthy diet, physical inactivity, medication nonadherence, presence of depression, memory problems no discharge advice at index admission and low income were associated increased risk of recurrence. Higher mean NIHSS score and a greater number of days of hospitalisation during index stroke had less risk of recurrence. Conditional logistic regression analysis revealed non adherence to medication (OR 7.46, 1.67-33.28) and not receiving discharge advice at index admission (OR 10.79, 2.38-49.02) were associated with increased risk of recurrence whereas lacunar stroke (OR 0.08, 0.01-0.59) and a greater number of days of hospitalization during index stroke (OR 0.82, 0.67-0.99) were associated with less risk of recurrence. CONCLUSION: Individualised patient education regarding stroke, recurrence risk, medication adherence, healthy lifestyle and risk factor control can reduce stroke recurrence risk.

International Survey of Mechanical Thrombectomy Stroke Systems of Care During COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic has strained the healthcare systems across the world but its impact on acute stroke care is just being elucidated. We hypothesized a major global impact of COVID-19 not only on stroke volumes but also on various aspects of thrombectomy systems. AIMS: We conducted a convenience electronic survey with a 21-item questionnaire aimed to identify the changes in stroke admission volumes and thrombectomy treatment practices seen during a specified time period of the COVID-19 pandemic. METHODS: The survey was designed using Qualtrics software and sent to stroke and neuro-interventional physicians around the world who are part of the Global Executive Committee (GEC) of Mission Thrombectomy 2020, a global coalition under the aegis of Society of Vascular and Interventional Neurology, between April 5th and May 15th, 2020. RESULTS: There were 113 responses to the survey across 25 countries with a response rate of 31% among the GEC members. Globally there was a median 33% decrease in stroke admissions and a 25% decrease in mechanical thrombectomy (MT) procedures during the COVID-19 pandemic period until May 15th, 2020 compared to pre-pandemic months. The intubation policy for MT procedures during the pandemic was highly variable across participating centers: 44% preferred intubating all patients, including 25% of centers that changed their policy to preferred-intubation (PI) from preferred non-intubation (PNI). On the other hand, 56% centers preferred not intubating patients undergoing MT, which included 27% centers that changed their policy from PI to PNI. There was no significant difference in rate of COVID-19 infection between PI versus PNI centers (p=0.60) or if intubation policy was changed in either direction (p=1.00). Low-volume (<10 stroke/month) compared with high-volume stroke centers (>20 strokes/month) were less likely to have neurointerventional suite specific written personal protective equipment protocols (74% vs 88%) and if present, these centers were more likely to report them to be inadequate (58% vs 92%). CONCLUSION: Our data provides a comprehensive snapshot of the impact on acute stroke care observed worldwide during the pandemic. Overall, respondents reported decreased stroke admissions as well as decreased cases of MT with no clear preponderance in intubation policy during MT. DATA ACCESS STATEMENT: The corresponding author will consider requests for sharing survey data. The study was exempt from institutional review board approval as it did not involve patient level data.

Standardising Dementia Diagnosis Across Linguistic and Educational Diversity: Study Design of the Indian Council of Medical Research-Neurocognitive Tool Box (ICMR-NCTB).

OBJECTIVES: While the burden of dementia is increasing in low- and middle-income countries, there is a low rate of diagnosis and paucity of research in these regions. A major challenge to study dementia is the limited availability of standardised diagnostic tools for use in populations with linguistic and educational diversity. The objectives of the study were to develop a standardised and comprehensive neurocognitive test battery to diagnose dementia and mild cognitive impairment (MCI) due to varied etiologies, across different languages and educational levels in India, to facilitate research efforts in diverse settings. METHODS: A multidisciplinary expert group formed by Indian Council of Medical Research (ICMR) collaborated towards adapting and validating a neurocognitive test battery, that is, the ICMR Neurocognitive Tool Box (ICMR-NCTB) in five Indian languages (Hindi, Bengali, Telugu, Kannada, and Malayalam), for illiterates and literates, to standardise diagnosis of dementia and MCI in India. RESULTS: Following a review of existing international and national efforts at standardising dementia diagnosis, the ICMR-NCTB was developed and adapted to the Indian setting of sociolinguistic diversity. The battery consisted of tests of cognition, behaviour, and functional activities. A uniform protocol for diagnosis of normal cognition, MCI, and dementia due to neurodegenerative diseases and stroke was followed in six centres. A systematic plan for validating the ICMR-NCTB and establishing cut-off values in a diverse multicentric cohort was developed. CONCLUSIONS: A key outcome was the development of a comprehensive diagnostic tool for diagnosis of dementia and MCI due to varied etiologies, in the diverse socio-demographic setting of India.

Correction to: Central Nervous System Manifestations Associated with COVID-19.

The original version contained incorrect formatting of Dr. Napolis. His first name should be Mario and his last name should be Di Napoli.

Central Nervous System Manifestations Associated with COVID-19.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) has become a global health crisis of our time. The disease arises from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that binds to angiotensin-converting enzyme 2 (ACE2) receptors on host cells for its internalization. COVID-19 has a wide range of respiratory symptoms from mild to severe and affects several other organs, increasing the complexity of the treatment. There is accumulating evidence to suggest that SARS-CoV-2 can target the nervous system. In this review, we provide an account of the COVID-19 central nervous system (CNS) manifestations. RECENT FINDINGS: A broad spectrum of the CNS manifestations including headache, impaired consciousness, delirium, loss of smell and taste, encephalitis, seizures, strokes, myelitis, acute disseminated encephalomyelitis, neurogenic respiratory failure, encephalopathy, silent hypoxemia, generalized myoclonus, neuroleptic malignant syndrome and Kawasaki syndrome has been reported in patients with COVID-19. CNS manifestations associated with COVID-19 should be considered in clinical practice. There is a need for modification of current protocols and standing orders to provide better care for COVID-19 patients presenting with neurological symptoms.

Identifying Resting-State Functional Connectivity Changes in the Motor Cortex Using fNIRS During Recovery from Stroke.

Resting-state functional imaging has been used to study the functional reorganization of the brain. The application of functional near-infrared spectroscopy (fNIRS) to assess resting-state functional connectivity (rsFC) has already been demonstrated in recent years. The present study aimed to identify the difference in rsFC patterns during the recovery from the upper-limb deficit due to stroke. Twenty patients with mild stroke having an onset of four to eight weeks were recruited from the stroke clinic of our institute and an equal number of healthy volunteers were included in the study after ethical committee approval. The fNIRS signals were recorded bilaterally over the premotor area and supplementary motor area and over the primary motor cortex. Pearson Correlation is the method used to compute rsFC for the healthy group and patient group. For the healthy group, both intra-hemispheric and inter-hemispheric connections were stronger. RSFC analysis demonstrated changes from the healthy pattern for the patient group with an upper-limb deficit. The left hemisphere affected group showed disrupted ipsilesional and an increased contra-lesional connectivity. The longitudinal data analysis of rsFC showed improvement in the connections in the ipsilesional hemisphere between the primary motor area, somatosensory area, and premotor areas. In the future, the rsFC changes during the recovery could be used to predict the extent of recovery from stroke motor deficits.

Risk factors of white matter hyperintensities in South Asian patients with transient ischemic attack and minor stroke.

PURPOSE: Aging and increased burden of cardiovascular risk factors are associated with severity of white matter hyperintensity (WMH). We assessed the burden and risk factor profile of WMHs in South Asian patients with transient ischemic attack (TIA) and minor stroke. METHODS: Patients with acute ischemic stroke with the National Institute of Health stroke scale (NIHSS) score ≤ 5 who underwent MRI were included. The severity of WMHs was assessed based on age-related white matter change (ARWMC) scale (0-30). A score of > 8 or more was considered moderate-severe involvement. Logistic regression analysis was performed to assess the association with risk factors. RESULTS: A total of 424 patients with a mean ± SD age of 57.4 ± 14.5 years [females, 108 (25.5%)] were analyzed. Fifty-four (12.7%) patients had moderate or severe WMHs (ARWMC score > 8). Age (OR 1.03, 95% CI 1.01-1.06; p = 0.004), hypertension (OR 2.3, 95% CI 1.1-5.1; p = 0.03) and smoking tobacco (OR 2.8, 95% CI 1.4-5.6; p = 0.003) were independently associated with ARWMC score > 8. The median (IQR) regional score in patients with ARWMC score > 8 was maximum in frontal areas 4 (4-6, p < 0.0001) and parietooccipital areas 4.5(4-6, p < 0.0001). The presence of microbleeds (OR 6.3, 95% CI 3.1-12.7; p < 0.0001) was independently associated with ARWMC score > 8. CONCLUSION: South Asian patients with TIA and minor stroke are relatively young, and few patients have moderate and severe WMHs. Hypertension and tobacco smoking increases the risk of WMH. Targeting modifiable risk factors may reduce the burden of WMHs and vascular dementia.