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Background and Objectives: Ischemic stroke (IS) in young is increasingly recognized as an important health problem in low- and middle-income countries (LMICs). Limited data is available from LMICs about the predictors of outcome and recurrence of IS in young. The study aims to assess the predictors of short-term and long-term functional outcome and the recurrence of the first-ever IS and transient ischemic attack in young. Methods: The clinical, radiological data, functional outcome, and recurrence of 569 IS patients aged 18–50 years were recorded. The etiological classification was done. The functional outcome was assessed using the modified Rankin scale (mRS), with a good outcome being mRS 0–2. Logistic regression was used to analyze the predictors of recurrence and outcome. Results: The most common risk factors were hypertension (40.3%) and diabetes mellitus (34.3%). Stroke of undetermined etiology (33.6%) was the most common etiological subtype. Among the cardioembolic subtypes, rheumatic heart disease constituted 47.4%. A good functional outcome at 1 year was seen in 76.3%. While baseline stroke severity predicted both the 3-month and 1-year functional outcome, age ≥40 years and male gender predicted poor outcome at 1 year. The risk of recurrent strokes at 1 year was 2.5%. On multiple logistic regression analysis, diabetes mellitus independently predicted recurrent vascular events at 1 year (odds ratio = 2.43, 95% confidence interval 1.07–5.50). Conclusions: We found a good functional outcome with a relatively low recurrence at 1 year among young IS patients. Baseline stroke severity, age, and male gender predicted a poor 1-year functional outcome.

BACKGROUND: There are multiple stroke guidelines globally. To synthesize these and summarize what existing stroke guidelines recommend about the management of people with stroke, the World Stroke Organization (WSO) Guideline committee, under the auspices of the WSO, reviewed available guidelines. AIMS: To systematically review the literature to identify stroke guidelines (excluding primary stroke prevention and subarachnoid hemorrhage) since 1 January 2011, evaluate quality (The international Appraisal of Guidelines, Research and Evaluation (AGREE II)), tabulate strong recommendations, and judge applicability according to stroke care available (minimal, essential, advanced). SUMMARY OF REVIEW: Searches identified 15,400 titles; 911 texts were retrieved, 200 publications scrutinized by the three subgroups (acute, secondary prevention, rehabilitation), and recommendations extracted from most recent version of relevant guidelines. For acute treatment, there were more guidelines about ischemic stroke than intracerebral hemorrhage; recommendations addressed pre-hospital, emergency, and acute hospital care. Strong recommendations were made for reperfusion therapies for acute ischemic stroke. For secondary prevention, strong recommendations included establishing etiological diagnosis; management of hypertension, weight, diabetes, lipids, and lifestyle modification; and for ischemic stroke, management of atrial fibrillation, valvular heart disease, left ventricular and atrial thrombi, patent foramen ovale, atherosclerotic extracranial large vessel disease, intracranial atherosclerotic disease, and antithrombotics in non-cardioembolic stroke. For rehabilitation, there were strong recommendations for organized stroke unit care, multidisciplinary rehabilitation, task-specific training, fitness training, and specific interventions for post-stroke impairments. Most recommendations were from high-income countries, and most did not consider comorbidity, resource implications, and implementation. Patient and public involvement was limited. CONCLUSION: The review identified a number of areas of stroke care where there was strong consensus. However, there was extensive repetition and redundancy in guideline recommendations. Future guideline groups should consider closer collaboration to improve efficiency, include more people with lived experience in the development process, consider comorbidity, and advise on implementation.

Abstract AKS-452, a subunit vaccine comprising an Fc fusion of the ancestral wild-type (WT) SARS-CoV-2 virus spike protein receptor binding domain (SP/RBD), was evaluated without adjuvant in a single cohort, non-randomized, open-labelled phase II study (NCT05124483) at a single site in The Netherlands for safety and immunogenicity. A single 90 µg subcutaneous booster dose of AKS-452 was administered to 71 adults previously primed with a registered mRNA- or adenovirus-based vaccine and evaluated for 273 days. All AEs were mild and no SAEs were attributable to AKS-452. While all subjects showed pre-existing SP/RBD binding and ACE2-inhibitory IgG titers, 60–68% responded to AKS-452 via ≥2-fold increase from days 28 to 90 and progressively decreased back to baseline by day 180 (days 28 and 90 mean fold-increases, 14.7 ± 6.3 and 8.0 ± 2.2). Similar response kinetics against RBD mutant proteins (including omicrons) were observed but with slightly reduced titers relative to WT. There was an expected strong inverse correlation between day-0 titers and the fold-increase in titers at day 28. AKS-452 enhanced neutralization potency against live virus, consistent with IgG titers. Nucleocapsid protein (Np) titers suggested infection occurred in 66% (46 of 70) of subjects, in which only 20 reported mild symptomatic COVID-19. These favorable safety and immunogenicity profiles support booster evaluation in a planned phase III universal booster study of this room-temperature stable vaccine that can be rapidly and inexpensively manufactured to serve vaccination at a global scale without the need of a complex distribution or cold chain.

Introduction Approximately half of all stroke survivors have persistent upper extremity functional impairment, leading to reduced self-care, independence and quality of life. High-intensity, task-oriented virtual reality rehabilitation improves motor recovery. However, its clinical efficacy over standard rehabilitation remains uncertain. This study aims to evaluate the feasibility and efficacy of a virtual reality-based comprehensive rehabilitation gaming system (VR-cRGS) in stroke survivors with upper extremity impairment and to characterise the structural and functional plasticity of the affected regions in the brain due to the proposed rehabilitation.Methods and analysis This study is a multicentric, open-label, randomised controlled trial with an intention-to-treat analysis. A total of 162 patients will be enrolled in two academic institutes in India that specialise in stroke care. Patients with a first-ever ischaemic stroke (18–70 years and 1–6 months of stroke onset) with upper extremity impairment with 1 and 1+ grades of spasticity as per the modified Ashworth Scale and 3, 4 or 5 stages on Brunnstrom recovery staging will be enrolled. They will be randomised (1:1) into two treatment groups to receive 12 weeks of training either on VR-cRGS or on conventional physiotherapy. The primary feasibility outcome is compliance with the treatment. The primary efficacy outcome is the functional recovery of the upper extremity assessed by the Fugl-Meyer Assessment-Upper Extremity and Wolf Motor Function Test. The secondary outcomes are the Barthel Index and the 36-item Short-Form Health Survey. Multimodal brain imaging will be done in all enrolled patients at baseline and post-treatment to evaluate the structural and functional connectivity changes. The outcome measures will be analysed using paired t-tests or non-parametric tests.Ethics and dissemination The study has been approved by the Institutional Ethics Review Board of the Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India (SCT/IEC/1415/AUGUST-2019) and the National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India (NIMHANS/IEC (BS and NS DIV.)/32nd Meeting/21). All participants will sign an informed consent form prior to participation. The study results will be disseminated through scholarly publication.Trial registration number CTRI/2021/11/038339.

Rationale Intracranial atherosclerotic disease (ICAD) is a pathological process that causes progressive stenosis and cerebral hypoperfusion, leading to stroke occurrence and recurrence around the world. The exact duration of dual antiplatelet therapy (DAPT) for ICAD is unclear in view of long-term risk of bleeding complications.Aim The current study aims to study the efficacy and safety of long-term DAPT (up to 12 months) in patients with ICAD.Sample size Using 80% power and an alpha error of 5 %, presuming a 10%–15% drop-out rate, a total of 2200 patients will be recruited for the study.Methodology This is a prospective, randomised, double-blind, placebo controlled trial.Study outcomes The primary outcomes include recurrent ischaemic stroke (IS) or transient ischaemic attack and any intracranial haemorrhage (ICH), major or minor systemic bleeding at the end of 12 months. Secondary outcomes include composite of any stroke, myocardial infarction or death at the end of 12 months. The safety outcomes include any ICH, major or minor bleeding as defined using GUSTO (Global Use of Streptokinase and tPA for occluded Coronary Arteries) classification at the end of 12 months and 1 month after completion of the drug treatment phase.Discussion The study will provide level I evidence on the duration of DAPT among patients with IS due to ICAD of more than or equal to 50%.

BackgroundFor the treatment of diabetes mellitus (DM) in dogs, novel insulins with decreased injection frequency while maintaining safety and efficacy are desirable. Insulin fused with immunoglobulin-fragment-crystallizable (Fc) has an ultra-long plasma half-life because it recycles through cells, protected from proteolysis.HypothesisGlycemic control can be achieved in diabetic dogs with a recombinant fusion protein of a synthetic insulin and canine Fc (AKS-218d) administered subcutaneously once-weekly.AnimalsFive client-owned dogs with naturally occurring DM.MethodsProspective clinical trial in dogs with DM that were recruited from the UC Davis Veterinary Teaching Hospital and local veterinary clinics. Dogs previously controlled using intermediate-acting insulin q12h were transitioned to once-weekly injections of a preliminary construct identified as AKS-218d. The dose of AKS-218d was titrated weekly for 8 weeks based on clinical response and continuous interstitial glucose monitoring. Clinical signs, body weight, serum fructosamine concentrations, and mean interstitial glucose concentrations (IG) over the preceding week were compared between baseline (before AKS-218d) and during the last week of treatment. Data were compared using nonparametric paired tests.ResultsOnce-weekly AKS-218d, compared to baseline twice-daily insulin therapy, resulted in no significant changes in clinical signs, median (range) body weight (+0.4 kg [-0.5-1.1]; P = .6), fructosamine concentration (-75 mmol/L [-215 to +126]; P = .4), or mean IG (+81 mg/dL [-282 to +144]; P = .8). No adverse reactions were reported.ConclusionControl of clinical signs, body weight, and maintenance of glycemia was achieved with this once-weekly novel insulin construct in 4 of 5 dogs.

Background: Identifying carotid pseudo-occlusion (PO) from true occlusion (TO) has implications in determining the candidacy and feasibility of successful endovascular thrombectomy (EVT) in acute ischemic stroke (AIS). Purpose: We reviewed the computed tomography angiographic (CTA) patterns differentiating a PO from a TO and analyzed the rate of successful recanalization after EVT. Materials and Methods: Patients with AIS and proximal internal carotid artery (ICA) occlusion who underwent EVT from 2014 to 2021 were identified. The patterns of carotid occlusion in CTA were classified into beak, dome, and flat patterns and correlated with microcatheter digital subtraction angiography (DSA) as PO and TO. The rates of successful recanalization in PO and TO were analyzed. Results: Of the 24 patients, 16 (66%) had ICA PO and eight (33%) had TO in DSA. A beak pattern of the proximal ICA on CTA was significantly higher among the PO group patients (87.5% vs. 25%, P = 0.005), and a flat pattern was significantly higher among the TO group patients (50% vs. 12%, P = 0.005). A gradual contrast decline of the proximal ICA on CTA images was seen only in PO group patients (85.7% vs. 0%, P = 0.05). There was no significant difference in the rate of successful recanalization between PO and TO group patients (81.25% vs. 62.5%, P = 0.362). Conclusion: Beak pattern and gradual contrast decline at the proximal ICA occlusion site in CTA are suggestive of carotid PO. Identification of PO in CTA can help in planning intervention strategies and prognostication.

Rationale Rapid and timely treatment with intravenous thrombolysis and endovascular treatment (EVT) in patients with acute ischaemic stroke (AIS) and large vessel occlusion (LVO) significantly improves patient outcomes. Bridging therapy is the current standard of care in these patients. However, an incompletely answered question is whether one thrombolytic agent is better than another during bridging therapy.Aim The current study aims to understand if one thrombolytic agent is superior to the other during bridging therapy in the treatment of AIS and LVO.Sample size estimates Using 80% power and an alpha error of 5 %, presuming a 10% drop out rate, a total of 372 patients will be recruited for the study.Methods and design This study is a prospective, randomised, multicentre, open-label trial with blinded outcome analysis design.Study outcomes The primary outcomes include proportion of patients who will be independent at 3 months (modified Rankin score (mRS) ≤2 as good outcome) and proportion of patients who achieve recanalisation modified thrombolysis in cerebral infarction grade 2b/3 at first angiography run at the end of EVT. Secondary outcomes include proportion of patients with early neurological improvement, rate of symptomatic intracerebral haemorrhage (ICH), rate of any ICH, rate of any systemic major or minor bleeding and duration of hospital stay. Safety outcomes include any intracranial bleeding or symptomatic ICH.Discussion This trial is envisioned to confirm the theoretical advantages and increase the strength and quality of evidence for use of tenecteplase (TNK) in practice. Also, it will help to generate data on the efficacy and safety of biosimilar TNK.Trial registration number CTRI/2022/01/039473.

IntroductionThe antigen-presenting cell function of insulin-reactive B cells promotes type 1 diabetes (T1D) in non-obese diabetic (NOD) mice by stimulating pathogenic T cells leading to destruction of insulin-producing β-cells of pancreatic islets.Methods/ResultsTo target insulin-reactive B cells, AKS-107, a human IgG1 Fc molecule fused with human insulin A and B chains, was engineered to retain conformational insulin epitopes that bound mouse and human B cell receptors but prevented binding to the insulin metabolic receptor. AKS-107 Fc-mediated deletion of insulin-reactive B cells was demonstrated via ex vivo and in vivo experiments with insulin-reactive B cell receptor transgenic mouse strains, VH125Tg/NOD and Tg125(H+L)/NOD. As an additional immune tolerance feature, the Y16A mutation of the insulin B(9-23) dominant T cell epitope was engineered into AKS-107 to suppress activation of insulin-specific T cells. In mice and non-human primates, AKS-107 was well-tolerated, non-immunogenic, did not cause hypoglycemia even at high doses, and showed an expectedly protracted pharmacokinetic profile. AKS-107 reproducibly prevented spontaneous diabetes from developing in NOD and VH125Tg/NOD mice that persisted for months after cessation of treatment, demonstrating durable immune tolerance.DiscussionThese preclinical outcomes position AKS-107 for clinical development in T1D prevention settings.

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.

BackgroundTreatment of diabetes mellitus (DM) in cats typically requires insulin injections q12h-q24h, posing a major compliance barrier for caregivers. Novel treatments enabling decreased injection frequency while maintaining safety are highly desirable. Insulin fused with feline immunoglobulin fragment crystallizable (Fc) has an ultra-long plasma half-life because it recycles through cells where it is protected from proteolysis.HypothesisGlycemic control can be achieved in diabetic cats with a recombinant fusion protein of a synthetic insulin and feline Fc (AKS-267c) administered SC weekly.AnimalsFive cats with spontaneous DM.MethodsCats previously controlled using insulin glargine q12h were transitioned to once-weekly injection of AKS-267c. The dose of AKS-267c was titrated weekly for 7 weeks based on continuous glucose monitoring. Clinical signs, body weight, fructosamine concentrations, and mean interstitial glucose concentrations (IG) were compared between baseline (week 0, on insulin glargine) and the last week of treatment. Data were assessed for normality and compared using parametric or nonparametric paired tests (as appropriate).ResultsAfter 7 weeks of once-weekly injections, compared to baseline, there were no significant changes in clinical signs, body weight (median [range] gain, 0.1 kg [-0.1 to +0.7]; P = .5), fructosamine (-60 mmol/L [-338 to +206]; P = .6), and mean IG concentrations (change = -153 mmol/L [-179 to +29]; P = .3), and no adverse reactions were reported.ConclusionSuccessful control of clinical signs and maintenance of glycemia was achieved with this once-weekly novel insulin treatment. The efficacy and safety of this novel formulation should be further assessed in a large clinical trial.

OBJECTIVE: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.

BackgroundThe emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran.MethodsThis study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model.ResultsDuring the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p

Background and purposeThe novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), now named coronavirus disease 2019 (COVID-19), may change the risk of stroke through an enhanced systemic inflammatory response, hypercoagulable state, and endothelial damage in the cerebrovascular system. Moreover, due to the current pandemic, some countries have prioritized health resources towards COVID-19 management, making it more challenging to appropriately care for other potentially disabling and fatal diseases such as stroke. The aim of this study is to identify and describe changes in stroke epidemiological trends before, during, and after the COVID-19 pandemic.MethodsThis is an international, multicenter, hospital-based study on stroke incidence and outcomes during the COVID-19 pandemic. We will describe patterns in stroke management, stroke hospitalization rate, and stroke severity, subtype (ischemic/hemorrhagic), and outcomes (including in-hospital mortality) in 2020 during COVID-19 pandemic, comparing them with the corresponding data from 2018 and 2019, and subsequently 2021. We will also use an interrupted time series (ITS) analysis to assess the change in stroke hospitalization rates before, during, and after COVID-19, in each participating center.ConclusionThe proposed study will potentially enable us to better understand the changes in stroke care protocols, differential hospitalization rate, and severity of stroke, as it pertains to the COVID-19 pandemic. Ultimately, this will help guide clinical-based policies surrounding COVID-19 and other similar global pandemics to ensure that management of cerebrovascular comorbidity is appropriately prioritized during the global crisis. It will also guide public health guidelines for at-risk populations to reduce risks of complications from such comorbidities.

Introduction: There are very limited data on the role of biomarkers correlating with the outcome in acute ischemic stroke (AIS). We evaluated the predictive values of the plasma concentrations of soluble serum stimulation-2 (sST2), matrix metalloproteinase-9 (MMP-9), and claudin-5 in AIS. Methods: The biomarker levels in the plasma samples of consecutive AIS patients collected at baseline, 12 h, and 24 h from stroke onset were quantified using immunoassays. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and functional outcome at 90 days using the modified Rankin Scale (mRS), with scores above 3 defined as poor outcome. Receiver operating characteristic curve analysis and multiple logistic regression were performed for evaluating the discriminative power of each marker. Results: We included 108 patients in the study (mean age 62.3 ± 11.7 years). Median NIHSS score was 12 (interquartile range 8–18). High baseline glucose levels, systolic blood pressure, baseline NIHSS, low Alberta Stroke Program Early CT Score, and hemorrhagic transformation were associated with poor outcomes. Elevated sST2 at 12 h (50.4 ± 51.0 ng/mL; p = 0.047) and 24 h (81.8 ± 101.3 ng/mL; p = 0.001) positively correlated with poor outcomes. MMP-9 (p = 0.086) and claudin-5 (p = 0.2) were not significantly associated with the outcome, although increased expressions of both markers were observed at 12 h. Multiple logistic regression showed that sST2 levels ≥71.8 ng/mL at 24 h, with a specificity of 96.9%, emerged as an independent predictor of poor functional outcome (OR: 6.44; 95% CI: 1.40–46.3; p = 0.029). Conclusion: Evaluation of sST2 may act as a reliable biomarker of functional outcome in AIS.

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 (F[subscript 2], [subscript 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.

Introduction: Around 9–25% of ischemic strokes are embolic stroke of undetermined source (ESUS) with an annual recurrence risk of 4.5–5%. Regarding ESUS, studies from India are limited. Here, we studied the prevalence of cryptogenic ESUS among stroke subtypes, recurrence risk and outcome at 1 year, and their predictors. Materials and Methods: We performed a single-center study of ambispective nature. Patients above 18 years of age with a diagnosis of cryptogenic (ESUS) strokes from January 1, 2017, to December 31, 2020 (4 years), with a 1-year follow-up were recruited in our study. All the patients underwent neuroimaging computerised tomography/magnetic resonance tomography (CT/MRI) with angiography, electrocardiogram (ECG), transthoracic echo (TTE), and rhythm monitoring. Functional outcome was measured using the modified Rankin scale with scores 0–2 taken as good outcome. Results: We had 234 (11.21% of total ischemic strokes) subjects satisfying the criteria for ESUS over the study period with a mean age of 58.2 ± 12.8 years. 46 patients had a history of stroke/transient ischemic attack (TIA) at admission. 9.4% had a recurrent event at 1 year. The most important neuroimaging predictor of recurrent strokes was multiple embolic followed by superficial watershed pattern. Around 10% had more than one marker of atrial cardiopathy positive. While the risk factors, coronary artery disease (CAD), and neuroimaging pattern showed an association with recurrent events at 1 year on bivariate analysis, only the latter two remained significant on multivariate analysis. Conclusions: Our cohort of ESUS had a higher annual recurrence risk than reported before. Though vascular risk factors and ipsilateral vessel abnormalities were more in the recurrent ESUS group, it did not significantly affect the recurrence risk at 1 year. CAD and multiple embolic patterns on imaging showed an association with recurrent strokes, suggesting a possible cardiac substrate in our ESUS population as well.

Byline: Sayooja. Sachithanandan, Harikrishnan. Ramachandran, E. Jayadevan, Santhosh. Kannath, Sapna. Sreedharan, P. Sylaja Background: Identifying carotid pseudo-occlusion (PO) from true occlusion (TO) has implications in determining the candidacy and feasibility [...]

Byline: P. Sylaja [INLINE:1] His life was gentle, and the elements So mixed in him, that Nature might stand up And say to all the world, 'THIS WAS A MAN'. [...]

Byline: P. Sylaja Dear AIAN readers, It is an honor and a great responsibility taking up the role of Editor-in-Chief of Annals of Indian Academy of Neurology (AIAN). I express [...]

Aim This qualitative study explores with health professionals the provision of, and challenges for, postdischarge stroke care, focussing on eating, drinking and psychological support across India.Design Qualitative semistructured interviews.Setting Seven geographically diverse hospitals taking part in a Global Health Research Programme on Improving Stroke Care in India.Participants A purposive sample of healthcare professionals with current experience of working with patients who had a stroke.Results Interviews with 66 healthcare professionals (23 nurses (14 staff nurses; 7 senior nurse officers; 1 intensive care unit nurse; 1 palliative care nurse)); 16 doctors (10 neurologists; 6 physicians); 10 physiotherapists; 5 speech and language therapists; 4 occupational therapists; 4 dieticians; 2 psychiatrists; and 2 social workers resulted in three main themes: integrated inpatient discharge care planning processes; postdischarge patient and caregiver role and challenges; patient and caregiver engagement post discharge.Conclusions Discharge planning was integrated and customised, although resources were limited in some sites. Task shifting compensated for a lack of specialists but was limited by staff education and training. Caregivers faced challenges in accessing and providing postdischarge care. Postdischarge care was mainly hospital based, supported by teleservices, especially for rural populations. Further research is needed to understand postdischarge care provision and the needs of stroke survivors and their caregivers.

Summary: The Southeast Asia Region (SEAR) accounts for nearly 50% of the developing world's stroke burden. With various commonalities across its countries concerning health services, user awareness, and healthcare-seeking behavior, SEAR still presents profound diversities in stroke-related services across the continuum of care. This review highlights the numerous systems and challenges in access to stroke care, acute stroke care services, and health care systems, including rehabilitation. The paper has also attempted to compile information on the availability of stroke specialized centers, Intravenous thrombolysis (IVT) ready centers, Endovascular therapy (EVT) ready centers, rehabilitation centers, and workforce against a backdrop of each country's population. Lastly, the efforts of WHO (SEARO)-CMCL (World Health Organization-South East Asia region, Christian Medical College & Hospital Ludhiana) collaboration towards improving stroke services and capacity among the SEAR have been described.

Summary: Surveillance of stroke is critical to track its burden and assess progress in prevention and treatment. We reviewed the literature to evaluate stroke surveillance efforts in the South-East Asia Region (SEAR) countries, identify progress and assess gaps. Epidemiological data on all the major parameters such as the incidence, prevalence and mortality of stroke were available for India and Thailand but for none of the other SEAR countries. Most of the epidemiological data came from investigator-initiated studies. National stroke surveillance was present only in India in the form of a National Stroke Registry Programme and Thailand has a national database that was used to obtain epidemiological data for stroke. Research on novel methods for stroke registration, such as using information technology, was absent. This review identified serious gaps in the monitoring and surveillance of stroke in SEAR countries. Systematic efforts are needed to fill those gaps.

Background and objectiveAutomated machine learning or autoML has been widely deployed in various industries. However, their adoption in healthcare, especially in clinical settings is constrained due to a lack of clear understanding and explainability. The aim of this study is to utilize autoML for the prediction of functional outcomes in patients who underwent mechanical thrombectomy and compare it with traditional ML models with a focus on the explainability of the trained models.MethodsA total of 156 patients of acute ischemic stroke with Large Vessel Occlusion (LVO) who underwent mechanical thrombectomy within 24 h of stroke onset were included in the study. A total of 34 treatment variables including clinical, demographic, imaging, and procedure-related data were extracted. Various conventional machine learning models such as decision tree classifier, logistic regression, random forest, kNN, and SVM as well as various autoML models such as AutoGluon, MLJAR, Auto-Sklearn, TPOT, and H2O were used to predict the modified Rankin score (mRS) at the time of patient discharge and 3 months follow-up. The sensitivity, specificity, accuracy, and AUC for traditional ML and autoML models were compared.ResultsThe autoML models outperformed the traditional ML models. For the prediction of mRS at discharge, the highest testing accuracy obtained by traditional ML models for the decision tree classifier was 74.11%, whereas for autoML which was obtained through AutoGluon, it showed an accuracy of 88.23%. Similarly, for mRS at 3 months, the highest testing accuracy of traditional ML was that of the SVM classifier at 76.5%, whereas that of autoML was 85.18% obtained through MLJAR. The 24-h ASPECTS score was the most important predictor for mRS at discharge whereas for prediction of mRS at 3 months, the most important factor was mRS at discharge.ConclusionAutomated machine learning models based on multiple treatment variables can predict the functional outcome in patients more accurately than traditional ML models. The ease of clinical coding and deployment can assist clinicians in the critical decision-making process. We have developed a demo application which can be accessed at https://mrs-score-calculator.onrender.com/.

Abstract Background For the treatment of diabetes mellitus (DM) in dogs, novel insulins with decreased injection frequency while maintaining safety and efficacy are desirable. Insulin fused with immunoglobulin‐fragment‐crystallizable (Fc) has an ultra‐long plasma half‐life because it recycles through cells, protected from proteolysis. Hypothesis Glycemic control can be achieved in diabetic dogs with a recombinant fusion protein of a synthetic insulin and canine Fc (AKS‐218d) administered subcutaneously once‐weekly. Animals Five client‐owned dogs with naturally occurring DM. Methods Prospective clinical trial in dogs with DM that were recruited from the UC Davis Veterinary Teaching Hospital and local veterinary clinics. Dogs previously controlled using intermediate‐acting insulin q12h were transitioned to once‐weekly injections of a preliminary construct identified as AKS‐218d. The dose of AKS‐218d was titrated weekly for 8 weeks based on clinical response and continuous interstitial glucose monitoring. Clinical signs, body weight, serum fructosamine concentrations, and mean interstitial glucose concentrations (IG) over the preceding week were compared between baseline (before AKS‐218d) and during the last week of treatment. Data were compared using nonparametric paired tests. Results Once‐weekly AKS‐218d, compared to baseline twice‐daily insulin therapy, resulted in no significant changes in clinical signs, median (range) body weight (+0.4 kg [−0.5‐1.1]; P = .6), fructosamine concentration (−75 mmol/L [−215 to +126]; P = .4), or mean IG (+81 mg/dL [−282 to +144]; P = .8). No adverse reactions were reported. Conclusion Control of clinical signs, body weight, and maintenance of glycemia was achieved with this once‐weekly novel insulin construct in 4 of 5 dogs.

Abstract Background MR plaque imaging is a valuable tool in characterizing carotid atherosclerotic plaque and identifying high-risk features. There are limited data on the role of the widely available single-shot diffusion-weighted imaging (DWI) in plaque characterization along with histological correlation. This study aimed to correlate the plaque characteristics identified by MR imaging in vivo at the level of maximum stenosis with histological plaque characteristics in the postoperative specimen. Methods Patients who underwent carotid endarterectomy in a tertiary care center during one and half years were prospectively recruited for non-contrast MR carotid plaque imaging (including single-shot EPI-DWI sequence) in a 3 Tesla MRI using a dedicated carotid coil. An experienced radiologist correlated DWI sequence findings with histopathology of postsurgical sections to confirm the high-risk features. Results Twenty-three patients (mean age 66.1 years ± SD 6.25) were evaluated, of which 65% were males and 96% were symptomatic. Apparent diffusion coefficient (ADC) values in location of plaques could differentiate histopathological unstable from stable plaques (0.83 × 10–3 mm2/s vs 1.7 × 10–3 mm2/s; p 0.001), with a sensitivity and specificity of 75% and 79%, respectively, at an ADC cutoff of 1.24 × 10–3 mm2/s. Plaques with and without lipid-rich necrotic core (0.86 × 10–3 mm2/s vs 1.44 × 10–3 mm2/s; p = 0.042) as well as intraplaque hemorrhage could be differentiated (0.751 × 10–3 mm2/s vs 1.352 × 10–3 mm2/s; p 0.037) using the apparent diffusion coefficients. Conclusion The widely available single-shot EPI-DWI in assessing plaque characteristics in carotid stenosis is promising and correlated with histopathological features. Diffusion-weighted imaging will be a helpful adjunct in patients when contrast administration is intolerable.

Byline: Jithin. George, P. Sylaja, Sapna. Sreedharan Introduction: Around 9-25% of ischemic strokes are embolic stroke of undetermined source (ESUS) with an annual recurrence risk of 4.5-5%. Regarding ESUS, studies [...]

Arrhythmias are irregular heartbeats that may be life-threatening. Proper monitoring and the right care at the right time are necessary to keep the heart healthy. Monitoring electrocardiogram (ECG) patterns on continuous monitoring devices is time-consuming. An intense manual inspection by caregivers is not an option. In addition, such an inspection could result in errors and inter-variability. This article proposes an automated ECG beat classification method based on deep neural networks (DNN) to aid in the detection of cardiac arrhythmias. The data collected by an Internet of Things enabled ECG monitoring device are transferred to a server. They are analysed by a deep learning model, and the results are shared with the primary caregiver. The proposed model is trained using the MIT-BIH ECG arrhythmia database to classify into four classes: normal beat (N), left bundle branch block beat (L), right bundle branch block beat (R), and premature ventricular contraction (V). The received data are sampled with an overlapping sliding window and divided into an 80:20 ratio for training and testing, with tenfold cross-validation. The proposed method achieves higher accuracy with a simple model without any preprocessing when compared with previous works. For the train and test sets, we achieved accuracy rates of 99.09 and 99.03%, respectively. A precision, recall, and F1 scores of 0.99 is obtained. The proposed model achieves its goal of developing a simple and accurate ECG monitoring system with improved performance. This simple and efficient deep learning approach for heartbeat classification could be applied in real-time telehealth monitoring systems.

Summary: Background: There is a high burden of stroke, including recurrent stroke, in India. We aimed to assess the effect of a structured semi-interactive stroke prevention package in patients with subacute stroke to reduce recurrent strokes, myocardial infarction, and death. Methods: This was a multicentre, randomised, clinical trial conducted in 31 centres of the Indian Stroke Clinical Trial Network (INSTRuCT). Adult patients with first stroke and access to a mobile cellular device were randomly allocated (1:1) to intervention and control groups by the research coordinators at each centre using a central, in-house, web-based randomisation system. The participants and research coordinators at each centre were not masked to group assignment. The intervention group received regular short SMS messages and videos that promoted risk factor control and medication adherence and an educational workbook, in one of 12 languages, and the control group received standard care. The primary outcome was a composite of recurrent stroke, high-risk transient ischaemic attack, acute coronary syndrome, and death at 1 year. The outcome and safety analyses were done in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT03228979 and Clinical Trials Registry-India (CTRI/2017/09/009600) and was stopped for futility after interim analysis. Findings: Between April 28, 2018, and Nov 30, 2021, 5640 patients were assessed for eligibility. 4298 patients were randomised to the intervention group (n=2148) or control group (n=2150). 620 patients were not followed up at 6 months and a further 595 patients were not followed up at 1 year because the trial was stopped for futility after interim analysis. 45 patients were lost to follow-up before 1 year. Acknowledgment of receipt of the SMS messages and videos by the intervention group patients was low (17%). The primary outcome occurred in 119 (5·5%) of 2148 patients in the intervention group and 106 (4·9%) of 2150 patients in the control group (adjusted odds ratio 1·12; 95% CI 0·85–1·47; p=0·370). Among the secondary outcome measures, alcohol cessation and smoking cessation were higher in the intervention group than in the control group (alcohol cessation 231 [85%] of 272 in the intervention group vs 255 [78%] of 326 in the control group; p=0·036; smoking cessation 202 [83%] vs 206 [75%]; p=0·035). Medication compliance was better in the intervention group than in the control group (1406 [93·6%] of 1502 vs 1379 [89·8%] of 1536; p

Primary angiitis of central nervous system (PACNS) is a rare idiopathic disorder affecting blood vessels of brain, spinal cord, and meninges, consequently leading to infarct and less frequently hemorrhage. CNS vasculitis can also occur as part of systemic vasculitis or secondary to autoimmune diseases or infections. The clinical manifestations of PACNS are non-specific and no single laboratory investigation or neuroimaging finding can reliably diagnose this condition. Histopathological evidence of transmural inflammation of blood vessels of CNS is the gold standard, but is generally pursued subsequent to conventional angiogram (CA) because of its invasive nature. The differentials of PACNS are exhaustive and include systemic vasculitis, secondary vasculitis, non-inflammatory intracranial vasculopathies, demyelination, and neoplasm. These alternative conditions can often be distinguished by history, examination, immunological testing, cerebrospinal fluid analysis, and neuroimaging. CA can detect vasculitic changes in the large to medium cerebral arteries but the specificity is low. Recent advancements in vessel wall imaging techniques have further enabled the distinction of various intracranial vasculopathies from CNS vasculitis. The disease has considerable morbidity and fatality unless timely treatment with immunosuppressive agents is initiated. Induction therapy with glucocorticoids and cyclophosphamide followed by azathioprine, mycophenolate mofetil, or methotrexate as maintenance therapy is the cornerstone of management. Biological agents such as rituximab and anti-tumour necrosis factor alpha inhibitors (infliximab and etanercept) may be used in refractory cases. This review discusses the approach to the diagnosis, determinants of outcome, and management.

Background: In LMICs, the medication adherence and risk factor control are suboptimal in the post-stroke follow-up period. With shortage of physicians, smartphone-based interventions can help stroke survivors in secondary stroke prevention. Objectives: We aim to validate a digital innovative technology-based intervention to improve the awareness, medication adherence, control of risk factors through timely intervention of physician among the stroke survivors. Methods: MAMOR is a smartphone-based application to improve the stroke awareness by heath education materials, reminders to timely adherence of medication, alerts on control of risk factors, video files, and timely physician intervention. The study will involve development of the app using contextual research (Delphi qualitative method) followed by a randomized, single center, double arm-controlled trial with 1:1 assignment. The app will be evaluated over a period of 6 months with a target to enroll 192 participants. Process evaluation will be conducted. The sample size was calculated as 192, considering medication adherence of 43.8%, 20% increase in medication adherence by app, power of 80%, and 10% loss to follow-up. Results: The primary outcome will be medication adherence, changes in the lifestyle and behavioral and control of vascular risk factors. The secondary outcome will include vascular events and functional outcome. Conclusion: This study will be one among the few studies for secondary prevention of stroke through digital technology innovation in LMICs with resource constraints. The evidences generated from this study will provide translational evidence for other similar settings for stroke survivors.

Background: Timely and effective recanalization to salvage the penumbra is the main determinant of outcome in acute ischemic strokes. Randomized controlled trials on late window mechanical thrombectomy (MT) have proved its safety and efficacy upto 24 h after stroke onset. We looked at the impact of time to reperfusion on vessel recanalization rates and short-term outcome in patients undergoing MT for large vessel occlusion. Methods: The clinical, imaging, and outcome of all patients undergoing MT upto 24 h from last seen normal was extracted from a prospectively maintained ischemic stroke database from January 2012 till September 2019. Results: There were 145 patients with a mean (SD) age of 58.2 (±14) years. Of them, 28 had wake up/unknown time of onset stroke and 9 presented beyond >360 min. There were 23 vertebrobasilar strokes. Median National Institute of Health Stroke scale score (NIHSS) at admission was 16.4 (Inter quartile range (IQR) 12–21). CT-Alberta Stroke program early CT score (CT-ASPECTS) was excellent (8–10) in 39 (31.6%) and fair (5–7) in 77 (63.6%) patients in anterior circulation strokes. About 25% underwent bridging therapy. Recanalization rates did not differ between those presenting early (

Introduction: Carotid Endarterectomy (CEA) is the standard treatment for patients with symptomatic carotid stenosis. Data from Low- and Middle-Income Countries (LMIC) is sparse on CEA and its outcomes. We aimed to describe the profile of our patients, and factors associated with periprocedural cerebral ischemic events in patients with symptomatic carotid stenosis who underwent CEA in our institute. Methods: Retrospective review of patients with symptomatic carotid stenosis(50-99%) who underwent CEA between January 2011 and December 2021 was done. Clinical and imaging parameters and their influence on periprocedural cerebral ischemic events were analysed. Results: Of the 319 patients (77% males) with a mean age of 64 years (SD ±8.6), 207 (65%) presented only after a stroke. Majority (85%) had high grade stenosis (70%) of the symptomatic carotid. The mean time to CEA was 50 days (SD ±36), however only 26 patients (8.2%) underwent surgery within 2 weeks. Minor strokes and TIA occurred in 2.2%, while major strokes and death occurred in 4.1% patients. None of the clinical or imaging parameters predicted the periprocedural cerebral ischemic events. The presence of co-existing significant (50%) tandem intracranial atherosclerosis (n=77, 24%) or contralateral occlusion (n=24, 7.5%) did not influence the periprocedural stroke risk. Conclusion: There is a delay in patients undergoing CEA for symptomatic carotid stenosis. Majority have high grade stenosis and present late only after a stroke reflecting a lack of awareness. CEA can be performed safely even in patients with significant intracranial tandem stenosis and contralateral carotid occlusion.

Background: The impact of gender on acute ischemic stroke, in terms of presentation, severity, etiology, and outcome, is increasingly getting recognized. Here, we analyzed the gender-related differences in etiology and outcome of ischemic stroke in South India. Methods: Patients with first ever ischemic stroke within 1 week of onset presenting to the Comprehensive Stroke Care Centre, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India, were included in our study. Clinical and risk factor profile was documented. The stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) at onset, and stroke subtype classification was done using Trial of Org 10172 in Acute Ischemic Stroke criteria. The 3-month functional outcome was assessed using the modified Rankin Scale (mRS) with excellent outcome defined as an mRS ≤2. Results: Of the 742 patients, 250 (33.7%) were females. The age, clinical profile, and rate of reperfusion therapies did not differ between the genders. Women suffered more severe strokes (mean NIHSS 9.5 vs. 8.4, p = 0.03). While large artery atherosclerosis was more common in men (21.3% vs. 14.8%, p = 0.03), cardioembolic strokes secondary to rheumatic heart disease were more common in women (27.2% vs. 19.7%, p = 0.02). Men had a better 3-month functional outcome compared to women (68.6% vs. 61.2%, p = 0.04), but was not statistically significant after adjusting for confounders. Conclusion: Our data, from a single comprehensive stroke unit from South India, suggest that stroke in women are different, yet similar in many ways to men. Guideline-based treatment can result in comparable short-term outcomes, irrespective of admission stroke severity.

Abstract Background Treatment of diabetes mellitus (DM) in cats typically requires insulin injections q12h‐q24h, posing a major compliance barrier for caregivers. Novel treatments enabling decreased injection frequency while maintaining safety are highly desirable. Insulin fused with feline immunoglobulin fragment crystallizable (Fc) has an ultra‐long plasma half‐life because it recycles through cells where it is protected from proteolysis. Hypothesis Glycemic control can be achieved in diabetic cats with a recombinant fusion protein of a synthetic insulin and feline Fc (AKS‐267c) administered SC weekly. Animals Five cats with spontaneous DM. Methods Cats previously controlled using insulin glargine q12h were transitioned to once‐weekly injection of AKS‐267c. The dose of AKS‐267c was titrated weekly for 7 weeks based on continuous glucose monitoring. Clinical signs, body weight, fructosamine concentrations, and mean interstitial glucose concentrations (IG) were compared between baseline (week 0, on insulin glargine) and the last week of treatment. Data were assessed for normality and compared using parametric or nonparametric paired tests (as appropriate). Results After 7 weeks of once‐weekly injections, compared to baseline, there were no significant changes in clinical signs, body weight (median [range] gain, 0.1 kg [−0.1 to +0.7]; P = .5), fructosamine (−60 mmol/L [−338 to +206]; P = .6), and mean IG concentrations (change = −153 mmol/L [−179 to +29]; P = .3), and no adverse reactions were reported. Conclusion Successful control of clinical signs and maintenance of glycemia was achieved with this once‐weekly novel insulin treatment. The efficacy and safety of this novel formulation should be further assessed in a large clinical trial.

Introduction: The immediate postoperative hemodynamic alterations occurring after carotid endarterectomy (CEA) is called postendarterectomy hypertension (PEH). PEH results in prolonged hospital admission, increased peri-operative morbidity, and mortality. The exact causes of the PEH whether it is due to carotid sinus denervation or due to the increased norepinephrine production in cerebral and peripheral circulation remain unclear. Materials and Methods: A prospective analysis of 62 patients who underwent CEA from 2018 to 2019 were carried out by dividing into two groups based on the technique of surgery (conventional CEA [c-CEA], n = 31; eversion CEA [e-CEA], n = 31), and the effect of four class of drugs mainly beta blockers (βBs), calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs), and alpha blockers (αBs) were studied for the prevention of PEH. Results: 72.6% of patients developed PEH irrespective of the technique of surgery (e-CEA n = 25 c-CEA n = 20; P = 0.15). The mean postoperative dose of antihypertensive drugs (Mpostoperative) were found significantly increased compared to mean preoperative dose (Mpreoperative) in all PEH patients among βB? group (Mpreoperative 18.95 mg vs. Mpostoperative 45.76 mg; P = 0.00); CCB group (preoperative Mpreoperative 6.21 mg vs. Mpostoperative 9.79 mg; P = 0.01); ARB group (Mpreoperative 14.03 mg vs. Mpostoperative 38.23 mg; P = 0.01); but those patients with preoperative αBs have well controlled BP in the postoperative period without significant change in mean dosage; αB (Mpreoperative 0.16 mg vs. Mpostoperative 3.74 mg: P = 0.27). Conclusions: This study indirectly showed that fluctuations of sympathetic system are happening in both e- and c-CEA irrespective of the technique of surgery. These fluctuations were better controlled in patients who had adequate sympathetic blockade preoperatively. In other words, αB can be considered a drug of choice for PEH.