Prevalence and Trajectories of Post-COVID-19 Neurological Manifestations: A Systematic Review and Meta-Analysis.

INTRODUCTION: The aim of this systematic review and meta-analysis was to evaluate the prevalence of thirteen neurological manifestations in people affected by COVID-19 during the acute phase and at 3, 6, 9 and 12-month follow-up time points. METHODS: The study protocol was registered with PROSPERO (CRD42022325505). MEDLINE (PubMed), Embase, and the Cochrane Library were used as information sources. Eligible studies included original articles of cohort studies, case-control studies, cross-sectional studies, and case series with ≥5 subjects that reported the prevalence and type of neurological manifestations, with a minimum follow-up of 3 months after the acute phase of COVID-19 disease. Two independent reviewers screened studies from January 1, 2020, to June 16, 2022. The following manifestations were assessed: neuromuscular disorders, encephalopathy/altered mental status/delirium, movement disorders, dysautonomia, cerebrovascular disorders, cognitive impairment/dementia, sleep disorders, seizures, syncope/transient loss of consciousness, fatigue, gait disturbances, anosmia/hyposmia, and headache. The pooled prevalence and their 95% confidence intervals were calculated at the six pre-specified times. RESULTS: 126 of 6,565 screened studies fulfilled the eligibility criteria, accounting for 1,542,300 subjects with COVID-19 disease. Of these, four studies only reported data on neurological conditions other than the 13 selected. The neurological disorders with the highest pooled prevalence estimates (per 100 subjects) during the acute phase of COVID-19 were anosmia/hyposmia, fatigue, headache, encephalopathy, cognitive impairment, and cerebrovascular disease. At 3-month follow-up, the pooled prevalence of fatigue, cognitive impairment, and sleep disorders was still 20% and higher. At six- and 9-month follow-up, there was a tendency for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache to further increase in prevalence. At 12-month follow-up, prevalence estimates decreased but remained high for some disorders, such as fatigue and anosmia/hyposmia. Other neurological disorders had a more fluctuating occurrence. DISCUSSION: Neurological manifestations were prevalent during the acute phase of COVID-19 and over the 1-year follow-up period, with the highest overall prevalence estimates for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache. There was a downward trend over time, suggesting that neurological manifestations in the early post-COVID-19 phase may be long-lasting but not permanent. However, especially for the 12-month follow-up time point, more robust data are needed to confirm this trend.

Ischaemic stroke in South Asians: The BRAINS study.

BACKGROUND AND PURPOSE: Studies on stroke in South Asian populations are sparse. The aim of this study was to compare differences in age of onset of ischaemic stroke in South Asian patients living in the United Kingdom and South Asian patients living in India versus White British stroke patients. METHODS: We studied the UK and Indian arms of the ongoing BRAINS study, an international prospective hospital-based study of South Asian stroke patients. The BRAINS study includes 4038 South Asian and White British patients with first-ever ischaemic stroke, recruited from sites in the United Kingdom and India. RESULTS: Of the included patients, 1126 were South Asians living in India (ISA), while 1176 were British South Asian (BSA) and 1736 were White British (WB) UK residents. Patients in the ISA and BSA groups experienced stroke 19.5 years and 7.2 years earlier than their WB counterparts, respectively (mean [interquartile range] age: BSA 64.3 [22] years vs. ISA 52.0 [18] years vs. WB 71.5 [19] years; p < 0.001). Patients in the BSA group had higher rates of hypertension, diabetes mellitus and hypercholesterolaemia than those in the ISA and WB groups. After adjustment for traditional stroke risk factors, an earlier age of stroke onset of 18.9 years (p < 0.001) and 8.9 years (p < 0.001) was still observed in the ISA and BSA groups, respectively. In multivariable stepwise linear regression analysis, ethnicity accounted for 24.7% of the variance in early age onset. CONCLUSION: Patients in the BSA and ISA groups experienced ischaemic stroke approximately 9 and 19 years earlier, respectively, than their WB counterparts. Ethnicity is an independent predictor of early age of stroke onset. Our study has considerable implications for public health policymakers in countries with sizable South Asian populations.

Carotid Intima-Media Thickness (cIMT) and Cognitive Performance: A Population-Based Cross-Sectional Study From North India.

INTRODUCTION: Atherosclerosis has been shown to impact cognitive impairment, with most of the evidence originating from European, African, or East Asian populations that have employed carotid intima-media thickness (cIMT) as a biomarker for atherosclerosis. Vascular disease is related to dementia/cognitive decline. There is no community-based study from India that has looked at the association of cIMT with cognitive performance. METHODS: In this cross-sectional study between December 2014 and 2019, we recruited 7505 persons [(mean age 64.6 (9.2) y) and 50.9% women] from a community-dwelling population in New Delhi. These persons underwent carotid ultrasound to quantify cIMT and a cognitive test battery that tapped into memory, processing speed, and executive function. We also computed the general cognitive factor (g-factor), which was identified as the first unrotated component of the principal component analysis and explained 37.4% of all variances in the cognitive tests. We constructed multivariate linear regression models adjusted for age, sex, education, and cardiovascular risk factors. Additional adjustment was made for depression, anxiety, and psychosocial support in the final model. RESULTS: We found a significant association of higher cIMT with worse performance in general cognition (ß=-0. 01(95% CI: -0.01; -0.01); P<0.001), processing speed (ß=-0.20; 95% CI: -0.34; -0.07); P=0.003), memory (ß=-0.29; 95% CI: -0.53; -0.05); P=0.016), and executive function (ß=-0.54; 95% CI: -0.75; -0.33); P=<0.001). There was no statistically significant association of cIMT with Mini-Mental Status Examination score (ß=0.02; 95% CI: -0.34; 0.40; 0.89). CONCLUSION: The cross-sectional study found significant associations of increased cIMT with worse performance in global cognition, information processing, memory, and executive function.

Consensus Clinical Guidance for Diagnosis and Management of Adult COVID-19 Encephalopathy Patients.

Encephalopathy, a common condition among patients hospitalized with COVID-19, can be a challenge to manage and negatively affect prognosis. While encephalopathy may present clinically as delirium, subsyndromal delirium, or coma and may be a result of systemic causes such as hypoxia, COVID-19 has also been associated with more prolonged encephalopathy due to less common but nevertheless severe complications, such as inflammation of the brain parenchyma (with or without cerebrovascular involvement), demyelination, or seizures, which may be disproportionate to COVID-19 severity and require specific management. Given the large number of patients hospitalized with severe acute respiratory syndrome coronavirus-2 infection, even these relatively unlikely complications are increasingly recognized and are particularly important because they require specific management. Therefore, the aim of this review is to provide pragmatic guidance on the management of COVID-19 encephalopathy through consensus agreement of the Global COVID-19 Neuro Research Coalition. A systematic literature search of MEDLINE, medRxiv, and bioRxiv was conducted between January 1, 2020, and June 21, 2021, with additional review of references cited within the identified bibliographies. A modified Delphi approach was then undertaken to develop recommendations, along with a parallel approach to score the strength of both the recommendations and the supporting evidence. This review presents analysis of contemporaneous evidence for the definition, epidemiology, and pathophysiology of COVID-19 encephalopathy and practical guidance for clinical assessment, investigation, and both acute and long-term management.

Metabolic risk factors and psychosocial problems independently explain poor sleep quality and obstructive sleep apnea symptoms among adults in urban India.

STUDY OBJECTIVES: To determine if metabolic risk factors are associated with poor sleep quality and obstructive sleep apnea-like symptoms (OSA symptoms) independent of psychosocial problems and demographic and lifestyle factors in older Indian adults. METHODOLOGY: We analyzed baseline data from adults (≥ 50 years) from a population-based cohort, the LoCARPoN study, in India. Variables were grouped as (a) demographic and lifestyle factors such as smoking, alcohol use, and physical activity; (b) psychosocial problems including symptoms of depression, anxiety, and perceived stress; and (c) metabolic risk factors including glycated hemoglobin, high-density lipoprotein, low-density lipoprotein, total cholesterol, body mass index, and hypertension. Variables were examined as predictors of poor sleep quality and OSA symptoms. Groups of variables were added stepwise to a logistic regression. Variance explained by nested models was quantified using McFadden's pseudo R2, and change was formally tested with the log-likelihood ratio test. RESULTS: Among 7505 adults, the prevalence of poor sleep quality was 16.9% (95% CI: 16.0, 17.7), and OSA symptoms were present in 7.0% (95% CI: 6.4, 7.6). Psychosocial problems had a strong independent association with both poor sleep quality (pseudo R2 increased from 0.10 to 0.15, p < 0.001) and more OSA symptoms (pseudo R2 increased from 0.08 to 0.10, p < 0.001). Metabolic risk factors had a modest independent association with sleep quality (pseudo R2 increased from 0.14 to 0.15, p < 0.01), but a strong association with OSA symptoms (pseudo R2 increased from 0.08 to 0.10, p < 0.001). CONCLUSION: Psychosocial and metabolic risk factors were independently associated with sleep quality and OSA symptoms. This fact implied that OSA symptoms may affect both mental health and physical health. Our findings have public health implications because the number and proportion of the elderly in India is increasing, while the prevalence of metabolic risk factors and psychosocial problems is high already. These facts have the potential to exacerbate not only the burden of sleep disorders and OSA symptoms but also associated cardiovascular and neurologic sequelae, further stretching the Indian health-care system.

Association of obstructive sleep apnea and sleep quality with cognitive function: a study of middle-aged and elderly persons in India.

INTRODUCTION: Symptoms of obstructive sleep apnea (OSA) and poor sleep quality affect around one in ten people in India. We aimed to determine if OSA symptoms and poor sleep quality are independently associated with cognition in middle-aged and elderly urban Indian populations. METHODS: We studied the cross-sectional association between OSA symptoms (by Berlin Questionnaire), poor sleep quality (by Pittsburgh Sleep Quality Index), and cognitive function in adults ≥ 50 years. Using a standard neuropsychological battery for cognitive function, a G-factor was derived as the first rotated principal component assessing domains of information processing, memory, and executive function. The associations of exposures with cognitive measures were modeled using linear regression, adjusted for metabolic risk factors, lifestyle factors, and psychosocial problems, followed by stratified analysis by decadal age group. RESULTS: A total of 7505 adults were enrolled. Excluding those with MMSE < 26 (n 710), of 6795 individuals (49.2% women), mean (SD) age 64.2 (9.0) years, 38.3% had high risk of OSA symptoms, and 15.9% had poor sleep quality. OSA symptoms were negatively associated with cognitive domains of information processing (adjusted beta coefficient of z-score - 0.02, p-value 0.006), memory (- 0.03, 0.014), and G-factor (- 0.11, 0.014) in full-model. Stratified analysis by age group showed significant adverse effects of OSA symptoms on cognition for middle-aged people (50-60 years) (- 0.26, 0.001), but not in later age groups. Poor sleep quality was also associated with lower cognitive scores for G-factor (- 0.48, < 0.001), memory (- 0.08, 0.005), and executive domains (- 0.12, < 0.001), but not with information domain. CONCLUSION: The findings suggest that both symptoms of OSA and poor sleep quality have a direct adverse impact on cognition in an Indian setting. A modest effect of age on the relationship of OSA and cognition was also observed.

Incremental Accuracy of Blood Biomarkers for Predicting Clinical Outcomes After Intracerebral Hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is associated with high mortality, morbidity, and recurrence. Studies have reported the accuracy of several blood biomarkers in predicting clinical outcomes; however, their independent contribution in prediction remains to be established. AIM: To investigate the incremental accuracy in predicting clinical outcomes in patients with ICH in a north Indian population using blood-based biomarkers. METHODS: In this study, a total of 250 ICH cases were recruited within 72 hours of onset. Baseline clinical and CT scan measurement were recorded. Homocysteine (HCY), C-reactive protein (CRP), matrix metalloproteinase-9 (MMP9), E-selectin (SELE), and P-selectin (SELP) levels were measured through ELISA. Telephonic follow-up was done by using mRS scale at three months. RESULTS: The mean age of cohort was 54.9 (SD±12.8) years with 64.8% patients being male. A total of 109 (43.6%) deaths were observed over three months follow-up. Area under the receiver operating characteristics curve-(AUROC) for 90-day mortality were 0.55 (HCY), 0.62 (CRP), 0.57 (MMP9), 0.60 (SELE) and 0.53 (SELP) and for poor outcome at 90-day (mRS: 3-6) were 0.60 (HCY), 0.62 (CRP), 0.54 (MMP9), 0.67 (SELE) and 0.54 (SELP). In multivariable model including age, ICH volume, IVH and GCS at admission, serum SELE (p=0.004) significant for poor outcome with improved AUROC (0.86) and HCY (p=0.04), CRP (p=0.003) & MMP9 (p=0.02) for mortality with least Akaike's Information Criterion-(AIC) (1060.5). CONCLUSIONS: Our findings suggest that the serum SELE is a significant predictor of poor outcome and HCY, CRP & MMP9 for Mortality in patients with ICH in the north Indian population.

Educating Caregivers to Reduce Complications and Improve Outcomes of Stroke Patients (ECCOS) - A Cluster-Randomized Trial.

OBJECTIVES: Stroke constitutes a significant public health problem in developing countries. Caregivers provide an important support system for patient care but usually lack knowledge and skill to attend their stroke patients. We assessed whether a caregiver-directed educational intervention would reduce hospital-acquired complications and improve stroke patients' outcomes. MATERIALS AND METHODS: We randomly assigned two Neurology inpatient wards to receive either standard care or an educational intervention. The coprimary outcomes included incidence of hospital-acquired complications and in-hospital mortality. Secondary outcomes included the modified Rankin Scale and mortality at three months. RESULTS: Among 164 patients recruited, 82 received intervention, and standard care each. The mean (Standard deviation) Glasgow coma scale of patients was 11.01 (3.4), and National Institute of Health Stroke Scale was 19.17 (8.54). The incidence of complications (72 in the intervention versus 81 in the control group; p=0.56) was not different. Ten patients (12.2%) in the intervention group and 16 (19.5%) in the control group (p=0.20) died in-hospital. Twenty patients (27.8%) in the intervention and twelve (18.2%) in the control group attained modified Rankin Scale 0-2 at three months (p=0.12). The mortality at three months (20 [24.4%] in the intervention versus 25 [30.5%] in the control group) was not different (p=0.38). The intervention group had fewer complications (42 versus 68 in the control group; p=0.01) during the initial ten days of hospital stay, but adjusted analysis revealed no difference. CONCLUSION: A structured educational intervention did not reduce the incidence of hospital-acquired complications, mortality, or morbidity. However, there was a trend towards fewer complications in the initial days of hospital stay. Extended hospital stay, caregiver fatigue, and dilution of the intervention over time might be reasons for the apparent lack of effect. CLINICAL TRIAL REGISTRATION-URL: http://www.ctri.nic.in. Unique identifier: CTRI/2018/11/016312.

CIMT as a risk factor for stroke subtype: A systematic review.

INTRODUCTION: An increase in the common carotid artery intima-media thickness (CCA-IMT) is generally considered an early marker of atherosclerosis and is a well-established predictor of cardiovascular disease (CVD). An association between changes in CCA-IMT and risk of stroke has been reported but has conflicting findings. OBJECTIVE: The present meta-analysis was aimed to clarify the association between CCA-IMT with the risk of stroke and its subtype by estimating pooled analysis of published literature. METHODS: Comprehensive search for all published articles was performed in electronic databases including PubMed, Embase, Cochrane Library, Trip Databases, Worldwide Science, CINAHL and Google Scholar from 01 January 1950 to 30 April 2020. RESULTS: In our meta-analysis, a total of 19 studies, of which sixteen studies involving 3475 ischaemic stroke (IS) cases and 11 826 controls; six studies with 902 large vessel disease (LVD) and 548 small vessel disease (SVD) of IS subtypes; five studies with 228 intracerebral haemorrhage (ICH) and 1032 IS cases, were included. Our findings suggest a strong association between increased CCA-IMT with risk of IS as compared to control subjects [SMD = 1.46, 95% CI = 0.90-2.02]. However, there is an increased risk of LVD as compared to the SVD subtype of IS [SMD = 0.36, 95% CI = 0.19-0.52] and more chance of occurrence of IS rather than ICH [SMD = 0.71, 95% CI = 0.28-1.41]. CONCLUSIONS: Carotid intima thickness measurements are found to be associated with the risk of stroke along with its subtypes and may be used as a diagnostic marker for predicting the risk of stroke events.

Cystatin C and Risk of Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.

INTRODUCTION: Cystatin C (Cys C) has been found as a novel biomarker of neurodegenerative diseases, such as dementia and Alzheimer's disease. Published studies on the role of Cys C as a biomarker of mild cognitive impairment (MCI) have not been reviewed systematically. OBJECTIVE: Present meta-analysis was performed to elucidate the association between Cys C and risk of MCI. METHODS: A comprehensive search was performed in PubMed, EMBASE, Cochrane Library, Trip databases, Worldwide Science, and Google Scholar from January 1, 1950, to April 30, 2020. Standardized mean difference (SMD) with 95% confidence interval (CI) using fixed or random effect models were used to calculate summary estimates. Quality of evidence was also assessed using the Diagnostic Accuracy Quality Scale (DAQS) and grading quality of evidence and strength of recommendations approach. RESULTS: In our meta-analysis, 12 studies with a total of 2,433 MCI patients and 1,034 controls were included. Our findings suggest a strong association between increased levels of Cys C and risk of MCI as compared to control subjects (SMD = 2.39, 95% CI = 0.22-4.57). Subgroup analysis based on ethnicity, a significant association for the high level of Cys C with the risk of MCI was observed in the Asian population (SMD = 1.63, 95% CI = 0.44-2.82) but not in the Caucasian population (SMD = 2.80, 95% CI = [-0.66]-6.26). CONCLUSION: Cys C was associated with MCI, and it could be considered as a predictor for the risk of cognitive impairment.

Role of glial fibrillary acidic protein as a biomarker in differentiating intracerebral haemorrhage from ischaemic stroke and stroke mimics: a meta-analysis.

Background: Studies have suggested promising evidence that glial fibrillary acidic protein (GFAP) could be used as a blood biomarker to distinguish between ischaemic stroke (IS) and intracerebral haemorrhage (ICH) in acute stage.Objective: To determine the available evidence for GFAP as a blood biomarker for differentiating ICH from IS and stroke mimics using a meta-analysis approach.Methods: Search terms were used for literature search: ("STROKE" [Mesh] OR "BIOMARKER" [Title/Abstract] OR "GFAP" [Title/Abstract])] OR "SPECIFICITY" OR "SENSTIVITY" at various search engines like PubMed, Google scholar, Trip database, clinicaltrial.gov for articles from 1990 to April 2019 using filter 'human subjects'. Data were analysed using software STATA version 13.Results: A pooled analysis including 12 studies suggested that GFAP if used as a biomarker to differentiate between different types of strokes (ICH from IS and mimics) had a sensitivity of 78% (95% CI: 67-86%) and a specificity of 95% (95% CI: 88-98%). Positive likelihood ratio (LR) was 14.4 and negative LR was 0.23. SROC with prediction and confidence contours suggests promising area under the curve 0.93, 95% CI ranges from 0.90 to 0.95. Diagnostic odds ratio with 95% CI was observed 63 (31-125).Conclusion: Our meta-analysis suggests that GFAP has a promising diagnostic accuracy for the differentiation of ICH from IS and mimics. Further, phase II and phase III diagnostic test studies are required to validate the findings before using GFAP as a blood based biomarker for clinical use. Trial Registration: This study was registered in OSF registries 10.17605/OSF.IO/B9JP4.

Sample size calculation with simple math for clinical researchers.

Clinicians often need a quick and rough idea of the sample size to assess the feasibility of their clinical research question, but developing countries often lack access to online calculators or its language. I describe a formula that clinicians, residents or any health researcher can remember and use to calculate sample size with mental arithmetic or with the use of a simple pocket calculator. This article covers controlled clinical trials. The formula for two equal-sized groups is simple: n = (16p [100-p])/d2 per group for dichotomous outcomes, where p is average of the two proportions with events, and d is the difference between the two proportions. For continuous scale outcomes, the formula is n=16s2/d2 per group where s is the standard deviation of the outcome data and d is the difference to be detected. The formula needs to be modified for unequal-sized groups. This simple formula may be helpful to clinicians, residents and clinical researchers to calculate sample size for their research questions. The feasibility of many research questions can be easily checked with the calculated sample size.

Anti-interleukin-6 therapies for Covid-19: A systematic review, critical appraisal and meta-analysis.

Background: . Coronavirus disease 2019 (Covid-19) has emerged as a pandemic by end-January 2020. Of the infected patients, 10%-15% may develop severe or critical illness. So far, no definite treatment is available for Covid-19. Cytokine release syndrome may underlie the pathogenesis of severe and critical disease. Anti-interleukin (IL)-6 therapies are being tried to improve clinical outcomes. Methods: . We did a systematic review to identify the available literature on anti-IL-6 therapies in the treatment of Covid-19 and used the GRADE method to assess the quality of evidence. Results: . Four case series and 10 case reports were identified. On critical assessment, we found that these studies reported some beneficial effect of anti-IL-6 therapy, but all the studies had a high risk of bias. The pooled estimate showed that 42% of patients improved but with a very wide confidence interval (CI) (95% CI 1%-91%) and substantial heterogeneity (I2 = 95%). The overall quality of evidence was graded as 'very low'. Conclusions: . Although promising, anti-IL-6 therapy for Covid-19 needs to be tested in randomized controlled trials to provide robust evidence.

Convalescent plasma therapy for Covid-19: A systematic review.

Background: Covid-19 has emerged as a pandemic affecting more than 20 million people till date with few, if any, proven therapy. Convalescent plasma (CP) containing antibodies against the virus has been used with some success. We did a systematic review to synthesize the available data on CP therapy for treatment of Covid-19 to study the efficacy and safety outcomes. Methods: Two reviewers searched the published and pre-published literature between 1 January 2019 and 23 June 2020 for studies comparing the use of CP with standard therapy for Covid-19 patients. Data from the selected studies were abstracted and analysed for efficacy and safety outcomes. Critical appraisal of the evidence was done by using the Joanna Briggs Institute tool and the quality of evidence was graded as per GRADE. Results: We found 13 case series and 1 randomized trial that fulfilled our search criteria. Of the 12 case series with a total of 264 patients that reported the efficacy outcomes, 11 studies showed favourable results with survival benefit. The only RCT with 103 patients did not show any mortality benefit but was terminated early prior to complete enrolment. A single large study of 5000 patients reported safety outcomes and showed no major adverse events in patient streated with CP. Conclusion: There is very low-quality evidence to suggest efficacy and safety of CP in patients with Covid-19 infection. Well-designed randomized trials are urgently needed to provide robust data.

Validation of ICH and ICH-GS Scores in an Indian Cohort: Impact of Medical and Surgical Management.

OBJECTIVE: Prognostic scores help in predicting mortality and functional outcome post intracerebral hemorrhage (ICH). We aimed to validate the ICH and ICH-GS scores in a cohort of Indian patients with ICH and observe the impact of any surgical intervention on prognostication. METHODS: This was an ambispective observational study of primary ICH cases enrolled between January 2014 and April 2018. Observed mortality on ICH and ICH GS scores for the entire cohort and individually for the medically and surgically managed patients was compared to the published mortality in the original derivation cohorts. RESULTS: 617 patients, (464 retrospective and 153 prospective) of ICH were included. In hospital mortality and 30-day mortality was 28.7% and 28.5% respectively. There was a significant association of increasing mortality with increasing ICH and ICH-GS scores. Area under receiver operating characteristic curve for 30-day mortality was 75.9% and 74.1% for ICH and ICH-GS scores respectively. However, mortality observed at individual scores was significantly less than previously reported. Among the surgically intervened patients (n = 265), both the expected mortality at baseline and discriminative ability of ICH and ICH-GS scores for 30-day mortality was significantly reduced following surgical intervention (ROC in surgically intervened groups: 59.9 (52.6-67.2) and 63(56-70) for ICH and ICH-GS scores respectively). CONCLUSIONS: Although ICH and ICH-GS scores are valid in Indian population, mortality at individual scores is lower than previously reported. Mortality prediction using ICH and ICH GS scores is significantly modified by surgical interventions. Thus, newer prognostic tools which incorporate surgical intervention need to be developed and validated in future.

Coronary Artery Disease in Patients with Ischemic Stroke and TIA.

BACKGROUND AND OBJECTIVES: Ischemic stroke (IS) and coronary artery disease (CAD) share common risk factors and one may be the harbinger of the other. We aimed to study prevalence of symptomatic and asymptomatic CAD in a cohort of consecutive patients with IS and assess its relationship with intracranial and extracranial large artery cerebrovascular disease (LAD). METHODS: All consecutive eligible IS and Transient Ischemic Attack (TIA) patients were recruited into the study. Both clinically suspected and asymptomatic patients (N = 259) underwent myocardial Stress-rest Gated Technetium-99m (Tc99m) MIBI Myocardial Perfusion SPECT scan performed on a dual head SPECT-CT to estimate evidence of myocardial ischemia. RESULTS: Three hundred patients completed the study. Forty one patients were previously diagnosed cases of definitive CAD. Twelve patients were clinically suspected to have CAD and 247 patients were asymptomatic. Among these, 12 patients (4.81%) had a positive SPECT. The overall prevalence of CAD was 17.67% (n = 53). Presence of diabetes was an independent predictor of CAD (OR 1.98, 95% CI 1.07-3.67. P .02). No significant association was found between the presence of LAD and CAD in all subgroup comparisons. However, there was a suggestion of higher LAD among patients with known CAD compared with others. CONCLUSIONS: CAD is prevalent in patients with ischemic stroke. No definitive relationship was found between CAD and intracranial or extracranial LAD. Population based stratification tools are needed to further assess the need to detect subclinical CAD in patients with stroke.

Stroke-related education to emergency department staff: An acute stroke care quality improvement initiative.

BACKGROUND: Acute ischemic stroke therapy is time sensitive, and optimum treatment is missed due to pre-hospital and/or in-hospital delay. MATERIALS AND METHODS: A prospective observational (before and after) study was conducted for 1 year.The study period was defined as phase-I or pre-education phase, phase-II or immediate post-education phase, and phase-III or delayed post-education phase, with each phase lasting for 4months. All consecutive stroke patients presenting within 12 hours of stroke onset were enrolled. Baseline and outcome data including acute stroke care quality matrices and functional outcomes were collected. RESULTS: A total of 264 patients were enrolled. All acute stroke care quality matrices improved significantly (P ≤ 0.01) with a median door to imaging time (DTI) of 114, 35, and 47 minutes in the three phases consecutively. In phase-II, proportions of patients imaged within 25 minutes of arrival increased by 35%. Mean door to needle (DTN) time were 142 ± 49.7,63.7 ± 25.1, and 83.9 ± 38.1 minutes in the three consecutive phases. Patients with DTN < 60 minutes of arrival increased by 63%. Modified Rankin score (mRS) at 3 months improved significantly in all ischemic stroke patients (P = 0.04) and patients with mRS of 0-2 increased by 22%. CONCLUSIONS: Stroke education to emergency department (ED) staff is an effective method to improve acute stroke care.

Brain Volumes and Longitudinal Cognitive Change: A Population-based Study.

OBJECTIVE: To investigate the association of brain volumes, white matter lesion (WML) volumes, and lacunes, with cognitive decline in a population-based cohort of nondemented persons. METHODS: Within the Rotterdam Study, 3624 participants underwent brain magnetic resonance imaging. Cognition was evaluated at baseline (2005 to 2009) and at the follow-up visit (2011 to 2013). We used a test battery that tapped into domains of executive function, information processing speed, motor speed, and memory. The volumetric measures assessed were total brain volume, lobar (gray matter and white matter) volumes, and hippocampal volumes. We also studied the association of WML volumes and lacunes with cognitive decline using linear regression models. RESULTS: Total brain volume was associated with decline in global cognition, information processing, and motor speed (P<0.001) in analyses controlled for demographic and vascular factors. Specifically, smaller frontal and parietal lobes were associated with decline in information processing and motor speed, and smaller temporal and parietal lobes were associated with decline in general cognition and motor speed (P<0.001 for all tests). Total WML volume was associated with decline in executive function. Lobar WML volume, hippocampal volume, and lacunes were not associated with cognitive decline. CONCLUSIONS: Lower brain volume is associated with subsequent cognitive decline. Although lower total brain volume was significantly associated with decline in global cognition, specific lobar volumes were associated with decline in certain cognitive domains.

Clinical spectrum and quality of life in patients with chronic polyneuropathy: A cross-sectional study.

Chronic polyneuropathy is a disabling condition of the peripheral nerves, characterized by symmetrical sensory motor symptoms and signs. There is paucity of studies on the etiological spectrum of polyneuropathy and its impact on quality of life (QoL). The present cross-sectional study in a referral based tertiary care center in North India found diabetic neuropathy as the commonest cause (25.5%) amongst 212 patients with chronic polyneuropathy. Idiopathic axonal polyneuropathy was present in 14.2% patients. Leprosy presenting as confluent mononeuritis multiplex constituted 11.3% of the patients. Additionally, it revealed a significantly worse QoL in these patients in all domains measured by short form (SF-36). This is the first study conducted in India to determine the QoL in chronic neuropathy patients. The current study demonstrates the clinical feasibility and applicability of the SF-36 generic health status in patients with polyneuropathies.

Intra-arterial transplantation of human bone marrow mesenchymal stem cells (hBMMSCs) improves behavioral deficits and alters gene expression in rodent stroke model.

Stroke is a multi-factorial polygenic disease and is a major cause of death and adult disability. Administration of bone marrow stem cells protects ischemic rat brain by facilitating recovery of neurological functions. But the molecular mechanism of stem cells action and their effect on gene expression is not well explored. In this study, we have transplanted 1 × 106 human bone marrow mesenchymal stem cells (hBMMSCs) in middle cerebral artery occluded (MCAo) adult male Wistar rats through intracarotid artery route at 24 h after surgery. Motor behavioral tests (rotarod and open field) were performed to assess the changes in motor functions at day 0 and day1, 4, 8 and 14. The expression of studied genes at mRNA and protein level was quantified by using Q-PCR and western blotting, respectively. Further, we have assessed the methylation pattern of promoter of these genes by using methylation-specific PCR. Data were analyzed statistically and correlated. A significant improvement in behavioral deficits was observed in stem cells treated group after 14th day post stroke. Significantly (p < 0.05) increased mRNA and protein levels of brain derived neurotrophic factor and ANP genes in hBMMSCs treated group along with decrease in methylation level at their promoter was observed. On the other hand, significantly decreased mRNA and protein level of TSP1 and WNK1 in hBMMSCs treated group was observed. In conclusion, hBMMSCs administration significantly improves the behavioral deficits by improving motor and locomotor coordination. The promoter of TSP1 and WNK1 genes was found to be hyper-methylated in hBMMSCs group resulting in their decreased expression while the promoter of ANP and brain derived neurotrophic factor was found to be hypo-methylated. This study might shed a light on how hBMMSCs affect the gene expression by modulating methylation status.