Correlation Between Optical Coherence Tomography Angiography Findings at 3 to 6 Weeks and Functional Outcome at 3 Months Following Acute Ischaemic Stroke Due to Extracranial Carotid Artery Atherosclerotic Disease.

We wanted to evaluate if optical coherence tomography angiography OCTA findings could predict the functional outcome in extracranial carotid artery atherosclerotic disease (ECAD) associated stroke. This exploratory study was performed on adults with acute ischaemic stroke due to ECAD at 3-6 weeks following stroke onset with risk factor matched controls without carotid artery stenosis. Twenty-three stroke patients (cases) and 23 controls were enrolled. There was significant difference between cases and controls in deep vessel density at the macula (p = .0007) and in radial peripapillary capillary perfusion density (RPCPD) at the optic nerve head (ONH) (p = .0007). Statistically significant difference was noted in the total superficial vessel density (SVD) at the macula (SVD within 1 standard deviation [SD] versus SVD beyond 1 SD of control data) in the ipsilateral eye and functional outcome at 3 months (poor versus very good outcome, modified Rankin scale [mRS] 0-1 versus mRS 2-6, respectively; p = .0361). There was statistically insignificant correlation between the RPCPD at the ONH and the National Institutes of Health Stroke Scale score at admission, mRS at discharge, and mRS at 3 months following stroke onset (r = .33, r = .35, r = .39; p = .11, p = .09, p = .06, respectively). The findings of this exploratory study suggested that OCTA findings may predict 3 month outcomes in cases of ECAD-related stroke and could be useful in decision making in future intervention studies as to whether intervene or not in patients having critical or non-critical ECAD for preventing stroke.

Acute bilateral sensorineural hearing loss as presentation of leptomeningeal metastases.

We describe a rare occurrence of bilateral acute severe sensorineural hearing loss in a middle-aged man that heralded the diagnosis of metastatic gastric cancer.

Shrinking lung syndrome mimicking diaphragmatic palsy in systemic lupus erythematosus.

A 25-year-old woman presented with 1 year of progressive orthopnoea, initially explained as bilateral diaphragmatic paresis caused by seronegative myasthenia gravis. She required assisted ventilation and received pyridostigmine and corticosteroids. She had minimal (particularly proximal) symmetrical tetraparesis with apparent bilateral diaphragmatic weakness, but had normal sensation. Further investigation suggested an overlap myositis with shrinking lung syndrome from systemic lupus erythematosus. She improved following immunosuppression with pulse corticosteroids and rituximab, and at 3 months no longer needed bilevel positive airway pressure support.

Impact of weight reduction on structural and functional parameters of the optic nerve in idiopathic intracranial hypertension.

PURPOSE: To evaluate the effect of weight reduction on the structural and functional parameters of the optic nerve in established cases of papilledema in Idiopathic Intracranial Hypertension (IIH). METHODS: A prospective observational study in early and established cases of papilledema in IIH presenting from December 2019 to February 2021. Functional parameters (visual acuity, contrast sensitivity, mean deviation, VER), structural parameters (RNFL, GCL-IPL, and optic disc height), and clinical grading of papilledema were measured at baseline and every 6 weeks for 6 months. All patients underwent medical (oral acetazolamide) and diet therapy. RESULTS: Mean body mass index (BMI) at presentation was 26.32 ± 3.52 kg/m² and the mean change in BMI over 6 months was 1.27 ± 0.50 kg/m². 67% of eyes had papilledema of grades 2-3 at the presentation. At the end of 6 months, 75% of eyes had grade 1 papilledema while 13% showed complete resolution. A reduction of 5.32 ± 3.58 in mean deviation (r = 0.316; p-value 0.01) and gain in VER P100 amplitude of 4.2 ± 2.7 µV (r = 0.40; p-value 0.003) were noted over 6 months with reduction in BMI over 6 months. A statistically significant reduction in optic disc height (ODH) was noticed with BMI reduction over 6 months (p = 0.0007; r = 0.45).A reduction of 1.72 ± 0.90 kg/m² (equivalent to 6.53% weight loss) in BMI was associated with a four-grade change in clinical grading of papilledema. CONCLUSION: Reduction in BMI had a significant impact on both structural and functional parameters of the optic nerve in IIH. The involvement of a well-certified dietician should be an integral part of treatment in IIH.

Safety and efficacy of N-acetylcysteine (NAC) as an adjunct to standard treatment in patients with acute ischemic stroke: a randomized controlled pilot trial (NACTLYS).

There is a pressing clinical need for thrombolytic agents that can effectively disaggregate arterial thrombi in acute ischemic stroke without significantly increasing the risk of bleeding. This pilot study aimed to investigate the safety and efficacy of N-acetylcysteine (NAC) as an adjunctive therapy to intravenous recombinant tissue plasminogen activator (rtPA or alteplase). A randomized, open-label, blinded assessor pilot study was conducted. Patients presenting with an acute ischemic stroke within 4.5 h from onset were randomized into two groups: intravenous NAC and rtPA or rtPA alone. Primary outcomes included intracerebral hemorrhage, symptomatic intracerebral hemorrhage, extracranial bleeding, and adverse reactions. Secondary outcomes comprised major neurological improvement assessed by (National Institute of Health Stroke Scale) NIHSS at 24 h, recanalization on first run of angiography in patients who underwent thrombectomy or on repeat vascular imaging at 24 h, modified Rankin scale, and three-month mortality. Forty patients were enrolled, with 21 receiving only rtPA and 19 receiving NAC with rtPA. Baseline characteristics were comparable among groups. No significant differences were observed in adverse events (p = 0.99), intracranial hemorrhage (p = 0.21), symptomatic intracerebral hemorrhage (p = 0.47), or extracranial bleeding (p = 0.21). Median NIHSS at 24 h was significantly lower in the intervention group (p = 0.03). Functional outcomes and three-month mortality were similar between groups (p = 0.85 and p = 0.99 respectively). The co-administration of N-acetylcysteine with alteplase did not significantly alter safety profiles, morbidity, or mortality at 3 months. While no substantial differences were noted, a slightly improved early neurological outcome was observed in the intervention arm. The study's findings were constrained by a small sample size, emphasizing the necessity for future large-scale trials to comprehensively evaluate the safety and efficacy of N-acetylcysteine as a thrombolytic agent in acute ischemic stroke.Trial Registration Clinical Trials Registry India-CTRI/2019/05/019305.

Cerebrospinal fluid proteins in idiopathic intracranial hypertension: An exploratory SWATH proteomics analysis.

PURPOSE: The pathogenesis of idiopathic intracranial hypertension (IIH) is currently poorly understood. This exploratory study aimed to identify potential cerebrospinal fluid (CSF) biomarkers in IIH cases compared to controls using SWATH-MS proteomics approach. EXPERIMENTAL DESIGN: CSF samples were collected prospectively from IIH cases and control subjects which were subjected to SWATH-MS based untargeted proteomics. Proteins with fold change > 1.5 or < 0.67 and p-value < 0.05 were considered significantly differentially expressed. Data are available via ProteomeXchange with identifier PXD027751. Statistical analysis was conducted in R version 3.6.2. RESULTS: We included CSF samples from 33 subjects, consisting of 13 IIH cases and 20 controls. A total of 262 proteins were identified in Proteinpilot search. Through SWATH analysis, we quantified 232 proteins. We observed 37 differentially expressed proteins between the two groups with 24 upregulated and 13 downregulated proteins. There were two differential proteins among overweight versus non-overweight IIH cases. Network for 23 proteins was highly connected in the interaction analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Neurosecretory, neuroendocrine, and inflammatory proteins were predominantly involved in causing IIH. This exploratory study served as a platform to identify 37 differentially expressed proteins in IIH and also showed significant differences between overweight and non-overweight IIH patients.

Clinical factors and vascular endothelial growth factor as determinants of disease progression in Indian patients with amyotrophic lateral sclerosis.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder. Prognostication remains sub-optimally defined. We aimed to assess clinical determinants of disease progression rates in Indian patients with ALS and to assess the role of vascular endothelial growth factor (VEGF) in disease progression. METHODS: In this cross-sectional study, consecutive patients with clinically definite/probable ALS according to the revised El Escorial criteria and controls were included. Patients were classified into fast or slow progressors based on disease progression rate (DPR). Serum and CSF VEGF level was assessed for patients and controls. RESULTS: Of 142 patients recruited, 93 (65.5%) were male. Mean age at enrollment was 49.37 ± 12.65 years. Mean duration of symptoms was 20.53 ± 20.88 months. Mean DPR was 1.14 ± 0.94. Based on DPR, 81 (57%) patients were slow progressors and 61 (43%) were fast progressors. Univariate analysis demonstrated a statistically significant association of DPR with age at onset, symptom duration, time to spread, wasting of small muscles of the hand, frontal release signs, and neurophysiologic bulbar abnormalities. On multivariate analysis, age at onset and symptom duration had a significant association with disease progression. The CSF VEGF levels of ALS patients (46.18 ± 27.8) were significantly elevated compared to controls (25.95 ± 25.64 pg/ml) (p = 0.001), but not serum VEGF. CONCLUSION: Age at symptom onset and duration of disease had a significant impact on disease progression in Indian patients with ALS. CSF VEGF levels were significantly elevated in ALS compared to controls, indicating the role of CSF VEGF as a potential biomarker.

Early neurological deterioration in acute ischemic stroke.

BACKGROUND AND AIMS: Early neurological deterioration (END) in acute ischemic stroke (AIS), patients is defined as clinical worsening or recurrence during first 72 h after onset of AIS. We have conducted this study to determine the association between END and functional outcome at 3 months of onset of AIS along with associated risk factors of END in AIS cases. METHODOLOGY: This study was conducted after approval of Institute Ethics Committee. Two hundred three consecutive patients were admitted from September 2020 to January 2022 at a tertiary care hospital. One hundred ninety patients were included in the study; patients were divided into two groups: (1) early neurological deterioration (END) and (2) non-early neurological deterioration (non-END). Patients were followed-up either telephonically or in person at approximately 3 months using modified Rankin Scale 0-6. All the clinically significant prognostic markers and p < 0.10 variables were considered significant in univariate analysis; P < 0.05 were considered statistically significant for the multivariate analysis. RESULTS: Out of 190 cases included in the cohort 34/190 (17.8%) cases showed END with mean age (56.56 (± 16.6)) and males (20/34 (58.8%)). END was independently associated with high blood glucose at admission (OR = 1.015; P = 0.002; 95%CI = 1.005-1.024) and low serum albumin (OR = 0.208; P = 0.002; 95%CI = 0.077-0.562). Patients with END showed poor functional outcome (mRS > 2) at end of 3 months (32 (94.1%); P < 0.001) and death was also statistically significant (22 (64.7%); P < 0.001) as compared to AIS cases having non-END. CONCLUSION: Our study showed END may be associated with poor functional outcome in AIS patients. Higher blood glucose at admission and low serum albumin may be statistically significant causing END. Future prospective cohort with larger sample size may confirm the findings.

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.

Challenges in setting up a large population-based prospective cohort study in India - learnings from the LoCARPoN cohort.

Population-based prospective cohort studies can yield vital new evidence. However, they are difficult to setup especially in non-western contexts such as India. We describe our experience in establishing the Longitudinal Cognition and Aging Research on Population of the National Capital Region (LoCARPoN) cohort, which was the first-of-its-kind public-funded study with target sample size of 15,000, 3 sites, and funds of approx. US$ five million for eight years (2014-2022). LoCARPoN aimed to study incident stroke and dementia in adults aged ≥50 years in urban and rural populations of north India. Among the numerous challenges encountered, important were inadequate funding, lack of adequate space for medical and field sites, difficulty in hiring manpower, lack of IT infrastructure, non-availability of storage facility for biological samples, and absence of dedicated MRI machines. Meticulous planning, adequate funding, trained personnel, institutional and community support are critical for establishing such cohorts in the non-western contexts. Funding: The LoCARPoN cohort study was funded by the Department of Biotechnology (Grant No. BT/IN/Netherlands/03/KP/2012 dated 14/02/2014); and Department of Health Research (Grant No. R.11012/15/2018-HR, dated 09/08/2018), Government of India. The Erasmus component was funded through the Erasmus Medical Centre, Rotterdam, The Netherlands, and the Erasmus University, Rotterdam (Alzheimer NederlandWE.15-2014-09).

Prevalence and determinants of post-stroke sleep disorders: a cross-sectional hospital-based study.

INTRODUCTION: Post-stroke sleep disorders (PSSD) are an important part of post-stroke disability. PSSD is neglected as a part of stroke rehabilitation. We aimed to study the prevalence and determinants of PSSD in a hospital based, single center setting. METHODS: In a cross-sectional study, adult patients (≥ 18 years) with stroke (one month to one year after the onset), were enrolled in the study. Demographic, clinical, radiological, and motor and functional disabilities were assessed. Sleep quality was assessed with Pittsburg Sleep Quality Index (PSQI) and STOP BANG questionnaire (for obstructive sleep apnea [OSA]). Patients with poor sleep quality (PSQI > 5) were analyzed for risk factors. RESULTS: A total of 103 patients were recruited in the study period (January 2021 to June 2022). The self-reported prevalence of PSSD was 16% which increased to 72% when the PSQI was administered. High risk of OSA was present in 33%. In bivariate analysis, factors associated with PSQI > 5 were involvement of ≥ 2 lobes, lower body mass index (BMI), worse modified Rankin Scale (mRS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) and Stroke Specific Quality of Life (SSQoL). In multivariate analysis, only depression was associated with PSQI > 5 (OR: 1.3 (1.0; 1.7); p-value = 0.03). CONCLUSION: PSSD had a prevalence of 72%. In multivariate analysis, the factor associated with PSQI > 5 was worse HAM-D score.

Biosimilar Tenecteplase Versus Alteplase in Acute Ischemic Stroke: A Real World Study.

Background and Purpose: There is an unmet need for a more effective thrombolytic agent in acute ischemic stroke (AIS) management. Various studies and meta-analysis suggest tenecteplase (TNK) as non-inferior over alteplase (rTPA). The present single-center study compares biosimilar TNK and rTPA in a tertiary care setting. Methods: Data of patients who presented with AIS and underwent intravenous thrombolysis (IVT) were recruited retrospectively from January 2018 to July 2021. Primary efficacy outcome was a modified Rankin score (mRS) at 90 days dichotomized at < = 2. Qualitative and quantitative variables were assessed using Chi-square test and Student's t-test, respectively. Results: A total of 160 patients, 103 in the rTPA and 57 in TNK group, were analyzed. The baseline characteristics were well matched apart from hypertension. Large artery atherosclerosis was the most frequent subtype of stroke among the two groups. Good functional outcome was seen in 47.92% of patients TNK and 64.77% of patients in rTPA group (p = 0.069). No difference was seen in the rates of any ICH (p = 0.29) and mortality at 3 months (p = 0.32) among the two groups. Conclusion: This present study observed no difference in the efficacy and safety between biosimilar TNK and rTPA. Our findings are in concordance with published trials showing equivalence between the two molecules.

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.

Association of periodontitis and gingivitis with stroke: A systematic review and meta-analysis.

BACKGROUND: Stroke is among the leading causes of morbidity and mortality. Chronic inflammatory conditions may lead to atherosclerosis and a subsequent stroke. OBJECTIVES: This systematic review and meta-analysis aimed to review the association of periodontitis and gingivitis with stroke. METHODS: An electronic search of PubMed, Ovid EMBASE, Ovid MEDLINE, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Science Citation Index, Database of Abstracts and Reviews of Effects (DARE), and various clinical trial registries was conducted to include studies published up to February 2022. Data was retrieved by 2 independent reviewers. The Stata software, v. 13, was used to conduct a meta-analysis. RESULTS: Thirteen studies stated an association between periodontitis, determined based on clinical attachment loss (CAL), and stroke. Meanwhile, 6 studies described an association between gingivitis, determined based on the gingival index (GI), and stroke. Out of the 6 studies on gingivitis, 5 also investigated CAL, which means the meta-analysis included 14 studies in total. The total number of participants from the included studies was 35,937, and they were all above 17 years of age. There was a significant association between periodontitis and gingivitis and stroke and its all types. There was a significant association between periodontitis and stroke and its all types in 13 studies (ES (effect size): 1.32; 95% CI (confidence interval): 1.04-1.60), and between gingivitis and all stroke types in 6 studies (ES: 1.17; 95% CI: 0.42-1.92). CONCLUSIONS: This systematic review indicated a significant association between stroke and periodontal disease in case-control, cohort and cross-sectional studies. The findings need to be further substantiated in prospective cohort studies with an optimal sample size.

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.

Comparison of dexamethasone regimens in tubercular meningitis (TBM): a randomized open label clinical trial.

INTRODUCTION: Corticosteroids are used as adjunctive treatment in tuberculous meningitis (TBM). However, there is no universally accepted regimen, type, duration, or route of steroid administration. METHODOLOGY: In a randomized open labelled pilot study, TBM patients were divided into overlap oral dexamethasone (OOD) and direct oral dexamethasone (DOD) arms. The total duration of steroid administration was 8 weeks. The primary outcome was symptomatic resolution at 1 month post randomization. The secondary outcomes were mortality and modified Rankin scale (mRS) at 3 and 6 months after initiation of steroids. RESULTS: Symptomatic resolution after one month of randomization in 53 randomized patients was similar in OOD (71.4% (15/21)) versus DOD ((85.0% (17/20)) arm (p value:0.45). Median mRS was also similar in OOD versus DOD (OOD: 2.5 (IQR: 1.0; 6.0) versus DOD: 1.0 (IQR: (0.0; 4.0); p value: 0.31)) arm at 6 months. The mortality at 6 months was 31.8% (7/22) in the OOD versus 20.0% (4/20) in the DOD arm (p value: 0.49). CONCLUSIONS: In this open label pilot study, the outcomes were similar in OOD versus DOD arms in terms of symptomatic resolution at 1 month, and morbidity, and mortality at 3 and 6 months. Patients with stage I to III TBM may be given injectable steroids for 1 week after which they may be switched to oral steroid. This regime cannot be applied to stage IV TBM and patients with complications like optico-chiasmatic or spinal arachnoiditis or vasculitic infarcts.