Clinicopathological Profile of Muscle Diseases Presenting the Adult Population in Northern India: Preliminary Analysis in a Limited Resource Setting.

BACKGROUND: Muscle diseases are of various types, viz., muscular dystrophies, inflammatory myopathies, myotonic disorders, congenital myopathies, and metabolic myopathies. They all present with muscle weakness, be it proximal or distal. The assessment of muscle biopsy with the help of enzyme histochemistry, histopathological, and immunohistochemical methods is an essential component in the diagnosis of neuromuscular disorders. The authors outline brief data on muscle diseases prevalent in the North Indian region. METHODS: Muscle biopsy was done, and the biopsy was freshly frozen in liquid nitrogen and sections were taken on a cryostat. Slides were then stained with hematoxylin and eosin (H&E), modified Gomori trichome (MGT), nicotinamide adenine dinucleotide hydrogenase (NADH), and succinic dehydrogenase (SDH) stains. Further specific immunohistochemistry tests were also done. RESULT: Out of n=16 cases, three cases were diagnosed as Becker's muscular dystrophy, two cases were diagnosed as inflammatory myopathy, four cases were diagnosed as Facioscapulohumeral muscular dystrophy, and one each case of dysferlinopathy and alpha sarcoglycanopathy. CONCLUSION: Muscle diseases can cause different levels of physical disability and thus it is important to diagnose at the appropriate time to ensure proper treatment.

HIV self-testing in India: implementation and qualitative evaluation of a web-based programme with virtual counsellor support.

INTRODUCTION: To achieve epidemic control of infectious diseases, engaging higher-burden populations with accessible diagnostic services is critical. HIV self-testing (HIVST) is a promising option. METHODS: We implemented an online HIVST programme for key populations across India. Eligible clients were 18 years or older, self-reported a negative or unknown HIV status and reported not taking antiretroviral therapy. Clients who reported a prior HIV diagnosis were not eligible to receive an HIVST kit. HIVST clients received kits via courier or in person at pre-determined pick-up points supported by trained counselling staff. Virtual counsellors engaged clients online and by phone and offered support to register, access, and complete HIVST free of cost. Virtual counsellors supported clients to report results and engage with follow-up services. Follow-up included linking clients with a positive result to confirmatory testing and HIV care services. We assessed programmatic data across HIV continuum outcomes and conducted a qualitative evaluation through interviews with purposively sampled clients. RESULTS: Between 30 June 2021 and 30 September 2022, 5324 clients ordered an HIVST kit (76% men, 13% women, 7% transgender people, 4% unknown gender). Of the 4282 clients reporting results (94% of those who received a kit), 6% screened positive, among whom 72% (n = 184) completed confirmatory testing. Themes from 41 client interviews included satisfaction about the convenience and privacy of services and the discreet nature of kit delivery. Respondents were drawn to the convenience of HIVST and appreciated gaining courage and comfort throughout the process from virtual counsellor support. For respondents who screened positive, challenges to care linkage included fearing judgemental questions from public providers and wanting more time before starting treatment. Clients shared concerns about kit accuracy and suggested that instructional materials be provided with more diverse language options. CONCLUSIONS: Web-based HIVST services with tailored support appeared to facilitate HIV service access and engagement of harder-to-reach populations across India. Assistance from a community-oriented counsellor proved important to overcome literacy barriers and mistrust  in order to support the HIVST process and service linkage. Learnings can inform global efforts to improve the critical step of diagnosis in achieving epidemic control for HIV and other infectious diseases.

Characterization of spinal cord tissue-derived extracellular vesicles in neuroinflammation.

Extracellular vesicles (EVs) are released by all cells, can cross the blood-brain barrier, and have been shown to play an important role in cellular communication, substance shuttling, and immune modulation. In recent years EVs have shifted into focus in multiple sclerosis (MS) research as potential plasma biomarkers and therapeutic vehicles. Yet little is known about the disease-associated changes in EVs in the central nervous system (CNS). To address this gap, we characterized the physical and proteomic changes of mouse spinal cord-derived EVs before and at 16 and 25 days after the induction of experimental autoimmune encephalomyelitis (EAE), a neuroinflammatory model of MS. Using various bioinformatic tools, we found changes in inflammatory, glial, and synaptic proteins and pathways, as well as a shift in the predicted contribution of immune and glial cell types over time. These results show that EVs provide snapshots of crucial disease processes such as CNS-compartmentalized inflammation, re/de-myelination, and synaptic pathology, and might also mediate these processes. Additionally, inflammatory plasma EV biomarkers previously identified in people with MS were also altered in EAE spinal cord EVs, suggesting commonalities of EV-related pathological processes during EAE and MS and overlap of EV proteomic changes between CNS and circulating EVs.

In Silico Prediction of Potential Inhibitors for Targeting RNA CAG Repeats via Molecular Docking and Dynamics Simulation: A Drug Discovery Approach.

Spinocerebellar ataxia (SCA) is a rare neurological illness inherited dominantly that causes severe impairment and premature mortality. While each rare disease may affect individuals infrequently, collectively they pose a significant healthcare challenge. It is mainly carried out due to the expansion of RNA triplet (CAG) repeats, although missense or point mutations can also be induced. Unfortunately, there is no cure; only symptomatic treatments are available. To date, SCA has about 48 subtypes, the most common of these being SCA 1, 2, 3, 6, 7, 12, and 17 having CAG repeats. Using molecular docking and molecular dynamics (MD) simulation, this study seeks to investigate effective natural herbal neuroprotective compounds against CAG repeats, which are therapeutically significant in treating SCA. Initially, virtual screening followed by molecular docking was used to estimate the binding affinity of neuroprotective natural compounds toward CAG repeats. The compound with the highest binding affinity, somniferine, was then chosen for MD simulation. The structural stability, interaction mechanism, and conformational dynamics of CAG repeats and somniferine were investigated via MD simulation. The MD study revealed that during the simulation period, the interaction between CAG repeats and somniferine stabilizes and results in fewer conformational variations. This in silico study suggests that Somniferine can be used as a therapeutic medication against RNA CAG repeats in SCA.

Post-COVID-19 headache- NDPH phenotype: a systematic review of case reports.

Background and objectives: Post-acute COVID-19 syndrome or "long COVID" affects patients even after the recovery from Covid infection in various ways. Persistent headache or New Daily Persistent Headache (NDPH) is one of such symptoms. In this review, we will discuss about the case-reports of post covid-19 headache- NDPH phenotype both after and in the course of COVID-19 infection. Methods: Case reports/studies talked about patients having NDPH around the disease either immediately or late post COVID were included. Data was taken from the source and synthesised on a qualitative basis. Results: Literature search showed 3,538 articles, out of which 12 were screened as per the eligibility criteria and finally, 4 case reports on NDPH and Covid-19 were chosen for analysis from the database and by human search. All case reports justify the criteria for acceptability in quality for this systematic review. Conclusion: NDPH in and around Covid 19 infection is something that is currently an ingenious debated topic in the scientific community. More case studies should be written and published on the same subject so that a large systematic review could be conducted. Trial Registration Information: The review is registered in Prospero with no. Identifier (CRD42022354912). Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO (CRD42022354912).

Persistent facial pain in post-stroke patients, a hospital-based cohort study; experience from North India.

Background: Post-stroke pain is common after a stroke and might be underreported. We describe Persistent Facial Pain (PFP) developed in post-stroke patients. Method: ology: This was a prospective hospital-based cohort study of stroke patients, and patients were followed up. Out of 415 stroke patients, 26 developed PFP. Result: Out of all PFP patients, six patients had an ischemic stroke, and 20 had a hemorrhagic stroke. 57.7% of patients had hypertension, while 34.6 patients had diabetes. The stroke location was left-sided in 12 patients and right-sided in 14 patients. 46.15% of patients responded to venlafaxine, 30.77% responded to amitriptyline, and 23.08% responded to pregabalin. Conclusion: Persistent facial pain is a pain syndrome that might be missed in patients post-stroke. It might be more common in hemorrhagic stroke patients than in ischemic stroke patients. It responds adequately to antidepressants. A high index of suspicion is required to diagnose and appropriately manage these patients.

Clinico-radiological factors associated with aphasia outcome in post stroke patients: A prospective follow up study from eastern part of India.

BACKGROUND: Aphasia is a language disorder acquired secondary to brain damage. This study aims to evaluate clinical and radiological profile of patients with post stroke aphasia and factors affecting its recovery. METHODS: We conducted a prospective study of patients with first left Middle or Anterior Cerebral Artery infarct or Intracerebral Hemorrhage (ICH) with aphasia admitted within 14 days of stroke onset. Aphasia Quotient (AQ) was assessed at 2 weeks (AQ1) and 3 months (AQ2) using Western Aphasia Battery-Hindi version. Magnetic Resonance Imaging of brain with Diffusion Tensor Imaging (DTI) of bilateral Arcuate Fasciculus (AF) and Corticospinal Tract was done at admission, and stroke volume, Laterality Indices of Fractional Anisotropy (LI-FA), Mean Diffusivity (LI-MD), Radial Diffusivity (LI-RD), Axial Diffusivity (LI-AD) and Apparent Diffusion Coefficient (LI-ADC) were obtained. RESULTS: 36 patients [8 ICH and 28 Acute Ischemic Stroke (AIS)] were included. AQ1 and AQ2 were significantly higher in subcortical stroke than cortical. AQ2 and increase in AQ scores (including its subscores) were significantly higher in ICH than AIS. National Institutes of Health Stroke Scale score at admission and volume of stroke had significant negative correlation with AQ1 and AQ2. Laterality Index of Fractional Anisotropy of Arcuate Fasciculus [LI-FA (AF)] had significant positive correlation with AQ2 and naming score at 3 months. Laterality Index of Mean Diffusivity of Arcuate Fasciculus [LI-MD (AF)] had significant negative correlation with AQ1, AQ2 and all subcomponents of AQ2. Significant positive correlation was seen between improvements in Modified Rankin Scale score and AQ. CONCLUSION: The study shows that DTI can be used to predict severity of aphasia at follow up and recovery in language and motor functions occur in parallel.

Genetic and in silico analysis of Indian sporadic young onset patient with amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is an old onset devastating neurodegenerative disorder. Young-onset ALS cases especially sporadic ones who are between 25 and 45 years are rarely affected by the disease. Despite the identification of numerous candidate genes associated with ALS, the etiology of the disease remains elusive due to extreme genetic and phenotypic variability. The advent of affordable whole exome sequencing (WES) has opened new avenues for unraveling the disease's pathophysiology better. Methods and results: We aimed to determine the genetic basis of an Indian-origin, young onset sporadic ALS patient with very rapid deterioration of the disease course without any cognitive decline who was screened for mutations in major ALS candidate genes by WES. Variants detected were reconfirmed by Sanger sequencing. The clinicopathological features were investigated and two heterozygous missense variants were identified: R452W, not previously associated with ALS, present in one of the four conserved C terminal domains in ANXA11 and R208W in SIGMAR1, respectively. Both of these variants were predicted to be damaging by pathogenicity prediction tools and various in silico methods. Conclusion: Our study revealed two potentially pathogenic variants in two ALS candidate genes. The genetic makeup of ALS patients from India has been the subject of a few prior studies, but none of them examined ANXA11 and SIGMAR1 genes so far. These results establish the framework for additional research into the pathogenic processes behind these variations that result in sporadic ALS disease and further our understanding of the genetic makeup of Indian ALS patients.

Incretin Therapy and Insulin Signaling: Therapeutic Targets for Diabetes And Associated Dementia.

Dementia is the primary cause of disability and dependence among the elderly population worldwide. The population living with dementia is anticipated to double in the next 17 years. Recent studies show the fact that compared to people without diabetes, people with Type 2 Diabetes (T2D) have about a 60% increased chance of developing dementia. In addition to cholinergic function being downregulated, improper insulin signalling also has a negative impact on synaptic plasticity and neuronal survival. Type 2 diabetes and dementia share various similar pathophysiological components. The ageing of the population and the ensuing rise in dementia prevalence are both results of ongoing medical advancements. It is possible that restoring insulin signaling could be a helpful therapy against dementia, as it is linked to both diminished cognitive function and the development of dementia, including AD. This review article comprehensively focused on scientific literature to analyze the relationship of Dementia with diabetes, recent experimental studies, and insight into incretin-based drug therapy for diabetes-related dementia.

The Genetic Drivers of Juvenile, Young, and Early-Onset Parkinson's Disease in India.

BACKGROUND: Recent studies have advanced our understanding of the genetic drivers of Parkinson's disease (PD). Rare variants in more than 20 genes are considered causal for PD, and the latest PD genome-wide association study (GWAS) identified 90 independent risk loci. However, there remains a gap in our understanding of PD genetics outside of the European populations in which the vast majority of these studies were focused. OBJECTIVE: The aim was to identify genetic risk factors for PD in a South Asian population. METHODS: A total of 674 PD subjects predominantly with age of onset (AoO) ≤50 years (encompassing juvenile, young, or early-onset PD) were recruited from 10 specialty movement disorder centers across India over a 2-year period; 1376 control subjects were selected from the reference population GenomeAsia, Phase 2. We performed various case-only and case-control genetic analyses for PD diagnosis and AoO. RESULTS: A genome-wide significant signal for PD diagnosis was identified in the SNCA region, strongly colocalizing with SNCA region signal from European PD GWAS. PD cases with pathogenic mutations in PD genes exhibited, on average, lower PD polygenic risk scores than PD cases lacking any PD gene mutations. Gene burden studies of rare, predicted deleterious variants identified BSN, encoding the presynaptic protein Bassoon that has been previously associated with neurodegenerative disease. CONCLUSIONS: This study constitutes the largest genetic investigation of PD in a South Asian population to date. Future work should seek to expand sample numbers in this population to enable improved statistical power to detect PD genes in this understudied group. © 2023 Denali Therapeutics and The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Comparison between Epley and Gans Repositioning Maneuvers for Posterior Canal BPPV: A Randomized Controlled Trial.

Objectives: Benign paroxysmal positional vertigo (BPPV) is a condition in which a patient gets severe vertigo on moving his head from one position to another. This study aims at comparing the traditional maneuver-Epley repositioning maneuver (ERM) and the newly emerged maneuver-Gans Repositioning maneuver (GRM). Design: A randomized controlled trial. Settings: Tertiary care teaching University Hospital. Participants: Posterior canal BPPV. Intervention: Two hundred and thirty-four patients with BPPV (PC-BPPV) of the posterior canal, diagnosed using the Dix-hallpike test (DH test), were recruited for the study as per random allocation. Two groups were divided by the random allocation method. One group was treated with the Epley maneuver and the other with Gans maneuver by two separate physiotherapists. Main Outcome Measures: DH test negativity (absence of vertigo and nystagmus), Vertigo Analogue Scale (VAS), and Dizziness Handicap Inventory (DHI). Twenty-four hours post-treatment assessments and data analysis were conducted by another (third) therapist. A one month follow-up subjective assessment was performed. Results: Results of one-variable Chi-square tests revealed significant improvement (P < .0001) in maximum (95%) patients of both groups whether subjects were given GRM or ERM. Also, objective improvement (DH test) was found in the Epley group (n = 118, 82.20%) and the Gans group (n = 116, 78.44%). Patients in both groups improved significantly with no dizziness on the VVAS scale (n = 118, 82.20%) in the Epley group and (n = 116, 78.44%) in the Gans group. Conclusion: GRM is as easy, effective, and safe maneuver as the ERM with the absence of recurrence for the treatment of posterior canal BPPV. Trial Registration: Clinical Trials Registry (CTRI/2019/10/021681).

Evaluating the Effect of Pregabalin in the Treatment of Carpal Tunnel Syndrome: A Prospective, Randomized, Triple-Blinded, Placebo-controlled Trial.

OBJECTIVE: This study aimed to determine the effectiveness of pregabalin for the control of symptoms in mild to moderate idiopathic Carpal tunnel syndrome (CTS). METHODS: In this randomized, placebo-controlled trial, 146 mild to moderate idiopathic CTS patients were randomized into pregabalin (n=74) and placebo groups (n=72). Per protocol, analysis was conducted with 131 patients; pregabalin (n=65) and placebo (n=66). The drug titration dose was 50 mg once daily for the first week, twice daily for the second week and thrice daily for the next 6 weeks. The primary outcome included a change in the Symptom Severity Scale and Functional Status Scale (FSS) of the Boston Carpal Tunnel Questionnaire after the eighth week. The secondary outcome was the change in clinical and electrophysiological grading after 8 weeks of therapy. RESULTS: There was a statistically significant improvement in the mean Symptom Severity Scale (14.92±3.72 vs. 16.55±4.45; P =0.025) and FSS (10.77±2.64 vs. 12.0±2.55; P =0.007) in the pregabalin group after 8 weeks. Mean clinical and electrophysiological grading changed significantly from 2.3±0.7 to 2.1±0.8 ( P =0.001) and 1.9±0.7 to 1.8±0.8 ( P =0.020), respectively in the pregabalin group but not in the placebo group. DISCUSSION: The results of this study demonstrates that pregabalin is effective in ameliorating symptoms and improving functional outcomes in mild to moderate idiopathic CTS.

A Cross-Sectional Study of the Haematological Profile of Patients With Chronic Liver Disease (CLD).

The liver keeps haematological parameters normal and preserves haemostasis by storing iron, vitamin B-12, and, folic acid, necessary for healthy haematopoiesis. Anaemia of various aetiologies affects approximately 75% of chronic liver disease (CLD) patients, specifically caused by iron deficiency, hypersplenism, chronic diseases, autoimmune haemolysis, folic acid deficiency, aplasticity, and as a side effect of antiviral drugs. This study sought to observe the derangements in haematological parameters in patients with CLD, analyse the spectrum of anaemia in patients with CLD, and predict CLD outcomes utilizing Child-Pugh Score. This cross-sectional observational research was carried out in the Department of General Medicine, Himalayan Institute of Medical Sciences (HIMS), Dehradun, India over the course of a year. The patients with CLD who were admitted to the ward participated in the study. Most patient's blood pictures reported normocytic normochromic with thrombocytopenia (TCP) (28.7%), macrocytic hypochromic with TCP (26%), microcytic hypochromic with TCP (13.3%) and macrocytic normochromic with TCP (9.3%). The incidence of anaemia was 85.3%: mild in 12.7% patients, moderate in 55.3% patients, and severe in 17.3% patients. Interestingly, this study also builds upon others suggesting that 85.9% of CLD patients have Class C Child-Pugh Score.

Thrombotic and Thromboembolic Complications After Vaccination Against COVID-19: A Systematic Review.

Thromboembolic complications after the COVID-19 vaccination have been reported from all over the world. We aimed to identify the thrombotic and thromboembolic complications that can arise after receiving various types of COVID-19 vaccines, their frequency, and distinguishing characteristics. Articles published in Medline/PubMed, Scopus, EMBASE, Google Scholar, EBSCO, Web of Science, the Cochrane Library, the CDC database, the WHO database, ClinicalTrials.gov, and servers like medRxiv.org and bioRxiv.org, as well as the websites of several reporting authorities between December 1, 2019, and July 29, 2021, were searched. Studies were included if they reported any thromboembolic complications post-COVID-19 vaccination and excluded editorials, systematic reviews, meta-analyses, narrative reviews, and commentaries. Two reviewers independently extracted the data and conducted the quality assessment. Thromboembolic events and associated hemorrhagic complications after various types of COVID-19 vaccines, their frequency, and distinguishing characteristics were assessed. The protocol was registered at PROSPERO (ID-CRD42021257862). There were 59 articles, enrolling 202 patients. We also studied data from two nationwide registries and surveillance. The mean age of presentation was 47 ± 15.5 (mean ± SD) years, and 71.1% of the reported cases were females. The majority of events were with the AstraZeneca vaccine and with the first dose. Of these, 74.8% were venous thromboembolic events, 12.7% were arterial thromboembolic events, and the rest were hemorrhagic complications. The most common reported event was cerebral venous sinus thrombosis (65.8%), followed by pulmonary embolism, splanchnic vein thrombosis, deep vein thrombosis, and ischemic and hemorrhagic stroke. The majority had thrombocytopenia, high D-dimer, and anti-PF4 antibodies. The case fatality rate was 26.5%. In our study, 26/59 of the papers were of fair quality. The data from two nationwide registries and surveillance revealed 6347 venous and arterial thromboembolic events post-COVID-19 vaccinations. COVID-19 vaccinations have been linked to thrombotic and thromboembolic complications. However, the benefits far outweigh the risks. Clinicians should be aware of these complications because they may be fatal and because prompt identification and treatment can prevent fatalities.

Spectrum of neurological diseases across gangetic belt: a hospital based prospective observational study.

OBJECTIVE: Neurological disorders are the most common cause of morbidity and mortality in riverside cities. Earlier studies reported the presence of heavy metals in the riverside of Gangetic belt. Our study objective was to determine the prevalence of neurological diseases in Ganga riverside and further divided into sections as just across riverside within 25 kms and non-riverside as 25 kms away from the Ganga river. METHODS: This was a prospective observational study conducted in a tertiary care hospital of selected Gangetic belt. RESULTS: A total of 2016 patients were recorded in this period. Mean age of the participants was 47.89 years, majority were males 59.2%. Most of the patients n = 1154 were from within 25 kms of Ganga riverside and n = 862 patients were from non-riverside (25 kms away from Ganga river). Common neurological diseases were ischemic stroke 22.7%, haemorrhagic stroke 20.7%, seizures 13.7%, septic encephalopathy 9.4%, neuropathy 8.9%, Parkinson's disease 4.3%, myopathy 4.1%, myelitis 2.8%, headache 2.4%, amyotrophic lateral sclerosis 1.9% and functional disorder 1.9%. CONCLUSION: Present study showed that neurological diseases were more common in Ganga riverside and stroke including ischemic and hemorrhagic are most common neurological diseases noted in our study.

The pattern of primary headache in the North India population: a hospital-based study.

BACKGROUND: The aim of the study was to investigate the clinical profile, disease burden, quality of life, and treatment patterns of various headache subtypes. METHOD: In this prospective observational study, 815 patients presenting with chief complaints of headache between January 2020 to September 2021 were registered. After a detailed history, clinical examination, and subtyping, they were assessed at baseline with well-validated scales for severity (Visual Analogue Scale-VAS), disability burden (Migraine Disability Assessment- MIDAS), Humanistic burden (Headache Impact Test-HIT-6), and quality of life (World health organization-quality of life-WHO-QoL-8) scores. After initiating adequate management, parameters were reassessed at 3 and 6 months. RESULTS: 549 (67.7%) patients had migraine (395-episodic migraine, 144-chronic migraine), 266 (32.2%) patients had tension-type headache (TTH). Loss of sleep, prolonged working hours, and stress were common triggers. Disease burden, severity, and poor life quality was quite high in migraine patients (76.5% with moderate to severe disability, 61.7% with severe headache at onset, and 72% with poor life quality). All parameters had statistically significant improvement with preventive medication and lifestyle changes. CONCLUSION: In our study, we found migraine was the most common primary headache followed by TTH. Migraine patients had more severity, disease burdens, and inferior quality of life at onset compared to other headaches. With early and proper diagnosis as well as preventive treatment (including lifestyle modifications), all parameters could be reversed positively in a brief time. This is the first study on headache burden and its effect on the quality of life in the north Indian population.