A video-atlas of levodopa-induced dyskinesia in Parkinson's disease: terminology matters.

Dyskinesia is a common complication of long-term levodopa therapy in patients with Parkinson's disease (PD), which often worsens the quality of life. It is usually dose-dependent and emerges possibly due to pulsatile stimulation of dopamine receptors. Delineating the pattern of dyskinesia is crucial for determining the most effective therapeutic approach, a task that often presents challenges for numerous neurologists. This article comprehensively describes various patterns of dyskinesia in PD patients and features video demonstration of some of the common forms of dyskinesia. We have used a real case scenario as an example to lead the discussion on the phenomenology, distinguishing features, and management of various types of dyskinesia. A comprehensive literature search was conducted in PubMed using "dyskinesia" as a keyword. The prototype case with videos highlights the differentiating features of dyskinesia along with the treatment strategies. A wide range of descriptive rubrics have been used for certain dyskinesia which are described in detail in this article. The newer types of dyskinesia associated with continuous dopaminergic stimulation in patients with advanced PD and their implications have been described. As there are distinct ways of managing various types of dyskinesia, understanding the phenomenology and chronology of dyskinesia is vital for the optimal management of dyskinetic PD patients. We suggest that dyskinesia should be classified broadly into peak-dose dyskinesia (PDD), biphasic dyskinesia (BD), and OFF-period dystonia. The occurrence of low-dose dyskinesia and complex dyskinesia of continuous dopaminergic treatments should be known to specialists and will require additional studies.

Effect of pranayama on perceived stress, well-being and quality of life of frontline healthcare professionals on COVID-19 duty: A quasi-randomised clinical trial.

Healthcare professionals (HCPs) had to perform their duties under extremely trying circumstances during the COVID-19 pandemic. High expectations further increased HCP's stress, which had an adverse impact on their mental health. The present quasi-randomised clinical trial examined how a specially designed pranayama regimen practised for 4 weeks affected the mental health of frontline, exposed HCPs in terms of perceived stress, wellness and quality of life. A total of 280 frontline HCPs on COVID-19 duties in five public hospitals of Delhi, India participated in this study. The intervention (n = 123) and control (n = 127) groups were alternately allocated. Data on perceived, self-reported mental health of HCPs were collected at baseline and post-test at the end-line (after 28 days of practice). We report that the intervention group (n = 123) had a substantial lower perceived stress at post-test at the end-line in comparison to the control group (n = 127, p-value: .028). Their overall WHO Quality-of-Life score also improved, of which the score on psychological domain increased significantly (p-value: .019). Accordingly, we conclude that a 28-day practice of the pranayama by the frontline HCPs in COVID-19 hospitals significantly decreased their level of perceived stress and enhanced their psychological quality of life.

Different Biofluids, Small Extracellular Vesicles or Exosomes: Structural Analysis in Atherosclerotic Cardiovascular Disease Using Electron Microscopy Techniques.

Small extracellular vesicles (sEVs) or exosomes are secretory vesicles largely involved in cell-cell communications and found to play a role in development as well as diseases including atherosclerosis. They hold a huge potential for translational research by devising better clinical diagnostics, biomarker discovery, drug delivery, and therapeutic strategies. Variations terms of morphology and distribution are crucial to biological function integrity. Moreover, it is dependent on susceptibility to influential factors of the environment like cell stress, inflammation, and secretion by different cells in subsequent biofluids. We have observed the morphological variations in sEVs or exosomes freshly isolated from patients with atherosclerotic cardiovascular disease (AsCVD), in blood plasma, saliva, and urine biofluids compared to healthy controls. High-resolution images were obtained by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) for the characterization of sEVs morphology. Western blotting and immuno-TEM gold labeling confirmed the presence of exosome markers. For the first time, we report size and shape variations, which suggest the existence of different functions of sEVs in the disease state. Morphological variations in sEVs were observed significantly in noninvasive AsCVD saliva and urine samples, important to understand the cell behavior and physiological state. These variations will be useful to investigate their possible role in the disease process.

Beyond Fever, Cough and Dyspnea: The Neurology of COVID-19.

The pandemic due to Severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) has rapidly engulfed the entire world, and continues to evolve at an aggressive pace. Although the characteristic concern in patients with COVID-19 is acute respiratory distress, there is meteoric accrual of data on neurological involvement. Neurological manifestations in COVID-19 have staggering diversity, ranging from mild olfactory and gustatory perception abnormalities to necrotising encephalopathy and stroke. Understanding of pathophysiological mechanisms underlying neurological invasion and disease is still nascent, and dictated largely by evidence from previous coronavirus infections which are known to have neuroinvasive potential. It has also been postulated that SARS CoV2 may affect the medullary respiratory centres in the brain stem thereby playing a possible role in causing neurogenic acute respiratory failure. Preliminary data suggest a role of immune hyperinflammation and hyperthrombosis mediating neurological features. Apart from acute neurological manifestations, immune dysregulation may contribute to para and post-infectious complications and potentially, neurodegenerative conditions. These concepts are paramount in developing therapeutic paradigms to mitigate the impact of the pandemic. In this review, we summarise putative pathophysiological underpinnings of neurological manifestations of COVID-19 and guidance for their management.

Comprehensive amino acid composition analysis of seed storage proteins of cereals and legumes: identification and understanding of intrinsically disordered and allergenic peptides.

The seed storage proteins of cereal and legumes are the primary source of amino acids which are required for sustaining the nitrogen and carbon demands during germination and growth. Humans derive most of their dietary proteins from storage proteins in form of a wide variety of foods, for consumption. The amino acid content of most of these proteins is biased and the need for this biasness is not understood. The high abundance of proline, glutamine, and cysteine in cereals makes the gluten fraction viscoelastic. The cereal proteins have less charge and legume proteins have more charge on them. Their non-polar amino acid distribution has large variations. These characteristics are strongly responsible for the partial and complete unfolding of several domains of the storage proteins. Many of the storage proteins share a highly conserved structural feature within the cupin superfamily spread across all kingdoms of life. The intrinsically disordered viscoelastic proteins help in making dough which is vital for the quality of bread. Unfolded regions harbor more immunogenic sequences and cause food-related allergies and intolerance. We have discussed these properties in terms of comparison of cereal and legume storage protein sequences and allergy. Our study supports the findings that large disordered regions contain allergen-representative peptides. Interestingly, a high number of allergen-representative peptides were cleavable by digestive enzymes. Furthermore, unfolded storage proteins mimic microbial immunogens to induce a memory immune response. Results findings can be used to guide the understanding of immunological characteristics of storage proteins and may assist in treatment decisions for food allergy.Communicated by Ramaswamy H. Sarma.

Telerehabilitation - historical perspectives and conceptual framework in reference to neurological disorders: A narrative review.

BACKGROUND: Telerehabilitation as a new subdiscipline of telehealth is the application of information technology to support and deliver rehabilitation services via two-way or multipoint interactive online telecommunication technology. This enables the therapist to optimize the timing, intensity, and duration of therapy which is often not possible within the constraints of face-to-face treatment protocols in current health systems. OBJECTIVE: To review the historical perspective and conceptual framework of telerehabilitation in neurological disorders. METHODS: A narrative review of the literature was performed for the historical perspective and a systematic review of the conceptual framework was performed using the PRISMA guidelines on chronic neurological disorders; multiple sclerosis, spinal cord injury, stroke, Parkinson's disease, cognitive impairment, and headaches. The search included articles from the past 20 years (2004 to 2024). RESULTS: Telerehabilitation dates back to the 1960s and early 1970s. Documented effective interventions were mostly on therapies for speech disorders. The conceptual framework consisted of three major components of telerehabilitation programmes including development, implementation, and evaluation. The COVID-19 pandemic suddenly made telerehabilitation come to the limelight because physical distancing became necessary. Out of the 110,000 articles downloaded, 43 met the inclusion criteria for review on the conceptual framework of telerehabilitation in relation to neurological disorders. The articles discussed multiple sclerosis (2), spinal cord disorders (1), stroke (17), Parkinson's disease (15), headaches (3), and cognitive disorders (5). All articles reviewed assessed the effectiveness of telemedicine except for the articles on multiple sclerosis and spinal cord disorders which examined the interphase between the technology and the end users. CONCLUSION: The future of telerehabilitation looks promising with the subsequent integration of innovative tools and applications. This will require the adaption of technology, continuous capacity building, education, and training of healthcare professionals to ensure that they are adequately equipped with the necessary skills to provide quality virtual reality rehabilitation care.

Tubercular Mediastinal Lymphadenopathy Presenting as an Isolated Unilateral Vocal Cord Palsy and the "Sail" Sign.

Tuberculosis continues to remain a major public health challenge, especially in low- and middle-income countries. Unilateral vocal cord palsy in adults as the sole manifestation of tubercular mediastinal lymphadenopathy has been rarely reported. A 22-year-old lady presented with a history of hoarseness of voice for the past month. The general physical examination revealed palpable lymph nodes in the left axilla. Axial CT sections at the level of the vocal cords demonstrated dilation of the right laryngeal ventricle and mild anteromedial deviation of the ipsilateral arytenoid cartilage ("sail" sign) suggestive of a right vocal cord palsy. Contrast-enhanced CT chest revealed right paratracheal, right hilar, and subcarinal lymph nodes with areas of central necrosis. She was started on anti-tubercular therapy and her voice completely improved after three months of treatment. The "Sail" sign on axial CT scans is a useful radiological sign for diagnosing unilateral vocal cord palsy. Rarely, compression of the recurrent laryngeal nerve by enlarged mediastinal lymph nodes due to tuberculosis can present with unilateral vocal cord palsy as the sole manifestation in adults.

Understanding Psychosocial Functioning, Caregiver Burden, and Neuropalliative Care in Parkinson's Disease - A Mixed-Methods Study.

BACKGROUND: Despite advancements in treatment, patients with Parkinson's disease (PD) experience a range of symptoms that affect their quality of life. There is a need to integrate neuropalliative care into standard care. The aim of the study is to understand the psychosocial functioning in persons with PD and explore their caregivers' burden. METHODS: The study utilizes a mixed-methods design where 50 patient-caregiver dyads attending the outpatient services of the movement disorder clinic at a tertiary care hospital were measured on psychosocial functioning and caregiver burden and palliative care outcomes for a period of 6 months. Focus group discussions were conducted with 18 patient-caregiver dyads to understand the needs of palliative care. RESULTS: It was found that caregiver burden was positively correlated with palliative care outcomes scores of patients ( r = 0.586) and caregivers ( r = 0.675) and psychosocial functioning was positively correlated with palliative care outcomes of patients ( r = 0.708). The psychosocial functioning score was higher among female patients (indicating worse functioning) than males, and female caregivers experienced significantly higher caregiver burden. The qualitative findings reveal that there is a substantial gap in awareness about palliative care, lack of information, presence of stigmatizing beliefs, and lack of adequate accessibility to palliative facilities. CONCLUSION: The study lays the foundation for future PD neuropalliative care research, guiding interventions, and exploration of regional variations in PD experiences in India. There is a need to address caregiver burden in PD in India.

An Extremely Rare LAMA2 Gene Variant c.442C>T (p.Arg148Trp) Causing Late-Onset LAMA2-Related Dystrophy.

Mutations in the alpha-2 subunits of the laminin gene (LAMA2) cause an autosomal recessive congenital muscular dystrophy (CMD) subtype known as laminin a2-related muscular dystrophies (LAMA2-RD). LAMA2-RD can present with a wide range of phenotypes ranging from severe infantile congenital muscular dystrophy to milder adult-onset limb-girdle muscular dystrophy. This case describes a 28-year-old Indian gentleman having childhood-onset focal seizures, gradually progressive proximal predominant lower-limb weakness for the past three years, elevated creatinine phosphokinase levels, and MRI brain suggestive of diffuse symmetrical periventricular white matter hyperintensities. The whole exome sequencing revealed a rare homozygous missense variant in exon 4 of the LAMA2 gene on chromosome 6 (c.442C>T[p.Arg148Trp]). Adult-onset limb-girdle muscular dystrophy with white matter imaging abnormalities, hyperCKemia, and seizures should evoke suspicion of LAMA2-RD. This case brings forth an ultra-rare genetic mutation that has not been previously reported in individuals of South Asian ethnicity leading to LAMA2-RD. More cases of late-onset LAMA2-RD from various ethnicities need to be reported to expand our understanding of the clinical-genetic spectrum of the disease.

Role of PON1 L55M Gene Polymorphism in Parkinson's Disease among North Indian Population.

BACKGROUND AND OBJECTIVES: The role of various genetic markers including alpha synuclein, Parkin, etc., is known in the pathogenesis of Parkinson's disease (PD). Novel genetic markers including paraoxonase 1 (PON1) have also been linked to PD pathogenesis in recent studies. The PON1 L55M allele carriers may have defective clearance of environmental toxins and may result in increased susceptibility to PD. Hence, we studied the role of PON1 L55M polymorphism in PD among a North Indian population. MATERIALS AND METHOD: Seventy-four PD patients and 74 age- and sex-matched controls were recruited in this hospital-based case-control study. Baseline characteristics were recorded using structured questionnaire. DNA was extracted from 3-4 ml of venous blood, followed by PCR and restriction digestion. PON1 L55M genotypes were visualized as bands: LL (177 bp), LM (177, 140 bp) and MM (140,44 bp) on 3% agarose gel. Mann-Whitney U test and Chi-squared test were used for comparing two groups of skewed and categorical variables, respectively. Measures of strength of association were calculated by binary regression analysis. P value < 0.05 was considered as significant. RESULTS: Parkinson's disease patients had significantly higher exposure to pesticides (12.2%; P (organophosphate exposure) < 0.001) and well water drinking (28.4%; P = 0.006) compared to controls. Frequency distribution of LL, LM, MM genotypes was 67.5% (50/74), 28.4% (21/74), and 4.1% (3/74), respectively, for cases and 72.6% (54/74), 26% (19/74) and 1.4% (1/74), respectively, for controls. PON1 L55M genotype distribution between Parkinson's disease cases and controls was not significant (P = 0.53). PON1 L55M polymorphism was not associated with PD after adjusting for confounders by binary regression analysis. CONCLUSION: There was no significant association between PON1 L55M polymorphism and PD. Larger population-based studies would be required from India before drawing any definite conclusions.

Field based research in the era of the pandemic in resource limited settings: challenges and lessons for the future.

The coronavirus pandemic that began in December 2019, has had an unprecedented impact on the global economy, health systems and infrastructure, in addition to being responsible for significant mortality and morbidity worldwide. The "new normal" has brought along, unforeseen challenges for the scientific community, owing to obstructions in conducting field-based research in lieu of minimizing exposure through in-person contact. This has had greater ramifications for the LMICs, adding to the already existing concerns. As a response to COVID-19 related movement restrictions, public health researchers across countries had to switch to remote data collections methods. However, impediments like lack of awareness and skepticism among participants, dependence on paper-based prescriptions, dearth of digitized patient records, gaps in connectivity, reliance on smart phones, concerns with participant privacy at home and greater loss to follow-up act as hurdles to carrying out a research study virtually, especially in resource-limited settings. Promoting health literacy through science communication, ensuring digitization of health records in hospitals, and employing measures to encourage research participation among the general public are some steps to tackle barriers to remote research in the long term. COVID-19 may not be a health emergency anymore, but we are not immune to future pandemics. A more holistic approach to research by turning obstacles into opportunities will not just ensure a more comprehensive public health response in the coming time, but also bolster the existing infrastructure for a stronger healthcare system for countries.

A comprehensive proteomic profiling of urinary exosomes and the identification of early non-invasive biomarker in patients with coronary artery disease.

Urinary small extracellular vesicles or exosomes (uEVs) source could be an emerging trove of biomarkers in coronary artery disease (CAD). It is a chronic inflammatory disease having a long asymptomatic phase of fatty-fibrous development in arteries leading to angina, myocardial infarction, and death. Our study was aimed at identifying differential protein expression profiling of uEVs in CAD. We collected urine samples of CAD patients (n = 41) age 18-65 years and gender matched healthy controls (n = 41). We isolated uEVs using differential ultracentrifugation. Further, uEV samples were characterized by western blotting exosome markers (Flotillin, TSG, CD63, and CD9), nano tracking analysis, and transmission and scanning electron microscopy. A total of 508 proteins were identified by iTRAQ-based mass spectrometry. We observed protein expression levels of AZGP1, SEMG1/2, ORM1, IGL, SERPINA5, HSPG2, prosaposin, gelsolin, and CD59 were upregulated, and UMOD, KNG1, AMBP, prothrombin, and TF were downregulated. Protein-protein interactions, gene ontology and pathway analysis were performed to functionally annotate identified uEVs proteins. A novel uEVs differential protein signature is shown. On validating UMOD protein by ELISA in two clinically different CAD, stable-CAD patients had lower levels than healthy controls whereas recent myocardial infarction patients had lowest. Our findings suggest UMOD importance as early diagnostic biomarker. SIGNIFICANCE: Coronary artery disease is a chronic inflammatory disease caused by gradual deposition of cholesterol and fat along with other proteins to develop plaque inside arteries. This further leads to blockage of artery, heart attack and death. There are no identifiable early biomarkers to diagnose this. For the first time, we have identified the differentially expressed proteins isolated from non-invasive uEV of CAD patients compared to healthy controls by using MS Orbitrap and iTRAQ labelling of peptides. We have identified decreased levels of UMOD protein in CAD. These findings have been confirmed by ELISA. Furthermore, the levels of UMOD were observed as more highly decreased in recent myocardial infarction CAD patients, indicating the importance of this protein as an early diagnostic biomarker. Conclusively, our study represents a non-invasive urinary EVs trove of differentially expressed proteins in CAD. This will form a groundwork for understanding the pathophysiology of CAD and will help in future translational research utilizing uEVs.

National plans and awareness campaigns as priorities for achieving global brain health.

Neurological conditions are the leading cause of death and disability combined. This public health crisis has become a global priority with the introduction of WHO's Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders 2022-2031 (IGAP). 18 months after this plan was adopted, global neurology stakeholders, including representatives of the OneNeurology Partnership (a consortium uniting global neurology organisations), take stock and advocate for urgent acceleration of IGAP implementation. Drawing on lessons from relevant global health contexts, this Health Policy identifies two priority IGAP targets to expedite national delivery of the entire 10-year plan: namely, to update national policies and plans, and to create awareness campaigns and advocacy programmes for neurological conditions and brain health. To ensure rapid attainment of the identified priority targets, six strategic drivers are proposed: universal community awareness, integrated neurology approaches, intersectoral governance, regionally coordinated IGAP domestication, lived experience-informed policy making, and neurological mainstreaming (advocating to embed brain health into broader policy agendas). Contextualised with globally emerging IGAP-directed efforts and key considerations for intersectoral policy design, this novel framework provides actionable recommendations for policy makers and IGAP implementation partners. Timely, synergistic pursuit of the six drivers might aid WHO member states in cultivating public awareness and policy structures required for successful intersectoral roll-out of IGAP by 2031, paving the way towards brain health for all.

Multi-Modal Rehabilitation Therapy in Parkinson's Disease and Related Disorders.

Long-term use of dopaminergic therapy in Parkinson's disease (PD) is associated with reduction in efficacy and disabling dyskinesias. The current medical or surgical treatment modalities are ineffective for atypical parkinsonism syndromes. Hence, there is a need for holistic and cost-effective non-pharmacological interventions that act via multiple mechanisms to improve motor as well as non-motor symptoms among PD patients. Rehabilitation strategies focusing on multiple mechanisms can lead to improvement in certain symptoms among PD patients, which may be refractory to medical and surgical therapy. However, there is scanty literature available on the role of various rehabilitation strategies in patients with atypical parkinsonism patients. Multiple rehabilitation strategies such physiotherapy, aerobic exercises, strength/resistance exercises, treadmill training, cueing, dance and music, speech language therapy, occupational therapy, hydrotherapy, and martial arts have been found to improve motor as well as non-motor symptoms among PD patients. Newer modalities such as virtual-reality-based devices, exergaming, wearable sensors, and robotic prosthetic devices may be exciting future prospects in rehabilitation among patients with PD and atypical parkinsonian syndromes. This narrative review assessed and summarized the current evidence regarding the role of various rehabilitation strategies in PD and atypical parkinsonian syndromes. Furthermore, evidence regarding recent advancements in rehabilitation for patients with parkinsonism was highlighted. Despite the beneficial effect of rehabilitation in PD, there is still scanty literature available from India on rehabilitation strategies among PD patients. Larger prospective randomized control trials from India and other low- and middle-income countries, focusing on various rehabilitation strategies among PD patients, are an unmet need.

Efficacy of pranayama in preventing COVID-19 in exposed healthcare professionals: A quasi-randomized clinical trial.

BACKGROUND: The global outbreak of COVID-19 has created a challenging situation, especially for the frontline Health Care Professionals (HCPs), who are routinely exposed and thus are at a higher risk of infection. Pranayama, a component of Yoga, is known to improve immune function and reduce infection. However, no clinical trial on the efficacy of Pranayama in preventing COVID-19 has yet been conducted. AIM AND OBJECTIVE: This quasi-randomized clinical trial assessed the efficacy of Pranayama in preventing COVID-19 infection in HCPs routinely exposed to COVID-19. METHODOLOGY: The study was conducted at 5 different COVID-19 hospitals, India in year 2020. The inclusion criteria were being an HCP exposed to COVID-19 patients and being negative on antibody tests. 280 HCPs were recruited sequential and assigned to intervention and control groups. Of these, 250 HCPs completed the study. The intervention was twice daily practice, for 28 days, of specially designed Pranayama modules under the online supervision of Yoga instructors. The HCPs in the control group were advised to continue their normal daily routine, but no pranayama sessions. Participants who developed symptoms suggestive of COVID-19 were subjected to Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) or Point of Care Rapid Antigen Test (RAT) for confirmation of the diagnosis. All the participants were tested for antibodies to COVID-19 on 28th day of the intervention to detect any asymptomatic infection. RESULTS: The intervention (123) and control (127) groups had comparable demographics and baseline characteristics. At end of 28 days of intervention, nine participants in the control group and one in the intervention group developed COVID-19 (P-value: 0.01, Odds Ratio: 0.107, 95% CI: 0.86; Risk Ratio: 0.11, 95% CI: 0.89). CONCLUSION: The intervention of twice daily practice of the Pranayama module for 28 days in HCPs might have made a noteworthy contribution and may have helped in preventing COVID-19 infection.

Neuropalliative Care in India - Barriers, Challenges and Future Directions.

Neuropalliative care is an emerging sub-specialty of neurology and palliative care that aims to relieve suffering from symptoms, reduce distress and improve the quality of life of people with life-limiting neurological conditions and their family caregivers. As advances are being made in the prevention, diagnosis, and treatment of neurological illnesses, there is an increasing need to guide and support patients and their families through complex choices involving immense uncertainty and important life-changing outcomes. The unmet need for palliative care in neurological illnesses is high, especially in a low-resource setting like India. This article discusses the scope of neuropalliative care in India, the barriers and challenges that impede the specialty's development, and the factors that could facilitate the development and scale-up delivery of neuropalliative services. The article also attempts to highlight priority areas for advancing neuropalliative care in India which include context-specific assessment tools, sensitization of the healthcare system, identification of intervention outcomes, the need for developing culturally sensitive models based on home-based or community-based care, evidence-based practices, and development of manpower and training resources.