Functional consequences of familial ALS-associated SOD1 in neuronal and muscle cells.

Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder characterized by progressive skeletal muscle denervation and loss of motor neurons that results in muscle atrophy and eventual death due to respiratory failure. Previously, we identified a novel SOD1 variation in a familial ALS case. In this study, we examined the functional consequences of SOD1 overexpression in the mouse motor neuron cell line (NSC-34).

Clinical and Genetic Analysis of A Father-Son Duo with Monomelic Amyotrophy: Case Report.

Monomelic Amyotrophy (MMA) is a rare neurological disorder restricted to one upper limb, predominantly affecting young males with an unknown aetiopathogenesis. We report a familial case of father-son duo affected by MMA. Whole exome sequencing identified genetic variations in and involved in axon guidance, calcium homeostasis and regulation of calmodulin signaling respectively.

Neuromuscular Junction Dysfunction in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive degeneration of motor neurons leading to skeletal muscle denervation. Earlier studies have shown that motor neuron degeneration begins in motor cortex and descends to the neuromuscular junction (NMJ) in a dying forward fashion. However, accumulating evidences support that ALS is a distal axonopathy where early pathological changes occur at the NMJ, prior to onset of clinical symptoms and propagates towards the motor neuron cell body supporting "dying back" hypothesis.

Burden of Stroke in India During 1960 to 2018: A Systematic Review and Meta-Analysis of Community Based Surveys.

Background: Stroke is a heterogeneous disorder comprising of clinical subtypes and many risk factors, also alluded to as cerebrovascular disorders (CVDs). Increase in the global burden of stroke in developed and developing countries has been alarming. To galvanize the efforts towards the prevention and treatment, there is a need for robust data on the burden of stroke.

Familial Prion Disease: First Indian Kindred with Gerstmann-Sträussler-Scheinker Syndrome.

Gerstmann-Sträussler-Scheinker (GSS) syndrome is a devastating hereditary prion disease, presenting in 4th-5th decade with progressive ataxia and dementia. Pathogenic variants in the PRNP gene lead to aggregation of misfolded prion protein which results in neurodegeneration and death within a few years of onset. A key feature of prion disorders is conversion of normal prion protein (PrPc) into its misfolded form (PrPSc).

Stem cell/cellular interventions in human spinal cord injury: Is it time to move from guidelines to regulations and legislations? Literature review and Spinal Cord Society position statement.

Purpose: In preclinical studies, many stem cell/cellular interventions demonstrated robust regeneration and/or repair in case of SCI and were considered a promising therapeutic candidate. However, data from clinical studies are not robust. Despite lack of substantial evidence for the efficacy of these interventions in spinal cord injury (SCI), many clinics around the world offer them as "therapy.

Neurodevelopmental disorders in children aged 2-9 years: Population-based burden estimates across five regions in India.

Background: Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden.

Methods And Findings: We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size).

Sleep disorders in amyotrophic lateral sclerosis: A questionnaire-based study from India.

Background: Amyotrophic lateral sclerosis (ALS) is a relatively rare neurological disorder affecting upper and lower motor neurons in the brain and spinal cord with survival for 3-5 years and rarely beyond 10 years. Sleep disturbances in ALS are underreported and undertreated and there is no related data from India. This study aimed to assess the frequency of sleep disorders in patients of ALS and their determinants.

Expression analysis of protein homeostasis pathways in the peripheral blood mononuclear cells of sporadic amyotrophic lateral sclerosis patients.

Misfolded protein aggregates are the hallmark of Amyotrophic Lateral Sclerosis (ALS) which suggests involvement of protein homeostasis pathways in etiology of ALS. However, status of protein homeostasis in peripheral blood of ALS is not well established. We analyzed expression levels of key genes of proteostasis pathways in peripheral blood mononuclear cells (PBMCs) of sporadic ALS (sALS) patients and healthy controls.

Six decades of Neurology at NIMHANS: A historical perspective.

The Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka has a long tradition of excellence in education, teaching, research, and patient care. Its exceptional alumni, as well as current and past faculty members, have made considerable contributions to the development of neurological services throughout the world. The six decades of its existence have seen a momentous growth in clinical, investigative, and community Neurology.

Analysis of C9orf72 repeat expansion in amyotrophic lateral sclerosis patients from North India.

Pathogenic expansion of a hexanucleotide repeat in C9orf72 is associated with ~30% of familial ALS and ~7% of sporadic ALS patients amongst different populations. This repeat expansion was screened in 75 ALS patients and 115 healthy individuals from North India. On analysis by repeat-primed PCR, pathogenic expansion was not observed either in ALS patients or healthy controls.

An insight into death wish among patients with amyotrophic lateral sclerosis in India using "Wish-to-Die Questionnaire".

Aims: In amyotrophic lateral sclerosis (ALS), death wish is expressed in a varying proportion of patients in different countries. In this first study from India, influence of belief system of religion/spirituality and attitude towards death, widely prevalent in the country, in decision making, was evaluated.

Material And Methods: Twenty ALS patients were assessed using 'Wish-to-Die Questionnaire' (WDQ) developed to reflect seven domains, namely religion/spirituality, belief in karma, meaning of life, hope, family support, financial support and death wish.

Amyotrophic lateral sclerosis and motor neuron syndromes in Asia.

While the past 2 decades have witnessed an increasing understanding of amyotrophic lateral sclerosis (ALS) arising from East Asia, particularly Japan, South Korea, Taiwan and China, knowledge of ALS throughout the whole of Asia remains limited. Asia represents >50% of the world population, making it host to the largest patient cohort of ALS. Furthermore, Asia represents a diverse population in terms of ethnic, social and cultural backgrounds.

Identification of L84F mutation with a novel nucleotide change c.255G > T in the superoxide dismutase gene in a North Indian family with amyotrophic lateral sclerosis.

Mutations in the superoxide dismutase (SOD1) gene account for ∼15% and in the transactive response DNA binding protein (TARDBP) gene for ∼5% of familial amyotrophic lateral sclerosis (FALS) cases. These two genes were analysed in two siblings from North India with ALS and a positive family history. The coding region of SOD1 and TARDBP genes was sequenced in both siblings.

Epidemiology of neurological disorders in India: review of background, prevalence and incidence of epilepsy, stroke, Parkinson's disease and tremors.

Growth and development of neuroepidemiology in India during the last four decades has been documented highlighting the historical milestones. The prevalence rates of the spectrum of neurological disorders from different regions of the country ranged from 967-4,070 with a mean of 2394 per 100,000 population, providing a rough estimate of over 30 million people with neurological disorders (excluding neuroinfections and traumatic injuries). Prevalence and incidence rates of common disorders including epilepsy, stroke, Parkinson's disease and tremors determined through population-based surveys show considerable variation across different regions of the country.