Insha Zahoor

No evidence for a role of Ile587Val polymorphism of EIF2B5 gene in multiple sclerosis in Kashmir Valley of India

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the nervous system with a profound genetic element. It is already known that alterations in Eukaryotic Translation Initiation Factor 2B (EIF2B) gene encoding the five subunits of eIF2B complex cause Vanishing White Matter (VWM) disease of the brain and emerging evidences have advocated certain resemblances between MS and VWM in terms of clinical and epidemiological characteristics, thus validating the association study between EIF2B and MS. Moreover, a recent study has implicated EIF2B5 Ile587Val (rs843358) polymorphism as a susceptibility factor for MS. In order to investigate the association of EIF2B5 Ile587Val polymorphism with MS susceptibility in Kashmir region in India, we screened EIF2B5 Exon 13 in 30 MS patients and 65 controls (a total of 95 participants). During the present course of study, we could not find statistically significant difference in the frequency of Ile587Val between MS patients and controls, thus indicating that such alteration does not appear to influence MS development in Kashmiri population. Our results provide evidence against a major role for Ile587Val polymorphism in MS susceptibility.

Human Immunodeficiency Virus and Multiple Sclerosis Risk: Probing for aConnection

Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disease of the nervous system, with intense genetic and environmental background. Its etiologyis poorly understood and likely multifactorialbutits epidemiology has been intensively studied. This complex disease displays heterogeneity in terms of geographic and genetic influences on incidence,insinuating an effect of local unknown environmental factors on its development.Among numerous potential factors putatively involved in the etiopathogenesis of MS, retroviruses appear to influence MS. The intent of this review is to highlight the association between human immunodeficiency virus (HIV) and the risk of developing MS while at the same time providing an overview of the insights gleaned from different studies. HIV infection is associated with a reduced risk of MS development, and perhaps, appears to be another wedge of the MS conundrum. The probable mechanisms for this relationship may be suppression of the immune system and/or antiretroviral drug therapy. While highlighting the relevance of antiretroviral medications as potential future alternatives for the effective treatment of MS, this review provides an impetus for further studies. We conclude that studies in this milieu hitherto are insufficient, and there is need for an upsurge in molecular epidemiological and clinical studies, with focus on the mechanism behind the impact of HIV/antiretroviral drugs on MS. Such inquiry could precisely establish the causes for associations between HIV and MS, perhaps impacting treatment options for both.

Multiple sclerosis in Kashmir: Where we stand

Multiple sclerosis (MS) is a disabling neurological disorder commonly diagnosed in young adults. Its causes still remain inexplicable and presently it can only be managed by different drug treatments. There has been a remarkable shift in MS perspective across world. One of its peculiar attribute is unstable (changing) prevalence rate across different parts of the world. Earlier MS was believed to be less prevalent in India, however, there has been growing evidence suggesting its increasing prevalence which has changed its perspective from being less prevalent to more prevalent. There is a complete lack of data on the prevalence rate and epidemiological basis of MS in Kashmir Valley of India. By and large MS research in this region seems to be hampered due to lack of proper research infrastructure, absence of MS registry, inadequate funding and more importantly by absence of active local and foreign collaborations between scientists and clinicians. This review tries to raise some key issues encountered while conducting MS research in Kashmir and at the same time highlighting the measures to be adopted for carrying out a large scale molecular epidemiological study.

Multiple Sclerosis and EIF2B5: A Paradox or a Missing Link

Multiple sclerosis (MS) is an encumbering inflammatory condition of the central nervous system (CNS) caused by axonal demyelination. There is sufficient evidence suggesting role of eukaryotic translation initiation factor 2B (EIF2B) gene family encoding the five subunits of eIF2B complex-α, β, γ, δ and ε respectively, in causing vanishing white matter (VWM) disease of the brain. Incidentally researchers have proposed overlapping between MS and VWM in terms of clinical, biochemical and genetic aspects, which incited us to write this chapter to explore the association between EIF2B5 and MS. eIF2B plays an essential role in translation initiation and its regulation in eukaryotes. Among EIF2B gene family, EIF2B5 gene encodes the catalytic and a crucial epsilon subunit of the eIF2B protein as most of the alterations have been found in this gene. The recent findings on the association between EIF2B5 and MS susceptibility point towards unfathomable and contentious role of EIF2B5 in MS development. This chapter briefly reviews the insights gleaned from recent studies conducted in understanding the association between EIF2B5 and MS risk. The need of hour is to conduct large scale conclusive studies aimed at expounding the mechanisms behind this relationship.

Demographic and clinical profile of Multiple Sclerosis in Kashmir: A short report

BACKGROUND Multiple sclerosis (MS) is a chronic autoimmune and inflammatory disease of the central nervous system (CNS). There have been only few population/hospital based studies on MS in India, and at the same time there is no data on its profile in Kashmir. METHODS A total of 41 MS patients diagnosed on the basis of 2010 Revised Mc Donald criteria were enrolled in this study from Kashmir region of India. Clinical, demographic, radiological and biochemical parameters were analyzed for most of the patients. RESULTS Male to female ratio was found to be 1:3.1 with mean age at the time of analysis 32.26±7.54 (range 18-48) years. The mean disease duration was found to be 3.2±3.6 years. The most common course was relapsing-remitting (RR) present in 87.80% of cases followed by secondary progressive (SP) in 9.76% and primary progressive (PP) in 2.44%. Numbness, weakness of limbs, prickling and tingling sensations, muscle stiffness, and visual disturbances were most common manifestations. Condition of bilateral internuclear ophthalmoplegia (INO) and vertigo was rarely observed. Oligoclonal bands (OCB) were present in cerebrospinal fluid (CSF) of majority of the patients. Symptomatic and steroidal treatment mode was given to majority of the patients (92.68%) and only 7.32% patients were given disease modifying drug. CONCLUSION This is the first preliminary report on MS profile in Kashmir. The high prevalence of female patients and RR course of MS, low prevalence of progressive cases, predominance of OCB positive cases, insignificant family history in all cases, predominance of cases with low socio-economic status, and high rate of less educated and unemployed cases are the most important findings. By and large MS pattern in Kashmir was found to be relatively similar to West and rest of the Asia. Larger comprehensive studies are mandatory to completely understand MS pattern in Kashmir. There is utmost requirement to maintain a local MS registry in Kashmir so as to get an idea about the actual number of persons suffering from the disease and compare the data with other regions of India.

Multiple sclerosis in India: Iceberg or volcano

Multiple sclerosis (MS)1 is a chronic neurodegenerative disease involving destruction of the myelin sheath around axons of the brain, spinal cord and optic nerve. There has been a tremendous transformation in its perspective across globe. In recent years, its prevalence has changed dramatically worldwide and India is no exception. Initially, MS was believed to be more common in the Caucasians of Northern Europe and United States; however, it has been found to be present in Indian subcontinent as well. There has been a considerable shift in MS prevalence in India and this has really changed the notion of considering India as a low risk zone for MS. In this review, a concise overview and latest update on changing scenario of MS in India is presented along with some major challenges regarding it persisting across globe even today. In India, remarkable upsurge is needed in carrying out large scale population-based epidemiological studies to get an idea about the true incidence and prevalence rates of MS viz a viz disease burden. Through this review, we have probably tried to identify the actual picture of MS prevalence in India and this could serve as harbinger for upcoming research and at the same time it would definitely aid in working out future strategies for MS management in the country.

Association Between Multiple Sclerosis Risk and Human Immunodeficiency Virus Infection: Insights and Challenges

Multiple sclerosis (MS) is a convoluted autoimmune and inflammatory disease of the central nervous system (CNS) in which the protective myelin sheath is eroded and the underlying nerve fibers are damaged. There is no conclusive knowledge on the role played by different etiological factors in its development, and studies have shown that it primarily results due to complex interactions between the genetic, geographic and infectious components. Among the risk factors reported to have a possible role in MS development, retroviruses also appear to influence it. Studies suggest human immunodeficiency virus (HIV) infection to be inversely related to MS risk, but to date, the association between the two remains enigmatic. This protec‐ tive inverse association has become an area of active research and the most plausible explanations for this may be immune suppression and/or antiretroviral medica‐ tions. The purpose of writing this chapter is to provide background information on the unfathomable relationship between HIV infection and the risk of developing MS while at the same time providing description of the insights garnered from recent studies. While highlighting the application of ART (antiretroviral therapy) as budding future alternative for MS management, this chapter provides momentum for further studies.