Ravouf Asimi

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.

Multiple cerebral infarctions with severe multi-organ dysfunction following multiple wasp stings.

Wasp and bee sting are commonly encountered worldwide. Local reactions are more common, generally are self-limiting and settle within a few hours. Multiple stings can lead to various clinical manifestations like vomiting, diarrhea, dyspnea, generalized edema, hypotension, syncope, acute renal failure, and even death. Rarely, they can cause vasculitis, serum sickness, neuritis, and encephalitis. We are reporting a case of 40-year-old male who presented with stroke, right hemiparesis with severe multi-organ dysfunction due to multiple wasp stings.

Decompressive hemicraniectomy in supra-tentorial malignant infarcts.

Background: Decompressive hemicraniectomy not only reduces the intracranial pressure but has been demonstrated to increase survival and decrease the morbidity in patients with supratentorial malignant brain infarcts (STMBI). The aim of this study was to assess the efficacy of surgical decompression to decrease the mortality and morbidity in patients with STMBI refractory to medical therapy and to compare the results with those of the medically managed patients. Methods: All the 24 consecutive patients with clinical and radiological diagnosis of STMBI, refractory to medical management in 2 years, were included. Option of surgical decompression after explaining the outcome, risk and benefits of the procedure was given to the attendants/relatives of all patients who were fulfilling the inclusion criteria. The patient group, whose attendants/relatives were not willing to undergo surgery, were subjected to the same medical therapy and they were taken as the “control group.” Results: Supratentorial malignant infarcts were more common in the age group of 41–60 years. Mean age of presentation was 42.16 ± 16.2 years and the mean GCS on admission was 7.83 ± 2.1. Mortality was 16.7% in the surgically and 25.0% in the medically managed group. Patients operated early (<48 h), age ≤60 years, midline shift <5 mm and size of infarct less than 2/3rd of the vascular territory involved showed good prognosis. The functional outcome revealed by modified Rankin Score (mRS) and Glasgow Outcome Score (GOS) was better in surgically managed patients. Results of the Zung Self-Rating Depression Score were better in surgically managed patients at 1 year. Barthal Index in the surgically managed group showed statistically significant results. Conclusions: Decompressive hemicraniectomy with duroplasty if performed early in STMBI not only decreases the mortality but also increases the functional outcome when compared with patients who were managed conservatively with medical therapy only.

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.

Effect of Fluoxetine on Motor Recovery after Acute Haemorrhagic Stroke: ARandomized Trial

Background: A few clinical trials have suggested that selective serotonin reuptake inhibitors (SSRI’s) enhance motor recovery after stroke but no study has been done in haemorhagic stroke patients. We therefore aimed to investigate whether fluoxetine, an SSRI would enhance motor recovery in patients of haemorrrhagic stroke. Methods: Patients who had haemorrhagic stroke with hemiplegia or hemiparesis and were aged between 18 years and 80 years were included in this double-blind, placebo-controlled trial. Patients were randomly assigned, in a 1:1 ratio to fluoxetine (20 mg/d, orally) or placebo for 3 months starting 5-10 days after the onset of stroke. All patients also had routine physiotherapy. The primary outcome measure was the change on the FMMS between day 0 and day 90 after the start of the study drug. Results: A total of 89 patients were assigned to fluoxetine (n=45) or placebo (n=44), group, and 84 were finally included in the analysis (42 vs 42) after 5 patients lost to follow up. Mean FMMS score improved significantly greater at day 90 in the fluoxetine group (mean 35.64 points) than in the placebo group (23.60 points; p =0.001). Conclusion: Use of fluoxetine in patients of haemorrhagic stroke in early post stroke period added to physiotherapy increased recovery in motor deficits at 3 months.

High prevalence of factor V Leiden and prothrombin G20101A mutations in Kashmiri patients with venous thromboembolism

AIM The genetic variants of the factor V (G1691A), prothrombin (G20210A) and MTHFR (C677T) genes have been widely implicated as inherited risk factors for developing venous thrombosis. This study was undertaken to reveal the frequency of these mutations in Kashmiri patients with venous thromboembolism. METHODOLOGY A case-control study was designed with 250 VTE patients and 250 healthy controls. The mutations were analysed using ARMS-PCR and PCR-RFLP approach. RESULT The factor V Leiden G1691A mutation was found in 17/250 (6.8%) VTE patients and prothrombin G20210A mutation was found in 7/250 (2.8%) VTE patients while no mutation was found in any of the healthy controls. Both the mutations were found to be significantly associated with the increased risk of VTE (p = 0.0001 and 0.0150 respectively) while no association of VTE risk with MTHFR C677T polymorphism was found (p = 0.53). CONCLUSION The increased frequency of factor V Leiden G1691A and prothrombin G20210A mutation in VTE patients indicates a significant role of these mutations in the development of VTE in our population. We therefore suggest the routine screening of these two mutations as thrombophilic markers in Kashmiri patients with venous thromboembolism.

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.

Nonalcoholic Wernicke's encephalopathy: A retrospective study from a tertiary care center in Northern India

Objective: The objective of this study was to describe the demographic features, clinical presentation, and management and outcome of fifty cases of nonalcoholic Wernickes encephalopathy from a tertiary care hospital of a region with reported incidence of thiamine deficiency disorders. Materials and Methods: In a retrospective study, fifty adult cases of Wernickes encephalopathy were analyzed. The diagnosis of Wernickes encephalopathy was made according to the European federation of neurological societies guidelines 2010. Response to thiamine replacement and associated brain magnetic resonance imaging (MRI) findings were also considered as supportive evidence. Results: The mean age of patients was 50.38 years with 20 males and 30 females. The most common clinical manifestations were alteration in sensorium in 30 (60%), ataxia in 18 (36%), memory impairment in 15 (30%), nystagmus in 35 (70%), ophthalmoparesis in 11 (22%), and seizures in 4 (8%). A total of 42 patients had a history of recurrent vomiting. All patients had polished rice as their staple diet. Thirty-five patients had associated polyneuropathy and 15 had a gastrointestinal disorder. Twenty patients underwent MRI which showed both typical and atypical lesions. Majority of patients showed partial or complete response to intravenous thiamine. On discharge, the most common residual symptoms were lower limb weakness, ataxia, and memory impairment. Conclusion: The study shows high incidence of nonalcoholic Wernickes encephalopathy in the region with predominant causative factor being a thiamine deficient diet. Recurrent vomiting can be a prominent early symptom of thiamine deficiency and its recognition can help in the early diagnosis of Wernickes encephalopathy and related thiamine deficiency disorders. Thiamine fortification of food should be done in areas with reported incidence of thiamine deficiency disorders.

Clinical profile of acute flaccid paralysis: A study from North India, Kashmir

Background and Aims: As a part of Global Polio Eradication Programme by the World Health Organization, 1988 surveillance of acute flaccid paralysis (AFP) was an important public health activity in many countries. With nearing the eradication of poliomyelitis, other causes of AFP are gaining importance in both children and adults. This study was designed to know the clinical characteristics, and differential diagnosis of causes of AFP, including distribution by age, gender, and time. This was a prospective observational study. Methods: AFP cases were diagnosed on the basis of history and physical examination. The underlying etiology was ascertained by appropriate laboratory investigations such as arterial blood gas analysis, urinary pH, electrolytes, thyroid profile, electrophysiological studies, cerebrospinal fluid analysis, and imaging. Results: Between July 2010 and September 2012, 106 cases of AFP were enrolled. Out of 106 patients, 58 (54.7%) were suffering from Guillain-Barrι syndrome (GBS), 15 (14.2%) from hypokalemic paralysis, 8 (7.5%) from myasthenia gravis, 8 (7.5%) from thiamine deficiency, 5 (4.7%) from transverse myelitis, and 2 (1.9%) from cord compression. Other diagnoses include; acute motor axonal neuropathy 3 (2.8%), acute disseminated encephalomyelitis 2 (1.9%), meningoencephalitis 2 (1.9%), diabetic polyneuropathy 2 (1.9%), and chemotherapy-induced neuropathy 1 (0.9%). Most cases, 42/106 (39.6%) were admitted during the spring season. Conclusion: GBS was the most common cause of AFP in all age groups. Most of the AFP cases occurred during the spring season. No case of poliomyelitis was found.