The Development of Rational Strategies for Selective Immunotherapy against Autoimmune Demyelinating Disease

Author(s):  
Lawrence Steinman
Author(s):  
Gürkan Atay ◽  
Demet Demirkol

AbstractTherapeutic plasma exchange (TPE) is a treatment administered with the aim of removing a pathogenic material or compound causing morbidity in a variety of neurologic, hematologic, renal, and autoimmune diseases. In this study, we aimed to assess the indications, efficacy, reliability, complications, and treatment response of pediatric patients for TPE. This retrospective study analyzed data from 39 patients aged from 0 to 18 years who underwent a total of 172 TPE sessions from January 2015 to April 2018 in a tertiary pediatric intensive care unit. Indications for TPE were, in order of frequency, macrophage activation syndrome (28.2%, n = 11), renal transplantation rejection (15.4%, n = 6), liver failure (15.4%, n = 6), Guillain–Barre's syndrome (15%, n = 6), hemolytic uremic syndrome (7.7%, n = 3), acute demyelinating disease (7.7%, n = 3), septic shock (5.1%, n = 2), and intoxication (5.1%, n = 2). No patient had any adverse event related to the TPE during the procedure. The TPE session was ended prematurely in one patient due to insufficient vascular access and lack of blood flow (2.6%). In the long term, thrombosis due to the indwelling central catheter occurred (5.1%, n = 2). TPE appears to be an effective first-stage or supplementary treatment in a variety of diseases, may be safely used in pediatric patients, and there are significant findings that its area of use will increase. In experienced hands and when assessed carefully, it appears that the rate of adverse reactions and vascular access problems may be low enough to be negligible.


2018 ◽  
Vol 7 (3) ◽  
pp. 217-221
Author(s):  
E. V. Shevchenko ◽  
G. R. Ramazanov ◽  
S. S. Petrikov

Background Acute dizziness may be the only symptom of stroke. Prevalence of this disease among patients with isolated dizziness differs significantly and depends on study design, inclusion criteria and diagnostic methods. In available investigations, we did not find any prospective studies where magnetic resonance imaging, positional maneuvers, and Halmagyi-Curthoys test had been used to clarify a pattern of diseases with isolated acute dizziness and suspected stroke.Aim of study To clarify the pattern of the causes of dizziness in patients with suspected acute stroke.Material and methods We examined 160 patients admitted to N.V. Sklifosovsky Research Institute for Emergency Medicine with suspected stroke and single or underlying complaint of dizziness. All patients were examined with assessment of neurological status, Dix-Hollpike and Pagnini-McClure maneuvers, HalmagyiCurthoys test, triplex scans of brachiocephalic arteries, transthoracic echocardiography, computed tomography (CT) and magnetic resonance imaging (MRI) of the brain with magnetic field strength 1.5 T. MRI of the brain was performed in patients without evidence of stroke by CT and in patients with stroke of undetermined etiology according to the TOAST classification.Results In 16 patients (10%), the cause of dizziness was a disease of the brain: ischemic stroke (n=14 (88%)), hemorrhage (n=1 (6%)), transient ischemic attack (TIA) of posterior circulation (n=1 (6%)). In 70.6% patients (n=113), the dizziness was associated with peripheral vestibulopathy: benign paroxysmal positional vertigo (n=85 (75%)), vestibular neuritis (n=19 (17%)), Meniere’s disease (n=7 (6%)), labyrinthitis (n=2 (1,3%)). In 6.9% patients (n=11), the cause of dizziness was hypertensive encephalopathy, 1.9% of patients (n=3) had heart rhythm disturbance, 9.4% of patients (n=15) had psychogenic dizziness, 0.6% of patients (n=1) had demyelinating disease, and 0.6% of patients (n=1) had hemic hypoxia associated with iron deficiency anemia.Conclusion In 70.6% patients with acute dizziness, admitted to hospital with a suspected stroke, peripheral vestibulopathy was revealed. Only 10% of patients had a stroke as a cause of dizziness.


2012 ◽  
Author(s):  
Nitin Karandikar ◽  
Venkatesh Kashi

2011 ◽  
Author(s):  
Nitin Karandikar ◽  
Venkatesh Kashi

2020 ◽  
Vol 19 (6) ◽  
pp. 376-385
Author(s):  
Md. A. Islam ◽  
Shoumik Kundu ◽  
Rosline Hassan

Multiple Sclerosis (MS) is the most common autoimmune demyelinating disease of the Central Nervous System (CNS). It is a multifactorial disease which develops in an immune-mediated way under the influences of both genetic and environmental factors. Demyelination is observed in the brain and spinal cord leading to neuro-axonal damage in patients with MS. Due to the infiltration of different immune cells such as T-cells, B-cells, monocytes and macrophages, focal lesions are observed in MS. Currently available medications treating MS are mainly based on two strategies; i) to ease specific symptoms or ii) to reduce disease progression. However, these medications tend to induce different adverse effects with limited therapeutic efficacy due to the protective function of the blood-brain barrier. Therefore, researchers have been working for the last four decades to discover better solutions by introducing gene therapy approaches in treating MS generally by following three strategies, i) prevention of specific symptoms, ii) halt or reverse disease progression and iii) heal CNS damage by promoting remyelination and axonal repair. In last two decades, there have been some remarkable successes of gene therapy approaches on the experimental mice model of MS - experimental autoimmune encephalomyelitis (EAE) which suggests that it is not far that the gene therapy approaches would start in human subjects ensuring the highest levels of safety and efficacy. In this review, we summarised the gene therapy approaches attempted in different animal models towards treating MS.


2020 ◽  
Vol 17 (2) ◽  
pp. 133-147
Author(s):  
Mina Zafarpiran ◽  
Roya Sharifi ◽  
Zeinab Shirvani-Farsani

Background: Multiple Sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system, and genetic factors play an important role in its susceptibility. The expressions of many inflammatory genes implicated in MS are regulated by microRNA (miRNAs), whose function is to suppress the translation by pairing with miRNA Recognition Elements (MREs) present in the 3' untranslated region (3'UTR) of target mRNA. Recently, it has been shown that the Single Nucleotide Polymorphism (SNPs) present within the 3'UTR of mRNAs can affect the miRNA-mediated gene regulation and susceptibility to a variety of human diseases. Objective: The aim of this study was to analyze the SNPs within the 3'UTR of miRNA inflammatory target genes related to multiple sclerosis. Methods: By DisGeNET, dbGaP, Ovid, DAVID, Web of knowledge, and SNPs databases, 3'UTR genetic variants were identified in all inflammatory genes associated with MS. Also, miRNA's target prediction databases were used for predicting the miRNA binding sites. Results: We identified 125 SNPs with MAF>0.05 located in the binding site of the miRNA of 35 genes among 59 inflammatory genes related to MS. Bioinformatics analysis predicted 62 MRE-modulating SNPs and 59 MRE-creating SNPs in the 3'UTR of MSimplicated inflammatory genes. These candidate SNPs within miRNA binding sites of inflammatory genes can alter the miRNAs binding, and consequently lead to the mRNA gene regulation. Conclusion: Therefore, these miRNA and MRE-SNPs may play important roles in personalized medicine of MS, and hence, they would be valuable for further functional verification investigations.


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