Is there an association between the Expanded Disability Status Scale and inflammatory markers in multiple sclerosis?

Güzel, Işıl; Mungan, Semra; Öztekin, Zeynep Neşe; Ak, Fikri

doi:10.1016/j.jcma.2015.08.010

Cited by 50 publications

(47 citation statements)

References 19 publications

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“…However, as mentioned earlier, in MS patients this correlation disappears and they tend to be inversely (but not significantly) associated. Prior studies find that EDSS value is strongly correlated with axonal damage and neurodegeneration [ 29 , 30 ]. Furthermore, a possible mechanism for MS progression and axonal loss could be via oxidative stress, caused by a decrease in antioxidant levels, which might lead to DNA damage [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Repetitive element hypermethylation in multiple sclerosis patients

et al. 2016

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BackgroundMultiple sclerosis (MS) is a complex disorder of the central nervous system whose cause is currently unknown. Evidence is increasing that DNA methylation alterations could be involved in inflammatory and neurodegenerative diseases and could contribute to MS pathogenesis. Repetitive elements Alu, LINE-1 and SAT-α, are widely known as estimators of global DNA methylation. We investigated Alu, LINE-1 and SAT-α methylation levels to evaluate their difference in a case–control setup and their role as a marker of disability.ResultsWe obtained blood samples from 51 MS patients and 137 healthy volunteers matched by gender, age and smoking. Methylation was assessed using bisulfite-PCR-pyrosequencing. For all participants, medical history, physical and neurological examinations and screening laboratory tests were collected. All repetitive elements were hypermethylated in MS patients compared to healthy controls. A lower Expanded Disability Status Scale (EDSS) score was associated with a lower levels of LINE-1 methylation for ‘EDSS = 1.0’ and ‘1.5 ≤ EDSS ≤ 2.5’ compared to an EDSS higher than 3, while Alu was associated with a higher level of methylation in these groups: ‘EDSS = 1.0’ and ‘1.5 ≤ EDSS ≤ 2.5’.ConclusionsMS patients exhibit an hypermethylation in repetitive elements compared to healthy controls. Alu and LINE-1 were associated with degree of EDSS score. Forthcoming studies focusing on epigenetics and the multifactorial pathogenetic mechanism of MS could elucidate these links further.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0395-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Repetitive element hypermethylation in multiple sclerosis patients

et al. 2016

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“…There is limited prior literature regarding the NLR in MS; Demirci and colleagues were the first to explore this area and found that an elevated NLR could discriminate MS from healthy controls, was related to neurological disability scores, and was further increased in flares compared to remission [20]. Several subsequent studies have confirmed similar findings [13, 20, 21], although one study could not replicate associations with disability scores [22]. None of these studies carefully examined the role of disease-modifying therapies however; nor did they look at MRI-related disease outcomes such as cerebral atrophy or quantified T2-hyperintense lesion volume.…”

Section: Introductionmentioning

confidence: 93%

The neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios are independently associated with neurological disability and brain atrophy in multiple sclerosis

et al. 2019

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BackgroundSerum hematological indices such as the neutrophil-lymphocyte ratio (NLR) or monocyte-lymphocyte ratio (MLR) have been used as biomarkers of pathogenic inflammation and prognostication in multiple areas of medicine; recent evidence shows correlation with psychological parameters as well.Objectives/Aims: To characterize clinical, neuroimaging, and psycho-neuro-immunological associations with NLR and MLR in persons with multiple sclerosis (MS).MethodsWe identified a large cohort of clinically well-defined patients from our longitudinal database that included MS-related outcomes, disease-modifying therapy, patient-reported outcome (PRO) measures, and quantified cerebral MRI at 1.5 T. We queried hospital records for complete blood counts within 2 months of each clinic visit and excluded those obtained during clinical relapses. Four hundred eighty-three patients, with a mean of 3 longitudinal observations each, were identified who met these criteria. Initial analyses assessed the association between NLR and MLR as the outcomes, and psychological and demographic predictors in univariable and multivariable models controlling for age, gender and treatment. The second set of analyses assessed the association between clinical and MRI outcomes including whole brain atrophy and T2-hyperintense lesion volume, with NLR and MLR as predictors in univariable and multivariable models. All analyses used a mixed effects linear or logistic regression model with repeated measures.ResultsUnadjusted analyses demonstrated significant associations between higher (log-transformed) NLR (but not MLR) and PRO measures including increasing depression (p = 0.01), fatigue (p < 0.01), and decreased physical quality of life (p < 0.01). Higher NLR and MLR strongly predicted increased MS-related disability as assessed by the Expanded Disability Status Scale, independent of all demographic, clinical, treatment-related, and psychosocial variables (p < 0.001). Lastly, higher NLR and MLR significantly discriminated progressive from relapsing status (p ≤ 0.01 for both), and higher MLR correlated with increased whole-brain atrophy (p < 0.05) but not T2 hyperintense lesion volume (p > 0.05) even after controlling for all clinical and demographic covariates. Sensitivity analyses using a subset of untreated patients (N = 146) corroborated these results.ConclusionsElevated NLR and MLR may represent hematopoetic bias toward increased production and pro-inflammatory priming of the myeloid innate immune system (numerator) in conjunction with dysregulated adaptive immune processes (denominator), and consequently reflect a complementary and independent marker for severity of MS-related neurological disability and MRI outcomes.Electronic supplementary materialThe online version of this article (10.1186/s12883-019-1245-2) contains supplementary material, which is available to authorized users.

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“…In addition, in this work it was revealed that, in patients with a higher concentration of homocysteine, there are increases in the concentration of tumor necrosis factor-alpha 1 receptor (TNF-α receptor 1) and ICAM. In the study by Guzel et al [ 50 ], it was shown that the concentration of homocysteine is statistically significantly higher in patients with an EDSS greater than 5. The data obtained confirm the association of hyperhomocysteinemia with the progression and severity of disability in patients with MS.…”

Section: The Role Of Homocysteine In Endothelial Dysfunction In Mumentioning

confidence: 99%

Hyperhomocysteinemia and Endothelial Dysfunction in Multiple Sclerosis

et al. 2020

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Endothelial dysfunction is recognized as one of the leading factors in the pathogenesis of diseases of the central nervous system of various etiologies. Numerous studies have shown the role of hyperhomocysteinemia in the development of endothelial dysfunction and the prothrombogenic state. The most important condition in the development of multiple sclerosis (MS) is a dysregulation of the blood-brain barrier (BBB) and transendothelial leukocyte migration. It has been proven that homocysteine also contributes to the damage of neurons by the mechanism of excitotoxicity and the induction of the apoptosis of neurons. These processes can be one of the factors of neurodegenerative brain damage, which plays a leading role in the progression of MS. This review describes the pleiotropic effect of homocysteine on these processes and its role in MS pathogenesis.

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Is there an association between the Expanded Disability Status Scale and inflammatory markers in multiple sclerosis?

Abstract: According to this study, inflammation may have a role in the pathogenesis of MS and in patients with EDSS > 5. Additionally, NLR and CRP levels may be discriminative factors of adverse clinical outcomes.

Cited by 50 publications

References 19 publications

Repetitive element hypermethylation in multiple sclerosis patients

Repetitive element hypermethylation in multiple sclerosis patients

The neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios are independently associated with neurological disability and brain atrophy in multiple sclerosis

Hyperhomocysteinemia and Endothelial Dysfunction in Multiple Sclerosis

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