UMMS Affiliation

Department of Neurology

Publication Date

2019-02-12

Document Type

Article

Disciplines

Biological Factors | Diagnosis | Hemic and Immune Systems | Hemic and Lymphatic Diseases | Immunopathology | Nervous System | Nervous System Diseases | Neuroscience and Neurobiology | Pathological Conditions, Signs and Symptoms

Abstract

BACKGROUND: Serum 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).

METHODS: We 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.

RESULTS: Unadjusted 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.

CONCLUSIONS: Elevated 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.

Keywords

Brain atrophy, MRI, Monocyte-to-Lympocyte ratio, Multiple sclerosis, Neutrophil-to-Lympocyte ratio, Patient-reported outcomes

Rights and Permissions

© The Author(s). 2019 Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

DOI of Published Version

10.1186/s12883-019-1245-2

Source

BMC Neurol. 2019 Feb 12;19(1):23. doi: 10.1186/s12883-019-1245-2. Link to article on publisher's site

Journal/Book/Conference Title

BMC neurology

Related Resources

Link to Article in PubMed

PubMed ID

30755165

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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