|
| Study | Study design | MS | HC | NLR cut-off | Sensitivity (%) | Specificity (%) | Findings/conclusions | Confounders addresseda | Strengths and/or limitations |
|
| Demirci, 2016 | Case control | 102 | 56 | 2.04 | 81 | 62.5 | NLR values were higher in MS compared with HC, and patients in relapse had higher NLR values than HC and patients in remission. Patients in remission had higher NLR values than HC. High NLR was an independent predictor of disability progression with EDSS >3 as the response variable. | DMT
Smoking
Conc. Dis. | All patients were nonsmokers and untreated for at least six months prior to inclusion.
However, no data on BMI were provided. |
| Guzel, 2016 | Retrospective cross-sectional | 127 | — | 4.52 | 96.1 | 57.1 | NLR values were higher in patients with EDSS >5 compared with patients with EDSS ≤5. The EDSS score had a weak to moderate correlation with NLR. | DMT
Conc. Dis. | The use of DMTs differed between the two EDSS stratified groups and they did not include data on BMI, smoking, or relapse status. |
| Bisgaard, 2017 | Case control | 219 and CIS: 19,
ON: 140 | 813 | — | — | — | NLR values were higher in MS compared with HC, and higher in patients in relapse than remission. NLR values did not predict an EDSS score ≥4.0. | DMT
Smoking
Conc. Dis. | The advantage of this study is that the sample size of each stage in MS patients is large and is not affected by other confounding factors. |
| Al-Hussain,2017 | Case control | 60 | 60 | — | — | — | NLR values were higher in MS compared with HC.
NLR values were correlated with stress scores. | | Did not report any data on confounding factors and these results should be interpreted carefully. |
| Hasselbalch, 2018 | Case control | 740 | 1420 | 2.07 | 49 | 70 | NLR values were higher in MS compared with HC.
NLR values correlated weakly with MSSS. | DMT
BMI
Smoking | The sample capacity of this study is large;
the patients have a blood test before taking DMT for the first time, so it has no effect on the drug. |
| D’Amico E, 2019 | Retrospective, observational | 84 | — | — | — | — | NLR values were higher in the “low disease activity” group compared with the “high activity group.” High activity was defined as (≥ 2 relapses in the year prior to study entry and (≥ 1 gadolinium-enhancing lesion at the time of the study.
No associations were observed between NLR values and patient characteristics (gender, age, and EDSS at onset). | DMT
Conc. Dis. | The sample size is small.
No data regarding concomitant diseases that could alter the neutrophil count or other data such as smoking status. |
| Hemond, 2019 | Cohort study, retrospective analysis | 483 | — | 2.1 | — | — | NLR values were higher for MS patients on cyclophosphamide and fingolimod treatment and significantly lower when treated with interferons and natalizumab.
Higher NLR values were associated with increased EDSS scores, and PMS was compared with RRMS.
Increased NLR values were associated with higher depression (CES-D) scores, higher fatigue scores (MFIS), and lower physical quality of life (SF-36). | DMT
BMI
Smoking | This study includes a large and well-characterized sample of MS patients, including self-reported psychological outcome measures, specific DMT use, and quantitative neuroimaging pathology,
while the results are of an associative nature only, and thus no conclusions should be drawn regarding causality. |
| Goldman D, 2020 | Retrospective, observational | 103 | — | 2.0 | — | — | At baseline, the NLR values were 2.5 ± 1.9 for all included patients. Over 50% of MS patients had high NLR (defined as NLR >2).
In the follow-up samples, after starting treatment with dimethyl fumarate, the NLR values were 3.6 ± 2.5. | DMT
BMI
Conc. Dis. | This study considered dimethyl fumarate-associated neutropenia.
The limitations of this study reflect its retrospective nature. |
| Yetkin MF,2020 | Cohort study, retrospective Analysis | 270 | — | 2.365 | 56.94 | 60.1 | NLR values were higher in MS patients who had breakthrough disease activity, defined as the escalation group (median (min-max): 2.5 (0.1–13.8)) compared with the nonescalation group (median (min-max): 2.1 (0.6–12.8)). | DMT
Smoking
Cont. Dis. | The strengths of this study are the number of subjects and long-term follow-up,
while not having detailed information about the comorbid status and lifestyle of the patients. |
| Gelibter, 2021 | Cohort study, retrospective analysis | 121 | — | — | — | — | Association was found neither between NLR and disease activity nor with other clinical measures. | DMT
BMI
Smoking | This study compared the validity of NLR with established markers, such as serum neurofilament light chain (nf). CSF microvesicles (CSF-MVs) and CSF IgG indices. The NLR was also investigated in relation to the brain and spinal cord MRI findings. |
| Akil, Alp, 2021 | Case- control | 83 | 44 | — | — | — | The NLR levels were found to be significantly higher in the patient group than in the HC group. There was also a significant difference between the serum NLR levels of the relapse and HC. | Smoking | The NLR levels of the RRMS patients were measured while in relapse, 1 month after relapse, and while in remission. Moreover, the patients were grouped based on the lesion burden of MRI,
while the sample size was limited. |
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