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*Corresponding Author: Ali Osman AVCI, Gülhane Askerî Tıp Akademisi, Turkey.
Citation: Ali Osman AVCI, (2023), Comparison of serum levels of SIL-2R, IL-6, IL-10, TNF-α, CRP, ESR and Fibrinogen in Patients with Active and Inactive Behçet’s Disease, International Journal of Clinical Case Reports and Reviews, 13(5); DOI: 10.31579/2690-4861/312
Copyright: © 2023, Ali Osman AVCI. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 09 May 2023 | Accepted: 22 May 2023 | Published: 31 May 2023
Keywords: Behçet’s Disease; SIL-2R; IL-6; IL-10; TNF-α
Behçet's disease (BD) is a chronic inflammatory illness that affects the entire body and is characterized by recurring episodes of oral aphthae, ocular and cutaneous lesions, and scrotal or vaginal ulcerations. The involvement of other organs and systems increases mortality in addition to the significant morbidity.
This study involved a total of 40 participants, 20 of whom were healthy controls and 20 of whom were patients (of the 20 Behçet's patients, 12 (60%) were in the active phase and 8 (40%) were in the inactive phase). There was no therapy being given to any of the 20 patients that would have affected their cytokine levels.
Only young men made up the patient and control groups because both early onset and male sex are signs of poor prognosis.
The ELISA method was used to measure the levels of serum cytokines. The statistical analysis of the derived numerical values employed the Mann-Whitney U Test.
We found a significant correlation between serum cytokine levels and classical acute phase markers in active Behçet’s patients. ESR (P < 0,001), CRP (P < 0,001), fibrinogen (P < 0,001), IL-10 (P < 0,001), IL-6 (P < 0,001), SIL-2R (P < 0,001) and TNFα (P < 0,001).
There was no statistically significant difference in serum levels of classical acute phase markers ESR (P = 0,746), CRP (P = 0,476) and fibrinogen (P = 0,940) when inactive Behçet’s patients and healthy controls were compared. However, serum levels of IL-10 (P < 0,001), IL-6 (P = 0,001), SIL-2R (P < 0,001) and TNFα (P = 0,001) were statistically different between inactive Behcet's patients and the control group.
Our research shows that even in the inactive phase, serum cytokine levels of Behçet’s patients are much higher than the healthy control group. However, the levels of ESR, CRP and fibrinogen, which are classical acute phase markers, were found at normal levels in Behçet’s patients in the inactive phase. These findings show that measurement of serum interleukin levels will enable us to take preventive measures for morbidity and mortality follow-up of Behçet's patients.
Behçet's disease (BD) is a systemic, long-term inflammatory condition marked by recurring episodes of oral aphthae, cutaneous, ophthalmic, and scrotal or vaginal lesions. Vascular, articular, gastrointestinal, cardiac, pulmonary, renal, and neurologic dysfunction are all linked to Behçet's Disease. Despite the fact that the discoveries date back to Hippocrates, Turkish Professor Dr. Hulusi Behçet was the first to describe it as a distinct illness in 1937 [1, 2].
The "Silk Road," the Middle East, the Mediterranean coast, and Central Asia all have higher rates of BD. The disease's greatest documented prevalence, which ranges from 110 to 420 cases per 100,000 individuals, was originally noted in Turkey. BD is present practically everywhere in the world, despite the fact that regional prevalence varies greatly. The disease, which affects both sexes equally, is the most It often occurs between the ages of 20–40. Male sex and disease early onset as causes of poor prognosis accepted [2, 3].
The exact cause of BD is not known yet. The theory that BD is an aberrant immune response that is brought on by bacterial, viral, and other environmental antigens or autoantigens like heat shock proteins (HSPs) is the one that is now most widely supported [4–7].
Only clinical signs and symptoms can be used to make the diagnosis of BD because there isn't a universally recognized diagnostic laboratory test for the condition. The most widely used and widely acknowledged diagnostic criteria for Behçet's disease are the International Working Group for the criteria for BD (the presence of either typical eye lesions, typical cutaneous lesions, or a positive skin pathergy test in addition to oral ulcers and recurrent genital ulcers). Increased serum levels of biochemical factors including CRP and cytokines have been suggested as indicators of disease activity [8–12].
In order to better understand the etiopathogenesis of BD, numerous cytokines have been studied. Regarding the blood cytokine levels of BP in the active and inactive stages, these investigations found remarkably disparate findings.
Patients with BD have higher levels of proinflammatory cytokines, particularly when the disease is active. The enhanced inflammatory response is thought to be caused by this elevation, particularly those implicated in Th1-mediated inflammation, along with genetic susceptibility. The SlL-2 receptor is thought to contribute to local inflammation. (13,14). TNFα enhances all types of humoral and cellular immune response and acts synergistically with IL-6 [15, 16].
Since IL-10 inhibits the production of various cytokines, IL-10 was designated as “Cytokine Synthesis Inhibitory Factor” (CSIF) when it was first identified. However, IL-10 reduces inflammation by reducing nitric oxide synthase induction and toxic oxygen radicals and monocyte prostaglandin H synthase-2 (COX-2) in macrophages [17–20].
It has been reported that circulating levels of SIL-2R, TNFα, and IL-6 are increased in Behçet’s patients [21]. It has been suggested that the increase in serum SIL-2R, TNFα and IL-6 levels is more pronounced in active-stage Behçet's patients.
It was also found that the increase in serum SIL-2R and IL-6 levels was more pronounced in BP with complications; It has been reported that IL-6 levels increase in the cerebrospinal fluid of patients with neuro-Behçet's disease. There are also studies reporting that serum SIL-2R, IL-6, IL-4, IL-10 and TNFα levels in Behçet’s patients do not increase in both active and inactive periods. Serum cytokine levels and conventional acute phase reactants have also been compared in several research [22–27].
This study was conducted to compare serum SIL-2R, IL-6, IL-10, TNF-α levels with serum CRP, ESR and fibrinogen levels in active and inactive young male Behçet's patients.
A total of 40 persons participated in this study, 20 of whom were Behçet’s Patients and 20 of whom were healthy controls. Only young men made up the patient and control groups because both early onset and male sex are signs of poor prognosis.
The patient and control groups were selected from among the young men who came for enlistment examinations. A control group was formed from those who did not have any health problems or complaints and had no pathological findings according to the results of physical examination and blood tests. Those who had a history of Behçet's disease and still had active findings and did not use drugs constituted the active patient group, and those without active findings constituted the inactive patient group. Those currently using any medication were not included in any group.
The patients with Behçet ranged in age from 20 to 30, with a mean age of 22.55 years. Their diagnoses were made in accordance with the clinical standards established by the "International Study Group". Twelve (12%) of the 20 Behçet’s patients were included in the trial during the inactive phase, while eighty (40%) were in the active phase. Patients with at least two of the oral ulcers, genital ulcers, eye lesions and active arthritis were considered active patients.
Healthy men in the same age range made up the control group. The control group's age range was 20 to 29, and the average age was 22.45 years.
Blood samples were taken from the patient and control groups in the morning, fasting, into sterile tubes for ESR, CRP, fibrinogen, cytokine levels (IL-6, IL-10, SIL-2R and TNFα). Blood samples taken for cytokine levels were centrifuged sterilely at 3000 rpm for 10 minutes and their serums were separated. The serums were placed in sterile tubes with patient names on them and stored in deep-freeze at -40°C.
Determination of Soluble Interleukin-2 Receptor: Serum SIL-2R level was measured using commercially available ELISA kit (CYTELISA; Cytimmunesciences, Paris, France).
Obtained results were evaluated by comparison with standard calibrators. The optical densities of the calibrators were analyzed with the graph obtained by performing linear-log regression analysis. The minimum SIL-2R level that the test can measure is 5 pg/ml. was in the form.
Tumor Necrosis Factor-α determination: Serum TNFα level was measured using commercially available ELISA kit (CYTELISA; Cytimmune sciences, Paris, France).
Obtained results were evaluated by comparison with standard calibrators. The optical densities of the calibrators were analyzed with the graph obtained by performing linear-log regression analysis. The minimum TNFα level that the test can measure is 5 pg/ml. was in the form.
Interleukin-6 determination: Serum IL-6 level was measured using commercially available ELISA kit (CYTELISA; The Cytoscreen, Paris, France).
Obtained results were evaluated by comparison with standard calibrators. The optical densities of the calibrators were analyzed with the graph obtained by performing linear-log regression analysis. The minimum IL-6 level that the test can measure is 10 pg/ml. was in the form.
Interleukin-10 determination: Serum IL-10 level was measured using commercially available ELISA kit (CYTELISA; The Cytoscreen, Paris, France).
Obtained results were evaluated by comparison with standard calibrators. The optical densities of the calibrators were analyzed with the graph obtained by performing linear-log regression analysis. The minimum IL-10 level that the test can measure is 5 pg/ml. was in the form.
In the statistical calculations of the numerical values obtained, the "Significance Test of the Difference Between Two Means" or the "Mann-Whitney U Test" was used in accordance with the number of cases. Results are given as arithmetic mean ± standard error. Values of P ≤ 0,05 were considered statistically significant.
Table 1 summarizes the results of the active (12 patients) BP, while Table 2 summarizes the results of the inactive (8 patients) BP. Table 3 summarizes the results of the control group.
| Lower value | Upper value | Average | Standard error | Standard deviation | |
|---|---|---|---|---|---|
| Age (Year) | 20 | 30 | 22,55 | 1,20 | 2,71 |
| ESR (mm/h) | 20 | 105 | 66,25 | 6,50 | 22,52 |
| CRP (mg/dl) | 11,00 | 47,00 | 25,25 | 3,36 | 11,63 |
| Fibrinogen (mg/dl) | 386 | 585 | 474,08 | 16,93 | 58,64 |
| IL-10 (pg/ml) | 93,40 | 500,00 | 257,78 | 45,54 | 157,76 |
| IL-6 (pg/ml) | 7,80 | 93,40 | 32,96 | 7,18 | 24,90 |
| SIL-2R (pg/ml) | 7,80 | 125,00 | 34,62 | 9,27 | 32,14 |
| TNF-α (pg/ml) | 7,80 | 62,50 | 47,36 | 5,53 | 19,17 |
Table 1: Findings of Active Behçet's Patients (n = 12)
| Lower value | Upper value | Average | Standard error error | Standard deviation | |
|---|---|---|---|---|---|
| Age (Year) | 20 | 30 | 22,60 | 1,18 | 2,68 |
| ESR (mm/h) | 3 | 20 | 12,38 | 4,51 | 8,40 |
| CRP (mg/dl) | 5,90 | 7,00 | 6,03 | 0,14 | 0,38 |
| Fibrinogen (mg/dl) | 265 | 622 | 391,50 | 38,56 | 109,05 |
| IL-10 (pg/ml) | 15,20 | 125,00 | 29,80 | 13,62 | 38,54 |
| IL-6 (pg/ml) | 7,80 | 22,40 | 11,45 | 2,38 | 6,75 |
| SIL-2R (pg/ml) | 7,80 | 15,60 | 10,72 | 1,42 | 4,03 |
| TNF-α (pg/ml) | 7,80 | 42,50 | 14,08 | 4,24 | 12,01 |
Table 2: Findings of Inactive Behçet's Patients (n = 8)
| Lower value | Upper value | Average | Standard error | Standard deviation | |
|---|---|---|---|---|---|
| Age (Year) | 20 | 29 | 22,45 | 1,30 | 2,61 |
| ESR (mm/h) | 2 | 20 | 7,65 | 3,25 | 4,48 |
| CRP (mg/dl) | 5,90 | 5,90 | 5,90 | 0,28 | 0,00 |
| Fibrinogen (mg/dl) | 191 | 382 | 288,20 | 21,45 | 47,05 |
| IL-10 (pg/ml) | 7,80 | 15,60 | 8,58 | 1,38 | 2,40 |
| IL-6 (pg/ml) | 7,80 | 15,60 | 10,14 | 1,45 | 3,66 |
| SIL-2R (pg/ml) | 7,80 | 15,60 | 9,36 | 1,40 | 3,20 |
| TNF-α (pg/ml) | 15,60 | 42,50 | 19,63 | 8,42 | 9,85 |
Table 3: Findings of the control group (n = 20)
Comparison the serum levels of conventional acute phase markers of active and inactive BP with control group is showed in Figure 1.
Figure 1: Comparison of serum levels of classical acute phase markers
Comparison the serum levels of SIL2-R, IL-6, IL-10 and TNFα of active and inactive BP with control group is showed in Figure 2.
Figure 2: Comparison of serum levels of cytokines
Serum levels of ESR (P < 0,001), CRP (P < 0,001), fibrinogen (P < 0,001), IL-10 (P < 0,001), IL-6 (P < 0,001), SIL-2R (P < 0,001), and TNFα (P < 0,001) were statistically different between active and inactive Behçet’s Patients (Table 4, Fig. 1).
| ESR | CRP | Fibrinogen | IL-10 | IL-6 | SIL-2R | TNF-α | |
|---|---|---|---|---|---|---|---|
| Mann-Whitney U | 0,500 | 0,000 | 18,500 | 10,500 | 22,500 | 14,500 | 8,000 |
| Wilcoxon W | 36,500 | 36,00 | 54,500 | 46,500 | 58,500 | 50,500 | 44,000 |
| Z value | -3,672 | -3,714 | -2,279 | -2,971 | -2,052 | -2,777 | -3,304 |
| Asymp. Sig. [2- tailed] | 0,000 | 0,000 | 0,023 | 0,003 | 0,017 | 0,005 | 0,001 |
| P value | 0,000 | 0,000 | 0,020 | 0,002 | 0,047 | 0,007 | 0,001 |
Table 4: Comparison of Findings of Active-Inactive Behçet's Patients
Serum levels of ESR (P < 0,001), CRP (P < 0,001), fibrinogen (P < 0,001), IL-10 (P < 0,021), IL-6 (P < 0,001), SIL-2R (P < 0,001), and TNFα (P < 0,001) were statistically different between active Behçet’s Patients and the control group (Table 5, Figure. 1).
| ESR | CRP | Fibrinogen | IL-10 | IL-6 | SIL-2R | TNF-α | |
|---|---|---|---|---|---|---|---|
| Mann-Whitney U | 0,500 | 0,000 | 13,500 | 2,000 | 24,000 | 11,500 | 6,000 |
| Wilcoxon W | 210,500 | 210,00 | 225,500 | 212,00 | 234,00 | 221,500 | 216,000 |
| Z value | -4,668 | -4,729 | -4,147 | -5,076 | -4,139 | -4,880 | -4,886 |
| Asymp. Sig. [2- tailed] | 0,000 | 0,000 | 0,000 | 0,000 | 0,000 | 0,000 | 0,000 |
| P value | 0,000 | 0,000 | 0,000 | 0,000 | 0,000 | 0,000 | 0,000 |
Table 5: Comparison of Active Behçet's Patients-Control Group.
Serum levels of ESR (P = 0,746), CRP (P = 0,746), and fibrinogen (P = 0,940)) were not statistically different between inactive Behçet’s Patients and the control group (Table 6, Fig. 1).
| ESR | CRP | Fibrinogen | IL-10 | IL-6 | SIL-2R | TNF-α | |
|---|---|---|---|---|---|---|---|
| Mann-Whitney U | 73,500 | 73,000 | 78,00 | 10,000 | 20,000 | 14,000 | 20,000 |
| Wilcoxon W | 109,500 | 283,00 | 114,00 | 220,000 | 223,000 | 224,000 | 223,000 |
| Z value | -0,334 | -0,373 | -0,102 | -4,170 | -3,517 | -4,287 | -4,291 |
| Asymp. Sig. [2- tailed] | 0,738 | 0,709 | 0,919 | 0,000 | 0,000 | 0,000 | 0,000 |
| P value | 0,746 | 0,746 | 0,940 | 0,000 | 0,001 | 0,000 | 0,001 |
Table 6: Comparison of Inactive Behçet's Patients-Control Group
Serum levels of IL-10 (P < 0,001), IL-6 (P = 0,001), SIL-2R (P < 0,001), and TNFα (P = 0,001) were statistically different between inactive Behçet’s patients and the control group (Fig. 2).
The exact cause of BD is not yet known. The theory that BD is an aberrant immune response in people who are genetically predisposed to the disease that is brought on by environmental antigens or autoantigens like heat shock proteins (HSPs) is currently the one with the greatest evidence [28, 29].
Patients with BD have higher levels of proinflammatory cytokines, particularly when the disease is active. The enhanced inflammatory response is thought to be caused by this elevation, particularly those implicated in Th1-mediated inflammation, along with genetic susceptibility [28–30].
The literature is replete with studies examining IL-10 serum levels. Sadeghi et al. discovered no significant difference in serum levels of IL-10 between Behçet's patients and a control group, according to Aridogan et al. and Guenane et al [31, 32].
However, in our study, we found a substantial difference in serum IL-10 levels between patients with active BD and the control group, as well as between patients with inactive BD and those who did not have it.
Acute phase reactant CRP is known to be increased in a range of inflammatory diseases. The CRP level may potentially be a sign of tissue damage caused by the immune system. In our investigation, a substantial difference was found between the CRP levels of active BP and the control group.
Numerous studies examining CRP serum levels have been published, and several of these studies (e.g. Karada et al., Müftüolu et al., Balta et al., Bekpınar et al., Adam et al.) reveal that serum CRP levels are elevated in individuals with active BD [33–35].
In several disorders, including Behçet's patients in the active phase, investigations have shown that ESR and CRP rise as acute phase reactants [36, 37]. Most active BD symptoms are linked to both ESR and CRP. They can be applied to Behçet's patients to forecast disease activity and active vascular symptoms [37].
In addition to serving as a marker of inflammation, fibrinogen, an acute phase reactant, is essential for the production of clots in both the fibrin network and platelet aggregation. In order to understand the vascular involvement and to demonstrate the disease activity, the increase in fibrinogen in Behçet's illness is crucial [38].
These cytokines were chosen because IL-6, SIL-2R and TNFα are proinflammatory; IL-10 is known as an anti-inflammatory cytokine and there is more research and knowledge about these cytokines. In addition, the increase in serum levels of these cytokines in many inflammatory diseases suggests that they will be effective both in the pathogenesis of the disease and in the evaluation of disease activity, as well as in the treatment.
This study can be criticized in two aspects: One of them is the low number of participants, and the other is that the results were obtained in this way because there may be organ involvement in Behçet's patients in the inactive period (no real inactive period). However, it is not easy to find young male patients who have never received treatment. Yes, it would be better if more young men participated in this study. Perhaps in the future, such a study will be conducted with a large number of participants.
Secondly, it is important that although the classical acute phase markers are normal, cytokines are high in these patients, even though Behçet's patients in the inactive period are not really in the inactive period due to organ involvement. Because detecting a condition that cannot be detected with conventional acute phase markers with cytokine levels is very important for morbidity and mortality follow-up.
Another question that may come to mind: Why was IL-10, an anti-inflammatory cytokine, found to be high, as well as high levels of proinflammatory cytokines in Behçet's patients in the inactive period? In response to this: Perhaps the inactive period of these patients is due to this anti-inflammatory cytokine. IL-10, which is an anti-inflammatory cytokine, increases more because proinflammatory cytokines increase more in the active period, and IL-10 increases less in the inactive period, since the increase in proinflammatory cytokines is less.
Acknowledgements
I would like to thank my thesis advisor, Prof. Dr. Yavuz Baykal and helping with statistics Prof. Dr. Mustafa Turan and Ankara Gülhane Military Medical Academy Internal Medicine Department nurses and Immunology and Biochemistry Laboratory staff.
Funding
No funding was received
Availability of data and materials
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Authors’ contributions
This article is derived from the specialty thesis in medicine. Therefore, the only author is Ali Osman Avcı, MD. Those who contributed during the thesis work are included in the acknowledgment section.
Ethics approval and consent to participate
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University Gulhane Military Medical Academy (2020/27).
Patient consent for publication
The author affirms that human research participants provided informed consent for publication.
Competing interests
The authors declare that they have no competing interests.
Additional Declarations
No competing interests reported.
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Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
