Are Systemic Inflammation Response Index and Systemic Immune-Inflammation Index an ideal biomarker for epileptic patients?

doi:10.21203/rs.3.rs-3797511/v1

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Are Systemic Inflammation Response Index and Systemic Immune-Inflammation Index an ideal biomarker for epileptic patients?

https://doi.org/10.21203/rs.3.rs-3797511/v1

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Background and Purpose

inflammation is considered responsible for the pathogenesis of epilepsy. Inflammation plays a pivotal role in epilepsy.Various inflammatory markers are known related to epilepsy. No study has yet investigated the relationship between epilepsy and systemic inflammation response index (SIRI) and systemic immune-inflammation index (SII). This study aimed to evaluate the systemic inflammation response index (SIRI) and systemic immune-inflammation index (SII) in epilepsy.

Methods

This study included patients with epilepsy who presented to the neurology department within last five years.

Results

The epileptic group included 110 patients (63 males, 47 females) and the control group included 65 healthy individuals (33 males, 32 females). The mean age of the epilepsy (n = 110) and healthy control group (n = 65) was 33.0 ± 14.0 and 34.0 ± 10.2 years, respectively. SII and SIRI levels were 603.0 ± 469,6 and 1,42 ± 1,08 in the epileptic group and 567.6 ± 218.9 and 1,16 ± 0,58 in the control group. There were no significant differences between two groups (p > 0.05).

Conclusion

Our study results suggest that although is an associated with inflammation, SII and SIRI are still not an ideal biomarker for epileptic patients. This study is important because it investigated SII and SIRI in patients with epilepsy for the first time. Further prospective studies involving a larger sample size should be performed to have more valuable results for interpretation.

systemic inflammation response index (SIRI) and systemic immune-inflammation index (SII)

epilepsy

Epilepsy disease, which is one of the most common problems related to the brain, affects more than 70 million people all over the world, especially during attacks, with the possibility of causing generalized seizures that cannot be stopped, it can cause patients to be exposed to risky situations that may require intensive care. It is the most common serious brain disease in the world. It is common in children, teenagers and the elderly. There is a predisposition to spontaneous epileptic seizures in brain cells. It can cause a wide range of neurobiological, cognitive, psychological, social, occupational and economic problems. The impact on a person's quality of life may be greater than that of some other chronic diseases. Epilepsy affects education, job opportunities, independence, ability to drive and obtaining a driver's license (1, 2).Clinical and experimental studies support the hypothesis that inflammatory processes in the brain involve common and critical pathways with mechanisms involved in the pathophysiology of seizures and epilepsy (3).Systemic inflammatory disorders can cause peripheral inflammation, which may contribute to the formation of inflammatory mediators. Peripheral and central inflammation may cause disruption of the blood brain barrier due to the regulation of inflammatory mediators. the inflammatory pathway is thought to have a key role (4). The destruction of the blood-brain barrier allows leukocyte infiltration, which produces neuronal hyperexcitability and regulates inflammatory mediators. Unregulated peripheral and central inflammation and disruption of the bloodbrain barrier can lead to morphological synaptic changes in the hippocampus and consequent development of epilepsy (5). Inflammation in the CNS(Central Nervous System) occurs due to leaky blood brain barrier and has been reported to participate in the induction of seizures as well as the progression of epileptogenesis (6).Chemokines expressed from microglia, astrocyte and endothelial cells in the brain direct inflammatory mediators and activate leukocytes. Many variants of chemokines can alter neuronal physiology (7). In addition to inflammatory cytokines, prostaglandins are one of the most important factors in the inflammatory process. Epileptogenesis is a picture characterized by complex, irregular inflammatory molecules and pathways found in both the nervous system and systemic tissues. The main theme of the subject is inflammation, and the data in the literature clearly reported that inflammation may play an important role in epilepsy, but there are debates about whether inflammation causes epilepsy and whether inflammation is the result or cause of epilepsy (8).The systemic inflammation response index (SIRI) was described as a novel inflammatory marker by Qi et al (9). SIRI, which is based on a combination of neutrophils, monocytes, and lymphocytes, is a prognostic indicator in patients with malignancy (10). Another inflammatory marker, the systemic immune-inflammation index (SII), which includes neutrophils, platelets, and lymphocytes, has also been reported. The utility of SII as a prognostic predictor in various cancers has also been assessed (11, 12, 13, 14, 15, 16).Furthermore, previous studies reported the association of SII with clinical outcomes of ischemic and hemorrhagic stroke(17, 18, 19). SIRI and SII can be used to comprehensively evaluate the inflammation status better than NLR, LMR, and PLR. To the best of our knowledge, the prognostic significance of SIRI and SII in patients who have undergone epilepsy has not yet been reported.

This study was approved by the local institutional review board of our center. We retrospectively reviewed prospectively collected data from the epilepsy database of our institution. Patients undergoing epilepsy from January 2018 to September 2022 were recruited. The following patients were excluded: patients with missing laboratory data or < 3 months follow-up; patients with signs of infection prior to blood sample collection, including pneumonia, urinary tract infection, pancreatitis, cholangitis and other active concomitant infections; patients with a history of autoimmune disease or malignancy; patients with a history of hematological disorders or immunosuppressive therapy; and patients with severe renal or hepatic dysfunction. Laboratory Measurements Laboratory findings, including high-sensitivity C-reactive protein, erythrocyte sedimentation rate, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, hemoglobin, platelets, and white blood cell differential counts were identified in peripheral venous blood samples acquired on admission.SIRI and SII were defined as follows: SIRI: neutrophil count x monocyte count/lymphocyte count and SII: platelet count x neutrophil count/lymphocyte count, respectively (9, 10, 11, 12).

Epilepsy type was divided into 3 groups as 1: focal 2: complex partial 3: generalized. Seizure frequency was divided into 3 groups as 1: seizures within 3 months, 2: seizures within 3–12 months, 3: seizures for 1 year or more(Fig. 1,2,3,4,5,6).

Statistical analyses were performed using MedCalc Statistical Software version v20.113 (MedCalc, Belgium). The variables were investigated using both visual (histograms and probability plots) and analytical methods (the Kolmogorov-Smirnov test) to determine whether or not they were distributed normally. Categorical measurements were reported as numbers and percentages. The chi-square test was used to compare categorical measurements Continuous variables that showed normal distribution were compared using the Student t-test and ANOVA (Bon Ferroni test was used for post hoc analysis), whereas the Mann–Whitney U test and Kruskal–Wallis test were used for abnormally distributed samples. The probability of making a type I error (alpha, significance) is 0.05 in all tests.

A total of 110 patients with epilepsy were enrolled. The baseline characteristics of patients are summarized in Table 1. The epileptic group included 110 patients (63 males, 47 females) and the control group included 65 healthy individuals (33 males, 32 females). In terms of laboratory findings, the platelet count was significantly decreased in the patients group compared with control group(242.1 ± 61.1, (279.2 ± 64.9 respectively; P = 0.001). The patient group had significantly higher PDW( Platelet distribution width )level compared with control group (16.9 ± 0.9, 16.2 ± 1.79 respectively; P = 0.0028). SII and SIRI levels were 603.0 ± 469,6 and 1,42 ± 1,08 in the epileptic group and 567.6 ± 218.9 and 1,16 ± 0,58 in the control group. There were no significant differences between two groups (p > 0.05). In addition, there was no statistical difference in the type and frequency of epilepsy in the SII and SIRI indices. SII Type 1,SII type 2,SII type 3 (196.5- 599.6,172.6–925.0, 40.0 -2405 ), and SII frequency 1, 2, 3 (104.6-2405.5, 172.6-1950.8,40.0-925.7)(P = 0.507, P = 0.333 respectively).SIRI Type 1,SIRI type 2,SIRI type 3 (0.45–2.12,0.23–2.29,0.0- 5.48), and SIRI frequency 1, 2, 3 (0.0-5.4,0.23–3.16,0.19–2.49)( P = 0.413, P = 0.118 respectively). (Fig. 1,2,3,4,5,6).

Table 1
	Patient N:110	Control N:65	p
Gender (Female)	42.7% (47)	49.2% (32)	0,610
Age	33.0 ± 14.0	34.0 ± 10.2	0,120
ALT	21.3 ± 22.3	22.0 ± 11.2	0,03
AST	22.6 ± 12	21.0 ± 4.9	0,301
Creatinin	0.69 ± 0.46	0.69 ± 0.16	0,04
Wbc	7.39 ± 2.30	7.43 ± 1.78	0,908
Rbc	4.68 ± 0.69	4.73 ± 0.50	0,642
Htc	40.1 ± 4.6	39.9 ± 4.4	0,803
Plt	242.1 ± 61.1	279.2.1 ± 64.9	0,001
Mpv	8.93 ± 1.07	8.75 ± 0.90	0,275
Pdw	16.9 ± 0.9	16.2 ± 1.7	0,0028
Neu	4,45 ± 1.95	4.39 ± 1.35	0,820
Lym	2.20 ± 1.16	2.21 ± 0.50	0,953
Mon	0.58 ± 0.21	0.55 ± 0.16	0,331
Crp	4.39 ± 5.51	1.94 ± 1.12	0,083
SIRI	1.42 ± 1.08	1.16 ± 0.58	0,541
SII Type Frequency	603 ± 469.6 1-N:23(20.9%) 2-N:84(76.9%) 3-N:3(2.7%) 1-N:78(70.9%) 2-N:7(6.4%) 3-N:25(22.7%) SIRI Type 1,SIRI type 2,SIRI type 3 (0.45–2.12,0.23–2.29,0.0- 5.48) SIRI frequency 1,SIRI frequency 2,SIRI frequency 3 (0.0-5.4,0.23–3.16,0.19–2.49) SII Type 1,SII type 2,SII type 3 (196.5- 599.6,172.6–925.0, 40.0 -2405 ) SII frequency 1, SII frequency2, SIRI frequency3 (104.6-2405.5, 172.6-1950.8,40.0-925.7)	567.6 ± 218.9 - - - - - -	0,568 - - - - - - 0,413 0,118 0,507 0,333

In the present study, we investigated the association between inflammatory markers including SIRI and SII in patients whit epilepsy. SII and SIRI do not increase significantly in patients with epilepsy. The platelet count was significantly decreased in the patients group compared with control group. The patient group had significantly higher PDW level compared with control group. SIRI is a novel inflammatory marker that can be used to evaluate inflammation status better than NLR( Neutrophil/lymphocyte ratio) or LMR (lymphocyte/monocyte ratio) because SIRI (neutrophil x monocyte/lymphocyte) reflects the status of 3 factors concurrently, whereas NLR (neutrophil/lymphocyte) and LMR (lymphocyte/monocyte) contain 2 factors. Thus, SII, which is based on a combination of neutrophils, lymphocytes, and platelets, is thought to reflect better than other inflammatory markers such as NLR, LMR, and PLR (Platelet/lymphocyte ratio).

A recent meta-analysis supports the idea that there is a relationship between NLR values and epilepsy disease, and it is claimed that this rate increases in epilepsy patients. It is stated that NLR can be a promising biomarker that can be easily obtained with a simple blood test. This meta-analysis includes 4 retrospective and 3 prospective studies. When the patients in all of these studies were combined, the number of patients was less than 400. In our study, which we conducted using peripheral blood hemogamy parameters and more sensitive indices, we could not find a statistically significant correlation between inflammatory markers and epileptic patient group (20).

Platelets can be considered as not just a hemostatic player but an inflammatory cell. It has crucial roles to play in the pathogenesis of various inflammatory conditions(21, 22, 23). Platelet distribution width (PDW) is a marker of platelet anisocytosis, which describes the size distribution of platelets produced by megakaryocytes and increases upon platelet activation. Mean platelet volume (MPV) and platelet distribution width (PDW), which are morphometric indices, are also quantitative measures of the size distribution and variability of platelets.Observed PDW change in patients suffering from numerous diseases .Platelets are cell fragments involved in the formation of blood clots, which are also related to inflammatory events. Mean platelet volume (MPV) and platelet distribution width (PDW) are commonly used to estimate the functional changes and activation of platelets. MPV may increase with acute myocardial infarction, renal artery stenosis, preeclampsia,many neurological disorders such as acute ischemic stroke and intracerebral hemorrhage (24, 25, 26). In the literature, the issue of MPV and PDW in adult epileptic patients has not been resolved yet. Our work is therefore an important milestone. Antiepileptic drug use may affect these immune cells both directly and indirectly and may regulate their function. In our study, we saw the change in platelet count and PDW.Considering that the MPV is normal with the decrease in the platelet count, the high PDW can be interpreted as a change due to the antiepileptics used rather than platelet activation.

Depending on the current results, we can speculate that inflammation in the brain in epilepsy does not affect on the relative levels of circulation inflammatory molecules. However, results related to epilepsy, including ours, should be evaluated cautiously because this study included a small number of patients.

Limitations Important limitations of this study are its retrospective nature and relatively small sample size. More accurate data may be obtained in prospective studies involving larger numbers of epileptic patients.

Conclusion Inflammatory parameters, SII and SIRI do not increase significantly in patients with epilepsy. It cannot be used as a marker for seizure frequency and seizure type. Further prospective studies involving a larger sample size should be performed to have more valuable results for interpretation. Despite limitations, this is the first study to demonstrate the SIRI and SII index in patients who underwent epilepsy.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Author Contribution

AS designed the study, wrote the main manuscript. PB and ZSŞ collected the data. ŞÖK analyzed the data. All authors reviewed the manuscript.

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No competing interests reported.

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Are Systemic Inflammation Response Index and Systemic Immune-Inflammation Index an ideal biomarker for epileptic patients?

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INTRODUCTION

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