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The relationship between leukocyte-based inflammation indices and essential tremor

Year 2024, , 473 - 480, 30.09.2024
https://doi.org/10.18663/tjcl.1503503

Abstract

Aim: Previous limited studies have indicated that pro-inflammatory cytokines are elevated in patients with essential tremor (ET). This elevation could lead to a more pronounced inflammatory response in these patients. Thus, this study aimed to investigate the relationship between leukocyte-based inflammatory indices and ET.
Material and Methods: In this retrospective study, 103 patients diagnosed with ET between January 2021 and December 2023 were included, along with 103 healthy individuals who were matched by age and gender, participated in check-up programs, and had no other comorbidities. To evaluate tremor severity, the Fahn-Tolosa-Marin (FTM) tremor rating scale was utilized. The leukocyte-based inflammatory indices were calculated as follows: NLR= neutrophils / lymphocytes, PLR = platelets / lymphocytes, systemic immune-inflammation index (SII) = platelets × neutrophils / lymphocytes, and systemic inflammatory response index (SIRI) = neutrophils × monocytes / lymphocytes.
Results: The ET group exhibited higher levels of leukocytes, their subtypes, CRP and leukocyte-based inflammatory indices compared to the control group. Increased CRP (OR= 3.71, p < 0.001) and SIRI (OR= 11.73, p < 0.001) levels were independent predictors of ET. In predicting ET. SIRI exhibited superior diagnostic performance compared to other inflammatory parameters. The threshold for SIRI levels was set at 7 and above, with a sensitivity of 85.4% and a specificity of 82.5%. There was a positive correlation between SIRI and FTM scores.
Conclusion: Among the leukocyte-based inflammation indices, SIRI demonstrated superior diagnostic performance in predicting ET and was associated with higher tremor severity. This suggests that inflammation may play a potential role in the pathophysiology of ET.

Ethical Statement

The study was performed in accordance with the Declaration of Helsinki, and was approved by the Istanbul Atlas University Medicine Hospital Clinical Research Ethics Committee (Date: 15.02.2023, Decision No: E-22686390-050.99-24274).

Project Number

E-22686390-050.99-24274

References

  • Shanker V. Essential tremor: diagnosis and management. BMJ. 2019; 366: l4485, DOI: 10.1136/bmj.l4485.
  • Louis ED, Huey ED, Gerbin M, et al. Depressive traits in essential tremor: impact on disability, quality of life, and medication adherence. Eur J Neurol. 2012; 19(10): 1349-1354, DOI: 10.1111/j.1468-1331.2012.03774.x.
  • Huang H, Yang X, Zhao Q, et al. Prevalence and Risk Factors of Depression and Anxiety in Essential Tremor Patients: A Cross-Sectional Study in Southwest China. Front Neurol. 2019; 10: 1194, DOI: 10.3389/fneur.2019.01194.
  • Louis ED. Non-motor symptoms in essential tremor: A review of the current data and state of the field. Parkinsonism Relat Disord. 2016; 22 Suppl 1(0 1): S115-118, DOI: 10.1016/j.parkreldis.2015.08.034.
  • Shill HA, Adler CH, Beach TG. Pathology in essential tremor. Parkinsonism Relat Disord. 2012; 18 Suppl 1: S135-137, DOI: 10.1016/S1353-8020(11)70042-6.
  • Lyman M, Lloyd DG, Ji X, et al. Neuroinflammation: the role and consequences. Neurosci Res. 2014; 79: 1-12, DOI: 10.1016/j.neures.2013.10.004.
  • Gelders G, Baekelandt V, Van der Perren A. Linking Neuroinflammation and Neurodegeneration in Parkinson's Disease. J Immunol Res. 2018; 2018: 4784268, DOI: 10.1155/2018/4784268.
  • McGeer PL, Itagaki S, Boyes BE, et al. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology. 1988; 38(8): 1285-1291, DOI: 10.1212/wnl.38.8.1285.
  • Muruzheva ZM, Ivleva IS, Traktirov DS, et al. The relationship between serum interleukin-1beta, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha levels and clinical features in essential tremor. Int J Neurosci. 2022; 132(11): 1143-1149, DOI: 10.1080/00207454.2020.1865952.
  • Tak AZA, Sengul Y. Evaluation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in essential tremor. Ideggyogy Sz. 2019; 72(1-2): 33-38, DOI: 10.18071/isz.72.0033.
  • Bhatia KP, Bain P, Bajaj N, et al. Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society. Mov Disord. 2018; 33(1): 75-87, DOI: 10.1002/mds.27121.
  • Jankovic J, Tolosa E. Parkinson's disease and movement disorders: Lippincott Williams & Wilkins; 2007.
  • Schober P, Boer C, Schwarte LA. Correlation Coefficients: Appropriate Use and Interpretation. Anesth Analg. 2018; 126(5): 1763-1768, DOI: 10.1213/ANE.0000000000002864.
  • DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988; 44(3): 837-845.
  • Eidson LN, Kannarkat GT, Barnum CJ, et al. Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson's disease. J Neuroinflammation. 2017; 14(1): 164, DOI: 10.1186/s12974-017-0935-1.
  • Muruzheva ZM, Traktirov DS, Tumashova OS, et al. Cluster analysis of clinical, biochemical and electrophysiological features of essential tremor patients. Exploratory study. Clin Neurol Neurosurg. 2022; 222: 107472, DOI: 10.1016/j.clineuro.2022.107472.
  • Kamel AS, Farrag SM, Mansour HM, et al. Dapagliflozin modulates neuronal injury via instigation of LKB1/p-AMPK/GABA(B) R2 signaling pathway and suppression of the inflammatory cascade in an essential tremor rat model. Expert Opin Ther Targets. 2023; 27(4-5): 373-392, DOI: 10.1080/14728222.2023.2206955.
  • Chen XL, Wang Y, Peng WW, et al. Effects of interleukin-6 and IL-6/AMPK signaling pathway on mitochondrial biogenesis and astrocytes viability under experimental septic condition. Int Immunopharmacol. 2018; 59: 287-294, DOI: 10.1016/j.intimp.2018.04.020.
  • Alard JE, Ortega-Gomez A, Wichapong K, et al. Recruitment of classical monocytes can be inhibited by disturbing heteromers of neutrophil HNP1 and platelet CCL5. Sci Transl Med. 2015; 7(317): 317ra196, DOI: 10.1126/scitranslmed.aad5330.
  • Ramirez GA, Manfredi AA, Maugeri N. Misunderstandings Between Platelets and Neutrophils Build in Chronic Inflammation. Front Immunol. 2019; 10: 2491, DOI: 10.3389/fimmu.2019.02491.
  • Domer D, Walther T, Moller S, et al. Neutrophil Extracellular Traps Activate Proinflammatory Functions of Human Neutrophils. Front Immunol. 2021; 12: 636954, DOI: 10.3389/fimmu.2021.636954.
  • Clark LN, Gao Y, Wang GT, et al. Whole genome sequencing identifies candidate genes for familial essential tremor and reveals biological pathways implicated in essential tremor aetiology. EBioMedicine. 2022; 85: 104290, DOI: 10.1016/j.ebiom.2022.104290.
  • Gao Y, Ding L, Liu J, et al. Exploring the diagnostic markers of essential tremor: A study based on machine learning algorithms. Open Life Sci. 2023; 18(1): 20220622, DOI: 10.1515/biol-2022-0622.
  • Rotzius P, Thams S, Soehnlein O, et al. Distinct infiltration of neutrophils in lesion shoulders in ApoE-/- mice. Am J Pathol. 2010; 177(1): 493-500, DOI: 10.2353/ajpath.2010.090480.
  • Bancaro N, Cali B, Troiani M, et al. Apolipoprotein E induces pathogenic senescent-like myeloid cells in prostate cancer. Cancer Cell. 2023; 41(3): 602-619 e611, DOI: 10.1016/j.ccell.2023.02.004.
  • Jimenez-Jimenez FJ, Alonso-Navarro H, Garcia-Martin E, et al. Genomic Markers for Essential Tremor. Pharmaceuticals (Basel). 2021; 14(6), DOI: 10.3390/ph14060516.
  • Alard J-E, Ortega-Gomez A, Wichapong K, et al. Recruitment of classical monocytes can be inhibited by disturbing heteromers of neutrophil HNP1 and platelet CCL5. Science translational medicine. 2015; 7(317): 317ra196-317ra196.
  • Ramirez GA, Manfredi AA, Maugeri N. Misunderstandings between platelets and neutrophils build in chronic inflammation. Frontiers in immunology. 2019; 10: 489488.
  • Bhatia KP, Bain P, Bajaj N, et al. Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society. Movement disorders. 2018; 33(1): 75-87.
  • DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988: 837-845.

Lökosit bazlı enflamasyon indeksleri ile esansiyel tremor arasındaki ilişki

Year 2024, , 473 - 480, 30.09.2024
https://doi.org/10.18663/tjcl.1503503

Abstract

Amaç: Daha önce yapılan sınırlı çalışmalar, esansiyel tremor (ET) hastalarında proinflamatuar sitokinlerin arttığını göstermiştir. Bu artış, bu hastalarda daha belirgin bir inflamatuar yanıtı tetikleyebilir. Bu nedenle, bu çalışma lökosit bazlı inflamasyon indeksleri ile ET arasındaki ilişkiyi araştırmayı amaçladı.
Gereç ve Yöntemler: Bu retrospektif çalışmaya, Ocak 2021 ile Aralık 2023 arasında ET tanısı alan 103 hasta ile yaş ve cinsiyet açısından eşleştirilen, check-up programlarına katılan ve başka komorbiditesi olmayan 103 sağlıklı birey dahil edilmiştir. Tremor şiddetini değerlendirmek için Fahn-Tolosa-Marin (FTM) tremor derecelendirme skalası kullanılmıştır. Lökosit bazlı inflamasyon indeksleri şu şekilde hesaplanmıştır: NLR = nötrofiller / lenfositler, PLR = trombositler / lenfositler, sistemik immün-enflamasyon indeksi (SII) = trombositler × nötrofiller / lenfositler ve sistemik inflamatuar yanıt indeksi (SIRI) = nötrofiller × monositler / lenfositler.
Bulgular: ET grubunda lökosit, alt tipleri, CRP ve lökosit bazlı inflamasyon indeksleri kontrol grubuna göre daha yüksek seviyelerdeydi. Artmış CRP (OR = 3.71, p < 0.001) ve SIRI (OR = 11.73, p < 0.001) seviyeleri, ET’nin bağımsız öngörücüleri olarak belirlendi. ET’yi öngörmede, SIRI diğer inflamatuar parametrelere göre üstün bir tanısal performans sergilemiştir. SIRI seviyeleri için eşik değer 7 ve üzeri olarak belirlendi ve bu değer %85.4 duyarlılık ve %82.5 özgüllük gösterdi. SIRI ile FTM skorları arasında pozitif bir korelasyon bulundu.
Sonuçlar: Lökosit bazlı inflamasyon indeksleri arasında, SIRI ET’yi öngörmede üstün bir tanısal performans sergilemiş ve daha yüksek tremor şiddeti ile ilişkilendirilmiştir. Bu da inflamasyonun ET’nin patofizyolojisinde potansiyel bir rol oynayabileceğini düşündürmektedir.

Project Number

E-22686390-050.99-24274

References

  • Shanker V. Essential tremor: diagnosis and management. BMJ. 2019; 366: l4485, DOI: 10.1136/bmj.l4485.
  • Louis ED, Huey ED, Gerbin M, et al. Depressive traits in essential tremor: impact on disability, quality of life, and medication adherence. Eur J Neurol. 2012; 19(10): 1349-1354, DOI: 10.1111/j.1468-1331.2012.03774.x.
  • Huang H, Yang X, Zhao Q, et al. Prevalence and Risk Factors of Depression and Anxiety in Essential Tremor Patients: A Cross-Sectional Study in Southwest China. Front Neurol. 2019; 10: 1194, DOI: 10.3389/fneur.2019.01194.
  • Louis ED. Non-motor symptoms in essential tremor: A review of the current data and state of the field. Parkinsonism Relat Disord. 2016; 22 Suppl 1(0 1): S115-118, DOI: 10.1016/j.parkreldis.2015.08.034.
  • Shill HA, Adler CH, Beach TG. Pathology in essential tremor. Parkinsonism Relat Disord. 2012; 18 Suppl 1: S135-137, DOI: 10.1016/S1353-8020(11)70042-6.
  • Lyman M, Lloyd DG, Ji X, et al. Neuroinflammation: the role and consequences. Neurosci Res. 2014; 79: 1-12, DOI: 10.1016/j.neures.2013.10.004.
  • Gelders G, Baekelandt V, Van der Perren A. Linking Neuroinflammation and Neurodegeneration in Parkinson's Disease. J Immunol Res. 2018; 2018: 4784268, DOI: 10.1155/2018/4784268.
  • McGeer PL, Itagaki S, Boyes BE, et al. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology. 1988; 38(8): 1285-1291, DOI: 10.1212/wnl.38.8.1285.
  • Muruzheva ZM, Ivleva IS, Traktirov DS, et al. The relationship between serum interleukin-1beta, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha levels and clinical features in essential tremor. Int J Neurosci. 2022; 132(11): 1143-1149, DOI: 10.1080/00207454.2020.1865952.
  • Tak AZA, Sengul Y. Evaluation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in essential tremor. Ideggyogy Sz. 2019; 72(1-2): 33-38, DOI: 10.18071/isz.72.0033.
  • Bhatia KP, Bain P, Bajaj N, et al. Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society. Mov Disord. 2018; 33(1): 75-87, DOI: 10.1002/mds.27121.
  • Jankovic J, Tolosa E. Parkinson's disease and movement disorders: Lippincott Williams & Wilkins; 2007.
  • Schober P, Boer C, Schwarte LA. Correlation Coefficients: Appropriate Use and Interpretation. Anesth Analg. 2018; 126(5): 1763-1768, DOI: 10.1213/ANE.0000000000002864.
  • DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988; 44(3): 837-845.
  • Eidson LN, Kannarkat GT, Barnum CJ, et al. Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson's disease. J Neuroinflammation. 2017; 14(1): 164, DOI: 10.1186/s12974-017-0935-1.
  • Muruzheva ZM, Traktirov DS, Tumashova OS, et al. Cluster analysis of clinical, biochemical and electrophysiological features of essential tremor patients. Exploratory study. Clin Neurol Neurosurg. 2022; 222: 107472, DOI: 10.1016/j.clineuro.2022.107472.
  • Kamel AS, Farrag SM, Mansour HM, et al. Dapagliflozin modulates neuronal injury via instigation of LKB1/p-AMPK/GABA(B) R2 signaling pathway and suppression of the inflammatory cascade in an essential tremor rat model. Expert Opin Ther Targets. 2023; 27(4-5): 373-392, DOI: 10.1080/14728222.2023.2206955.
  • Chen XL, Wang Y, Peng WW, et al. Effects of interleukin-6 and IL-6/AMPK signaling pathway on mitochondrial biogenesis and astrocytes viability under experimental septic condition. Int Immunopharmacol. 2018; 59: 287-294, DOI: 10.1016/j.intimp.2018.04.020.
  • Alard JE, Ortega-Gomez A, Wichapong K, et al. Recruitment of classical monocytes can be inhibited by disturbing heteromers of neutrophil HNP1 and platelet CCL5. Sci Transl Med. 2015; 7(317): 317ra196, DOI: 10.1126/scitranslmed.aad5330.
  • Ramirez GA, Manfredi AA, Maugeri N. Misunderstandings Between Platelets and Neutrophils Build in Chronic Inflammation. Front Immunol. 2019; 10: 2491, DOI: 10.3389/fimmu.2019.02491.
  • Domer D, Walther T, Moller S, et al. Neutrophil Extracellular Traps Activate Proinflammatory Functions of Human Neutrophils. Front Immunol. 2021; 12: 636954, DOI: 10.3389/fimmu.2021.636954.
  • Clark LN, Gao Y, Wang GT, et al. Whole genome sequencing identifies candidate genes for familial essential tremor and reveals biological pathways implicated in essential tremor aetiology. EBioMedicine. 2022; 85: 104290, DOI: 10.1016/j.ebiom.2022.104290.
  • Gao Y, Ding L, Liu J, et al. Exploring the diagnostic markers of essential tremor: A study based on machine learning algorithms. Open Life Sci. 2023; 18(1): 20220622, DOI: 10.1515/biol-2022-0622.
  • Rotzius P, Thams S, Soehnlein O, et al. Distinct infiltration of neutrophils in lesion shoulders in ApoE-/- mice. Am J Pathol. 2010; 177(1): 493-500, DOI: 10.2353/ajpath.2010.090480.
  • Bancaro N, Cali B, Troiani M, et al. Apolipoprotein E induces pathogenic senescent-like myeloid cells in prostate cancer. Cancer Cell. 2023; 41(3): 602-619 e611, DOI: 10.1016/j.ccell.2023.02.004.
  • Jimenez-Jimenez FJ, Alonso-Navarro H, Garcia-Martin E, et al. Genomic Markers for Essential Tremor. Pharmaceuticals (Basel). 2021; 14(6), DOI: 10.3390/ph14060516.
  • Alard J-E, Ortega-Gomez A, Wichapong K, et al. Recruitment of classical monocytes can be inhibited by disturbing heteromers of neutrophil HNP1 and platelet CCL5. Science translational medicine. 2015; 7(317): 317ra196-317ra196.
  • Ramirez GA, Manfredi AA, Maugeri N. Misunderstandings between platelets and neutrophils build in chronic inflammation. Frontiers in immunology. 2019; 10: 489488.
  • Bhatia KP, Bain P, Bajaj N, et al. Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society. Movement disorders. 2018; 33(1): 75-87.
  • DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988: 837-845.
There are 30 citations in total.

Details

Primary Language English
Subjects Neurology and Neuromuscular Diseases
Journal Section Research Article
Authors

Demet Aygün 0000-0002-1828-1811

Bagnu Dundar 0000-0003-1052-5911

Project Number E-22686390-050.99-24274
Publication Date September 30, 2024
Submission Date September 7, 2024
Acceptance Date September 25, 2024
Published in Issue Year 2024

Cite

APA Aygün, D., & Dundar, B. (2024). The relationship between leukocyte-based inflammation indices and essential tremor. Turkish Journal of Clinics and Laboratory, 15(3), 473-480. https://doi.org/10.18663/tjcl.1503503
AMA Aygün D, Dundar B. The relationship between leukocyte-based inflammation indices and essential tremor. TJCL. September 2024;15(3):473-480. doi:10.18663/tjcl.1503503
Chicago Aygün, Demet, and Bagnu Dundar. “The Relationship Between Leukocyte-Based Inflammation Indices and Essential Tremor”. Turkish Journal of Clinics and Laboratory 15, no. 3 (September 2024): 473-80. https://doi.org/10.18663/tjcl.1503503.
EndNote Aygün D, Dundar B (September 1, 2024) The relationship between leukocyte-based inflammation indices and essential tremor. Turkish Journal of Clinics and Laboratory 15 3 473–480.
IEEE D. Aygün and B. Dundar, “The relationship between leukocyte-based inflammation indices and essential tremor”, TJCL, vol. 15, no. 3, pp. 473–480, 2024, doi: 10.18663/tjcl.1503503.
ISNAD Aygün, Demet - Dundar, Bagnu. “The Relationship Between Leukocyte-Based Inflammation Indices and Essential Tremor”. Turkish Journal of Clinics and Laboratory 15/3 (September 2024), 473-480. https://doi.org/10.18663/tjcl.1503503.
JAMA Aygün D, Dundar B. The relationship between leukocyte-based inflammation indices and essential tremor. TJCL. 2024;15:473–480.
MLA Aygün, Demet and Bagnu Dundar. “The Relationship Between Leukocyte-Based Inflammation Indices and Essential Tremor”. Turkish Journal of Clinics and Laboratory, vol. 15, no. 3, 2024, pp. 473-80, doi:10.18663/tjcl.1503503.
Vancouver Aygün D, Dundar B. The relationship between leukocyte-based inflammation indices and essential tremor. TJCL. 2024;15(3):473-80.


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