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ORIGINAL ARTICLE
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Platelet-to-lymphocyte ratio as a predictor to differentiate between childhood migraine and tension-type headache


 Department of Pediatric Neurology, Haseki Education and Training Hospital, İstanbul, Turkey

Date of Submission07-Aug-2021
Date of Decision04-Jan-2022
Date of Acceptance02-Mar-2022
Date of Web Publication12-Jul-2022

Correspondence Address:
Senem Ayca,
Department of Pediatric Neurology, Haseki Education and Training Hospital, Sultangazi, İstanbul
Turkey
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpn.JPN_162_21

 

   Abstract 

Background: Migraine and tension-type headache (TTH) are common neurological disorders in children, and it is often difficult to differentiate between them. As migraine is associated with inflammation, hematological parameters, which can be used to indicate systemic inflammation, may be useful in its diagnosis. This study investigated whether hematological parameters could be used to predict childhood migraines and distinguish them from TTH. Materials and Methods: A total of 186 children (59 diagnosed with migraine, 65 diagnosed with TTH, and 62 healthy children) were included in the study. Hematological parameters, neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) of the participants were measured and compared. Results: Children with migraine had a significantly higher (p = 0.002) PLR than those with TTH. A comparison of NLR of three groups did not significantly differ (p = 0.18). Conclusion: Our findings indicate that childhood migraine is characterized by an elevated PLR, marking this parameter as a potential predictor of the disorder. Moreover, this work suggests that PLR could function as a simple, inexpensive biomarker for distinguishing between childhood migraine and TTH.


Keywords: Childhood migraine, platelet to lymphocyte ratio, tension-type headache



How to cite this URL:
Ayca S, Ayta S. Platelet-to-lymphocyte ratio as a predictor to differentiate between childhood migraine and tension-type headache. J Pediatr Neurosci [Epub ahead of print] [cited 2022 Dec 9]. Available from: https://www.pediatricneurosciences.com/preprintarticle.asp?id=350278





   Introduction Top


Migraine and tension-type headache (TTH) are the most common headache disorders in children. Unfortunately, differentiating these headaches in children is complicated because the accurate collection of diagnostic information from children regarding the characteristics and symptoms of the headache, such as photophonophobia or nausea, can be difficult.

Although the etiology of migraine is still debated, the current theory proposes a key role for inflammatory processes. Studies have shown that certain hematological parameters can be used as an indicator of systemic inflammation.[1],[2],[3],[4] This work investigated the relationship between migraine headaches and hematological parameters to identify a predictor for childhood migraine and distinguish it from TTH.


   Materials and Methods Top


All participants were between 10 and 18 years of age and patients at the Haseki Education and Training Hospital. The study included 59 children diagnosed with migraine and 65 children diagnosed with TTH from the pediatric neurology clinic. Migraine and TTH diagnoses were in accordance with the criteria of the International Classification of Headache Disorders 3rd Edition (ICHD-3) and the diagnostic ICHD-3 beta version, respectively.[5] The control group included 62 healthy children admitted to the child outpatient clinic with nonspecific complaints. Children with chronic diseases, psychiatric disorders or currently taking medication were excluded from the study.

A detailed diagnostic history was collected from the participants diagnosed with migraine headaches, including family history of migraine, number of migraine attacks, description of pain (e.g., localization, characteristics, duration, and frequency), history of aura, symptomology (e.g., nausea, vomiting, photophobia, phonophobia, and worsening pain with physical activity), and response to analgesic therapy. Also, a detailed diagnostic history was collected from the participants diagnosed with TTH, including the number of attacks, the description of pain, and symptomology. Participants who had a chronic type (≥15 days/months on average for >3 months) of migraine or TTH were excluded from the study. All the participants of the migraine group had an episodic type of headache and all the participants of the TTH group had at least 10 episodes of headache occurring frequently (≥1 but <l5 day/month for at least three months). Venous blood samples were obtained between episodic attacks. Hemogram samples from all participants were collected in K2-EDTA-containing blood collection tubes (Becton, Dickinson U.K. Ltd., Berkshire, UK) and examined by using an LH 780 hematology analyzer (Beckman Coulter, Inc., Indianapolis, IN, USA) to measure the neutrophil, lymphocyte, and platelet levels, the mean platelet volume (MPV), the neutrophil/lymphocyte ratio (NLR), and the platelet/lymphocyte ratio (PLR).

Statistical analysis

Statistical analyses were performed by using SPSS v.15.0 for Windows (SPSS Inc., Chicago, IL, USA). Categorical variables were converted to percentages and reported as mean ± standard deviation. Numerical variables were reported as minimum, maximum, median, and interquartile range. Numerical variables for >2 groups were compared by using one-way analysis of variance (ANOVA) for normal distribution or the Kruskal-Wallis test for non-normal distributions. The Bonferroni test was used for the parametric subgroup analyses, whereas the Mann-Whitney U test with Bonferroni correction was used for the nonparametric analyses. Spearman’s correlation was used to describe relationships between the data, as parametric test conditions were not met. Group ratios were compared by using the χ2 test. The statistical significance level of alpha was accepted as p < 0.05.


   Results Top


The mean age of the healthy children and that of the children diagnosed with migraine or TTH were 13.5 ± 1.9, 13.5 ± 2.4, and 13.9 ± 2.0 years, respectively. Females comprised more than half of the migraine, TTH, and healthy groups, accounting for 41 (69.5%), 41 (63.1%), and 38 (61.3%) children, respectively. There was no significant difference between the age (p = 0.43) and sex (p = 0.61) of the three groups [Table 1].
Table 1: Demographic features of the migraine, TTH, and control groups

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Most of the children diagnosed with migraine (58 children, 98.3%) had photophonophobia, nausea, and vomiting (47 subjects, 79.7%). Children with TTH did not exhibit photophonophobia, nausea, or vomiting. Most of the children with migraine had a pulsatile type of pain (55 children, 93.2%) and all of them exhibited moderate or severe intensity of pain. All of the children with TTH had mild or moderate intensity of pressing, as well as a nonpulsatile headache. The worsening with physical activity was observed in 47 (79.7%) children with migraine; however, in children with TTH, it was not influenced by routine activity. The mean value of attack frequency in children with migraine was 5.5 ± 1.7 (1–10) days for a month with a mean duration of 15.7 ± 16.0 (1–72) h. The mean value of attack frequency in children with TTH was 5.8 ± 1.9 (1–10) days for a month with a mean duration of 19.8 ± 21.3 (1–96) h.

Significant differences in the mean lymphocyte level (p = 0.046) and PLR (p = 0.002) were observed between the migraine and TTH groups. Children with migraine had a significantly lower lymphocyte level and a significantly higher (p = 0.002) PLR than those with TTH. A comparison of NLR (p = 0.18) of the three groups did not show significant differences [Table 2], [Table 3]. There was no significant relationship between the PLR and the duration (p = 0.748) or the number (p = 0.920) of headaches.
Table 2: Comparison of the hematological parameters of migraine, TTH, and control groups

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Table 3: Comparison of LYM and PLR values of migraine, TTH, and control groups

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PLR was determined as a cutoff value of “110.5” for the childhood migraine to distinguish between the childhood migraine and TTH, with a sensitivity of 76.5% and a specificity of 56.5% (p < 0.001).


   Discussion Top


Migraine pathophysiology is believed to be associated with reduced antioxidant levels and increased oxidative stress. These conditions result in neuroinflammation that is characterized by neuropeptide release, leading to vasodilation, edema, and mast cell degranulation, which activate the trigeminovascular system.[6],[7] Hematological parameters, which can be used to indicate systemic inflammation, may be useful in the diagnosis of childhood migraine. Our findings indicate that childhood migraine is characterized by an elevated PLR, marking this parameter as a potential predictor of the disorder.

The role of neuroinflammation in migraine pathogenesis in adults and the identification of potential inflammation biomarkers have recently been investigated. Several hematological parameters that can function as biomarkers for neuroinflammation are easily evaluated by a simple, complete blood count. For example, NLR and PLR are common inflammation biomarkers for neurological disorders.[8],[9],[10],[11] Yazar et al. found that neutrophil, NLR, and PLR levels were elevated in adult migraine cases.[4] Karabulut et al. reported higher NLR values for adults experiencing migraines than a healthy control group.[3] Sarıçam et al. observed that PLR levels were significantly higher in subjects experiencing migraine without aura than in a healthy control group.[1] Although the NLR levels did not differ significantly between the children diagnosed with migraine and those diagnosed with TTH in our study, the PLR levels were significantly higher in the migraine group. In some studies, PLR was found to be a better predictor of inflammation than NLR; we also found that PLR could be a superior prognostic biomarker to NLR in childhood migraine.[12],[13]

The work by Danese et al. suggests an association between platelets and migraine.[14] The impairment of platelet function and increased platelet activation was reported to play a role in inflammation.[15],[16] Poyrazoğlu et al. observed increased MPV levels in children with migraine. Similarly, Varol et al. found that adult patients with migraine have higher MPV levels.[2],[17] However, the MPV levels did not differ significantly across the groups in our study.

In our study, the mean frequency of headache was 5.5 days for a month in children with migraine and there was no significant relationship between PLR and headache frequency. Children with chronic migraine and TTH were not included in our study, and the hemogram samples were taken between the headache episodes. PLR values may be more informative in the presence of headache episode or chronic migraine. A significant cutoff value of PLR could practically help in the clinic to distinguish between childhood migraine and TTH. The cutoff value of PLR was found to be “110.5” in our study, and PLR levels higher than “110.5” could be considered a potential predictor for childhood migraine.

Migraine and TTH symptoms can overlap, and making differentiation between the two headache types could be difficult. Owing to these difficulties, predictors that are capable of distinguishing childhood migraine from TTH are necessary. Our findings suggest that an elevated PLR is indicative of childhood migraine and could function as a unique predictor for distinguishing this disorder from TTH.

Study limitations and strengths

There are a limited number of studies evaluating the relationship between childhood migraine and hematological parameters. To the best of our knowledge, this is the first study comparing the hematological parameters between children suffering from migraine and those suffering from TTH. However, as the sample size is small, larger and more extensive studies will be needed to detail neuroinflammation in children with migraine and to confirm the value of PLR and other diagnostic predictors.


   Conclusion Top


Distinguishing between childhood migraine and TTH is often difficult. As such, a high number of children suffering from headaches cannot be accurately diagnosed. This study found that PLR distinguished between childhood migraine and TTH; therefore, PLR could be considered a valuable, new predictor aiding in the accurate diagnosis of childhood migraine.

Authors’ contribution

Surgical and Medical Practices: S.A., S.A.; Concept: S.A, S.A; Design: S.A, S.A.; Data Collection or Processing: S.A., S.A.; Analysis or Interpretation: S.A., S.A.; Literature Search: S.A., S.A.; Writing: S.A.

All authors have read and approved the final version of the article.

Ethical approval

The study design was approved by the Ethical Committee of the Haseki Sultangazi Education and Training Hospital (Date: 03.06.20; Protocol No.: 2020–101).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Sarıcam G. Relationship between migraine headache and hematological parameters. Acta Neurol Belg 2021;121:899-905.  Back to cited text no. 1
    
2.
Poyrazoğlu HG, Ozturk AB. Predictive value of laboratory parameters in childhood migraine. Acta Neurol Belg 2019;6:1-8.  Back to cited text no. 2
    
3.
Karabulut KU, Egercioglu TU, Uyar M, Ucar Y. The change of neutrophils/lymphocytes ratio in migraine attacks: a case-controlled study. Ann Med Surg (Lond) 2016;10:52-6.  Back to cited text no. 3
    
4.
Yazar HO, Yazar T, Aygün A, Kaygisiz Ş, Kirbaş D. Evaluation of simple inflammatory blood parameters in patients with migraine. Ir J Med Sci 2020;189:677-83.  Back to cited text no. 4
    
5.
Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013;33:629-808.  Back to cited text no. 5
    
6.
Ramachandran R. Neurogenic inflammation and its role in migraine. Semin Immunopathol 2018;40:301-14.  Back to cited text no. 6
    
7.
Waeber C, Moskowitz MA. Migraine as a inflammatory disorder. Neurology 2005;64:9-15.  Back to cited text no. 7
    
8.
Yang DH, Qian MZ, Wei MM, Li J, Yu MM, Lu XM, et al. The correlation of neutrophil-to-lymphocyte ratio with the presence and activity of myasthenia gravis. Oncotarget 2017;8:76099-107.  Back to cited text no. 8
    
9.
Kirlioglu SS, Balcioglu YH, Kalelioglu T, Erten E, Karamustafalioglu N. Comparison of the complete blood count-derived inflammatory markers in bipolar patients with manic and mixed episodes. Bratisl Lek Listy 2019;120:195-9.  Back to cited text no. 9
    
10.
Eryigit U, Altunayoglu Cakmak V, Sahin A, Tatli O, Pasli S, Gazioglu G, et al. The diagnostic value of the neutrophil-lymphocyte ratio in distinguishing between subarachnoid hemorrhage and migraine. Am J Emerg Med 2017;35: 1276-80.  Back to cited text no. 10
    
11.
Park MG, Kim MK, Chae SH, Kim HK, Han J, Park KP. Lymphocyte-to-monocyte ratio on day 7 is associated with outcomes in acute ischemic stroke. Neurol Sci 2018;39: 243-9.  Back to cited text no. 11
    
12.
Zhang WW, Liu KJ, Hu GL, Liang WJ. Preoperative platelet/lymphocyte ratio is a superior prognostic factor compared to other systemic inflammatory response markers in ovarian cancer patients. Tumour Biol 2015;36:8831-7.  Back to cited text no. 12
    
13.
Huang Q, Diao P, Li CL, Peng Q, Xie T, Tan Y, et al. Preoperative platelet-lymphocyte ratio is a superior prognostic biomarker to other systemic inflammatory response markers in non-small cell lung cancer. Medicine (Baltimore) 2020;99: e18607.  Back to cited text no. 13
    
14.
Danese E, Montagnana M, Lippi G. Platelets and migraine. Thromb Res 2014;134:17-22.  Back to cited text no. 14
    
15.
Lechner H, Ott E, Fazekas F, Pilger E. Evidence of enhanced platelet aggregation and platelet sensitivity in migraine patients. Cephalalgia 1985;5:89-91.  Back to cited text no. 15
    
16.
Zeller JA, Lindner V, Frahm K, Baron R, Deuschl G. Platelet activation and platelet-leucocyte interaction in patients with migraine. Subtype differences and influence of triptans. Cephalalgia 2005;25:536-41.  Back to cited text no. 16
    
17.
Varol S, Akıl E, Çevik MU, Çelepkolu T, Yücel Y, Tanrıverdi MH, et al. Investigation of mean platelet volume and platelet count in the blood of patient with migraine. Turk J Neurol 2013;19:90-92.  Back to cited text no. 17
    



 
 
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  [Table 1], [Table 2], [Table 3]



 

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