Association between interictal high Plasma Calcitonin Gene-Related Peptide and cognition affection in childhood migraine

Association between interictal high Plasma Calcitonin Gene-Related Peptide and cognition affection in childhood migraine | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association between interictal high Plasma Calcitonin Gene-Related Peptide and cognition affection in childhood migraine ahmed gamal, Hala Mahmoud El khawas, Sherien Mohamed Farag Borham, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7448411/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Feb, 2026 Read the published version in The Egyptian Journal of Neurology, Psychiatry and Neurosurgery → Version 1 posted 9 You are reading this latest preprint version Abstract Background Cognitive impairment is recognized as a comorbidity in childhood migraine. Calcitonin Gene-Related Peptide (CGRP) has been involved in migraine pathophysiology, but its relationship with cognitive dysfunction remains unclear. This study investigates the association between interictal CGRP plasma levels and cognitive impairment in pediatric migraineurs. Methods This is a cross-sectional study which was conducted on 89 participants (44 migraine patients and 45 controls). Demographic data, migraine severity and disability were assessed, and patients were furthermore classified to chronic or episodic migraineurs. plasma CGRP level was measured, and neuropsychological functions were evaluated using digit span, similarities, Benton visual retention, and Trail Making Tests. Statistical comparisons were performed between groups. Results Migraine patients showed significantly lower performance on digit span, similarities, and Benton visual retention tests and took significantly longer time to complete Trail making test A and B. There were no significant differences in demographic data, including age, sex, and BMI, between the patients and control groups. Plasma CGRP levels were significantly higher in migraine patients compared to controls and chronic compared to episodic migraineures. CGRP levels correlated positively with migraine severity, frequency, and disability. Conclusion Interictal high plasma CGRP levels were correlated with affecting attention, psychomotor speed, and visual memory. CGRP may serve as a biomarker for migraine-associated cognitive impairment. CGRP Childhood Cognitive dysfunction Pediatric migraine PedMIDAS Figures Figure 1 Figure 2 Figure 3 Figure 4 INTRODUCTION Migraine is a debilitating neurological disorder that affects children and adults, and often significantly disrupts daily life 1 . In pediatric patients, migraine is not only associated with pain but also difficulties with attention, memory, and executive functioning. Cognitive impairment can interfere with academic performance and scholastic achievement, making it a substantial area of study 2 .One of the leading keys in the pathophysiology of migraine type headache is calcitonin gene-related peptide (CGRP), an important neuropeptide that contributes in pain transmission. it was shown that CGRP levels rise during migraine attacks, suggesting its involvement in migraine firing. In adults, CGRP has been widely studied, and therapies targeting CGRP pathways have shown promising results in migraine management. However, its role in childhood migraine, particularly in relation to cognitive function, remains obscured 3 Children with migraine often report poverty in concentration, slower processing speed, and memory lapses, yet the mechanisms underlying these cognitive changes are not fully understood 4 SUBJECTS AND METHODS This study was a cross-sectional which conducted at the “Neurology Department, Ain Shams University Hospitals” between July 2022 and December 2023. Eighty-nine participants, including 44 pediatric patients diagnosed with migraine and 45 healthy controls matched for age and sex were recruited. Through the assessment of multiple cognitive domains including attention, memory, processing speed, and abstract thinking alongside CGRP level measurements. The research focuses on evaluating cognitive function during interictal periods in pediatric migraine patients and exploring the relationship between these cognitive measures and plasma CGRP concentrations. The study was conducted in accordance with the Declaration of Helsinki. It was approved by the Ethics committee of the Faculty of Medicine, Ain Shams University and informed consent was obtained from every patient and control. Inclusion and Exclusion Criteria A total of 44 pediatric patients with migraine were recruited for this study based on well-defined eligibility criteria. The inclusion criteria required participants to be between 8 and 18 years of age, ensuring reliability and validity for neuropsychological assessment. All included patients were drug-naïve regarding prophylactic migraine medications at the time of evaluation. The diagnosis of pediatric migraine was established according to the criteria of the International Classification of Headache Disorders, 3rd Edition (Beta Version) 5 . To avoid confounding effects of the postdromal phase on cognitive performance and neurochemical markers, cognitive testing and blood sampling were conducted at least two days following the last migraine attack, during a headache-free (interictal) period. The exclusion criteria comprised a history of severe head trauma, epilepsy, the presence of psychiatric disorders, neurological or neuroradiological abnormalities, or intellectual disability. Additionally, children with major systemic illness, chronic medical conditions, or congenital or chromosomal anomalies were excluded to minimize confounding variables. A control group of 45 healthy age-matched subjects without any history of headaches was recruited randomly from the same geographical and sociodemographic area. Informed written consent was obtained from all participants and/or their legal guardians, in accordance with ethical guidelines. All participants (both patients and controls) underwent a comprehensive evaluation, including a detailed medical history, neurological examination, and structured headache assessment. Headache features including attack frequency (number of attacks per month), duration (in hours), intensity, associated symptoms, and degree of disability were systematically documented. Headache intensity was rated using an 11-point numeric pain scale, with 0 representing no headache and 10 indicating the most severe pain 5 . The functional impact of headache was measured using the Pediatric Migraine Disability Assessment Scale (PedMIDAS), a validated tool to quantify headache-related disability in school-aged children and adolescents 6 . Neuropsychological evaluation was conducted by a trained psychologist. “Digit Span from Wechsler intelligence scale for (Verbal immediate memory and working memory), Similarities from Wechsler intelligence scale for (Abstract thinking), Benton Visual Retention Test for (Visual memory) and Trial Making Test (A and B) for (Attention and psychomotor speed)”. These were traditional and widely used neuropsychological instruments for children and adolescents with migraine 4 . Laboratory assessment Plasma CGRP Measurement Blood samples were collected from each participant between 9:00 and 11:00 AM after an overnight fast to account for circadian variations in biomarker levels. Three milliliters of venous blood were drawn into EDTA-coated tubes, centrifuged, and stored at − 80°C until analysis. In the Central Laboratory, Clinical Pathology Department, Ain Shams University Hospitals plasma calcitonin gene-related peptide (CGRP) levels were measured using an enzyme-linked immunosorbent assay (ELISA) using a commercially available ELISA kit provided by Bioassay Technology laboratory, Jiaxing, Zhejiang Province, China. Statistical Analysis Data was analyzed using IBM SPSS Statistics, Version 27. Quantitative variables were tested for normality and presented as mean ± standard deviation (SD) or median (interquartile range, IQR) depending on data distribution. Categorical variables were expressed as frequencies and percentages. RESULTS As shown in table (1), our patients group age range was 8 – 17.9 with mean age (13.41 ± 2.69) and control group age range 8.9 – 17.8 with mean age (12.89 ± 2.51). Males were 10 (22.7%) and female were 34 (77.3%) in patients group. In control group males were 19 (42.2%) and females were 26 (57.8%). There was no significant difference between patients and control group regarding age, gender and BMI . Table ( 1 ): Comparison between control group and patients group regarding demographic data, anthropometric measures and general examination. Patients group Control group Test value P-value Sig. No.= 44 No.= 45 Age (yrs) Mean ± SD 13.41 ± 2.69 12.89 ± 2.51 -0.941• 0.349 NS Range 8 – 17.9 8.9 – 17.8 Gender Female 34 (77.3%) 26 (57.8%) 3.849 * 0.050 NS Male 10 (22.7%) 19 (42.2%) BMI Mean ± SD 21.21 ± 3.44 20.34 ± 2.31 -1.405• 0.164 NS Range 18.4 – 38.02 17.9 – 28.5 Body mass index (BMI) P-value > 0.05: Non-significant; P-value < 0.05: Significant; P-value < 0.01: Highly significant *: Chi-square test; •: Independent t-test Regarding figure (1), twenty (45.5%) of patients had positive family history and 24 (54.5%) of them were without positive family history of migraine. figure (2) Of all migraineurs, chronic patients were 20 (45.5%) but episodic patients were 24 (54.5%). Neuropsychological evaluation of Verbal immediate memory and working memory by digit span test, Abstract thinking by similarities test and visual memory by Benton A and B test 9, 10, 30, 27 respectively were lower in patients group, additionally attention and psychomotor speed by Trail making test A and B test time 68 and 225 respectively took longer duration in patients group than control group 10, 12, 45, 45, 53, 161 respectively. Table (2) showed that there was significant difference between patients and control regard digit span test with (p-value 0.028) and the difference were highly significant between them regarding similarities test (p-value<0.001), Benton visual retention test A and B test (p-value<0.001) and TMT A and B test (p-value<0.001). Table (2): Comparison between control group and patients group regarding neuropsychological evaluation Patients group Control group Test value P-value Sig. No.= 44 No.= 45 Digit span test Median (IQR) 9 (8 – 10) 10 (8 – 12) 2.191• 0.028 S Range 4 – 15 4 – 17 Similarities test Median (IQR) 10 (9 – 11) 12 (11 – 15) 4.607• <0.001 HS Range 6 – 15 9 – 20 Benton visual retention-A No 30 (68.2%) 45 (100%) 16.991 * <0.001 HS Yes 14 (31.8%) 0 (0%) Benton visual retention -B No 27 (61.4%) 45 (100%) 21.491 * <0.001 HS Yes 17 (38.6%) 0 (0%) Trail making test-A Mean ± SD 68.73 ± 23.06 53.78 ± 16.79 -3.502• 0.001 HS Range 38 – 126 20 – 100 Trail making test-B Mean ± SD 225.25 ± 50.72 161.07 ± 76.56 -4.651• 0.05: Non-significant; P-value < 0.05: Significant; P-value < 0.01: Highly significant *: Chi-square test; •: Independent t-test; ≠: Mann-Whitney test As regarding table (3), CGRP level was higher in patients 247,05 compared to control group 27.57 with highly significant difference (p-value <0.001). Table (3): Comparison between control group and patients group regarding CGRP plasma level Patients group Control group Test value P-value Sig. No.= 44 No.= 45 CGRP Median (IQR) 247.05 (141.75 - 366.6) 27.57 (17.98 - 33.8) -8.075≠ 0.05: Non-significant; P-value < 0.05: Significant; P-value < 0.01: Highly significant ≠: Mann-Whitney test The ROC curve showed that the best cut of point between patients and control groups regarding CGRP level was more than 60.66 with sensitivity of 100% and specificity of 97.78% and AUC of 0.997 figure (3). The ROC curve showed that the best cut of point between chronic and episodic patients regarding CGRP level was >166.3 with sensitivity of 90% and specificity of 62.50% and AUC of 0.683 figure (4). These results in table (4), shown that there was interictal high CGRP in all patients highly correlated with younger age of onset of migraine (p-value 0.002), more sever attacks (p-value <0.001) and more disable attacks with PEDMIDAS (p-value <0.001) . Also, it correlated with longer attack duration without medication (p-value0.037) . AGE and BMI had shown no clinical correlation. Table (4): Correlation between CGRP with demographic data, intensity and disability among all patients group CGRP plasma level r p-value AGE -0.252 0.104 BMI -0.058 0.708 Attack duration Without medic 0.316* 0.037 Age of onset of migraine(years) -0.456** 0.002 Duration of disease(yrs) 0.232 0.129 11-point scale(intensity) 0.531** <0.001 pedMiDAs 0.540** <0.001 Peadiatric Migraine Disability Assessment Scale (PEDMIDAS) *: Significant at P <0.05; **: Significant at p <0.01 These results in table (5), showed that higher interictal CGRP level highly correlated with more affection psychomotor speed and attention by Trail making test A and B test (p-value 0.002 and <0.001) . Also revealed correlation with affected working and immediate memory tested by digit span test (p-value 0.015) and visual memory by Benton visual retention-B test (p-value 0.023) . Similarities test for abstract thinking had shown no clinical correlation. Table (5): Correlation between CGRP with the neuropsychological parameters among all patients group CGRP plasma level r p-value Digit span test -0.364* 0.015 Similarities test -0.115 0.458 Benton visual retention test -A 0.289 0.057 Benton visual retention test -B 0.342* 0.023 Trail Making Test-A 0.454** 0.002 Trail Making Test -B 0.565** <0.001 *: Significant at P <0.05; **: Significant at p <0.01 Spearman correlation coefficients DISCUSSION The study population age range was 8–17.9 with mean age (13.41 ± 2.69) and control group age range 8.9–17.8 with mean age (12.89 ± 2.51). Female were 34 (77.3%) more than Males 10 (22.7%) in migraine group which suggest that female gender is a risk factor for migraine and this in agreement with observed difference in early report between both gender, and this may be due to hormonal changes at puberty 7 . However, clinical gender-related differences in pain perception are less clear, previous study found that there was no gender difference in pain perception result in peadiatric studies 8 . These differences may be explained by the different ages of the populations and different methodologies used. This study revealed that there was no significant difference between patients and control group regarding BMI, and in line with our result no significant difference has been noted previously 5 as regard BMI. However, an early literature noted that BMI was to be significantly higher in the migraine group and this may be due to difference methodologies and study settings 9 . Thus, it is possible that only patients with severe migraine headache symptoms, either chronic or episodic, were included in this study. We found that 20 (45.5%) of patients had positive family history and 24 (54.5%) of them without positive family history of migraine thus, family history may be an initial risk factor for migraine and this finding in agreement with early study which found that (32.7%) of migraine patients with positive family history 9 . Also, this finding corroborates findings reports that migraine expression depends on a robust genetic predisposition 10 . Thus, family history is postulated to be a strong risk factor, and this work confirms this hypothesis. In the present work, we also found Significant difference between patients and control group regarding digit span test (Verbal immediate memory and working memory), and the difference were highly significant between them regarding similarities test (abstract thinking), Benton visual retention test A and B test (visual memory) and Trail making test A and B test (Attention and psychomotor speed).this work results are consistent with a literature cleared that there were significant difference between children with migraine and control group as regard attention, executive function, visual and working memory 4 . There is no consistent data in literature on abstract thinking in children with migraine. Although, the exact mechanism regarding association between migraine and cognitive impairment is still not fully understood, there is information for alterations in brain functional reorganization of cognitive cerebral networks. Also shown that, the predominant involvement of processing speed, learning and memory could suggest a preferential dysfunction of the prefrontal and temporal cortices and or frontal subcortical white matter during migraine attack 11 . We observed in this work that CGRP level was higher in patients group to healthy volunteers with highly significance difference with p-value < 0.001. The ROC curve showed that the best cut of point between patients and control groups regarding CGRP level was more than 60.66 with sensitivity of 100% and specificity of 97.78%. Additionally, there was a statistically significant difference between chronic and episodic patients of migraine regarding CGRP level which was higher in chronic patients. The ROC curve showed that the best cut of point between chronic and episodic patients regarding CGRP level was > 166.3 with sensitivity of 90% and specificity of 62.50% and AUC of 0.683. Similarly, previous findings revealed that plasma CGRP level was significantly higher in patients than control and could help in diagnosis of migraine and differentiate between chronic and episodic migraine in children. However, CGRP sampling was during and between migraine attacks 5 , 12 . It was reported that CGRP concentrations in patients with episodic and chronic migraine was higher compared to healthy volunteers 13 , but another one found no difference between migraineurs and control group, between migraine with and without aura, between episodic and chronic migraine, and between ictal and interictal phases and not show interictally elevated CGRP concentrations in participants with frequent or chronic migraine 14 . The discrepancies between studies can be explained by differences in sample sizes, designs, participant selection criteria, blood processing protocols, and assays used for the CGRP measuring 15 . Additionally, commercially available CGRP assays are variable and not well validated. Most assays might detect not only an entire peptide but also its fragments and relative peptides, such as βCGRP and amylin. Standardization of blood processing protocols and thorough validation of assays are needed to achieve better comparisons between studies 16 . We found in this work that higher interictal CGRP level inversely proportionate with younger age of onset of migraine and direct proportionate with more frequent, severe, disabled and longer attacks of headache in all patients. It was early revealed that serum CGRP level showed a positive relationship with the severity of pain and disability but not headache duration, however sampling of CGRP was ictal and these studied patients were adult 17 . Also, our findings confirm reports which found that childhood migraine tends to be more chronic, frequent, sever and disable with higher CGRP level during and between attacks 5 . In contrast, other literature found only a weak positive correlation was apparent between age and CGRP concentration 18 . Moreover, there is no association between interictally elevated CGRP concentrations in participants with migraine and headache monthly frequency, intensity, and impact on quality of life 14 . In this work we reported that higher CGRP level proportionate with longer duration of Trail making test with a highly significant correlation between interictal CGRP and TMT A and B (impairment of attention and psychomotor speed) and inversely proportionate with achievement in Digit span and Benton visual retention test with statistically significant correlation with digit span test (affection working memory) and Benton visual retention test-B (affection visual memory). To our best knowledge, there was no data in literature about the correlation between interictal CGRP level and cognition affection. These findings provide new insight and indirectly suggest that CGRP play an important role in the pathogenesis of migraine itself and may have a role in affection cognition network in migraine. These findings are strengthened by reports about mechanisms of CGRP mediating pediatric migraine which involved in vasodilation theory, neurogenic inflammation, peripheral and central sensitization, and cortical spread depression (CSD), and nitric oxide generation 12 . Our findings are important especially for young and school age children who cannot clearly describe their headache symptoms and may be disabled by migraine. Also, it may provide a new insight into clinical practice for the diagnosis, prognosis and management in childhood migraine. Interictal CGRP is recommended for early detection of cognitive impairment beside diagnosis and differentiation between migraine types. Limitations of the Study Several limitations of this study should be acknowledged. First, the sample was restricted to patients recruited from a tertiary hospital, who may have experienced more intense migraine attacks than the general population. This may account for the higher rate of chronicity and frequency observed among participants. Second, the relatively small sample size may have introduced statistical bias. Third, the symptoms of migraine attacks described by younger children may have been unclear or inconsistently reported. Despite these limitations, the study had notable strengths. Unlike many studies that utilize non-standardized classification systems, which hinder comparison across research, this study employed standardized diagnostic criteria. Furthermore, participants with psychiatric disorders were excluded, thereby minimizing confounding effects on neuropsychological evaluation. CONCLUSION This study highlights significant cognitive impairments in pediatric migraine patients. Higher CGRP levels were strongly correlated with worse cognitive performance, particularly in tasks assessing attention, working memory, and visual memory, thus may take part in prognostication of learning difficulties in children. These results suggest that a broader function of CGRP in migraine pathophysiology beyond pain perception, potentially contributing to cognitive impairment. Additionally, suggesting that CGRP is a good indicator for diagnosis pediatric migraine, differentiation between episodic and chronic migraine type-headache. Further research is warranted to explore CGRP as a biomarker for cognitive dysfunction in migraine and to determine whether targeting CGRP pathways could help preserve cognitive Interictal CGRP is recommended for early detection of cognitive impairment besides diagnosis and differentiation between migraine types, especially for younger children who cannot express their sufferings. Declarations Ethics approval and consent to participate All procedures performed in the study were in accordance with the ethical standards of the faculty of medicine, Ain Shams university research and ethical committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. We obtained approval from research ethics committee no. FWA 000017585. On 28/7/2022 (Approval Number: FMASU MD 157a/2022/2023). Consent to participate: Written informed consent was obtained from participants for participation. We obtained approval from research ethics committee no. FWA 000017585. On 28/7/2022 (Approval Number: FMASU MD 157a/2022/2023). Consent for publication: Not applicable Funding This research did not receive any specific grant from funding agencies in the public, commercial, or nonprofit sectors. Author Contribution A.G Conceptualization, data collection, manuscript writing.N.S, H.M, S.M, E.M supervision and analysis of data, revision of manuscript.Y.M supervision and interpretation of CGRP samplingA.K revision of manuscript, supervision on psychometric tests.All authors have agreed to conditions noted on the Authorship Agreement Form and have read and approved the final version submitted.The content of the manuscript has not been published or submitted for publication elsewhere Acknowledgement The authors would like to thank the Neurology department and headache team, faculty of medicine, Ain Shams University, for their help in recruiting patients. References Khan A, Liu S, Tao F. Current trends in pediatric migraine: Clinical insights and therapeutic strategies. Brain Sci. 2025;15(3):280. Termine C, Bartoli B, Agosti MA, et al. Cognitive impairment in children and adolescents with migraine. Front Neurol. 2018;9:667. Huang Y, Li H, Yu Q, et al. 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Acta Neurol Belg. 2020;120:1123–31. Gil-Gouveia R, Martins IP. Cognition and cognitive impairment in migraine. Curr Pain Headache Rep. 2019;23:1–10. Gu L, Wang Y, Shu H. Association between migraine and cognitive impairment. J Headache Pain. 2022;23(1):88. Liu J, Wang G, Dan Y, et al. CGRP and PACAP-38 play an important role in diagnosing pediatric migraine. J Headache Pain. 2022;23(1):68. Charles A, Pozo-Rosich P. Targeting calcitonin gene-related peptide: A new era in migraine therapy. Lancet. 2019;394(10210):1765–74. Lee MJ, Lee SY, Cho S, et al. Feasibility of serum CGRP measurement as a biomarker of chronic migraine: A critical reappraisal. J Headache Pain. 2018;19:1–8. Tchivileva IE, Johnson KW, Chai X, et al. Evaluation of plasma calcitonin gene-related peptide as a biomarker for painful temporomandibular disorder and migraine. J Pain Res. 2023;16:2331–46. Cheng Y, Gao Y, Zhang S, et al. Detection of calcitonin gene-related peptide based on increased antigen-driven interaction with antibody variable regions. Front Bioeng Biotechnol. 2024;12:1395330. Vural S, Albayrak L. Can calcitonin gene-related peptide (CGRP) and pentraxin-3 (PTX-3) be useful in diagnosing acute migraine attack? J Recept Signal Transduct. 2022;42(6):562–6. Fekrazad R, Sardarian A, Azma K, et al. Interictal levels of calcitonin gene-related peptide in gingival crevicular fluid of chronic migraine patients. Neurol Sci. 2018;39:1217–23. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 09 Feb, 2026 Read the published version in The Egyptian Journal of Neurology, Psychiatry and Neurosurgery → Version 1 posted Editorial decision: Revision requested 08 Oct, 2025 Reviews received at journal 07 Oct, 2025 Reviews received at journal 05 Oct, 2025 Reviewers agreed at journal 05 Oct, 2025 Reviewers agreed at journal 28 Sep, 2025 Reviewers invited by journal 25 Sep, 2025 Editor assigned by journal 03 Sep, 2025 Submission checks completed at journal 03 Sep, 2025 First submitted to journal 24 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7448411","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":508710161,"identity":"dc07dffd-066f-4e2e-a6b2-e0f4def22ef0","order_by":0,"name":"ahmed 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Mahmood","lastName":"Ali","suffix":""},{"id":508710166,"identity":"164cbb8f-95a6-468e-82d1-d441acda6c8c","order_by":5,"name":"Abdel Gawad khalifa Abou Zied","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"prefix":"","firstName":"Abdel","middleName":"Gawad khalifa Abou","lastName":"Zied","suffix":""},{"id":508710167,"identity":"888db05d-f56f-4bf6-ae94-3eea94e9f05f","order_by":6,"name":"Nahed Salah El-Din Ahmed","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"prefix":"","firstName":"Nahed","middleName":"Salah El-Din","lastName":"Ahmed","suffix":""}],"badges":[],"createdAt":"2025-08-24 22:23:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7448411/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7448411/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s41983-026-01084-6","type":"published","date":"2026-02-09T15:56:50+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":90485675,"identity":"888c7b4c-6f03-4257-83cd-1b6f83164ebb","added_by":"auto","created_at":"2025-09-03 08:49:29","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":27833,"visible":true,"origin":"","legend":"\u003cp\u003ePercentage of patients with family history among the studied patients\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7448411/v1/b02fee737608e6e0b836969e.png"},{"id":90487150,"identity":"8fe1f583-72ec-4b8f-989d-adf097170495","added_by":"auto","created_at":"2025-09-03 08:57:29","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":27383,"visible":true,"origin":"","legend":"\u003cp\u003eType of migraine among the studied patients\u003c/p\u003e","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7448411/v1/d22a6212bee95e065649c7fa.png"},{"id":90487149,"identity":"a41af44c-71b3-45e8-9d4e-0c45a7c86097","added_by":"auto","created_at":"2025-09-03 08:57:29","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":29107,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver operating characteristic curve (ROC) for interictal CGRP plasma level to differentiate between patients group and control group\u003c/p\u003e","description":"","filename":"figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7448411/v1/df6da0ce81180f766b47d6bd.png"},{"id":90485678,"identity":"0532aa4c-780b-4d41-b1ba-32f6b66b5358","added_by":"auto","created_at":"2025-09-03 08:49:29","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":25860,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver operating characteristic curve (ROC) for CGRP plasma level to differentiate chronic group from episodic group.\u003c/p\u003e","description":"","filename":"figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-7448411/v1/877baaa3523fd5c0698d41d9.png"},{"id":102785183,"identity":"1da2b983-ca27-44e7-a188-d3afef0885d7","added_by":"auto","created_at":"2026-02-16 16:01:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":962927,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7448411/v1/a6f2ecdb-7ed1-4738-8a68-3fbd60b16c13.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association between interictal high Plasma Calcitonin Gene-Related Peptide and cognition affection in childhood migraine","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eMigraine is a debilitating neurological disorder that affects children and adults, and often significantly disrupts daily life \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. In pediatric patients, migraine is not only associated with pain but also difficulties with attention, memory, and executive functioning. Cognitive impairment can interfere with academic performance and scholastic achievement, making it a substantial area of study \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e .One of the leading keys in the pathophysiology of migraine type headache is calcitonin gene-related peptide (CGRP), an important neuropeptide that contributes in pain transmission. it was shown that CGRP levels rise during migraine attacks, suggesting its involvement in migraine firing. In adults, CGRP has been widely studied, and therapies targeting CGRP pathways have shown promising results in migraine management. However, its role in childhood migraine, particularly in relation to cognitive function, remains obscured \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eChildren with migraine often report poverty in concentration, slower processing speed, and memory lapses, yet the mechanisms underlying these cognitive changes are not fully understood \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e"},{"header":"SUBJECTS AND METHODS","content":"\u003cp\u003eThis study was a cross-sectional which conducted at the \u0026ldquo;Neurology Department, Ain Shams University Hospitals\u0026rdquo; between July 2022 and December 2023. Eighty-nine participants, including 44 pediatric patients diagnosed with migraine and 45 healthy controls matched for age and sex were recruited. Through the assessment of multiple cognitive domains including attention, memory, processing speed, and abstract thinking alongside CGRP level measurements. The research focuses on evaluating cognitive function during interictal periods in pediatric migraine patients and exploring the relationship between these cognitive measures and plasma CGRP concentrations.\u003c/p\u003e\u003cp\u003e The study was conducted in accordance with the Declaration of Helsinki. It was approved by the Ethics committee of the Faculty of Medicine, Ain Shams University and informed consent was obtained from every patient and control.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eInclusion and Exclusion Criteria\u003c/h2\u003e\u003cp\u003eA total of 44 pediatric patients with migraine were recruited for this study based on well-defined eligibility criteria. The inclusion criteria required participants to be between 8 and 18 years of age, ensuring reliability and validity for neuropsychological assessment. All included patients were drug-na\u0026iuml;ve regarding prophylactic migraine medications at the time of evaluation. The diagnosis of pediatric migraine was established according to the criteria of the International Classification of Headache Disorders, 3rd Edition (Beta Version) \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. To avoid confounding effects of the postdromal phase on cognitive performance and neurochemical markers, cognitive testing and blood sampling were conducted at least two days following the last migraine attack, during a headache-free (interictal) period.\u003c/p\u003e\u003cp\u003eThe exclusion criteria comprised a history of severe head trauma, epilepsy, the presence of psychiatric disorders, neurological or neuroradiological abnormalities, or intellectual disability. Additionally, children with major systemic illness, chronic medical conditions, or congenital or chromosomal anomalies were excluded to minimize confounding variables.\u003c/p\u003e\u003cp\u003eA control group of 45 healthy age-matched subjects without any history of headaches was recruited randomly from the same geographical and sociodemographic area. Informed written consent was obtained from all participants and/or their legal guardians, in accordance with ethical guidelines.\u003c/p\u003e\u003cp\u003eAll participants (both patients and controls) underwent a comprehensive evaluation, including a detailed medical history, neurological examination, and structured headache assessment. Headache features including attack frequency (number of attacks per month), duration (in hours), intensity, associated symptoms, and degree of disability were systematically documented. Headache intensity was rated using an 11-point numeric pain scale, with 0 representing no headache and 10 indicating the most severe pain \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. The functional impact of headache was measured using the Pediatric Migraine Disability Assessment Scale (PedMIDAS), a validated tool to quantify headache-related disability in school-aged children and adolescents \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eNeuropsychological evaluation\u003c/b\u003e was conducted by a trained psychologist. \u0026ldquo;Digit Span from Wechsler intelligence scale for (Verbal immediate memory and working memory), Similarities from Wechsler intelligence scale for (Abstract thinking), Benton Visual Retention Test for (Visual memory) and Trial Making Test (A and B) for (Attention and psychomotor speed)\u0026rdquo;. These were traditional and widely used neuropsychological instruments for children and adolescents with migraine \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eLaboratory assessment\u003c/h3\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003ePlasma CGRP Measurement\u003c/h2\u003e\u003cp\u003eBlood samples were collected from each participant between 9:00 and 11:00 AM after an overnight fast to account for circadian variations in biomarker levels. Three milliliters of venous blood were drawn into EDTA-coated tubes, centrifuged, and stored at \u0026minus;\u0026thinsp;80\u0026deg;C until analysis.\u003c/p\u003e\u003cp\u003e In the Central Laboratory, Clinical Pathology Department, Ain Shams University Hospitals plasma calcitonin gene-related peptide (CGRP) levels were measured using an enzyme-linked immunosorbent assay (ELISA) using a commercially available ELISA kit provided by Bioassay Technology laboratory, Jiaxing, Zhejiang Province, China.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eData was analyzed using IBM SPSS Statistics, Version 27. Quantitative variables were tested for normality and presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or median (interquartile range, IQR) depending on data distribution. Categorical variables were expressed as frequencies and percentages.\u003c/p\u003e\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eAs shown in \u003cstrong\u003etable (1),\u003c/strong\u003e our patients group age range was 8 \u0026ndash; 17.9 with mean age (13.41 \u0026plusmn; 2.69) and control group age range 8.9 \u0026ndash; 17.8 with mean age (12.89 \u0026plusmn; 2.51). Males were 10 (22.7%) and female were 34 (77.3%) in patients group. In control group males were 19 (42.2%) and females were 26 (57.8%). There was no significant difference between patients and control group regarding age, gender and BMI\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003cstrong\u003e):\u003c/strong\u003e Comparison between control group and patients group regarding demographic data, anthropometric measures and general examination.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 28px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTest value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSig.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.= 44\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.= 45\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 13px;\"\u003e\n \u003cp\u003eAge (yrs)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eMean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e13.41 \u0026plusmn; 2.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e12.89 \u0026plusmn; 2.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-0.941\u0026bull;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.349\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e8 \u0026ndash; 17.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e8.9 \u0026ndash; 17.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 13px;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e34 (77.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e26 (57.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3.849\u003cstrong\u003e\u003cspan dir=\"RTL\"\u003e*\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e10 (22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e19 (42.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 13px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eMean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e21.21 \u0026plusmn; 3.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e20.34 \u0026plusmn; 2.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-1.405\u0026bull;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.164\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e18.4 \u0026ndash; 38.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e17.9 \u0026ndash; 28.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eBody mass index (BMI)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;P-value \u0026gt; 0.05: Non-significant; P-value \u0026lt; 0.05: Significant; P-value \u0026lt; 0.01: Highly significant\u003c/p\u003e\n\u003cp\u003e*: Chi-square test; \u0026bull;: Independent t-test\u003c/p\u003e\n\u003cp\u003eRegarding\u0026nbsp;\u003cstrong\u003efigure (1),\u003c/strong\u003e twenty (45.5%) of patients had positive family history and 24 (54.5%) of them were without positive family history of migraine.\u0026nbsp;\u003c/p\u003e\n\u003cp id=\"_Toc174010948\"\u003e\u003cstrong\u003efigure (2)\u003c/strong\u003e Of all migraineurs, chronic patients were 20 (45.5%) but episodic patients were 24 (54.5%).\u003c/p\u003e\n\u003cp\u003eNeuropsychological evaluation of Verbal immediate memory and working memory by digit span test, Abstract thinking by similarities test and visual memory by Benton A and B test 9, 10, 30, 27 respectively were lower in patients group, additionally attention and psychomotor speed by Trail making test A and B test time 68 and 225 respectively took longer duration in patients group than control group 10, 12, 45, 45, 53, 161 respectively. \u003cstrong\u003eTable (2)\u0026nbsp;\u003c/strong\u003eshowed that there was significant difference between patients and control regard digit span test with (p-value 0.028) and the difference were highly significant between them regarding similarities test (p-value\u0026lt;0.001), Benton visual retention test A and B test (p-value\u0026lt;0.001) and TMT A and B test (p-value\u0026lt;0.001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (2):\u003c/strong\u003e Comparison between control group and patients group regarding neuropsychological evaluation\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTest value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSig.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.= 44\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.= 45\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 22px;\"\u003e\n \u003cp\u003eDigit span test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eMedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e9 (8 \u0026ndash; 10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e10 (8 \u0026ndash; 12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.191\u0026bull;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 7px;\"\u003e\n \u003cp\u003e0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 4px;\"\u003e\n \u003cp\u003eS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e4 \u0026ndash; 15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e4 \u0026ndash; 17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 22px;\"\u003e\n \u003cp\u003eSimilarities test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eMedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e10 (9 \u0026ndash; 11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e12 (11 \u0026ndash; 15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.607\u0026bull;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 4px;\"\u003e\n \u003cp\u003eHS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e6 \u0026ndash; 15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e9 \u0026ndash; 20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 22px;\"\u003e\n \u003cp\u003eBenton visual retention-A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e30 (68.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e45 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 9px;\"\u003e\n \u003cp\u003e16.991\u003cstrong\u003e\u003cspan dir=\"RTL\"\u003e*\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 4px;\"\u003e\n \u003cp\u003eHS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e14 (31.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 22px;\"\u003e\n \u003cp\u003eBenton visual retention -B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e27 (61.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e45 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 9px;\"\u003e\n \u003cp\u003e21.491\u003cstrong\u003e\u003cspan dir=\"RTL\"\u003e*\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 4px;\"\u003e\n \u003cp\u003eHS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e17 (38.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 22px;\"\u003e\n \u003cp\u003eTrail making test-A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eMean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e68.73 \u0026plusmn; 23.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e53.78 \u0026plusmn; 16.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-3.502\u0026bull;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 7px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 4px;\"\u003e\n \u003cp\u003eHS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e38 \u0026ndash; 126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e20 \u0026ndash; 100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 22px;\"\u003e\n \u003cp\u003eTrail making test-B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eMean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e225.25 \u0026plusmn; 50.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e161.07 \u0026plusmn; 76.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-4.651\u0026bull;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 4px;\"\u003e\n \u003cp\u003eHS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e155 \u0026ndash; 332\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e61 \u0026ndash; 362\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eP-value \u0026gt; 0.05: Non-significant; P-value \u0026lt; 0.05: Significant; P-value \u0026lt; 0.01: Highly significant\u003c/p\u003e\n\u003cp\u003e*: Chi-square test; \u0026bull;: Independent t-test; \u0026ne;: Mann-Whitney test\u003c/p\u003e\n\u003cp\u003eAs regarding \u003cstrong\u003etable (3),\u003c/strong\u003e CGRP level was higher in patients 247,05 compared to control group 27.57 with highly significant difference (p-value \u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (3):\u0026nbsp;\u003c/strong\u003eComparison between control group and patients group regarding CGRP plasma level\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTest value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSig.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.= 44\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.= 45\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCGRP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e247.05 (141.75 - 366.6)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e27.57 (17.98 - 33.8)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-8.075\u0026ne;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRange\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e61.2 \u0026ndash; 640\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6.5 \u0026ndash; 118\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eP-value \u0026gt; 0.05: Non-significant; P-value \u0026lt; 0.05: Significant; P-value \u0026lt; 0.01: Highly significant\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026ne;: Mann-Whitney test\u003c/p\u003e\n\u003cp\u003eThe ROC curve showed that the best cut of point between patients and control groups regarding CGRP level was more than 60.66 with sensitivity of 100% and specificity of 97.78% and AUC of 0.997 \u003cstrong\u003efigure (3).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe ROC curve showed that the best cut of point between chronic and episodic patients regarding CGRP level was \u0026gt;166.3 with sensitivity of 90% and specificity of 62.50% and AUC of 0.683 \u003cstrong\u003efigure (4).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThese results in \u003cstrong\u003etable (4),\u003c/strong\u003e shown that there was interictal high CGRP in all patients highly correlated with younger age of onset of migraine (p-value 0.002), more sever attacks (p-value \u0026lt;0.001) and more disable attacks with PEDMIDAS (p-value \u0026lt;0.001)\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eAlso, it correlated with longer attack duration without medication (p-value0.037) \u003cstrong\u003e.\u003c/strong\u003e AGE and BMI had shown no clinical correlation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (4):\u003c/strong\u003e Correlation between CGRP with demographic data, intensity and disability among all patients group\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"bottom\" style=\"width: 52px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCGRP plasma level\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003er\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 52px;\"\u003e\n \u003cp\u003eAGE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0.252\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.104\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 52px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0.058\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.708\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 52px;\"\u003e\n \u003cp\u003eAttack duration Without medic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.316*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.037\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 52px;\"\u003e\n \u003cp\u003eAge of onset of migraine(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0.456**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 52px;\"\u003e\n \u003cp\u003eDuration of disease(yrs)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.232\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.129\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 52px;\"\u003e\n \u003cp\u003e11-point scale(intensity)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.531**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 52px;\"\u003e\n \u003cp\u003epedMiDAs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.540**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ePeadiatric Migraine Disability Assessment Scale (PEDMIDAS)\u003c/p\u003e\n\u003cp\u003e*: Significant at P \u0026lt;0.05; **: Significant at p \u0026lt;0.01\u003c/p\u003e\n\u003cp\u003eThese results in \u003cstrong\u003etable (5),\u003c/strong\u003e showed that higher interictal CGRP level highly correlated with more affection psychomotor speed and attention by Trail making test A and B test (p-value 0.002 and \u0026lt;0.001)\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eAlso revealed correlation with affected working and immediate memory tested by digit span test (p-value 0.015) and visual memory by Benton visual retention-B test (p-value 0.023)\u003cstrong\u003e.\u003c/strong\u003e Similarities test for abstract thinking had shown no clinical correlation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (5):\u003c/strong\u003e Correlation between CGRP with the neuropsychological parameters among all patients group\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"bottom\" style=\"width: 52px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCGRP plasma level\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003er\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 52px;\"\u003e\n \u003cp\u003eDigit span test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0.364*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.015\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 52px;\"\u003e\n \u003cp\u003eSimilarities test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e-0.115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.458\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 52px;\"\u003e\n \u003cp\u003eBenton visual retention test -A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.289\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 52px;\"\u003e\n \u003cp\u003eBenton visual retention test -B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.342*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.023\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 52px;\"\u003e\n \u003cp\u003eTrail Making Test-A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.454**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 52px;\"\u003e\n \u003cp\u003eTrail Making Test -B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.565**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*: Significant at P \u0026lt;0.05; **: Significant at p \u0026lt;0.01\u003c/p\u003e\n\u003cp\u003eSpearman correlation coefficients\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe study population age range was 8\u0026ndash;17.9 with mean age (13.41\u0026thinsp;\u0026plusmn;\u0026thinsp;2.69) and control group age range 8.9\u0026ndash;17.8 with mean age (12.89\u0026thinsp;\u0026plusmn;\u0026thinsp;2.51). Female were 34 (77.3%) more than Males 10 (22.7%) in migraine group which suggest that female gender is a risk factor for migraine and this in agreement with observed difference in early report between both gender, and this may be due to hormonal changes at puberty \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. However, clinical gender-related differences in pain perception are less clear, previous study found that there was no gender difference in pain perception result in peadiatric studies \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. These differences may be explained by the different ages of the populations and different methodologies used.\u003c/p\u003e\u003cp\u003eThis study revealed that there was no significant difference between patients and control group regarding BMI, and in line with our result no significant difference has been noted previously \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e as regard BMI. However, an early literature noted that BMI was to be significantly higher in the migraine group and this may be due to difference methodologies and study settings \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Thus, it is possible that only patients with severe migraine headache symptoms, either chronic or episodic, were included in this study.\u003c/p\u003e\u003cp\u003eWe found that 20 (45.5%) of patients had positive family history and 24 (54.5%) of them without positive family history of migraine thus, family history may be an initial risk factor for migraine and this finding in agreement with early study which found that (32.7%) of migraine patients with positive family history \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Also, this finding corroborates findings reports that migraine expression depends on a robust genetic predisposition \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Thus, family history is postulated to be a strong risk factor, and this work confirms this hypothesis.\u003c/p\u003e\u003cp\u003eIn the present work, we also found Significant difference between patients and control group regarding digit span test (Verbal immediate memory and working memory), and the difference were highly significant between them regarding similarities test (abstract thinking), Benton visual retention test A and B test (visual memory) and Trail making test A and B test (Attention and psychomotor speed).this work results are consistent with a literature cleared that there were significant difference between children with migraine and control group as regard attention, executive function, visual and working memory \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. There is no consistent data in literature on abstract thinking in children with migraine.\u003c/p\u003e\u003cp\u003eAlthough, the exact mechanism regarding association between migraine and cognitive impairment is still not fully understood, there is information for alterations in brain functional reorganization of cognitive cerebral networks. Also shown that, the predominant involvement of processing speed, learning and memory could suggest a preferential dysfunction of the prefrontal and temporal cortices and or frontal subcortical white matter during migraine attack \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eWe observed in this work that CGRP level was higher in patients group to healthy volunteers with highly significance difference with p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001. The ROC curve showed that the best cut of point between patients and control groups regarding CGRP level was more than 60.66 with sensitivity of 100% and specificity of 97.78%. Additionally, there was a statistically significant difference between chronic and episodic patients of migraine regarding CGRP level which was higher in chronic patients. The ROC curve showed that the best cut of point between chronic and episodic patients regarding CGRP level was \u0026gt;\u0026thinsp;166.3 with sensitivity of 90% and specificity of 62.50% and AUC of 0.683.\u003c/p\u003e\u003cp\u003eSimilarly, previous findings revealed that plasma CGRP level was significantly higher in patients than control and could help in diagnosis of migraine and differentiate between chronic and episodic migraine in children. However, CGRP sampling was during and between migraine attacks \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIt was reported that CGRP concentrations in patients with episodic and chronic migraine was higher compared to healthy volunteers \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e, but another one found no difference between migraineurs and control group, between migraine with and without aura, between episodic and chronic migraine, and between ictal and interictal phases and not show interictally elevated CGRP concentrations in participants with frequent or chronic migraine \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe discrepancies between studies can be explained by differences in sample sizes, designs, participant selection criteria, blood processing protocols, and assays used for the CGRP measuring \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Additionally, commercially available CGRP assays are variable and not well validated. Most assays might detect not only an entire peptide but also its fragments and relative peptides, such as βCGRP and amylin. Standardization of blood processing protocols and thorough validation of assays are needed to achieve better comparisons between studies \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eWe found in this work that higher interictal CGRP level inversely proportionate with younger age of onset of migraine and direct proportionate with more frequent, severe, disabled and longer attacks of headache in all patients.\u003c/p\u003e\u003cp\u003eIt was early revealed that serum CGRP level showed a positive relationship with the severity of pain and disability but not headache duration, however sampling of CGRP was ictal and these studied patients were adult \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Also, our findings confirm reports which found that childhood migraine tends to be more chronic, frequent, sever and disable with higher CGRP level during and between attacks \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn contrast, other literature found only a weak positive correlation was apparent between age and CGRP concentration \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Moreover, there is no association between interictally elevated CGRP concentrations in participants with migraine and headache monthly frequency, intensity, and impact on quality of life \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn this work we reported that higher CGRP level proportionate with longer duration of Trail making test with a highly significant correlation between interictal CGRP and TMT A and B (impairment of attention and psychomotor speed) and inversely proportionate with achievement in Digit span and Benton visual retention test with statistically significant correlation with digit span test (affection working memory) and Benton visual retention test-B (affection visual memory).\u003c/p\u003e\u003cp\u003eTo our best knowledge, there was no data in literature about the correlation between interictal CGRP level and cognition affection. These findings provide new insight and indirectly suggest that CGRP play an important role in the pathogenesis of migraine itself and may have a role in affection cognition network in migraine. These findings are strengthened by reports about mechanisms of CGRP mediating pediatric migraine which involved in vasodilation theory, neurogenic inflammation, peripheral and central sensitization, and cortical spread depression (CSD), and nitric oxide generation \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOur findings are important especially for young and school age children who cannot clearly describe their headache symptoms and may be disabled by migraine. Also, it may provide a new insight into clinical practice for the diagnosis, prognosis and management in childhood migraine. Interictal CGRP is recommended for early detection of cognitive impairment beside diagnosis and differentiation between migraine types.\u003c/p\u003e\n\u003ch3\u003eLimitations of the Study\u003c/h3\u003e\n\u003cp\u003eSeveral limitations of this study should be acknowledged. First, the sample was restricted to patients recruited from a tertiary hospital, who may have experienced more intense migraine attacks than the general population. This may account for the higher rate of chronicity and frequency observed among participants. Second, the relatively small sample size may have introduced statistical bias. Third, the symptoms of migraine attacks described by younger children may have been unclear or inconsistently reported. Despite these limitations, the study had notable strengths. Unlike many studies that utilize non-standardized classification systems, which hinder comparison across research, this study employed standardized diagnostic criteria. Furthermore, participants with psychiatric disorders were excluded, thereby minimizing confounding effects on neuropsychological evaluation.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis study highlights significant cognitive impairments in pediatric migraine patients. Higher CGRP levels were strongly correlated with worse cognitive performance, particularly in tasks assessing attention, working memory, and visual memory, thus may take part in prognostication of learning difficulties in children. These results suggest that a broader function of CGRP in migraine pathophysiology beyond pain perception, potentially contributing to cognitive impairment. Additionally, suggesting that CGRP is a good indicator for diagnosis pediatric migraine, differentiation between episodic and chronic migraine type-headache.\u003c/p\u003e\u003cp\u003eFurther research is warranted to explore CGRP as a biomarker for cognitive dysfunction in migraine and to determine whether targeting CGRP pathways could help preserve cognitive\u003c/p\u003e\u003cp\u003eInterictal CGRP is recommended for early detection of cognitive impairment besides diagnosis and differentiation between migraine types, especially for younger children who cannot express their sufferings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in the study were in accordance with the ethical standards of the faculty of medicine, Ain Shams university research and ethical committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. We obtained approval from research ethics committee no. FWA 000017585. On 28/7/2022 (Approval Number: FMASU MD 157a/2022/2023).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from participants for participation. We obtained approval from research ethics committee no. FWA 000017585. On 28/7/2022 (Approval Number: FMASU MD 157a/2022/2023).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or nonprofit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA.G Conceptualization, data collection, manuscript writing.N.S, H.M, S.M, E.M supervision and analysis of data, revision of manuscript.Y.M supervision and interpretation of CGRP samplingA.K revision of manuscript, supervision on psychometric tests.All authors have agreed to conditions noted on the Authorship Agreement Form and have read and approved the final version submitted.The content of the manuscript has not been published or submitted for publication elsewhere\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the Neurology department and headache team, faculty of medicine, Ain Shams University, for their help in recruiting patients.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKhan A, Liu S, Tao F. Current trends in pediatric migraine: Clinical insights and therapeutic strategies. Brain Sci. 2025;15(3):280.\u003c/li\u003e\n\u003cli\u003eTermine C, Bartoli B, Agosti MA, et al. Cognitive impairment in children and adolescents with migraine. Front Neurol. 2018;9:667.\u003c/li\u003e\n\u003cli\u003eHuang Y, Li H, Yu Q, et al. A narrative review of autophagy in migraine. Front Neurosci. 2025;19:1500189.\u003c/li\u003e\n\u003cli\u003eCosta-Silva MA, Prado AC, Souza LC, et al. Cognitive functioning in adolescents with migraine. Dement Neuropsychol. 2016;10(1):47\u0026ndash;51.\u003c/li\u003e\n\u003cli\u003eFan PC, Kuo PH, Lee MT, et al. Plasma calcitonin gene-related peptide: A potential biomarker for diagnosis and therapeutic responses in pediatric migraine. Front Neurol. 2019;10:10.\u003c/li\u003e\n\u003cli\u003eSampaio Rocha-Filho PA, Hershey AD. Pediatric Migraine Disability Assessment (PedMIDAS): Translation into Brazilian Portuguese and cross-cultural adaptation. Headache. 2017;57(9):1409\u0026ndash;15.\u003c/li\u003e\n\u003cli\u003eEidlitz-Markus T, Zeharia A. Symptoms and clinical parameters of pediatric and adolescent migraine, by gender: A retrospective cohort study. J Headache Pain. 2017;18:1\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eAlmeida GF, Longo DL, Trevizan M, et al. Sex differences in pediatric dental pain perception. J Dent Child (Chic). 2016;83:120\u0026ndash;4.\u003c/li\u003e\n\u003cli\u003eHancı F, Kabakuş N, T\u0026uuml;ray S, et al. The role of obesity and vitamin D deficiency in primary headaches in childhood. Acta Neurol Belg. 2020;120:1123\u0026ndash;31.\u003c/li\u003e\n\u003cli\u003eGil-Gouveia R, Martins IP. Cognition and cognitive impairment in migraine. Curr Pain Headache Rep. 2019;23:1\u0026ndash;10.\u003c/li\u003e\n\u003cli\u003eGu L, Wang Y, Shu H. Association between migraine and cognitive impairment. J Headache Pain. 2022;23(1):88.\u003c/li\u003e\n\u003cli\u003eLiu J, Wang G, Dan Y, et al. CGRP and PACAP-38 play an important role in diagnosing pediatric migraine. J Headache Pain. 2022;23(1):68.\u003c/li\u003e\n\u003cli\u003eCharles A, Pozo-Rosich P. Targeting calcitonin gene-related peptide: A new era in migraine therapy. Lancet. 2019;394(10210):1765\u0026ndash;74.\u003c/li\u003e\n\u003cli\u003eLee MJ, Lee SY, Cho S, et al. Feasibility of serum CGRP measurement as a biomarker of chronic migraine: A critical reappraisal. J Headache Pain. 2018;19:1\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eTchivileva IE, Johnson KW, Chai X, et al. Evaluation of plasma calcitonin gene-related peptide as a biomarker for painful temporomandibular disorder and migraine. J Pain Res. 2023;16:2331\u0026ndash;46.\u003c/li\u003e\n\u003cli\u003eCheng Y, Gao Y, Zhang S, et al. Detection of calcitonin gene-related peptide based on increased antigen-driven interaction with antibody variable regions. Front Bioeng Biotechnol. 2024;12:1395330.\u003c/li\u003e\n\u003cli\u003eVural S, Albayrak L. Can calcitonin gene-related peptide (CGRP) and pentraxin-3 (PTX-3) be useful in diagnosing acute migraine attack? J Recept Signal Transduct. 2022;42(6):562\u0026ndash;6.\u003c/li\u003e\n\u003cli\u003eFekrazad R, Sardarian A, Azma K, et al. Interictal levels of calcitonin gene-related peptide in gingival crevicular fluid of chronic migraine patients. Neurol Sci. 2018;39:1217\u0026ndash;23.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-egyptian-journal-of-neurology-psychiatry-and-neurosurgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejnp","sideBox":"Learn more about [The Egyptian Journal of Neurology, Psychiatry and Neurosurgery](http://ejnpn.springeropen.com)","snPcode":"41983","submissionUrl":"https://submission.springernature.com/new-submission/41983/3","title":"The Egyptian Journal of Neurology, Psychiatry and Neurosurgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"CGRP, Childhood, Cognitive dysfunction, Pediatric migraine, PedMIDAS","lastPublishedDoi":"10.21203/rs.3.rs-7448411/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7448411/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eCognitive impairment is recognized as a comorbidity in childhood migraine. Calcitonin Gene-Related Peptide (CGRP) has been involved in migraine pathophysiology, but its relationship with cognitive dysfunction remains unclear. This study investigates the association between interictal CGRP plasma levels and cognitive impairment in pediatric migraineurs.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis is a cross-sectional study which was conducted on 89 participants (44 migraine patients and 45 controls). Demographic data, migraine severity and disability were assessed, and patients were furthermore classified to chronic or episodic migraineurs. plasma CGRP level was measured, and neuropsychological functions were evaluated using digit span, similarities, Benton visual retention, and Trail Making Tests. Statistical comparisons were performed between groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eMigraine patients showed significantly lower performance on digit span, similarities, and Benton visual retention tests and took significantly longer time to complete Trail making test A and B. There were no significant differences in demographic data, including age, sex, and BMI, between the patients and control groups. Plasma CGRP levels were significantly higher in migraine patients compared to controls and chronic compared to episodic migraineures. CGRP levels correlated positively with migraine severity, frequency, and disability.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eInterictal high plasma CGRP levels were correlated with affecting attention, psychomotor speed, and visual memory. CGRP may serve as a biomarker for migraine-associated cognitive impairment.\u003c/p\u003e","manuscriptTitle":"Association between interictal high Plasma Calcitonin Gene-Related Peptide and cognition affection in childhood migraine","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-03 08:49:25","doi":"10.21203/rs.3.rs-7448411/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-08T10:22:59+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-07T19:16:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-05T07:31:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"229846257271352413885760191608418904251","date":"2025-10-05T06:37:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"81613439585802481993699090531995619582","date":"2025-09-28T19:51:07+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-25T13:22:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-03T08:54:56+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-03T08:53:59+00:00","index":"","fulltext":""},{"type":"submitted","content":"The Egyptian Journal of Neurology, Psychiatry and Neurosurgery","date":"2025-08-24T22:09:46+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-egyptian-journal-of-neurology-psychiatry-and-neurosurgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejnp","sideBox":"Learn more about [The Egyptian Journal of Neurology, Psychiatry and Neurosurgery](http://ejnpn.springeropen.com)","snPcode":"41983","submissionUrl":"https://submission.springernature.com/new-submission/41983/3","title":"The Egyptian Journal of Neurology, Psychiatry and Neurosurgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"f0d9016d-4364-4d2f-94aa-00ac22e2506a","owner":[],"postedDate":"September 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-16T16:00:16+00:00","versionOfRecord":{"articleIdentity":"rs-7448411","link":"https://doi.org/10.1186/s41983-026-01084-6","journal":{"identity":"the-egyptian-journal-of-neurology-psychiatry-and-neurosurgery","isVorOnly":false,"title":"The Egyptian Journal of Neurology, Psychiatry and Neurosurgery"},"publishedOn":"2026-02-09 15:56:50","publishedOnDateReadable":"February 9th, 2026"},"versionCreatedAt":"2025-09-03 08:49:25","video":"","vorDoi":"10.1186/s41983-026-01084-6","vorDoiUrl":"https://doi.org/10.1186/s41983-026-01084-6","workflowStages":[]},"version":"v1","identity":"rs-7448411","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7448411","identity":"rs-7448411","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}