Promote Biomarker Discovery by Identifying Homogenous Primary Headache Subgroups

Frederiksen, Simona Denise

doi:10.1111/head.13499

Cited by 4 publications

(7 citation statements)

References 48 publications

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“…When comparing the results from 2 recently published CGRP studies with focus on migraine, contradictory results also occurred 40,46 . This has in part been discussed by Frederiksen 64 . In this SR‐MA, a tendency appeared showing that the most notable results were obtained when investigating CGRP in central blood from migraine patients in the ictal compared with the interictal headache phase.…”

Section: Discussionmentioning

confidence: 93%

“…Reporting a wide range of factors in future studies with focus on signaling molecules will allow us to assess different sources of confounding in future SR‐MAs which distort the exposure‐outcome association and thus, promote the biomarker discovery process (eg, the EQUATOR and SAMPL guidelines might be of use 101 ). Other ideas on how to promote primary headache biomarker discovery were discussed by Frederiksen 64 …”

Section: Discussionmentioning

confidence: 99%

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Serotonin and Neuropeptides in Blood From Episodic and Chronic Migraine and Cluster Headache Patients in Case‐Control and Case‐Crossover Settings: A Systematic Review and Meta‐Analysis

Frederiksen¹,

Dunbar

Snoer

et al. 2020

Headache

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Objective.-The aim of this systematic review and meta-analysis (SR-MA) was to identify signaling molecule profiles and blood-derived biomarkers in migraine and cluster headache (CH) patients.Background.-Currently no migraine and CH valid biomarkers are available. Blood tests based on biomarker profiles have been used to gather information about the nervous system. Such tests have not yet been established within the primary headache field.Methods.-Case-control and case-crossover studies investigating whole blood, plasma, and serum were identified worldwide. The qualitative synthesis focused on 9 signaling molecules (serotonin [5-HT], calcitonin gene-related peptide [CGRP], endothelin-1 [ET-1], neurokinin A, neurokinin B, neuropeptide Y, pituitary adenylate cyclase-activating peptide 38 [PACAP-38], substance P (SP), and vasoactive intestinal peptide) and the quantitative synthesis on 5-HT and CGRP (≥5 comparisons available). The meta-analysis was conducted using standard and 3-level random effect models.Results.-Fifty-four eligible studies were identified (87.0% migraine, 9.3% CH, 3.7% migraine, and CH), and 2768 headache patients and 1165 controls included. Comparable fluctuations of 5-HT, CGRP, ET-1, PACAP-38, and SP in blood were generally observed between migraine and CH. Significant findings were observed for some subgroups and strata, for example, higher interictal and ictal 5-HT venous blood levels (ratio of means = 1.32, 95% CI: 1.08; 1.61; ratio of means = 1.23, 95% CI: 1.01; 1.49) in episodic migraine with aura with a female-dominated case group, higher interictal CGRP blood levels in episodic migraine (ratio of means = 1.63, 95% CI: 1.18; 2.26), and chronic migraine (ratio of means = 1.89, 95% CI: 1.33; 2.68), and higher ictal CGRP blood levels (ratio of means = 1.35, 95% CI: 1.09; 1.68) in episodic migraine were observed. In most subgroups, the quantitative synthesis revealed a high degree of heterogeneity between studies in part explained by the blood sampling site, specimen source, blood specimen, and sex distribution. Other potential confounders were age, aura, study quality, menstrual cycle, and methodology (eg, storage temperature).Conclusions.-Potential migraine and CH signaling molecule profiles and biomarkers were revealed. Nevertheless, the high degree of heterogeneity between studies impedes identification of valid biomarkers but allowed us to assess the presence of confounders. Consideration of the potential confounders identified in this SR-MA might be of importance in the experimental planning of future studies. This consideration could be incorporated through establishment of specific guidelines. Abbreviations: 2SD 2 times standard deviation, 5-HIAA 5-hydroxyindoleacetic acid, 5-HT serotonin, 5-HT 1B/1D serotonin receptor 1B/1D, CC, column chromatography, CC-RIA column chromatography and radioimmunoassay, CGRP calcitonin gene-related peptide, CH cluster headache, CI confidence interval, CSF cerebrospinal fluid, CTRL controls, CV coefficient of variation, D Cook's distance, EIA enzyme immun...

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Serotonin and Neuropeptides in Blood From Episodic and Chronic Migraine and Cluster Headache Patients in Case‐Control and Case‐Crossover Settings: A Systematic Review and Meta‐Analysis

Frederiksen¹,

Dunbar

Snoer

et al. 2020

Headache

Self Cite

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“…Measuring CGRP in migraine patients has led to a better understanding of pain in migraine pathophysiology as well as it laid the foundation of the development of new abortive and prophylactic treatments ( 40 ). Further, the neuropeptide is recognized as a marker for the acute migraine attack and it might be a marker for migraine itself which could help to objectify the diagnosis in the future ( 67 ).…”

Section: Discussionmentioning

confidence: 99%

“…From these studies, it can be concluded that CGRP is a marker of the migraine attack. However, due to inconsistent findings in the overall studies, standardization of study procedures is needed to draw further conclusions (67)(68)(69).…”

Section: Figure 2 |mentioning

confidence: 99%

CGRP and Migraine: What Have We Learned From Measuring CGRP in Migraine Patients So Far?

Kamm

2022

Front. Neurol.

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The multi-functional neuropeptide calcitonin gene-related peptide (CGRP) plays a major role in the pathophysiology of migraine. The detection of elevated CGRP levels during acute migraine headache was the first evidence of the importance of the peptide. Since then, elevated CGRP levels have been detected not only during spontaneous and experimentally induced migraine attacks but also interictally. However, the detection of CGRP in peripheral blood shows conflicting results. In this respect, alternative detection methods are needed and have been already proposed. This article summarizes what we have learned from studies investigating CGRP in jugular and peripheral blood and reviews the latest state of research concerning the detection of CGRP in saliva and tear fluid as well as their contribution to our understanding of migraine pathophysiology.

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“…Migraine is a highly prevalent and a disabling neurological disease (1) and, so far, specific biomarkers have yet not been validated, which reflects its complexity and dynamic character (2–4). However, the most studied molecule is the calcitonin gene related peptide (CGRP), which has a clear implication in migraine pathophysiology (5,6), underpinned by the arrival of effective therapies targeting CGRP pathways (7).…”

Section: Introductionmentioning

confidence: 99%

Salivary CGRP can monitor the different migraine phases: CGRP (in)dependent attacks

et al. 2021

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Background CGRP plays a key role in the transmission and modulation of nociceptive signals and is a critical component in the pathogenesis of migraine. Objective To assess saliva as a substrate to measure CGRP by comparing interictal levels in patients with episodic migraine and controls; and to evaluate CGRP’s temporal profile during migraine attacks. Methods This prospective observational pilot study included young women with episodic migraine and healthy controls. We monitored salivary CGRP-like immunoreactivity (CGRP-LI) during 30 consecutive days and during migraine attacks. We considered six timepoints for the analysis: interictal (72h headache free), preictal (PRE-24h before the attack), ictal (headache onset, after 2h, after 8h), postictal (POST-24h after the attack). CGRP levels were quantified by ELISA. Results 44 women (22 with episodic migraine, 22 healthy controls) were recruited. Differences in interictal salivary levels of CGRP between patients and controls (Me [IQR]: 98.0 [80.3] (95% CI 56.6, 124.0) vs. 54.3 [44.0] (95% CI 42.2, 70.1) pg/mL, p = 0.034) were found. An increase in CGRP levels during migraine attacks was detected (pre:169.0 [95% CI 104.2–234.0]; headache onset: 247.0 [181.9–312.0]; after 2h: 143.0 [77.6–208.0]; after 8h: 169.0 [103.5–234.0], post: 173.0 [107.8–238.0]). Patients were classified as having CGRP-dependent (79.6%) and non-CGRP dependent migraine attacks (20.4%) according to the magnitude of change between preictal and ictal phase. Accompanying symptoms such as photophobia and phonophobia were significantly associated to the first group. Conclusions Salivary CGRP-LI levels, which interictally are elevated in episodic migraine patients, usually increase during a migraine attack in the majority of patients. However, not every attack is CGRP-dependent, which in turn, might explain different underlying pathophysiology and response to treatment.

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Promote Biomarker Discovery by Identifying Homogenous Primary Headache Subgroups

Cited by 4 publications

References 48 publications

Serotonin and Neuropeptides in Blood From Episodic and Chronic Migraine and Cluster Headache Patients in Case‐Control and Case‐Crossover Settings: A Systematic Review and Meta‐Analysis

Serotonin and Neuropeptides in Blood From Episodic and Chronic Migraine and Cluster Headache Patients in Case‐Control and Case‐Crossover Settings: A Systematic Review and Meta‐Analysis

CGRP and Migraine: What Have We Learned From Measuring CGRP in Migraine Patients So Far?

Salivary CGRP can monitor the different migraine phases: CGRP (in)dependent attacks

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