Calcitonin gene-related peptide in newly diagnosed idiopathic intracranial hypertension: a prospective, cross-sectional, case-control study of cerebrospinal fluid and plasma

Abstract Background Calcitonin Gene-Related Peptide (CGRP) is involved in migraine pain signaling, and blockage hereof is effective in migraine treatment. Headache in idiopathic intracranial hypertension (IIH) is often migraine-like but the underlying mechanisms are not understood. We report levels...

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Main Authors: Nadja Skadkær Hansen, Johanne Juhl Korsbaek, Lasse Kristoffer Bak, Niklas Rye Jørgensen, Dagmar Beier, Rigmor Højland Jensen
Format: Article
Language:English
Published: BMC 2025-04-01
Series:The Journal of Headache and Pain
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Online Access:https://doi.org/10.1186/s10194-025-02042-y
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author Nadja Skadkær Hansen
Johanne Juhl Korsbaek
Lasse Kristoffer Bak
Niklas Rye Jørgensen
Dagmar Beier
Rigmor Højland Jensen
author_facet Nadja Skadkær Hansen
Johanne Juhl Korsbaek
Lasse Kristoffer Bak
Niklas Rye Jørgensen
Dagmar Beier
Rigmor Højland Jensen
author_sort Nadja Skadkær Hansen
collection DOAJ
description Abstract Background Calcitonin Gene-Related Peptide (CGRP) is involved in migraine pain signaling, and blockage hereof is effective in migraine treatment. Headache in idiopathic intracranial hypertension (IIH) is often migraine-like but the underlying mechanisms are not understood. We report levels of CGRP in plasma and cerebrospinal fluid (CSF) of patients with newly diagnosed IIH to elucidate CGRP involvement in the pathogenesis of headache in IIH. Method We consecutively enrolled patients suspected of having IIH in a prospective cohort at two Danish tertiary headache centers. Patients are confirmed to have IIH or disproven of it (non-IIH). We included non-IIH with primary headache disorders as headache controls to IIH cases. We also recruited sex-, age- and BMI-matched healthy controls (HC). All participants had CSF and blood drawn and CGRP was analyzed using a validated radioimmunoassay. CSF plasma-ratios were calculated. Between-group levels were compared with ANOVA or Kruskal-Walli’s test. In sub-analyses we restricted comparison of HC to non-IIH/IIH with chronic migraine; we also compared IIH with versus without headache. We correlated CGRP to lumbar opening pressure (OP), and BMI, and assessed the correlation between CGRP in plasma and CSF. Generalized or linear regression was applied to adjust for confounding by BMI, age, and active smoking. Results Comparing 97 patients with IIH, 52 non-IIH, and 37 HC, we found no between-group differences in CGRP levels in plasma (p = 0.78), CSF (p = 0.79), or in CSF:plasma-ratio (p = 0.13). Adjusting for BMI, age, and smoking yielded similar results. CGRP levels were neither associated with having a migraine phenotype or chronic headache, nor with having any headache versus no headache in IIH. CGRP in plasma correlated with CGRP in CSF (p < 0.0001). CGRP did not correlate with OP or BMI. Conclusion CGRP levels in plasma and CSF and their ratios were comparable in IIH, non-IIH patients with headache, and sex-, age-, and BMI-matched HC. CGRP in plasma correlated with CGRP in CSF. Due to methodology, we probably measured basal resting CGRP. The role of CGRP in IIH-headache needs further clarification. A headache preventive effect in IIH of anti-CGRP targeted therapy remains a relevant unexplored area. Graphical Abstract
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spelling doaj-art-8406331d15e04e6496f3c6dec51923f52025-08-20T02:10:50ZengBMCThe Journal of Headache and Pain1129-23772025-04-0126111410.1186/s10194-025-02042-yCalcitonin gene-related peptide in newly diagnosed idiopathic intracranial hypertension: a prospective, cross-sectional, case-control study of cerebrospinal fluid and plasmaNadja Skadkær Hansen0Johanne Juhl Korsbaek1Lasse Kristoffer Bak2Niklas Rye Jørgensen3Dagmar Beier4Rigmor Højland Jensen5Danish Headache Center, Department of Neurology, Rigshospitalet-Glostrup, University of CopenhagenDanish Headache Center, Department of Neurology, Rigshospitalet-Glostrup, University of CopenhagenDepartment of Clinical Biochemistry, Copenhagen University HospitalDepartment of Clinical Biochemistry, Copenhagen University HospitalDepartment of Neurology, Odense University HospitalDanish Headache Center, Department of Neurology, Rigshospitalet-Glostrup, University of CopenhagenAbstract Background Calcitonin Gene-Related Peptide (CGRP) is involved in migraine pain signaling, and blockage hereof is effective in migraine treatment. Headache in idiopathic intracranial hypertension (IIH) is often migraine-like but the underlying mechanisms are not understood. We report levels of CGRP in plasma and cerebrospinal fluid (CSF) of patients with newly diagnosed IIH to elucidate CGRP involvement in the pathogenesis of headache in IIH. Method We consecutively enrolled patients suspected of having IIH in a prospective cohort at two Danish tertiary headache centers. Patients are confirmed to have IIH or disproven of it (non-IIH). We included non-IIH with primary headache disorders as headache controls to IIH cases. We also recruited sex-, age- and BMI-matched healthy controls (HC). All participants had CSF and blood drawn and CGRP was analyzed using a validated radioimmunoassay. CSF plasma-ratios were calculated. Between-group levels were compared with ANOVA or Kruskal-Walli’s test. In sub-analyses we restricted comparison of HC to non-IIH/IIH with chronic migraine; we also compared IIH with versus without headache. We correlated CGRP to lumbar opening pressure (OP), and BMI, and assessed the correlation between CGRP in plasma and CSF. Generalized or linear regression was applied to adjust for confounding by BMI, age, and active smoking. Results Comparing 97 patients with IIH, 52 non-IIH, and 37 HC, we found no between-group differences in CGRP levels in plasma (p = 0.78), CSF (p = 0.79), or in CSF:plasma-ratio (p = 0.13). Adjusting for BMI, age, and smoking yielded similar results. CGRP levels were neither associated with having a migraine phenotype or chronic headache, nor with having any headache versus no headache in IIH. CGRP in plasma correlated with CGRP in CSF (p < 0.0001). CGRP did not correlate with OP or BMI. Conclusion CGRP levels in plasma and CSF and their ratios were comparable in IIH, non-IIH patients with headache, and sex-, age-, and BMI-matched HC. CGRP in plasma correlated with CGRP in CSF. Due to methodology, we probably measured basal resting CGRP. The role of CGRP in IIH-headache needs further clarification. A headache preventive effect in IIH of anti-CGRP targeted therapy remains a relevant unexplored area. Graphical Abstracthttps://doi.org/10.1186/s10194-025-02042-yCGRPIIHIntracranial pressureSecondary headacheCerebrospinal fluidMigraine
spellingShingle Nadja Skadkær Hansen
Johanne Juhl Korsbaek
Lasse Kristoffer Bak
Niklas Rye Jørgensen
Dagmar Beier
Rigmor Højland Jensen
Calcitonin gene-related peptide in newly diagnosed idiopathic intracranial hypertension: a prospective, cross-sectional, case-control study of cerebrospinal fluid and plasma
The Journal of Headache and Pain
CGRP
IIH
Intracranial pressure
Secondary headache
Cerebrospinal fluid
Migraine
title Calcitonin gene-related peptide in newly diagnosed idiopathic intracranial hypertension: a prospective, cross-sectional, case-control study of cerebrospinal fluid and plasma
title_full Calcitonin gene-related peptide in newly diagnosed idiopathic intracranial hypertension: a prospective, cross-sectional, case-control study of cerebrospinal fluid and plasma
title_fullStr Calcitonin gene-related peptide in newly diagnosed idiopathic intracranial hypertension: a prospective, cross-sectional, case-control study of cerebrospinal fluid and plasma
title_full_unstemmed Calcitonin gene-related peptide in newly diagnosed idiopathic intracranial hypertension: a prospective, cross-sectional, case-control study of cerebrospinal fluid and plasma
title_short Calcitonin gene-related peptide in newly diagnosed idiopathic intracranial hypertension: a prospective, cross-sectional, case-control study of cerebrospinal fluid and plasma
title_sort calcitonin gene related peptide in newly diagnosed idiopathic intracranial hypertension a prospective cross sectional case control study of cerebrospinal fluid and plasma
topic CGRP
IIH
Intracranial pressure
Secondary headache
Cerebrospinal fluid
Migraine
url https://doi.org/10.1186/s10194-025-02042-y
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