CGRP Levels Are Not Elevated in Patients with Idiopathic Intracranial Hypertension Despite Migraine-Like Headaches | Research

The takeaway

Basal CGRP levels in plasma and cerebrospinal fluid are not elevated in idiopathic intracranial hypertension patients, suggesting the headache mechanism in IIH may differ from typical migraine.

No CGRP elevation in IIH (p=0.78)
Despite migraine-like headaches, IIH patients had identical basal CGRP levels to both headache controls and healthy volunteers in both plasma and cerebrospinal fluid.

What the researchers found

CGRP levels in both plasma and cerebrospinal fluid were not elevated in patients with idiopathic intracranial hypertension (IIH) compared to headache controls or healthy controls. No differences were found after adjusting for BMI, age, and smoking. CGRP levels were not associated with having migraine-like headache, chronic headache, or any headache versus no headache in IIH patients. However, plasma CGRP correlated significantly with CSF CGRP levels (p<0.0001). The results suggest basal CGRP levels do not differ in IIH, though the role of CGRP in IIH headache remains unclear.

Why it matters

Headache in IIH is often migraine-like, which raised the question of whether CGRP — the key peptide target in modern migraine treatment — might also be elevated in IIH. This well-designed study found no evidence of elevated basal CGRP, suggesting the headache mechanism in IIH may differ from migraine. However, the authors note that anti-CGRP therapy in IIH remains an unexplored area that could still be beneficial regardless of basal levels.

The numbers in context

97 IIH patients · 52 non-IIH headache controls · 37 healthy controls · no difference in plasma CGRP (p=0.78) · no difference in CSF CGRP (p=0.79) · plasma-CSF CGRP correlation (p<0.0001)

How the study worked

This prospective, cross-sectional, case-control study enrolled patients at two Danish tertiary headache centers. Participants included 97 newly diagnosed IIH patients, 52 non-IIH headache controls, and 37 sex-, age-, and BMI-matched healthy controls. CGRP was measured in both plasma and cerebrospinal fluid using a validated radioimmunoassay. CSF:plasma ratios were calculated. Statistical comparisons used ANOVA/Kruskal-Wallis tests with regression adjustments for confounders.

Who was studied

97 newly diagnosed IIH patients, 52 non-IIH headache controls, and 37 sex/age/BMI-matched healthy controls from two Danish headache centers

What this study cannot tell us

The study measured basal resting CGRP levels, which may not reflect CGRP release during active headache episodes. CGRP levels could still be elevated during headache attacks even if baseline levels are normal. The cross-sectional design provides only a snapshot. The radioimmunoassay methodology may not capture all CGRP isoforms relevant to headache pathology.

How to read the evidence

This is a well-designed prospective case-control study with 186 participants, appropriate controls (both headache and healthy), and BMI-matched healthy volunteers. The validated radioimmunoassay and adjustment for confounders strengthen the findings. The main limitation is measuring basal rather than ictal CGRP levels.

When this study was published

Published in 2025, this is a very recent study addressing a clinically relevant question about whether CGRP-targeted therapies could be useful beyond migraine.

The bigger picture

Anti-CGRP therapies have revolutionized migraine treatment, leading to interest in whether they might help other headache conditions. This study suggests that IIH headache does not involve the same basal CGRP elevation seen in some migraine studies, potentially pointing to different pathophysiology. However, it doesn't rule out a therapeutic role for anti-CGRP drugs in IIH, and clinical trials testing this remain an important next step.

Questions still open

Are CGRP levels elevated during active IIH headache attacks even if basal levels are normal?
Could anti-CGRP monoclonal antibodies still be effective for IIH headache despite normal basal CGRP levels?
What other neuropeptides or pain signaling molecules might be driving migraine-like headache in IIH?

Common questions

If CGRP isn't elevated in IIH, why do the headaches feel like migraines?

IIH headaches can feel migraine-like because increased intracranial pressure can activate some of the same pain pathways and brain structures involved in migraine. However, the underlying trigger is different — in migraine, CGRP release from trigeminal nerves drives the pain, while in IIH, the increased pressure itself may be the primary pain stimulus. The similar symptoms don't necessarily mean the same molecular mechanisms are involved.

Does this mean anti-CGRP drugs won't work for IIH headaches?

Not necessarily. Basal CGRP levels may be normal at rest, but CGRP could still be released during active headache episodes. Also, blocking CGRP might reduce pain signaling regardless of whether baseline levels are elevated. The authors specifically note that testing anti-CGRP therapy in IIH remains an important unexplored area.

Read the original research

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, 26(1), 95

View on PubMed ↗Publisher’s paper ↗

Citation

Hansen, Nadja Skadkær; Korsbaek, Johanne Juhl; Bak, Lasse Kristoffer; Jørgensen, Niklas Rye; Beier, Dagmar; Jensen, Rigmor Højland. (2025). 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, 26(1), 95. https://doi.org/10.1186/s10194-025-02042-y