Tear fluid Calcitonin gene-related peptide in patients with idiopathic intracranial hypertension headache – a prospective case-control study

BACKGROUND: Headache is the most common symptom of idiopathic intracranial hypertension (IIH) and may persist despite therapy, with a significant impact on quality of life. Since calcitonin gene-related peptide (CGRP) plays a crucial role in the pathophysiology and management of primary headaches such as migraine, this raises the question whether CGRP also contributes to headache in IIH. Therefore, we compared tear fluid CGRP levels between IIH patients with headache and healthy controls, and in IIH patients before and after CSF pressure normalization by therapeutic lumbar puncture. METHODS: IIH patients with headache attributed to IIH and healthy controls were included. To avoid confounding with chronic migraine, IIH patients with a chronic migraine phenotype were excluded. Tear fluid was collected from IIH patients and controls. In IIH patients, an additional measurement was performed approximately 3 h after therapeutic lumbar puncture. CGRP levels were analyzed using a commercially available ELISA. RESULTS: Twenty-three IIH patients (all female; age: 34.0 ± 8.8 years) and 20 healthy controls (all female, age: 25.7 ± 5.5 years) were included. IIH patients had 16.4 ± 12.3 headache days per month and headache was mostly bilateral and pressing. Baseline tear fluid CGRP levels were significantly lower in IIH patients compared to healthy controls (2.4 ± 1.2 ng/ml vs. 4.9 ± 4.2 ng/ml, p < 0.001). There was no significant change in CGRP levels in IIH patients before vs. after therapeutic lumbar puncture (2.4 ± 1.2 vs. 2.4 ± 1.7 ng/ml, p = 0.236). Similarly, in the subgroup with immediate headache improvement, CGRP levels remained unchanged (before: 2.2 ± 0.9 ng/ml, after: 2.8 ± 2.4 ng/ml; p = 0.674). CONCLUSIONS: Tear fluid CGRP levels were lower in IIH patients with headache but without a chronic migraine phenotype compared to healthy controls. In addition, CSF pressure normalization was not associated with changes in CGRP levels after 3 h. These results do not support a major role of CGRP in IIH-associated headache without a chronic migraine phenotype. TRIAL REGISTRATION: The study was previously registered at the German Clinical Trial Register (DRKS www.drks.de) (DRKS00025278), Trial registration date 25.06.2021.