Intracranial pressure directly predicts headache morbidity in idiopathic intracranial hypertension

Abstract

Objective: Headache is the predominant disabler in idiopathic intracranial hypertension (IIH). The aim was to characterise headache and investigate the association with intracranial pressure.

Methods: IIH:WT was a randomised controlled parallel group multicentre trial in the United Kingdom investigating weight management methods in IIH. Participants with active IIH (evidenced by papilloedema) and a body mass index (BMI) ≥35 kg/m2 were recruited. At baseline, 12 months and 24 months headache characteristics and quality of life outcome measures were collected and lumbar puncture measurements were performed.

Results: Sixty-six women with active IIH were included with a mean age of 32.0 years (SD ± 7.8), and mean body mass index of 43.9 ± 7.0 kg/m2. The headache phenotype was migraine-like in 90%. Headache severity correlated with ICP at baseline (r = 0.285; p = 0.024); change in headache severity and monthly headache days correlated with change in ICP at 12 months (r = 0.454, p = 0.001 and r = 0.419, p = 0.002 respectively). Cutaneous allodynia was significantly correlated with ICP at 12 months. (r = 0.479, p < 0.001). Boot strap analysis noted a positive association between ICP at 12 and 24 months and enabled prediction of both change in headache severity and monthly headache days. ICP was associated with significant improvements in quality of life (SF-36).

Conclusions: We demonstrate a positive relationship between ICP and headache and cutaneous allodynia, which has not been previously reported in IIH. Those with the greatest reduction in ICP over 12 months had the greatest reduction in headache frequency and severity; this was associated with improvement of quality of life measures.

Trial registration: This work provides Class IIa evidence of the association of raised intracranial pressure and headache. ClinicalTrials.gov number, NCT02124486 .

Keywords: Allodynia; Calcitonin gene related peptide; Idiopathic intracranial hypertension; Intracranial pressure; Migraine.

Conflict of interest statement

SM - Royalties - Springer publishing: Neuro-Ophthalmology, Global Trends in Diagnosis, Treatment and Management; Consultancy - Invex therapeutics, Neurodiem, Honoraria - Novartis, Santen, Santhera, Allergan, Chuagi, Chiesi; Data safety/advisory boards - Roche, Janssen, Invex therapeutics. BW - Consultancy, Invex Therapeutics; Director Ceftronics Limited; Patent pending, Uk - 1907237.0. ZA – none. JM – none. RO – none. AY - fees for educational talk – TEVA. MT – none. AG – none. OG – none. GL – none. KB - Consultancy, Invex Therapeutics; stock - Astrazenica, GlaxoSmithKline. AS - Honoraria - Chiesi; Safet board/advisory - Novartis; Director / Share options - Invex therapeutics.

© 2021. The Author(s).

Figures

Fig. 1

Relationship between ICP and headache. Correlation of baseline headache severity (HS) against baseline intracranial pressure (ICP) (A); ICP correlated with change in HS (B) change in monthly headache days (MHD) (C) Change in MHD correlated with ICP between baseline and 12 months. Correlation of the change allodynia scores between baseline and 12 months against change in HS (D); change in MHD (E); ICP (F) between baseline and 12 months

Fig. 2

Bootstrap surrogacy analysis of ICP and headache outcomes. The x-axis reflects change in headache outcomes with change in ICP on the y-axis. The lines are simple linear regressions and the shaded regions are 95% confidence intervals of the mean. Changes in intracranial pressure are plotted at 12 and 24 months. Each positive value represent improvement i.e. reduction in ICP and headaches outcomes, with the larger the angle of the slope the greater the relationship. A Illustrates headache severity on the y axis with a positive association with ICP over the time horizons. B Illustrates monthly headache days (MHD) on the y axis with a positive association with ICP over the time horizons. C Illustrates quality of life physical component score (PCS) on the y axis with a positive association with ICP over the time horizons

Fig. 3

Correlation of change in Quality of Life SF-36 physical component score (PCS) score and change in headache severity (HS) between baseline and 12 months (A) baseline and 24 months (B); Intracranial Pressure (ICP) between baseline and 12 months (C) between baseline and 24 months (D)