# Autonomic dysfunction in patients with episodic cluster headache during remission period

**Authors:** Alba López-Bravo, Elena Bellosta Diago, Marisa de la Rica Escuín, Laura Díez Galán, Sonia Santos Lasaosa

PMC · DOI: 10.1007/s13760-025-02915-8 · Acta Neurologica Belgica · 2025-10-13

## TL;DR

This study finds that patients with episodic cluster headache show signs of autonomic dysfunction even when not experiencing an attack.

## Contribution

The study is the first to demonstrate autonomic nervous system imbalance in cluster headache patients during remission.

## Key findings

- Heart rate variability was significantly lower in cluster headache patients during remission.
- Plasma norepinephrine levels were higher in cluster headache patients compared to controls.
- Mean heart rate was significantly higher in cluster headache patients during the study.

## Abstract

The hypothalamus is involved in cluster headache (CH) pathophysiology and is a hub for autonomic control. While cranial autonomic symptoms are prominent during attacks, other autonomic manifestations may be present in CH. This study aims to explore the autonomic nervous system (ANS) in patients with CH during remission period.

Cross-sectional study including 30 CH and 30 age- and sex-matched controls. We analysed time- and frequency-domain parameters of heart rate variability (HRV) and active orthostatic tests. To investigate the sympathetic nervous system, plasma norepinephrine (NE) levels were determined. All assessments were performed during remission period.

All HRV parameters were lower in CH; the percentage of adjacent R-R intervals that differ by more than 50 milliseconds (pNN50) and standard deviation of normal-to-normal R-R intervals in 24 h (SDNN) were significantly lower in CH (pNN50, 31.0 [5.3–44.3] vs. 44.5 [25.8–58.5], p = 0.043; SDNN, 79.6 ± 42.6 vs. 99.6 ± 42.6, p = 0.004). All other time-domain parameters, including the root mean square of successive R-R differences (RMSSD) were lower in CH than in controls (RMSSD 59.5 ± 36.9 vs. 77.3 ± 39.4, p = 0.077). Compared to controls, mean HR was significantly higher in CH (64.2 [59.6–75.8] vs. 60.4 [57.3–62.7], p = 0.038). Supine and upright NE levels were significantly higher in CH, (supine 228.9 [161.6-324.1] vs. 209.9 [151.2-314.1], p = 0.015; standing 376.1 [264.6-527.8 vs. 327.4 [256.4-400.9], p = 0.019).

The present study indicates a significant decrease in HRV and an upward trend of plasmatic NE levels in CH during remission periods, suggesting an imbalance of the ANS in this state.

## Linked entities

- **Chemicals:** norepinephrine (PubChem CID 951)
- **Diseases:** cluster headache (MONDO:0043537)

## Full-text entities

- **Diseases:** Autonomic dysfunction (MESH:D001342), CH (MESH:D003027)
- **Chemicals:** NE (MESH:D009638)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

3 references — full list in the complete paper: https://tomesphere.com/paper/PMC12987825/full.md

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Source: https://tomesphere.com/paper/PMC12987825