Autonomic dysfunction in patients with episodic cluster headache during remission period

Background. 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. Methods. 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. Results. 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 24h (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 329.27 pg/ml ± 172.71 vs 224.91 pg/ml ± 99.03, p = 0.015; standing 489.93 pg/ml ± 206.82 vs 354.24 pg/ml ± 154.21, p = 0.019). Conclusions. 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.