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. 2021 Oct;61(9):1452-1459.
doi: 10.1111/head.14222. Epub 2021 Oct 7.

Enlarging the spectrum of cluster headache: Extracranial autonomic involvement revealed by voice analysis

Marcello Silvestro  1 , Francesca M Dovetto  2 , Virginia Corvino  3 , Pasqualina Apisa  3 , Rita Malesci  3 , Alessandro Tessitore  1 , Paolo Milizia  4 , Gioacchino Tedeschi  1 , Elio Marciano  3 , Antonio Russo  1
Affiliations

Enlarging the spectrum of cluster headache: Extracranial autonomic involvement revealed by voice analysis

Marcello Silvestro et al. Headache. 2021 Oct.

Abstract

Background: People with cluster headache (CH) are frequently burdened by misdiagnosis or diagnostic delay. The peculiar somatic and behavioral changes characterizing patients with CH are not useful to improve diagnostic accuracy. In our clinical experience, we noticed a typical voice quality with low and croaking tone in patients with CH. In this cross-sectional study, we evaluated, by digital voice analysis, whether it is possible to identify typical voice quality characterizing patients with CH compared with healthy controls (HCs). Furthermore, to investigate whether putative differences in voice characteristics could be underpinned by constitutional aspects or pathological processes of vocal cords, subjects underwent a videolaryngostroboscopy. Smoking habits and alcohol consumption were specifically investigated.

Methods: After conducting digital recording of the voices from both patients with CH and HCs in a soundproof insulated cabin in the laboratory of the Audiology Department, a set of voice parameters was analyzed. We included the measures of fundamental frequency, calculations of jitter and shimmer, and noise-to-harmonics ratios as well as quantities related to the spectral tilt (i.e., H1-H2, H1-A1, H1-A2, and H1-A3) in 20 patients with CH and in 13 HCs. A videolaryngostroboscopy was performed in all subjects.

Results: Patients with CH, explored during the cluster bout period, showed significantly lower second harmonic (H1-H2) values compared with HCs (-6.9 ± 7.6 vs. 2.1 ± 6.7, p = 0.002), usually characterizing the so-called creaky voice. By using a laryngoscopy investigation, a significantly higher prevalence of mild to moderate vocal cord edema and laryngopharyngeal reflux signs were found in patients with CH (100% of patients with CH vs. 15% of HC, p < 0.001).

Conclusion: Creaky phonation is a "physiological mode of laryngeal operation" usually underpinned by shortened and thickened vocal folds. Creaky voice phonation can be due to a vocal fold's reduced capability to become slack or flaccid secondary to vocal cord edema underpinned by laryngopharyngeal reflux affecting the phonatory mechanisms in patients with CH. The laryngopharyngeal reflux may represent a dysautonomic sign related to the increased parasympathetic tone during in-bout period, reinforcing the hypothesis of an extracranial autonomic dysfunction as part of CH clinical picture.

Keywords: cluster headache; creaky voice; extracranial autonomic symptoms; laryngoscopy; vocal cord edema; voice analysis.

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Conflict of interest statement

The authors declare the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Silvestro has received speaker honoraria from Lilly, Novartis, and Teva. Professor Russo has received speaker honoraria from Allergan, Lilly, Novartis, and Teva and serves as an associate editor of Frontiers in Neurology (Headache Medicine and Facial Pain session). Professor Tessitore has received speaker honoraria from Novartis, Schwarz Pharma/UCB, Lundbeck, Abbvie, and Glaxo. Professor Tedeschi has received speaker honoraria from Sanofi Aventis, Merck Serono, Bayer Schering Pharma, Novartis, Biogen‐Dompe´ AG, Teva, and Lilly; has received funding for travel from Bayer Schering Pharma, Biogen‐Dompe´ AG, Merck Serono, Novartis, and Sanofi Aventis; and serves as an associate editor of Neurological Sciences. The other authors have no conflict of interest to declare.

Figures

FIGURE 1
FIGURE 1
(A) Laryngoscopic image showing signs of laryngeal irritation associated with reflux: Interarytenoid bar is identified by the yellow asterisk; Arytenoid medial wall erythema/edema is identified by the green asterisks; Reinke's edema is identified by the blue asterisks. (B) Normotrophic true vocal folds in the absence of signs of laryngeal inflammation
See this image and copyright information in PMC

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