Laryngeal motility alteration: A missing link between sleep apnea and vagus nerve stimulation for epilepsy

Abstract

SUMMARYThis study aimed to evaluate the prevalence and the relationship of sleep breathing disorders (SBDs) and laryngeal motility alterations in patients with drug-resistant epilepsy after vagus nerve stimulator (VNS) implantation. Twenty-three consecutive patients with medically refractory epilepsy underwent out-of-center sleep testing before and after VNS implantation. Eighteen eligible subjects underwent endoscopic laryngeal examination post-VNS implantation. Statistical analysis was carried out to assess an association between laryngeal motility alterations and the onset/worsening of SBDs. After VNS implantation, 11 patients showed a new-onset mild/moderate SBD. Half of the patients already affected by obstructive sleep apnea (OSA) showed worsening of SBD. All of the patients with a new-onset OSA had a laryngeal pattern with left vocal cord adduction (LVCA) during VNS stimulation. The association between VNS-induced LVCA and SBD was statistically significant. This study suggests an association between VNS and SBD, hinting to a pivotal role of laryngeal motility alterations. The relationship between SBD and VNS-induced LVCA supports the need to routinely investigate sleep respiratory and laryngeal motility patterns before and after VNS implantation. KEY WORDS: Sleep breathing disorders, Drug-resistant epilepsy, Vocal cord dysfunction.Sleep breathing disorder (SBD) appearance in patients with epilepsy who are treated with vagus nerve stimulator (VNS) was first reported by Malow and colleagues and confirmed by other authors. [1][2][3][4][5][6][7][8] The mechanisms by which VNS can induce SBD are not clearly understood. A possible explanation is based on the effects on laryngeal muscles related to VNS. 9 The aim of this study is to evaluate the prevalence of SBD and laryngeal functional obstruction after VNS implantation in order to ascertain the correlation between these two clinical issues. Materials and Methods PatientsTwenty-three consecutive patients (16 female) were recruited from the Regional Epilepsy Centre of San Paolo Hospital, University of Milan, Italy. All of the patients were affected by drug-resistant epilepsy and were taking antiepileptic polytherapy. Patients' demographics and clinical characteristics are summarized in Table S1.All patients underwent an out-of-center sleep testing (OCST) before and after VNS implantation. All patients with sufficient collaboration (18 patients) underwent postimplantation awake endoscopic laryngeal examination.VNS stimulation parameters, body mass index (BMI), and epileptologic data for each patient are reported in Table S2. OCSTAll 23 patients underwent an OCST with a portable device, Embletta (Embla, Broomfield, CO, U.S.A.), which allows measurement of thoracic and abdominal respiratory 10 Respiratory events index (REI) was used to describe obstructive sleep apnea (OSA). REI equals the ratio between apnea and hypopnea events to reported total sleep time. An REI ≥5 was chosen to define clinically significant OSA.In addition, we analyzed variation of REI in the...

Decreased heart rate and enhanced sinus arrhythmia during interictal sleep demonstrate autonomic imbalance in generalized epilepsy

“…VNS has been shown to regulate sympathetic activation of the sinoatrial node (Zhou et al 2016) and reduce resting HR (Mulders et al 2015) and is believed to enhance parasympathetic activity (Kampusch et al 2015). Additionally, VNS is hypothesized to worsen sleepbreathing disorders via altered laryngeal motility (Zambrelli et al 2016) and has been shown to trigger obstructive sleep apnea, a condition often coupled with an overexpression of parasympathetic activity (Ebben et al 2008;Parhizgar et al 2011;Vollono et al 2015).…”

Pharyngolaryngeal spasm‐induced dysphagia in an epileptic patient undergoing vagus nerve stimulation therapy

“…Early complications consist in intraoperative bradycardia (1/1000 cases), infections (3%‐8%), and VN injury. Late complications consist mainly in laryngeal dysfunction with hoarseness, dyspnoea and cough, usually related to the frequency of stimulation, vocal fold palsy, laryngopharyngeal reflux, and obstructive sleep breathing disorders . While most of these alterations have been related to the variation of vocal cord movements during stimulation or to the orthodromic effect of VN stimulation, no study associated, at present, abnormal laryngopharyngeal movements with dysphagia symptoms, which are nevertheless well‐known in VNS patients.…”

Impact of vagus nerve stimulation on sleep-related breathing disorders in adults with epilepsy

“…To date, however, the prevalence of SAS in patients with VNS remains largely unknown, due to the fact that the aforementioned studies included relatively small groups of patients selected from a sleep medicine angle, who are not necessarily representative of the whole population of patients with epilepsy implanted with VNS. Nevertheless, VNS related SAS seems to be frequent enough that sleep study screening before implantation is considered [8,9,12,13,16,17]. Screening after the implantation could be also important, in as much as VNS increases wakefulness [18], which could mask one of the cardinal symptoms of SAS, daytime somnolence [6,19,20].…”

“…While lacking an evidence-based approach, many treatment options have been described for patients with VNS related SAS: continuous positive airway pressure (cPAP) [8,9,13,14,16,17,21]; positional therapy [8,9]; changes in stimulator settings (especially increasing OFF time or decreasing stimulation frequency) [6,8,16,17,22]. It has been suggested that VNS parameters modifications might further enhance the cPAP impact [14].…”

“…It has been suggested that VNS parameters modifications might further enhance the cPAP impact [14]. In severe cases, VNS deactivation at night has been mentioned [8,16,17]. Treating SAS seems important not only for the quality of life, but also because sleep disruption can increase seizure frequency [6,8,17], on top of representing an independent cardiovascular risk factor [19,23].…”