Introduction

The spectrum of sleep-disordered breathing (SDB) includes many disorders from snoring to obstructive sleep apnoea (OSA), characterized by repeated and recurrent upper airway collapses during sleep. These conditions can lead to recurrent desaturations, fragmented sleep, significant fluctuations in arterial blood pressure, and increased sympathetic nervous system activity. About one billion adults between 30 and 69 years old suffer from OSA, a complex disease with a multifactorial pathophysiology. The majority of patients (60%) have mild OSA, while the remaining 40% present a moderate to severe degree [1]. Habitual snoring is very common in the middle-aged population and it is considered a prelude to OSA [2]. OSA is based on the reduction of upper airway dimensions, resulting from both anatomical and functional alterations, and the increase of pharyngeal collapsibility due to reduced neuromuscular compensation and lack of the pharyngeal protective reflex during sleep. The decreased upper airway size and increased resistance can cause the vibration of the soft palate, the uvula and/or the lateral walls of the pharynx, with consequent snoring [3]. The most common collapse site is the velum, but it is very common to find multilevel collapses also involving the tongue base and lateral walls of pharynx [4]. According to guidelines, continuous positive airway pressure (CPAP) remains the gold standard for treatment of moderate and severe OSA. However, this therapy has poor compliance rates since long-term adherence to CPAP treatment has been reported to fail in 25 to 50% of cases [5]. Although OSA treatment is well established, currently there are no specific guidelines on snoring and management of mild OSA. It has been shown that insufficient sleep may lead to adverse changes in energy intake, weight gain, insulin sensitivity, blood pressure, inflammatory markers, cognitive performance, and markers of neurodegenerative disorders, such as Alzheimer’s disease [6]. Analysis has shown how snoring affects the electroencephalogram (EEG) such that snoring sounds, even if they do not wake up the individual, do affect the deep restorative sleep. Snorers may have attention deficits, difficulty in concentrating, and forgetfulness during the daytime [7]. Many lifestyle modifications can improve snoring such as cessation of smoking and drinking as well as weight reduction. In addition, the American Academy of Sleep Medicine (AASM) and the American Academy of Dental Sleep Medicine (AADSM) suggest the application of mandibular advancement devices (MAD), as opposed to no therapy, for adults with primary snoring [8]. It is well known that an increase of the pharyngeal muscle activity or tone may reduce upper airway collapsibility. Transcutaneous electrical stimulation activates dysfunctional skeletal muscles, significantly improving muscle tone and function recovery. Similarly, the electrical stimulation may activate tongue muscles, leading to a similar effect during sleep [8]. Recently, following the rapid dissemination of wearable devices, new non-invasive electrical stimulation devices have been developed to increase tongue muscle tone for patients with mild OSA and snorers. However, there are no systematic reviews regarding the use of these new devices. The aim of this study was to systematically review the first reports regarding the efficacy of these new devices for snoring and mild OSA.

Methods

General study design

The study was designed using the recommendations of the Centre for review and Dissemination’s Guidance for Under-taking Review in Health Care and is being reported in adherence with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement [9].

Data sources

An electronic search was performed on PubMed/MEDLINE, Google Scholar, and Ovid databases. Searches were adjusted to fit the specific requirements for each database. An example of a search strategy is the one used for PubMed/MEDLINE: “electric stimulation therapy” and “snoring”, “awake stimulation therapy” and “obstructive sleep apnea”, “electric stimulation therapy” and “obstructive sleep apnea”, “electric stimulation therapy” and “sleep apnea syndrome”, “electric stimulation therapy” and “upper respiratory airways”, “ electric stimulation therapy” and “ primary snoring”, “intraoral device” and “awake stimulation therapy”, “neuromuscular electric stimulation” and “ intraoral device”, “neuromuscular electric stimulation” and “muscle tonus”, “intraoral device” and “snoring”. Three reviewers (AM, LC, and LG), working independently, screened all abstracts and titles for candidate studies. Then, a cross-reference search of the included studies was performed to minimize the risk of missing relevant data. The last search was run in September 2021.

Inclusion/exclusion criteria

The selection of the studies was based on original articles that reported the use of an intraoral device that performs an awake neuromuscular electric stimulation of the tongue muscles. Exclusion criteria for the study were as follows: (1) studies not in English; (2) case reports, reviews, conference abstracts, letters, and paediatric studies; and (3) studies with unclear and/or incomplete data. No publication date restriction was imposed.

Data extraction and data analysis

All articles were initially screened by title and abstract. The full-text version of each publication was assessed, and those whose content was judged not to be strictly related to the subject of this review were excluded. Data extraction of the studies included the population demographics, control conditions, study designs, and outcomes.

Results

Search criteria returned 987 articles and 878 were removed because they were not clinical trials. These remaining articles were screened and a further 105 were excluded, resulting in 4 studies meeting criteria for inclusion in this review. A total of 283 patients who met all selected criteria were enrolled in the studies, of whom 28 were lost at follow-up. A total of 265 patients (aged between 24 and 79 years) completed the trials. The flow diagram shown in Fig. 1 (PRISMA Flow Diagram) depicts the selection process. The baseline characteristics of these studies are reported in Table 1: study design, sleep breathing disorders (snoring/OSA), number of patients included and mean age, sex, BMI, and follow-up visits. In Table 2, we describe the studies included in the review specifying type of device investigated, pre- and post-treatment values (apnoea–hypopnoea index (AHI), Epworth sleepiness scale (ESS), and Pittsburgh sleep quality index (PSQI)). In addition, the risk of bias for the randomized controlled studies was evaluated using the Cochrane risk of bias tool (Fig. 2).

Fig. 1
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Flowchart outlining the paper selection process of the systematic review (based on PRISMA guidelines). PRISMA indicates preferred reporting items for systematic review and meta-analysis

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Table 1 General characteristics of included studies
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Table 2 Summary of studies reporting data on non-invasive electrical stimulation devices
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Fig. 2
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Assessment of the Risk of Bias of the included studies

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Apone-Stim 400 Muscle Stimulator

The first study was conducted by Randerath et al. in 2003 [10]. They performed a randomized, placebo-controlled, double-blind study including 77 patients with primary snoring and mild OSA divided into treatment groups (33 patients) and placebo groups (34 patients). The treatment group was subjected to tongue muscle training using the Apone-Stim 400 Muscle Stimulator device. This single-channel output device produces a symmetric biphasic output delivered twice a day for 20 min for 8 weeks. One electrode is placed in the mouth under the tongue, and the other is placed externally under the chin. At the end of the study, the authors noticed that there was no improvement in AHI observed after training in either group. However, in the study group the number of snoring epochs significantly decreased (baseline 63.9 ± 23.1 epochs per hour versus 47.5 ± 31.2; P < 0.05)

EXciteOSA

Three studies were found using EXciteOSA device. This device works by delivering bipolar biphasic current (0–20 Hz) through a washable flexible mouthpiece with four electrodes placed in pairs above and below the tongue. It is used for 20 min once a day during a wakeful state, for a period of 6 weeks. Following this protocol, Wessolleck et al. in 2018 [11] included 16 patients with snoring and mild OSA showing a statistically significant reduction in the snoring VAS (p < 0.05), from 5.6 ± 1.1 (baseline) to 3.2 ± 2.7 (after the treatment), remaining stable after the treatment. This parameter lowered on average of 44% by the end of the treatment phase, but no effect was noticed on AHI.

In 2021, Kotecha et al. [12] included 32 simple snorers and 38 patients affected by mild OSA. After the treatment, they noted an objective reduction of snoring in 95% of participants, with an average snoring time reduction of 48%. Also the VAS reported by partners demonstrated a snoring reduction in 95% of patients. In addition, in a subset of 38 patients with mild OSA, the authors showed a significant reduction in AHI values (from 9.8 to 4.7 events/h), oxygen desaturation index (ODI) values (from 7.8 to 4.3 events/h), and ESS values (from 9.0 to 5.1).

In 2021, Baptista et al. [8] conducted a multicenter prospective study on 115 patients with primary snoring (50 patients) and mild OSA (65). Ninety percent of patients demonstrated an improvement in their objective snoring time, with a mean reduction of 41%. A mean improvement of 52% in snoring intensity was demonstrated. Bed partner reported snoring reduced significantly by 39%. ESS and total PSQI scores reduced significantly (p < 0.001) as well as bed partner PSQI (p = 0.017). The authors noted a significant reduction in AHI (from 6.85 to 5.03/h) and ODI (from 5.68 to 4.33/h).

Figures 3 and 4 show the mean values of snoring VAS and AHI before and after the treatment with EXciteOSA. For the first parameter, there was a reduction of slightly less than 50% of the initial score, while the AHI decreased after treatment, though this difference was not statistically significant (p = 0.12).

Fig. 3
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Snoring VAS values before and after treatment

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Fig. 4
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AHI values before and after treatment

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Discussion

While sleeping, the activity and the tone of the pharyngeal dilator muscles naturally tend to decrease, leading to an increased supraglottic resistance to respiration airflow. This phenomenon is more exaggerated in patients with OSA due to the presence of antero-posterior collapse of the tongue base or multilevel collapse. The reduced upper airway diameter significantly increases the speed of the inhalation airflow and leads to local pressure variations, causing soft tissues vibrations and snoring [11]. Primary snoring can be intermittent or continuous and it is characterized by a remarkable heterogeneity.

According to some studies, based on the frequency of the sound of snoring, it is possible to trace the anatomical site that caused it. In particular, the frequency might be 200 Hz at the level of the palate and 1000 Hz at the tongue base [7]. The intraoral neuromuscular electric stimulation (NMES) technique is a non-invasive approach, involving the application of an electric current through electrodes placed over the target muscles inducing muscular contractions even in portions that are generally not active during voluntary movements. Through this muscular contraction, the technique can improve muscle tone and activity of the pharyngeal dilator muscles, preventing the upper airway collapse and reducing snoring and the number of apnoea and hypopnoea episodes. The devices based on this principle use a direct transmucosal stimulation of tongue’s intrinsic and extrinsic (genioglossus) muscles. It has been shown that NMES leads to a change in myofibrillar protein expression, inducing phenotype shift of fatigue-prone to fatigue-resistant (i.e. fibre type II to IIa changes or I), with a strengthening of the cytoskeleton. It is likely that a similar mechanism of action occurs in the oral cavity when the snorers use these devices (in particular EXciteOSA), leading to improvement in sleep indices [8]. The most common device in this field is EXciteOSA. This innovative device is composed of three components: a washable flexible mouthpiece with an electrode array that fits onto the tongue, a rechargeable control unit, and a smartphone app managing the functions of this device. The mouthpiece is placed under the tongue, and a bipolar biphasic current is delivered with a predetermined setpoint, migrating between three frequencies (0–20Hz). Using the designed app, the patient controls the current intensity and has full control of the device via remote control, making it safe and attractive. No similar information has been reported for the other included device, Apone-Stim 400 Muscle Stimulator.

Another important aspect of the EXciteOSA is that it is a daytime therapy device with a low burden of use for the patient. This makes patient tolerability and acceptance of the therapy much more feasible than night therapies such as MAD [1, 5]. EXciteOSA has shown an adherence to therapy over 80%. Another well-accepted daytime treatment is myofunctional therapy with high adherence in patients reaching a compliance rate of 90% [13]. However, it is necessary to underscore that there is only one short-term study on tolerability of EXciteOSA. Long-term follow-up trials would be desirable in order to confirm these results.

Recently, the AASM, in collaboration with AADSM published a meta-analysis on 11 randomized control trials (RCT), evaluating adherence rates with MAD versus CPAP in patients with mild OSA. The study showed that the adherence rates for both devices were found to be approximately 4 h of use per night [8]. As EXciteOSA is a daytime therapy, no direct comparison can be undertaken for night-time adherence.

Four main findings emerge from this systematic review. First, all studies suggested that these new non-invasive electrical stimulation devices effectively improve snoring by approximately 50% (Fig. 2). In particular, there was an objective snoring improvement based on polysomnography findings, with 41% improvement in the percentage of time spent snoring and 52% in snoring intensity [8]. From a subjective point of view the patients seemed satisfied with the improvements, as shown by the good results of the subjective parameters investigated (VAS snoring, ESS and PSQI).

Second, only two investigations [8, 12] showed a significant AHI improvement in mild OSA. Third, in this review, no significant complications were recorded, while only few minor side effects were described, such as excessive salivation, tongue or tooth discomfort, tongue tingling, dental filling sensitivity, metallic taste, gagging, and tight jaw. Tooth discomfort and filling sensitivity were typically linked to an increase in stimulation intensity and alleviated by repositioning the mouthpiece or with a reduction in the intensity of the therapy. Fourth, EXciteOSA was found to be useful only for snoring and mild OSA and, consequently, cannot be considered as an alternative to CPAP therapy prescribed for moderate and severe OSA. However, there is evidence suggesting that primary snoring may increase a person’s risk of cardiovascular and cerebrovascular diseases as well as metabolic syndrome with impaired glucose tolerance. Many studies have shown an increased risk from 1.3 to 1.7 times for hypertension, myocardial infarction, and stroke in snorers compared to non-snorers [14, 15]. In this review, there are many limitations. The lack of numerous studies on this topic (only four studies) is a substantial limitation. Additionally, these studies lack control groups, so it was not possible to perform a comparison with other similar treatment and/or no treatment. The samples included in this review were very heterogeneous: only Kotecha et al. [12] and Baptista et al. [8] recorded the effect of these new devices on two different subtypes of patients, those with OSA and snorers, while the other authors investigated the effects in mixed groups composed of snorers and patients with OSA without distinction [10, 11]. Studies of larger scale and with longer follow-up periods will be needed regarding durability of the effects after the discontinuation of therapy.

Conclusion

Intraoral neuromuscular electric stimulation can be considered as an option to current therapies for snoring. The studies included in this review showed both objective and subjective data in terms of snoring reduction. Data on improvement in sleep quality are very encouraging. Further studies are needed to support these interesting new devices.