A variety of different therapeutic methods are now available for the treatment of neurogenic dysphagia. Since the indication for a specific treatment is determined not only by the phenotype of swallowing impairment, but also by the underlying etiology of dysphagia, an appropriately focused diagnostic work-up (see above) is essential before the final therapeutic strategy is determined. In this section, dietary, behavioral, pharmacological, and local interventional treatment options as well as neurostimulation procedures are presented and the importance of oral hygiene in patients with dysphagia is explained.
Dietary interventions
Recommendation 29: Texture-modified diets, thickened liquids and / or systematic modifications of bolus size should only be prescribed based on the findings of a swallow examination.
Recommendation 30: Thickening of liquids can be used in patients with neurogenic dysphagia who show aspirations with liquids.
Recommendation 31: To improve patient compliance, different types of thickeners should be offered and tested.
Recommendation 32: Texture-modified diet can be used in patients with chronic dysphagia to improve their nutritional status.
Recommendation 33: Despite the use of texture-modified food and thickened liquids, patients with neurogenic dysphagia are at increased risk of malnutrition, dehydration, and aspiration pneumonia and should, therefore, be monitored for these complications.
The use of texture-modified foods and thickened liquids has become one of the most common therapeutic strategies to address neurogenic dysphagia. The idea behind this approach arises from the assumption that modifying the properties of normal food and liquids will make them easier and safer to swallow [
140]. Despite the widespread use of this intervention, its scientific foundation in many areas is still incomplete or not convincing.
For decades there were no established and universally used terminology and definitions to describe the target consistency recommended for patients with OD and to guide its preparation [
140]. Only recently the “International Dysphagia Diet Standardisation Initiative” (IDDSI) has been established that pursues the goal to develop global standardized terminology and definitions for texture modified food and thickened liquids for individuals of all ages, in all care settings, and all cultures [
141].
Despite this ongoing discussion focused on terminology and definition issues [
142], the effect of liquid thickening on the safety and efficacy of the swallow has been extensively investigated [
143]. The results of more than 30 studies were summarized and analyzed in two recent systematic reviews and a white paper [
140,
144,
145]. Those papers unanimously conclude that thickening liquids reduces the risk of aspiration in different patient groups. Although the available data are insufficient to suggest particular viscosity values, the analysis put forward by Newman and colleagues suggest that on the continuum covering the whole spectrum from “thin”, “nectar”, “honey” to “spoon thick”, there seems to be a dose-response characteristic with thicker liquids being safer than thinner liquids [
145]. As a flip side of the coin, liquid thickening seems to increase the risk of post-swallow residues [
140,
144,
145]. Although not as unequivocal and as frequently studied as aspiration, several studies reported oral and/or pharyngeal residues with ultra-thick liquids [
37,
72,
146,
147].
As an alternative or supplement to viscosity adaptation, the bolus volume can also be adjusted. As shown in a systematic review, bolus volumes ≤ 5 ml have a lower aspiration risk than bolus volumes ≥ 10 ml [
148].
In addition to these effects focused on the physiology of swallowing, clinically relevant endpoints have also been studied in the context of liquid thickening and texture modifications. Contrasting with its positive effect on swallowing safety, liquid thickening has failed to substantially improve fluid intake in several studies [
149,
150] and systematic reviews [
151,
152]. The main reason for this is that thickened liquids are poorly tolerated due to changes in taste, a “coating feeling in the mouth” and an insufficient alleviation of thirst [
153]. In addition to a compliance-related, reduced fluid intake, thickening of liquids, therefore, correlated with a reduced quality of life [
154].
Apart from viscosity, thickening agents also influence other characteristics of the liquids, such as texture, taste, and appearance. There is first evidence that different types of thickeners, in particular starch and rubber-based products, differ in this respect, which can have an impact on patient compliance [
147].
The impact of feeding strategies involving texture modified diets on oral intake has been assessed in one small RCT [
155]. In elderly dysphagic nursing home residents both food intake and nutritional status were improved in the intervention group over a time period of 12 weeks. In addition, a cohort study recruiting acute stroke patients showed that by being given a dysphagia diet, patients could achieve more than 75% of their energy requirements [
156].
The effect of dietary interventions to prevent aspiration pneumonia has been studied in several systematic reviews and Cochrane analyses related to patients with dementia [
157,
158], geriatric stroke patients [
159] and geriatric patients with oropharyngeal dysphagia of heterogeneous etiologies [
151]. It is generally concluded that the number of high-quality studies is too low to recommend the use of texture modified food and thickened liquids for the prevention of aspiration pneumonia. Of particular relevance in this context is the large RCT by Robbins and co-workers, which included more than 500 patients with dysphagia due to Parkinson’s disease or dementia and proven aspiration of thin liquids in VFSS. This study did not find a significant difference in the incidence of aspiration pneumonia between the group receiving thickened liquids and the group being treated with chin-down posture and normal liquids [
160].
While dietary interventions in isolation appear to have only a small effect size, this approach may be more effective and meaningful when used within a multidimensional concept to prevent aspiration pneumonia. Thus, the so-called „Minimal-Massive Intervention (MMI)", which aims to reach as many patients as possible with a resource-saving (minimal) intervention and thereby achieve a large ("massive") effect, comprises the components (i) fluid and food texture adaptation, (ii) dedicated oral care (see below) and (iii) nutritional supplementation and targets the group of frail geriatric patients [
161]
In a prospective non-controlled intervention study, this set of measures was used to reduce mortality, pneumonia rates and the rate of re-hospitalization and to improve the nutritional status of patients compared to a historical control group [
161].
Behavioral swallowing interventions
Recommendation 34: Before initiating behavioral swallowing interventions, the etiology and phenotype of dysphagia should be determined.
Recommendation 35: The Shaker maneuver should be used in patients with pharyngeal residues and impaired opening of the UES.
Recommendation 36: Expiratory muscle strength training (EMST) should be used to treat dysphagia in patients with motor neuron disease, stroke and M. Parkinson. EMST should preferentially be applied within prospective clinical trials.
Recommendation 37: The chin-tuck maneuver should be used to improve swallowing safety in patients with impaired oral bolus control and consecutive premature spillage with subsequent predeglutitive aspiration.
Recommendation 38: Effortful swallowing can be used to improve tongue strength and swallowing physiology.
Recommendation 39: A systematic, regular and individualized behavioral swallowing therapy should be used early on in patients with neurogenic dysphagia, especially in patients with post-stroke dysphagia.
Exercises and maneuvers probably constitute the most widespread treatment approach for patients with neurogenic dysphagia. In German-speaking countries, non-swallow specific concepts such as Kay Coombes’ Facial-Oral Tract Therapy (F.O.T.T.®) and Castillo Morales’ orofacial regulation therapy (ORT) are as well used as the so-called functional dysphagia therapy (FDT), which was significantly developed and put into practice by Gudrun Bartolome. The latter approach selects interventions according to the concrete pattern of neurogenic dysphagia that is present in a given patient [
162,
163]. Most studies in this scientific area are devoted to the FDT or single elements of it.
Restorative techniques are intended to restore impaired swallowing functions or to promote residual functions. This is done via pre-swallow stimulation (e.g., thermal stimuli), mobilization techniques (e.g., tongue pressing against resistance), and specific motor exercises (e.g., Shaker exercise, Masako maneuver, EMST).
In contrast, compensatory methods are used during the swallow to enable effective and safe deglutition despite functional impairments. A distinction is made between postural maneuvers (e.g., chin-tuck or head-turn maneuvers) and special swallowing techniques (e.g. Mendelsohn maneuvers, supraglottic swallowing). Despite their great importance for the treatment of dysphagia in everyday care, the scientific evidence for the efficacy of this type of treatment is heterogeneous with a general lack of large RCTs providing clinical meaningful endpoints [
164].
The Shaker head lift is one of the best studied exercises used in dysphagia rehabilitation for many years and is designed for patients with weakness of the suprahyoid muscles and impaired opening of the upper oesophageal sphincter [
162,
163]. This procedure is a head rising exercise with an isometric high-intensity portion with three head lifts held for 60 s with a 60 s rest period between each one and an isokinetic low-intensity portion that included 30 consecutive head lifts of constant velocity without holding. The Shaker head lift has been evaluated in systematic reviews [
165] and several RCT [
166‐
169] showing that this treatment improves strengths and endurance of the suprahyoid muscles and upper oesophageal sphincter opening. In addition, there is evidence that residues and aspiration events are reduced.
The tongue muscles can also be trained through targeted exercises. Basically, tongue strength decreases with age [
170], and reduced tongue strength proved to be a risk factor for aspiration [
171]. Tongue strength training has been evaluated in several cohort studies and one RCT for the treatment of neurogenic dysphagia. These trials report different improvements of swallowing variables like vallecular residues and swallowing safety [
172,
173].
The Masako maneuver involves swallowing while protruding the tongue beyond the lips, holding it between one’s teeth. It is meant to have a strengthening effect on the tongue and the pharyngeal walls after a period of training [
162,
163]. Studies in healthy subjects did not find immediate effects on swallowing physiology [
174]. A RCT including healthy subjects exposed to a four-week training with the Masako maneuver or a control task found no effect on the swallow [
175]. In a small RCT recruiting subacute stroke patients the Masako maneuver was compared with neuromuscular electrical stimulation. In that trial both groups showed improvement of swallowing function, however, since a control group was missing, these results need further confirmation [
176].
The so-called Lee Silverman Voice Treatment (LSVT-LOUD®) was originally developed to treat Parkinson-related dysphonia. In two smaller observational studies on 8 respectively 20 Parkinson patients, the authors also found improvements in various parameters of the oral and pharyngeal phase evaluated by VFSS [
177,
178].
Expiratory muscle strength training (EMST) involves exhaling quickly and forcefully into a mouthpiece attached to a one-way valve, blocking the flow of the air until the patient produces sufficient expiratory pressure. It is meant to strengthen the expiratory and submental muscles by increasing the physiologic load [
164]. This treatment has shown significant effects on swallowing safety in a RCT in Parkinson patients [
179], has improved swallowing safety and feeding status in an RCT in subacute stroke patients [
180,
181], has been associated with positive effect on swallowing-related muscle strength in elderly participants [
182], and improved swallowing safety in patients with multiple sclerosis [
183]. In ALS patients, an RCT and a cohort-study with pre-post design found that EMST improved swallow kinematics, in particular hyo-laryngeal elevation [
80]. In patients with Huntington's disease, on the other hand, no effect of EMST was found on various parameters of swallowing physiology and clinical endpoints [
184]. A meta-analysis summarizing this evidence across different disease categories also came to a positive conclusion [
185].
The chin-down is a technique used for patients who have decreased airway protection associated with delayed swallow initiation and/or reduced tongue base retraction. To perform this maneuver, patients lower the chin towards the chest and keep this position during swallowing [
162,
163]. In several studies physiological changes like expansion of the vallecular recesses, approximation of the tongue base toward the pharyngeal wall, narrowing of the entrance to the laryngeal vestibule, expedited onset of laryngeal vestibule closure, reduction in distance between hyoid and larynx, and increased duration of swallowing apnea [
186]. In two well-designed cohort studies the aspiration risk could be reduced by 50% [
187,
188].
In patients with unilateral pharyngeal palsy, a head turn towards the paretic side may be applied, which, if the respective swallowing impairment also affects the oral swallowing muscles, may be supplemented by a head tilt to the non-affected side [
162,
163]. These maneuvers allow swallowing over the non-affected side and thus lead to a more effective pharyngeal bolus transfer [
189].
The effortful swallow is mainly used in patients with an inefficient swallowing act characterized by residues in the valleculae or the sinus piriformes [
162,
163]. A variety of effects on swallowing physiology could be attributed to this maneuver in studies involving both, healthy subjects and patients with neurogenic dysphagia. Thus, the effortful swallow has been shown to increase hyolaryngeal excursion, duration of hyoid elevation and UES opening, laryngeal closure, lingual pressures, peristaltic amplitudes in the distal oesophagus and pressure and duration of tongue base retraction in healthy subjects [
190,
191]. In an RCT in which healthy subjects were treated with either effortful swallowing or a sham exercise, a non-significant increase in tongue strength was found in the treatment group after 4 weeks of intervention [
192]. In a small RCT, in which dysphagic stroke patients either used effortful swallowing or performed a sham exercise (saliva swallowing), the intervention was associated with a significant improvement in tongue strength and oral swallowing function [
193]. In addition, a small cohort study of Parkinson patients showed an increase in manometric pharyngeal pressure levels [
194].
The Mendelsohn maneuver is a technique used for patients with decreased hyolaryngeal excursion and/or decreased duration of UES opening and is frequently combined with some form of biofeedback to help the patient perform it. To execute this maneuver, patients are instructed to keep the thyoid cartilage for several seconds in an elevated position before finishing the swallow [
162,
163]. Studies with healthy subjects, have demonstrated with different methods of instrumental assessment that the Mendelsohn maneuver leads to various changes in the swallowing process. In particular a prolonged contraction of the submental and pharyngeal muscles, as well as the hyolaryngeal elevators have been witnessed [
195]. According to a recent review, the effect on hyolaryngeal elevation can be improved by simultaneous EMG biofeedback [
100]. In a small observational study, the combined use of effortful swallowing and the Mendelsohn maneuver in 3 dysphagic stroke patients reduced the aspiration risk. Long-term effects of the Mendelsohn maneuver have been evaluated in one RCT in stroke patients [
196,
197]. In that study the authors could demonstrate that hyoid movement and upper oesophageal sphincter opening improved after treatment.
The super-supraglottic swallow is used as compensatory maneuver for patients with reduced airway closure. This maneuver involves the patient holding a tight breath, swallowing while keeping the airway closed, then immediately coughing after the swallow. It has been shown in several studies that the super-supraglottic swallow has immediate effects on swallowing physiology [
198]. Studies with relevant clinical endpoints are not available so far [
164].
Since patients with neurogenic dysphagia usually have variable and complex disorders, a combination of various adaptive, compensatory and restorative techniques has often been used in intervention studies. In their systematic review, Speyer et al. summarized 4 RCTs and 27 non-randomized studies, most of which found a significant improvement in swallowing function and other related endpoints [
152]. In a Cochrane Review, updated in 2018, with focus on the treatment of post-stroke dysphagia, the use of behavioral techniques showed no effects on the key endpoints mortality and global functional outcomes. However, behavioral swallowing interventions was associated with a significant improvement in swallowing function and there was a trend for a reduction in length of hospital stay and a reduction in respiratory complications [
199]. The largest RCT to date has been performed by Carnaby and co-workers [
200] in stroke patients. The authors randomized 306 patients with acute dysphagic stroke to a control group receiving speech therapy according to local conditions, or in two therapy groups receiving either standardized, low-frequency or standardized high-frequency dysphagia therapy. The primary endpoint of the study was the proportion of patients taking a regular oral nutrition six months after stroke. Although the primary endpoint was narrowly missed (56% of the control group and 67% of the two therapy groups achieved the primary endpoint), standardized behavioral swallowing interventions (either low or high-intensity) showed a trend to reduce the combined endpoint of mortality or institutionalization and significantly reduced the rate of medical complications and the frequency of bronchopneumonia [
200].
In addition, several comprehensive treatment programs have been evaluated in non-randomized trials. The McNeill dysphagia treatment protocol improved swallowing physiology in an observational study [
201], as well as diet and clinical swallowing ability in a case-control and cohort study [
202,
203]. The intensive dysphagia rehabilitation protocol was tested in a small observational study and improved the severity of aspiration and level of oral intake [
204]. Similar results were found in a prospective study recruiting a small cohort of dysphagic geriatric patients. Here, swallowing function improved after 8 weeks of systematic swallowing treatment [
205].
Oral hygiene in patients with neurogenic dysphagia
Recommendation 40: In patients with neurogenic dysphagia, good oral health should be established to reduce the risk of pneumonia and, if necessary, consistent oral hygiene should be performed.
Poor oral health in combination with dysphagia has been identified in particular in stroke and geriatric patients as a risk factor for aspiration pneumonia [
206,
207]. In addition to periodontitis, gingivitis, plaque formation and caries, respiratory pathogens such as Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella oxytoca, Pseudomonas aeruginosa and Escherichia coli have frequently been detected in the oral cavity of these patients [
208]. The aspiration of bacterial contaminated saliva is therefore considered to be the main pathogenic mechanism of pulmonary infections in severely dysphagic patients fed via a gastric tube [
209]. In order to avoid aspiration-related respiratory infections, interventions to improve oral health and reduce oral germ load are considered as therapeutic option in various collectives. Studies in stroke patients have shown that both, establishing simple protocols for the oral hygiene and also the use of more complex procedures for oral and dental cleaning, lead to an improvement of oral health [
210]. In two RCTs the rate of respiratory infections in the intervention group was significantly lower than in the control group [
211,
212], while another study failed to demonstrate such an effect [
213]. In another RCT, the effect of selective oral decontamination was evaluated. In this study, both the pneumonia rate as well as the proportion of patients being colonized with oral pathogenetic bacteria were reduced in the intervention group that received non-absorbable antibiotics and antifungals, while there was no difference in mortality [
214]. In several cohort studies, RCTs and systematic reviews targeting mixed geriatric collectives and nursing home residents different forms of oral hygiene (regular brushing of teeth, chlorhexidine mouth rinses, professional dental cleaning) also reduced pneumonia rates [
215‐
219], while a smaller number of studies could not confirm this effect [
220‐
222]. Consistent oral hygiene is also part of the already mentioned "Minimal-Massive Intervention (MMI)" to avoid aspiration pneumonia in frail elderly people [
161].
Pharmacotherapy of neurogenic dysphagia
Recommendation 41: Before initiating pharmacotherapy in patients with neurogenic dysphagia, the pattern of swallowing impairment should be determined as precisely as possible.
Recommendation 42: Pharmacological therapies of neurogenic dysphagia can be considered as a supplement to behavioral swallowing interventions in particular in patients with a delayed swallow response.
Recommendation 43: Due to the limited evidence for pharmacological therapeutic approaches, these therapies should be considered on a case-by-case basis based on a careful risk-benefit analysis.
Pharmacological treatment of OD involves the use of drugs that stimulate the neural pathways of deglutition either on the peripheral sensory level or at different levels of the central nervous system [
20]. Classes of pharmacological agents that have been evaluated for their potential to improve disordered swallowing are TRPV1 agonists (Transient Receptor Potential Cation Channel Subfamiliy 1), ACE-inhibitors, dopaminergic agents and Sigma-1 receptor agonists. Currently, the potential of this treatment approach has not been fully explored. Despite some promising studies focused on swallowing physiology and a few well-made Proof-of-Principle-studies, sufficiently large multicenter RCTs with clinically relevant endpoints are not available for any of the mentioned pharmaceuticals.
TRPV1 agonists, in particular capsaicinoids and piperine, stimulate TRPV1 receptors expressed at free nerve endings of the superior laryngeal nerve and the glossopharyngeal nerve [
223]. In several case-control studies, observation studies and three RCTs in different patient collectives, it has been shown that these substances increase the safety of the swallowing by shortening the latency of the swallowing reflex, by shortening laryngeal vestibule closure time and improving laryngeal elevation [
71,
224‐
226]. In another RCT, the administration of capsaicin was associated with an increase in salivary substance P and an improvement in subjective swallowing capacity [
227]. Finally, an RCT in stroke patients using capsaicin in addition to defined dietary and behavioral interventions showed that clinically evaluated swallowing function showed better recovery in patients receiving capsaicin compared to placebo after a 3-week treatment period [
228]. However, studies with clinically relevant endpoints are still missing.
Disease-related loss of dopaminergic neurons, e.g. due to stroke or neurodegenerative diseases, contributes to the development of neurogenic dysphagia and is particularly associated with a delayed swallowing reflex [
229]. Application of L-Dopa has been shown to normalize the onset of the pharyngeal swallow in a RCT with cross-over design that recruited patients with post-stroke dysphagia [
230]. A second RCT, which also recruited chronic stroke patients, showed that nocturnal aspiration episodes could be reduced by a treatment with either amantadine or the dopamine receptor agonist cabergoline [
231]. Finally, in the largest RCT to date that recruited 163 chronic stroke patients with persistent dysphagia, Nakagawa and co-workers showed that treatment with 100 mg amantadine per day significantly decreased the rate of pneumonia over the study period of three years [
232].
ACE inhibitors are among the most commonly used antihypertensives. Their typical side effects include a dry cough caused by a reduced degradation of bradykinin and substance P. Substance P, which is released by free nerve endings in the pharynx and larynx, is known to enhance the swallow and cough reflex and there is evidence that decreased sputum levels of this neurotransmitter are associated with aspiration pneumonia [
233]. In accordance with this pathophysiological concept, ACE inhibitors have been shown to shorten the latency of the swallowing reflex, increase the spontaneous swallowing frequency and reduce the risk of nocturnal aspiration [
234‐
236]. Although these data suggest that ACE inhibitors can in principle lead to a strengthening of protective reflexes, studies targeting clinically relevant endpoints, in particular aspiration pneumonia, provided inconsistent results so far. On the one hand, a meta-analysis considering 5 RCTs and several case-control studies described a significant reduction in pneumonia risk associated with ACE inhibitor therapy [
237]. On the other hand, a multicenter RCT randomizing tube-fed post-stroke patients to 2.5 mg Lisinopril or placebo was prematurely terminated because of an excess of mortality in the intervention group. There was no difference in the incidence of pneumonia [
238].
Dextrometorphan (DM) is a weak NMDA receptor antagonist and also a Sigma-1 receptor agonist. Sigma-1 receptors are mainly found in the cerebellum and brain stem and, in particular, have been detected in bulbar motor neurons [
239]. Probably by using this biochemical pathway, DM in combination with quinidine (DM/C), which inhibits its degradation, has been shown to improve pseudobulbar affect disorder in patients with ALS and MS. In 2010, DM/C was therefore approved by the FDA for this indication and in the following years the use of this drug in everyday clinical practice was extended to patients with Parkinson's disease and dementia [
240]. In view of its pharmacological properties, Smith and colleagues investigated in a randomized clinical study using a cross-over design whether DM/C also had an impact on dysphagia in patients with ALS and clinically relevant bulbar symptoms [
241]. As a main result, this study showed a significant improvement of subjectively perceived swallowing function (primary endpoint), while no effect on objective parameters of swallowing function were found (secondary endpoint).
Neurostimulation
Recommendation 44: Before initiating dysphagia treatment with a neurostimulation approach, the pattern of swallowing impairment should be determined as precisely as possible.
Recommendation 45: All neurostimulation methods should be used as a supplement to the behavioral swallowing therapy.
Recommendation 46: Due to limited data, neurostimulation methods in principle should be used in clinical trials or registries.
Recommendation 47: Pharyngeal electrical stimulation (PES) should be used to treat dysphagia in tracheotomized stroke patients with supratentorial lesion. Participation in prospective clinical registries is recommended.
In recent years, various methods of peripheral (neuromuscular electrical simulation (NMES), pharyngeal electrical stimulation (PES)) and central neurostimulation (repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS)) have reached a stage of development that makes their use in the clinical context outside from controlled trials increasingly conceivable in the near future [
26]. Although these methods have been tested in a number of studies and in different patient populations of late, larger multicenter RCTs with clinically relevant endpoints are needed for a final assessment of their respective effectiveness.
Neuromuscular electrical simulation (NMES) stimulates sensory or motor nerve fibers involved in swallowing transcutaneously. Its mechanism of action is thought to include accelerating the development of muscle strength and promoting central nervous system recovery. NMES is commonly used in addition to behavioral swallowing therapy. Meta-analyses of predominantly smaller randomized and non-randomized studies showed a moderate effect of NMES on swallowing function and level of diet [
242‐
245]. These findings have been confirmed in two RCTs. Park and co-workers showed improved hyoid-movement in subacute stroke patients after treatment with NMES in combination with effortful swallowing compared to effortful swallowing alone [
246]. Terre and Mearin found improved feeding status in patients with OD after stroke or traumatic brain injury when being exposed to NMES and conventional swallowing therapy compared to conventional swallowing therapy alone [
247]. Another scientifically sound RCT, however, showed no additional benefit of sensory or motor NMES when supplementing behavioral swallowing therapy in patients with Parkinson's disease related dysphagia. Regardless of whether the patients received behavioral swallowing therapy alone or combined with sensory or motor NMES, a similar improvement of a variety of oral and pharyngeal phase parameters were demonstrated by instrumental swallowing assessment [
248].
In pharyngeal electrical stimulation (PES), the tongue base and the back of the pharyngeal wall are electrically stimulated via a transnasally inserted feeding tube housing a pair of bipolar ring electrodes. PES induces neuroplasticity within the swallowing network by targeting the pharyngeal motor and sensory cortices and possibly also working on the peripheral sensory afferent system. Muscle contraction, in contrast to NMES focusing on pure muscle strengthening, is not the aim of treatment. In smaller RCTs in dysphagic stroke patients and patients with neurogenic dysphagia due to multiple sclerosis, PES has been shown to improve dysphagia and, in some cases, even shorten the times to hospital discharge [
249‐
251]. The STEPS study, however, a large multicenter RCT investigating the effect of PES for the treatment of dysphagia in acute and subacute stroke patients, showed no effect of the intervention compared to sham stimulation [
252]. On the other hand, the multi-center PHAST-TRAC study, which recruited severely dysphagic, tracheotomized stroke patients with supratentorial lesions, showed a significant benefit of PES. While in the therapy group almost 50% of patients could be decannulated after a three-day PES intervention, in the control group a spontaneous remission of dysphagia allowing the patients to be decannulated, was witnessed in only 9% of the patients [
126]. A meta-analysis that considered the results of a single center RCT in addition to PHAST-TRAC [
253], confirmed this therapeutic effect [
126].
Both rTMS (repetitive transcranial magnetic stimulation) and tDCS (transcranial direct current stimulation) have been used for direct, non-invasive stimulation of the swallowing network with the aim of influencing the functionally relevant level of excitability and activity [
254]. In the meantime, a large number of smaller RCTs and cohort studies were summarized in several meta-analyses, which were able to show a moderate but persistent therapeutic effect on swallowing function for both neurostimulation methods [
245,
255‐
257]. In the largest single-center RCT on this topic to date, contralesional tDCS in acute dysphagic stroke patients was not only associated with an improvement in dysphagia, but also a neurophysiological detectable modulation of the swallowing network was found in spatial proximity to stimulation [
258]. Apart from post-stroke dysphagia, a positive effect of transcranial stimulation on swallowing function was also demonstrated in MS patients with strategic brain stem lesion [
259,
260]. In addition to the supratentorial stimulation evaluated in these studies, there is also initial evidence that cerebellar stimulation can also contribute to a reorganization of the swallowing network and improve swallowing function [
261,
262].
Treatment of hypersalivation in patients with neurogenic dysphagia
Recommendation 48: Debilitating hypersalivation in patients with neurogenic dysphagia can be treated with botulinum toxin injections into the salivary glands and/or anticholinergic drugs.
Recommendation 49: If pharmacological treatment does not provide adequate symptom control or if side effects prevent from its continuation, radiotherapy of the salivary glands may be considered.
The treatment of hypersalivation, a condition which is highly important for the management of patients with neurogenic dysphagia, has been comprehensively elaborated in the S2k guidelines “Hypersalivation”. This guideline was developed by the German Society of Otolaryngology, Head and Neck Surgery (DGHNO KHC) with the participation of other professional societies and associations (DGPP, DGSS, DGPPN, DGN, DGP, DPV, DNP, DEGRO, DGMKG) and was updated in 2019 [
27]. Therefore, a comprehensive presentation of this topic is omitted here and the available therapeutic options are summarized referring to the guideline above.
The pharmacological therapy of hypersalivation consists on the one hand in the inhibition of the salivary glands by anticholinergic muscarin-receptor antagonists. These agents can be administered orally, intravenously, by intramuscular injection, transdermally or quasi local (e.g. sublingual application of drops or spray). In Germany, atropine, scopolamine, and glycopyrrolate are mainly used. The application of these substances in adults is off-label, only glycopyrrolate has been approved for the symptomatic treatment of severe hypersalivation in children from 3 years on and adolescents throughout Europe in 2016. On the other hand, the cholinergic neuroglandular transmission of the salivary glands can be reversible and significantly reduced by the intraglandular injection of botulinum toxin into the large salivary glands. After successful completion of an RCT in which 184 patients with typical (70.7%) or atypical (8.7%) Parkinson syndromes, stroke (19%) or traumatic brain injury (2.7%) were included, Incobotulinum toxin A has been approved in Europe for the treatment of hypersalivation in adults irrespective of the underlying etiology in 2019 [
263,
264]. Radiotherapy can also be used for the treatment of hypersalivation in individual cases, e.g. if the treatment with anticholinergic drugs or the injection therapy with botulinum toxin do not provide sufficient symptom control or repeated injections are not feasible. While the fundamental and long-lasting efficacy of external irradiation of the salivary glands has been convincingly demonstrated, the possible side effects as well as the inherent carcinogenic potential must be taken into account [
27].
Minimally invasive and surgical therapies
Recommendation 50: For the treatment of cricopharyngeal dysfunction with impaired opening of the UES, cricopharyngeal myotomy (open or endoscopic), dilatation (by balloon or bougie) and botulinum toxin injection (transcutaneous or endoscopic) are considered.
Recommendation 51: The indication should be made by a multi-professional team of experts. The procedure should only be carried out at specialized centers.
Recommendation 52: The indication for interventional or surgical treatment of cricopharyngeal dysfunction and impaired opening disorder of the UES in the context of neurogenic dysphagia should consider the following criteria:
1.
The diagnosis is based on VFSS and HRM.
2.
The phenotype and etiology of dysphagia have been clarified.
3.
A sufficiently long (approx. 1 year) conservative therapy (treatment of the underlying disease; swallowing therapy by Shaker exercise, Mendelsohn maneuvers, EMST) has not been successful.
4.
A refractory gastro-oesophageal reflux has been ruled out.
5.
A sufficient hyolaryngeal elevation is present.
Recommendation 53: For the treatment of therapy-refractory glottal closure insufficiency, minimal-invasive surgical procedures for medialization of the vocal folds may be chosen. This treatment aims at improving cough and reducing the risk of aspiration.
Minimal-invasive and surgical therapy procedures can be applied for the treatment of severe opening disorders of the UES, if this disorder is relevant to the overall impression of the swallowing disorder. In case of cricopharyngeal myotomy the muscles forming the UES (cricopharyngeal muscle, inferior pharyngeal constrictor muscle as well as the upper striated muscles of the oesophagus) either can be cut through in the longitudinal direction by open or endoscopic access [
92,
265]. Minimal-invasive treatment options consist of the dilatation of the UES (with a balloon or bougie) [
266] and the endoscopic or transcutaneous injection of botulinum toxin [
267]. These procedures have so far been tested in patients with inclusion body myositis, oculopharyngeal muscle dystrophy, multiple sclerosis, amyotrophic lateral sclerosis, stroke and M. Parkinson. As consistently summarized in several reviews and two Cochrane analyses, these therapeutic options have mainly been evaluated within retrospective, uncontrolled case series [
92,
265,
268]. Only in one randomized pilot study balloon dilatation was compared with laser myotomy in 8 patients. Both treatments resulted in an increase in the diameter of the UES and a subjective improvement of dysphagia [
269]. In a systematic review summarizing the results of 32 studies, available therapeutic options were compared in terms of effectiveness and side effects [
270]. Weighted average success rates of each intervention were 78% for myotomy (84% for endoscopic myotomy and 71% for open surgery), 73% for dilatation and 49% for botulinum toxin injection. The weighted average complication rates were 7% for myotomy (2% for endoscopic myotomy and 11% for open surgery), 5% for dilatation and 4% for botulinum toxin injection. Complications included fistula, supraglottic edema, mediastinitis, retropharyngeal hematoma, oesophageal injuries, laryngospasm and severe bleeding [
270]. Although these figures do not allow for a reliable comparison of the different methods due to limited data, they nevertheless indicate that all of the therapeutic options basically may be employed. Since the indication is difficult and side effects can be serious, even life-threatening, these interventions should only be performed in specialized centers involving surgeons, gastroenterologists, otolaryngologists and neurologists with appropriate relevant expertise. The following expert recommendations can be considered in this context. 1. Any intervention targeting the UES should be performed after comprehensive diagnostics including VFSS and HRM; 2. An etiological classification of the underlying dysphagia should have been made; 3. A sufficiently long (approx. 1 year) conservative therapy (treatment of the underlying disease; swallowing therapy by Shaker exercise, Mendelsohn maneuvers, EMST) should have been carried out and found to be ineffective; 4. The presence of a therapy-refractory reflux should have been ruled out; 5. A sufficient hyolaryngeal elevation should be present.
Minimally invasive and surgical procedures are also helpful for the treatment of glottal insufficiency (GI). In addition to improving the quality of voice, these treatments may also lead to an improvement in swallowing safety. Vocal fold palsy due to the affection of the vagal nerve and its branches as well as pronounced vocal fold atrophies, which occur e.g. in M. Parkinson or ALS [
271], can cause GI that causes an impairment of laryngeal protective functions [
272]. Aspiration and reduced cough strength with subsequent impaired laryngeal and bronchial clearing are likely consequences [
273]. In the case of brain stem or vagal nerve lesions, the risk of aspiration is particularly high due to the associated UES dysfunction and severe sensory loss [
272].
If, despite sufficient long and intensive speech therapy, no sufficient improvement of GI is achieved, surgical medialization techniques can be used as support. As a consequence of medializing the vocal fold, the laryngeal protective function improves by preventing aspiration and increasing cough strength [
274]. The treatment strategy of a persistent GI with aspiration essentially comprises of vocal fold augmentation, which is performed in local anaesthesia and office-based with temporary or permanent injectates [
275,
276]. In case of larger GIs, thyroplasty, in which the vocal fold is medialized from the outside through the laryngeal framework, e.g. with a silicone wedge, goretex or titanium, has been established [
277].
Although glottic narrowing interventions have been successfully used for many years to improve voice and swallowing, there are no randomized trials or systematic reviews investigating their effectiveness in neurogenic dysphagia. However, the results of the published case series and smaller case studies mostly show that the medialization techniques improve not only the subjective but also the objective swallowing capacity by reducing aspiration and improving the cough [
278,
279]. In vocal fold augmentation, the complications are generally rare and mainly include laryngeal edema, material intolerance, overcorrections and bleeding. Since with the help of laryngoscopy indicating this treatment is simple and the procedure is gentle and quick, the medialization of the vocal fold can be a useful supplement in the therapy of neurogenic dysphagia with GI.