Neurogenic Dysphagia

By Tobias Warnecke, Rainer Dziewas and Susan Langmore

This book is a clinical manual that covers the whole spectrum of swallowing and its disorders. It starts with physiology of swallowing, pathophysiology of disordered deglutition, diagnostic methods (clinical and instrumental) and ends with an in-depth’s and up-to-date presentation of current treatment options. The clinically most relevant topics of dysphagia management on the stroke unit and the intensive care unit are dealt with in separate chapters. Also the closely intertwined issue of nutritional management is specifically addressed.  Most importantly, the book covers all obligatory topics of the Flexible Endoscopic Evaluation of Swallowing (FEES)-curriculum, an educational initiative that started in Germany in 2014 and is currently being extended to other European and non-European countries. The book is richly illustrated and an online video section provides a number of typical patient cases.  

FEES is probably the most commonly chosen method for the objective assessment of swallowing and its disorders. It is used in stroke units, intensive care facilities, geriatric wards but also in rehabilitation clinics and within dedicated outpatient services.

This book on neurogenic dysphagia therefore addresses a wide range of different medical disciplines, such as neurologists, geriatricians, intensive care physicians, rehabilitation physicians, gastroenterologists, otolaryngologists, phoniatrists and also speech-language pathologists.

• Language: English
• Publisher: Springer
• Release date: Mar 5, 2021
• ISBN: 9783030421403

Book preview

© Springer Nature Switzerland AG 2021

T. Warnecke et al.Neurogenic Dysphagiahttps://doi.org/10.1007/978-3-030-42140-3_1

1. Neuroanatomy and Physiology of Deglutition

Tobias Warnecke¹  , Rainer Dziewas²   and Susan Langmore³  

(1)

Department of Neurology, University of Münster, Münster, Germany

(2)

Department of Neurology and Neurorehabilitation, Klinikum Osnabrück, Osnabrück, Germany

(3)

Department of Otolaryngology, Boston University, Boston, MA, USA

Tobias Warnecke (Corresponding author)

Email: [e-mail]

Rainer Dziewas

Email: [e-mail]

Susan Langmore

Email: [e-mail]

1.1 The Unimpaired Swallow

1.2 The Impaired Swallow

1.3 Central Coordination of Swallowing

1.3.1 Brainstem Swallowing Centers

1.3.2 Supramedullary Coordination of Swallowing

1.3.3 Hemispheric Specialization

1.3.4 Cortical Plasticity: Compensation of Disease-Related Dysfunction

1.3.5 Cortical Plasticity: Sensory Stimulation to Enhance Reorganization

References

1.1 The Unimpaired Swallow

Swallowing is a vital human motor activity. The act of swallowing transports saliva and food from the oral cavity into the stomach while simultaneously protecting the respiratory tract. Although swallowing can be initiated voluntarily, most swallows occur without conscious input. While awake, a healthy person swallows about once a minute between meals depending on saliva production, whereas during deep sleep, salivation and swallowing are almost completely suspended. The rate of swallowing increases to up to three times per minute when a person sucks on a piece of candy, and a small meal requires about 30 swallows on average (Martin et al. 1994). During a single day, a healthy adult swallows approximately 1000 times (Dodds 1989).

Swallowing can be divided into four phases: the oral preparatory phase, the oral phase, the pharyngeal phase, and the esophageal phase. These phases are not strictly separated; rather, they smoothly merge into each other. Hiimae and Palmer have described the oral phase of swallowing in detailed reports (see Heiimae and Palmer 1999).

1.

In the oral preparatory phase, food is chewed and mixed with saliva. The soft palate (velum palatinum) is lowered and raised in synchrony with jaw movement during mastication. During this process, the airway remains open and the pharynx and larynx remain in the resting position. As a food bolus is processed by the tongue and mixed with saliva, the part that has been titrated is moved to the back of the mouth while new sections are processed in the more anterior oral cavity (stage 1 and 2 transport). Over time, the titrated portion of the bolus falls into the oropharynx, gradually filling the valleculae. Toward the end of this phase, as the oral processing and transport stages end, the oral propulsive stage is seen where the tongue propels the entire bolus, both the part in the oropharynx and the part still in the oral cavity into the pharynx to be swallowed. Synchronously with tongue propulsion, the pharyngeal phase of the swallow begins. Therefore, spillage of food into the hypopharynx prior to swallow initiation is normal, not pathologic.

Liquids have a very different pattern of oral preparation. The tongue contains the liquid by cupping it within a depression in the anterior one- or two-thirds of the tongue (Dodds 1989). There is no spillage of portions of the liquid bolus into the oropharynx; instead, the entire liquid bolus is swallowed together. However, the head of the bolus may fall as low as the piriforms before the pharyngeal phase begins. The duration of this spillage is usually less than 2 s and sometimes shorter.

2.

In the oral phase, whether for food or liquid, the tongue elevates and rolls posteriorly in a peristaltic motion, making sequential contact with the hard and soft palate and thereby propelling the bolus into the pharynx (Dodds 1989). The lips remain closed and the buccinator muscles remain contracted, thereby enabling slight negative pressure in the oral cavity to facilitate the bolus transport. The oral propulsive phase is executed voluntarily, (Fig. 1.1) and lasts less than 1 s.

3.

Once the pharyngeal phase begins, it is invariant in sequence (Kendall et al. 2003). At the beginning of the reflexive movement pattern, the velum rises to close the nasopharynx (velopharyngeal closure) and prevent nasal regurgitation of bolus material. The swallow is usually initiated during the expiratory phase of respiration. During the swallow, breathing is interrupted briefly. A rapid, piston-like backward movement of the base of the tongue presses the bolus into the hypopharynx. At the same time, the airway begins its closure, first at the level of the arytenoids, followed immediately by the hyoid and larynx rising and the epiglottis retroflexing. The vocal folds close last, about 0.6 s after the arytenoids begin their medial and anterior movement to contact the petiole of the epiglottis. The pharyngeal constrictors are the last muscle groups to contract. They squeeze medially in a sequential fashion to close the airspace. At the same time that the pharyngeal constrictors begin contracting, the upper esophageal sphincter relaxes and opens. The rising of the larynx and the expansion of the opened esophageal entrance result in negative pressure, which pulls the bolus downward. The bolus slides over the epiglottis and the piriform sinus and is transported downstream by sequential contractions of the pharyngeal constrictors into the upper esophageal sphincter and the esophagus (Fig. 1.1). The pharyngeal phase lasts about 0.7 s (Kendall et al. 2003; VanDaele et al. 2005).

4.

The passage of the pharyngeal peristalsis contraction wave through the upper esophageal sphincter terminates its relaxation and marks the transition to the esophageal phase of swallowing. During this phase, the hyoid, the larynx, and the epiglottis return to their resting positions. The velum relaxes, thereby reopening the nasopharynx and allowing breathing to continue. A primary peristaltic wave of the esophageal musculature propagates the bolus into the stomach. Secondary peristaltic cleaning waves are induced by local extensor stimuli. The esophageal phase can take up to 10 s, depending on bolus consistency and size (Fig. 1.1; Dodds et al. 1990; Bartolome and Schröter-Morasch 2013).

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig1_HTML.png

Fig. 1.1

Phases of swallowing (© 2012–2017 Heike Blum, University Hospital Muenster). (a) Oral preparatory phase; (b) oral phase; (c) triggering of swallow reflex at beginning of pharyngeal phase; (d) pharyngeal phase, (e) end of pharyngeal phase shortly before closure of upper esophageal sphincter; (f) esophageal phase. Reproduced with permission

Overall, the seemingly straightforward yet highly complex process of swallowing requires bilateral, coordinated activation and inhibition of more than 25 pairs of muscles in the oral cavity, pharynx, larynx, and esophagus (Fig. 1.2).

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig2a_HTML.png../images/467919_1_En_1_Chapter/467919_1_En_1_Fig2b_HTML.png

Fig. 1.2

(a, b) Anatomy of swallowing muscles (© 2017 Esther Gollan). Reproduced with permission

The act of swallowing involves five cranial nerves as well as the ansa cervicalis (C1–C3). The coordination of the masticatory muscles is mediated by the 3rd branch (V3) of the trigeminal nerve (V). The orofacial musculature—which is important for oral closure—is innervated by the facial nerve (VII). The hypoglossal nerve (XII) supplies the intrinsic tongue muscles, whereas accompanying spinal nerves C1–C3 innervate the extrinsic muscles of the tongue. The muscles of the soft palate and the pharyngeal isthmus as well as the constrictor and levator muscles of the pharynx are activated by the glossopharyngeal (IX) and vagal (X) nerves (Fig. 1.3). The vagus nerve (X) innervates the intrinsic laryngeal muscles and the esophagus. The trigeminal nerve (V3), the facial nerve (VII), and the ansa cervicalis innervate the supra- and infrahyoid muscles, which coordinate the movement of the hyoid and larynx (Donner 1985; Dodds et al. 1990).

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig3_HTML.png

Fig. 1.3

Pathway of glossopharyngeal and vagal nerves (© 2017 Heike Blum, University Hospital Muenster). Reproduced with permission

A timely opening and closing of the upper esophageal sphincter (UES) is particularly important to the unimpaired swallow. This central element of the pharyngeal phase is executed by the fine-tuned contraction and relaxation of the opening and closing muscle groups of the UES. The UES opening muscles are differentiated into anterior and posterior muscle groups (Lang 2012). The anterior muscle group includes the upper hyoid muscles (geniohyoid muscle, mylohyoid muscle, stylohyoid muscle, hypoglossal muscle, anterior digastric muscle). Each of these muscles originates above the hyoid and attaches to the top of it. When they contract, they pull the hyolaryngeal complex forward and upward. The lower hyoid muscles include the thyrohyoid muscle, the sternohyoid muscle, the sternothyroid muscle, and the omohyoid muscle. These muscles attach to the underside of the hyoid and pull the hyolaryngeal complex forward and downward. The posterior muscle group is formed by the stylopharyngeus muscle, the palatopharyngeus muscle, and the pterygopharyngeus muscle. These muscles attach to the back of the pharynx and pull it backward and upward. The UES closing muscles consist of the cricopharyngeal muscle, caudal portions of the inferior pharyngeal muscle, and the cervical esophageal musculature. The cricopharyngeal muscle attaches to the cricoid cartilage and forms a muscular band at the junction of the pharynx and the esophagus. Its pars obliqua ends in a median raphe of the inferior pharyngeal constrictor muscle, while its pars transversa does not form a median raphe. The Kilian’s triangle is formed by these two parts of the cricopharyngeal muscle and constitutes a weak spot and predilection site of the Zenker’s diverticulum. The striated musculature of the cervical esophagus is attached below the pars transversa (Lang 2012).

The act of swallowing is subdivided into the oral preparatory, oral, pharyngeal, and esophageal phases. Cranial nerves V, VII, IX, X, and XII as well as more than 25 pairs of muscles are involved in the control and execution of swallowing. The upper esophageal sphincter—which consists of opening and closing muscles—has special clinical significance for the unimpaired swallow.

1.2 The Impaired Swallow

The impaired swallow is referred to medically as dysphagia. The term dysphagia is derived from the ancient Greek prefix dys, meaning disturbed, and the verb phagein, meaning to eat. The literal meaning of the term is thus eating disturbance. Although the epidemiology of dysphagia in the general population has not been sufficiently studied, it has been estimated that more than 5% of the general population suffer from a swallowing disorder. Oropharyngeal dysphagia—which is more common than esophageal dysphagia—occurs more frequently among the general population and is about as common as the most widespread metabolic disorder, diabetes mellitus. Oropharyngeal dysphagia affects 13% of the total population over the age of 65. The highest prevalence of oropharyngeal dysphagia is among old patients with neurological diseases. The prevalence of oropharyngeal dysphagia increases with increasing age. It remains at 16% among individuals between 70 and 79 who live independently and increases to 33% for individuals 80 and older. As a result, the prevalence of oropharyngeal dysphagia has been increasing worldwide in so-called aging societies (Kuhlemeier 1994; Clavé and Shaker 2015; Wirth et al. 2016; Dziewas et al. 2017).

Neurological disorders are the most common cause of dysphagia. Swallowing impairments caused by disorders affecting the central swallowing network or downstream peripheral nerves and muscles are referred to as neurogenic dysphagia. The term neurogenic in this context thus includes both all types of neurological diseases and dysphagia caused by myopathies. No differentiation is made between neurogenic and myogenic, a differentiation that is otherwise fundamental in neurology. The term myogenic dysphagia is therefore not common in German- or English-speaking countries. It is necessary to differentiate swallowing disorders caused by diseases in the field of otorhinolaryngology (e.g., tumors or inflammation of the pharynx or larynx—usually called structural dysphagia), internal medicine and gastroenterology (e.g., Zenker’s diverticulum or reflux disease), and psychiatry (e.g., globus pharyngis) from neurogenic dysphagia. It is also important to note a special element of this classification: If an otorhinolaryngological disease causes a swallowing impairment due to lesions of cranial nerves that are relevant to the act of swallowing, the dysphagia could also be formally classified as neurogenic because the affection of the (peripheral) nervous system would then constitute the underlying pathophysiology. Usually, however, swallowing disorders caused in this manner are allocated to the field of otorhinolaryngology since their diagnosis and therapy essentially fall into this field of specialization.

It is estimated that about 50% of all neurological patients suffer from neurogenic dysphagia (Clavé and Shaker 2015). As early as 2001, Doggett et al. (2001) calculated that approximately 300,000–600,000 people develop neurogenic dysphagia every year in the USA. The most common form of neurogenic dysphagia is stroke-related dysphagia. Neurogenic dysphagia can lead to disorders in one, several, or all phases of swallowing described in Sect. 1.1, which leads to a variety of symptoms, the most important of which are briefly described below:

Premature spillage: The bolus slides forward and out of the mouth uncontrolledly (anterior spillage) or backward into the throat (posterior spillage).

Delayed triggering of the swallow reflex: The swallowing reflex is triggered too late. The result is often a pooling (accumulation) of bolus parts in the hypopharynx before the swallowing reflex is triggered.

Penetration: The bolus enters the laryngeal vestibule but remains above the true vocal folds.

Aspiration: The bolus enters the laryngeal vestibule and descends below the level of the true vocal folds and into the upper trachea.

Silent penetration/aspiration: Bolus material enters the laryngeal vestibule or the subglottic region without triggering a cough or swallow reflex. Silent penetration/aspiration is particularly dangerous because it is neither perceived by the patient nor detected in the clinical examination.

Residue or retention: Bolus material remains in the swallowing tract after the swallow and is not transported further (in the oral cavity: oral residue; in the throat: pharyngeal residue; in the esophagus: esophageal residue). Retention actually refers to the process that leads to residue, but both terms are usually applied interchangeably in international usage.

Reflux: Material from lower parts of the swallowing tract flows back into higher parts. Gastro-pharyngeal or esophago-pharyngeal reflux are the most common types of reflux.

Odynophagia: Swallowing is painful. Painful swallowing is rarely seen as an isolated symptom of neurogenic dysphagia.

Hypersalivation: There is an increase in salivation, which—in neurogenic dysphagia—is mostly due to the reduced ability to swallow saliva and not due to an increased salivary production. The terms pseudo-hypersalivation and sialorrhea are also used.

Figure 1.4 illustrates major symptoms of neurogenic dysphagia. A detailed description can be found in Sect. 3.​1.

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig4a_HTML.jpg../images/467919_1_En_1_Chapter/467919_1_En_1_Fig4b_HTML.jpg

Fig. 1.4

Clinically relevant symptoms of neurogenic dysphagia (© 2017 Heike Blum). (a) Spillage (a disorder of the oral preparatory phase and/or of the oral phase); (b) delayed swallowing reflex (a disorder of the pharyngeal phase); (c) residue; (d) penetration; (e) aspiration. Reproduced with permission

Clinical effects of neurogenic dysphagia include a significant reduction in the quality of life, malnutrition, dehydration, aspiration pneumonia , and dependency on artificial feeding. In most severe cases of dysphagia, a tracheostomy and the implantation of a tracheal cannula may be required to protect the airway against aspiration. In addition, aspiration pneumonia resulting from dysphagia is the most common cause of death in many neurological disorders.

Swallowing disorders that are caused by a variety of neurological disorders are referred to as neurogenic dysphagia. Neurogenic dysphagia can potentially affect all four phases of swallowing.

Knowledge of the central nervous control of swallowing is essential to provide an adequate understanding of the complex patterns of disordered swallowing in neurogenic dysphagia as well as of the available therapies. This topic is therefore addressed in the following section.

1.3 Central Coordination of Swallowing

1.3.1 Brainstem Swallowing Centers

The precise pattern of sequential stimulation and inhibition of the various muscles involved in swallowing is regulated by a swallowing center located in the brainstem. This center can be divided into three functional levels (Broussard and Altschuler 2000). The input level of the swallowing center is formed by peripheral afferents and efferent cortical signals. The neurons of the output level are connected to the motor cranial nerve nuclei. The organizational level consists of a group of interconnected interneurons that form the central pattern generator (CPG) for swallowing. The CPG is divided into a dorsal swallowing group (DSG)—which lies in the solitary nucleus (SN) as well as in the adjacent reticular formation—and into a ventral swallowing group (VSG)—which lies above the nucleus ambiguus in the ventrolateral medulla oblongata. There is one CPG on each side of the brainstem, both of which work in strict synchrony. After unilateral sensory stimulation, the act of swallowing is first programmed in the ipsilateral center and then transmitted to the contralateral CPG .

Afferent sensory information from the oral cavity and the pharynx reaches the swallowing center via cranial nerves V, IX, and X and converges in the SN . The sensory input plays an important role in the initiation of the swallowing reflex. Moreover, the continuous sensory feedback has a modulating effect on the swallowing network, which enables the movement program to be adapted to the specific environmental condition. The DSG’s generator neurons trigger and modulate the swallowing sequence. They activate the VSG’s distribution neurons, which relay the information to motor cranial nerve nuclei V, VII, and XII as well as to the nucleus ambiguus (IX, X) and the dorsal vagus nucleus (Fig. 1.5).

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig5_HTML.png

Fig. 1.5

Schematic organization of medullary swallowing center (a) (© 2017 Heike Blum) and the swallowing network (b). Peripheral and central information reaches the swallowing center via the solitary nucleus (SN) of the dorsal swallowing group (DSG), which activates the ventral swallowing group (VSG) of the ventrolateral medulla oblongata (VLM) near the nucleus ambiguus (NA). The VSG forwards the movement program to the motor cranial nerve nuclei and to spinal nerves C1–C3 (Fig. 1.5a) (adapted from Jean 2001, reproduced with permission). The brainstem swallowing centers are integrated in the widely distributed swallowing network (Fig. 1.5b)

At the level of the brainstem, swallowing is regulated by the central pattern generator, which consists of a dorsal and a ventral swallowing group in the medulla oblongata.

1.3.2 Supramedullary Coordination of Swallowing

The reflexive pattern coordinated by the brainstem swallowing centers can in fact be generated without the influence of supramedullary structures. Under physiological conditions, however, the network receives multiple signals from higher centers, and these signals are processed in the DSG in addition to the sensory information (Jean 2001). Even before the act of swallowing begins, internal and external anticipatory stimuli—including the gustatory and visual properties of food—are processed in the cerebrum and influence the subsequent swallowing phases via feedforward regulation (Leopold and Daniels 2010). A behavioral study was thus able to demonstrate a decrease in swallowing latency after displaying images that were intended to stimulate drinking, whereas no temporal alterations of the swallowing latency were observed in the control condition consisting of neutral images (Maeda et al. 2004). An imaging study using functional magnetic resonance imaging (fMRI) additionally demonstrated that unlike neutral images, images of food activated the insular cortex as well as the superior temporal, parahippocampal, and hippocampal gyri (St-Onge et al. 2005). In the oral preparatory phase, the different bolus characteristics of temperature, taste, viscosity, and texture activated an extensive sensory network that—in addition to the insular cortex, the amygdala, and orbitofrontal cortex—also includes primary and secondary sensory areas (S1, S2) as well as the parietal association cortex (Kadohisa et al. 2004; Rolls 2007). During the chewing process, the primary motor cortex, the premotor cortex, and the supplementary motor areas were activated in addition to the aforementioned sensory areas (Takada and Miyamoto 2004).

The supramedullary coordination of the oral phase of swallowing has received the greatest amount of scientific attention to date. Methodologically, studies have made use of positron emission tomography (PET; Hamdy et al. 1999), electroencephalography (EEG ; Satow et al. 2004), magnetoencephalography (MEG ; Dziewas et al. 2003; Furlong et al. 2004), and transcranial magnetic stimulation (TMS; Hamdy et al. 1996) in addition to functional magnetic resonance imaging (fMRI; Mosier et al. 1999a, b; Martin et al. 2001). The cortical and subcortical activation patterns described in these studies varied according to the adopted swallowing paradigms, including involuntary versus voluntary swallowing, saliva versus water swallowing, the properties of the bolus, and the attention that the respective paradigms required of the subjects. Regardless of the chosen swallowing paradigm and technical approach, activations of the primary sensorimotor cortex, the supplementary motor areas, the cingulate cortex, the frontal operculum, the insular cortex, secondary sensory areas, and the parietal association cortex have been described in almost all studies. Moreover, individual studies have additionally shown activation of the hippocampal gyrus, the cuneus and precuneus, the basal ganglia, and the cerebellum. The activity of the supramedullary swallowing network also appears to directly depend on the extent of oropharyngeal stimulation. For example, in one fMRI study, the activated cortical volume was four times larger when water as opposed to saliva was swallowed (Martin et al. 2007). Finally, irrespective of the methods used, several studies have found the cortical representation of the pharyngeal musculature to be more medial than was described in Penfield’s original depiction of the homunculus (Hamdy et al. 1996; Furlong et al. 2004; Teismann et al. 2007). This discrepancy is possibly explained by additional afferent and efferent projections related to the act of swallowing, which are not exclusively localized in the primary motor areas (Hamdy et al. 1998a, b).

As described above, the involuntary pharyngeal and esophageal phases of swallowing are coordinated and executed in the brainstem. Nevertheless, several studies have also been able to demonstrate a concomitant cortical activation during the swallowing reflex that includes frontal brain regions in addition to the primary sensorimotor cortex and that should also be interpreted as an indication for a cortical modulation of the pharyngeal phase (Hamdy et al. 1999; Mosier et al. 1999a, b; Zald and Pardo 1999; Dziewas et al. 2003). Similarly, esophageal motility during swallowing also features a distinct cortical contribution, as shown by functional neuroimaging (Dziewas et al. 2005; Aziz et al. 2000).

These findings—which are based on numerous individual studies—can be summarized in a supramedullary swallowing network (Leopold and Daniels 2010). As shown in Fig. 1.6, the axis of motor execution—which extends from the premotor areas through the primary motor cortex to the swallowing centers of the brainstem—is modulated by sensory, cognitive, and emotional pathways that are interconnected at different levels. In future investigations, further evidence in support of this comprehensive model of central control needs to be sought and should aim to integrate the temporal dimension, which has been lacking thus far.

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig6_HTML.png

Fig. 1.6

Supramedullary swallowing network (© 2012/2017 Heike Blum). The four images depict the brain areas activated during the initiation and execution of swallowing. (a) Oral preparatory phase; (b) transition from oral preparatory phase to oral phase; (c) oral phase; (d) pharyngeal phase. OFC Orbitofrontal cortex, pre-MC premotor cortex. Reproduced with permission

Swallowing is regulated by a differentiated and complex supramedullary network that includes the insular cortex, the basal ganglia, the cingulate cortex, as well as the premotor areas and the primary sensorimotor cortex.

1.3.3 Hemispheric Specialization

In its simplest definition, hemispheric specialization refers to the presence of a dominant hemisphere for swallowing processing, which is comparable, for example, with left-hemispheric language dominance. Using TMS to investigate downstream motor pathways to the submental and pharyngeal musculature has provided evidence for considerable inter-individual variability of laterality, with some cases even displaying pronounced intra-individual variability of lateralization with regard to the different muscle groups (Hamdy et al. 1996). In the first relevant work on the subject by Hamdy and co-workers, four, seven, and nine of 20 healthy individuals displayed predominantly right-hemispheric, left-hemispheric, and bilateral representation of the submental musculature, respectively. In contrast, ten, three, and seven of the 20 subjects displayed a predominantly right-hemispheric, left-hemispheric, and bilateral representation of the pharyngeal musculature, respectively, whereas intra-individually, the lateralization of the submental and pharyngeal musculature only coincided in half of them (Hamdy et al. 1996). Subsequent studies predominantly using fMRI and MEG have revealed different degrees of lateralization in different regions of the brain. Left-dominant activation of the primary sensorimotor cortex has been reported most frequently (Dziewas et al. 2003; Martin et al. 2004, 2007); however, some authors have found predominantly bilateral or right-dominant activation (Mosier et al. 1999a, b; Kern et al. 2001; Malandraki et al. 2009, 2010; Humbert et al. 2009). Heterogeneous results have also been demonstrated in studies focusing on the activation of the insular cortex and the frontal operculum during swallowing. While one study found a left-dominant activation of this anatomical region (Dziewas et al. 2003), which also coincided with similarly localized taste processing (Cerf-Ducastel et al. 2001), other studies have found bilateral or right-lateralized activity (Hamdy et al. 1999; Mosier et al. 1999a, b; Suzuki et al. 2003).

One of the main reasons for these inconsistent results is likely the neglect of the temporal dimension in the spatial analysis of swallow-related brain activation. For example, an MEG study that examined cortical activation in a 1-s interval immediately before and during maximum swallow-related muscle contraction, demonstrated a time-dependent shift in activation from the left to the right hemisphere. In this study, exclusive involvement of the left primary sensorimotor cortex could be observed in the first 600 ms, with bilateral activation occurred between 600 and 800 ms, followed by right-hemispheric lateralization at the end of the analyzed time segment (Fig. 1.7; Teismann et al. 2009a).

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig7_HTML.jpg

Fig. 1.7

Time-dependent cortical activation during swallowing. Representation of the time-dependent shift of brain activation from the left to the right hemisphere. In the figure above, the brain activation of the primary sensorimotor cortex during volitional swallowing is displayed across a time interval of 1 s, whereas the bottom image displays the five corresponding 200-ms epochs (Reprinted from Teismann et al. 2009a with permission from Wiley)

These results—which have recently been confirmed in an fMRI study (Mihai et al. 2014)—suggest that the left hemisphere specializes in the earlier phases of swallowing, particularly in the oral preparatory phase and the oral phase, whereas the right hemisphere appears to be responsible for the subsequent pharyngeal phase. Consistent with this hypothesis, Malandraki et al. (2010) demonstrated left-lateralized cortical activation during swallowing preparation in an fMRI study. In addition, an examination of dysphagia patterns in stroke patients revealed that left-hemispheric strokes were associated with a prolonged oral transfer of the bolus (Robbins et al. 1993), which also suggests that the coordination of the lips, tongue, and mandibular muscles during the oral phase is coordinated in the left hemisphere. On the other hand, patients with a right-hemispheric stroke displayed a prolonged and disturbed pharyngeal phase with a greater incidence of penetration and aspiration (Robbins et al. 1993; Daniels et al. 1996). This finding was confirmed in a recent lesion study. In a group of 200 acute stroke patients, lesions of the right primary and secondary sensorimotor cortex were particularly prone to being associated with severe dysphagia as well as with penetration and aspiration (Fig. 1.8; Suntrup et al. 2015a, 2017). In line with this finding, another study of 215 stroke patients revealed that right-hemispheric strokes were strongly associated with an increased risk of pneumonia (Kemmling et al. 2013).

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig8_HTML.png

Fig. 1.8

Correlation of affected brain region and dysphagia severity during acute stroke. Color-coding is used to indicate brain regions with significant differences in lesion volume between (a) patients with and without dysphagia, (b) patients with severe versus mild dysphagia, and (c) patients with and without penetration or aspiration. The odds ratio (OR) is color-coded (Reprinted from Suntrup et al. 2015a with permission from Wiley)

The individual swallowing phases feature differently lateralized cortical representations. The early phases of swallowing (oral preparatory phase, oral phase) are predominantly controlled by the left hemisphere, and the pharyngeal phase is predominantly coordinated by the right hemisphere.

1.3.4 Cortical Plasticity: Compensation of Disease-Related Dysfunction

Cortical plasticity refers to the brain’s ability to develop modified organizational structures in response to morphological changes or altered environmental conditions. Numerous studies have demonstrated that the cerebrum displays reorganization phenomena as a result of peripheral and central lesions. Thus, for example, several studies of stroke patients who show functional recovery after a basal ganglia infarction have revealed that movements of the affected limb led to extensive bilateral activation of the motor system, activation of sensory and secondary motor areas normally not active during this task in healthy individuals, and large-scale activation of the ipsilateral sensorimotor cortex (Weiller et al. 1992, 1993). During functional recovery, a decrease in contralesional activation of the primary sensorimotor cortex has been observed by several authors, yet the contralesional premotor cortex remained activated (Calautti et al. 2001; Feydy et al. 2002).

While cortical plasticity has long been known in the domains of speech, hearing, and the motor system as a physiological response to damage to the CNS, the PNS, and the muscle-band apparatus, more recently, it has also been extensively studied in patients with neurogenic dysphagia of various etiologies and anatomical lesion localizations (Fig. 1.9).

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig9_HTML.png

Fig. 1.9

Disease-related cortical reorganization (© 2012/2017 Heike Blum). Reproduced with permission. Lesion sites associated with neurogenic dysphagia of different etiologies in CNS, PNS, and musculature. These disorders can cause disease-related reorganization phenomena within the swallowing cortex

Most attention in this context has been devoted to reorganization phenomena during the rehabilitation of stroke-related dysphagia. In the first 2 weeks after a supratentorial stroke, patients with both a left- and a right-sided brain infarction experience a massive reduction in ipsilateral brain activity and a loss of contralesional brain activity (Fig. 1.10). In contrast, patients with non-dysphagic strokes display activation of the sensorimotor cortex similar to that found in healthy subjects (Teismann et al. 2011a).

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig10_HTML.png

Fig. 1.10

Change in swallowing-related brain activation in acute stage of stroke (Teismann et al. 2011a). LHS = left-hemispheric stroke, RHS = right-hemispheric stroke

This finding of contralesional loss of cortical activation—which has also been observed in a similar form in aphasic stroke patients (Saur et al. 2006)—is likely due to a severe, stroke-related disruption of the functional connectivity of the cortical and subcortical swallowing network. In neurophysiology, the term diaschisis has been coined to describe this phenomenon (Greek: dia = through, skizo = to cut). According to this concept, the loss of activation in a structurally intact brain region far away from the lesion occurs only temporarily. As soon as the long-distance impact of the brain lesion subsides, functional recovery of the primarily non-damaged network areas takes place (Nelles 2004). Remarkably, this second step of functional recovery has also been reproduced in imaging studies of stroke patients. In line with the results of the above-cited MEG study, dysphagic strokes patients who were studied with TMS during the acute stage of the disease displayed a significantly smaller representation of the pharyngeal musculature in the non-affected hemisphere than did the non-dysphagic control group (Hamdy et al. 1997). During the subsequent follow-up, the group of patients who regained normal swallowing function displayed a significant increase in contralesional pharyngeal motor representation, whereas this representation remained unchanged in patients with persistent dysphagia (Fig. 1.11; Hamdy et al. 1998a, b).

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig11_HTML.png

Fig. 1.11

Changes in cortical representation of swallowing in chronic phase of stroke. (a) Mapping of motor-evoked potentials of the pharyngeal musculature in three stroke patients at the time of admission, after 1 month, and after 3 months (Hamdy et al. 1998b). Patient A had no dysphagia, patient B was initially dysphagic but experienced a remission after 1 month, and patient C had persistent dysphagia over the 3 months of the study. X denotes the vertex, and the hemisphere affected by the stroke is outlined in gray. While there was no relevant change in the mapping of pharyngeal, evoked potential over time in patient A or patient C, patient B demonstrated a pronounced reorganization of the pharyngeal representation in the hemisphere unaffected by the stroke. (b) Mappings of the thenar and pharyngeal muscles of a stroke patient over time (Hamdy et al. 1998b). The patient with a cortical stroke in the left hemisphere initially suffered from dysphagia, but the condition improved after 1 month. This improvement was accompanied by an increase in motor representation in the contralateral hemisphere, which was unaffected by the stroke. In contrast, the representation of thenar muscles in the ipsilesional hemisphere expanded over time. (Reprinted from Hamdy et al. 1998b with permission from Elsevier)

These data suggest that after a stroke, the cortical reorganization that accompanies the remission of dysphagia primarily takes place in the healthy hemisphere. In contrast, as shown above, an increase in motor representation can be found in the damaged hemisphere as a means of cortical compensation for stroke-related limb paresis (Foltys et al. 2003). The neurophysiological mechanisms that facilitate the rehabilitation of the swallowing function may thus be fundamentally different from the reorganization phenomena that support the rehabilitation of limb paralysis.

Central reorganization as a response to isolated damage to the motor system has been studied in patients with motor neuron disease. This category includes amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA, also known as Kennedy’s disease, KD). While there are significant differences between ALS and SBMA with regard to the respective prognoses and therapeutic approaches, both entities cause neurogenic dysphagia in almost all patients during the course of the disease. Pathophysiologically, ALS is characterized by a degeneration of the first and second motor neurons. Dysphagia is one of the most serious clinical complications and typically occurs several months after the onset of the disease. Approximately one-fourth of patients display bulbar symptoms at the onset of the illness that are caused by the early degeneration of the corticobulbar fibers of cranial nerves IX–XII. Dysphagia is mainly characterized by an impairment of the pharyngeal phase (Ertekin et al. 2000b; Leder et al. 2004), with prolonged activation of the laryngeal elevators and a delayed opening of the upper esophageal sphincter, whereas the oral phase is usually affected later in the course of the disease (Higo et al. 2004). SBMA is a rare disease caused by a mutation of the androgen receptor that leads to a selective degeneration of the spinal and bulbar motor neurons (second motor neuron). During middle age, affected patients develop slowly progressive dysphagia as well as proximal limb paresis with muscle atrophy and fasciculation in addition to a characteristic gynaecomastia. Analogous to the disturbance pattern observed in ALS patients, patients suffering from SBMA also experience dysfunction of the pharyngeal phase of swallowing (Warnecke et al. 2009).

In two independent studies, each of which used a voluntary swallowing paradigm, no cortical reorganization similar to that seen in stroke patients could be found in ALS patients (Li et al. 2009; Teismann et al. 2011b). Instead, these studies revealed a significant decrease in sensorimotor cortical activation in the ALS group that correlated with the severity of the dysphagia (Fig. 1.12).

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig12a_HTML.png../images/467919_1_En_1_Chapter/467919_1_En_1_Fig12b_HTML.png

Fig. 1.12

Change in cortical activation in dysphagic ALS patients. (A) Cortical activation of the sensorimotor cortex in the MEG during swallowing in (a) healthy control subjects, (b) ALS patients with moderate dysphagia, and (c) ALS patients with severe dysphagia (Reprinted from Teismann et al. 2011b). (B) Brain activation registered via fMRI during swallowing in (a) healthy control subjects, (b) ALS patients without dysphagia, and (c) ALS patients with dysphagia (Reprinted from Li et al. 2009 with permission from Taylor & Francis)

This finding differs from studies of ALS patients that have investigated simple motor tasks, such as finger tapping. An increase and expansion of the cortical representation has generally been observed in a variety of motor- and non-motor areas in ALS patients as compared with healthy control subjects (Kew et al. 1994; Konrad et al. 2002). The main reason for the lack of cortical compensation of dysphagia in ALS patients is probably the disease-related damage in both cortical swallowing centers, which prevents recruitment of homologous structures, such as the supplementary motor areas and the premotor cortex. The hypothesis that the integrity of at least one cortical swallowing center is a prerequisite for cortical adaptation processes has been supported by the examination of patients with SBMA. In contrast to ALS patients, patients with SBMA display a broader swallowing-related activation in the primary sensorimotor cortex and additional activation of the premotor and somatosensory integration cortices when compared with healthy control subjects (Fig. 1.13; Dziewas et al. 2009).

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig13_HTML.png

Fig. 1.13

Change in cortical activation in dysphagic patients with SBMA. (a) Cortical activation of the sensorimotor cortex in an MEG during swallowing in patients with SBMA; (b) cortical activation in healthy control subjects; SBMA = spinal and bulbar muscular atrophy (Reprinted from Dziewas et al. 2009 with permission from Wiley)

Regardless of the increase in cortical activity in SBMA patients and the decrease in cortical activity in ALS patients, both diseases display a shift in hemispheric lateralization when compared with a healthy control group (Dziewas et al. 2009; Teismann et al. 2011b; Figs. 1.12 and 1.13). While healthy volunteers in both studies displayed a slight preponderance of left-hemispheric activation, the right sensorimotor cortex was predominantly involved in both patient groups. In ALS patients, this right-hemispheric shift even tended to increase with disease progression. These results support the above-mentioned hypothesis of swallowing lateralization and particularly support the notion of right-hemispheric control of the pharyngeal phase.

While studying the effect and cortical reorganization phenomena in a condition leading to subcortical damage to the swallowing network, a MEG study investigated swallow-related cortical activation in a cohort of on Parkinson’s disease (PD) patients (Suntrup et al. 2013). Pathophysiologically, PD is caused by a degeneration of dopaminergic neurons and other cell populations that originate in the brainstem and gradually extend into cortical areas (Braak et al. 2004). In light of the early affection of the brainstem’s swallowing centers by the characteristic pathology, it is astonishing that clinically severe oropharyngeal dysphagia only manifests in most PD patients at an advanced stage of the disease. In the aforementioned MEG study, PD patients without swallowing impairment displayed a hypoactivation of the supplementary motor area as well as a prominent shift in maximum activity to the caudo-lateral motor- and premotor cortex (Fig. 1.14).

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig14_HTML.png

Fig. 1.14

Change in cortical brain activation in PD patients with and without dysphagia compared with age-matched control group (Reprinted from Suntrup et al. 2013 with permission from Oxford University press)

This pattern was no longer observed in PD patients with clinically manifest dysphagia. This patient group showed only residual swallow-related cortical activity confined to the medial primary sensorimotor cortex. Remarkably, this finding fully matches with the studies of Braak et al. (2004), which suggest that these cortical regions are affected by PD-associated neurodegeneration only during the final stages of the disease (Fig. 1.15).

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig15_HTML.png

Fig. 1.15

Distribution of PD pathology (alpha-synucleinopathy) from dorsal motor vagus nucleus and adjacent nuclei of lower brainstem to basal parts of mid- and forebrain and up to cerebral cortex (Reprinted from Braak et al. 2004 with permission from Springer Nature)

To fully understand this changing pattern of swallow-related cortical activation in PD patients, it is necessary to refer to the different neuronal loops that contribute to the control of the motor system (Roland 1984; Frey et al. 2011). Due to damage to the putamen that occurs early on in PD, the frontal striato-thalamocortical loop that mainly projects to the SMA and coordinates internally generated movements is affected during the first stages of PD. As observed in Suntrup et al.’s study, this affection causes hypoactivation of the SMA, which in turn results in the clinical impairment of movement planning and movement initiation as well as in the typical clinical symptoms of freezing and akinesia. The cerebellar-parietal-premotor loop responsible for externally or sensory-cued movements receives projections from the minimally affected caudate nucleus (Alexander and Crutcher 1990) and therefore remains functionally intact for a relatively longer period of time. This regulatory circuit allows for the initiation of movement upon receiving a stimulus. Studies on limb mobility in PD suggest that unlike in healthy individuals, this longer-preserved loop is preferentially used in PD patients for motor control (Samuel et al. 1997). The activity shift measured in the MEG study discussed here therefore also suggests an alternative recruitment of this parallel pathway for the central control of swallowing. With increased utilization of oropharyngeal afferent stimuli (which represents an external cue), the bilaterally represented swallowing function can initially be maintained in a similar manner as the unilaterally controlled limb motor function. The compensatory recruitment of this alternative pathway breaks off as the disease progresses, presumably as a result of increasing degeneration of the relevant cortical areas themselves. This in turn leads to an onset of dysphagia.

In addition to disorders of the CNS and the peripheral nervous system, diseases of the motor end plate (e.g., myasthenia gravis) and of the muscles themselves (e.g., myositis) lead to frequently severe swallowing disorders. Despite the large number of different pathologies, data on cortical adaptation mechanisms remain scarce. Basically, due to the integrity of the cortical swallowing centers, cerebral compensatory mechanisms should be expected to be found in these purely peripheral forms of dysphagia, much as they have also been found in SBMA. However, this assumption has only been confirmed in patients with oropharyngeal tumors with partial glossectomy.

Thus, one fMRI study compared swallow-related brain activation both pre- and post-surgery (Haupage et al. 2010), and a second study matched activation maps after the operation with those of a healthy control group (Mosier et al. 2005). Both studies revealed that patients displayed a significantly greater cerebral activation post-surgery—presumably as a result of cortical reorganization—that was mainly confined to the primary sensorimotor cortex, the supplementary motor areas, the parietal cortex, and the cingulate cortex.

Finally, preliminary study results fuel the assumption that functional dysphagia—which is generally considered to be of psychogenic origin—is accompanied by changes to the cortical processing of swallowing. Basically, despite the frequent use of this diagnosis in clinical practice, functional dysphagia is much less common than true neurogenic dysphagia, which is often falsely attributed to a psychogenic cause. For example, Ravich et al. found an organic correlate in 65% of cases after an extensive re-evaluation of 23 patients who had been diagnosed with a functional swallowing disorder (Ravich et al. 1989). In a recent MEG pilot study, five patients were enrolled in whom no cause of the swallow-related complaints could be detected despite a comprehensive diagnostic work-up (Suntrup et al. 2014). Compared with healthy control subjects, patients showed significant alteration in the cortical control of swallowing consisting of an excess of activation in the right insular cortex and the dorsolateral prefrontal cortex (DLPFC) as well as in the inferior parietal lobe, whereas activation was reduced in the supplementary motor area and the medial primary somatosensory cortex (Fig. 1.16).

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig16_HTML.png

Fig. 1.16

Areas of brain with a significant difference in swallowing-related brain activation between patients with functional dysphagia and healthy subjects (Reprinted from Suntrup et al. 2014). Increased activation is shown in blue-green; decreased activation is shown in white-yellow

Against the background of previous imaging studies on conversion disorders and functional digestive disorders, the previously mentioned regions represent interfaces between the perception of internal body signals, cognitive assessment processes, attention control, and sensorimotor control (Browning et al. 2011). According to the visceral hypersensitivity hypothesis (Bonaz 2003), a disturbed interaction in this network may be accompanied by increased self-observation and a negative self-perception and thereby also by increased cognitive arousal, which, in turn, reinforces self-observation. This vicious circle ultimately results in persistent oropharyngeal hypersensitivity, which leads to a conscious perception of symptoms despite an objectively regular movement pattern during the swallow. With regard to movement planning and execution, the reduced activity of the SMA observed in the MEG study summarized above could indeed be responsible for a subtle imbalance in the swallowing network, which in turn may result in feelings of difficult initiation or hesitation when swallowing (Suntrup et al. 2014).

In addition to disease-related reorganization, age-related changes in swallowing—called presbyphagia—seem to be associated with central adaptation mechanisms. The aging process is accompanied by changes in all phases of deglutition. Thus, in older individuals, a prolonged oral phase (Kim et al. 2005), reduced pharyngeal sensitivity (Aviv 1997a, b), smaller volumes per swallow, a premature passage of the bolus into the pharynx, an accumulation of pharyngeal residues, and a higher rate of laryngeal penetration (Yoshikawa et al. 2005) have been found. Both an fMRI- and an MEG study in groups of older subjects have revealed a swallowing-related increase in sensorimotor cortical activation compared with younger adults (Humbert et al. 2009; Teismann et al. 2010). This activation extended to the premotor cortex, the supplementary motor areas, and the operculum in addition to the primary sensorimotor cortex (Fig. 1.17).

../images/467919_1_En_1_Chapter/467919_1_En_1_Fig17_HTML.jpg

Fig. 1.17

Age-related changes of the central regulation of swallowing. The upper row depicts the brain regions that are significantly more active in older compared with younger subjects during swallowing, whereas the lower row depicts the brain regions that display greater activity in younger subjects (Reprinted from Humbert et al. 2009 with permission from Elsevier). IPG = inferior parietal gyurs, S1 = primary somatosensory cortex, M1 = primary motor cortex, IFG = inferior frontal gyrus, MFG = middle frontal gyrus, SFG = superior frontal gyrus, Tri = triangularis)

An age-related increase of cortical activation is