Chapter 13 Neurogenic Dysphagia
Normal Swallowing
Swallowing is a surprisingly complicated and intricate phenomenon. It comprises a mixture of voluntary and reflex, or automatic, actions engineered and carried out by a combination of the 55 muscles of the oropharyngeal, laryngeal, and esophageal regions, along with five cranial nerves and two cervical nerve roots that in turn receive directions from centers within the central nervous system (Schaller et al., 2006). Reflex swallowing is coordinated and carried out at a brainstem level, where centers act directly on information received from sensory structures within the oropharynx and esophagus. Volitional swallowing is, not surprisingly, accompanied by additional activity that originates not only in motor and sensory cortices, but also in other cerebral structures (Hamdy et al., 1999; Zald and Pardo, 1999).
In the oral, or swallow-preparatory phase, food is taken into the mouth and, if needed, chewed. Saliva is secreted to provide both lubrication and the initial “dose” of digestive enzymes, and the food bolus is formed and shaped by the tongue. The tongue then propels the bolus backward to the pharyngeal inlet where, in a piston-like action, it delivers the bolus into the pharynx. This initiates the pharyngeal phase, in which a cascade of intricate, extremely rapid, and exquisitely coordinated movements seal off the nasal passages and protect the trachea while the cricopharyngeal muscle, which functions as the upper esophageal sphincter (UES), relaxes and allows the bolus to enter the pharynx. As an example of the intricacy of movements during this phase of swallowing, the UES, prompted in part by traction produced by elevation of the larynx, actually relaxes just prior to arrival of the food bolus, creating suction that assists in guiding the bolus into the pharynx. The bolus then enters the esophagus where peristaltic contractions usher it distally and, on relaxation of the lower-esophageal sphincter, into the stomach. Synchronization of swallowing with respiration such that expiration rather than inspiration immediately follows a swallow, thus reducing the risk of aspiration, is another example of the finely tuned coordination involved in the swallowing mechanism(Mehanna and Jankovic, 2010).
Neurophysiology of Swallowing
It is perhaps not surprising that the strongest activation in PET studies of volitional swallowing occurs in the lateral motor cortex within the inferior precentral gyrus, wherein lie the cortical representations of tongue and face. There is disagreement among investigators, however, in that some have noted bilaterally symmetrical activation of the lateral motor cortex (Zald and Pardo, 1999), whereas others have noted a distinctly asymmetrical activation, at least in a portion of subjects tested (Hamdy et al., 1999).
Some additional and perhaps somewhat surprising brain areas are also activated during volitional swallowing (Hamdy et al., 1999; Schaller et al., 2006; Zald and Pardo, 1999). The supplementary motor area may play a role in preparation for volitional swallowing, and the anterior cingulate cortex may be involved with monitoring autonomic and vegetative functions. Another area of activation during volitional swallowing is the anterior insula, particularly on the right. It has been suggested that this activation may provide the substrate that allows gustatory and other intraoral sensations to modulate swallowing. Lesions in the insula may also increase the swallowing threshold and delay the pharyngeal phase of swallowing (Schaller et al., 2006). PET studies also consistently demonstrate distinctly asymmetrical left-sided activation of the cerebellum during swallowing. This activation may reflect cerebellar input concerning coordination, timing, and sequencing of swallowing. Activation of putamen has also been noted during volitional swallowing, but it has not been possible to differentiate this activation from that seen with tongue movement alone.
Within the brainstem, swallowing appears to be regulated by central pattern generators that contain the programs directing the sequential movements of the various muscles involved. The dorsomedial pattern generator resides in the medial reticular formation of the rostral medulla and the reticulum adjacent to the nucleus tractus solitarius and is involved with the initiation and organization of the swallowing sequence (Schaller et al., 2006). A second central pattern generator, the ventrolateral pattern generator, lies near the nucleus ambiguus and its surrounding reticular formation (Prosiegel et al., 2005; Schaller et al., 2006). It serves primarily as a connecting pathway to motor nuclei such as the nucleus ambiguus and the dorsal motor nucleus of the vagus, which directly control motor output to the pharyngeal musculature and proximal esophagus.
Mechanical Dysphagia
Structural abnormalities, both within and adjacent to the mouth, pharynx, and esophagus, can interfere with swallowing on a strictly mechanical basis, despite fully intact and functioning nervous and musculoskeletal systems (Box 13.1). Within the mouth, macroglossia, temporomandibular joint dislocation, certain congenital anomalies, and intraoral tumors can impede effective swallowing and produce mechanical dysphagia. Pharyngeal function can be compromised by processes such as retropharyngeal tumor or abscess, cervical anterior osteophyte formation, Zenker diverticulum, or thyroid gland enlargement. An even broader array of structural lesions can interfere with esophageal function, including malignant or benign esophageal tumors, metastatic carcinoma, esophageal stricture from numerous causes, vascular abnormalities such as aortic aneurysm or aberrant origin of the subclavian artery, or even primary gastric abnormalities such as hiatal hernia or complications from gastric banding procedures. Gastroesophageal reflux can also produce dysphagia. Individuals with these problems, however, are more likely to be seen by the gastroenterologist rather than the neurologist.
Neuromuscular Dysphagia
A variety of neuromuscular disease processes of diverse etiology can involve the oropharyngeal and esophageal musculature and produce dysphagia as part of their broader neuromuscular clinical picture (Box 13.2). Certain muscular dystrophies, inflammatory myopathies, and mitochondrial myopathies all can display dysphagia, as can disease processes affecting the myoneural junction, such as myasthenia gravis.
Oculopharyngeal Muscular Dystrophy
Oculopharyngeal muscular dystrophy (OPMD) is a rare autosomal dominant disorder that has a worldwide distribution. It was initially described and is most frequently encountered in individuals with a French-Canadian ethnic background, although its highest reported prevalence is among the Bukhara Jews in Israel (Abu-Baker and Rouleau, 2007). It is the consequence of a GCG trinucleotide repeat expansion in the polyadenylate-binding protein, nuclear 1 gene (PABPN1; also known as poly(A)-binding protein 2 [PABP2]) on chromosome 14. OPMD is unique among the muscular dystrophies because of its appearance in older individuals, with symptoms typically first appearing between ages 40 and 60. It is characterized by slowly progressive ptosis, dysphagia, and proximal limb weakness. Because of the ptosis, patients with OPMD may assume an unusual posture characterized by raised eyebrows and extended neck.
Dysphagia in OPMD is due to impaired function of the oropharyngeal musculature. Although it evolves slowly over many years, OPMD can eventually result not only in difficulty or discomfort with swallowing, but also in weight loss, malnutrition, and aspiration. No specific treatment for the muscular dystrophy itself is available, but cricopharyngeal myotomy affords dysphagia relief in over 80% of treated individuals (Fradet et al., 1997). More recently, botulinum toxin injections have been successfully used to treat dysphagia in OPMD.
Myotonic Dystrophy
Myotonic dystrophy is an autosomal dominant disorder whose phenotypic picture includes not only skeletal muscle but also cardiac, ophthalmological, and endocrinological involvement. Mutations at two distinct locations have now been associated with the clinical picture of myotonic dystrophy (Turner and Hilton-Jones, 2010). Type 1 myotonic dystrophy is due to a CTG expansion in the myotonic dystrophy protein kinase (DMPK) gene on chromosome 19; type 2 is the consequence of a CCTG repeat expansion in the zinc finger protein 9 (ZNF9) gene on chromosome 3.
Gastrointestinal (GI) symptoms develop in more than 50% of individuals with the clinical phenotype of myotonic dystrophy. These may be the most disabling component of the disorder in 25% of individuals with type 1 myotonic dystrophy, and GI symptoms may actually antedate the appearance of other neuromuscular features (Turner and Hilton-Jones, 2010). Subjective dysphagia is one of the most prevalent GI features and has been reported in 37% to 56% of patients (Ertekin et al., 2001b). Coughing when eating, suggestive of aspiration, may occur in 33%. Objective measures paint a picture of even more pervasive impairment, demonstrating disturbances in swallowing in 70% to 80% of persons with myotonic dystrophy (Ertekin et al., 2001b). In one study, 75% of patients asymptomatic for dysphagia were still noted to have abnormalities on objective testing (Marcon et al., 1998).
A variety of abnormalities in objective measures of swallowing have been documented in myotonic dystrophy. Abnormal cricopharyngeal muscle activity is present in 40% of patients during electromyographic (EMG) testing (Ertekin et al., 2001b). Impaired esophageal peristalsis has also been noted in affected individuals studied with esophageal manometry. On videofluoroscopic testing, incomplete relaxation of the UES and esophageal hypotonia are the most frequently noted abnormalities (Marcon et al., 1998). Both muscle weakness and myotonia are felt to play a role in the development of dysphagia in persons with myotonic dystrophy (Ertekin et al., 2001b), and in at least one study, a correlation was noted between the size of the CTG repeat expansion and the number of radiological abnormalities in myotonic patients (Marcon et al., 1998).
Inflammatory Myopathies
Although dysphagia can develop in both conditions, it more frequently is present in dermatomyositis and when present is more severe. Dysphagia is present in 20% to 55% of individuals with dermatomyositis but in only 18% with polymyositis (Parodi et al., 2002). It is the consequence of involvement of striated muscle in the pharynx and proximal esophagus. Involvement of pharyngeal and esophageal musculature in polymyositis and dermatomyositis is an indicator of poor prognosis and can be the source of significant morbidity. A 1-year mortality rate of 31% has been reported in individuals with inflammatory myopathy and dysphagia (Williams et al., 2003), although other investigators have reported a 1-year survival rate of 89% (Oh et al., 2007).
Dysphagia in persons with inflammatory myopathy may be due to restrictive pharyngo-esophageal abnormalities such as cricopharyngeal bar, Zenker diverticulum, and stenosis. In fact, in one study of 13 patients with inflammatory myopathy, radiographic constrictions were noted in 9 (69%) individuals, compared with 1 of 17 controls with dysphagia of neurogenic origin (Williams et al., 2003). Aspiration was also more common in the patients with myositis (61% versus 41%). The resulting dysphagia can be severe enough to require enteral feeding. Acute total obstruction by the cricopharyngeal muscle has been reported in dermatomyositis, necessitating cricopharyngeal myotomy. Other investigators have reported improvement in 50% of individuals 1 month following cricopharyngeal bar disruption; improvement was still present in 25% at 6 months (Williams et al., 2003). The reason for the formation of restrictive abnormalities in inflammatory myopathy is uncertain, but it may be that long-standing inflammation of the cricopharyngeus muscle impedes its compliance and ability to open fully (Williams et al., 2003).
Dysphagia may also develop in inclusion body myositis. It may even be the presenting symptom (Cox et al., 2009). In the late stages of the disorder, the frequency of dysphagia may actually exceed that seen in dermatomyositis and polymyositis. In a group of individuals in whom inclusion-body myositis mimicked and was confused with motor neuron disease, dysphagia was present in 44% (Dabby et al., 2001). In another study, dysphagia was documented in 37 of 57 (65%) patients with inclusion-body myositis (Cox et al., 2009). Abnormal function of the cricopharyngeal sphincter, probably due to inflammatory involvement of the cricopharyngeal muscle, with consequently reduced compliance, was documented in 37%. A focal inflammatory myopathy involving the pharyngeal muscles and producing isolated pharyngeal dysphagia has also been described in individuals older than age 69. It has been suggested that this is a distinct clinical entity characterized by cricopharyngeal hypertrophy, although polymyositis localized to the pharyngeal musculature has also been reported.
Dysphagia in both dermatomyositis and polymyositis may respond to corticosteroids and other immunosuppressive drugs, and these remain the mainstay of treatment. Intravenous immunoglobulin therapy has produced dramatic improvement in dysphagia in individuals who were unresponsive to steroids. However, inclusion-body myositis typically responds poorly to these agents, and myotomy is often necessary (Ebert, 2010; Oh et al., 2007).
