Gastrointestinal Complications of Neuromuscular Disorders

Impairment of Deglutition (Dysphagia)

Dysphagia is one of the most disabling conditions arising from neuromuscular disorders, with high morbidity, mortality, and cost ( ; ). Dysphagia typically refers to difficulty in eating as a result of disruption in the swallowing process. It is a subjective sensation that suggests the presence of an organic abnormality in the passage of liquids or solids from the oral cavity to the stomach. Patients’ complaints range from the inability to initiate a swallow to the sensation of solids or liquids being hindered during their passage through the esophagus into the stomach. The prevalence of dysphagia in selected neuromuscular disorders is depicted in Table 4.1 ( ).

Dysphagia can be classified as either oropharyngeal or esophageal. Oropharyngeal dysphagia, also called transfer dysphagia, arises from disorders that affect the function of the oropharynx, larynx, and upper esophageal sphincter (UES). Neurogenic and myogenic disorders as well as oropharyngeal tumors are the most common underlying causes for oropharyngeal dysphagia. Esophageal dysphagia arises within the body of the esophagus, the lower esophageal sphincter, or cardia and is most commonly due to mechanical causes or a motility disturbance. However, some neuromuscular disorders affect the esophagus as inflammatory myopathies.

Normal swallowing consists of three phases (oral, pharyngeal, and esophageal), which are usually performed effortlessly up to 600 times a day. A total of five cranial nerves (V, VII, IX, X, and XII) and 26 muscle groups are involved in coordinating the act of swallowing. In the oral phase, the food is chewed and the bolus is pushed to the pharynx under voluntary control. In the pharyngeal phase, the nasopharynx closes to prevent food entry into the nasal passages. The vocal cords approximate and the epiglottis tilts downward to prevent entry of food into the airway. Relaxation of the upper esophageal sphincter and progressive waves of muscular contraction propel the food bolus into the esophagus. In the esophageal phase, peristalsis moves the food bolus through the esophagus and the lower esophageal sphincter into the stomach.

Dysphagia in Motor Neuron Disorders

Dysphagia due to bulbar or pseudobulbar palsy occurs in up to 25% of amyotrophic lateral sclerosis (ALS) patients at the onset of the disease ( ). Dysphagia occurs very early in patients with bulbar onset as compared to those with spinal onset, in which the disease duration influences the occurrence of dysphagia ( ). Eventually, almost all patients with ALS have at least some degree of dysphagia ( ). In motor neuron disorder (MND), weakness of the orolingual as well as the pharyngeal muscles leads to swallowing difficulties. Pharyngeal constrictor muscle weakness results in choking or coughing during or immediately after swallowing. Sialorrhea (drooling) is common and results from impaired pharyngeal clearance and weakness of oral muscles rather than an increase in salivation. Progression of dysphagia results in weight loss because of the patient’s inability to maintain adequate caloric intake with oral feedings alone. Dysphagia affects not only caloric intake but also the delivery of effective disease-modifying drug therapy like Riluzole in patients with ALS. Riluzole is available in an oral suspension, which can be used as an alternative to tablets for patients with dysphagia. Riluzole did not impact survival either in dysphagic or in nondysphagic ALS patients ( ).

Dysphagia in Primary Muscular Disorders

Dysphagia in myopathies arises from impairment of pharyngeal and esophageal phases ( ).

Unlike neurogenic disorders (neuropathies and motor neuron disease) and disorders of neuromuscular transmission, there is usually no significant impairment of mastication. However, to avoid aspiration, patients may spend a long time chewing their food. Nasal regurgitation and dysarthria are also less frequent ( ).

Although in theory any muscular disorder may present with impairment of swallowing, abnormalities of deglutition tend to predominate in some types of muscle disease. These include certain muscular dystrophies such as oculopharyngeal muscular dystrophy (OPMD) ( ), myotonic dystrophy (MD) and patients with advanced stages of Duchenne muscular dystrophy (DMD), and fascioscapulohumeral myopathy ( ; ; ; ). Inflammatory disorders such as polymyositis (PM), dermatomyositis (DM), and inclusion body myositis can involve the muscles of deglutition. Metabolic myopathies, particularly mitochondrial myopathies, may present with impairment of swallowing as well ( ). Some patients who have cricopharyngeal (CP) achalasia with associated impairment of the CP muscle function and its ability to relax can present with oropharyngeal dysphagia.

Recently, some authors have suggested that a combined myopathic-neuropathic etiology could provide a more satisfactory explanation for the pharyngo-esophageal symptoms of MD, but at present, this remains speculative ( ). Marked atrophy of the esophageal striated muscle, but only small changes in the smooth muscle, was observed in one study ( ), and using electron microscopy in another study, detected mild degenerative changes with disoriented filaments of the smooth muscle.

MD (Steinert disease) is the most common adult-onset form of muscular dystrophy. There are frequent dysarthria and dysphagia owing to weakness of the palatal and pharyngeal muscles ( ). In MD, different studies have reported a prevalence of dysphagia ranging from 25% to 80% ( ; ; ).

OPMD, an autosomal dominant disorder, manifests as bilateral symmetrical ptosis, external ophthalmoparesis, and dysphagia ( ). Dysphagia is frequent and may be the presenting symptom with impairment mainly of the pharyngeal phase, although lingual and oral phases can also be affected. Patients usually develop symptoms between the fourth and fifth decades. In one study, retroflexion of the head because of ptosis was noted to deteriorate preexisting dysphagia in OPMD patients. Subjective and objective reduction of swallowing problems was found when patients were instructed to eat and drink with a slightly flexed head position ( ). Complications including dysphonia and aspiration can develop after years of progression.

In DMD, there is some involvement of the oropharyngeal muscles ( ). The occurrence of macroglossia further complicates the oral phase of swallowing. In the oral preparatory phase, occasional difficulties in bringing food to the mouth, chewing difficulty, and malocclusion have been observed in patients with DMD, including tongue biting due to macroglossia.

Dysphagia in Inflammatory Myopathies and Neuromuscular Junction Disorders

Among inflammatory myopathies, PM associated with connective tissue disease and inclusion body myositis (IBM) are most likely associated with dysphagia ( ; ). Of all the inflammatory myopathies, IBM is notorious for esophageal involvement and a steroid resistant disease course ( ; ). Dysphagia occurs primarily from the involvement of striated muscles, but in some cases the upper third of the esophagus may be affected. Dysphagia is often an early presenting symptom in older patients affected with inflammatory myopathy. Disorders affecting neuromuscular junction including myasthenia gravis can present with intermittent swallowing problem and are often associated with oculomotor abnormalities, including diplopia, and facial muscle weakness. Clinical symptoms range from problems with chewing food or moving it in their mouth to problems related to the pharyngeal phase. Involvement of the pharyngeal muscles in Lambert-Eaton syndrome has been described, and only a small number of patients develop dysphagia.

Dysphagia in Peripheral Neuropathy

Peripheral neuropathy seldom involves the pharyngeal muscles. However, polyradiculoneuropathies, both acute (Guillain-Barre Syndrome) and chronic inflammatory demyelinating neuropathy involving cranial nerves, can lead to pharyngeal and cervical muscle weakness.

Dysphagia Diagnosis and Evaluation

Various noninstrumental examinations (volume-viscosity swallow test, Eating Assessment Tool 10) as well as instrumental examinations (videofluoroscopic swallowing study [VFSS] or fiberoptic endoscopic evaluation of swallowing [FEES]) can be utilized to evaluate and screen patients with MND for dysphagia. VFSS, in conjunction with an oropharyngeal examination by a speech pathologist, can provide a more objective measurement of swallowing ( ). Videofluoroscopy involves the swallowing by the patient of barium suspension of varying consistency, fluid and semisolid. An analysis of the various stages of swallowing is made, and laryngeal penetration can be reliably detected by videofluoroscopy. Videofluoroscopy can also help guide decisions about feeding regimes and estimate the patient’s risk of respiratory complications from oral feeding. Videofluoroscopy could be used to assess risks of aspiration. The presence of laryngeal penetration on videofluoroscopy in the setting of clinical dysphagia indicates a high risk of aspiration pneumonia ( Figs. 4.1 and 4.2 ). Cineradiographic studies of the pharynx in MD patients have revealed abnormalities such as weak and asymmetric contractions of the pharynx and cricopharyngeus, myotonia of the tongue and pharynx with stasis, and pooling of contrast in the pyriform sinuses and valleculae. The combined techniques of videofibrolaryngoscopy and videofluoroscopy can be the best methods for evaluating dysphagia.

Manometry is useful in detecting motility disturbances, which show in the form of asymmetric contractions of the pharynx and weak contractions of the upper esophageal sphincter. In the esophageal body, significant decreases in the peristaltic amplitude and/or simultaneous waves have often been reported among patients with MD ( ; ; ; ; ; ). However, manometric findings are not significantly different between symptomatic and asymptomatic patients or in patients with different degrees of striated muscular involvement. Eleven patients with an established diagnosis of OPMD were studied by . They found that nine of these patients showed abnormal UES and pharyngeal manometrics, with the most common abnormalities found in the pharynx (UES and pharyngeal incoordination, prolonged pharyngeal contraction, low pharyngeal pressure, and low pharyngeal contraction rate). Another procedure that has been used for evaluation of dysphagia in MND patients is the use of electromyographic (EMG) techniques.

Routine endoscopy is not helpful in the majority of patients unless underlying esophageal inflammation with complications related to reflux needs endoscopic evaluation. A study comparing VFSS with FEES found that VFSS had a significantly greater sensitivity in detecting swallowing alterations as compared to FEES ( ). The authors of the paper also recommended FEES only if VFSS is not available or if the patient cannot be positioned for the study or is bedridden.

Noninvasive studies are quick, cost-effective, highly sensitive, and specific tools for screening, which can be confirmed using instrumental examinations when the aspiration status is still unclear from noninvasive studies ( ).