**2. Physiopathology of dysphagia: focusing on ALS**

Swallowing is a complex act that involves the coordination of multiple sensory and motor systems. During the oral phase, the tongue forms and holds a bolus on the anterior tongue. Currently, the posterior tongue prevents the food from entering the pharynx prematurely. After bolus formation, the posterior transport of the bolus is initiated by the anterior tongue pressing against the hard palate. In the pharyngeal phase, the posterior tongue retracts against the pharyngeal wall and contributes to the downward propulsion of the bolus [16].

ALS may present with a combination of spastic and flaccid weakness that can affect swallowing significantly. Dysphagia in ALS results from bulbar sensory-motor neurodegeneration, which is a pathognomonic feature of ALS [1]. Involvement of the motor nuclei located in the brainstem causes the characteristic bulbar muscle weakness and atrophy, leading to dysphagia. Oropharyngeal impairment of the tongue has been identified, but the underlying mechanisms of its motor dysfunction are not completely understood [17].

Impairment of the tongue seems to represent a major risk factor for aspiration [18]. One study showed a correlation between tongue pressure and the severity of dysphagia and physical performance in 39 patients with ALS [19]. Although swallowing pressures are known to be considerably weaker than maximum pressure exerted by tongue-palate contact pressure tasks, specific measures of maximum tongue strength have been shown to be associated with overall swallowing performance [20].

The occurrence of dysphagia in ALS patients is also related to impairments in the upper aerodigestive tract and respiratory and laryngeal muscles to the extent that they affect the expiratory phase of voluntary cough. There is a strong connection between poor effective voluntary cough and the presence of penetration/aspiration events [21].

One study looked into the pathophysiological mechanisms of dysphagia in 43 patients with sporadic ALS, using clinical and electrophysiological methods that objectively measured the oropharyngeal phase of voluntarily initiated swallowing, and compared them with those obtained from 50 age-matched control subjects [22]. Laryngeal movements were detected by a piezoelectric sensor and muscle electromyography (EMG) of submental muscles, while needle EMG recorded the activity of the cricopharyngeal muscle of the upper esophageal sphincter (UES) during swallowing. ALS patients with dysphagia displayed the following abnormal findings: 1) submental muscle activity of the laryngeal elevators, which produce reflex upward deflection of the larynx during wet swallowing, was significantly prolonged, whereas the laryngeal relocation time of the swallowing reflex remained within normal limits; 2) concerning the cricopharyngeal sphincter muscle, EMG demonstrated severe abnormalities during voluntarily initiated swallows. The opening of the sphincter was delayed and/or the closure occurred prematurely, the total duration of opening was shortened, and, at times, unexpected motor unit bursts appeared during this period; and 3) during voluntarily initiated swallow, there was a significant lack of coordination between the laryngeal elevator muscles and the cricopharyngeal sphincter muscle. These results point at two pathophysiological

mechanisms that cause dysphagia in ALS patients: 1) the triggering of the swallowing reflex for the voluntarily initiated swallow is delayed and eventually abolished, whereas the spontaneous reflexive swallows are preserved until the preterminal stage of ALS; 2) the cricopharyngeal sphincter muscle of the UES becomes hyperreflexic and hypertonic. As a result, the laryngeal protective system and the bolus transport system of deglutition lose their coordination during voluntarily initiated swallowing.

Another study investigated the variations of esophageal peristalsis in 28 ALS patients with predominantly bulbar or predominantly pseudobulbar clinical presentation by using esophageal manometry (EM) [23]. Swallowing was initiated with 5–10 mL of water (wet swallows) and saliva (dry swallows) and repeated at 30-second intervals. The manometric parameters were measured automatically and visualized by the computer system. In patients with pseudobulbar presentation, an increase of the resting pressure value in the UES >45 mmHg, a wave-like course of resting pressure, and toothed peristaltic waves were observed. In patients with bulbar presentation, a low amplitude of peristaltic waves <30 mmHg (mean: 17 ± 5) was recorded, without signs of esophageal motility disturbance at onset or during progression. EM procedure allows objectively distinguishing dysphagia in ALS patients due to bulbar syndrome from dysphagia due to pseudobulbar syndrome. It is crucial to identify patients with pseudobulbar clinical presentation due to their high risk of aspiration.

When considering management and treatment of dysphagia, visualization of physiology is the only reliable method to understand the pathophysiology of this condition [24].

## **3. Dysphagia assessment**

The diagnosis of dysphagia is of utmost importance, given the burden of this symptom, causing malnutrition, dehydration, aspiration pneumonia, respiratory failure, and reduced quality of life. Aspiration and malnutrition increase the risk of death [25]. Early identification of dysphagia facilitates improved management, reduced risk of malnutrition and postponed percutaneous endoscopic gastrostomy (PEG) tube placement [26, 27]. The search for dysphagia as early as possible is key in order to prevent its complications.

The diagnosis of dysphagia is more easily performed at multidisciplinary clinics. A dysphagia assessment should be performed in all patients with ALS, both at diagnosis and during follow-up, with a recommended frequency of every 3 months, as part of a complete clinical and neurological evaluation [12].

Dysphagia can be underestimated in ALS due to progressive adaptation to the slow bulbar deterioration and given the inconsistencies in what patients report about the condition. Often, oral stage deficits like difficulties in chewing or oral residue are not reported by the patient until pharyngeal stage deficits, such as coughing or choking, are observed.

A clinical swallow evaluation for suspected dysphagia involves medical history, physical inspection of swallowing, instrumental evaluation, pulmonary function, and bulbar function. However, most importantly, a screening test for dysphagia should be carried out.

Medical history. This includes the reporting of symptoms related to dysphagia, kind of diet, assistance with feeding, changes in body weight, coughing or choking with meals, length of time needed for food intake and saliva management. A validated questionnaire to assess these symptoms is the Eating assessment tool 10 (EAT-10), which has been validated for use in ALS [27]. This study reported high

#### *Dysphagia of Neurological Origin – Amyotrophic Lateral Sclerosis DOI: http://dx.doi.org/10.5772/intechopen.101753*

clinical utility and ability to detect aspiration risk in ALS (86% sensitivity, 76% specificity and 95% negative predictive value). However, the validation of the test was performed only against penetration and aspiration scores on the videofluoroscopic swallowing study (VFSS) and not against any overall parameter of swallowing efficiency and safety. The kind of diet can be evaluated by the Neuromuscular Disease Swallowing Status Scale (NdSSS) and the Swallowing subscale on Amyotrophic Lateral Sclerosis Severity Scale (ALSSS). However, these scales do not detect all the patients with alterations in swallowing [28]. An important parameter related to dysphagia and intake is weight loss, which is, therefore, mandatorily recorded at all visits. Moreover, it is important to remember that weight loss and dietary intake are associated with more than just dysphagia.

Physical inspection of systems involved in swallowing and swallowing musculature should go beyond the mere observation of swallowing competence with test swallows. A dysphagia/aspiration screening evaluation is useful when determining the dysphagia risk; however, only limited validation has been completed in ALS. One study validated the volume-viscosity swallowing test (V-VST) against VFSS in 20 ALS patients and reported 93% sensitivity and 80% specificity, respectively [29]. The V-VST is a screening evaluation that involves determining safety and efficiency of swallowing, following the administration of multiple volumes and viscosities of liquids. Another method is the sequential water swallowing (SWS), which involves drinking 100 ml of water in a single, uninterrupted swallow. One study reported that 43% of patients with ALS have a disorganized pattern in their sequential swallows [30].

Instrumental evaluation, such as VFSS or functional endoscopic evaluation of swallow (FEES), is used to visualize the swallowing physiology. These techniques are essential and are the most commonly used, being considered the gold standard in the exploration of dysphagia in ALS, due to the high risk for silent aspiration that these patients have. In fact, one study suggests that up to 55% of ALS patients may present with silent aspiration [31]. VFSS can be used to evaluate problems in the oral phase of the swallowing process, and intradeglutitive silent aspiration can be detected. The interpretation of VFSS results can be done with the videofluoroscopic dysphagia scale (VDS), which contains 14 categories that represent oral functions (lip closure, mastication, bolus formation, premature bolus loss, apraxia, and oral transit time) and pharyngeal functions (pharyngeal triggering, laryngeal elevation, epiglottic closure, pharyngeal transit time, pharyngeal coating, vallecular and pyriform sinus residues, and tracheal aspiration) [32]. A modified version of VSD (mVSD) has been developed to overcome low inter-rater reliability of some categories in the VDS [33]. FEES is a valid, repeatable, and low-cost alternative, used to directly visualize the swallowing process and the saliva movement, and it is able to evaluate pharyngo-laryngeal sensitivity in addition to motility [34]. Other instrumental methods are manometry, in addition to VFSS, electromyography of submental, laryngeal, pharyngeal and diaphragmatic nerves, esophageal scintography [35], tongue sonography and electromagnetic articulography.

Pulmonary function, generally assessed with forced vital capacity (FVC) and cough function, must be explored in patients with dysphagia. Patients with deteriorated pulmonary function are more likely to aspirate.

Bulbar function consists of the evaluation of the anatomy and physiology of head and neck structures involved in swallowing, including an evaluation of the cranial nerves essential for swallowing. The Centre for Neurologic Study Bulbar Function Scale (CNS-BFS) is a useful metric for assessing bulbar function. Among bulbar muscles, the tongue musculature appears to be disproportionally more affected by ALS [36], and tongue strength is a prognostic indicator of survival at

the time of ALS diagnosis [37]. Besides, measuring the maximum tongue strength is useful for early detection of dysphagia in ALS [38]. Other important signs of bulbar impairment are weak cough and dysarthria, which should be investigated.

It is imperative to derivate to a speech-language pathologist (SLP) if any bulbar dysfunction is identified. SLP plays an important role in the care of patients with speech, language, or swallowing difficulties that can result from a variety of medical condition.

One of the ways to improve reliability of clinical evaluations is to use standardized and validated protocols. A comprehensive assessment protocol, such as the Mann Assessment of Swallowing Ability (MASA), may be useful to carry out research in the ALS population. MASA, developed and validated for stroke, includes a detailed oral mechanism examination, cranial nerve testing and swallowing function evaluation [39].

Despite this, there is a lack of studies related to the diagnosis of dysphagia in patients with ALS, which is reflected in a significant variability and inconsistency in the management of dysphagia in ALS, as shown in a survey of current clinical practice patterns at 38 ALS centers in the United States in 2017 [40]. In another survey study performed in 2020, 88.9% of SLP performed an instrumental dysphagia evaluation in ALS patients, although the timing of when the evaluation occurred varied significantly; 42.2% of the clinicians carried it out at baseline even prior to the appearance of any bulbar symptoms [41].
