Mechanism of swallowing

Swallowing is an incredibly complicated and intricate phenomenon.  It comprises a mixture of voluntary and reflex, or automatic, actions engineered and carried out by some of the more than 30 pairs of muscles within 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.

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.  Differentiation can be made between voluntary swallowing, which occurs when a person desires to eat or drink during the awake and aware state, and spontaneous swallowing in response to accumulated saliva in the mouth.  Volitional swallowing is, not surprisingly, accompanied by additional activity that originates not only in motor and sensory cortices but also in other cerebral structures.

Swallowing occurs in 3 phases.  It is a continuum as the events occurring in each of these 3 phases are related to each other and dysfunction at one phase can impact and influence the other phases.  The 3 phases are oral, pharyngeal, and esophageal, which some subdivide into oral preparatory and oral propulsive, pharyngeal, and esophageal.  These components have also been distilled into what has been designated the horizontal and vertical subsystems, reflecting the direction of bolus flow in each component (when the individual is upright while swallowing). The horizontal subsystem comprises the oral phase of swallowing and is largely volitional; the vertical subsystem comprises the pharyngeal and esophageal phases, which are primarily under reflex control.  These events occur rapidly.  

Oral phase (preparatory and propulsive phase):  The start of the oral phase is ingestion (eating or drinking).  What happens during this phase depends upon what one is consuming.  When consuming a liquid it is immediately transported back into the pharynx by the tongue pushing along the palate and stripping the contents creating pressure from tongue to palatal contact.  The pressure is important to ensure clearance of the bolus.  But if one is ingesting something more solid.  Then chewing will be completed first.  It depends upon highly coordinated efforts between the jaw, the tongue, and the muscles of mastication.  Following this, there is a backward propulsion of the bolus by the tongue in the oropharynx.  Sensory receptors alerting the nuclei in the medulla and brainstem which houses the central pattern generator for swallowing initiate a response of pharyngeal swallow. 

In the oral 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; the food bolus is then formed and shaped by the tongue.  In the oral propulsive phase, the tongue 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 protects the trachea while the cricopharyngeal muscle, which functions as the primary component of the upper esophageal sphincter (UES), relaxes and allows the bolus to enter the esophagus.  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 before the arrival of the food bolus, creating suction that assists in guiding the bolus into the esophagus.  The bolus then enters the esophagus, where peristaltic contractions usher it distally and, on relaxation of the lower esophageal sphincter, into the stomach.

Swallowing is synchronized with respiration, such that expiration rather than inspiration immediately follows a swallow, thus reducing the risk of aspiration—another example of the finely tuned coordination involved in the swallowing mechanism.

Pharngeal phase:  It involves rapid and nearly simultaneous events that allows the pharynx to transfer the bolus into the opening of the esophagus.  

Esophageal phase: The upper esophagus will close behind the tail of the bolus.  Esophageal peristalsis occurs and is food is shifted downward assisted by gravity since we tend to eat when upright.  The bolus go through the relaxed lower esophageal sphincter and passes into the stomach.  Once the bolus passes through the lower esophageal sphincter, the sphincter closes.  

Neurophysiology of swallowing

Central control of swallowing has traditionally been ascribed to brainstem structures, with cortical supervision and modulation emanating from the inferior precentral gyrus.  However, positron emission tomography (PET), transcranial magnetic stimulation (TMS), and functional magnetic resonance imaging (fMRI) studies of volitional swallowing reveal a considerably more complex picture in which a broad network of brain regions is active in the control and execution of swallowing.

It is perhaps not surprising that in PET studies, the strongest activation 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 whereas others have noted a distinctly asymmetrical activation, at least in some of the subjects tested.

Additional and perhaps somewhat surprising brain areas also are activated during volitional swallowing .  The supplementary motor area may play a role in preparing 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.  PET studies also consistently demonstrate distinctly asymmetrical left-sided activation of the cerebellum during swallowing.  This activation may reflect cerebellar input concerning the 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.  A second central pattern generator, the ventrolateral pattern generator, lies near the nucleus ambiguus and its surrounding reticular formation.  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. The enteric nervous system also plays a role in controlling esophageal function, apparently involving both motor and sensory components.  It has become evident that a large network of structures participates in the act of swallowing, especially volitional swallowing.  The presence of this network presumably accounts for the broad array of neurological disease processes that can produce dysphagia as a part of the clinical picture.

Impaired swallowing, or dysphagia, can originate from disturbances in the mouth, pharynx, or esophagus that may be generated by mechanical, musculoskeletal, or neurogenic mechanisms.

Epidemiology:  Dysphagia is surprisingly common and has been reported to be present in 3% of the general population and in 10% of individuals over age 65.  Dysphagia occurs quite frequently in neurological patients and can occur in a broad array of neurological or neuromuscular conditions.  It has been estimated that neurogenic dysphagia develops in approximately 400,000 to 800,000 people per year, and that dysphagia is present in roughly 50% of inhabitants of long-term care units.  Moreover, dysphagia can lead to superimposed problems such as inadequate nutrition, dehydration, recurrent upper respiratory infections, and frank aspiration with consequent pneumonia and even asphyxia.  It thus constitutes a formidable and frequent problem confronting the neurologist in everyday practice.

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.  Certain muscular dystrophies, inflammatory myopathies, and mitochondrial myopathies can all display dysphagia, as can disease processes affecting the myoneural junction, such as myasthenia gravis (MG).

Clue Cause of Dysphagia

• Difficulty initiating swallowing :  Oropharyngeal dysfunction

• Repetitive swallowing:  Oropharyngeal dysfunction

• Retrosternal “hanging-up” sensation:  Esophageal dysfunction

• Difficulty with solids but not liquids:  Mechanical obstruction

• Difficulty with both solids and liquids:  Esophageal dysmotility

• Regurgitation of undigested food:  Zenker diverticulum

• Halitosis:  Zenker diverticulum

Dysphagia limit:

Normal subjects can swallow a 20-mL bolus of water in a single attempt, but persons with dysphagia must divide the bolus into two or more parts in order to complete the swallow.  If individuals are given stepwise increases in bolus volume, the volume of fluid at which the division of the bolus first occurs is labeled the dysphagia limit.  The investigators consider a dysphagia limit of less than 20 mL as abnormal and indicative of dysphagia.

FOIS (functional oral intake scale)

https://eatspeakthink.com/wp-content/uploads/2019/06/9-free-swallow-assmt-tools.pdf

Dysphagia in Adult Myopathies

Neuromuscular Dysphagia

Oropharyngeal

• Inflammatory myopathies: Dermatomyositis, Inclusion body myositis, Polymyositis, SLONM, ICI-associated IMNM

• Mitochondrial myopathies: Kearns-Sayre syndrome, MNGIE,

• Muscular dystrophies: Duchenne, Facioscapulohumeral, Limb girdle muscular dystrophy, Myotonic dystrophy, OPMD, congenital myopathies, Pompe'sdisease, myofibrillar myopathy, Miscellaneous (MEGF10 myopathies, Vocal cord and pharyngeal weakness with distal myopathy, matrin-3)

• Neuromuscular junction disorders: Botulism, Lambert-Eaton syndrome, Myasthenia gravis

• Others: Tetanus, Scleroderma, Stiff man syndrome, amyloid-associated myopathy.

Esophageal

• Amyloidosis

• Inflammatory myopathies: Dermatomyositis, Polymyositis, Scleroderma.

Neurogenic Dysphagia

Oropharyngeal

• Arnold-Chiari malformation

• Basal ganglia disease: Biotin responsive, Corticobasal degeneration, DLB, HD, Multiple system atrophy, Neuroacanthocytosis, PD, PSP, WD, Central pontine myelinolysis, Cerebral palsy,

• Drug related: Cyclosporine, Tardive dyskinesia, Vincristine.

• Infectious: Brainstem encephalitis, Diphtheria, Epstein-Barr virus, Listeria, Poliomyelitis, Progressive multifocal leukoencephalopathy, Rabies

• Mass lesions: Abscess, Hemorrhage, Metastatic tumor, Primary tumor.

• Motor neuron diseases: ALS, MS

• Peripheral neuropathic processes: Charcot-Marie-Tooth disease, Guillain-Barré syndrome (Miller Fisher variant)

• Spinocerebellar ataxias

• Stroke

• Syringobulbia

Esophageal

• Achalasia

• Autonomic neuropathies: Diabetes mellitus, Familial dysautonomia, Paraneoplastic syndromes.

• Basal ganglia disorders: PD

• Chagas disease

• Esophageal motility disorders

• Scleroderma

Mechanical Dysphagia

Oral

• Amyloidosis

• Congenital abnormalities

• Intraoral tumors

• Lip injuries: Burns, Trauma

• Macroglossia

• Scleroderma

• Temporomandibular joint dysfunction

• Xerostomia: Sjögren syndrome

Pharyngeal

• Cervical anterior osteophytes

• Infection: Diphtheria

• Thyromegaly

• Retropharyngeal abscess

• Retropharyngeal tumor

• Zenker diverticulum

Esophageal

• Aberrant origin of right subclavian artery

• Caustic injury

• Esophageal carcinoma

• Esophageal diverticulum

• Esophageal infection: Candida albicans, Cytomegalovirus, Herpes simplex virus, Varicella zoster virus

• Esophageal intramural pseudodiverticula

• Esophageal stricture

• Esophageal ulceration

• Esophageal webs or rings

• Gastroesophageal reflux disease

• Hiatal hernia

• Metastatic carcinoma

• Posterior mediastinal mass

• Thoracic aortic aneurysm

Diagnostic Tests:

Oropharyngeal

• Clinical examination

• Cervical auscultation

• Timed swallowing tests

• 3-oz water swallow test

• Modified barium swallow test

• Pharyngeal videoendoscopy

• Pharyngeal manometry

• Videomanofluorometry

• Electromyographic recording

• Dysphagia limit

Esophageal

• Endoscopy

• Esophageal manometry

• Videofluoroscopy

Muscle disorder that affect swallowing

https://www.nature.com/gimo/contents/pt1/full/gimo34.html

Neurological disorders affecting oral, pharyngeal swallowing

Dysphagia Testing

If Oral Phase Dysfunction Is Suspected

• Screening tests:

  • Clinical examination

  • Cervical auscultation

  • 3-oz water swallow

Primary test:  Modified barium swallow

If Pharyngeal Phase Dysfunction Is Suspected

• Screening tests:

  • Clinical examination

  • 3-oz water swallow

  • Timed swallowing

Primary test: Modified barium swallow

Complementary tests: Pharyngeal videoendoscopy, Pharyngeal manometry, Electromyography, Videomanofluorometry,

If Esophageal Dysfunction Is Suspected

Primary tests: Videofluoroscopy, Endoscopy

Complementary test: Esophageal manometry

Diagnosis of neurogenic dysphagia  - review 

Management of neurogenic dysphagia

Anti-IgLON5 Disease (neurology.org) 

EAT-10: A Swallowing Screening Tool | Nestlé Health Science (nestlehealthscience.com) 

SWAL-QOL

Endoscopic evaluation of oral and pharyngeal phases of swallowing : GI Motility online (nature.com) 

https://www.nature.com/gimo/contents/pt1/full/gimo19.html

https://www.nature.com/gimo/contents/pt1/full/gimo46.html

ttps://www.nature.com/gimo/contents/pt1/full/gimo18.html

https://www.nature.com/gimo/contents/pt1/full/gimo41.html

https://www.nature.com/gimo/contents/pt1/full/gimo34.html

https://www.nature.com/gimo/contents/pt1/full/gimo18.html

Evaluating swallowing muscles for Hyolaryngeal elevation

https://www.nature.com/gimo/contents/pt1/full/gimo34.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760404/

Lingual tonsillar hypertrophy

He has subacute onset dysphagia starting early in October 2023 with symptoms of tightness in his throat causing difficulty in swallowing solid food.  EGD on 08/09 2023 reportedly showed ulcerative esophagitis with esophageal stricture that was subsequently dilated.  Swallow evaluation deemed his swallowing to be unsafe and inefficient; with a risk for aspiration.  PEG-T was placed on 08/15/2023.  He was supposed to be on enteral feed but has disregarded this and resumed eating his meals orally.  According to his sister (Cathy) who is accompanying him today, he aspirated and developed pneumonia as a result.  He has lost significant weight and is cachectic and malnourished as a result of dysphagia.  He was evaluated by speech pathology to raise the question of possible central etiology involving the brainstem.  MRI of the brain (09/26/2023) does not show any evidence of acute stroke.  He was referred for neuromuscular evaluation to rule out neurogenic dysphagia particularly related to  neurodegenerative conditions.

 The differential diagnosis of dysphagia in his case is broad and includes: 

Mechanical obstruction:  GI causes to include esophageal stricture, esophageal webs or rings.  Given his history of right parotitis, retropharyngeal masses/phlegmon or tumor resulting in mechanical obstruction  Posterior mediastinal mass, CP bar secondary to GERD, Zenker diverticulum retrosternal goiter, thoracic aortic aneurysm, cervical anterior osteophytes, DISH, are less likely since dysphagia is unrelated and does not worsen when laying supine.  He will require a repeat swallow evaluation.  Pharyngeal manometry, EGD, and esophageal manometry, videomanofluoremetry check for cricopharyngeal achalasia and other gastrointestinal causes.

Neurogenic causes: Neurodegenerative/MND:  Patient has dysphagia is out of proportion to dysarthria which is atypical for bulbar onset motor neuron disease where typically dysarthria proceeds dysphagia; but this is not absolute.  However, in bulbar onset MND, one would expect onset of mixed (spastic/flaccid) dysarthria, respiratory insufficiency by this time, which is not seen.  He has slowness of speech and dysarthria which is can be partly related to loose dentures and the copious amounts of Polligrip denture cream, he uses copiously.  Additionally, he does not have tongue atrophy.  He has gag reflex and  his palatal arch elevates midline.  Patient has significant weight loss and loss of muscle bulk, diffusely - cachectic.  He does not have focal muscle atrophy.  During the clinical interview and exam, patient became tearful and cried loud; however this was within the context of his difficulties with his current condition.  It was unclear that this may be due to pseudobulbar affect but his sister mentioned that he has had frequent emotional breakdown, attributed to his bipolar disorder.  Pertinent differential diagnosis to consider include:  Brainstem stroke, post-stroke dysphagia, CPM, brainstem encephalitis, brainstem glioma, skull base tumors including clival meningioma - however, he does not have features of these clinical syndromes.  Syringobulbia.  Progressive supranuclear palsy, isolated bulbar ALS, bulbar onset ALS, primary lateral sclerosis SBMA (Kennedy’s disease, IgLON5 bulbar paralysis.  

 Muscle/NMJ:  SLONM, overlap polymyositis, systemic sclerosis or mixed connective tissue disorders. Dysphagia may be an early feature in older patients affected with IBM and rarely with inflammatory myopathy.  Dysphagia is seen in dermatomyositis (TIF-1 gamma) more than polymyositis.  Disorders of neuromuscular junction transmission such as Myasthenia gravis, MuSK myasthenia, botulism, and LEMS are less likely given lack of additional clinical findings that would be expected (ocular, respiratory, and limb involvement). Amyloidosis. He does not have clinical features suggestive of OPMD, CPEO, FSHD, MNGIE, or  myotonic dystrophy which have a slower pace of onset,  

 In rare cases of Guillain-Barré syndrome, such as the pharyngeal-cervical-brachial weakness where pharyngeal and cervical muscles are predominantly affected, and patients have prominent dysphagia.  MFS (does not have features of ophthalmoplegia, ataxia), and areflexia).  . 

He is at risk for continued malnutrition and dehydration.  Since, he decided to resume eating by mouth and is not nothing by mouth, he is prone to recurrent upper respiratory infections, and frank aspiration.

PLAN:

• EMG/NCS of left upper and lower extremiteis, test thoracic paraspinal, craniobulbar muscles especially tongue, facial, and masseter muscles.

• MRI cervical spine wwo contrast

• CT chest without iv contrast; Future

• Adult Video Fluoroscopic Swallowing Study With Esophagus

• Labs:

  • Comprehensive Metabolic Profile; Future

  • CBC and Differential; Future

  • B12 and Folate, serum; Future

  • ANA Screen and Titer; Future

  • Syphilis Serology; Future

  • Kappa Lambda Light Chains, Free; Future

  • Monoclonal Protein Serum Screen; Future

  • ENA Ro/La Antibody; Future

  • ENA SM RNP Antibody; Future

  • CPK, total; Future

  • LDH, total

  • PTH, intact; Future

  • Thyroid Screen; Future

  • Vitamin D25 Hydroxy (symptomatic patients only for screening, no longer broadly indicated); Future

  • Zinc, serum; Future

  • Copper, serum; Future

  • Ceruloplasmin; Future

  • Liver Profile; Future

  • C-Reactive Protein; Future

  • Hu Antibody; Future

  • Acute Hepatitis Screen; Future

  • Ganglioside Monosialic Antibodies; Future

  • Vitamin E; Future

  • Neuroimmunology Antibody Follow-up, Serum (Mayo) which include panel that test for GM1, Gd1b, GM1, Gd1b, AChR Ganglionic, IGLON5, VGCC, P/Q

  • Ganglioside Monosialic Antibodies; Future

  • Further recommendations will be made based on the results of the above tests

Vagal nerve lesion and vocal cord palsy

Case report:  https://pmc.ncbi.nlm.nih.gov/articles/PMC10831208/

Unilateral vocal fold paralysis (UVFP) occurs from a dysfunction of the recurrent laryngeal or vagus nerve innervating the larynx.

It causes a characteristic breathy voice often accompanied by swallowing disability, a weak cough, and the sensation of shortness of breath. This is a common cause of neurogenic hoarseness. When this paralysis is properly evaluated and treated, a normal speaking voice is typically restored. 

Workup in unilateral vocal fold paralysis

Computed tomography (CT) scanning or magnetic resonance imaging (MRI) of the path of the vagus/recurrent laryngeal nerve should be performed as part of a workup for a UVFP of unknown etiology. The imaging should include the entire path of the vagus/recurrent laryngeal nerve involved.

Other tests in the workup of UVFP include the following:

• Voice evaluation - Voice recording provides documentation of the baseline voice quality and ability

• Laryngeal electromyography (LEMG) - LEMG findings can be diagnostic and prognostic and can therefore be a useful tool to guide therapy

Management of unilateral vocal fold paralysis

Voice therapy can play a role in the treatment of UVFP. It can be used as a sole treatment or as part of a combined treatment with surgical medialization of the paralyzed vocal fold. Voice therapy is the primary treatment for patients who have a favorable (i.e., median) position of their vocal fold paralysis and fairly equal tonicity between the vocal folds, as well as for individuals who are unwilling or unable to undergo surgery due to psychological or medical limitations.  Multiple surgeries are available for the treatment of UVFP, and they can be broadly categorized into temporary and permanent procedures. Temporary treatment involves endoscopic injection of a resorbable material into the affected vocal fold, lateral to the thyroarytenoid muscle in the paraglottic space.

Permanent vocal fold surgical treatment can be divided into vocal fold injection and laryngeal framework surgery

Unilateral vocal cord paralysis: https://www.ncbi.nlm.nih.gov/books/NBK519060/

https://link.springer.com/article/10.1186/s13244-019-0786-7

https://caringmedical.com/prolotherapy-news/vagus-nerve-related-cervical-dysphagia-laryngeal-stenosis/