- Email: [email protected]
Distal Esophageal Spasm: A Review
Accepted Manuscript Title: Distal Esophageal Spasm: A Review Author: Mohamed Khalaf, Sejal Chowdhary, Puja Sukhwani Elias, Donald Castell PII: DOI: Reference:
S0002-9343(18)30284-5 https://doi.org/10.1016/j.amjmed.2018.02.031 AJM 14587
To appear in:
The American Journal of Medicine
Please cite this article as: Mohamed Khalaf, Sejal Chowdhary, Puja Sukhwani Elias, Donald Castell, Distal Esophageal Spasm: A Review, The American Journal of Medicine (2018), https://doi.org/10.1016/j.amjmed.2018.02.031. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Distal Esophageal Spasm: A Review
Short title: Distal Esophageal Spasm: A Review Authors: Mohamed Khalaf, MD Esophageal motility research fellow Division of Gastroenterology & Hepatology Medical University of South Carolina, Charleston, USA Sejal Chowdhary, MD PGY1 West Virginia University Hospital [email protected] Puja Sukhwani Elias, M.D., MPH Assisstant Professor of Medicine Division of Gastroenterology & Hepatology Medical University of South Carolina, Charleston, USA [email protected] Donald Castell, MD Director of the Esophageal Disorders Program Division of Gastroenterology & Hepatology Medical University of South Carolina, Charleston, USA [email protected] Corresponding author Mohamed Khalaf, MD MUSC GI & Hepatology 114 Doughty Street, Suite 249 MSC 702 Charleston, SC 29425-2900 P: 843-876-1966
Page 1 of 26
F:843-876-7232 Email: [email protected] Mohamed Khalaf: defining the topic, searching the literature, drafting the manuscript. Sejal Chowdhary: searching the literature, drafting the manuscript Puja Sukhwani Elias: critical revision of the manuscript for important content. Donald Castell: critical revision of the manuscript for important content. Funding source: None. There are no conflicts of interest to declare. The manuscript represents original work and not under consideration for publication elsewhere Keywords: esophagus; motility; chest pain; dysphagia
1 Page 2 of 26
Clinical Significance Esophageal spasm relation to reflux is controversial, and progression to achalasia is unlikely. Manometry remains the gold standard in diagnosis, while barium radiography is complimentary. Simultaneous contraction is the hallmark diagnostic criterion. Peppermint oil is effective in some patients. Chest pain is difficult to treat; endoscopic and surgical management are more effective in dysphagia. Hierarchy of treatment options based on the best evidence in the literature is provided.
Abstract: Distal esophageal spasm is a rare motility disorder presenting principally with nonobstructive dysphagia and non-cardiac chest pain. In symptomatic patients, the manometric diagnosis is made when > 10% of the wet swallows have simultaneous and/or premature contractions intermixed with normal peristalsis. We characterize manometry and barium as complimentary diagnostic approaches, and given the intermittent nature of the disorder, one should be always aware that IT IS ALMOST IMPOSSIBLE TO RULE OUT SPASM. Treatment is difficult; we propose an approach beginning with the least invasive intervention. Introduction: In 2001 Spechler and Castell
(1)
published, perhaps the first scheme of a classification
system for esophageal motility abnormalities based on conventional manometry metrics. They reported that apart from achalasia and scleroderma esophagus which are considered “real” diseases, the rest of the manometric abnormalities had neither known
2 Page 3 of 26
etiologies nor pathophysiological bases. Esophageal motility abnormalities were classified as either achalasia or other abnormal motility patterns which were further subclassified into those with hypercontractile, hypocontractile, or discoordinated motility. More recently, the Chicago classification
(2)
has been established based on new metrics
developed from high resolution manometry , however, the basis for diagnosis of the esophageal motility disorders remains the same. In this review we will focus on the pathophysiology, clinical features, diagnosis, and management of an uncommon esophageal motility disorder characterised by discoordinated contractions: distal esophageal spasm.
Background: Distal esophageal spasm is an idiopathic disorder that is manifested clinically by episodes of dysphagia and/or chest pain , radiographically by non-peristaltic contractions, often with a
“cork screw“ appearance of the esophagus, and
manometrically by uncoordinated (“spastic”) activity in the distal smooth muscle part of the esophagus.(1) Osgood(3) first reported spasm in 1889 in a case series of six patients who had symptoms of constricting pain in the epigastrium. Subsequently, Osler used the term “oesophagismus” to suggest that esophageal spasm may be a cause of otherwise unexplained chest pain.(4) In 1934, Moersh and Camp
(5)
reported that the lower esophagus during a barium
swallow became suddenly distorted with puckering, giving a beaded appearance. The earliest manometric description of esophageal spasm was made in 1958 by Creamer and associates
(6)
. It was commonly known as diffuse esophageal spasm, and
3 Page 4 of 26
the common manometric feature described was the presence of simultaneous onset or peak of pressure contractions in two adjacent orifices in the esophagus. Is it diffuse or distal esophageal spasm? Interestingly, from its earliest radiographic and manometric descriptions, esophageal spasms had been consistently described by involvement of the lower part of the esophagus. Hence, Sperandio and colleagues(7), assessed the diffuse or limited nature of the disorder and concluded that diffuse esophageal spasm is a misnomer and is more appropriately described as “distal” esophageal spasm. This new name was adopted by the latest version of the Chicago classification of esophageal motility disorders.(2)
Epidemiology: It is an uncommon motility disorder; its prevalence is between 3 - 9 % in symptomatic patients. The mean age is approximately 60 years with a slight female predominance (55%). (8, 9)
Pathophysiology and etiology: The etiology remains poorly understood, as there is a lack of histopathological information, since patients with this condition are rarely autopsied.
(10)
Several studies
have suggested that deficient tissue nitric oxide (NO) may impair the inhibitory innervation and allow simultaneous contractions, as well as possible abnormal relaxation of the esophagogastric junction.(11) Administration of a NO scavenger to healthy normal subjects results in simultaneous contractions in the distal esophagus, while replacement of NO reverses the defect (12) (13). 4 Page 5 of 26
In addition, partial mechanical obstruction at the level of the gastroesophageal junction was found to be associated with a manometric pattern characteristic of spasm. (11) Burton and colleagues(14), investigated esophageal motility in patients after placing laparoscopic adjustable gastric bands and a pattern of repetitive esophageal contractions was observed in 40% of swallows. It was also found that a substantial percentage (38%) of patients diagnosed with so called esophago-gastric outflow obstruction, had abnormal motility in the esophageal body including distal spasm. (15) Almansa et al
(9)
noted that spasm patients have several comorbidities like hypertension,
diabetes, and psychiatric conditions (depression and anxiety). There was no control group to compare with in this study, which made it difficult to conclude an association. In another study, Clouse et al
(16)
reported that a psychiatric diagnosis was present in 84%
of patients with abnormal manometric findings including simultaneous contractions.
Distal esophageal spasm and gastroesophageal reflux (GERD): The relationship with GERD is unclear, here is some conflicting data on the effect of acid perfusion on esophageal motility. In 1963, Siegel and Hendrix
(17)
described "non-
progressive” esophageal contractions during periods of acid-induced symptoms in patients with reflux esophagitis. While Richter et al
(18)
showed that acid perfusion during
a standard “Bernstein test” failed to produce simultaneous contractions. In addition, Crozier et al
(19)
showed that 90/275 patients with non-cardiac chest pain and normal
manometries had acid-provoked esophageal spasm on acid perfusion. In another study, GERD was identified by pH testing or endoscopy in 38% of esophageal spasm patients, 5 Page 6 of 26
however causality was not proven and the impact of PPI therapy on spasm was not studied. (20)
Relationship with Achalasia: Achalasia has a similar pathophysiologic mechanism as esophageal spasm, that being deficiency of NO in the distal esophagus. However in achalasia there is complete loss of NO inhibitory myenteric neurons after chronic ganglionitis, leading to impaired lower sphincter relaxation associated with spastic esophageal contractions, which constitutes “type 3 or spastic achalasia”.(21) (22) This relationship in addition to some case reports has led some authors to hypothesize that distal spasm can progress to achalasia. Khatami et al
(27)
(23-26)
followed 12 patients with spasm for up to 10 years after the initial
diagnosis. Achalasia developed in one case (8%), seven (58%) patients continued to have spasm, three (25%) had normal motility, and one (8%) had nutcracker esophagus. These findings suggest that progression from to achalasia is uncommon.
Clinical picture:
6 Page 7 of 26
The initial description of esophageal spasm by Osgood(3) was in patients with chest pain, however, it has been found over the years that a manometric pattern of spasm can also be found in patients complaining of dysphagia. Clinically, spasm patients are a heterogeneous group presenting with various esophageal symptoms ranging in severity from mild to severe, typically intermittent in nature lasting from seconds to minutes, and may be induced by ingestion of solids or fluids but can occur unrelated to meals.(28) Also, it should be noted that patients in whom the manometric pattern of spasm is identified rarely present with one symptom. Tutuian et al
(8)
analysed 71 patients with a manometric diagnosis of esophageal spasm and
found that dysphagia was the most common symptom (32%), followed by chest pain (22%), typical GERD symptoms (20%) and atypical GERD symptoms (cough, hoarseness; 13%). This study tried to explain the mechanism of which spasm can produce these symptoms and suggested that pain may be associated with strong esophageal contraction amplitudes, while dysphagia may be associated with impaired bolus transit. However, these symptoms are non-specific; Dalton et al(29) reported that less than 5% of patients referred to their laboratory with dysphagia and chest pain had esophageal spasm. Thus, full clinical evaluation should be performed to exclude more prevalent and life threatening disorders (e.g. cardiac etiology) before attributing these symptoms to a rare and relatively less dangerous disorder like esophageal spasm. (30) It was
reported that unlike achalasia, weight loss is an uncommon finding in distal
spasm.(31) However, a study showed that 30% of spasm patients reported weight loss ranging between 6 and 70 lbs. It was speculated that the cause of weight loss is the modification of dietary habits to avoid symptoms.(9)
7 Page 8 of 26
The same study confirmed the notion that patients with spasm tend to seek medical advice late. This may be attributed to the rarity of the disorder and thus the lack of public and physician awareness. Also, the heterogeneity of spasm symptoms may contribute to the delay in recognition.
Diagnosis: Esophageal manometry: Esophageal manometry is considered to be the gold standard in diagnosing patients with suspected distal esophageal spasm.(32) Although the spasm-attributed motility may be observed during manometry, testing patients often do not encounter their principal symptoms at that time, so it is difficult to extrapolate that the abnormalities witnessed are the cause of their symptoms. On the other hand, because of the intermittent nature of this disorder, absence of these manometric abnormalities cannot exclude esophageal spasm.
(33)
Thus, it is almost
impossible to rule out a diagnosis of spasm. In 1984, Richter and Castell(34) called for a reappraisal of the diagnostic criteria for spasm and emphasised the importance of non-peristaltic simultaneous contractions induced by wet swallows as the hallmark diagnostic criterion for this disorder.
Also, it is worth
mentioning that to distinguish the disorder from achalasia, it was shown that the esophagus in spasm had not completely lost its peristaltic ability; therefore, the presence of simultaneous waves should be intermixed with normal peristaltic sequences. In 1987, Richter et al
(35)
studied 95 healthy normal volunteers to determine the normal
range of esophageal manometry parameters which were poorly defined at that time.
8 Page 9 of 26
They showed that only 4 of the 95 subjects had one simultaneous contraction (propagation velocity > 8cm/second) and that none of these individuals had more than one in a series of 10 swallows. Based on this study, Spechler and Castell
(1)
established
the essential manometric criteria to diagnose spasm into:- 1- the presence of 20% or more simultaneous contractions with amplitudes more than 30 mm/Hg (to differentiate from scleroderma); and 2- the presence of some normal esophageal peristalsis (to distinguish it from achalasia). In addition to these criteria, other manometric features were described and were termed “associated spasm findings” including repetitive contractions and multipeaked (≥3 peaks) contractions.(36) With the introduction of high resolution manometry (HRM), the definition of distal spasm was modified. Initially, the Chicago classification recommended that the HRM definition of spasm should be based on rapid contractions (the equivalent of simultaneous contractions in conventional motility studies). However, the working group recently introduced the distal latency (DL) as a new and reliable HRM metric to measure spasm. DL was defined as the time between the swallow induced upper esophageal sphincter relaxation and the contractile deceleration point in the distal esophagus where propagation velocity slows down (figure 1). DL is considered a reflection of the activity of the inhibitory myenteric neurons involved in the timing of contraction in the distal esophagus.(37) A contraction with DL of less than 4.5 seconds was given the term “premature contraction” (figure 2).(38) The most recent Chicago classification version 3.0 defines distal spasm by the presence of premature contractions in ≥ 20% of wet swallows coupled with a normal lower sphincter relaxation pressure. This new definition switched the focus from the peristaltic velocity to the timing (latency) as the defining criterion for spasm.
(2)
9 Page 10 of 26
In our clinical experience, we found many cases of simultaneous contractions with normal latency and vice versa (premature contractions with normal velocity). This raises the question of whether we should consider premature contractions and simultaneous as 2 separate entities particularly considering that the new classification completely abandoned this criterion (simultaneous) as an abnormal finding. De Schepper et al
(39)
retrospectively studied the clinical characteristics and the HRM
findings of patients with “simultaneous contractions” with normal latency (figure 3) and compared them to those fulfilling the Chicago classification criteria for distal esophageal spasm (≥ 20% premature contractions). Their hypothesis was that latency is not always the sole defining feature of spasm.
They found most patients with simultaneous
contractions with normal latency had symptoms and radiological signs consistent with distal spasm and they proposed the presence of two variants (short and long latency spasm), with the short latency type proposed to be a more advanced form.
Their
conclusion confirmed what we find in our clinical practice that simultaneous contractions with normal latency represent a form of spasm, and should not be considered normal. Therefore, we propose to modify the HRM definition of distal esophageal spasm to incorporate these patients with simultaneous contractions. Spasm should be considered manometrically when ≥ 20% of the wet swallows show premature and /or simultaneous contractions intermixed with normal peristalsis. Also, despite of the rarity of the presence of repetitive or triple-peaked contractions (figure 4), we shouldn’t ignore them and their presence should raise the suspicion of spasm especially if the patient presents with unexplained dysphagia and/or chest pain.
Barium esophagram: 10 Page 11 of 26
Barium is more widely available than manometry and it may be suggestive of spasm. The best known radiological descriptions include the ‘corkscrew’ or ‘rosary bead’ esophagus (figure 5). Moreover, barium has the ability to detect any anatomic abnormalities that may be associated with spasm like epiphrenic diverticula (figure 6).(40) However, radiological protocols do not necessarily use defined swallow volumes and record only a limited number of swallows due to the radiation exposure. Therefore, these findings are neither specific nor sensitive in diagnosing esophageal spasm, a condition characterized by intermittent simultaneous contractions.
(41)
Treatment: Unfortunately, a regularly effective treatment for esophageal spasm has not been found. This could be due to lack of enough clinical trials and the different manifestations and pathology of the disease.(36) Pharmacologic treatment As the etiology is unknown, all medical therapies are directed at the symptoms rather than the cause. 1. Nitrates: may have an effect on improving manometric findings in spasm as well as providing symptomatic relief.
(11, 42)
Konturek et al
(12)
showed that nitrates can
decrease contraction duration, but not the amplitude. An example of nitrate therapy is isosorbide dinitrate. It causes smooth muscle relaxation through the 11 Page 12 of 26
increase of tissue nitric oxide.(43) The usual dosage is approximately around 5-10 mg sublingual, 5-10 minutes before meals if dysphagia is the presenting symptom or “on demand” for chest pain.(44) 2. PDI-5 inhibitors: such as sildenafil, work by causing relaxation of the smooth muscle through the release of nitric oxide controlled by cyclic GMP, leading to reduction in the esophageal contractile amplitude.(45)
(46)
showed symptomatic relief in patients with spastic motility.
Sildenafil (50 mg/day) (36)
The cost and lack
of insurance coverage for this indication makes it a difficult drug to evaluate.(11) 3. Calcium channel blockers (CCBs): The mechanism of action involves inhibition of L-type calcium channels which in turn leads to smooth muscle relaxation and more effective esophageal emptying in dysphagia patients. Diltiazem at 180-240 mg/day and nifedipine at 10-30 mg approximately 10-15 minutes before meals are the recommended dosages(36) 4. Tricyclic antidepressants (TCAs): Patients with a primary symptom of chest pain are likely candidates to try a TCA as initial treatment. Imipramine 25-50 mg at bedtime is the recommended dosage. Studies done with TCAs showed that trazodone and imipramine were effective in relieving non-cardiac chest pain in patients with esophageal motility disorders. (47, 48) 5. Other pharmacologic options: proton pump inhibitors may be helpful for some patients if there is associated GERD.(49) Peppermint oil has recently gained some attention in the treatment of esophageal spasm. Because of its smooth muscle relaxing properties, , it is used in treating patients with headache, dyspepsia, and irritable bowel
(50)
Peppermint effect on the esophageal manometric findings was
studied on eight spasm patients and it reduced the number of simultaneous esophageal contractions.(51) Preliminary data from our clinic evaluated the
12 Page 13 of 26
response to sublingual dissolvable peppermint tablets in patients with dysphagia and non-cardiac chest pain. Spasm patients were found to have the most favorable response among other motility disorders. (52)
Endoscopic options 1. Peroral endoscopic myotomy (POEM): has provided some patients with spasm and nutcracker esophagus with some relief for a short period of time, but due to the possible post-operative complications and limited data, it is not usually recommended.(36) It is minimally invasive but equivalent in treatment to a surgical myotomy, and the esophageal and gastric myotomy are done with an endoscope. Several case reports have shown the effectiveness of POEM in spasm, however a recent study showed better results in achalasia than in distal spasm.(53-56) Possible complications of the procedure include mucosal tears, pneumoperitoneum, bleeding, pneumothorax, and reflux. 2. Botulinum toxin (Botox): is another treatment option. The mechanism of action involves inhibition of the release of acetylcholine from the cholinergic neurons, therefore leading to paralysis of the muscle.(44) The recommened dosage is 80100 U, injected endoscopically into
four quadrants of the lower esophageal
sphincter.(43) Vanuytsel et al (57) conducted a double blind placebo-controlled study comparing endoscopic botox injection vs saline in treatment of spasm and nutcracker esophagus. After botox injections, patients had significant decreases in 13 Page 14 of 26
their dysphagia score, however, Botox failed to produce significant reduction in the chest pain score. Evidence also suggests that administration of botulinum toxin may complicate future procedures including surgical myotomy.(44)
Some
limitations of botulinum toxin are the shorter duration of symptom relief (6 months) and the need for an upper endoscopy.(36) 3. Esophageal dilation: This approach is particularly considered in esophageal spasm with dysphagia. Bougie dilators and through-the-scope balloons have not been adequately studied in spasm, however pneumatic dilation has been successful in alleviating dysphagia in some patients, but this is limited to those who may need to be categorized as an achalasia diagnosis instead.
(11, 37)
Pneumatic balloons stretch the
lower esophageal sphincter until a tear in the muscular layer is produced, therefore weakening it and decreasing the pressure. Patients may need further dilations if their symptoms do not improve. Patients with achalasia find the most relief with this treatment, but it has been effective as well in some patients with spasm.(58)
Surgical treatment Laparoscopic myotomy extending from the lower esophageal sphincter proximally onto the esophageal body has been used to treat patients with spastic disorders. However Its role in esophageal spasm treatment is debatable, and controlled trials are needed to compare it against medical and endoscopic treatments. Leconte et al
(59)
evaluated 20
patients after myotomy; dysphagia and chest pain were significantly improved after a median follow-up of 50 months. Treatment summary
14 Page 15 of 26
Therapies have been shown to have limited effects on symptomatic relief for spasm.(30) Thus, a reasonable approach is to “play the list” shown in table 1, titrating each drug against patient response, using a “start low and go slow” philosophy to identify a potential therapeutic window.
References: 1. 2.
3. 4. 5. 6. 7. 8.
9. 10. 11. 12. 13. 14.
15.
16. 17.
Spechler S, Castell D. Classification of oesophageal motility abnormalities. Gut 2001;49:145-51. International High Resolution Manometry Working G. The Chicago Classification of Esophageal Motility Disorders, v3.0. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society 2015;27:160-74. Osgood H. A Peculiar Form of Œsorhagismus. The Boston Medical and Surgical Journal 1889;120:401-5. Osler H. Oesophagismus. In: Principles and practice of medicine 1892. Moersch HJ CJ. Diffuse spasm of the lower part of the esoph-agus. Ann Otol Rhinol Laryngol 1934;43:1165, 934. Creamer B, Donoghue E, Code CF. Pattern of esophageal motility in diffuse spasm. Gastroenterology 1958;34:782-96. Sperandio M, Tutuian R, Gideon RM, et al. Diffuse esophageal spasm: not diffuse but distal esophageal spasm (DES). Dig Dis Sci 2003;48:1380-4. Tutuian R, Mainie I, Agrawal A, et al. Symptom and Function Heterogenicity Among Patients with Distal Esophageal Spasm: Studies Using Combined Impedance-Manometry. Am J Gastroenterol 2006;101:464-9. Almansa CC. Esophageal spasm: demographic, clinical, radiographic, and manometric features in 108 patients. Diseases of the Esophagus;25:214-21. Achem SR, Gerson LB. Distal Esophageal Spasm: An Update. Current Gastroenterology Reports 2013;15:325. Roman S, Kahrilas PJ. Management of spastic disorders of the esophagus. Gastroenterology clinics of North America 2013;42:27-43. Konturek JW, Gillessen A, Domschke W. Diffuse esophageal spasm: a malfunction that involves nitric oxide? Scand J Gastroenterol 1995;30:1041-5. Murray JA, Ledlow A, Launspach J, et al. The effects of recombinant human hemoglobin on esophageal motor functions in humans. Gastroenterology 1995;109:1241-8. Burton PR, Brown W, Laurie C, et al. The Effect of Laparoscopic Adjustable Gastric Bands on Esophageal Motility and the Gastroesophageal Junction: Analysis Using High-Resolution Video Manometry. Obesity Surgery 2009;19:905-14. Zheng E, Sloan J, Matthew Gideon R, et al. EGJ Outflow Obstruction is Often Associated with Coexistent Abnormal Esophageal Body Motility and Abnormal Bolus Transit. Gastroenterology;152:S326. Clouse RE, Lustman PJ. Psychiatric illness and contraction abnormalities of the esophagus. The New England journal of medicine 1983;309:1337-42. Siegel CI, Hendrix TR. Esophageal Motor Abnormalities Induced By Acid Perfusion In Patients With Heartburn. Journal of Clinical Investigation 1963;42:686-95.
15 Page 16 of 26
18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32.
33. 34. 35.
36. 37. 38. 39. 40.
41. 42.
Richter JE, Johns DN, Wu WC, et al. Are esophageal motility abnormalities produced during the intraesophageal acid perfusion test? JAMA 1985;253:1914-7. Crozier RE, Glick ME, Gibb SP, et al. Acid-provoked esophageal spasm as a cause of noncardiac chest pain. Am J Gastroenterol 1991;86:1576-80. Campo S, Traube M. Manometric characteristics in idiopathic and reflux-associated esophageal spasm. American Journal of Gastroenterology 1992;87. Boeckxstaens GE, Zaninotto G, Richter JE. Achalasia. Lancet 2014;383:83-93. Roman S, Kahrilas PJ. Distal Esophageal Spasm. Dysphagia 2012;27:115-23. Millan MS, Bourdages R, Beck IT, et al. Transition from diffuse esophageal spasm to achalasia. J Clin Gastroenterol 1979;1:107-17. Robson K, Rosenberg S, Lembo T. GERD progressing to diffuse esophageal spasm and then to achalasia. Dig Dis Sci 2000;45:110-3. Longstreth GF, Foroozan P. Evolution of symptomatic diffuse esophageal spasm to achalasia. South Med J 1982;75:217-20. Samo S, Carlson DA, Kahrilas PJ, et al. Ineffective Esophageal Motility Progressing into Distal Esophageal Spasm and Then Type III Achalasia. ACG Case Reports Journal 2016;3:e183. Khatami SS, Khandwala F, Shay SS, et al. Does Diffuse Esophageal Spasm Progress to Achalasia? A Prospective Cohort Study. Digestive Diseases and Sciences 2005;50:1605-10. Grubel C, Borovicka J, Schwizer W, et al. Diffuse Esophageal Spasm. Am J Gastroenterol 2008;103:450-7. Dalton CB, Castell DO, Hewson EG, et al. Diffuse esophageal spasm. A rare motility disorder not characterized by high-amplitude contractions. Dig Dis Sci 1991;36:1025-8. Roman S, Kahrilas PJ. Management of spastic disorders of the esophagus. Gastroenterol Clin North Am 2013;42:27-43. Sifrim D, Fornari F. Non-achalasic motor disorders of the oesophagus. Best practice & research. Clinical gastroenterology 2007;21:575-93. Lee EM, Park MI, Moon W, et al. A Case of Symptomatic Diffuse Esophageal Spasm During Multiple Rapid Swallowing Test on High-Resolution Manometry. Journal of Neurogastroenterology and Motility 2010;16:433-6. Tsuboi K, Mittal SK. Diffuse esophageal spasm: has the term lost its relevance? Analysis of 217 cases. Dis Esophagus 2011;24:354-9. Richter JE, Castell DO. Diffuse esophageal spasm: a reappraisal. Ann Intern Med 1984;100:242-5. Richter JE, Wu WC, Johns DN, et al. Esophageal manometry in 95 healthy adult volunteers. Variability of pressures with age and frequency of "abnormal" contractions. Dig Dis Sci 1987;32:583-92. Castell DO. Esophageal motility disorders: Clinical manifestations, diagnosis, and management: UpToDate, Waltham, MA, 2017. Achem SR. Diffuse Esophageal Spasm in the Era of High-Resolution Manometry. Gastroenterology & Hepatology 2014;10:130-3. Pandolfino JE, Roman S, Carlson D, et al. Distal esophageal spasm in high-resolution esophageal pressure topography: defining clinical phenotypes. Gastroenterology 2011;141:469-75. De Schepper HUH. Distal esophageal spasm and the Chicago classification: is timing everything? Neurogastroenterology and Motility;28:260-5. Taniguchi Y, Takahashi T, Nakajima K, et al. Multiple huge epiphrenic esophageal diverticula with motility disease treated with video-assisted thoracoscopic and hand-assisted laparoscopic esophagectomy: a case report. Surg Case Rep 2017;3:63. Tutuian R, Castell DO. Review article: oesophageal spasm – diagnosis and management. Alimentary Pharmacology & Therapeutics 2006;23:1393-402. Orlando RC, Bozymski EM. Clinical and manometric effects of nitroglycerin in diffuse esophageal spasm. The New England journal of medicine 1973;289:23-5.
16 Page 17 of 26
43. 44. 45. 46. 47. 48.
49. 50. 51. 52. 53. 54.
55. 56.
57.
58. 59.
Khalaf M, Castell DO. Achalasia: Common Features of an Uncommon Disease. Practical Gastroenterology 2016. Vaezi MF, Pandolfino JE, Vela MF. ACG clinical guideline: diagnosis and management of achalasia. Am J Gastroenterol 2013;108:1238-49; quiz 50. Moreland RB, Goldstein I, Traish A. Sildenafil, a novel inhibitor of phosphodiesterase type 5 in human corpus cavernosum smooth muscle cells. Life Sci 1998;62:Pl 309-18. Eherer AJ, Schwetz I, Hammer HF, et al. Effect of sildenafil on oesophageal motor function in healthy subjects and patients with oesophageal motor disorders. Gut 2002;50:758-64. Cannon RO, 3rd, Quyyumi AA, Mincemoyer R, et al. Imipramine in patients with chest pain despite normal coronary angiograms. The New England journal of medicine 1994;330:1411-7. Clouse RE, Lustman PJ, Eckert TC, et al. Low-dose trazodone for symptomatic patients with esophageal contraction abnormalities. A double-blind, placebo-controlled trial. Gastroenterology 1987;92:1027-36. Achem SR. Management of Esophageal Chest Pain. Gastroenterology & Hepatology 2007;3:765-7. Kligler B, Chaudhary S. Peppermint oil. Am Fam Physician 2007;75:1027-30. Pimentel M, Bonorris GG, Chow EJ, et al. Peppermint oil improves the manometric findings in diffuse esophageal spasm. J Clin Gastroenterol 2001;33:27-31. Chowdhary TS, Khalaf M, Elias PS, Castell DO. Peppermint oil relieves dysphagia and non-cardiac chest pain secondary to esophageal motility disorders. Am J Gastroenterol 2017;112:S168-S225. Louis H, Covas A, Coppens E, et al. Distal esophageal spasm treated by peroral endoscopic myotomy. Am J Gastroenterol 2012;107:1926-7. Khashab MA, Saxena P, Kumbhari V, et al. Peroral endoscopic myotomy as a platform for the treatment of spastic esophageal disorders refractory to medical therapy (with video). Gastrointest Endosc 2014;79:136-9. Shiwaku H, Inoue H, Beppu R, et al. Successful treatment of diffuse esophageal spasm by peroral endoscopic myotomy. Gastrointest Endosc 2013;77:149-50. Sharata AM, Dunst CM, Pescarus R, et al. Peroral endoscopic myotomy (POEM) for esophageal primary motility disorders: analysis of 100 consecutive patients. J Gastrointest Surg 2015;19:16170; discussion 70. Vanuytsel T, Bisschops R, Farré R, et al. Botulinum Toxin Reduces Dysphagia in Patients With Nonachalasia Primary Esophageal Motility Disorders. Clinical Gastroenterology and Hepatology;11:1115-21.e2. Pandolfino JE, Kwiatek MA, Nealis T, et al. Achalasia: a new clinically relevant classification by high-resolution manometry. Gastroenterology 2008;135:1526-33. Leconte M, Douard R, Gaudric M, et al. Functional results after extended myotomy for diffuse oesophageal spasm. Br J Surg 2007;94:1113-8.
17 Page 18 of 26
Figure legends:
Figure 1: High resolution motility (HRM) showing a normal peristaltic swallow with normal velocity (< 8 cm/sec), and normal distal latency (DL) (> 4.5 sec). Normal velocity in HRM is easily recognised visually, giving the contraction its sloping appearance. The DL is the time measured from the upper sphincter relaxation (A) to the contractile deceleration point (B).
Figure 2: HRM showing a premature contraction with a distal latency (DL) < 4.5 sec. This contraction can be also described as simultaneous (velocity > 8 cm/sec), and this can be easily visualised in HRM, giving the contraction this vertical appearance.
Figure 3: HRM showing a simultaneous contraction (velocity > 8cm/sec) with normal latency (> 4.5 sec). Thus, we emphasize on the fact that presence of simultaneous contractions in ≥ 20% of the swallows is the hallmark diagnostic criterion for distal esophageal spasm (even if not associated with short latency).
Figure 4: HRM featuring a triple-peaked contraction. This is considered a rare feature of spasm, that shouldn't be ignored.
Figure 5: Barium esophagram showing the characteristic cork screw appearance that may be seen in esophageal spasm.
Figure 6: Barium swallow showing large esophageal diverticulum complicating a case of esophageal spasm.
Page 19 of 26
Table 1: Suggested hierarchy of treatment options for distal esophageal spasm, starting with the least invasive
1. Concentrated peppermint oil 2. Nitrates or phosphodiesterase-5 inhibitors 3. Calcium channel blockers 4. Tricyclic antidepressants 5. Endoscopic Botox injection 6. Pneumatic dilation 7. Myotomy (POEM or surgical)
Page 20 of 26
Figure-1.DPI_300.jpg
1 Page 21 of 26
Figure-2.DPI_300.jpg
2 Page 22 of 26
Figure-3.DPI_300.jpg
3 Page 23 of 26
Figure-4.DPI_301.jpg
4 Page 24 of 26
Figure-5.DPI_301.jpg
5 Page 25 of 26
Figure-6.DPI_300.jpg
6 Page 26 of 26
S0002-9343(18)30284-5 https://doi.org/10.1016/j.amjmed.2018.02.031 AJM 14587
To appear in:
The American Journal of Medicine
Please cite this article as: Mohamed Khalaf, Sejal Chowdhary, Puja Sukhwani Elias, Donald Castell, Distal Esophageal Spasm: A Review, The American Journal of Medicine (2018), https://doi.org/10.1016/j.amjmed.2018.02.031. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Distal Esophageal Spasm: A Review
Short title: Distal Esophageal Spasm: A Review Authors: Mohamed Khalaf, MD Esophageal motility research fellow Division of Gastroenterology & Hepatology Medical University of South Carolina, Charleston, USA Sejal Chowdhary, MD PGY1 West Virginia University Hospital [email protected] Puja Sukhwani Elias, M.D., MPH Assisstant Professor of Medicine Division of Gastroenterology & Hepatology Medical University of South Carolina, Charleston, USA [email protected] Donald Castell, MD Director of the Esophageal Disorders Program Division of Gastroenterology & Hepatology Medical University of South Carolina, Charleston, USA [email protected] Corresponding author Mohamed Khalaf, MD MUSC GI & Hepatology 114 Doughty Street, Suite 249 MSC 702 Charleston, SC 29425-2900 P: 843-876-1966
Page 1 of 26
F:843-876-7232 Email: [email protected] Mohamed Khalaf: defining the topic, searching the literature, drafting the manuscript. Sejal Chowdhary: searching the literature, drafting the manuscript Puja Sukhwani Elias: critical revision of the manuscript for important content. Donald Castell: critical revision of the manuscript for important content. Funding source: None. There are no conflicts of interest to declare. The manuscript represents original work and not under consideration for publication elsewhere Keywords: esophagus; motility; chest pain; dysphagia
1 Page 2 of 26
Clinical Significance Esophageal spasm relation to reflux is controversial, and progression to achalasia is unlikely. Manometry remains the gold standard in diagnosis, while barium radiography is complimentary. Simultaneous contraction is the hallmark diagnostic criterion. Peppermint oil is effective in some patients. Chest pain is difficult to treat; endoscopic and surgical management are more effective in dysphagia. Hierarchy of treatment options based on the best evidence in the literature is provided.
Abstract: Distal esophageal spasm is a rare motility disorder presenting principally with nonobstructive dysphagia and non-cardiac chest pain. In symptomatic patients, the manometric diagnosis is made when > 10% of the wet swallows have simultaneous and/or premature contractions intermixed with normal peristalsis. We characterize manometry and barium as complimentary diagnostic approaches, and given the intermittent nature of the disorder, one should be always aware that IT IS ALMOST IMPOSSIBLE TO RULE OUT SPASM. Treatment is difficult; we propose an approach beginning with the least invasive intervention. Introduction: In 2001 Spechler and Castell
(1)
published, perhaps the first scheme of a classification
system for esophageal motility abnormalities based on conventional manometry metrics. They reported that apart from achalasia and scleroderma esophagus which are considered “real” diseases, the rest of the manometric abnormalities had neither known
2 Page 3 of 26
etiologies nor pathophysiological bases. Esophageal motility abnormalities were classified as either achalasia or other abnormal motility patterns which were further subclassified into those with hypercontractile, hypocontractile, or discoordinated motility. More recently, the Chicago classification
(2)
has been established based on new metrics
developed from high resolution manometry , however, the basis for diagnosis of the esophageal motility disorders remains the same. In this review we will focus on the pathophysiology, clinical features, diagnosis, and management of an uncommon esophageal motility disorder characterised by discoordinated contractions: distal esophageal spasm.
Background: Distal esophageal spasm is an idiopathic disorder that is manifested clinically by episodes of dysphagia and/or chest pain , radiographically by non-peristaltic contractions, often with a
“cork screw“ appearance of the esophagus, and
manometrically by uncoordinated (“spastic”) activity in the distal smooth muscle part of the esophagus.(1) Osgood(3) first reported spasm in 1889 in a case series of six patients who had symptoms of constricting pain in the epigastrium. Subsequently, Osler used the term “oesophagismus” to suggest that esophageal spasm may be a cause of otherwise unexplained chest pain.(4) In 1934, Moersh and Camp
(5)
reported that the lower esophagus during a barium
swallow became suddenly distorted with puckering, giving a beaded appearance. The earliest manometric description of esophageal spasm was made in 1958 by Creamer and associates
(6)
. It was commonly known as diffuse esophageal spasm, and
3 Page 4 of 26
the common manometric feature described was the presence of simultaneous onset or peak of pressure contractions in two adjacent orifices in the esophagus. Is it diffuse or distal esophageal spasm? Interestingly, from its earliest radiographic and manometric descriptions, esophageal spasms had been consistently described by involvement of the lower part of the esophagus. Hence, Sperandio and colleagues(7), assessed the diffuse or limited nature of the disorder and concluded that diffuse esophageal spasm is a misnomer and is more appropriately described as “distal” esophageal spasm. This new name was adopted by the latest version of the Chicago classification of esophageal motility disorders.(2)
Epidemiology: It is an uncommon motility disorder; its prevalence is between 3 - 9 % in symptomatic patients. The mean age is approximately 60 years with a slight female predominance (55%). (8, 9)
Pathophysiology and etiology: The etiology remains poorly understood, as there is a lack of histopathological information, since patients with this condition are rarely autopsied.
(10)
Several studies
have suggested that deficient tissue nitric oxide (NO) may impair the inhibitory innervation and allow simultaneous contractions, as well as possible abnormal relaxation of the esophagogastric junction.(11) Administration of a NO scavenger to healthy normal subjects results in simultaneous contractions in the distal esophagus, while replacement of NO reverses the defect (12) (13). 4 Page 5 of 26
In addition, partial mechanical obstruction at the level of the gastroesophageal junction was found to be associated with a manometric pattern characteristic of spasm. (11) Burton and colleagues(14), investigated esophageal motility in patients after placing laparoscopic adjustable gastric bands and a pattern of repetitive esophageal contractions was observed in 40% of swallows. It was also found that a substantial percentage (38%) of patients diagnosed with so called esophago-gastric outflow obstruction, had abnormal motility in the esophageal body including distal spasm. (15) Almansa et al
(9)
noted that spasm patients have several comorbidities like hypertension,
diabetes, and psychiatric conditions (depression and anxiety). There was no control group to compare with in this study, which made it difficult to conclude an association. In another study, Clouse et al
(16)
reported that a psychiatric diagnosis was present in 84%
of patients with abnormal manometric findings including simultaneous contractions.
Distal esophageal spasm and gastroesophageal reflux (GERD): The relationship with GERD is unclear, here is some conflicting data on the effect of acid perfusion on esophageal motility. In 1963, Siegel and Hendrix
(17)
described "non-
progressive” esophageal contractions during periods of acid-induced symptoms in patients with reflux esophagitis. While Richter et al
(18)
showed that acid perfusion during
a standard “Bernstein test” failed to produce simultaneous contractions. In addition, Crozier et al
(19)
showed that 90/275 patients with non-cardiac chest pain and normal
manometries had acid-provoked esophageal spasm on acid perfusion. In another study, GERD was identified by pH testing or endoscopy in 38% of esophageal spasm patients, 5 Page 6 of 26
however causality was not proven and the impact of PPI therapy on spasm was not studied. (20)
Relationship with Achalasia: Achalasia has a similar pathophysiologic mechanism as esophageal spasm, that being deficiency of NO in the distal esophagus. However in achalasia there is complete loss of NO inhibitory myenteric neurons after chronic ganglionitis, leading to impaired lower sphincter relaxation associated with spastic esophageal contractions, which constitutes “type 3 or spastic achalasia”.(21) (22) This relationship in addition to some case reports has led some authors to hypothesize that distal spasm can progress to achalasia. Khatami et al
(27)
(23-26)
followed 12 patients with spasm for up to 10 years after the initial
diagnosis. Achalasia developed in one case (8%), seven (58%) patients continued to have spasm, three (25%) had normal motility, and one (8%) had nutcracker esophagus. These findings suggest that progression from to achalasia is uncommon.
Clinical picture:
6 Page 7 of 26
The initial description of esophageal spasm by Osgood(3) was in patients with chest pain, however, it has been found over the years that a manometric pattern of spasm can also be found in patients complaining of dysphagia. Clinically, spasm patients are a heterogeneous group presenting with various esophageal symptoms ranging in severity from mild to severe, typically intermittent in nature lasting from seconds to minutes, and may be induced by ingestion of solids or fluids but can occur unrelated to meals.(28) Also, it should be noted that patients in whom the manometric pattern of spasm is identified rarely present with one symptom. Tutuian et al
(8)
analysed 71 patients with a manometric diagnosis of esophageal spasm and
found that dysphagia was the most common symptom (32%), followed by chest pain (22%), typical GERD symptoms (20%) and atypical GERD symptoms (cough, hoarseness; 13%). This study tried to explain the mechanism of which spasm can produce these symptoms and suggested that pain may be associated with strong esophageal contraction amplitudes, while dysphagia may be associated with impaired bolus transit. However, these symptoms are non-specific; Dalton et al(29) reported that less than 5% of patients referred to their laboratory with dysphagia and chest pain had esophageal spasm. Thus, full clinical evaluation should be performed to exclude more prevalent and life threatening disorders (e.g. cardiac etiology) before attributing these symptoms to a rare and relatively less dangerous disorder like esophageal spasm. (30) It was
reported that unlike achalasia, weight loss is an uncommon finding in distal
spasm.(31) However, a study showed that 30% of spasm patients reported weight loss ranging between 6 and 70 lbs. It was speculated that the cause of weight loss is the modification of dietary habits to avoid symptoms.(9)
7 Page 8 of 26
The same study confirmed the notion that patients with spasm tend to seek medical advice late. This may be attributed to the rarity of the disorder and thus the lack of public and physician awareness. Also, the heterogeneity of spasm symptoms may contribute to the delay in recognition.
Diagnosis: Esophageal manometry: Esophageal manometry is considered to be the gold standard in diagnosing patients with suspected distal esophageal spasm.(32) Although the spasm-attributed motility may be observed during manometry, testing patients often do not encounter their principal symptoms at that time, so it is difficult to extrapolate that the abnormalities witnessed are the cause of their symptoms. On the other hand, because of the intermittent nature of this disorder, absence of these manometric abnormalities cannot exclude esophageal spasm.
(33)
Thus, it is almost
impossible to rule out a diagnosis of spasm. In 1984, Richter and Castell(34) called for a reappraisal of the diagnostic criteria for spasm and emphasised the importance of non-peristaltic simultaneous contractions induced by wet swallows as the hallmark diagnostic criterion for this disorder.
Also, it is worth
mentioning that to distinguish the disorder from achalasia, it was shown that the esophagus in spasm had not completely lost its peristaltic ability; therefore, the presence of simultaneous waves should be intermixed with normal peristaltic sequences. In 1987, Richter et al
(35)
studied 95 healthy normal volunteers to determine the normal
range of esophageal manometry parameters which were poorly defined at that time.
8 Page 9 of 26
They showed that only 4 of the 95 subjects had one simultaneous contraction (propagation velocity > 8cm/second) and that none of these individuals had more than one in a series of 10 swallows. Based on this study, Spechler and Castell
(1)
established
the essential manometric criteria to diagnose spasm into:- 1- the presence of 20% or more simultaneous contractions with amplitudes more than 30 mm/Hg (to differentiate from scleroderma); and 2- the presence of some normal esophageal peristalsis (to distinguish it from achalasia). In addition to these criteria, other manometric features were described and were termed “associated spasm findings” including repetitive contractions and multipeaked (≥3 peaks) contractions.(36) With the introduction of high resolution manometry (HRM), the definition of distal spasm was modified. Initially, the Chicago classification recommended that the HRM definition of spasm should be based on rapid contractions (the equivalent of simultaneous contractions in conventional motility studies). However, the working group recently introduced the distal latency (DL) as a new and reliable HRM metric to measure spasm. DL was defined as the time between the swallow induced upper esophageal sphincter relaxation and the contractile deceleration point in the distal esophagus where propagation velocity slows down (figure 1). DL is considered a reflection of the activity of the inhibitory myenteric neurons involved in the timing of contraction in the distal esophagus.(37) A contraction with DL of less than 4.5 seconds was given the term “premature contraction” (figure 2).(38) The most recent Chicago classification version 3.0 defines distal spasm by the presence of premature contractions in ≥ 20% of wet swallows coupled with a normal lower sphincter relaxation pressure. This new definition switched the focus from the peristaltic velocity to the timing (latency) as the defining criterion for spasm.
(2)
9 Page 10 of 26
In our clinical experience, we found many cases of simultaneous contractions with normal latency and vice versa (premature contractions with normal velocity). This raises the question of whether we should consider premature contractions and simultaneous as 2 separate entities particularly considering that the new classification completely abandoned this criterion (simultaneous) as an abnormal finding. De Schepper et al
(39)
retrospectively studied the clinical characteristics and the HRM
findings of patients with “simultaneous contractions” with normal latency (figure 3) and compared them to those fulfilling the Chicago classification criteria for distal esophageal spasm (≥ 20% premature contractions). Their hypothesis was that latency is not always the sole defining feature of spasm.
They found most patients with simultaneous
contractions with normal latency had symptoms and radiological signs consistent with distal spasm and they proposed the presence of two variants (short and long latency spasm), with the short latency type proposed to be a more advanced form.
Their
conclusion confirmed what we find in our clinical practice that simultaneous contractions with normal latency represent a form of spasm, and should not be considered normal. Therefore, we propose to modify the HRM definition of distal esophageal spasm to incorporate these patients with simultaneous contractions. Spasm should be considered manometrically when ≥ 20% of the wet swallows show premature and /or simultaneous contractions intermixed with normal peristalsis. Also, despite of the rarity of the presence of repetitive or triple-peaked contractions (figure 4), we shouldn’t ignore them and their presence should raise the suspicion of spasm especially if the patient presents with unexplained dysphagia and/or chest pain.
Barium esophagram: 10 Page 11 of 26
Barium is more widely available than manometry and it may be suggestive of spasm. The best known radiological descriptions include the ‘corkscrew’ or ‘rosary bead’ esophagus (figure 5). Moreover, barium has the ability to detect any anatomic abnormalities that may be associated with spasm like epiphrenic diverticula (figure 6).(40) However, radiological protocols do not necessarily use defined swallow volumes and record only a limited number of swallows due to the radiation exposure. Therefore, these findings are neither specific nor sensitive in diagnosing esophageal spasm, a condition characterized by intermittent simultaneous contractions.
(41)
Treatment: Unfortunately, a regularly effective treatment for esophageal spasm has not been found. This could be due to lack of enough clinical trials and the different manifestations and pathology of the disease.(36) Pharmacologic treatment As the etiology is unknown, all medical therapies are directed at the symptoms rather than the cause. 1. Nitrates: may have an effect on improving manometric findings in spasm as well as providing symptomatic relief.
(11, 42)
Konturek et al
(12)
showed that nitrates can
decrease contraction duration, but not the amplitude. An example of nitrate therapy is isosorbide dinitrate. It causes smooth muscle relaxation through the 11 Page 12 of 26
increase of tissue nitric oxide.(43) The usual dosage is approximately around 5-10 mg sublingual, 5-10 minutes before meals if dysphagia is the presenting symptom or “on demand” for chest pain.(44) 2. PDI-5 inhibitors: such as sildenafil, work by causing relaxation of the smooth muscle through the release of nitric oxide controlled by cyclic GMP, leading to reduction in the esophageal contractile amplitude.(45)
(46)
showed symptomatic relief in patients with spastic motility.
Sildenafil (50 mg/day) (36)
The cost and lack
of insurance coverage for this indication makes it a difficult drug to evaluate.(11) 3. Calcium channel blockers (CCBs): The mechanism of action involves inhibition of L-type calcium channels which in turn leads to smooth muscle relaxation and more effective esophageal emptying in dysphagia patients. Diltiazem at 180-240 mg/day and nifedipine at 10-30 mg approximately 10-15 minutes before meals are the recommended dosages(36) 4. Tricyclic antidepressants (TCAs): Patients with a primary symptom of chest pain are likely candidates to try a TCA as initial treatment. Imipramine 25-50 mg at bedtime is the recommended dosage. Studies done with TCAs showed that trazodone and imipramine were effective in relieving non-cardiac chest pain in patients with esophageal motility disorders. (47, 48) 5. Other pharmacologic options: proton pump inhibitors may be helpful for some patients if there is associated GERD.(49) Peppermint oil has recently gained some attention in the treatment of esophageal spasm. Because of its smooth muscle relaxing properties, , it is used in treating patients with headache, dyspepsia, and irritable bowel
(50)
Peppermint effect on the esophageal manometric findings was
studied on eight spasm patients and it reduced the number of simultaneous esophageal contractions.(51) Preliminary data from our clinic evaluated the
12 Page 13 of 26
response to sublingual dissolvable peppermint tablets in patients with dysphagia and non-cardiac chest pain. Spasm patients were found to have the most favorable response among other motility disorders. (52)
Endoscopic options 1. Peroral endoscopic myotomy (POEM): has provided some patients with spasm and nutcracker esophagus with some relief for a short period of time, but due to the possible post-operative complications and limited data, it is not usually recommended.(36) It is minimally invasive but equivalent in treatment to a surgical myotomy, and the esophageal and gastric myotomy are done with an endoscope. Several case reports have shown the effectiveness of POEM in spasm, however a recent study showed better results in achalasia than in distal spasm.(53-56) Possible complications of the procedure include mucosal tears, pneumoperitoneum, bleeding, pneumothorax, and reflux. 2. Botulinum toxin (Botox): is another treatment option. The mechanism of action involves inhibition of the release of acetylcholine from the cholinergic neurons, therefore leading to paralysis of the muscle.(44) The recommened dosage is 80100 U, injected endoscopically into
four quadrants of the lower esophageal
sphincter.(43) Vanuytsel et al (57) conducted a double blind placebo-controlled study comparing endoscopic botox injection vs saline in treatment of spasm and nutcracker esophagus. After botox injections, patients had significant decreases in 13 Page 14 of 26
their dysphagia score, however, Botox failed to produce significant reduction in the chest pain score. Evidence also suggests that administration of botulinum toxin may complicate future procedures including surgical myotomy.(44)
Some
limitations of botulinum toxin are the shorter duration of symptom relief (6 months) and the need for an upper endoscopy.(36) 3. Esophageal dilation: This approach is particularly considered in esophageal spasm with dysphagia. Bougie dilators and through-the-scope balloons have not been adequately studied in spasm, however pneumatic dilation has been successful in alleviating dysphagia in some patients, but this is limited to those who may need to be categorized as an achalasia diagnosis instead.
(11, 37)
Pneumatic balloons stretch the
lower esophageal sphincter until a tear in the muscular layer is produced, therefore weakening it and decreasing the pressure. Patients may need further dilations if their symptoms do not improve. Patients with achalasia find the most relief with this treatment, but it has been effective as well in some patients with spasm.(58)
Surgical treatment Laparoscopic myotomy extending from the lower esophageal sphincter proximally onto the esophageal body has been used to treat patients with spastic disorders. However Its role in esophageal spasm treatment is debatable, and controlled trials are needed to compare it against medical and endoscopic treatments. Leconte et al
(59)
evaluated 20
patients after myotomy; dysphagia and chest pain were significantly improved after a median follow-up of 50 months. Treatment summary
14 Page 15 of 26
Therapies have been shown to have limited effects on symptomatic relief for spasm.(30) Thus, a reasonable approach is to “play the list” shown in table 1, titrating each drug against patient response, using a “start low and go slow” philosophy to identify a potential therapeutic window.
References: 1. 2.
3. 4. 5. 6. 7. 8.
9. 10. 11. 12. 13. 14.
15.
16. 17.
Spechler S, Castell D. Classification of oesophageal motility abnormalities. Gut 2001;49:145-51. International High Resolution Manometry Working G. The Chicago Classification of Esophageal Motility Disorders, v3.0. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society 2015;27:160-74. Osgood H. A Peculiar Form of Œsorhagismus. The Boston Medical and Surgical Journal 1889;120:401-5. Osler H. Oesophagismus. In: Principles and practice of medicine 1892. Moersch HJ CJ. Diffuse spasm of the lower part of the esoph-agus. Ann Otol Rhinol Laryngol 1934;43:1165, 934. Creamer B, Donoghue E, Code CF. Pattern of esophageal motility in diffuse spasm. Gastroenterology 1958;34:782-96. Sperandio M, Tutuian R, Gideon RM, et al. Diffuse esophageal spasm: not diffuse but distal esophageal spasm (DES). Dig Dis Sci 2003;48:1380-4. Tutuian R, Mainie I, Agrawal A, et al. Symptom and Function Heterogenicity Among Patients with Distal Esophageal Spasm: Studies Using Combined Impedance-Manometry. Am J Gastroenterol 2006;101:464-9. Almansa CC. Esophageal spasm: demographic, clinical, radiographic, and manometric features in 108 patients. Diseases of the Esophagus;25:214-21. Achem SR, Gerson LB. Distal Esophageal Spasm: An Update. Current Gastroenterology Reports 2013;15:325. Roman S, Kahrilas PJ. Management of spastic disorders of the esophagus. Gastroenterology clinics of North America 2013;42:27-43. Konturek JW, Gillessen A, Domschke W. Diffuse esophageal spasm: a malfunction that involves nitric oxide? Scand J Gastroenterol 1995;30:1041-5. Murray JA, Ledlow A, Launspach J, et al. The effects of recombinant human hemoglobin on esophageal motor functions in humans. Gastroenterology 1995;109:1241-8. Burton PR, Brown W, Laurie C, et al. The Effect of Laparoscopic Adjustable Gastric Bands on Esophageal Motility and the Gastroesophageal Junction: Analysis Using High-Resolution Video Manometry. Obesity Surgery 2009;19:905-14. Zheng E, Sloan J, Matthew Gideon R, et al. EGJ Outflow Obstruction is Often Associated with Coexistent Abnormal Esophageal Body Motility and Abnormal Bolus Transit. Gastroenterology;152:S326. Clouse RE, Lustman PJ. Psychiatric illness and contraction abnormalities of the esophagus. The New England journal of medicine 1983;309:1337-42. Siegel CI, Hendrix TR. Esophageal Motor Abnormalities Induced By Acid Perfusion In Patients With Heartburn. Journal of Clinical Investigation 1963;42:686-95.
15 Page 16 of 26
18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32.
33. 34. 35.
36. 37. 38. 39. 40.
41. 42.
Richter JE, Johns DN, Wu WC, et al. Are esophageal motility abnormalities produced during the intraesophageal acid perfusion test? JAMA 1985;253:1914-7. Crozier RE, Glick ME, Gibb SP, et al. Acid-provoked esophageal spasm as a cause of noncardiac chest pain. Am J Gastroenterol 1991;86:1576-80. Campo S, Traube M. Manometric characteristics in idiopathic and reflux-associated esophageal spasm. American Journal of Gastroenterology 1992;87. Boeckxstaens GE, Zaninotto G, Richter JE. Achalasia. Lancet 2014;383:83-93. Roman S, Kahrilas PJ. Distal Esophageal Spasm. Dysphagia 2012;27:115-23. Millan MS, Bourdages R, Beck IT, et al. Transition from diffuse esophageal spasm to achalasia. J Clin Gastroenterol 1979;1:107-17. Robson K, Rosenberg S, Lembo T. GERD progressing to diffuse esophageal spasm and then to achalasia. Dig Dis Sci 2000;45:110-3. Longstreth GF, Foroozan P. Evolution of symptomatic diffuse esophageal spasm to achalasia. South Med J 1982;75:217-20. Samo S, Carlson DA, Kahrilas PJ, et al. Ineffective Esophageal Motility Progressing into Distal Esophageal Spasm and Then Type III Achalasia. ACG Case Reports Journal 2016;3:e183. Khatami SS, Khandwala F, Shay SS, et al. Does Diffuse Esophageal Spasm Progress to Achalasia? A Prospective Cohort Study. Digestive Diseases and Sciences 2005;50:1605-10. Grubel C, Borovicka J, Schwizer W, et al. Diffuse Esophageal Spasm. Am J Gastroenterol 2008;103:450-7. Dalton CB, Castell DO, Hewson EG, et al. Diffuse esophageal spasm. A rare motility disorder not characterized by high-amplitude contractions. Dig Dis Sci 1991;36:1025-8. Roman S, Kahrilas PJ. Management of spastic disorders of the esophagus. Gastroenterol Clin North Am 2013;42:27-43. Sifrim D, Fornari F. Non-achalasic motor disorders of the oesophagus. Best practice & research. Clinical gastroenterology 2007;21:575-93. Lee EM, Park MI, Moon W, et al. A Case of Symptomatic Diffuse Esophageal Spasm During Multiple Rapid Swallowing Test on High-Resolution Manometry. Journal of Neurogastroenterology and Motility 2010;16:433-6. Tsuboi K, Mittal SK. Diffuse esophageal spasm: has the term lost its relevance? Analysis of 217 cases. Dis Esophagus 2011;24:354-9. Richter JE, Castell DO. Diffuse esophageal spasm: a reappraisal. Ann Intern Med 1984;100:242-5. Richter JE, Wu WC, Johns DN, et al. Esophageal manometry in 95 healthy adult volunteers. Variability of pressures with age and frequency of "abnormal" contractions. Dig Dis Sci 1987;32:583-92. Castell DO. Esophageal motility disorders: Clinical manifestations, diagnosis, and management: UpToDate, Waltham, MA, 2017. Achem SR. Diffuse Esophageal Spasm in the Era of High-Resolution Manometry. Gastroenterology & Hepatology 2014;10:130-3. Pandolfino JE, Roman S, Carlson D, et al. Distal esophageal spasm in high-resolution esophageal pressure topography: defining clinical phenotypes. Gastroenterology 2011;141:469-75. De Schepper HUH. Distal esophageal spasm and the Chicago classification: is timing everything? Neurogastroenterology and Motility;28:260-5. Taniguchi Y, Takahashi T, Nakajima K, et al. Multiple huge epiphrenic esophageal diverticula with motility disease treated with video-assisted thoracoscopic and hand-assisted laparoscopic esophagectomy: a case report. Surg Case Rep 2017;3:63. Tutuian R, Castell DO. Review article: oesophageal spasm – diagnosis and management. Alimentary Pharmacology & Therapeutics 2006;23:1393-402. Orlando RC, Bozymski EM. Clinical and manometric effects of nitroglycerin in diffuse esophageal spasm. The New England journal of medicine 1973;289:23-5.
16 Page 17 of 26
43. 44. 45. 46. 47. 48.
49. 50. 51. 52. 53. 54.
55. 56.
57.
58. 59.
Khalaf M, Castell DO. Achalasia: Common Features of an Uncommon Disease. Practical Gastroenterology 2016. Vaezi MF, Pandolfino JE, Vela MF. ACG clinical guideline: diagnosis and management of achalasia. Am J Gastroenterol 2013;108:1238-49; quiz 50. Moreland RB, Goldstein I, Traish A. Sildenafil, a novel inhibitor of phosphodiesterase type 5 in human corpus cavernosum smooth muscle cells. Life Sci 1998;62:Pl 309-18. Eherer AJ, Schwetz I, Hammer HF, et al. Effect of sildenafil on oesophageal motor function in healthy subjects and patients with oesophageal motor disorders. Gut 2002;50:758-64. Cannon RO, 3rd, Quyyumi AA, Mincemoyer R, et al. Imipramine in patients with chest pain despite normal coronary angiograms. The New England journal of medicine 1994;330:1411-7. Clouse RE, Lustman PJ, Eckert TC, et al. Low-dose trazodone for symptomatic patients with esophageal contraction abnormalities. A double-blind, placebo-controlled trial. Gastroenterology 1987;92:1027-36. Achem SR. Management of Esophageal Chest Pain. Gastroenterology & Hepatology 2007;3:765-7. Kligler B, Chaudhary S. Peppermint oil. Am Fam Physician 2007;75:1027-30. Pimentel M, Bonorris GG, Chow EJ, et al. Peppermint oil improves the manometric findings in diffuse esophageal spasm. J Clin Gastroenterol 2001;33:27-31. Chowdhary TS, Khalaf M, Elias PS, Castell DO. Peppermint oil relieves dysphagia and non-cardiac chest pain secondary to esophageal motility disorders. Am J Gastroenterol 2017;112:S168-S225. Louis H, Covas A, Coppens E, et al. Distal esophageal spasm treated by peroral endoscopic myotomy. Am J Gastroenterol 2012;107:1926-7. Khashab MA, Saxena P, Kumbhari V, et al. Peroral endoscopic myotomy as a platform for the treatment of spastic esophageal disorders refractory to medical therapy (with video). Gastrointest Endosc 2014;79:136-9. Shiwaku H, Inoue H, Beppu R, et al. Successful treatment of diffuse esophageal spasm by peroral endoscopic myotomy. Gastrointest Endosc 2013;77:149-50. Sharata AM, Dunst CM, Pescarus R, et al. Peroral endoscopic myotomy (POEM) for esophageal primary motility disorders: analysis of 100 consecutive patients. J Gastrointest Surg 2015;19:16170; discussion 70. Vanuytsel T, Bisschops R, Farré R, et al. Botulinum Toxin Reduces Dysphagia in Patients With Nonachalasia Primary Esophageal Motility Disorders. Clinical Gastroenterology and Hepatology;11:1115-21.e2. Pandolfino JE, Kwiatek MA, Nealis T, et al. Achalasia: a new clinically relevant classification by high-resolution manometry. Gastroenterology 2008;135:1526-33. Leconte M, Douard R, Gaudric M, et al. Functional results after extended myotomy for diffuse oesophageal spasm. Br J Surg 2007;94:1113-8.
17 Page 18 of 26
Figure legends:
Figure 1: High resolution motility (HRM) showing a normal peristaltic swallow with normal velocity (< 8 cm/sec), and normal distal latency (DL) (> 4.5 sec). Normal velocity in HRM is easily recognised visually, giving the contraction its sloping appearance. The DL is the time measured from the upper sphincter relaxation (A) to the contractile deceleration point (B).
Figure 2: HRM showing a premature contraction with a distal latency (DL) < 4.5 sec. This contraction can be also described as simultaneous (velocity > 8 cm/sec), and this can be easily visualised in HRM, giving the contraction this vertical appearance.
Figure 3: HRM showing a simultaneous contraction (velocity > 8cm/sec) with normal latency (> 4.5 sec). Thus, we emphasize on the fact that presence of simultaneous contractions in ≥ 20% of the swallows is the hallmark diagnostic criterion for distal esophageal spasm (even if not associated with short latency).
Figure 4: HRM featuring a triple-peaked contraction. This is considered a rare feature of spasm, that shouldn't be ignored.
Figure 5: Barium esophagram showing the characteristic cork screw appearance that may be seen in esophageal spasm.
Figure 6: Barium swallow showing large esophageal diverticulum complicating a case of esophageal spasm.
Page 19 of 26
Table 1: Suggested hierarchy of treatment options for distal esophageal spasm, starting with the least invasive
1. Concentrated peppermint oil 2. Nitrates or phosphodiesterase-5 inhibitors 3. Calcium channel blockers 4. Tricyclic antidepressants 5. Endoscopic Botox injection 6. Pneumatic dilation 7. Myotomy (POEM or surgical)
Page 20 of 26
Figure-1.DPI_300.jpg
1 Page 21 of 26
Figure-2.DPI_300.jpg
2 Page 22 of 26
Figure-3.DPI_300.jpg
3 Page 23 of 26
Figure-4.DPI_301.jpg
4 Page 24 of 26
Figure-5.DPI_301.jpg
5 Page 25 of 26
Figure-6.DPI_300.jpg
6 Page 26 of 26