Abstract
Achalasia is primarily a smooth muscle motility disorder of the esophagus driven by aberrant peristalsis and failure of sphincter relaxation. Notably, achalasia is a heterogeneous disease with primarily 3 possible pattern subtypes. According to the review of current cases and literature regarding achalasia, patients primarily present with dysphagia, usually to solids and, if progressed, to solids and liquids. Rarely, untreated achalasia may result in thiamine deficiency and present as Wernicke-Korsakoff syndrome (WKS). This acute neurologic condition primarily affects the central and peripheral nervous system and is known by the triad of ataxia, ophthalmoplegia, and confusion. Individuals who present with WKS typically have a notable history of chronic alcohol abuse with decreased thiamine intake and metabolism. Although less common, individuals with WKS may have a pertinent history of starvation, anorexia nervosa, and malnutrition. This case highlights a unique presentation of Wernicke’s encephalopathy (WE) in a 30-year-old woman with severe type II achalasia complicated by a 60-pound weight loss in a span of 2 months. According to our literature review, there have only been 2 previously reported cases of severe achalasia leading to the development of WE. Considering the limited number of case reports available, WE must be in the differentials in patients with underlying achalasia, and our case report highlights this unusual presentation with corresponding brain imaging and manometry testing.
Keywords
This is a 30-year-old, 83.9 kg, 1.6 m Caucasian female patient with a medical history significant for bipolar 1 disorder, polycystic ovarian syndrome, acute pancreatitis, and history of opioid use disorder who presented to our emergency department for acute encephalopathy with confabulation, complete bilateral loss of vision, ocular motility abnormalities, lower extremity weakness, and gait instability worsening over the span of 3 to 5 days. Notably, her changes in vision bilaterally began 2 months prior to presentation with gradual progression to complete bilateral vision loss. In association with her symptoms, she reported a 5-month history of intractable nausea, vomiting associated with progressive oropharyngeal and esophageal dysphagia associated with 27 kg weight loss from a baseline weight of 110.9 kg. Four months prior to this admission, the patient underwent esophagogastroduodenoscopy (EGD) for her oropharyngeal and esophageal dysphagia, remarkable only for nonspecific reactive changes. The EGD was otherwise negative for esophageal strictures, masses, dilation of the esophagus, tight lower esophageal sphincter (LES), or retention of food products to suggest a culprit underlying motility disorder. Further patient examination revealed neurologic findings of bilateral lower extremity weakness (Grade 2-3) with areflexia. A full neurologic examination demonstrated the following pertinent findings: inability to follow commands, poor language output, extraocular muscle palsy, reflex blink to visual threat absent bilaterally, movement strongly resisted in bilateral upper extremities, and Achilles reflexes graded at 3. Notably, nystagmus was not elicited during examination and gait testing was deferred given severe patient agitation. Neurology was consulted for evaluation of WE given her classical triad presentation, including altered mental status, ophthalmoplegia, and reported ataxia. Subsequent brain magnetic resonance imaging (MRI) revealed hyperintensities of the bilateral walls of the third ventricle and mammillary bodies. In the setting of impaired nutritional intake due to severe oropharyngeal dysphagia resulting in severe weight loss, full nutritional and metabolic panel were ordered to assess for suspected nutritional deficiencies contributing to her mental status (Table 1). Her nutrition panel was notable for vitamin B1 deficiency, low B12, and elevated homocysteine level. In addition, her metabolic panel demonstrated low albumin, prealbumin, transaminitis, and an elevated albumin/globulin ratio. Her MRI in relation to her nutritional panel revealed hyperintensities of the bilateral walls of the third ventricle and mammillary bodies (Figures 1 and 2).
Nutritional Panel With Values on Admission, 1 Week Post Repletion Protocol Initiation, and 2 Months Post Initiation of Repletion Protocol.
DWI axial MRI sequence demonstrating symmetrical hyperintensities of the periventricular region of the third ventricle. The hyperintense lesions are indicative of the edematous and high-water content nature of the lesions.
FLAIR axial MRI sequence demonstrating symmetrical hyperintensities of the periventricular region of the third ventricle. The hyperintense lesions are indicative of the edematous and high-water content nature of the lesions.
A lumbar puncture revealed elevated oligoclonal bands with elevated IgG, further imaging did not demonstrate lesions consistent with a demyelinating process. Appropriate physical examination was limited by lack of cooperation, and empiric management for suspected WE and suspected beriberi peripheral neuropathy was initiated with high-dose 500 mg intravenous thiamine 3 times daily for 2 to 3 days followed by daily oral repletion. Although there was mild improvement in vision and cognition 5 to 6 days post empiric Wernicke’s encephalopathy protocol initiation, her mental status continued to fluctuate with associated confabulations and both visual and auditory hallucinations. Hospital admission was further complicated by psychiatric comorbidities and concerns for rumination syndrome in the setting of ongoing dysphagia with previously normal EGD. During her admission, further radiographic testing with magnetic resonance enterography (MRE) was completed and did not show evidence of active inflammatory bowel disease, penetrating disease, or stricture formation. Barium esophagram demonstrated inability of barium pill to pass though the distally tapered esophagus and slow passage of contrast into the stomach. High-resolution manometry demonstrated abnormal relaxation of the esophagogastric junction (EGJ), abnormal relaxation median supine integrative relaxation pressure (IRP) (46 mm Hg), IRB 70 mm Hg in upright position, hypertensive lower esophageal sphincer (LES), absence of normal peristalsis with pan-esophageal pressurization in all swallows, scattered jackhammer activity, and retrograde peristalsis and negligible upper esophageal sphincter (UES) tone (Figures 3 and 4).
Clouse plot: Demonstration of high-resolution normal manometry testing, time located on the x-axis and distance from nostril on the y-axis. Manometry testing utilizes 36 solid-state sensors for detection of pressure along the esophagus. The color-coded pressures demonstrated on the Clouse plot are indicative of intraluminal pressures, with elevated pressures demonstrated by red-maroon colors. The pressures, phase, and time plot assess the esophageal sphincter and primary peristalsis. Prior to initiation of swallowing, the upper esophageal sphincter (UES) and esophagogastric junction (EGJ) are high pressure zones. The objective metrics are incorporated into the Chicago Classification System for determination of pressures including integrated relaxation pressure (IRP), a reflection of the average function of the lower esophageal sphincter.
Clouse plot: Manometry study respective to our patient with type II achalasia. According to the Chicago Classification System, type II achalasia is defined by an integrated relaxation pressure (IRP) above the upper limit of normal, 100% failed peristalsis, and over 20% pan-esophageal pressurization (PEP). The PEP reflects the compartmentalization of pressure from the upper esophageal sphincter (UES) to the lower esophageal sphincter (LES) at the threshold of the 30 mm Hg isobaric contour. This Clouse Plot for our patient demonstrated an IRP of 46 mm Hg, isobaric paraesophageal pressurization, and complete absence of normal peristalsis.
This patient underwent laparoscopic Heller esophagomyotomy for severe type II achalasia, as well as hiatal hernia repair and Toupet fundoplication. Postoperative course was briefly complicated by postsurgical pain and nausea, with gradual symptomatic improvement and transition to a full liquid diet. Outpatient follow-up 1 week after her laparoscopic Heller myotomy with Toupet fundoplication revealed moderate improvement of dysphagia, patient adequately maintaining appropriate weight and albumin values. During this encounter, hallucinations, confabulations, and visual disturbances were noted to have complete resolution. Additional laboratory testing and upper gastrointestinal fluoroscopy testing was recommended; however, she was lost to follow-up given relocation to another state.
Discussion
Achalasia incidence rates were perceived lower until annual rates have risen to 1.6 in 100 000 versus 0.5 to 1.2 in 100 000. Patients upon presentation typically present with dysphagia to solids and/or liquids, regurgitation, and weight loss, with nutritional deficiencies being present with delayed diagnosis. 1 Given the role of thiamine as a cofactor for the generation of adenosine trisphosphate (ATP) in addition to its role in nerve signal propagation and maintenance of myelin sheath, thiamine deficiency due to poor intake can progress to profound effects on the nervous system as seen in WE. 2 Figures 1 and 2 demonstrate diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) axial MRIs with symmetrical third ventricle periventricular hyperintensities, classically seen in WE.
Within the esophageal motility and motor disorders, achalasia is characterized by failed peristalsis and lack of LES relaxation due to nerve damage. In the initial phase of achalasia, there is a predominantly vigorous phase with high-amplitude non-peristaltic contractions due to myenteric plexus insult and nerve fiber degeneration. 3 Several inciting etiologies of nerve fiber degeneration have been proposed, including parasitic infections, viral infections, genetic associations in rare familiar disorders, and traumatic injury. 4 Progression of the cholinergic neuronal loss and reduction in ganglion cells resulting in dilation and minimal amplitude contractions in the esophagus. 3 Achalasia is further stratified into 3 different subtypes according to the Chicago Classification. All the subtypes must meet the criteria of integrated relaxation pressures (IRP) above the upper limit of normal. Classic achalasia (Type I) is classically seen at the end stage of achalasia, with diagnostic criteria including 100% failed peristalsis. Of note, failed peristalsis is classified by premature contractions with distal contractile integral (DCI) values less than 450 mm Hg. Achalasia with pressurization (Type II) has diagnostic criteria including 100% failed peristalsis, pan-esophageal pressurization in greater than 20% of swallows. Finally, the diagnostic criteria for spastic achalasia (Type III) includes absence of normal peristalsis and premature contractions with DCI values greater than 450 mm Hg with greater than 20% of swallows. Diagnostic workup includes barium swallow evolution, endoscopy, and high-resolution manometry, the current standard for achalasia diagnosis. 5 Figures 3 and 4 include a normal high-resolution manometry test and manometry testing respective to our patient with type II achalasia, respectively. Figure 4 demonstrates the hallmark pan-esophageal pressurization and 100% failed peristalsis of type II achalasia.
Achalasia management involves pharmacologic, endoscopic, and surgical approaches. As in our patient and the patient in Pacei et al, 6 the laparoscopic Heller myotomy is the standard surgical procedure via disruption of the LES hypertonic fibers. This may be completed in conjunction with a procedure such as a Dor or Toupet fundoplication to reduce the incidence of postoperative gastroesophageal reflux and development of Battertt’s esophagus. 7 Pneumatic balloon dilation is the first-line nonsurgical intervention recommended for individuals with contraindications for surgery, and this intervention shows similar therapeutic success in matched patients. 8 Pharmacologic modalities including utilizing calcium channel blockers and oral nitrates may be further considered for sole or additional management.
Conclusion
Achalasia appears to affect individuals by bimodal age distribution at diagnosis with the greatest incidence in the third to fourth decade and the other at 60 years of age, close to the median age of our patients with achalasia and WE. 9 Histories from patients presenting with constant dysphagia to both solids and liquids must be carefully obtained, utilizing symptoms of regurgitation, heartburn, and chest pain to differentiate between etiologies requiring different diagnostic and management modalities. There is often a delay in diagnosis, commonly because associated regurgitation is mistaken as gastroesophageal reflux disease. Identifying achalasia via clinical history and diagnostic testing is critical in preventing progression and complications such as weight loss, nutritional deficiencies, and irreversible neurological sequelae. 10 WE is a rare and poorly documented delayed complication of untreated achalasia. Patients affected by WE commonly have a history of alcohol abuse and malabsorptive disorders as a result of gastrointestinal malignancies. According to Zuccoli et al, 11 patients with WE may have changes in mentation ranging from mild confusion to coma. Associated presenting characteristics include ocular changes and ataxia. According to Table 2, highlighting our literature review, common presenting symptoms in severe achalasia patients presenting as WE include early satiety, nausea, and post-prandial epigastric pain both with and without vomiting. They all differed in timing of neurologic presentation, all having ocular involvement, ataxia, and confabulations. Although respective thiamine levels were not available for the patient in Ehrlich et al, patients had both MRI findings consistent with WE in the setting of reportedly low total thiamine levels. Unfortunately, 2 of the 3 cases available highlight the lingering effects of WE, including persistent ataxia, anterograde memory loss, visual disturbances, and confabulations, resulting in morbidity and long-term disability. Although the sample size is small, this case report and literature review highlights WE as an atypical presentation of achalasia and outcomes despite aggressive management at the late stage of disease.
Literature Review and Case Reports of WE in the Setting of Achalasia, Presenting Symptoms, Extraintestinal Manifestations, Initial Thiamine Level, Pertinent Testing, Treatment, and Outcomes.
Abbreviations: WE, Wernicke’s encephalopathy; MRI, magnetic resonance imaging; LES, lower esophageal sphincter; IV, intravenous; GI, gastrointestinal; EGD, esophagogastroduodenoscopy; FLAIR, fluid-attenuated inversion recovery; TID, 3 times per day.
Footnotes
Acknowledgements
We would like to acknowledge the internal medicine and gastroenterology departments at UF Health Shands Hospital for supporting us academically and professionally.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Ethics approval
Our institution does not require ethical approval for reporting individual cases or case series.
Informed consent
Verbal consent was obtained from the patient for their anonymized information to be published in this article.