What is the best approach to manage diffuse esophageal spasm in a patient with adult onset Pantothenate Kinase-Associated Neurodegeneration (PKAN)?

Diffuse Esophageal Spasm in Adult-Onset PKAN: Association and Management

Is DES Associated with PKAN?

Diffuse esophageal spasm in a 46-year-old male with adult-onset PKAN is most likely unrelated to the neurological condition, and should be evaluated and managed as a primary esophageal motility disorder using standard approaches.

There is no established literature linking PKAN (Pantothenate Kinase-Associated Neurodegeneration) to diffuse esophageal spasm. PKAN primarily affects the basal ganglia and causes movement disorders, dystonia, and parkinsonism, but does not typically involve esophageal smooth muscle dysfunction 1. The co-occurrence in this patient is likely coincidental, and the DES should be approached as a separate primary esophageal motility disorder.

Diagnostic Confirmation Required

Before initiating treatment, confirm the diagnosis with:

• High-resolution manometry (HRM) to document simultaneous contractions in the distal esophagus alternating with normal peristalsis, which is the manometric hallmark of DES 1, 2
• Upper endoscopy to exclude structural abnormalities, eosinophilic esophagitis, and GERD-related complications 3
• Ambulatory impedance-pH monitoring if GERD overlap is suspected, as this can mimic or coexist with DES 3

Treatment Algorithm for Diffuse Esophageal Spasm

First-Line: Pharmacological Management

Start with smooth muscle relaxants as initial therapy, recognizing that clinical benefit is often disappointing despite manometric improvements 3, 4:

• Calcium channel blockers (e.g., diltiazem 30-60mg before meals) can reduce esophageal contractile force and provide benefit in some patients 4, 5
• Nitrates (e.g., isosorbide dinitrate 5-10mg sublingual before meals) as an alternative or combination therapy 4
• PPIs should be added if any GERD component is suspected, as symptom overlap is common 3
• Neuromodulators (tricyclic antidepressants like imipramine 25-50mg at bedtime) may help with visceral hypersensitivity and the psychological component of symptom perception 3, 4

Second-Line: Endoscopic Botulinum Toxin Injection

If pharmacological therapy fails after 4-8 weeks, proceed to endoscopic botulinum toxin injection, which is the best-studied treatment option for DES 6, 5:

• Inject 100 IU botulinum toxin diluted in 10mL saline at multiple sites along the esophageal wall, beginning at the lower esophageal sphincter and moving proximally in 1-1.5cm intervals 6
• Expect symptomatic improvement in approximately 78-89% of patients within 1 month, with effects lasting 6-24 months 6
• Reinjection is effective for symptom relapse and can be repeated as needed 6, 5
• This approach has superior evidence compared to medical therapy, with prospective data showing sustained benefit 6

Third-Line: Surgical Myotomy (POEM or Open)

Reserve surgical intervention for patients refractory to both medical therapy and botulinum toxin injections 3, 7, 2:

• Per-oral endoscopic myotomy (POEM) is the preferred surgical approach, as it allows unlimited proximal extension of the myotomy to address the full extent of esophageal spasm 1, 3
• POEM should be considered particularly for type III achalasia-like presentations or when spastic contractions extend proximally 1
• Traditional long esophageal myotomy via thoracoscopy achieves satisfactory results in only about 70% of cases, inferior to outcomes in achalasia 7, 2
• An antireflux procedure may be needed to prevent postoperative GERD 7

Critical Caveats

• Do not confuse DES with esophagogastric junction outflow obstruction (EGJOO), which requires different evaluation and should not prompt immediate invasive intervention 1
• Exclude achalasia before proceeding with any treatment, as management differs significantly; functional luminal impedance planimetry (FLIP) can help differentiate when manometry is equivocal 1
• Medical therapy has limited long-term efficacy despite manometric improvements, so set realistic expectations with patients 4, 5
• Psychological factors play a role in symptom perception; consider cognitive behavioral therapy or esophageal-directed hypnotherapy as adjunctive treatment 3, 4

PKAN-Specific Considerations

While managing the DES, be aware that:

• Swallowing dysfunction in PKAN would more likely manifest as oropharyngeal dysphagia from dystonia or parkinsonism, not as a primary esophageal motility disorder 1
• If oropharyngeal dysphagia coexists, consider expiratory muscle strength training (EMST) and the Shaker head lift exercise for upper esophageal sphincter dysfunction 1
• The patient's neurological medications for PKAN should be reviewed, as some can affect esophageal motility, though this is uncommon