Botulinum toxin use in pediatric esophageal achalasia: A case report

Botulinum

Toxin Use in Pediatric Esophageal Achalasia: A Case Report By J.M. Walton Hamilton,

l Esophageal achalasia (EA) has been historically treated by esophageal dilatation or myotomy with or without fundoplication. Botulinum toxin (Botox-Allergan) use in pediatric EA has not been previously described. The authors’ objective was to observe the efficacy of botulinum toxin injection into the lower esophageal sphincter (LES) for EA. An II-year-old boy presented with a g-month history of frequent pneumonia, productive cough, and a l-year history of chest discomfort and odynophagia. Chest radiograph showed changes compatible with aspiration. Upper gastrointestinal (UGI) series showed typical narrowing of the LES, and 24-hour pH study showed no reflux. Esophageal manometry showed classic findings of achalasia. An upper gastrointestinal endoscopy was performed showing a huge volume of retained food. A direct four-quadrant injection was performed with a total of 100 U of botulinum toxin into the LES. UGI series showed improvement in esophageal emptying. Esophageal manometry showed impressive improvement in LES pressure (preinjection, 44.1 mm Hg to postinjection mean of 16.6 mm Hg), percent relaxation (preinjection, 30% to postinjection, 58.8%), and duration of relaxation (preinjection, 1.9 seconds to postinjection, 11 seconds). The patient has not had any further rekpiratory symptoms, chest pain, or odynophagia in 8 months of follow-up. Botulinum toxin injection is simple and effective for EA and merits its study in a prospective manner in the pediatric population. Copyright o 1997 by W. B. Saunders Company

INDEX

WORDS:

Achalasia,

botulinum

toxin.

A

CHALASIA of the esophagus is a rare disorder in children and is characterized by absent peristalsis, elevated lower esophageal sphincter pressure, and failure of the lower eiophageal sphincter to relax during swallowing.Q Most series are small but document and recommend the use of esophageal dilatation or esophageal myotomy (with or without fundoplication).3~4 Successful short- and long-term results using intrasphincteric botulinum toxin injection have been demonstrated in a randomized prospective trial in adults, but there have been no published data on its use in children for achalasia.2*5 Long-term effects are not known with injection of this From the Divwon of Surgery at the Chlldreni Hospital, and the Gastrointestinal Disease Unit, McMaster Universit) Medical Center: Chedoke-McMaster Hospitals. Han&on, Ontario. Presented at the 28th Anruuzl Meeting of the Canadian Association of Paediatrzc Surgeons, Halifax, Nova. Scorla. August 18-20, 1996. Address reprmt requests to J.M. Walton, MD, FRCSC, Chddren’s Hospital at Chedoke-McMastel; McMaster University Medical Centec 1200 Marn St U: Room 4E3. Hamrlton, Olltavio. Cunada L8N 32.5. Copyright 0 1997 by WB. Saunders Company 0022-3468/97’3206-0028$03.00/O

916

and G. Tougas Ontario

neurotoxin, but its efficacy is usually short term requiring reinjection.(j We report the first successful use of intrasphincteric botulinum toxin for esophageal achalasia in a child. CASE

REPORT

An 1 l-year-old boy presented with a 1 -year history of odynophagla and chest discomfort and a 9-mouth history of recurrent pneumonia and productive cough. There was no history of weight loss. Chest radiograph showed chronic changes compattble with multiple episodes of aspiration pneumonia. Pulmonary function tests showed a functional vital capacity of 79% and forced expiratory volume (1 second) of 41% of predicted. with a peak flow of 26%. Upper gastrointestinal (UGI) series showed typical bird beak deformity of the lower esophagus with delayed emptymg (Fig 1). Results of rachonuclide esophageal clearance test showed poor emptymg with little entermg the stomach after 30 minutes. Results of the 24hour pH study showed no episodes of acid reflux. Esophageal manometry was diagnostic of achalasia with absence of discernible swallow-induced peristaltic actlvay. general reduction in the amplitude of contraWon, and a hypertonic lower esophageal sphincter (Table 1). UGI endoscopy showed a large amount of retained food m the esophagus. During endoscopy a four-quadrant injection of 100 U of botulinum toxin (Botox-Allergan) was placed in the lower esophageal sphincter. UGI series after injection showed Improved emptying of the esophagus but with a persistent 7.5-cm column of barium. Esophageal manometry showed marked improvement in all parameters (Table 1). The patient has had no further episodes of pneumoma, chest pain. or odynophagia during the S-month follow-up period

DISCUSSION

Esophageal achalasia in the pediatric population has historically been treated by LES balloon dilatation4.7 or esophageal myotomy with or without fundoplication.3,8 Pneumatic dilatation success is often short lived in children, risks perforation, and often results in subsequent esophageal myotomy.3,7 Transabdominal esophageal myotomy results in achalasia have been good, with complete resolution of symptoms in 80% of patients, but this does involve major surgery. Endoscopically injected intrasphincteric botulinum toxin seems to be minor procedure by comparison. Botulinum toxin has been use in both striated (strabismus, blepharospasm, and laryngeal dystonial.6) and smooth muscle disorders.‘,6 Its mechanism of action in skeletal muscle is related to binding to the presynaptic cholinergic terminals leading to a chemical denervation (via inhibition of acetylcholine release) and possibly muscle atrophy. Smooth muscle relaxation may occur via blockage of the excitatory acetylcholine release, balancing out the loss of the inhibitory nerves in achalasia.2.9

Journal

ofPediatric

Surgery,

Vol 32, No 6 (June),

1997:

pp 916-917

BOTULINUM

TOXIN

917

IN ACHALASIA

Table

Mean

1. Esophageal

Mean relaxation, % (range) Duration of relaxation, seconds

bird-beak sphincter.

deformity

in the

Parameters

Prebotulin Toxin

Postbotulin Toxin

44.1 (35-49)

16.6 (12-22)

30 (12-60)

58.5 (45-60)

LES pressure,

mm Hg (range)

Fig 1. Prone UGI series shows typical prebotulinum injection lower esophageal

Manometry

1.9

11

the initial botulinum toxin injection.5 In these responders median duration of symptoms’ relief is 15.6 months with second botulinum injections leading to response in 60% of adults.5 Similar data are not available for children. Long-term adverse effects have not been noted in skeletal muscle problems over 10 to 1.5 years’ use.6 Short- and long-term experience in smooth muscle disorders support its safety with some instances of heartburn from subsel quent gastroesophageal reflux.2,5 Dosige guidelines are not available for the younger age range of the pediatric population, but for children over the age of 10 years, adult dosages can be used. 2,5 Although results are not permanent with botulinum toxin injection, it may be an excellent means to improve nutritional and pulmonary status before esophageal myotomy in which repeated injectibns are unattractive or ineffective.5 Botulinum toxin has not been previously studied in pediatric EA, but our excellent short-term results in this case would warrant further investigation in pediatric esophageal achalasia. ADDENDUM

Intrasphincteric botulinum toxin for achalasia in adults has been shown to be safe and simple with good shortand long-term results. 2,5Two thirds of adults respond to

Since presentation this child has undergone a second intrasphinceric botulinum toxin injection, 1 year after the first injection, with good initial results.

REFERENCES 1. Cohen S, Parkman HP: Editorial: Treatment of achalasia-From whalebone to botulin toxin. N Engl J Med 332:815-816, 1995 2. Pasricha PJ, Ravich WJ, Hendrix TR, et al: Intrasphincteric botulin toxin for the treatment of achalasia. N Engl J Med 332:774-778, loo< 3. Vane DW, esophagomyotomy .^^^

Cosby K, West K, et al: Late results following in children with achalasia. J Pediatr Surg 6:515-519,

IYXX

4. Boyle JT, Cohen S, Watkins JB: Successful treatment of achalasia in childhood by pneumatic dilatation. J Pediatr 99:35-40, 1981 5. Pasricha PS, Rai R, Ravich WJ, et al: Botulinum toxin for

achalasia: Long-term outcome and predictors of response. Gastroenterology 110:1410-1415, 1996 6. Jankovic J, Brin MF: Therapeutic uses of botulin toxin. N Engl J Med 324:1186-1194,199l 7. Eckardt VF, Aignherr C, Bernhard G: Predictors of outcome in patients with achalasia treated by pneumatic dilatation. Gastroenterology 103:1732-1738,1992 8. Myers NA, Jolley SG, Taylor R: Achalasia of the cardia in children: A worldwide survey. J Pediatr Surg 10:1375-1379, 1994 9. Holloway RH, Dodds WJ, Helm JF, et al: Integrity of the cholinergic innervation to the lower esophageal sphincter in achalasia. Gastroenterology 90:924-929, 1986