Acta Otorrinolaringol Esp. 2012;63(6):465---469

www.elsevier.es/otorrino

BRIEF COMMUNICATION

Cricopharyngeal Myotomy in the Treatment of OculopharyngealMuscular Dystrophy�

Antonio Gómez-Torres,a,∗ Antonio Abrante Jiménez,a Eloy Rivas Infante,b

Alicia Menoyo Bueno,a Isabel Tirado Zamora,a Francisco Esteban Ortegaa

a Unidad de Gestión Clínica de Otorrinolaringología, Hospital Universitario Virgen del Rocío, Sevilla, Spainb Servicio de Anatomía Patológica, Hospital Universitario Virgen del Rocío, Sevilla, Spain

Received 16 March 2012; accepted 4 June 2012

KEYWORDSOculopharyngealmuscular dystrophy;Dysphagia;Treatment;Cricopharyngealmyotomy

Abstract Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant myopathicdisease which provokes oropharyngeal dysphagia, palpabral ptosis and proximal limb weak-ness. It is the abnormal expression of the GCG triplet in the PABPN1 gene on chromosome 14that causes this disease. The study of the oropharyngeal dysphagia that these patients sufferfrom should include upper gastrointestinal endoscopy, barium video-radiology and oesophagealmanometry. Genetic study confirms the diagnosis. We report 6 patients (3 of whom were siblings)referred to our department with a confirmed diagnosis of OPMD, who underwent cricopharyngealmyotomy to achieve normal swallowing.© 2012 Elsevier España, S.L. All rights reserved.

PALABRAS CLAVEDistrofia muscularoculofaríngea;Disfagia;Tratamiento;Miotomía delcricofaríngeo

Miotomía del cricofaríngeo en el tratamiento de la distrofia muscular oculofaríngea

Resumen La distrofia muscular oculofaríngea (DMOF) es una enfermedad hereditariaautosómica dominante que causa disfagia orofaríngea, ptosis palpebral y debilidad muscularproximal. Es causada por una expresión anormal del triplete GCG del gen PABPN1, situado en elcromosoma 14. El estudio de la disfagia orofaríngea que sufren estos pacientes se basa en la his-toria clínica, la endoscopia digestiva alta, la radiología con contraste baritado y la manometría

esofágica. El diagnóstico definitivo se confirma con el estudio genético. Presentamos 6 casos,3 de ellos de una misma familia, remitidos a nuestro departamento con el diagnóstico confir-mado de DMOF, los cuales se sometieron a una miotomía del cricofaríngeo para conseguir unadeglución normal.© 2012 Elsevier España, S.L. Tod

� Please cite this article as: Gómez-Torres A, et al. Miotomíadel cricofaríngeo en el tratamiento de la distrofia muscular oculo-faríngea. Acta Otorrinolaringol Esp. 2012;63:465---9.

∗ Corresponding author.E-mail address: gotoa83@hotmail.com (A. Gómez-Torres).

I

OanG

2173-5735/$ – see front matter © 2012 Elsevier España, S.L. All rights re

os los derechos reservados.

ntroduction

culopharyngeal muscular dystrophy (OPMD) is a late-onsetutosomal dominant muscular illness. Progressive weak-ess of the ocular musculature was described by vonreafe in 1868 as ‘‘external progressive ophthalmoplegia’’.1

served.

466 A. Gómez-Torres et al.

Table 1 Clinical and Epidemiological Characteristics of the Patients.

Patient Gender Age Symptoms Personal History

1 Female 67 Dysphagia +++ Of no interestOperated palpebral ptosisProximal muscle weakness +

2 Female 71 Dysphagia +++ Of no interestOperated palpebral ptosisProximal muscle weakness +

3 Female 72 Dysphagia ++ Of no interestPalpebral ptosis

4 Male 78 Dysphagia ++ Raised bloodpressurePalpebral ptosis

5 Male 58 Dysphagia ++ Of no interestPalpebral ptosis

6 Male 57 Dysphagia ++ Of no interestPalpebral ptosis

Opbntfemegoopi

M

WpdsaOa

reseaA

R

CiFSomo

mmT(rt

rsrtTtr

D

Opmcst1wC2Ctgbipaw

+: mild symptom; ++: moderate symptom; +++: severe symptom.

PMD causes palpebral ptosis, oropharyngeal dysphagia androximal weakness in the limbs. OPMD was finally describedy Taylor in 1915.2 The incidence and prevalence of this ill-ess are very low, but cases have been reported all overhe world. The population most affected by OPMD is to beound in the Quebec region of Canada, with a prevalencestimated at 1:10003 and in Israeli immigrants, with an esti-ated prevalence of 1:600.4 OPMD is caused by the short

xpansion of the repeated triplet (GCG) 8---13 in the PABPN1ene located in chromosome 14.5 In this paper, we reportn 6 patients, 3 of them from the same family, referred tour department with a confirmed diagnosis of OPMD for theerformance of cricopharyngeal myotomy (CM) in order tomprove swallowing.

aterials and Methods

e conducted a prospective observational study of 6atients diagnosed as having OPMD and referred to ourepartment for assessment of surgery as treatment for theirymptoms. The diagnosis had been genetically confirmed inll patients. Following surgery, they were monitored via thetorhinolaryngology Out-Patients Clinic. Patients’ clinicalnd epidemiological characteristics are listed in Table 1.

During the surgical procedure, a sample of the cricopha-yngeal and sternocleidomastoid muscles was taken fromach patient for study by pathologists. These samples wereubjected to the normal tests for muscles (haematoxylin-osin, Gomori’s trichromic test, Oil Red O and PAS), as wells special histoenzymatic techniques (COX, SDH, NADH andTPases 9.4, 4.6 and 4.3) (Figs. 1---3).

esults

M was performed on all 6 patients. The approach consistedn a right cervicotomy, after placement of an inflatedoley catheter at the level of the Upper Oesophageal

phincter (UOS), followed by exposure and identificationf the cricopharyngeal muscle, and the performance ofyotomy on the latter. Patients were discharged with-

ut complications the day after the procedure and were

csta

onitored through the ENT Out-Patient Clinic, with a mini-um follow-up of 18 months and a maximum of 37 months.he improvement in dysphagia was moderate in 2 patients33.3%) and considerable in the other four (66.6%). Theesults obtained and the review fibroendoscopic examina-ions are shown in Table 2.

The pathology study of the cricopharyngeal muscleevealed severe atrophy of the muscle fibres, with fibro-is and adipose substitution, with identification of vacuolesimmed with basophilic material, characteristic of OPMD;here was neither necrosis nor inflammatory infiltrates.here were much more discreet in the sternocleidomas-oid muscle, with no fibrosis but some atrophic fibres withimmed vacuoles.

iscussion

PMD is an autosomal dominant myopathic disorder causingalpebral ptosis, oculopharyngeal dysphagia and proximaluscle weakness. This disease is included within those

aused by triplet repetition. OPMD is caused by the expan-ion of a GCG triplet located on the first exon of gene 1 inhe polyadenylate binding protein (PABPN1), in chromosome4 (14q11.2---q13).5 Nonetheless, cases have been describedith other mutations and other phenotypes, albeit rarely.6

ases of OPMD have been reported all over the world. The largest populations of these individuals can be found inanada, due to a family of French origin that emigratedo Canada in 1634,3 and among Bukhara Jews who emi-rated to Israel from Uzbekistan.4 Smaller populations haveeen described in Europe and in the United States of Amer-ca. Clinical signs include palpebral ptosis, dysphagia androximal muscle weakness. Palpebral ptosis may precede orppear together with dysphagia in most patients; muscleeakness may appear after ptosis and dysphagia.

Swallowing is a neurophysiologically complex action. The

orrect operation of the UOS is an essential part of correctwallowing; its alteration may lead to potentially life-hreatening dysphagia. Barium meals and video-endoscopyre 2 major tools for determining the severity of dysphagia.

Cricopharyngeal myotomy in the treatment of oculopharyngeal muscular dystrophy 467

Table 2 Results Obtained and Follow-up.

Patient Date of Operation Follow-up,months

Improvementin Dysphagia

Fibroendoscopic Examination

1 October, 2008 37 months ++ Discreet salivary stasis in rightpyriform sinus

2 September, 2009 28 months +++ Paralysis of left vocal cordwith good glottal closure

3 March, 2010 18 months +++ Normal4 March, 2010 18 months ++ Minimal salivary stasis

in pyriform sinuses5 March, 2010 18 months +++ Normal6 March, 2010 18 months +++ Normal

ble im

aH

+: mild improvement; ++: moderate improvement; +++: considera

A manometric study will show repetitive weak contractionsof the hypopharyngeal and oesophageal muscles; relaxation

of the UOS may be delayed and incomplete due to the weak-ness of the hypopharyngeal muscles.7 The role of musclebiopsy has been relegated to a secondary level; no biopsy isnecessary with a complete case history for the individual

ados

Cricopharyngeal muscle

Rimmed vacuole

Figure 1 Patient four. Severe fibrosis can be seen in the cricophathere are rimmed vacuoles; in the sternocleidomastoid muscle, the

provement.

nd the immediate family, and a positive genetic study.owever, when faced with a strong diagnostic suspicion

nd a negative genetic study, the biopsy may clarify theiagnosis.8 Differential diagnosis must include mitochondri-pathies and illnesses affecting neuromuscular transmission,uch as myasthenia gravis.8

Sternocleidomastoid muscle

Rimmed vacuole

ryngeal muscle, with adipose substitution and severe atrophy;fibrosis is mild, with scant rimmed vacuoles.

468 A. Gómez-Torres et al.

Cricopharyngeal muscle Sternocleidomastoid muscle

Rimmed vacuole

s are

odtttimb

t(

ttetout

gai

wi

tfntdsfgm

psdapp

Figure 2 Patient five. The change

There is so far no curative treatment. Treatment consistsf measures to reduce the impact of palpebral ptosis andysphagia, with its subsequent malnutrition. The optimiza-ion of the swallowing process begins with rehabilitationherapy, including advice on food consistency or the posi-ioning of the head during swallowing.9,10 A protein-rich diets recommended for an optimal nutritional balance.11 Pneu-onia due to aspiration is a frequent complication that muste forestalled.12

If the manometric study shows hypertonia of the UOS,reatment with nifedipine (20=40 mg) or isosorbide dinitrate5 mg) may be started.13

Around 80% of patients may benefit from CM, accordingo the series published. However, these studies do not refero the duration of the follow-up of patients.14---17 The pres-nce of dysarthria is a prognostic factor for poor responseo CM.14 In our paper, we have performed clinical follow-upf at least 18 months, with a mean of 22.8 months of follow-p; none of the patients presented dysarthria at the time ofhe procedure.

The injection of botulinum toxin into the cricopharyn-eal muscle, under endoscopy, with 50---100 U per session,chieves paralysis (relaxation) of the muscle and swallowingn a few days. The disadvantage is that the effect gradually

bwCp

less marked with respect to Fig. 1.

ears off, but the sessions can be repeated.13 It is indicatedn patients at high risk for surgery.18

Percutaneous gastrostomy constitutes the definitivereatment for dysphagia but definitively alters the patient’seeding through the natural route.8 Nonetheless, percuta-eous gastrostomy does not completely prevent aspiration;he use of a jejunostomy catheter during gastrostomyiminishes the risk of aspiration with respect to atandard gastrostomy catheter. Baseline aspiration (i.e. non-ood-related aspiration) is still present in patients withastrostomy. Gastrostomy in patients with altered sensitivityay increase the risk of aspiration.19

Gastrostomy improves quality of life and longevity inatients with muscular dystrophy. Its use should be con-idered in the following situations: (1) initial stages ofysphagia, prior to gradual weight loss, and pulmonarylteration; and (2) during peri-operative periods in whichatients must be checked exhaustively due to their unstableulmonary status.20

In our case, CM was performed on all 6 patients. After

eing discharged the day after the surgical procedure, theyere monitored via the Ear, Nose and Throat Out-Patientslinic. The improvement in dysphagia was moderate in 2atients (33.3%) and considerable in the other 4 patients

Cricopharyngeal myotomy in the treatment of oculopharyngeal m

1

1

1

1

1

1

1

1

1

1

Figure 3 Patient five. Enlarged image of rimmed vacuoles.

(66.6%). In terms of complications, one patient presentedparamedian paralysis of the left vocal cord, but with goodcompensation in the contralateral cord and good glottal clo-sure. Patients improved in terms of choking and aspirationepisodes. None of the patients have required any other kindof endoscopic treatment or open surgery, they merely con-tinue with swallowing therapy.

In summary, CM must be considered as a good method fortreating dysphagia in patients with OPMD and a moderatelyor severely compromised swallowing function as it elimi-nates the barrier effect present at the level of this muscle(Figs. 1---3).

Conflict of Interest

The authors have no conflict of interests to declare.

References

1. von Graefe A. Verhandlungen ärztlicher Gesellschaften: Sitzungvom 19 Der Berliner medizinischen Gesellschaft. Berl KlinWochenschr. 1868;5:127.

2. Taylor EW. Progressive vagus-glossopharyngeal paralysis withptosis. A contribution to the group of family diseases. J NervMent Dis. 1915;42:124---39.

3. Duranceau AC, Beauchamp G, Jamieson GG, Barbeau A. Orop-

haryngeal dysphagia and oculopharyngeal muscular dystrophy.Surg Clin North Am. 1983;63:825---32.

4. Blumen SC, Sadeh M, Korczyn AD, Rouche A, Nisipeanu P,Asherov A, et al. Intranuclear inclusions in oculopharyngeal

2

uscular dystrophy 469

muscular dystrophy among Bukhara Jews. Neurology. 1996;46:1324---8.

5. Brais B, Bouchard JP, Xie YG, Rochefort DL, Chrétien N, ToméFM, et al. Short GCG expansions in the PABP2 gene cause ocu-lopharyngeal muscular dystrophy. Nat Genet. 1998;18:164---7.

6. Blumen SC, Brais B, Korczyn AD, Medisnky S, Chapman J,Asherov A, et al. Homoczygotes for oculopharyngeal muscu-lar dystrophy have a severe form of the disease. Ann Neurol.1999;46:115---8.

7. Young EC, Durant-Jones L. Gradual onset of dysphagia: a studyof patients with oculopharyngeal muscular dystrophy. Dyspha-gia. 1997;12:196---201.

8. Ruegg S, Lehky H, Hohl U, Kappos L, Fuhr P, Plasilov M, et al.Oculopharyngeal muscular dystrophy----an under diagnosed dis-order. Swiss Med Wkly. 2005;135:574---86.

9. Domenech E, Kelly J. Swallowing disorders. Med Clin North Am.1999;83:97---113.

0. Palmer J, Drennan J, Baba M. Evaluation and treatment of swal-lowing impairments. Am Fam Physician. 2000;61:2453---62.

1. Schindler A, Grosso E, Tiddia C, Cavalot AI, Ricca G, Otta-viani F, et al. Swallowing disorders: management data. ActaOtolaryngol Ital. 2003;23:180---4.

2. Bumm K, Zenker M, Bozzato A. Oculopharyngeal musculardystrophy as a rare differential diagnosis for unexplained dys-phagia: a case report. Cases J. 2009;28:94.

3. Hernández-Montero E, Mesa-Marrero M, de Frías-Berzosa G,Rivas-Lacarte P. Distrofia muscular óculo-faríngea: presentaciónde un caso y revisión de la literatura. Acta Otorrinolaringol Esp.2011. http://dx.doi.org/10.1016/j.otorri.2011.04.005.

4. Poirier NC, Bonavina L, Taillefer R, Nosadini A, Peracchia A,Duranceau A. Cricopharyngeal myotomy for neurogenic orop-haryngeal dysphagia. J Thorac Cardiovasc Surg. 1997;113:233---41.

5. Duranceau A. Cricopharyngeal myotomy in the managementof neuogenic and muscular dysphagia. Neuromuscul Disord.1997;7:85---9.

6. Fradet G, Pouliot D, Robichaud R, St-Pierre S, Bouchard JP.Upper esophageal sphincter myotomy in oculopharyngeal mus-cular dystrophy: long-term clinical results. Neuromuscul Disord.1997;7:90---5.

7. Périé S, Eymard B, Laccourreye L, Chaussade S, Fardeau M, St-Guily JL. Dysphagia in oculopharyngeal muscular dystrophy: aseries of 22 French cases. Neuromuscul Disord. 1997;7:96---9.

8. Clavé P, Arreola V, Velasco M, Quer M, Castellvi JM, García PerisP, et al. Diagnóstico y tratamiento de la disfagia orofaríngeafuncional. Aspectos de interés para el cirujano digestivo. CirEsp. 2007;82:62---76.

9. Carrau RL, Murry T. Evaluation and management of adult dys-phagia and aspiration. Curr Opin Otolaryngol Head Neck Surg.2000;8:489---96.

0. Mizuno T, Komaki H, Sasaki T, Tokanoha S, Kuroda K, KonK, et al. Efficacy and tolerance of gastrostomy feedingin Japanese musculardystrophy patients. Brain Dev. 2011.http://dx.doi.org/10.1016/j.braindev.2011.11.012.