Gut, 1987, 28, 1522-1526

Case report

Achalasia like disorder of the oesophagus in vonRecklinghausen's neurofibromatosisP N FOSTER, MARGARET STEWART, J S LOWE,AND MICHAEL ATKINSON

From the University Hospital, Quieen 's Medical Centre, Nottinighamtl

SUMMARY The association of achalasia like disorder of the oesophagus with von Recklinghausen'sneurofibromatosis to our knowledge not previously reported is described in a 56 year old man whoalso had bladder dysfunction. At necropsy the oesophageal myenteric plexus showed ganglion celldepletion with nerve fibre hyperplasia probably the result of Schwann cell hyperplasia. We suggestthat the disturbances of oesophageal and bladder function were a consequence of involvement ofthe autonomic nervous system by neurofibromatosis.

Neurofibromatosis has been estimated to be presentin one person in 3000 of the population at birth and25%'/ of those with the disease have been reported tohave alimentary involvement.' Most of these haveneoplasm, predominantly neurofibroma with someleiomyoma, but megacolon from involvement of theautonomic nervous system, by neurofibromatosis, isa well established entity. We report a patient with anachalasia like disorder of the oesophagus and withbladder dysfunction complicating hereditary neuro-fibromatosis.

Case report

A 56 year old man with neurofibromatosis (Fig. 1)presented in acute renal failure as a result of urinaryretention with a blood urea of 73 mmol/l, potassium7.6 mmol/l, sodium 129 mmol/l. His mother and amaternal stepbrother also suffered from neuro-fibromatosis. Catheterisation of the bladder resultedin the drainage of 4450 ml urine and the blood ureaand electrolytes returned to normal concentrations.Myelography excluded cord compression. An intra-venous urogram revealed normal sized kidneys andno pelvicalyceal or ureteric dilatation. At cystoscopythe bladder was seen to be trabeculated and hadmany diverticula; the prostate appeared small andthe serum acid phosphatase (7 U/I) and tartrate labilefraction (2 U/I) were normal. He subsequently under-went transurethral resection of the prostate.Addrcss for corrcspoiidicnicc I)r P N Fo.tcr (iG strointcesinl 1 tIt I 1c(Gcncral Ilnfirmirv (Grcat (icorge Sftrect Leeds S IXRcccivedfor puhlicition 6 April 1987.

In addition to his immediate genitourinary prob-lems, the patient mentioned that for several years hehad had difficulty in swallowing both liquids andsolids and occasionally he regurgitated food that hehad eaten as long as 48 hours previously. Chestradiograph showed an air containing mediastinalmass. A barium swallow (Fig. 2) showed a grosslydilated oesophagus filled with food residue, and asmooth, narrowed, distal segment suggestive ofachalasia. Fibreoptic endoscopy revealed a dilatedhypotonic oesophagus containing food debris; thecardia was tightly closed but admitted the instrument(GIFT Olympus) easily.Manometric studies showed that swallowing pro-

duced simultaneous, single waves of low amplitude

Fig. 1 PatetiVt's cutaneous stigmata oJ n1eurofibromatosis.1522

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Achalasia like disorder oft/e oesoplhaiguts in von Recklinig/auasens .s nieurofihromato1sis

Fig. 2 Barium swallow which shows a dilated oesophaguscontaining food residue with a smooth, narrowed distalsegment suggestive ofachalasia.

throughout the oesophagus and no relaxation of thelower oesophageal sphincter. The resting loweroesophageal sphincter pressure was 25 cm H,O. Adiagnosis of achalasia was made and the patientunderwent pneumatic bag dilatation of the cardiawith considerable immediate relief of his dysphagia.

Because of the bladder and oesophageal dysfunc-tion evidence of an autonomic neuropathy was

sought: there was no postural hypotension and pulserate variability with deep respiration was normal. Asearch was made for involvement of the large bowelby barium enema which showed a few diverticula butno other abnormality.Three weeks after discharge from hospital the

patient was readmitted having collapsed at home.Examination revealed that he was deeply uncon-

scious with signs of brain stem dysfunction. Acomputerised tomographic brain scan was suggestiveof a pontine infarct. The patient died 20 hours afteradmission.

NECROPSY FIN DINGS

External examination showed multiple cutaneousneurofibromata.The macroscopic appearances of the oesophagus

were typical of achalasia with dilatation maximal in

the middle third and thickening of the wall. Nostricture or neurofibromata were visible.

Histological examinationi of the oesophagusshowed stratified squamous epithelium, submucosalfibrosis and a mild chronic inflammatory infiltrate.The striated muscle of the upper one third showedevidence of neurogenic atrophy (Fig. 3) whilst thesmooth muscle in the lower two thirds was hyper-trophic. Very few ganglion cells were seen in themyenteric plexus and only four were identified in 22sections taken at 2 cm intervals throughout the lengthof the oesophagus. The nerves of the myentericplexus appeared enlarged because of Schwann celland fibroblast proliferation (Fig. 4).The serosal nerves, including the vagi, were also

enlarged many showing perineural fibrosis and otlhersa plexiform diffuse form of neurofibromatosis(Fig. 5).The remainder of the gastrointestinal tract was

macroscopically normal. Normal numbers ofganglion cells were present in the wall of the rectumand stomach. Small neurofibromata were micro-scopically identified in the gastric serosa. The onlynodular neurofibroma grossly identified on internalexamination was in the abdominal para-aorticregion. There was bilateral mild hydronephroses andhydroureters, and the bladder was enlarged withformation of diverticula. Histological examinationshowed extensive plexiform neurofibromatosisinvolving nerves around the base of the bladder andthe prostate gland (vesical and prostatic plexuses).The brain and spinal cord had detailed neuro-

pathological examination. The mlacroscopic appear-ances were normal, but microscopic examinationshowed terminal hypoxic neuronal cell death in thehippocampus and the cerebellum. No pontine infarc-tion was seen. Neuronal cell counts in the dorsalmotor nuclei of the vagi were within normal limitsalthough there was mild reactive gliosis suggestingthat there may have been a minor degree of neuronalcell death.There were no further relevant findings in the

other viscera.

Discussion

The radiological and manometric features togetherwith the histological oesophageal findings of hypo-ganglionosis, fibrosis with a chronic inflammatorycell infiltrate, and smooth muscle hypertrophy, foundin this patient are typical of achalasia of the cardia.The striking enlargement of myenteric nerve fibresand the neurogenic atrophy of oesophageal striatedmuscle fibres, however, are not features of idiopathicachalasia. To our knowledge this is a hithertounreported association of von Recklinghausen's

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Fig. 3 Oesophageal striated musclefrom the upper third showing neurogenic atrophy and a serosal nerve showing perineuralfibrosi.s. (H and E).

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Fig. 4 Hvpertrophied nerve in the mventeric plexus in the middle third of the oesophagus (H atnd E).

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Fig. 5 Serosal nerve showing partial involvement by neurofibromatosis. (H and E).

neurofibromatosis. In addition this patient hadbladder dysfunction in association with plexiformneurofibromatosis. The likelihood that the disturb-ances of oesophageal and bladder function werecaused by the neurofibromatosis gains supportfrom reports of autonomic dysfunction involvingthe colon'4 and bladder7 in patients with vonRecklinghausen's disease.Where megacolon is associated with neurofibro-

matosis, enlargement of the nerves of the myentericplexus in the colon is a common feature and in onecase which came to necropsy,' these changes werenoted throughout the gastrointestinal tract, includingthe oesophagus. Enlargement of myenteric nervefibres was noted in the oesophagus of our patient.A recent review' states that hypertrophy of themyenteric plexus occurs in 50(% of patients with vonRecklinghausen's disease. Functional gastro-intestinal disturbance is less common, however,although constipation sometimes associated withmegacolon, occurs in about 10% of patients withneurofibromatosis."

Hypoganglionosis in the oesophageal myentericplexus is generally recognised to be a feature ofachalasia although the absolute counts vary widely,"'and in our patient was especially severe. Ganglioncells in the colon of patients with neurofibromatosis

and megacolon are either present in normal" ordecreased4" numbers and Feinstat et al' emphasisedthat the reduction may be patchily distributed. Suchmarked hypoganglionosis, however, as seen in theoesophagus of our patient has not been describedpreviously. Thus it seems unlikely that the hypo-ganglionosis is entirely explicable on the basis ofmyenteric plexus enlargement which was present inour patient and those cases of megacolon previouslyreported. The observation of involvement of serosalnerves with neurofibromatosis and associated neuro-genic atrophy of oesophageal striated muscle raisesthe possibility that the hypoganglionosis may haveresulted from trans-synaptic degeneration, althoughthis is a doubtful entity in the autonomic nervoussystem. Another possibility is that the hypo-ganglionosis results from the abnormal embryo-logical development of neural crest cells, which giverise to cranial and spinal sensory ganglia, sympatheticand parasympathetic plexuses, Schwann cells, andmany other tissues, as proposed by Bolande.

This case report highlights the fact that significantdisturbances of gastrointestinal motility occur inneurofibromatosis as well as the better recognisedassociation of gastrointestinal tumours." Themechanism underlying the abnormal motility is notcertain.

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1526 Foster, Ste wart, Loawe, atndAikinso,i

References

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