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Eur J Cardiothorac Surg 2000;17:101-105
© 2000 Elsevier Science NL

Autonomic dysfunction in non-specific disorders of oesophageal motility

Oesophageal Laboratory, Northern General Hospital, Sheffield S57AU, Yorkshire, UK

Corresponding author. Thoracic Unit, Jubilee Building, Leeds General Infirmary, Leeds LS13EX, UK. Tel.: +44-113-392-5737; fax: +44-113-392-6657

	Abstract

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 
Objective: Non-specific disorders of oesophageal motility are common manometric findings in patients presenting with non-cardiac chest pain, dysphagia, odynophagia, regurgitation and symptoms of gastro-oesophageal reflux disease. Impairment of vagal function has been reported in gastro-oesophageal reflux disease and achalasia. The role of autonomic dysfunction in patients with non-specific oesophageal disorders is unknown. The aim of this study was to assess autonomic function in patients with non-specific disorders of oesophageal motility. Method: An automated computerized system (AUTOCAFT) was used to evaluate autonomic function in 62 patients presenting with non-cardiac chest pain and associated oesophageal symptoms. Cardiovascular reflex responses to deep breathing, Valsalva manoeuvre, posture and sustained handgrip were measured and results compared with 14 sex- and age-matched control subjects. Results: Forty percent of patients with non-specific disorders of oesophageal motility proved to have significant abnormalities of vagal function. There was also a high incidence of gastro-oesophageal reflux (50%). Conclusions: There appears to be autonomic dysfunction in patients with non-specific oesophageal motility disorders. Autonomic function tests may prove to be a useful tool in the assessment of oesophageal function.

Key Words: Autonomic function • Oesophageal manometry • Motility disorder

	1. Introduction

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 
In 1983 Benjamin and Castell proposed the term non-specific oesophageal motility disorder (NSOMD) to describe patients with symptoms suggestive of oesophageal disease who have recognizable manometric abnormalities and do not have systemic disease e.g. diabetes and scleroderma [1]. These manometric abnormalities cannot be readily classified as achalasia, diffuse oesophageal spasm (DOS) or Nutcracker oesophagus by conventional laboratory criteria. Non-specific disorders of motility are idiopathic and are commonly diagnosed in the oesophageal laboratory in patients presenting with oesophageal symptoms and in 20% patients with NCCP [2] Some reports question the validity of NSOMD, others demonstrate that these are permanent motility disorders and are associated with delayed oesophageal clearance [3,4].

Peristaltic abnormalities and spastic activity are commonly seen in patients with gastro-oesophageal reflux disease (GORD) and vagal dysfunction has been implicated as a primary aetiological factor [5].

This study investigates the role of the autonomic system in NSOMD.

	2. Materials and methods

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 
A prospective controlled study of autonomic function was carried out in 62 patients with non-cardiac chest pain (NCCP), symptoms of regurgitation and/or dysphagia (male 22, female 40, mean age 51 years, range 30–72 years). There were 14 healthy volunteers who acted as control subjects (male four, female ten, mean age 38 years, range 31–49 years).

Consent for investigation was obtained in all cases and the study approved by the hospital Ethics Committee. All patients were interviewed with a symptom questionnaire before and after treatment.

Patients with established heart disease, angina, diabetes, rheumatoid arthritis or patients taking cardioactive drugs were excluded from the study.

Oesophageal manometry was performed with a station pull-through technique using a Gaeltec triple miniature transducer probe with sensors at 5-cm intervals. Peristaltic activity in response to ten wet swallows and lower and upper sphincter pressures were recorded. An antimony micro-pH electrode was then placed 5 cm above the manometrically determined proximal border of the lower oesophageal sphincter (LOS) and an ambulatory 24-h pH study carried out using a Synectics Digitrapper. This was downloaded later to a PC and analyzed using Esophagram Version 5.7.

Significant reflux being defined as pH<4 for greater than 4% of the 24-h period and scored according to DeMeester [6].

A non-specific oesophageal motility disorder was manometrically defined as abnormal motility including one or more of the following criteria [7]:

1. increased non-transmitted contractions (>20% wet swallows);
   
2. prolonged duration of peristaltic waves (>6 s);
   
3. retrograde contractions;
   
4. multiple/triple peaked contractions;
   
5. low amplitude swallow waves (<30 mmHg)/synchronous activity;
   
6. isolated incomplete lower oesophageal sphincter relaxation (residual pressure 0.8 mmHg).
   

Autonomic function tests were then carried out. This utilized the Autocaft computerized system for the evaluation of autonomic (sympathetic and parasympathetic) function. Autocaft is a computer programme that provides a fully automated data collection analysis and recall system for a standard set of cardiovascular autonomic nervous function tests continuously recording and analyzing heart rate and blood pressure. The University of Edinburgh (Unived Technologies Ltd.) developed this dedicated programme [8,9].

Three tests assess cardiac parasympathetic function by measuring heart response to deep breathing, standing from the lying position and Valsalva manoeuvre. Two tests assess sympathetic function with continuous blood pressure measurements in response to standing and sustained handgrip. Continuous blood pressure and heart rate monitoring were performed using a Datascope Accutorr 4.

The Valsalva manoeuvre was standardized by asking patients to blow into a mouthpiece attached to a hand held sphygmomanometer maintaining a pressure of 40 mmHg for a timed period of 15 s. The blood pressure response to sustained handgrip was performed using a handgrip dynamometer. Handgrip was sustained at 30% of maximum for as long as possible. Radiological assessment and endoscopy were performed as indicated but not completed in all cases. All patients were asked to complete a simple questionnaire documenting duration of symptoms, medication and satisfaction with treatment given.

The computer-analyzed data was assessed and results categorized into one of four groups according to Ewing and Clarke [9].

(1) Normal, (2) early autonomic damage with results of one of the three heart tests abnormal, (3) definite autonomic damage with results of at least two of the heart tests abnormal and (4) severe damage where in addition to abnormal heart rate tests one or both of the blood pressure tests are abnormal. An autonomic score was given by the programme with 0, 1 or 2 for each borderline or abnormal test giving a potential total score 0–10. A score 2 was significant.

	3. Results

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 
An abnormal autonomic function score was obtained in 24 patients in the study group (40%). A mean autonomic score of 2.5 (range 2–6) suggests early autonomic dysfunction NSOMD. Only one case in the control group had a significant score. A statistical analysis incorporating Fisher's Exact test showed a significant difference between the two groups (P=0.0287).

All 62 patients in the study group were initially diagnosed to have NSOMD on manometry by the oesophageal technician (L.F.S.). However after review by the senior author (J.A.C.T.), 21 recordings were difficult to interpret and did not exactly fulfil the diagnostic criteria for NSOMD as described earlier. Eighteen were reclassified as atypical, 24 NSOMD, 11 hypomotility/low LOSp/HH, three Nutcracker, three Scleroderma, two diffuse oesophageal spasm and one achalasia (Fig. 1).

View larger version (63K): [in this window] [in a new window]   Fig. 1. The incidence of significant gastro-oesophageal reflux and abnormal autonomic function in patients with in the NSOMD group compared with other motility disorders and Control subjects. (+Aft, positive autonomic function tests).

In patients with atypical manometry, 44% had significant reflux and 33% an abnormal autonomic score. This pattern of reflux is very similar to the true NSOMD group. Patients with scleroderma and Nutcracker oesophagus also demonstrated reflux (Fig. 1).

All 24-h pH studies in the control group were normal.

Fibreoptic oesophagogastroscopy was performed in 66% of patients (40/62). Reflux oesophagitis was proven in seven cases. Demonstrable radiological abnormalities e.g. hiatus hernia were recorded in six patients.

A modified DeMeester reflux questionnaire [10] was completed in all cases and duration of symptoms, relief of symptoms, satisfaction with treatment and medication recorded. The symptoms of heartburn, regurgitation, bleeding, dysphagia, dyspepsia, vomiting and nocturnal symptoms were scored on a 0–3 basis (maximum score, 18). The mean score was 8.4 with dysphagia the most prominent symptom. There was poor correlation between symptoms and the outcome of investigations.

Twenty-eight patients were worse, 24 improved and ten had no change. Twenty-nine patients were satisfied with their management (69%). The majority of patients were taking proton pump inhibitors alone or in combination with simple antacids or prokinetic agents.

	4. Discussion

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 
There is yet no ideal classification for oesophageal motility disorders that has a pathological basis.

Achalasia, scleroderma, Chagas disease represent ‘classical’ diseases in which identifiable and specific pathological changes can be recognized clinically, radiologically, manometrically and at histopathology [11]. The remaining motility disorders e.g. diffuse oesophageal spasm (DOS), Nutcracker oesophagus, hypertensive LOS and NSOMD have no readily identifiable aetiology or pathology. They are diagnosed clinically on their manometric patterns (Table 1) [7].

Many oesophageal disorders do not fulfil the current recording criteria for the ‘classical’ disorders of oesophageal motility and are therefore termed NSOMD. These disorders are commonly diagnosed in the oesophageal laboratory especially in patients with non-cardiac chest pain and odynophagia. Although initially considered as artefact, NSOMD have increasing clinical relevance as these motility disorders are usually not transient on follow up manometry and patients have continued symptoms at 2–5-year follow-up [3]. NSOMD are characterized manometrically by increased non-transmitted episodes, low amplitude peristalsis, low amplitude spastic activity and isolated incomplete LOS relaxation. Little research has been done in this group of patients.

There is increasing evidence that the innervation of the oesophagus is impaired in patients with GORD and this also contributes to delay in oesophageal clearance and gastric emptying [5]. Vagal stimulation studies in the canine model and in man have shown vagal impairment in hiatal hernia, GORD and in other motility disorders [14].

In achalasia, Chagas disease and DOS there is evidence of inflammatory cell infiltration, fibrosis and damage to the intrinsic nervous system of the oesophagus especially in Auerbachs plexus. Immunoglobulin deposition has also been identified around nerve endings. These histological changes reinforce the concept of neuronal damage, which may be primary or secondary [15,16]. Denervation may be an important factor in the aetiology of motility disorder. DOS and Nutcracker oesophagus have been reported to evolve into achalasia and it is not uncommon in the laboratory to see changing patterns of motility disturbance [17,18]. The variety of motility disorders seen clinically may reflect varying degrees of autonomic denervation.

Little research has been performed on the role of the extrinsic and intrinsic nervous system of the oesophagus and the contribution of the autonomic system [19,20].

Autonomic dysfunction plays a major role in the pathophysiology of many medical conditions e.g. diabetes mellitus, sleep apnoea, cardiac failure [21,22]. Cardiovascular reflex tests are now well established in the clinical evaluation of autonomic dysfunction and the development of non-invasive techniques with computerized systems have proved reliable [23]. The Autocaft programme is cheap, effective, reproducible and not operator dependant [23]. Autonomic function tests have not previously been used in the oesophageal laboratory although radiological oesophageal motility abnormalities have been associated with diabetic neuropathy [24].

This study has investigated autonomic function in a group of patients with NSOMD and the results demonstrate a high incidence of abnormal vagal function. The motility patterns in patients with NSOMD are variable and achalasia, scleroderma, nutcracker oesophagus and reflux associated dysmotilty should be carefully excluded.

Measurement of autonomic function in patients with oesophageal motility disorders may prove to be an important tool in the oesophageal laboratory and may be of value in further classifying motility disorders.

The presence of significant reflux in this group is a complicating factor. In a recent study NSOMD are more likely to be associated with GOR than with a normal pH study. Also the greater number of normal amplitude contractions in patients with NSOMD the less the degree of reflux [25]. Gastro-oesophageal reflux may be an important trigger in the development of NSOMD and further research should be aimed at evaluating its relevance.

Many patients have symptoms despite medication and have persistent abnormalities at follow up manometry. In this study the DeMeester reflux questionnaire was used to score patients symptoms before and after treatment. This has been shown to be a useful scoring system [10]. However in patients with motility disorders there appears to be a poor correlation between score and the outcome of investigations. This suggests that NSOMD are significant and not merely artefact and further research should attempt to define these abnormalities more clearly. Ineffective motility commonly occurs when peristaltic amplitude is less than 30 mmHg and this has been a primary finding in patients with NSOMD [26]. These studies suggest that NSOMD represent a significant motility disorder.

Treatment relies on the intelligent use of antacids, prokinetic agents and nitrates. Surgical intervention is rarely necessary although in carefully selected patients oesophageal dilatation and oesophagomyotomy may be of benefit [27].

	Acknowledgments

 
I would like to thank Hans Borst and the European Society of Cardio-thoracic Surgeons for providing a travelling grant for Dr Ainis Pirtniecks of Latvia to visit a Thoracic Unit in the UK and to enable him to participate in this project. The Northern General Hospital research committee also kindly gave financial support.

	References

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 

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