Does the absence of neural abnormalities in DES allow to exclude a neurogenic origin ?
K. Geboes, N. Ectors, J. Mebis (Leuven), I. El-Dosoky (Mansoura)
The term « diffuse spasm of the lower part of the esophagus » was used for the first time by Moersch and Camp in 1934 , for a neuromuscular motor disorder of the esophagus characterized by substernal distress or dysphagia. The disease has since been described under various names such as localized esophageal spasm, muscular hypertrophy of the esophagus, hypertensive gastroesophageal sphincter, but the term « diffuse esophageal spasm » is at present generally accepted. Muscular thickening, especially of the internal layer of the esophageal musculosa and of the muscularis mucosae, has been observed in most cases. The primary lesion responsible for this disease is unknown, and only limited pathologic data are available.
Sparsity of the submucosal plexus has occasionally been described , but this plexus is usually not extensively studied.
Most histological studies have not disclosed significant changes of Auerbach's plexus [3, 4]. A mild increase in small round cells in and sometimes around the plexus has been interpreted as evidence for inflammation [5, 6, 7], but the possibility that these cells are Schwann cells or so-called satellite cells, remains. Neuronal loss and chromatolysis have been described in one study  but this finding has not been confirmed. In fact, ganglion cells are often not seen  or not accurately evaluated because of the limited size of myotomy specimens. Therefore, their appearance is frequently not discussed [10-12], The same is true for intramural nerve endings. They are reported to be normal , slightly reduced in number, but with normal morphology  or not discussed .
According to an electron microscopic study, the nerve endings are completely normal. In the three cases described by Faussone-Pellegrini, it is mentioned that the synaptic vesicles are normal and that the contacts with the interstitial cells of Cajal are well preserved. Electron microscopic evidence for Wallerian degeneration of afferent vagal nerve fibers has been reported twice [11, 13]. In diffuse esophageal spasm, the lesions were considered to be generalized in contrast with the focal involvement in cases of achalasia, but these findings were not confirmed. Alterations of the « interstitial cells of Cajal » have been described in 3 cases. These alterations include a slight reduction in number of cells but an increase in mitochondria, as well as the presence of a well developed smooth endoplasmic reticulum. The latter two features can be considered to be a sign of hyperactivity.
According to these findings, the sequence : nerve endings-interstitial cells of Cajal-smooth muscle cells, seems intact, like in the normal esophagus, but all interstitial cells of Cajal would be hyperfunctioning.
In conclusion, we can say that, at present time, we have only limited data on the pathology of diffuse esophageal spasm. This is due to the rarity and the very nature of the disease. Surgical treatment is not always considered and, if surgery is performed, the treatment is usually a myotomy and hence the biopsy specimen
is of limited size. Adequate evaluation of the intramural nerve plexus and of the extrinsic innervation is difficult in these specimens. Yet, from the data available, it does not appear that major alterations of the innervation are present.
We can however today not yet completely rule out a neurologic origin for diffuse esophageal spasm, as we do neither know the precise microanatomy of the intramural nerve plexus in this condition, nor the morphological behavior of various neuro-peptides (functional evaluation) or neurofilaments (structural evaluation) and other morphologic parameters of the plexus.
9. Faussone-Pellegrini MS, Cortesini C (1985) The muscle coat of the lower esophageal sphincter in patients with achalasia and hypertensive sphincter. An electron microscopic study. J Submicrosc Cytol 17: 673-685.