Mucosal nerve deficiency in chronic childhood constipation: a postmigration defect?
OBJECTIVE
Idiopathic chronic childhood constipation (ICCC) includes children who are severely constipated and who are resistant to behavioral or medical treatments. These children are distinguished from those with Hirschsprung's disease (HSCR) by the presence of enteric ganglia in rectal biopsy specimens. We investigated potential autonomic dysfunction by examining nerves in rectal mucosa.


METHODS
Immunostaining, confocal microscopy, and nerve analysis were performed on formalin-fixed and on Zamboni-fixed rectal biopsy specimens from children who were severely constipated. A computer-assisted neuron tracing technique was used to determine mucosal nerve density in Zamboni-fixed biopsy sections.


RESULTS
Nerves in Zamboni-fixed biopsy specimens were better stained than in formalin-fixed biopsy specimens. Regardless of fixation method, a deficiency of mucosal nerves was observed in ICCC when compared to children who are not constipated. Analysis of autotraced mucosal nerves confirmed the deficiency in ICCC biopsy specimens. Mucosal nerves were also severely deficient in patients with HSCR, even in transitional segments that contained ganglia.


CONCLUSIONS
Most patients with ICCC had decreased innervation of the rectal mucosa. Because mucosal nerves are critical for the peristaltic reflex, water secretion, and absorption, their deficiency can be related to patient constipation. Mucosal nerve density provides a pathologic basis for diagnosis of dysfunction in children who do not have HSCR but are chronically constipated. The study validates the neuron tracing method for objective evaluation of mucosal innervation.
Wendelschafer-Crabb
Gwen
G
Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. crabb001@umn.edu
Neppalli
Vishala
V
Jessurun
Jose
J
Hodges
James
J
Vance
Karl
K
Saltzman
Daniel
D
Acton
Robert
R
Kennedy
William R
WR
D000293:Adolescent; D001707:Biopsy, Needle; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003248:Constipation / Q000175:diagnosis / Q000473:pathology*; D003937:Diagnosis, Differential; D017615:Enteric Nervous System / Q000503:physiopathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006627:Hirschsprung Disease / Q000175:diagnosis / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007413:Intestinal Mucosa / Q000294:innervation* / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D016065:Myoelectric Complex, Migrating / Q000502:physiology; D016612:Paraffin Embedding; D011336:Probability; D012007:Rectum / Q000294:innervation* / Q000473:pathology; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric