ASSOCIATIONS BETWEEN AUTONOMIC DYSFUNCTION, COLONIC DYSMOTILITY AND ABSENT DEFECATION REFLEXES IN PATIENTS WITH CHRONIC REFRACTORY CONSTIPATION

摘要

Background A defecation reflex involves sensory information from the colon sent to the central nervous system which results in propulsive motor patterns in the colon through programmed neural activity from the autonomic nervous system. Neurological causes of constipation are recognized but specific neurological pathways that contribute to pathophysiology of the disease is underexplored. Diagnosis and treatment usually do not involve the autonomic nervous system. Aims Our objective was to assess autonomic dysfunction and abnormal defecation reflexes as a possible cause of chronic constipation. Methods Defecation reflexes were assessed by high-resolution colonic manometry through balloon distention, meal intake, and rectal bisacodyl. Specific heart rate variability (HRV) parameters were used to assess general orthostatic autonomic reactivity, and autonomic functioning during high resolution colonic manometry, in 14 patients with chronic refractory constipation considered for surgery. Results All patients had a unique combination of motility, reflex ability and HRV profiles. Patients overall did not generate HAPWs or had lower HAPW amplitude and lower propulsive activity compared to healthy individuals. Half of the 14 patients were tested to have high sympathetic tone based on Baevsky’s stress index prior to HRCM, and 11 of the patients had sympathetic hyper-reactivity and/or low parasympathetic reactivity to at least one type of colonic stimulation during HRCM. Abnormal autonomic tone or autonomic reactivity to colonic stimulation was present in all four patients with absence of the vagosacral defecation reflex. Five of the seven patients with absence of the sacral defecation reflex showed high sympathetic tone or high sympathetic reactivity to stimulation. Only two patients had abnormality in coloanal coordination and this was associated with low parasympathetic reactivity to stimulation in both patients. Conclusions The assumption that colonic resection was needed to remove an inert colon was wrong in most patients, but most patients had some form of reflex abnormality. Sympathetic dominance far outweighed parasympathetic dysfunction. Incorporation of assessments of defecation reflexes and autonomic nervous system activity into diagnosis of chronic refractory constipation provides a comprehensive pathophysiological understanding of specific defective neurological pathways contributing to dysmotility. This forms the basis for our individualized treatment efforts through sacral neuromodulation. Open in new tab Download slide (A and B) Proximal balloon distention initiated HAPWs propagating from the proximal colon to the splenic flexure without relaxation of the anal sphincters, showing abnormal coloanal coordination in a patient with low parasympathetic reactivity, represented by respiratory sinus arrhythmia (RSA), during HRCM.(C and D) Five patients with absence of sacral defecation reflex showing high sympathetic activity to parasympathetic activity ratio during orthostatic autonomic assessment and/or HRCM interventions, reflected by the ratio of Baevsky’s Stress Index (SI) to RSA.Dashed lines are the normal range, mean ± 1 SD obtained from 34 healthy subjects for orthostatic assessment (C) and 11 healthy subjects during HRCM (B and D). Open in new tab Download slide (A and B) Proximal balloon distention initiated HAPWs propagating from the proximal colon to the splenic flexure without relaxation of the anal sphincters, showing abnormal coloanal coordination in a patient with low parasympathetic reactivity, represented by respiratory sinus arrhythmia (RSA), during HRCM.(C and D) Five patients with absence of sacral defecation reflex showing high sympathetic activity to parasympathetic activity ratio during orthostatic autonomic assessment and/or HRCM interventions, reflected by the ratio of Baevsky’s Stress Index (SI) to RSA.Dashed lines are the normal range, mean ± 1 SD obtained from 34 healthy subjects for orthostatic assessment (C) and 11 healthy subjects during HRCM (B and D).