Autoimmune encephalitis and gastrointestinal dysmotility: achalasia, gastroparesis, and slow transit constipation

Background Neurological autoimmune disorders (NAD) are caused by autoimmune inflammation triggered by specific antibody subtypes. NAD may disturb the gut-brain axis at several levels including brain, spinal cord, peripheral, or enteric nervous system. Case report We present a case with antinuclear neuronal Hu (ANNA-1)- and antiglial nuclear (SOX-1) autoimmune antibody-positive limbic encephalitis and significant gastrointestinal dysmotility consisting of achalasia type II, gastroparesis, altered small intestinal interdigestive motility, and severe slow transit constipation. The autoantibodies of the patient’s serum labeled enteric neurons and interstitial cells of Cajal but no other cells in the gut wall. Achalasia was treated successfully by pneumatic cardia dilation and gastrointestinal dysmotility successfully with prucalopride. Conclusion NAD may disturb gastrointestinal motility by altering various levels of the gut-brain axis.

Vagal innervation modulates motor pattern but not initiation of canine gastric migrating motor complex

To determine the role of vagal nerves in initiation and modulation of the gastric migrating motor complex (MMC), motor activity was recorded in four dogs before and after total abdominal vagotomy during fasting, after exogenous intravenous motilin and insulin, and after feeding. After vagotomy, a temporally coordinated cyclic gastric and small bowel MMC persisted with an unchanged period. During gastric phase III, vagotomy decreased number of contractions (42 ± 4 vs. 16 ± 2), number of groupings of contractions (14 ± 1 vs. 7 ± 1), and motility index (12 ± 1 vs. 10 ± 1) and increased the duration between groupings (1 ± 1 vs. 3 ± 1 min) ( P< 0.05 in each). Before and after vagotomy, motilin and insulin induced a premature MMC with minor changes in contractile pattern. A 200-g liver meal but not a 50-g liver meal inhibited the gastric MMC after vagotomy. A cyclic MMC persisted after vagotomy, but the contractile pattern during gastric phase III was altered. After a short recovery period, vagal innervation to the stomach modulates the pattern but not the presence of gastric interdigestive motility during phase III.

Actions of the 5-hydroxytryptamine 1 receptor agonist sumatriptan on interdigestive gastrointestinal motility in man

Background—Pharmacological studies of the enteric nervous system have shown the presence of several subtypes of 5-hydroxytryptamine (5HT) receptor, which might be involved in control of the migrating motor complex.Aims—To study the effect of sumatriptan, an agonist of enteric neuronal 5HT1P receptors, on interdigestive motility in man.Subjects and methods—In 12 healthy subjects, interdigestive motility was recorded manometrically in the upper gastrointestinal tract. In seven subjects blood samples were drawn every 15 minutes for radioimmunoassay of motilin and somatostatin. After two phase 3s of the migrating motor complex, 6 mg of sumatriptan was administered subcutaneously. Recording continued until two more phase 3s had occurred.Results—Sumatriptan induced a premature phase 3 in the jejunum after a median of 10 (8) minutes. The duration of the migrating motor complex cycle was shortened at the expense of phase 2. After sumatriptan, plasma somatostatin concentrations were reduced and gastric phase 3s were suppressed, although median motilin concentrations and the occurrence of plasma motilin peaks were not affected. Phase 3s of the migrating motor complex preceding sumatriptan were associated with motilin peaks, while phase 3s after sumatriptan were not. Furthermore, pretreatment with sumatriptan prevented the induction of a gastric phase 3 by the motilin agonist erythromycin.Conclusions—Administration of the 5HT1P receptor agonist sumatriptan induces a premature intestinal phase 3, suppresses gastric phase 3s, prevents induct- ion of a gastric phase 3 by erythromycin, and reduces plasma somatostatin concentrations.

Mechanisms behind changes in gastric acid and bicarbonate outputs during the human interdigestive motility cycle

Human gastric interdigestive acid and bicarbonate outputs vary cyclically in association with the migrating motor complex (MMC). These phenomena were studied in 26 healthy volunteers by constant-flow gastric perfusion, with continuous recording of pH and Pco2 in mixed gastric effluent and concomitant open-tip manometry of gastroduodenal motility. Stable acid and bicarbonate outputs were registered during less than 50% of the MMC cycle. Acid secretion started to increase 71 +/- 3% into the cycle, with maximum output during antral phase III. Bicarbonate output increased biphasically 1) 40 +/- 5% into the cycle, coinciding with reflux of bile, and 2) at the end of duodenal phase III when the aspirate was devoid of bile. The bicarbonate peak associated with phase III was abolished by atropine (0.01 mg/kg iv, n = 8) and by pyloric occlusion (n = 9) but remained unchanged after omeprazole (n = 10). The acid peak was abolished by both atropine and omeprazole. It is concluded that the MMC-related changes in acid and alkaline outputs represent two different and independent phenomena. Acid secretion cyclicity is due to periodical variations in cholinergic stimulation of the parietal cells. In contrast, the phase III-associated increase in bicarbonate output is due to duodenogastric reflux.

Duodenal pH governs interdigestive motility in humans

In this study, we examined the potential influence of duodenal pH in regulating the occurrence of the interdigestive migrating myoelectric complex (IMMC). Fasting gastroduodenal motility, duodenal pH, and plasma motilin were studied in 15 healthy subjects. During phase I, duodenal pH remained stable at 7 +/- 0.2. Phase II was accompanied by a lowering of duodenal pH, which fluctuated between 2.0 and 7.5. During late phase II, the duodenal pH increased to 6.9 +/- 0.3 and remained in the alkaline range during phase III. In six of 46 episodes of the IMMC, the occurrence of gastric phase III was delayed. This was associated with a persistently low duodenal pH (< 4) during late phase II. Despite a normal cyclic increase of plasma motilin, no gastric phase III activity was observed until the duodenal pH exceeded 7.0. Further studies showed that lowering of duodenal pH by intraduodenal perfusion of HCl prevented the occurrence of gastric phase III. We concluded that regularity of IMMC is governed by duodenal pH. An alkaline pH is essential for the initiation of gastric phase III; lowering of duodenal pH prevents its occurrence despite normal cyclic increase of plasma motilin.