A recent retrospective study (LN Zhang et al. J Pediatr 2019; 205: 133-44) reviewed the records of 103 consecutive children with orthostatic intolerance and gastrointestinal symptoms, all of whom had undergone antroduodenal manometry (ADM). The median age was 17 years with a 3:1 female predominance. The same group has published a smaller study in 2016 with 35 children (A Darbari et al JPGN 2016; 63: 329-35).
In their methods, the authors stated that neurogenic intestinal dysmotility was diagnosed if there was
1. lack of fasting MMC III
2. presence of simultaneous nonpropagative or retrograde phases
3. prolonged >30 min high amplitude clusters in duodenum
4. increase in basal tone >30 mmHg for >3 minutes during phase II MMC in a fasting state
5. lack of conversion from fasting MMC-III to fed MMC-II after meals
6. bursts of nonpropagating phase contractions w/in 30 minutes of meals
- At baseline, the authors state that 12 (12%) had neurogenic intestinal dysmotility and 8 (8%) had significant antral hypomoility.
- When ADM was undertaken in conjunction with tilt testing, the authors identified neurogenic intestinal dysmotility in 51 (50%), rumination/regurgitation in 23 (22%), and visceral hyperalgesia in 11 (11%).
- Abnormalities in ADM did not have any correlation with abnormal gastric emptying studies (GES)s (which were performed in 83 of 103). For example, among those with abnormal ADM (n=83), 48 (73%) had normal GES. And, among those with normal GES (n=58), 48 (83%) had abnormal ADM.
- “Analysis of EGD biopsy samples revealed nonspecific esophagitis and/or gastritis in 16 of 103 patients (15%)”
While this research provides some insight into why children with orthostatic intolerance may have gastrointestinal symptoms, I remain skeptical of the usefulness of ADM as a routine study in clinical practice. The authors claim that ADM has ‘potential importance…in its utility in targeting future therapies.’
There are many hurdles, in my view, in making these studies worthwhile clinically:
- More uniformity in interpretation of ADM studies. I do not have specialized neurogastroenterology training, but my understanding is that the difference between normal and abnormal is often blurry.
- More effective motility agents including prokinetics and agents to improve visceral hyperalgesia. How helpful is it to identify subtle manometric abnormalities without effective therapeutic agents?
- If GI problems are only demonstrated during tilt testing, how important is this? I suspect that many individuals would have abnormalities if ADM was done while they were on a roller coaster, but I doubt that this would help me determine treatment for GI symptoms induced by this type of stimulus.
My take: This study confirms that EGDs are rarely useful in this setting and suggests that ADM could be. While the study identifies frequent abnormalities when ADM was combined with tilt testing, it remains uncertain whether this will improve clinical management.
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While a recent study (A Darbari et al JPGN 2016; 63: 329-35) provides some interesting data regarding the potential origin of gastrointestinal symptoms in the setting of orthostatic intolerance, I cannot support their conclusion that antroduodenal manometry (ADM) “should” be part of the evaluation of these affected children.
- Retrospective study which included only subjects with a positive tilt test
- Among 35 children with orthostatic intolerance due to either neurally mediated hypotension (NMH) or postural orthostatic tachycardia syndrome (POTS), ADM was abnormal at baseline or during tilt table testing in 26 (75%).
- ADM studies were more often abnormal than gastric emptying studies, which were normal in 12 or 25.
- Specific findings included neurogenic intestinal dysmotility in 15, antral hypomotility in 4, visceral hyperalgesia in 2, and regurgitation in 5.
- GI symptoms of nausea, abdominal pain or vomiting were reproduced during tilt testing in 31 of 35 patients (89%).
Based on the discussion, the authors imply that ADM testing could help determine if the symptoms are due to neurogastrointestinal pathology or if normal, could indicate a central origin for the GI symptoms. Thus, they conclude that motility testing “should” be part of comprehensive” orthostatic intolerance evaluation.
I would argue that this study does not show that ADM testing can reliably distinguish whether symptoms are due to a neurogastroenterological pathology or central pathology. And, in fact, there are better tests to examine for central origin. I wouldn’t be surprised if many of their subjects had brain imaging, though this is not reported.
In addition, the authors acknowledge that ADM testing may not influence therapeutic decisions. “The clinical response to promotility agents in children with POTS is generally low.”
My take: This study provides a useful mechanistic explanation of symptoms associated with orthostatic intolerance. However, “I’m not there yet” on supporting ADM for all children with OI.
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