Periodically I will hear from a patient about excess bloating. They are not alone. The gastrointestinal (GI) system is involved to some degree in over 90% of patients with Parkinson disease (PD), which has been discussed here in MPDN. (1-3) GI issues may affect drug absorption, PD motor symptoms, and quality of life. Before we get started with the problems, let’s take a moment for the sake of terminology, to know that doctors tend to divide the GI system as follows: upper GI: mouth to stomach, and lower GI: small intestine to rectum. The GI tract is controlled to some degree by nerve centers in the brainstem dorsal motor nucleus (DMN) via the vagus nerve “the wanderer.” There is also an enteric nervous system (ENS), which some refer to as “the second brain,” consisting of about 100 million neurons. If that sounds like a lot, consider a healthy adult brain, which is estimated to be made up of 80-100 billion neurons (and many, many more glial cells).
Why are there GI issues in PD?
That is a big topic, too big to cover in depth here. The issues are likely multifactorial. Alpha-synuclein aggregation in neurons of the gut and the DMN, and issues with the gut-brain axis are big factors. For more on those issues, read articles 1 and 4 in the references below.
Let’s talk about the stomach
The stomach is a single chamber, which is functionally considered in three regions: the proximal stomach, the distal stomach, and the pylorus. These regions operate in unison to maintain normal gastric emptying. The stomach must also maintain intragastric pressure in order to allow continued meal ingestion until satiation. In other words, the stomach contains the food you have eaten so that you can eat until you feel appropriately satisfied. There are many variations on that theme however, which may in part explain some under-, and overweight individuals. Whatever the case, in normal circumstances after a meal, strong contractile pulses in the distal stomach break up food particles. This allows the stomach to empty into the first part of the small intestine. But emptying of the stomach may not occur on time.
Delayed gastric emptying affects 70% of PD patients at some point. If the problem becomes chronic and symptomatic doctors refer to it as “gastroparesis.” The symptoms of gastroparesis include nausea, vomiting, retching, early satiety, bloating, loss of appetite, and abdominal discomfort. Longer PD duration is not associated with worse gastroparesis as you might expect. However, advancing motor severity (the stiffness, slowness, and tremors of PD) does correlate with worse gastric emptying delay. This is largely to do with where L-dopa (levodopa) is absorbed: the small intestine. Obviously, if the drug cannot get there, it cannot be absorbed. Gastric emptying speed is therefore the rate-limiting step in the absorption of L-dopa. Because of these drug absorption problems, gastroparesis contributes to drug response fluctuations. This means some doses of L-dopa might be delayed in working, work only partially, abruptly stop working at an unpredictable time, or not work at all. (5,6)
Is there a treatment for gastroparesis in PD?
Some doctors attempt to use the dopamine receptor antagonist metoclopramide (Reglan). This drug does help empty the stomach, but has the unfortunate function of blocking dopamine receptors in the brain. This not only prevents dopamine from doing its job, but can cause severe PD symptoms. While metoclopramide is the mainstay of treatment for gastroparesis in the general population, there is the potential for so-called extrapyramidal side effects such as “parkinsonism.” In people with PD or parkinsonism, metoclopramide is not suitable for long-term use. I tend to use this drug very rarely in my practice.
Domperidone is not FDA-approved for any indication in the United States, but is in trials (7), and is used by U.S. movement disorder and gastroenterology doctors nonetheless (usually via compounding pharmacies). In the U.S., compounding domperidone is an expensive proposition. Because the drug is available in Canada (and many other countries), it can be purchased much less expensively over the internet (usually from Canada). However you get it, Medicare and most insurance companies will not pay for it due to the above lack of an indication per the FDA. In terms of how it works, and whether it might affect parkinsonism, domperidone does not cross the blood brain barrier, has been shown to enhance gastric emptying, and to enhance L-dopa bioavailability (allowing L-dopa to function). It is the drug of choice for delayed gastric emptying in PD in essentially the rest of the world.
Macrolide antibiotics (such as erythromycin) are sometimes used for short periods of time (antimicrobial properties, i.e., action against bacteria, limit its long-term use). These drugs enhance gastric emptying and are effective in gastroparesis.
It should be noted that a small number of patients with gastric complaints will be colonized with the bacteria Helicobactor pylori. This microbe is also known to be a culprit in gastric ulcer formation. Among PD patients evidence of H. pylori colonization is associated with motor fluctuations. And, after H. pylori eradication, L-dopa absorption and motor fluctuations can be improved. (8,9)
If you think you might have delayed gastric emptying or gastroparesis, talk with your doctor. Severe symptoms might require a gastroenterology consultation. Very mild symptoms might be due to some other factor, or respond to minor medication changes.
References
- What is the Gut-Brain Axis? Maine PD News, April 2017. https://mainepdnews.org/2017/04/17/what-is-the-gut-brain-axis/
- Constipation in PD. Maine PD News, June 2016. https://mainepdnews.org/2016/06/12/constipation-in-pd/
- PD and diet. Maine PD News, January 2017. https://mainepdnews.org/2017/01/11/pd-and-diet/
- What’s so bad about alpha-synuclein? Maine PD News. April 2016. https://mainepdnews.org/2016/04/25/whats-so-bad-about-alpha-synuclein/
- Doi H, Sakakibara R, Sato M, et al. Plasma levodopa peak delay and impaired gastric emptying in Parkinson’s disease. J Neurol Sci 2012;319:86-88.
- Muller T, Erdmann C, Bremen D, et al. Impact of gastric emptying on levodopa pharmacokinetics in Parkinson disease patients. Clin Neuropharmacol 2006;29:61-67.
- Pipeline drugs, part 2: gastric emptying agents. Maine PD News. June 2018. https://mainepdnews.org/2018/06/21/pipeline-drugs-part-2-gastric-emptying-agents/
- Lee WY, Yoon WT, Shin HY, Jeon SH, Rhee P-L. Helicobacter pylori infection and motor fluctuations in patients with Parkinson’s disease. Mov Disord 2008;23:1696-1700.
- Pierantozzi M, Pietroiusti A, Brusa L, et al. Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations. Neurology 2006;66:1824-1829.
