Myasthenia Gravis (MG) is a condition caused by the production of antibodies that block acetylcholine receptors. This blockade of neuromuscular signaling results in rapid muscular fatigue and weakness. Increased activity tends to worsen muscular issues which usually resolve with rest. Prominent symptoms of MG include drooping eyelids, double vision — OMG (ocular myasthenia gravis)– difficulty swallowing, slurred speech, and shortness of breath. Generally, muscles in the face and throat are considered to be the most commonly impacted by Myasthenia Gravis. However, this condition can affect any muscle group throughout the body (1). Gastrointestinal (GI) manifestations such as abdominal pain, recurrent vomiting, and constipation have been reported by individuals with MG. A case presenting to the Summit Medical Center located at 9,100 feet illustrates an unusually severe manifestation:

A 70 year old woman was brought to the emergency department (ED) with severe abdominal and chest pain, concerned that she had a dissecting aortic aneurysm. She reported three previous episodes of severe  pain in the 2 weeks leading up to the ED visit, all starting in the afternoon, increasing to prostration by 5 pm and resolving with bed rest. Past medical history was significant for myasthenia gravis for which she took azathioprine 100 mg BID (twice daily). Two months previously she had a flare with ptosis and double vision, treated with prednisone 40 mg daily. 

Laboratory tests were normal. Imaging showed distended loops of bowel consistent with ileus. She was treated with pain medication and symptoms resolved.

The patient continued to have episodes once or twice a month, including another ED visit, precipitated by treatment with duoneb, which has  anticholinergic activity, a tonic water drink, and guaifenesin, both antimuscarinic substances that interact with the cholinergic receptors in the viscera.. Taking pyridostigmine, a cholinesterase inhibitor, led to resolution within 2 hours, marked by “sparkly” sensations in her arms and legs and reactivation of bowel sounds with flatus. 

Until recently, GI symptoms were considered rare in myasthenia gravis. Then a case study in 2001 demonstrated that gastric dysmotility was a common feature among individuals with Myasthenia Gravis (2). Among all the motility dysfunction reported, gastroparesis was found to be a common autonomic feature in MG patients (2). Gastroparesis is the slowing or stopping of movement in the GI tract resulting in delayed gastric emptying. Further research demonstrated that intestinal pseudo-obstruction was considered to be one of the most common GI manifestations of individuals with MG(3,4,5).

In 2007 it was demonstrated that receptors in gut muscles were structurally similar to skeletal muscle receptors, indicating that GI motility could be highly impacted by the presence or lack of acetylcholine (6). Considering that antibody production in Myasthenia Gravis Individuals can decrease acetylcholine binding to receptors, the presence of GI symptoms among other autonomic dysfunction symptoms suggests inadequate treatment which can result in a poor prognosis for these individuals (7). 

What was previously considered a rare symptom within a rare condition, is now being proposed as an early identification tool. Taking into account receptor similarity,  GI symptoms can be used as early indicators of myasthenia gravis, specifically gastrointestinal dysmotility (8). The case study showed that MG developed less than a decade after the initial onset of gastrointestinal dysmotility symptoms (8). There is a clear need to identify GI symptoms earlier in MG individuals. This will allow for better treatment and improved long-term health outcomes for these individuals. 

At altitude, the low barometric pressure causes gaseous distension in normal individuals producing increased flatus (see blog on HAFE). Combined with MG, GI manifestations can be even more severe. Medical providers treating residents of  high altitude communities should consider MG in the differential of patients with abdominal complaints and treat recognized MG patients with anticholinesterase medications to control symptoms. None of this patient’s providers were aware of this manifestation of MG, including the neurologist who specializes in MG, the gastroenterologist who performed an  upper endoscopy and colonoscopy, the ED staff, the radiologist and the primary care provider. Patients with MG and their providers need to be aware of medications that interact with the cholinergic receptors in all parts of the body and screen for these as possible precipitators of symptoms outside the classic description of the disease.

Submitted by Ana Campos, PA-S.

References 

1. (NHS) https://www.nhs.uk/conditions/myasthenia-gravis/ 

2. Vernino S, et al. Myasthenia gravis with autoimmune autonomic neuropathy. Auton Neurosci. 2001;88(3):187–192.

3. Pande R, Leis AA. Myasthenia gravis, thymoma, intestinal pseudo-obstruction, and neuronal nicotinic acetylcholine receptor antibody. Muscle Nerve 1999;22:1600-1602

4. Musthafa CP, Moosa A, Chandrashekharan PA, Nandakumar R, Narayanan AV, Balakrishnan V. Intestinal pseudo-obstruction as initial presentation of thymoma. Indian J Gastroenterol 2006;25:264-265. 

5. Seretis C, Seretis F, Gemenetzis G, Gourgiotis S, Lagoudianakis E, Pappas A, Keramidaris D, Salemis N. Adhesive ileus complicating recurrent intestinal pseudo-obstruction in a patient with myasthenia gravis. Case Rep Gastroenterol. 2012 

6. Mandl, P, Kiss, JP. Role of presynaptic nicotinic acetylcholine receptors in the regulation of gastrointestinal motility. Brain Res Bull. 2007;72:194–200 

7. Putri Aaliyah. Autonomic Dysfunciton. Gastroparesis as autonomic manifestation of myasthenia Gravis: A rare case report. Clinical Neurophysiology. 132: 94-95, 2021 8. Alnajjar, S., Idiaquez Rios, J., Fathi, D., Liu, G., & Bril, V. (2022). Gastrointestinal Dysmotility as the First Manifestation of Myasthenia Gravis. Canadian Journal of Neurological Sciences, 1-2.

8. Alnajjar, S., Idiaquez Rios, J., Fathi, D., Liu, G., & Bril, V. (2022). Gastrointestinal Dysmotility as the First Manifestation of Myasthenia Gravis. Canadian Journal of Neurological Sciences, 1-2.