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7 Signs of a Cholinergic Crisis With Myasthenia Gravis

Posted on April 8, 2024

If you’re living with myasthenia gravis (MG), it’s important to know about a potential emergency complication called a cholinergic crisis. A cholinergic crisis can happen suddenly, and knowing the signs can make a big difference in getting help quickly and preventing serious complications.

During a cholinergic crisis, you may have muscle weakness that interferes with your ability to breathe, making it look and feel like a myasthenic crisis. Although a cholinergic crisis and myasthenic crisis have some similar symptoms, they have different causes and treatments. A cholinergic crisis occurs as a complication of MG overtreatment, whereas a myasthenic crisis is caused by a worsening of MG itself.

This article will help you recognize the signs and symptoms of a cholinergic crisis so you can get help fast.

What Causes a Cholinergic Crisis?

Before we dive into the signs and symptoms of a cholinergic crisis, let’s learn more about what happens when a cholinergic crisis occurs.

A cholinergic crisis occurs when too much acetylcholine — a chemical that helps your nerves and muscles communicate — overstimulates your nervous system. People with MG may develop a cholinergic crisis from taking a high dose of acetylcholinesterase (AChE) inhibitors — a common treatment option for MG to increase muscle strength.

AChE inhibitors (also known as cholinesterase inhibitors) are a class of medications used to help improve the symptoms of MG, such as muscle weakness. These drugs work by increasing the amount of acetylcholine in the neuromuscular junction (NMJ) — the space where your nerves and muscles meet.

AChE inhibitors can increase the amount of acetylcholine in the NMJ by blocking a protein that breaks down acetylcholine. Pyridostigmine (Mestinon) and neostigmine methylsulfate (Bloxiverz) are examples of AChE inhibitors.

The dosage of these medications is also important. A cholinergic crisis is very rare in people taking the dosages normally prescribed for MG.

Cholinergic Crisis in People Without MG

People who don’t have MG can also develop a cholinergic crisis if they’re exposed to certain drugs or chemicals. Possible causes of cholinergic crisis in people without MG include:

  • High doses of acetylcholinesterase inhibitors, used to reverse the effect of nerve-blocking agents used in surgery
  • Exposure to pesticides or insecticides
  • Exposure to nerve gas in chemical warfare

7 Signs and Symptoms of a Cholinergic Crisis

Keep reading to learn about the seven signs and symptoms of a cholinergic crisis.

1. Difficulty Breathing

AChE inhibitors usually help increase muscle strength. However, if the dose is too high, it can cause muscle weakness. If the muscles used to help you breathe are affected, it may cause respiratory failure — when your lungs can’t provide enough oxygen.

In addition to weakening your respiratory muscles, too much AChE can make breathing more difficult by increasing your mucus secretions and tightening your airways.

Without treatment, respiratory failure caused by a cholinergic crisis can lead to death.

2. Stomach-Related Problems

Too much acetylcholine can also cause diarrhea by increasing how quickly food moves through your gastrointestinal tract.

You may also experience other digestive problems similar to the side effects of AChE inhibitors, such as nausea, vomiting, and stomach cramps.

If vomiting and diarrhea are severe, you may lose too much of certain minerals, causing additional problems.

3. Increased Sweat and Saliva Production

Certain nerves regulate how your body makes certain body fluids, such as sweat, saliva, tears, and mucus. Overstimulation of these nerves can increase your body’s production of these fluids. In addition to an increase in mucus, you may notice more salivation and excessive sweating.

4. Blurry Vision

Overstimulation of acetylcholine receptors in your eyes can cause changes in your vision and make it more difficult to see. Too much acetylcholine can cause your pupils to constrict. When your pupils are smaller, focusing your eyes may be difficult.

During a cholinergic crisis, your eyes may produce more tears than usual, making your vision blurry.

5. Changes in Heart Rate and Blood Pressure

Other nerve receptors influence your heart rate and blood pressure. Overstimulation of these receptors cause bradycardia (low heart rate), defined as fewer than 60 beats per minute. It can also cause your blood pressure to increase or decrease to unsafe levels.

Changes in your heart rate or blood pressure may cause symptoms such as:

  • Fatigue
  • Dizziness or lightheadedness
  • Heart palpitations (feeling a fluttering heartbeat)
  • Chest pain
  • Confusion or difficulty concentrating
  • Changes in your behavior

6. Muscle Twitching

Increasing the amount of acetylcholine in your NMJ usually increases your muscle strength. However, too much acetylcholine can cause problems with your muscles.

Muscle twitching can happen when nerve receptors become overstimulated by acetylcholine. Muscle twitches due to a cholinergic crisis happen in the muscles you control, such as those in your arms and legs.

7. Increased Urination

Nerve receptors in your bladder help to regulate the way your urinary bladder works. When the muscarinic receptors become overstimulated, you may feel like you have to urinate (pee) more often and more urgently than usual.

What’s the Difference Between a Cholinergic Crisis and a Myasthenic Crisis?

Distinguishing between a cholinergic crisis and a myasthenic crisis can be difficult because both conditions can cause muscle weakness. Life-threatening respiratory failure due to weak respiratory muscles can happen due to either a cholinergic crisis or a myasthenic crisis.

No matter the cause, it’s important to get help quickly.

Causes

The major difference between these two types of emergencies is that a cholinergic crisis is caused by a dose of AChE inhibitors that’s too high.

When your MG symptoms become worse, it’s a sign of a myasthenic crisis. Most people notice increasing weakness or myasthenia exacerbation (also called a flare-up) before a myasthenic crisis. A myasthenic crisis can occur as part of the natural course of the disease or may be triggered by an event, such as infection, surgery, or pregnancy.

Diagnosis

Your symptoms can help your health care team tell the difference between a cholinergic crisis and a myasthenic crisis. Tracking your symptoms is helpful to recognize a potential crisis.

In addition to your symptoms, your health care team may perform a test to tell the difference between a myasthenic and cholinergic crisis. During this test, your health care provider will give you a drug called edrophonium. If your symptoms get worse, a cholinergic crisis is likely the cause of your symptoms. If your symptoms get better, a myasthenic crisis is likely the cause.

Treatment

The treatment for a cholinergic crisis also differs from the treatment for a myasthenic crisis. Both conditions may require medical procedures to help you breathe, such as mechanical ventilation or intubation.

A cholinergic crisis requires an antidote — a drug that counteracts the effect of AChE inhibitors. Atropine and pralidoxime are examples of antidotes used in a cholinergic crisis.

Treatments for a myasthenic crisis include intravenous immunoglobulin and plasma exchange.

Being aware of the signs of a cholinergic crisis is essential for anyone living with myasthenia gravis. By recognizing these signs, you can take prompt action, seek help swiftly, and potentially avoid serious complications. Remember, staying informed helps you navigate any challenges that may arise.

Find Your Team

On MGteam, the social network for people living with myasthenia gravis and their loved ones, members come together to ask questions, give advice, and share their stories with others who understand life with myasthenia gravis.

Have you or a loved one experienced a cholinergic crisis? How did you recognize the signs and symptoms? Share your experience in the comments below, or start a conversation by posting on your Activities page.

Posted on April 8, 2024
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Luc Jasmin, M.D., Ph.D., FRCS (C), FACS is a board-certified neurosurgery specialist. Learn more about him here.
Amanda Jacot, PharmD earned a Bachelor of Science in biology from the University of Texas at Austin in 2009 and a Doctor of Pharmacy from the University of Texas College of Pharmacy in 2014. Learn more about her here.

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