The Snowflake Disease – Revisited

I haven’t spoken about how Myasthenia Gravis (MG) is called the “Snowflake Disease” in a while. It’s such a unique part of MG, I thought perhaps it was time to revisit for any new readers.

One of the reasons MG is often left undiagnosed is because symptoms come and go. A person may be experiencing eyelid droop, weakness in the legs, or a host of other symptoms only to have those symptoms disappear after the person rests. Here one moment; gone the next. Much like a snowflake.

When I was young, I always waited in anticipation of the first snowfall. Where I lived in the Midwest, it usually came sometime in November, although I remember a few years where we got our first snow before Halloween. Early snows usually didn’t last long before melting away without leaving a trace. As soon as the first snow arrived, I’d run outside and try to catch a snowflake in the palm of my hand. The problem was, if I caught one, it didn’t last long before it melted away.

If you ever want to have a good philosophical debate with someone, ask them this question. “Where does the white go when the snow melts?” Lots of different theories on that one.

Just like a snowflake is here one moment and gone the next, so do the symptoms of Myasthenia Gravis. Not only can they go away quickly, they can appear quickly as well. You can be perfectly fine one moment and suddenly your eyelid, or eyelids, begin to droop. Or your eyelids are drooping, you rest for a few minutes, and suddenly they’re back to normal. You can see why this causes difficulty for doctors as oftentimes the person is not displaying the symptoms they describe having during their appointment. That’s why a doctor has to evaluate what the patient is saying and pursue clinical and laboratory testing to determine if a person has MG.

Now here’s where it gets fun. Myasthenia Gravis is considered a rare disease. It was estimated in 2021 that only 12.4 out of 100,000 people in the world have been diagnosed with MG. It’s unknown how many people actually have MG, as many more could have it and never been tested or diagnosed.

Why is it so hard to diagnose? Well, there’s the snowflake symptoms we’ve already talked about, but the real reason is we don’t yet know enough about MG to find all the markers for the disease. The first blood test usually run by doctors on someone suspected of having MG is looking for the AChR antibody marker. Results are positive in as many as 90% of patients who have generalized MG, but in only 50-70% of patients who have only ocular MG.

Before we go any further, I should probably explain the difference. In generalized MG, numerous muscles in the body are affected. It can affect the legs, the diaphragm, the eyes, the mouth, the throat, the arms or just about any voluntary muscle. In ocular MG, only the eye muscles are affected.

The next test usually run for MG is normally the anti-MuSK antibody marker. 40-70% of the people who tested negative under the AChR antibody marker test will test positive for anti-MuSK. Notice this isn’t an additional 40-70%, but only 40-70% of people who tested negative to the AChR marker test. Let me provide an example. Let’s say you have 100 people who are diagnosed with MG. Using the percentages, 90 of those people will probably be AChR-positive and 4 to 7 people will probably be MuSK-positive.

If the above two tests are both negative, but your doctor still thinks you may have MG, there are still a few more tests that can be run. The next most common is the anti-LRP4 antibodies marker test. This test will show positive in 2-50% of the people with MG who have not show positive for either AChR or MuSK. So, back to our example, of the 100 people, 90 people would be positive for AChR, 4-7 would be positive for MuSK, and there would be an additional 1-5 people who would show up as LRP4-positive.

If the person is still negative, there are some additional tests that can be run, but 2-5% of people with MG will be considered triple seronegative meaning they tested negative on the big three previously mentioned tests. That’s where I fall. I have triple seronegative Myasthenia Gravis; the rarest of the rare.

So, how can you have MG if you test negative for all the tests? As my neurologist explained to me, we still haven’t discovered all the markers for MG and someday the marker for the kind of MG I have will be discovered. It used to be the AChR test was the only blood marker for MG. Then they discovered the MuSK marker. More recently they discovered the LRP4 marker. As research continues, they will find more. He was able to diagnose me through clinical findings. One of the most apparent was when he started me on Mestinon. After one dose, suddenly my symptoms were less severe or went away only to return at the end of the dose. Mestinon only lasts about 3-4 hours, so I take it every 4 hours to control my symptoms. Even with Mestinon, I still have break-through symptoms, but the Mestinon has helped immensely. I’m now going through a new study that may help pinpoint the type of MG I have and may help open the door for more effective treatment.

Here’s the key. I was considered “Suspect for Myasthenia Gravis” for over 35 years. Back then they had even fewer options for diagnosing. I displayed symptoms, but the AChR test came back negative. I was fortunate my MG went into remission. I still had a few symptoms, but they weren’t as bad and I could easily live with them. A couple of years ago, after contracting COVID-19, my symptoms came back worse than before. That’s when I went to see a neurologist. He felt my MG may have been retriggered by COVID-19.

The “Snowflake Disease”. Symptoms here one minute and gone the next. Sometimes it even goes into remission, only to come back at a later time.

For those of you helping or caring for someone with Myasthenia Gravis or “Suspect for Myasthenia Gravis”, keep this in mind. It’s difficult understanding how we can have symptoms one minute and they go away the next. We don’t even understand it. It’s easy to fall into the trap of thinking perhaps our symptoms aren’t real if they go away so easily. Perhaps we just want attention. Perhaps we just want you to feel sorry for us. I’m not blaming you. That’s the logical conclusion. Only MG isn’t logical.

For a long time I suspected people thought I was lying or exaggerating. For a long time, I was embarrassed when my symptoms showed up. I’d try to hide them. For a long time, I wondered myself if it was really just all in my head. It wasn’t.

I still try to hide my symptoms. That’s human nature. You don’t want people to think of you as deficient. Some symptoms I can’t hide, however. When my eyelids droop, they droop. I can’t lift them back up into a normal position. When my voice gets hoarse, trying to talk louder only makes it worse. When my legs get weak, they get weak. The only thing I can do is stay on my medication exactly like my doctor has prescribed.

When you hold a snowflake in the palm of your hand, it melts and disappears, but you didn’t imagine it. It wasn’t all in your head. It was real and it was there. For someone who has Myasthenia Gravis, their symptoms are real. The symptoms may have melted away, but they were there.