SEPTEMBER 07, 2017
James Radke and Mathew Shanley
Periodic paralyses are a group of rare diseases best characterized by episodes of skeletal muscles becoming weak or flaccid (i.e., paralysis).
The conditions are mostly genetic in nature, and researchers have determined that most cases stem from genetic abnormalities related to ion channels, leading to an imbalance of potassium within the muscle—which leads to the paralysis. The 2 most common forms of periodic paralysis pertain to potassium levels either being too high (hyperkalemic periodic paralysis) or too low (hypokalemic periodic paralysis).
The nature of periodic paralysis means that patients can go years without a correct diagnosis, and the sporadic characteristics of the condition mean that neurologists might not observe it firsthand, but instead hear about it from the patient or an emergency department physician. Knowing how to recognize the symptoms can dramatically reduce the time to diagnosis. With treatment now available to help patients manage their attacks, getting a diagnosis can greatly improve a their long term prognosis and quality of life.
Rare Disease Report spoke with Robert Griggs, MD, professor of neurology at the University of Rochester Medical Center in Rochester, New York about periodic paralysis.
Rare Disease Report: How long can some patients with periodic paralysis go before getting a proper diagnosis?
Dr. Griggs: It can often take many years to get a correct diagnosis because patients will typically develop weakness, and they develop this temporary weakness against the background of completely normal strength.
The only time they tend to get diagnosed more quickly is if they have really severe symptoms and they go to an emergency department as essentially quadriplegic; they can’t move their arms or legs. That gets people’s attention, but sometimes even with that situation, a diagnosis is not made because by the time they get evaluated by somebody for muscle strength, they may be getting back to normal and doctors may be suspicious that it is a psychological disturbance.
But for the really paralyzed patients, they are more likely to get diagnosed because emergency departments frequently do blood tests right when they walk through the door, and abnormal potassium levels can help guide a diagnosis.
RDR: What about the less severe cases?
Griggs: One of the rules in all of medicine is that patients often have weakness and feel like they can’t do things. Many patients may not recognize that it’s weakness and so they may not complain to a doctor they may feel weak occasionally. Patients generally don’t say to their doctor “Well, I had trouble getting up in the morning, getting out of bed, and getting off to work.” I don’t find it all that easy to go to work myself either on some days, so if somebody doesn’t really realize that the weakness is a problem, it can go for 10, 20, or 30 years before they are recognized. This is less common now than it used to be because now patients tend to get evaluated more thoroughly.
RDR: How are blood potassium levels related to the diagnosis?
Griggs: In a blood test, they’ll often find that the potassium is low in hypokalemic periodic paralysis or some of the time it’s high in hyperkalemic periodic paralysis.
If a patient has a very low potassium and they’re very weak, the low potassium is typically going to be the cause of the weakness. However, there are a dozen or more things that can cause a low potassium weakness so that doesn’t necessarily mean that somebody has a periodic paralysis and the same is true of a high potassium.
Often times, it’s more likely to be an endocrine problem, or a kidney problem, or something else. You often have to look for the other things that cause a low or high potassium before you suspect a periodic paralysis.
So, you have to look at thyroid function, endocrine function, kidney function, and a number of other things to be sure that the potassium weakness is not related to something else. A tumor in the colon or in the adrenal can cause the body to lose potassium. These things are all uncommon but they’re probably as uncommon as periodic paralysis so figuring out why the potassium is abnormal in a weak patient is really a tricky thing to do and requires a lot of diagnostic care.
The electrolytes are tip-off but a lot of work needs to be done to rule out other conditions. Measuring muscle activity can also help in suspecting if the person has periodic paralysis. If you have the patient with periodic paralysis do the exercise test, there’s often a decrease in the amount of strength that the muscle shows on it’s electrical activity.
RDR: What is the gold standard for a diagnosis?
Griggs: The gold standard is genetic testing, and that is now available. Almost all patients who really have periodic paralysis have a genetic abnormality. Sometimes, it takes a more sophisticated laboratory to actually figure it out but genetic testing is becoming the gold standard for making the diagnosis.
RDR: How is periodic paralysis treated?
Griggs: If patients are troubled by their attacks of weakness, it’s very important that they prevent the attacks for 2 reasons. One, because the attacks often interfere with quality of life and two, because after the attacks, patients often develop progressive weakness between attacks. It’s not uncommon for a patient who has attacks to end up in a wheelchair. We think that if you can prevent the attacks, you may prevent that weakness.
Ways to prevent attacks include watching foods for low potassium. You don’t want patients to eat a lot of carbohydrates or salt loads. Foods like pizza or pasta often will precipitate an attack, and patients often know that.
Also, for hyperkalemic periodic paralysis, you want them to avoid things that are high in potassium.
Dietary counselling is important. Also, a graded exercise program can often reduce the severity and frequency of attacks.
As for medications, if a patient has an attack of hypokalemic periodic paralysis, giving oral potassium can often shorten the attack and brings about rapid recovery from the attack. If they have high potassium, then taking things to lower the potassium like a carbohydrate load will often improve strength.
Unfortunately, giving potassium or lowering the potassium by foods doesn’t usually prevent attacks completely and patients often need to have medications.
There is only one FDA-approved treatment, and it was approved about one and half or two years ago: it is Keveyis (dichlorphenamide), a carbonic anhydrase inhibitor. Because the condition is so rare – maybe 1 in 100,000 – the drug is available only through specialized pharmacy. It works in both hypo- and hyperkalemic cases, and it can often prevent attacks completely in hypokalemic periodic paralysis.
There are other treatments out there. For hyperkalemic patients, there are diuretics that can help. And hypokalemic patients, they are actually some diuretics that will raise the potassium instead of lowering that are sometimes effective, if patients can’t take the carbonic anhydrase inhibitor.