Michael M. Segal MD PhD1, Karin Jurkat-Rott MD PhD2, Jacob Levitt MD3, Frank Lehmann-Horn MD PhD2
1 SimulConsult Inc., USA
2 University of Ulm, Germany
3 Mt. Sinai Medical Center, New York, USA
5 June 2009
This article focuses on questions that arise about diagnosis and treatment for people with hypokalemic periodic paralysis. We will focus on the familial form of hypokalemic periodic paralysis that is due to mutations in one of various genes for ion channels. We will only briefly mention other “secondary” forms such as those due to hormone abnormalities or due to kidney disorders that result in chronically low potassium levels in the blood. One can be the only one in a family known to have familial hypokalemic periodic paralysis if there has been a new mutation or if others in the family are not aware of their illness. For more general background about hypokalemic periodic paralysis, a variety of descriptions of the disease are available, aimed at physicians or patients.
The best tests to diagnose hypokalemic periodic paralysis are measuring the blood potassium level during an attack of paralysis and checking for known gene mutations. Other tests sometimes used in diagnosing periodic paralysis patients are the Compound Muscle Action Potential (CMAP) and Exercise EMG; further details are here.
The most definitive way to make the diagnosis is to identify one of the calcium channel gene mutations or sodium channel gene mutations known to cause the disease. However, known mutations are found in only 70% of people with hypokalemic periodic paralysis (60% have known calcium channel mutations and 10% have known sodium channel mutations). This situation will improve as further mutations are identified. In the meantime, if potassium helps relieve or prevent episodes, this fits with hypokalemic periodic paralysis.
No. Although having low levels of blood potassium during attacks is typical of hypokalemic periodic paralysis, between attacks, people with hypokalemic periodic paralysis can have a normal blood potassium level (frequently in the low normal range).
Attacks of paralysis are typically triggered by the level of potassium dropping in the blood. Such potassium fluctuations occur in everyone, but in people with familial hypokalemic periodic paralysis, these drops in potassium can produce episodes of paralysis. For example, a large carbohydrate meal results in secretion of insulin into the blood, which results in a drop of the blood potassium level as potassium and glucose enter cells. In normal people, such a drop in blood potassium produces no symptoms. In people with familial hypokalemic periodic paralysis, however, the drop in blood potassium often triggers an episode of paralysis.
Potassium levels in the blood can remain low as muscle is recovering from a recent attack. During an attack, muscles that become paralyzed swell and take up potassium, causing a drop in potassium in the blood. But as the swelling resolves, the level of potassium in the blood returns to the normal range. Consequently, a normal blood potassium after such a recovery should not be considered evidence against a person having hypokalemic periodic paralysis.
When evaluating blood potassium levels it is important to take into account recent treatments. Having just taken potassium or being on a drug that lowers blood potassium, such as acetazolamide, will have effects on blood potassium levels.
It is also important to consider other reasons for potassium being low. Some people have chronic low blood potassium, for example due to kidney disease (e.g., Bartter syndrome). They can have "secondary" or "symptomatic" periodic paralysis despite not having one of the familial "primary" periodic paralysis channel disorders.
Paralysis can affect all major muscles or can affect a single limb, for example after lots of exercise using that limb or after pain to the limb. Respiratory muscles can be involved, typically in a very severe attack or after anesthesia.
Hypokalemic periodic paralysis is an autosomal dominant disorder, which means that one abnormal copy of the gene is all that is needed to have symptoms. Typically, this means that one parent has the disease, but it is possible to have the gene as a result of a new mutation not present in the parents, or it is possible that a parent has the gene but is not expressing symptoms enough to be clinically evident. Typically, someone will first show clear signs of hypokalemic periodic paralysis sometime in the teens, but with careful observation and knowledge of the paralysis triggers, the disease can be recognized earlier and in higher percentages of those carrying the gene abnormality.
Other diagnoses to consider are:
People with genetically-proven hypokalemic periodic paralysis often have other symptoms besides the paralysis:
Among the 30% of people who appear to have hypokalemic periodic paralysis but don’t have mutations in the two genes known to cause hypokalemic periodic paralysis the following are often noted:
If you are thought to have hypokalemic periodic paralysis, a muscle biopsy can show some relatively non-specific changes such as vacuoles or tubular aggregates, which can support a diagnosis of hypokalemic periodic paralysis. However, such abnormalities are not specific enough to make a diagnosis definite. If your doctors are considering other possible disorders, for example mitochondrial disease, a muscle biopsy may be the key to making that diagnosis.
The most important interventions are managing the triggers described above. There are also a variety of drug interventions described in an article Practical aspects in the management of hypokalemic periodic paralysis by one of us who has hypokalemic periodic paralysis.
Dietary interventions are primarily a matter of avoiding triggers and increasing potassium. Implementation, however, is not simple. For example, bananas are widely known as a food high in potassium, but they also contain high levels of carbohydrates, so they are far from an ideal source of potassium. Other foods, such as shredded wheat cereal, which is typically high in potassium and contains slowly released carbohydrates, can be more helpful. Guidance from a nutritionist who understands hypokalemic periodic paralysis can be very helpful.
In individuals with hypokalemic periodic paralysis who have blood potassium values in the low normal range between attacks, it is difficult to keep blood potassium levels high enough to result in less muscle pain, less permanent weakness, and less frequent spells. So, in addition to aiming for potassium values in the normal to slightly high range, it is often helpful to use medications. A combination of acetazolamide, which slightly reduces blood potassium levels, and a potassium-sparing diuretic is preferred (typically triamterene, amiloride or aldosterone antagonists such as spironolactone or the newer agent eplerenone, which has less hormonal side effects compared to spironolactone). Sometimes, additional oral potassium intake is required. Individuals with hypokalemic periodic paralysis can become hyperkalemic and weak under this triple treatment. Therefore, potassium levels should be checked, typically weekly at the beginning, then monthly. Also, potassium should be checked when people are weak during a spell but do not recover within several hours.
The body does tend to restore potassium levels, but during a severe episode there can be lasting effects on muscle. Many people with hypokalemic periodic paralysis develop chronic muscle weakness as they get older. In addition, some people are at risk of other effects such as heart rhythm disturbances or severe difficulty breathing, which can be life-threatening. That said, potassium almost uniformly restores muscle strength during an acute attack. With repeated attacks, and possibly simply with time, some people do experience an overall weakening of their muscles, especially of the thighs and shoulders.
There is a detailed description here on the Periodic Paralysis International website. At present, this is not an U.S. FDA-approved device for checking potassium and is not endorsed by most leaders in the field as a reliable method for checking potassium to guide therapy. Some patients, at risk of false readings and non-standardized, non-validated protocols, have managed themselves successfully using this device.
No. The rarity of the potassium-related diseases, the large amounts of potassium that would need to be given and the dangers of giving too much potassium make it unlikely that we will see “potassium pumps” used on patients other than for intravenous administration under medical supervision.
Muscles have a large capability to grow with exercise, so even after some muscle damage it is possible to regain much strength. Some people have found that a program of regular exercise and muscle building is a way to keep paralysis at bay. However, following continued or severe attacks there can be some residual weakness and then exercise can do more harm than good.
With general anesthesia there is an increased risk of weakness and respiratory distress, so anesthesiologists must be told about a channelopathy diagnosis. Hypothermia, hypokalemia, sodium chloride and glucose infusions as well as myotoxic substances like succinylcholine in the operating room often lead to flaccid muscle weakness and respiratory distress in the recovery room. With local anesthetics the chief risk is from epinephrine added to local anesthetics to slow diffusion of the anesthetic away from the area. A separate issue is the insensitivity to the local anesthetic lidocaine seen in some people with hypokalemic periodic paralysis.
When should I start using a wheelchair? Should I start using a motorized wheel chair? Who will pay for my wheelchair? How can someone find out more about wheelchairs/scooters?
Permanent weakness occurs in about 50 % of people with hypokalemic periodic paralysis and slowly progresses with age. Over years the weak muscles can regain strength with proper treatment and precautions. If the majority of muscles is replaced by fat and connective tissue, current medication will not restore the muscles.
Few individuals will require a wheelchair. If a wheelchair is required it is best to choose one that is battery powered. Extended use of arms to propel a manual chair is discouraged. Patients should be aware that remaining physically mobile for as long as possible is desired. However, if the risk of falling becomes great, it is better to use a powered mobility device rather than to risk other bodily injuries in falls. During periodic paralysis attacks the use of a wheelchair can be useful to conserve strength during the recovery process. The Muscular Dystrophy Association will help patients with the purchase of both manual and motorized mobility devices. Many insurance carriers also cover these costs. If you have questions about this coverage you may contact the Periodic Paralysis Association (see resources).
The difficulty arises from the fact that the disease is rare, attacks can be infrequent and that there are variants of hypokalemic periodic paralysis with symptoms that tend to get dismissed as psychiatric.
For people with the standard form of hypokalemic periodic paralysis, convincing family members is primarily a matter of educating them about the existence of the disease. This can be done by making them aware of articles about the disease or by enlisting a physician who is aware of the disease to make clear that it is real, even though it is rare in the general population and the episodes of paralysis can be infrequent in an affected individual.
For people with the hypokalemic periodic paralysis variant with additional symptoms, the best that can be offered now is help avoiding episodes, and the prospect that the situation will improve as the relevant genes are identified.
Sometimes, speaking with others who have dealt with similar issues can help give you ideas about explaining others about your problem. To this end, various listservs are available (see Resources).
Copyright © 2009 by the authors. Individuals may make copies for their own personal use.