Hyperkalemic Periodic Paralysis
Periodic paralysis is a rare genetic disorder that is characterized by temporary attacks of extreme muscle weakness or paralysis.
These attacks can be triggered by a variety of things, with the most common triggers being resting after exercise, cold temperatures, and having too much or too little potassium. There are several types of periodic paralysis. Understanding the different types can be difficult, but we are here to give you guidance.
Periodic paralysis is caused by muscle cells that do not have the right balance of chemicals to work properly. Muscle cells have openings called channels that open and close to let particles such as sodium, potassium, and calcium go in and out. These particles are called ions, and muscle cells can only work if the right kinds of ions enter and exit the cells at the right times. When the channels don’t open and close the way they’re supposed to, the ions become imbalanced, and muscles aren’t able to function normally.
Hyperkalemic periodic paralysis (HyperPP or HyperKPP) is a type of periodic paralysis in which attacks are often associated with high potassium levels in the blood or that are triggered by elevation of blood potassium.
Blood potassium levels can sometimes rise during attacks, too. “Hyper” means that there is a high amount of something, and “kalemic” refers to potassium in blood. There is another periodic paralysis type with a similar name, “hypokalemic,” so it’s important to not confuse the two types.
Hyperkalemic periodic paralysis causes sufferers to have attacks of extreme muscle weakness, stiffness, or paralysis. These attacks usually last from around ten minutes to an hour, but in some cases, they can stretch on for one or two days. Frequency of attacks can vary greatly between different people. Some people have attacks every day, others have them several times per month, while there are others who have them every few months or less often. The strength of the attacks isn’t always consistent — sometimes, the patient feels fatigued, but can still move around slowly. Other times, they aren’t able to move at all. The onset of muscle weakness is gradual and does not cause “drop attacks”. On the other hand, an affected individual may underestimate the severity of a developing episode while seated and then suddenly fall when attempting to walk.
These kinds of attacks can affect one area of the body or multiple areas. Even the facial muscles can be affected, meaning that patients might find it difficult to make facial expressions due to stiff muscles.. Regional muscle stiffness may improve over a few minutes with repeated efforts for the same muscle group (warm up). Muscle stiffness is known as myotonia. If the loss of force has not progressed to full paralysis, then light exercise may enhance the return of strength.
Attacks of hyperkalemic periodic paralysis can be triggered when the potassium level increases in their blood (AKA serum potassium). Potassium levels may rise during attacks, but not always. Then, as the attack is ending, the blood potassium returns to the normal range or may even drop to a lower than normal level for a short time. This temporary potassium drop should not be mistakenly diagnosed as hypokalemic periodic paralysis. The patient is really hyperkalemic. These shifts of blood potassium levels over time is why establishing a diagnosis of hyperkalemic or hypokalemic periodic paralysis is not as simple as a blood test for potassium.
Individuals with HyperPP have varying degrees of transient muscle stiffness (myotonia) and episodes of weakness. If the predominant feature is muscle stiffness that is aggravated by cold temperatures and paradoxically worsens over the first few repeated attempts of movement, then this disorder is usually called paramyotonia congenita (PMC). HyperPP and PMC have overlapping conditions with similar symptoms, similar biological mechanisms, and similar treatment plans. Within one family, some affected members may be more “HyperPP-like” while others are more “PMC-like”, even though they all share the same channel mutation.
Many patients with HyperPP will eventually develop a slowly progressive permanent muscle weakness, which is called myopathy. This might happen as the patient reaches their 50s or 60s. Some patients with myopathy use a wheelchair or scooter to help them get around outside the house to ease the strain on their weakened muscles. However, they are still able to have fulfilling lives and do many kinds of activities.
People who have hyperkalemic periodic paralysis must try to avoid situations that trigger their attacks. Because this type of periodic paralysis is hyperkalemic, one major attack trigger is eating potassium-rich foods. Blood potassium often increases while fasting, which may trigger an attack. Another example of a common trigger is being in a cold environment, so going outside in cold weather can cause an attack to happen. Stress can be a trigger as well. The more stress a patient feels in their day-to-day life, the more likely it is that they will have an attack.
Another common trigger is resting after exercise. However, even without exercising, it’s possible to have an attack just from not moving for a long period of time, such as when sitting through a movie. Sleep is also a trigger because of the fact that sleeping involves being inactive for a long period of time. Patients often have attacks in the morning when they wake up, making it hard to get out of bed.
Because there are many triggers and different people will have different triggers, it is recommended that patients keep a trigger diary. After you have an attack, you should write down what happened, how you felt, what you were doing before the attack, and how you were able to recover from it. After doing this for a while, you’ll be able to look back on your previous diary entries and notice certain patterns.
Hyperkalemic periodic paralysis symptoms almost always begin during the childhood or teen years. The frequency of attacks can change throughout the patient’s lifetime. Usually, the attacks start out not being very frequent, but as the patient reaches their 30s, there are more attacks. Then, in their 50s, the patient might have fewer attacks, but their muscles have been permanently weakened (myopathy).
The impact that this disorder can have on a person’s life is determined by how many years went by before they received a correct diagnosis. Because it is such a rare disorder, doctors often mistake it for other more common conditions. This results in patients spending a large portion of their lives with the wrong diagnosis, which means they are not receiving the proper treatment. Getting the right diagnosis makes a big difference!
Giving doctors your family’s health history and your trigger diary can help them come closer to a periodic paralysis diagnosis, and there are other diagnostic tools available, too. Hyperkalemic periodic paralysis is a genetic disorder, and commercial lab genetic tests can be performed that can detect the disorder in some patients. However, genetic testing is not perfect and does not always detect all cases. Another diagnosis method is the Compound Muscle Action Potential test, which measures the electrical activity of muscles. This test can’t always detect periodic paralysis, but it can do so in a lot of cases.
Attacks of hyperkalemic periodic paralysis can vary in severity. For more mild attacks, it’s possible to do simple things to recover, such as eating or drinking a high-carb food or beverage or slowly making small movements in order to work off muscle weakness or stiffness. Medication might be needed if these methods don’t work. Albuterol inhalers may hasten recovery from weakness and potassium-wasting diuretics may reduce attack frequency or severity. Medications that inhibit carbonic anhydrase (acetazolamide or dichlorphenamide) may be taken regularly to reduce the likelihood of having an attack. Dichlorphenamide (KEVEYIS) is the only FDA-approved drug for symptom management in periodic paralysis. Severe attacks might affect the heart or breathing, so patients experiencing a severe attack must receive hospital treatment.
Patients should try their best to live a lifestyle that prioritizes minimizing triggers when possible. Living somewhere with a warm climate can help reduce the chances of an attack happening. Keeping stress levels low is another important way to make attacks less likely to happen. Avoid exercise that is overly intense, because resting after an intense workout can be a trigger. Planning your diet carefully is necessary to have fewer attacks because it’s crucial to stay away from potassium-rich foods.
Your Next Steps
If you think you may have hyperkalemic periodic paralysis, please talk with your doctor. Speaking with a doctor about a rare disorder can be intimidating, and many doctors have little to no prior knowledge about periodic paralysis. The PPA has many resources to help you become a better advocate for yourself. Click here to learn about other types of periodic paralysis. You can also submit a question to our Ask the Experts panel. Remember, we are here to support you all the way as you take action to advocate for your health!
Diagnostic Work Up
Chief Complaint: I had a bout of weakness. I think I have periodic paralysis.
Primary Medical Doctors can:
- Involve an Endocrinologist to rule out adrenal causes of hyperkalemia.
- Attack triggers (diet history to exclude licorice, diuretic abuse, laxative abuse)
- Duration of attack
- Family history
- Medication history
- Features of attacks – describe what happens to you
- Do attacks have periodicity/recurrent
- The above gives you pre-test probability
- Suspect hypoPP or hyperPP
- Check serum potassium in an attack (often difficult to catch, may require standby EMS and/or arrangements with a local emergency room)
- Check serum potassium outside an attack (if normal, speaks less for renal disease)
- CK (skeletal muscle)
- Thyroid studies (for hypoPP) – TSH, free T4, and free T3
- Rarely, rule out RTA IV, licorice use, diuretic abuse, laxative abuse, renin-aldosterone-angiotensis axis in the context of hypokalemia or hyperkalemia (r/o Conn’s syndrome vs. Addison’s disease). Ask the nephrologist about specific tests
A neurologist can:
- Neurological investigation – EMG (exclude myotonia) and exercise test (if abnormal then suggestive, but if normal, does not exclude)
- Routine MRI to judge how much muscle bulk is preserved and the presence of edema (should be done before diuretic therapy); if possible, Na MRI is ideal but only investigational now
- Genetic testing
- Empiric therapy sequentially with potassium supplementation, and either eplerenone or acetazolamide
- Repeat MRI after 4-6 weeks of empiric therapy looking for a decrease in edema
- Biopsy if genetic testing is negative
- Provocative test – dangerous
- Refer back to PMD once the diagnosis is established for continued management
MRI of muscles looking for fatty degeneration, which is a feature of permanent muscle weakness (PMW)
The significance of elevated Creatine Phosphokinase (CK or CPK) during or after attacks is unclear, and for now, does not aid in the diagnosis.Further study is warranted given that some patients may present with this lab abnormality.Involve an Endocrinologist to rule out adrenal causes of hypokalemia. Specific studies they might perform to rule in or out hypoPP are: (more information to follow)Involve a Nephrologist to rule out renal disease and to get advice about electrolyte management. Specific tests they might perform to rule in or out hypokalemic periodic paralysis are: (more information to follow)
There are some images of muscle from someone with HypoPP at http://neuromuscular.wustl.edu/pathol/hopp.htm. These muscles have vacuoles, often seen in lipid storage diseases, but here described as containing “amorphous debris”.
In the era of genetic testing, the glucose or glucose/insulin challenge test, which is dangerous, is essentially obsolete. Indeed, those with an obvious diagnosis of familial hypokalemic periodic paralysis would likely not need a challenge test. Those with unclear diagnoses are often more sick, many times with cardiac symptoms during attacks, such that the challenge tests are disfavored unless absolutely necessary.
CMAP (McManis Protocol)
McManis EMG protocol to diagnose periodic paralysis:
The Long exercise nerve conduction test:
- This will be performed in accordance with the protocol described by McManis. All nerve conduction testing will be done on the abductor digiti minimi muscle with stimulation of the ulnar nerve at the wrist. Ambient skin temperature should be approximately 31-32 degrees F or 0 degrees C.
- Compound muscle action potentials (CMAPs) are evoked with a single supramaximal stimulus and repeated every minute for 5 minutes to ensure a stable baseline.
- Maximal, voluntary, isometric exercise of the muscle is performed in 10 second intervals followed by 5 seconds of rest for a total of 5 minutes. CMAP amplitudes are then recorded every 1 minute for 5 minutes then every 5 minutes for 30 minutes.
- A decrement of >40% is highly suggestive of periodic paralysis. It does not differentiate, however, between the primary and secondary forms of periodic paralysis.
Please see the following link for Genetic Testing.
In terms of genetic counseling, the disease is autosomal dominant. A variety of mutations in sodium, calcium, and potassium channel genes in muscle have been reported to cause hypokalemic periodic paralysis. One Lab in the United States, one lab in Germany, one lab in France, and one lab in the U.K. perform the genetic testing. The genetic test has very high specificity but poor sensitivity — that is, a positive test is confirmatory, but a negative test.
DO NOT rule out periodic paralysis.
Currently, there are only limited data to support a certain genotype predicting disease phenotype (i.e. severity and likelihood of responding to treatment). So, at this time, genetic testing may be helpful in establishing the diagnosis, for family planning, or for research purposes. There is a 50% chance the patient will give the disorder to his offspring. Penetrance is felt to be less in females.
Hyperkalemic Periodic Paralysis Management: Acute Attack
Control of hyperkalemia:
- Consider just giving a candy bar and waiting. Depends on the degree of paralysis.
- Insulin (with glucose to prevent hypoglycemia)
- Albuterol nebulizer
- Sodium Bicarbonate – 44-50 mEq over 5 min.
- Hypertonic saline
- Calcium administration intravenously (1 amp of 10% calcium gluconate) – under cardiac monitoring and only if EKG shows signs of severe hyperkalemia
- Position patient comfortably
- EKG for rhythm, especially QT interval.
- Monitor serum potassium q30min to 120min, depending on the condition of the patient and the medications being administered.
- Do not leave patients unattended! Conditions can change for better or worse rapidly. Risk of aspiration.
If associated with myoclonus (jerks), consider a small dose of benzodiazepine as jerk represents exercise and the trigger of paralysis is rest after exercise.
For myotonia, keep muscles warm (temperature).
Some experts feel that there is no role for kayexalate, a potassium binding resin, in the treatment of hyperkalemic periodic paralysis. This is because kayexalate is relatively slow-acting and corrective shifts in potassium needed for the treatment of attacks of hyperkalemic periodic paralysis must be rapid, as induced by glucose and either endogenous or exogenous insulin or albuterol. Chronic potassium lowering is achieved with potassium-wasting diuretics rather than a potassium-binding resin.
Some patients find that sleeping late on weekends triggers attacks (perhaps from prolonged rest or from too long a time without eating). HyperPP patients find that keeping their weekday waking schedule during the weekends helps to avoid weekend morning attacks. Some find that even getting up just to eat and then returning to bed can be helpful.
The following survey was published in Journal of Neurology