Hypokalemic 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.
Hypokalemic periodic paralysis (HypoPP) is the most common type of periodic paralysis.
In this type, low blood potassium levels trigger attacks, and potassium levels usually drop during attacks as well. “Hypo” means that there is a low amount of something, and “kalemic” refers to potassium. There is another periodic paralysis type with a similar name, “hyperkalemic,” so it’s important to not confuse these two types.
Hypokalemic periodic paralysis causes sufferers to have attacks of extreme muscle weakness or paralysis. These attacks may last from a few hours to a few days. The 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 and they may seem like they are unconscious (even though they really are conscious). Attacks may affect one area, like an arm or leg, or many areas at once around the body.
Attacks of hypokalemic periodic paralysis can be triggered by the patient not having enough potassium in their blood (AKA serum potassium). Potassium levels usually fall during an attack, although not always. The reason there is not enough potassium in the blood is that too much potassium has moved from the blood into the muscles, causing a chemical imbalance that prevents the muscles from moving the way they should.
Another symptom that can occur in middle-aged and older adults is myopathy, which is permanent muscle weakness. This is a result of the large number of attacks that have damaged the muscles over the years. Getting treatment early on can reduce the chances of myopathy occurring in later years.
Hypokalemic periodic paralysis attacks have several different triggers, and not every person has the exact same set of triggers. Eating high-carb foods or high-sodium foods might bring about an attack. Each person who has this disorder has to figure out over time which foods are triggers for them and which foods are not. Being cold is also a trigger, which presents major challenges for people living in cold climates.
Exercising and then resting afterward can trigger an attack, especially if the exercise was intense. Sleeping can be a trigger, because some people unknowingly have attacks while they are sleeping, and many have attacks as soon as they wake up. Stressful emotions tend to trigger attacks, too. It may be helpful to keep a trigger diary to record what time attacks happen, how you felt during the attacks, and what you were doing before attacks.
People who have hypokalemic periodic paralysis usually begin having symptoms during their childhood or teen years. In many cases, they have never heard of periodic paralysis and are not sure why they are having attacks of muscle weakness. Many doctors do not know anything about periodic paralysis either, so when they see patients who have it, doctors often give them the wrong diagnosis. Sadly, it’s common for people to go many years without having the correct diagnosis of periodic paralysis.
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. Hypokalemic 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. A muscle biopsy is sometimes needed for doctors to diagnose periodic paralysis. This means that the doctor must remove and examine a small piece of the patient’s muscle tissue during or after an attack to see if the muscle tissue is abnormal. 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.
One way to treat hypokalemic periodic paralysis attacks while they are happening is by giving the patient potassium chloride (KCl) taken orally. However, this may not be effective in an emergency situation, where the patient is having a severe attack that makes it difficult for them to swallow or breathe. In these cases, the patient might have to be given potassium chloride through an IV.
In between attacks, it’s important for people with hypokalemic periodic paralysis to live a lifestyle that minimizes triggers. Staying in warm environments, keeping stress under control, eating a low-sodium and low-carb diet, and avoiding strenuous exercise can reduce the likelihood of an attack happening. Potassium supplements might reduce attacks as well. In addition, there are medications that can help, such as acetazolamide, methazolamide, spironolactone, and dichlorphenamide (KEVEYIS, the only FDA-approved periodic paralysis treatment). Different patients will have different combinations of medications that are right for them.
Your Next Steps
If you think you may have hypokalemic 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!
Presenting Symptoms and Common Characteristics Associated with the Periodic Paralyses
- Attacks may last from minutes to days, and occur sporadically.
- Weakness can be local or generalized.
- The deep tendon reflexes become depressed, diminished, or lost in the course of the attacks.
- The muscle fibers become unresponsive to either direct or indirect electrical stimulation during attacks.
- The generalized attacks usually begin in proximal muscles and then spread to distal ones.
- Respiratory and cranial muscles tend to be spared but eventually may also be paralyzed.
- Rest after exercise tends to provoke weakness of the muscles that had been exercised, but continued mild exercise may abort attacks.
- Exercise restricted to a single muscle or a small group of muscles can induce weakness of the exercised muscles without a detectable change of the potassium level in the systemic circulation.
- Exposure to cold may provoke weakness in the primary forms of the disease.
- Complete recovery usually occurs after initial attacks.
- Permanent weakness and irreversible pathological changes in muscle can develop after repeated attacks.
- Onset at puberty is common. The reason for this still remains a mystery.
Some signs and symptoms noted at the PPA Conference that may also be part of familial hypokalemic periodic paralysis (but have not been formally validated) are:
- muscle pain with and after attacks,
- mental confusion with attacks,
- having an off-mood/bad mood/irritability during attacks,
- non-restorative sleep with attacks,
- dark circles under the eyes prior to and during an attack,
- feeling sleepy after attacks,
- attacks due to exposure to cold.
Diagnostic Work Up
Chief Complaint: I had a bout of weakness. I think I have periodic paralysis.
Primary Medical Doctor can do:
- 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 nephrologist about specific tests
- Neurological investigation – CMAP (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 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
- Refer back to PMD once the diagnosis is established for continued management
Other Types of Specialists Involved
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. CPK is a helpful test as it shows muscle breakdown during an attack. The CPK can be very high.
Involve an Endocrinologist to rule out adrenal causes of hypokalemia.
Involve a Nephrologist to rule out renal disease and to get advice about electrolyte management.
CMAP (McMannis 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 DOES NOT rule out periodic paralysis. Currently, there are only limited data to support a certain genotype predicting disease phenotype (i.e. severity and the 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.
Management of Potassium:
- Oral K preferred over IV K. Aqueous K favored over pill form.
- Dosing: 40-60mEq p.o. of potassium, in the absence of underlying deficit (as is the case in hypokalemic periodic paralysis), should cause a rise of 1.0-1.5 mEq in serum potassium. 135-160mEq p.o. of potassium should cause a rise of 2.5 to 3.5 mEq in serum potassium.
- No D5 in i.v. fluids. If possible, no saline in fluids – may try mannitol 5% to give a bolus of potassium.
- No more than 10-20mEq/hr [i.e. 250-500cc of 40mEq/L solution/hr]. Concentrations >= 60mEq/L causes pain and phlebitis in peripheral veins. So, expect pain with 10-20 mEq K+ in 100cc of 5% mannitol.
- Albuterol and insulin EXACERBATE attacks.
- If the patient has not taken K+ before coming to ER, consider dosing a bolus of 60mEq p.o. by aqueous solution. Wait 1 hour. Then re-dose.
- Be careful not to overcorrect. Wait 20-60min. before re-dosing. Patience is key.
- Position patient comfortably in “coma position” if possible. This means turning them to the left or right side so they do not aspirate.
- EKG for rhythm, especially QT interval.
- Monitor serum potassium q30min to q120min, depending on the condition of the patient and medications being administered.
- Do not leave the patient unattended! The condition can change for better or worse rapidly. Risk of aspiration.
- There is probably no role for acetazolamide or potassium-sparing diuretics in the management of an acute paralysis attack; however, no evidence-based study has proven this hypothesis.
- 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).
- Fluid to deliver potassium can be Ringers Lactate as well as Mannitol as many hospitals do not stock Mannitol.
Potassium Metabolism and Dosing
Potassium replacement must be done in accordance with clinical findings (muscle weakness and cardiac rhythm abnormalities) taking precedence over the numerical value of serum potassium.
In normal people:
A decrease from 4.0 to 3.0 mEq can correspond to 200-400mEq potassium deficit.
A decrease from 3.0 to 2.0 mEq can correspond to 200-400mEq potassium deficit.
Decreases below 2.0mEq can represent a deficit larger than 800mEq as intracellular potassium begins to compensate.
In periodic paralysis, these deficits may or may not hold true. The hypokalemia in hypokalemic periodic paralysis is due to POTASSIUM SHIFTS rather than a deficit. Therefore, more conservative (i.e., less aggressive) potassium replacement is needed. Doses above 200mEq over a period of two hours are rarely ever required.
There is no reason to believe that patients with periodic paralysis have an impaired muscle repair capability. In general, patients should remain as active as possible. How much exercise they can do depends on their individual threshold for inducing an attack of periodic paralysis is. If a particular exercise is inducing an attack then they are doing too much. For all patients with muscle disease, it is less desirable to do progressive resistive exercises meant to “bulk up”. Rather, patients should do more toning/aerobic types of exercises with less weight/resistance and more repetition. Specifically, eccentric contraction should be avoided.
Patients should NOT do repetitive exercise. It is better to do exercise that uses all muscles at the same time such as swimming (only with a partner), martial arts, and yoga.
The role of a physical therapist has yet to be defined. Some find passive stretching and massage to be helpful, but no formal recommendations can be made at this time.
Diet and Nutrition
Contact the National Kidney Foundation: 1-800-622-9010
HypoKPP can benefit from increased dietary potassium and in general, should:
- Avoid Sodium
- Avoid High Carbohydrate Meals
- Avoid Sugar, Honey, and other natural sweeteners
J Transl Med. 2008; 6:18.
An excellent discussion of potassium metabolism and management can be found in:
Rose, Burton David. Clinical Physiology of Acid-Base and Electrolyte Disorders Fourth Edition. New York, 1994, McGraw-Hill, Inc. Health Professions Division, pp. 763-852.
We thank Periodic Paralysis International for this link: