Rare Disease Report

Chapter 9: Periodic Paralysis

Periodic paralysis is a rare genetic condition in which a person has episodes of paralysis that can either be short and limited to a portion of the body or that can last hours or days and involve several limbs.

In most cases, the disease is due to a genetic mutation that predisposes ion channels in muscles to malfunctioning under certain circumstances. Changes in the chemistry around the ion channel can, under the right circumstances, cause dysfunction. In most cases, extreme levels of potassium, either high or low, lead to the paralysis.

Hypokalemic periodic paralysis, the more common form of this rare disease, is due to low potassium levels. However, some patients do become paralyzed when their potassium level is high, a condition referred to as hyperkalemic periodic paralysis.

Periodic paralysis is often difficult to diagnose because in persons with mild forms of the condition, the sporadic weakness may not be something they are concerned about, so they do not tell their doctor about it. In more severe cases, the paralysis can be fairly short-lived, and by the time the person gets to the emergency department to be evaluated by a physician familiar with muscle physiology, the paralysis may have subsided. Since the condition is so rare, most physicians may not be familiar with its unique symptomology. As a result, a person with this disorder can go years before being properly diagnosed.
It has been hypothesized that some of the people that Sigmund Freud evaluated who had bouts of weakness or paralysis may have suffered from periodic paralysis. They were not diagnosed with that condition by Dr Freud. Instead, patients were believed to have hysteria paralysis likely due to a childhood sexual trauma.

Times have changed.

Symptoms vary dramatically between patients, but common symptoms that may be observed in hypokalemic periodic paralysis include:
  • Weakness or paralysis in muscles in the hips, shoulders, arms, legs, and/or eyes
  • Symptoms appear after sleep or rest
  • Activities that appear to trigger an attack include:
    • Exercising
    • Eating a high-carbohydrate or high-salt meal
    • Consuming alcohol
  • Paralysis usually lasts 3 to 24 hours
  • Potassium blood levels are low

Other symptoms observed in hyperkalemic periodic paralysis may include:
  • Weakness after strenuous exercise or during fasting
  • “Heavy” or “stiff” muscles
  • High potassium blood levels

The gold standard for diagnosing periodic paralysis is a genetic test that identifies one of the calcium channel gene mutations or sodium channel gene mutations known to cause the disease. These genetic mutations or variants are continuing to be tabulated. At present, a known mutation can be found in 70% to 80% of individuals with hypokalemic periodic paralysis.

One way to investigate if a patient has hypokalemic periodic paralysis is to administer an oral potassium solution when he or she is having an attack. If the attack subsides, hypokalemic periodic paralysis is likely. Similarly, if a person is suspected of having hyperkalemic periodic paralysis, giving a high-carbohydrate snack can often relieve the symptoms and help in the diagnosis.

Since weakness and potassium fluctuations can be due to a variety of reasons, a thorough examination to rule out endocrine or cancerous reasons for the condition need to be addressed. A family history of weakness can also help clinicians in their differential diagnosis.

Once a diagnosis is confirmed, periodic paralysis is largely managed through lifestyle modifications.

For hypokalemic periodic paralyses, patients are advised to adhere to a low-carbohydrate and low-sodium diet to decrease the frequency of attacks; ingesting low levels of potassium may also improve the weakness. Diet, however, will not completely prevent attacks and medication will be necessary.

There is 1 FDA-approved treatment for both hypokalemic and hyperkalemic periodic paralysis: dichlorphenamide, a carbonic anhydrase inhibitor. Studies have shown that as a prophylactic agent, it can dramatically reduce the quantity of attacks.

For treating attacks, oral potassium can help treat a hypokalemic attack and a high carbohydrate snack, a hyperkalemic attack.

Patient Advocacy
The Peridiodic Paralysis Association (periodicparalysis.org/site/) is a nonprofit advocacy group founded by Jacob Levitt, MD, who is both a patient with periodic paralysis and a leading clinical expert in the field.
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