Periodic paralysis syndrome

ALSO KNOWN AS: Familial periodic paralysis; hypokalemic periodic paralysis; hyperkalemic periodic paralysis; Andersen-Tawil syndrome; paraneoplastic periodic paralysis; paramyotonia congenita

DEFINITION Periodic paralysis is a rare inherited condition that causes occasional episodes of severe muscle weakness. The two most common types of periodic paralysis are hypokalemic and hyperkalemic.

Risk Factors

Individuals should tell their doctors if they have any of the risk factors for periodic paralysis. Risk factors include having a family history of the condition and thyroid disorder; the latter factor is a particular risk for Asian males.

Etiology and Genetics

“Periodic paralysis syndrome” is a general term that refers to any of several rare genetic diseases, all of which are inherited as autosomal dominant disorders. This means that a single copy of the defective gene is sufficient to cause the disease, although not all family members who carry the gene are affected to the same extent. An affected individual has a 50 percent chance of transmitting the mutation to each of his or her children. Many cases of periodic paralysis syndrome, however, result from a spontaneous new mutation, so in these instances affected individuals will have unaffected parents.

Mutations in at least four different genes are known to cause this syndrome. All these genes encode ion channel proteins, which form bridges across cell membranes to facilitate the movement of electrically charged ions, such as potassium, sodium, and calcium. Mutations can result in nonfunctional or partially functioning ion channels that allow ions to leak in or out of muscle cells and result in the symptoms associated with the syndrome.

In hypokalemic periodic paralysis, potassium leaks into muscle cells from the blood. This condition is caused by mutations in the genes KCNE3 (at chromosomal position 11q13-q14), CACNL1A3 (at position 1q32), and SCN4A (at position 17q23.1-25.3). Different mutations in SCN4A can cause hyperkalemic periodic paralysis, in which potassium leaks out of muscle cells.

A fourth gene, KCNJ2 (at position 17q23.1-q24.2), is associated with Andersen-Tawil syndrome, a condition that involves changes in heart rhythms and other developmental abnormalities in addition to the characteristic periodic muscle weakness. It encodes an ion channel protein that is particularly prevalent in cardiac muscle, as well as skeletal muscle.

Symptoms

While muscle strength returns to normal between attacks, repeated bouts of weakness may lead to chronic muscle weakness later in life. An individual remains alert and aware during attacks, and there is no accompanying loss of sensation.

Episodic bouts of severe weakness in the arms and legs are the most prominent symptom of periodic paralysis. Typically, these bouts occur during sleep, especially after strenuous activity. Cold, stress, and alcohol may also produce attacks. Other, less common symptoms may include weakness in the eyelids and face muscles, muscle pain, and irregular heartbeats (arrhythmias). Another symptom may be difficulty breathing or swallowing, which requires emergency care.

Some features are specific to the type of periodic paralysis. In the hypokalemic type, potassium levels are low during attacks and the frequency of attacks varies from daily to yearly. Attacks usually last between four and twenty-four hours, but can last for several days. Attacks usually begin in adolescence, but they can occur before age ten.

In the hyperkalemic type, potassium levels are high or normal during attacks. Attacks are usually shorter (lasting one to two hours), more frequent, and less severe than in the hypokalemic form; breathing and swallowing difficulties are extremely rare. Between attacks, patients often experience muscle spasms or difficulty relaxing their muscles, a condition known as myotonia.

Individuals with some types of periodic paralysis are at risk for a condition known as malignant hyperthermia, which can occur during the use of general anesthesia. Anyone with a family history of periodic paralysis needs to notify the anesthesiologist of this history prior to any surgery.

Screening and Diagnosis

Because this primarily is an inherited condition, the most important aspect of diagnosis is obtaining a family history. In addition to asking about symptoms and a patient’s medical history, the doctor will perform a physical exam.

Attacks do not usually occur during an office visit, so the doctor may prescribe several blood tests to check potassium levels during an attack. The doctor may wish to bring on an attack during an office visit. This should be done only under careful monitoring by an experienced neurologist.

If an attack is triggered, several tests may be done, including blood tests to look for the gene mutation or to look for antibodies that may cause these types of symptoms; an electrocardiogram (ECG), a test that records the heart’s activity by measuring electrical currents through the heart muscle; and electromyography (EMG) to test the functioning of nerves and muscles. If the diagnosis is in question, the doctor may do a muscle biopsy.

Treatment and Therapy

Since there is no cure for periodic paralysis, lifelong treatment is usually required. Treatment focuses on preventing attacks and relieving symptoms. Individuals can adopt a few behaviors to reduce the frequency and severity of attacks. For individuals with hypokalemic period paralysis, these lifestyle changes include eating a low-carbohydrate, low-sodium diet and avoiding strenuous exercise. Individuals with the hyperkalemic type can eat a low-potassium diet; stay warm; and avoid fasting, alcohol, and heavy exercise.

Medications for both hypokalemic and hyperkalemic periodic paralysis include acetazolamide (Diamox), which may prevent an attack by reducing the flow of potassium from the bloodstream into the cells of the body. For patients with the hypokalemic type, potassium in pill or liquid form may stop an attack; intravenous potassium may be prescribed for severe weakness. Avoiding certain commonly prescribed medications may help reduce the onset of attacks. If these patients also have thyroid conditions, they should be sure to get treatment for these conditions.

Medications for patients with hyperkalemic periodic paralysis include thiazide diuretics, or water pills, which may be prescribed to prevent an attack; and glucose, glucose and insulin, or calcium carbonate, which may be prescribed to slow or stop an attack.

Prevention and Outcomes

Familial periodic paralysis cannot be prevented. Because it can be inherited, genetic counseling may be advised for couples at risk of passing on the disorder.

For the hypokalemic type, patients may reduce attacks by avoiding corticosteroids and glucose infusions and following a diet low in carbohydrates and sodium and rich in potassium. For the hyperkalemic type, patients may reduce attacks by avoiding high-potassium foods, fasting, and drugs known to increase potassium levels. Patients may also decrease attacks by engaging in regular, mild exercise.

Bibliography

Buchanan, Jill. “Periodic Paralysis Syndrome.” Health Library. EBSCO Information Services, 11 May 2013. Web. 5 Aug. 2014.

“Hyperkalemic Periodic Paralysis.” DynaMed. EBSCO Information Services, 30 Apr. 2013. Web. 5 Aug. 2014.

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Kim, S. J., Y. J. Lee, and J. B. Kim. “Reduced Expression and Abnormal Localization of the K(ATP) Channel Subunit SUR2A in Patients with Familial Hypokalemic Periodic Paralysis.” Biochemical and Biophysical Research Communications 391.1 (2010): 974–78. Print.

Levitt, J., P. Cochran, and J. Jankowiak. “Patient Page: Attacks of Immobility Caused by Diet or Exercise? The Mystery of Periodic Paralyses.” Neurology 63.9 (2004): E17–18. Print.

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Sripathi, Naganand. "Periodic Paralysis." Medscape, 4 June 2024, emedicine.medscape.com/article/1171678-overview?form=fpf. Accessed 9 Sept. 2024.