Rare Disease Report

Ask the Experts: Dr. Jaya Trivedi Talks Periodic Paralysis

SEPTEMBER 14, 2017
Jaya Trivedi, MD
Periodic paralyses are a group of rare diseases best characterized by episodes of skeletal muscles becoming weak or flaccid (ie, paralysis). The conditions are mostly genetic in nature, and researchers have determined that most cases stem from genetic abnormalities related to ion channels, leading to an imbalance of potassium within the muscle—which leads to the paralysis. The 2 most common forms of periodic paralysis pertain to potassium levels either being too high (hyperkalemic periodic paralysis) or too low (hypokalemic periodic paralysis).

The nature of periodic paralysis means that patients can go years without a correct diagnosis, and the sporadic characteristics of the condition mean that neurologists might not observe it firsthand, but instead hear about it from the patient or an emergency department physician. A careful history of the patient, their family, and the nature of the attacks, however, can make diagnosis and management fairly straightforward.

Rare Disease Report® spoke with Jaya Trivedi, MD, professor of neurology at UT Southwestern Medical Center in Dallas, Texas, about periodic paralysis.

Rare Disease Report®: What is periodic paralysis?
Dr Trivedi: Periodic paralysis is a skeletal muscle channelopathy. It is due to a genetic abnormality in the ion channels of the skeletal muscle.
There are 2 broad categories: hyperkalemic and hypokalemic periodic paralysis. In the hyperkalemic periodic paralysis, the potassium levels are high during attacks of paralysis, and in hypokalemic, the potassium levels are low.

Patients with hyper- or hypokalemic periodic paralysis will often have similar symptoms. The classic symptoms include a sudden onset of paralysis [that] could be [in] both legs or both legs and [arms]. Some patients will report truncal weakness or weakness in the neck. In extreme cases, patients can report trouble breathing.

The paralysis episodes can last minutes to hours to days. Patients with hypokalemic periodic paralysis can have attacks that last hours, if not days, but in hyperkalemic paralysis, the episodes are usually of shorter durations, lasting a few minutes to a few hours. Both hypo- and hyperkalemic versions are, in most cases, genetic conditions.

There are 2 broad types of attacks: major attacks and minor attacks. The major attacks are, like described earlier, paralysis of the muscles. Very often, patients will also have minor episodes where there is some muscle weakness but not complete paralysis. These minor attacks may be more frequent and occur multiple times in a day or week.

RDR®: What can trigger an attack?
Trivedi: For hypokalemic periodic paralysis, things that drop potassium levels can trigger an attack. These include eating certain foods (eg, carbohydrates, salty foods) or overexertion. Many people have attacks when they wake up in the morning and that may be related to an activity they did the night before—a baseball game, band practice, eating carbohydrates, drinking sodas, etc. For hyperkalemic periodic paralysis, fasting can lead to an attack.

RDR®: What symptoms, or pattern of symptoms, should lead a doctor to suspect periodic paralysis?
Trivedi: The semiology of the attack of weakness, the age of onset, and the things that trigger an episode.

RDR®: Is genetic testing the gold standard for diagnosis?
Trivedi: Genetic testing is the gold standard to make a definitive diagnosis. It can also help guide the patient toward genetic counselling so that other family members can be made aware of the risk and be tested for this condition.

RDR®: Are there other atypical forms of periodic paralysis?
Trivedi: There is a very rare condition called Andersen-Tawil Syndrome. With [this] condition, patients can have periodic paralysis, but also heart rhythm disturbances and skeletal deformities.

RDR®: What are the treatment options for patients with periodic paralysis?
Trivedi: For hypokalemic patients, the person should keep a diary to determine what their triggers are for an attack. Also, they can be treated with potassium supplements.

There are 2 additional treatments for patients with periodic paralysis. Both are carbonic anhydrase inhibitors. The first is acetazolamide. This can be taken on a daily basis by both hypokalemic and hyperkalemic patients to reduce the number of attacks. In some patients, it might work, and in some, it might not. But in all patients, you should offer the treatment.

The second treatment option is dichlorphenamide, which was approved a couple years ago for reducing attacks in patients with either hypokalemic and hyperkalemic periodic paralysis. I was involved in the clinical trial that led to this drug’s approval and did find the drug to be effective.

For hyperkalemic periodic paralyses, patients should avoid fasting states and are encouraged to take carbohydrates during an attack to help lower the potassium.

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