Hypokalemic periodic paralysis

Hypokalemic periodic paralysis is a rare channelopathy characterized by muscle weakness or paralysis with a matching fall in potassium levels in the blood. In individuals with this mutation, attacks often begin in adolescence and are triggered by strenuous exercise followed by rest, high carbohydrate meals, sudden changes in temperature and even excitement, noise or flashing lights. Weakness may be mild and limited to certain muscle groups, or more severe full body paralysis. Attacks may last for a few hours or persist for several days. Recovery is usually sudden when it occurs. Some patients may fall into an abortive attack or develop chronic muscle weakness later in life.

Diagnosis
Patients often report years wasted with wrong diagnosis, wrong treatments, deadends and multiple doctors, test and clinics. The CMAP (Compound Muscle Amplitude Potential) test, also called the exercise EMG or X-EMG, is diagnostic in 70-80% of cases when done correctly. Besides the patient history or a report of serum potassium low normal or low during an attack, the CMAP is the current standard for medical testing. Genetic diagnosis is often unreliable as only a few of the more common gene locations are tested. Standard EMG testing cannot diagnose a patient unless they are in a full blown attack at the time of testing. Provoking an attack with exercise and diet then trying oral potassium can be diagnostic, but also dangerous as this form of PP has an evil twin called Hyperkalemic Periodic Paralysis. The symptoms are almost the same, but the treatment is different. The old glucose insulin challenge is dangerous and risky to the point of being life threatening and should never be done when other options are so readily available.

Treatment
Treatment of hypokalemic periodic paralysis focuses on preventing further attacks and relieving acute symptoms. Avoiding carbohydrate-rich meals and strenuous exercise, and taking acetazolamide or another carbonic anhydrase inhibitor, may help prevent attacks of weakness. Paralysis attacks can be managed by drinking effervescent potassium bicarbonate dissolved in water, or potassium chloride oral solution. Some patients find positive results with time release potassium tablets. IV potassium is seldom justified unless the patient is unable to swallow. Daily potassium dosage may need to be much higher than for potassium replacement from simple hypokalemia: 100-150 mEqs of potassium bicarbonate is often needed to manage daily fluctuations in muscle strength and function.

Prognosis
The prognosis for periodic paralysis varies. Over activity, bad diet or simply an unfortunate gene mutation can lead to a type of chronic, low level weakness called an "abortive attack," or to permanent muscle damage. Abortive attacks often respond to extra potassium, cutting carbohydrates, getting plenty of rest, increasing doses of medication and gentle daily exercise such as short walks. Permanent muscle weakness is just what it sounds like, permanent, irreparable damage to the muscles. Vacuoles and tubular aggregates form and destroy healthy muscle tissue. This type of damage should show on a muscle biopsy. Not even anabolic steroids can bring these damaged muscles back.

Life span is expected to be normal, but attacks can drop potassium to levels low enough to cause life threatening breathing problems or heart rhythm difficulties. Patients often report muscle pain and cognitive problems during attacks. Migraines occur in up to 50% of all hypokalemic periodic paralysis patients and may include less common symptoms like phantom smells, sensitivity to light and sound or loss of words. Medical literatures states that muscle strength is normal between attacks, but patients tell a different story. "Normal" for them is not exactly the same as "normal" for everyone else.

Because there are dozens of possible gene mutations, some drugs and treatments that work fine for one patient will not work for another. For example, most patients do well on acetazolamide, but some don't. Most patients will do well with extra magnesium (the body's natural ion channel blocker) or fish oil, while these same nutrients will make other patients worse. Patients and care givers should take extreme caution with all new drugs and treatment plans.

Genetics
Mutations in the CACNA1S and SCN4A genes cause hypokalemic periodic paralysis.

The CACNA1S and SCN4A genes provide instructions for making proteins that play an essential role in muscles used for movement (skeletal muscles). For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of certain positively charged atoms (ions) into muscle cells. The CACNA1S and SCN4A proteins form channels that control the flow of these ions. The channel formed by the CACNA1S protein transports calcium ions into cells, while the channel formed by the SCN4A protein transports sodium ions.

Mutations in the CACNA1S or SCN4A gene alter the usual structure and function of calcium or sodium channels. The altered channels cannot properly regulate the flow of ions into muscle cells, which reduces the ability of skeletal muscles to contract. Because muscle contraction is needed for movement, a disruption in normal ion transport leads to episodes of severe muscle weakness or paralysis.

A small percentage of people with the characteristic features of hypokalemic periodic paralysis do not have identified mutations in the CACNA1S or SCN4A gene. In these cases, the cause of the condition is unknown.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.