What is Hypokalemic Periodic Paralysis?
Hypokalemic periodic paralysis (hypoPP) is a rare condition brought on by changes in muscle cell proteins, mainly impacting those connected with calcium or sodium flow. The condition is marked by sudden, severe weaknesses in muscles, commonly triggered by intense physical activity or a diet high in carbohydrates. Individuals with hypoPP deal with a sudden onset of flaccid paralysis, which is a state of severe muscle weakness, linked to low levels of potassium in their blood. This can last for many hours before it dissipates naturally.
Generally, HypoPP is passed down through a family’s genes. This genetic form of HypoPP results from changes in either calcium or sodium muscle cell proteins. Cases of this condition that aren’t inherited are also discovered and are often connected with an overactive thyroid. The specific genetic change that causes HypoPP, found in the CACNA1S gene, was first identified by scientists named Jurkat-Rott and others, in the year 1994.
What Causes Hypokalemic Periodic Paralysis?
Hypokalemic periodic paralysis (hypoPP) is a condition that can either be inherited or acquired later in life.
Inherited hypoPP happens due to changes, or mutations, in one of two genes related to calcium or sodium ions. Ions are electrically charged atoms or molecules, and these ions are crucial for nerve and muscle function. One mutation related to the calcium channel gene (CACNA1S) leads to the most common form of inherited hypoPP, called type 1. Another type of inherited hypoPP, called type 2, is caused by a mutation in the sodium channel gene (SCN4A). There are also mutations in other genes – KCNJ2 and KCNJ18 – which regulate potassium channels, and have been linked to hypoPP.
Acquired hypoPP, on the other hand, is linked to a condition called thyrotoxicosis, which is an excess of thyroid hormones in the body. This, together with the inherited forms, make up the main types of hypoPP.
This condition can also occur due to low levels of potassium in the blood, or hypokalemia, which can be a result of kidney or digestive system problems, like renal tubular acidosis or gastroenteritis, or due to hormonal-related causes. This potassium loss can bring on episodes of muscle weakness.
Risk Factors and Frequency for Hypokalemic Periodic Paralysis
HypoPP, or hypokalemic periodic paralysis, is a rare condition, occurring in about 1 in 100,000 people. It’s often found in families due to genetics, with the condition tending to be less severe in women due to a trait known as incomplete penetrance. Additionally, women usually have fewer episodes of muscle weakness than men.
- It’s a rare disorder affecting 1 in every 100,000 people.
- HypoPP is often passed down within families, particularly showing up in an autosomal dominant pattern.
- Women tend to show fewer symptoms due to lower penetrance and attack rates.
- Some cases occur due to new genetic mutations, without a family history of the disease.
- A specific type of HypoPP linked to thyrotoxicosis is usually found in individuals of Asian descent, and is up to 9 times more common in males.
Signs and Symptoms of Hypokalemic Periodic Paralysis
Hypokalemic periodic paralysis (HypoPP) is a health condition that often affects individuals in their first or second decade of life (late childhood or teenage years), becoming less frequent as the person ages. People with thyrotoxic HypoPP usually experience the onset of symptoms after they turn 20. The condition is characterized by random episodes of weakness that can be triggered by factors such as resting after intense exercise or eating a lot of carbohydrates.
When these triggers cause a rise in adrenaline or insulin in the blood, it results in potassium moving inside the cells and reducing the serum potassium levels, causing episodes of weakness. Other less consistent triggers include strong emotions such as excitement or fear, exposure to cold, high salt in the diet, using corticosteroids, drinking alcohol, or having anesthesia for surgery. Patients typically experience sudden, severe attacks of generalized muscle weakness that impact the muscles closer to the body’s core more than the distant ones, and are accompanied by significantly decreased serum potassium levels. These attacks of muscle weakness often occur during the night or early in the morning.
Patients may also experience warning signs like being tired, pins and needles sensations, and changes in behavior a day before an attack of muscle weakness. However, incomplete attacks usually affect the legs more than the arms. Muscles that help in swallowing, eye movement, and breathing tend to be spared, but if the last group is affected, it can be life-threatening. The frequency and duration of these attacks can vary greatly, and women usually have fewer attacks than men. During an attack, examinations generally show generalized muscle weakness, less reflex responses or none at all, and the legs being more affected than the arms in incomplete attacks.
Between attacks, some patients may experience a milder, fluctuating form of muscle weakness that improves with light exercise. In a particular case study of HypoPP, patients with no identified mutations showed differences compared to those with mutations. These differences included disease onset at an older age, absence of dietary triggers, and their muscle biopsies not showing a specific type of muscle damage. Also, patients with different types of mutations exhibited varying characteristics.
Testing for Hypokalemic Periodic Paralysis
Hypokalemic periodic paralysis (HypoPP) is a condition that can be suspected when a person suddenly experiences a weakness in their muscles, especially in the upper body, even though their reflexes seem normal or reduced. This is typically seen after the person is exposed to certain triggers. If the person or their family members have had similar episodes in the past, it raises the chances of HypoPP.
If the family history of HypoPP is known, additional tests may not be necessary to confirm HypoPP during a paralysis episode. But, in the absence of a family history, if blood tests show low levels of potassium (a mineral important for nerve and muscle cell functioning) during a weakness episode, it helps confirm the condition.
The diagnosis of HypoPP is usually straightforward, but sometimes additional tests are conducted to rule out other causes. For example, the thyroid function test measures the levels of thyroid hormones to exclude hyperthyroidism (overactive thyroid). An electrocardiogram (ECG – test that records the electrical activity of the heart) can show changes related to low potassium levels and hint at conditions like Anderson syndrome, which can prolong the time between heartbeats.
Hypokalemic periodic paralysis diagnosis can be difficult between attack episodes as potassium levels usually remain normal during these periods. Low potassium levels outside of an attack may point towards another cause of HypoPP.
Other tests that can be used for diagnosis include genetic testing, provocative testing, and electromyography (EMG – a test that measures the electrical activity of muscles). Genetic testing can identify gene mutations often seen in HypoPP. However, not all mutations can be picked up by this test.
In cases when genetic testing doesn’t reveal a mutation, provocative testing and EMG can help understand the condition better. Provocative testing involves administering potassium, insulin, or glucose to diagnose HypoPP. But this can be risky as it can potentially lead to dangerous heart rhythm problems or low blood sugar levels. Hence, patients undergoing provocative testing need to be closely monitored in a hospital setting.
Electromyography (EMG) can be helpful during a muscle weakness episode as it can show reduced muscle electrical activity, how much of which depends on the degree of muscle weakness during the attack. Between attacks, EMG can help monitor change in muscle fiber activity because of the disease process. This tool can bring on a muscle weakness episode by making a single muscle exercise hard for 2 to 5 minutes, tracking the muscle activity post-exercise. An abnormal and usual occurrence is a 40% or more reduction in muscle activity, which is a confirmed indicator of periodic paralysis. Interestingly, an alternative way to diagnose HypoPP between attacks may be to measure the range of little finger movement after exercise.
Biopsy, a procedure that involves taking a small tissue sample for examination, is not typically performed between HypoPP attack episodes as its findings don’t directly point towards periodic paralysis.
Treatment Options for Hypokalemic Periodic Paralysis
In the treatment of hypoPP, a condition that causes sudden muscle weakness, the main goals are to ease the symptoms of an acute attack, prevent immediate and future complications, and stop subsequent attacks from happening.
In an acute hypoPP attack, the main treatment is to use oral potassium chloride to bring the levels of potassium in the blood back to normal. This aids in reducing symptoms of muscle weakness. In starting treatment, a carefully measured amount of oral potassium chloride is given. If it does not have any effect, another dose may be given every 30 minutes. In some situations, the rate of administration may be slowed down to avoid a sudden surge in potassium levels. Anyone requiring a high amount of oral potassium must be closely monitored. Doctors will also utilize ECG to monitor heart activity, check muscle strength periodically ,and continue to monitor potassium levels for a day after treatment, as elevated post-treatment potassium levels may have negative impacts.
Intravenous (IV) potassium is usually not the first choice for treatment – it is kept for specific scenarios such as abnormal heart rhythms caused by low potassium, swallowing issues, or when respiratory muscles are paralyzed. If IV potassium is required, it is given preferably with mannitol and not dextrose or saline to avoid triggering muscle weakness. This type of treatment needs to be given in a hospital with continuous monitoring of the heart’s electrical activity.
For milder attacks, low-level exercises can also help improve the functioning of muscles and lessen the severity of symptoms during attacks.
Preventive treatment to stop future attacks includes both pharmacological and non-pharmacological methods. Non-drug interventions involve educating patients about factors that can cause attacks and teaching them how to make lifestyle adjustments to avoid these factors. When lifestyle changes alone don’t reduce the frequency of attacks, drug treatments such as chronic potassium supplementation, carbonic anhydrase inhibitors, and potassium-sparing diuretics can be used. Carbonic anhydrase inhibitors have been shown to decrease future attacks of muscle weakness in hypoPP patients, but the exact process by which it works isn’t thoroughly understood. Some patients have also seen benefits from adding a potassium-sparing diuretic, which can increase the amount of potassium in the body.
Some considerations are necessary for patients with hypoPP going through surgery, as they are at increased risk of a severe reaction to certain anesthetic drugs, termed malignant hyperthermia. Therefore, surgeons need to be cautious about using such anesthetics and be ready to manage any possible occurrence of this reaction. Also, stress and certain factors during surgery can trigger muscle weakness in these patients, so close monitoring of potassium is crucial.
For women who are pregnant with hypoPP, managing potassium levels during attacks should remain the same as before pregnancy, but certain medications including acetazolamide and dichlorphenamide are categorized as potentially risky during pregnancy. Thus, their use should be considered carefully, and risks versus benefits should be weighed. Some women may choose not to take these drugs due to concerns about potential risks during pregnancy.
What else can Hypokalemic Periodic Paralysis be?
In simpler terms, when the disease known as primary Hypokalemic Periodic Paralysis (hypoPP) is suspected, other conditions that could induce similar symptoms also have to be considered. These include:
- Periodic paralysis that’s associated with normal or heightened potassium levels
- Andersen-Tawil syndrome
- Secondary hypokalemia
- Myasthenia gravis
- Paramyotonia congenita
The symptoms common for these conditions are episodes of low potassium, attacks of muscle weakness, and weakness or stiffness following exercise.
In normokalemic and hyperkalemic periodic paralysis, there’s a difference from hypoPP in various ways such as normal or elevated potassium levels during attacks, absence of certain triggers, a younger age of onset, and different findings on electromyography (EMG) testing. The response to potassium might differ as well from that of hypoPP, which could ease or worsen symptoms.
Andersen-Tawil syndrome arises from mutation in the KCNJ2 gene, accounting for various symptoms like periodic paralysis, cardiac issues, distinctive facial features and skeletal anomalies. These symptoms usually appear early in life, in the first or second decade, and serum potassium levels could be high, normal or low. Despite many cardiac issues, serious heart conditions are rarely observed in Andersen-Tawil syndrome. This syndrome also shows similar EMG responses to hypoPP, necessitating genetic testing for the correct diagnosis.
Paramyotonia congenita is an inherited muscle weakness disorder that gets worse with cold weather and continued activity. Patients often start showing symptoms during childhood with myotonia and weakness lasting for minutes to hours post-activity. Special tests can show mutations in the SCN4A gene which are responsible for the disease.
Thyrotoxic periodic paralysis is similar to hypoPP but requires the presence of hyperthyroidism for symptoms to occur. The manifestation of symptoms is generally later in life than in hypoPP, and most cases lack a positive family history. Muscle paralysis associated with this condition disappears when thyroid function is within normal levels. Examinations can show mutation in the potassium channels coded by KCNJ18 in about one third of patients.
Secondary Hypokalemia is another condition where the main symptom is muscle weakness. Chronic hypokalemia can happen because of various other conditions and doctors look for low potassium levels between attacks to diagnose it. Some causes of chronic hypokalemia include certain drug usage, various renal, gastrointestinal, endocrine and artificially induced conditions.
Other potential conditions include Metabolic Myopathies, which typically present with fatigue, difficulty tolerating exercise and muscle pain. And Myasthenia Gravis, which is recognized for muscle weakness that’s not episodic as in periodic paralysis and more predictable as it’s often triggered by physical exertion.
Understanding these differences and similarities is essential for accurate diagnosis and effective treatment.
What to expect with Hypokalemic Periodic Paralysis
The outcome of hypoPP, a condition that causes episodes of muscle weakness, can greatly differ from person to person. Typically, people do well after taking oral potassium when they have episodes of muscle weakness. However, if these episodes keep happening, they can lead to serious health problems and increase the need for hospital stays, which can also affect a person’s day-to-day life and work life.
While it’s uncommon for someone to die directly because of these muscle weakness episodes, there have been cases where complications like aspiration pneumonia, a lung infection that happens after you’ve inhaled (aspirated) food, drink, vomit, or saliva into your lungs, have led to death.
Possible Complications When Diagnosed with Hypokalemic Periodic Paralysis
: During a muscle weakness attack, two potentially life-threatening complications may happen:
- Heart rhythm problems (cardiac arrhythmias) caused by low potassium in the blood (hypokalemia)
- Breathing issues because the muscles used for breathing become paralyzed (respiratory insufficiency)
It’s important to note that hypoPP, a condition causing episodes of muscle weakness, doesn’t usually affect the heart. However, cases of heart rhythm problems have been reported during muscle weakness attacks.
Between the episodes of paralysis, which we call the interictal period, patients with hypoPP commonly experience long-lasting muscle weakness. The exact reasons and how often this happens are not yet known. It’s thought that this weakness might be caused by too much sodium intake due to leaks in the cell’s ‘gates’. Potassium or acetazolamide treatment may help manage these symptoms.
As the condition progresses, most patients develop a muscle condition called myopathy. This typically becomes noticeable after the age of 50 and causes less changeable muscle weakness that’s not very responsive to medications. This suggests ongoing muscle degeneration. The muscle weakness often shows up in the muscles around the hip area and the closer parts of the arms and legs. A muscle biopsy might show signs of myopathy before symptoms appear.
The severity of myopathy in hypoPP varies from person to person. While some people only develop mild muscle weakness that doesn’t interfere with their daily activities, others may develop severe myopathy and become reliant on a wheelchair for mobility. However, there’s not enough evidence to say whether developing myopathy is directly related to the number or intensity of muscle weakness episodes.
One recognized side effect of acetazolamide treatment is nephrolithiasis, or kidney stones. Up to 15% of long-term acetazolamide users may develop kidney stones. Management of this side-effect involves removing the stones while continuing with the treatment.
Preventing Hypokalemic Periodic Paralysis
Learning about their condition is crucial for people with hypoPP, a rare condition that causes muscle weakness. By understanding their condition, patients can make lifestyle changes to avoid things that trigger their symptoms. These changes can help prevent future episodes, reduce the number of times they need to go to the hospital, improve their quality of life, and save money on hospital bills.
Everyone is different, so what triggers an episode for one person might not trigger it for another. Some of the things people can do to avoid triggering an episode include not overdoing it with exercise, eating smaller meals more often to avoid a buildup of carbohydrates, lowering the amount of salt they eat, trying to avoid stressful situations, and trying to stay active so they don’t spend too much time lying or sitting down.
People with hypoPP need to identify what’s causing their episodes because it can vary from person to person. These episodes often happen in the morning when the person first wakes up or in the middle of the night. It’s important to make sure their bedroom is safe to prevent them from falling and hurting themselves. Tips include keeping the floor free from anything they might slip on, positioning the bed away from open windows or air conditioning units to prevent them from getting too cold when they can’t move during an episode.
If something does happen and they can’t move during an episode, they should have a plan for alerting someone or calling 911. Also, it’s a good idea for people with hypoPP to keep their potassium tablets easily accessible in case they need them during an episode. This might mean keeping tablets by the bed, at work, in their pocket, or in the car.
