Periodic paralysis (PP)

Muscle channelopathies are a group of neuromuscular conditions. They are divided into two main types: the periodic paralyses (PP) and the non-dystrophic myotonias (NDM), depending on their main symptom.

PP are rare genetic conditions that cause episodes of muscle weakness or paralysis. These episodes are temporary but vary in how severe they are and how long they last.

There are three main forms of periodic paralysis:

• Hypokalaemic periodic paralysis (HypoPP) – triggered by low blood potassium levels
• Hyperkalaemic periodic paralysis (HyperPP) – triggered by high blood potassium levels
• Andersen-Tawil Syndrome

Hypokalaemic periodic paralysis (HypoPP)

Symptoms of HypoPP usually start in the early teens. Episodes of muscle weakness or paralysis can happen when potassium levels in the blood are low. This could be triggered by stress, high-carbohydrate meals, exercise, or periods of rest and immobility after exercise. Episodes often develop during sleep and weakness is sometimes felt during the night or in the morning after waking up.

Episodes typically last several hours but can sometimes continue for days. Episodes can make it difficult to move, walk, or lift the arms and legs. The frequency of episodes varies widely. They may occur several times a week or only once or twice a year. Normal muscle strength and function usually returns between episodes. Often the episodes become less frequent by mid-adulthood, but some people may develop permanent weakness in their legs and arms at this age. This can lead to walking at a slower pace or make daily activities like walking up stairs harder.

Hyperkalemic periodic paralysis (HyperPP)

Symptoms of HyperPP usually start during childhood or adolescence. Episodes of muscle weakness or paralysis can happen when potassium levels in the blood are high. This could be triggered by cold environments, stress, potassium-rich foods, or resting after exercise. Episodes can happen at any time of day and can last minutes to hours, with the weakness mainly affecting the arms and legs. Those affected may experience some muscle stiffness (myotonia). The frequency of episodes varies widely, from several times a week to only once or twice a year. Normal muscle strength and function usually returns between episodes, but recovery can take some time. With age, some people may develop permanent muscle weakness in their arms and legs. This can lead to walking at a slower pace or daily activities like walking up stairs harder.

Andersen-Tawil syndrome

Andersen-Tawil syndrome is unique among the periodic paralyses because it affects not only the skeletal muscles needed for voluntary movement but also the heart muscle. It can also cause distinctive facial features and bone structure.

Symptoms of Andersen-Tawil syndrome typically begin during childhood or adolescence but can start later. Episodes of weakness are usually like those seen in hypokalemic periodic paralysis (HypoPP) and can be triggered by stress, rest after exercise, and carbohydrate-rich foods. Weakness mostly affects the arms and legs and typically lasts from hours to days.

Some people with Andersen-Tawil syndrome may develop cardiac arrhythmias (changes in heart rhythm). This can cause symptoms of palpitations, shortness of breath, or chest pain. If severe, this can cause fainting. Monitoring of the heart by a cardiologist (a heart doctor) is essential.

Andersen-Tawil syndrome can also cause distinctive physical features. For example, a small chin, fingers, and toes or short stature. These features vary and not all of them are present in everyone.

Genetic changes

The periodic paralyses are caused by genetic changes affecting ion channels in muscle cells. Ion channels control the flow of electrical signals that tell muscles to contract and relax. These channels don’t always work properly in people with PP, leading to episodes of muscle weakness. In some cases, this can lead to permanent muscle damage, causing some muscle wasting and fixed, rather than episodic, weakness.

• Hypokalemic periodic paralysis: CACNA1S and SCN4A gene changes occur and affect the muscle calcium or sodium channels.
• Hyperkalemic periodic paralysis: SCN4A gene changes occur and affect the muscle sodium channels.
• Andersen-Tawil syndrome: KCNJ2 gene changes occur and affect the muscle and cardiac potassium channels.

Inheritance

All types of PP follow an autosomal dominant inheritance pattern. This means that only one changed gene, from one parent, needs to be inherited to cause the condition and symptoms. There is a 1 in 2 chance of passing on the condition to each child.

For more information, see our inheritance and genetics page.

Episodes of muscle weakness or paralysis should be reported to a GP, who can make a referral to a neurologist. A neurologist is a doctor who specialises in diagnosing, treating, and managing conditions that affect the muscles and nervous system. They may use a combination of the following to diagnose PP:

• History of symptoms – what occurs and when
• Physical examination
• Blood tests – to measure creatine kinase (CK) levels and electrolytes
• Electrocardiogram (ECG) – to look at electrical conduction through the heart
• Nerve conduction study and electromyography (EMG) – to test the function of nerves and muscles. This may include a test called a long exercise test which records electrical activity in the muscles before, during, and after sustained exercise

Genetic testing, using a blood sample, can confirm a suspected diagnosis by identifying changes in the genes known to cause PP.

For more information, see our diagnosis page.

People with PP should have access to a consultant or healthcare team with knowledge of PP to review their condition. Symptoms can be managed with medication, alongside dietary and lifestyle changes. If you do not have a specialist doctor, speak to your GP about getting access to one.

Exercise and staying active is important for everyone, but because exercise can be a trigger in PP, people should get advice before starting exercise. A physiotherapist can put together a suitable exercise plan and methods to help prevent episodes. A physiotherapist is a healthcare professional who helps manage symptoms through movement, exercise, and manual therapy.

Patients in England have access to the highly specialised muscle channelopathy service based in London. This service offers specialist diagnosis and treatment for patients with NDM or PP.

Hypokalaemic periodic paralysis (HypoPP)

Treatment for HypoPP focuses on maintaining normal blood potassium levels to prevent episodes of weakness. Identifying and avoiding triggers as much as possible can effectively prevent episodes. Triggers can include eating carbohydrates late at night and strenuous exercise. Mild episodes may need no treatment, and some people find that gentle exercise, such as walking around slowly, can stop severe weakness from occurring or reduce the time it is present.

During more severe episodes, it may be necessary to help restore potassium levels in the blood. This can be achieved by consuming potassium-rich foods or taking dissolvable potassium tablets with water. Occasionally intravenous fluids (IV) containing potassium are needed but this can only be given in hospital. If episodes are frequent or prolonged, acetazolamide is a medication that can be taken daily to try and prevent episodes or reduce how often they occur. If they continue despite potassium supplements and acetazolamide, then potassium-sparing diuretics may be recommended. These medications help to keep potassium in the body. When taking medications, blood tests may be necessary to monitor potassium levels, and yearly kidney ultrasounds to check for potential kidney stones that can develop with acetazolamide.

Hyperkalaemic periodic paralysis (HyperPP)

Treatment for HyperPP focuses on maintaining normal potassium levels in the blood to prevent episodes of weakness. Triggers like potassium-rich foods, strenuous exercise, and exposure to cold environments should be avoided as much as possible to prevent episodes.

Most episodes are brief and may improve after consuming carbohydrate-rich foods, such as sweet drinks or bread, which lower potassium levels in the blood. If episodes are frequent or prolonged, acetazolamide is a medication that can be taken daily to try and prevent them or reduce how often they occur. If episodes continue despite acetazolamide, thiazide diuretics may be recommended. These medications help remove potassium from the body through the kidneys and urine. Potassium levels will need to be monitored, using blood tests, to make sure they stay within a safe range and do not go too low. A yearly kidney ultrasound scan might be needed to check for potential kidney stones that can develop with acetazolamide.

Andersen-Tawil syndrome

Episodes in Andersen-Tawil syndrome are usually caused by low potassium levels, so it is treated in a similar way to hypokalemic periodic paralysis (see above). Sometimes episodes can also be caused by high potassium levels, so close monitoring and blood tests are necessary.

It’s essential that all people with Andersen-Tawil syndrome have an annual review with a cardiologist, even if they don’t experience any heart symptoms. Electrocardiogram (ECG) and extended monitoring (for example 24-hour Holter monitor) is useful to detect arrhythmias (abnormal heart rhythms) and begin treatment with medicines such as beta blockers, if needed. Some people may need to be fitted with a pacemaker, which is a small device that can regulate the heartbeat.

Anaesthesia stops a person feeling pain during a procedure or surgery. People with PP are at a higher risk of complications when using general anaesthesia. It is essential that, where possible, the anaesthetist and surgical team are aware of the diagnosis beforehand.

Local or regional anaesthesia is preferred over general anaesthesia. If using general anaesthesia, avoid depolarising agents or suxamethonium as these can cause prolonged weakness and potentially trigger a myotonic crisis with severe muscle stiffness (in people with HyperPP). If severe myotonia occurs, it may need to be treated quickly with intravenous sodium channel blockers such as lidocaine.