Periodic Paralysis

Periodic Paralysis

The periodic paralyses are characterised by episodic weakness that is triggered by a change in potassium level. What type of periodic paralysis a patient has is determined by their underlying genetic mutation. 

There are 3 main types of periodic paralysis: hyperkalaemic periodic paralysis, hypokalaemic periodic paralysis and Andersen-Tawil syndrome and each have a distinct clinical phenotype.

Hypokalaemic Periodic paralysis

Hypokalaemic periodic paralysis (HypoPP) is characterised by episodes of weakness triggered by low potassium levels. 

Clinical Presentation

Patients with HypoPP typically present in the 1st or 2nd decade of life. They will usually describe episodes of weakness of the arms and legs, often on waking lasting several hours to days. The attacks of weakness will often be triggered by a large carbohydrate meal the evening before or excessive exercise. If a blood potassium level is taken during the attack, it will usually be low and in severe attacks we will often see potassium levels <2.0. Patients may also describe more minor attacks of a single limb or of much more subtle weakness after exercise.

Patients do not get weakness above the neck so they should not experience facial weakness, eye weakness or difficulty with speech and if these aspects are present then an alternative diagnosis should be considered. It is also very rare to have respiratory weakness during an attack. 

On examination during an attack, patients will have hypotonia and areflexia. In between attacks, patients are usually normal. In later life patients may develop some fixed proximal weakness.

Genetic Diagnosis

Patients with HypoPP most commonly have mutations in the calcium channel gene expressed in muscle, CACNA1S. In approximately 12% of cases patients may have a mutation in the sodium channel gene, SCN4A. Mutations in these genes typically affect the voltage-sensing part of the channel causing the formation of a leak current which allows cations to leak into muscle. This in turn causes prolonged membrane depolaristion which then leads to inexcitable muscle and manifests clinically as paralysis.  

HypoPP is dominantly inherited and therefore there is a 50% chance of passing it on to each child. 

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Hyperkalaemic Periodic Paralysis

Hyperkalaemic periodic paralysis (HyperPP) is characterised by episodes of weakness associated with elevated potassium levels. 

Clinical Presentation

Patients with HyperPP typically present in the 1st decade of life, usually earlier than seen in HypoPP. They typically have shorter attacks often only lasting minutes to hours but rarely they may experience more prolonged attacks. Attacks often affect a single or 2 limbs but patients may have more generalised attacks of all 4 limbs.

Common triggers include cold and inactivity. Patients may find they are more likely to have an attack if they have high potassium foods. During attacks patients may have elevated potassium levels but some patients will have normal potassium levels.

Some patients may also have myotonia either during or distinct from the episodes of weakness. In older age it is increasingly being recognised that these patients may develop proximal weakness.

On examination during attacks, patients will have weakness and if severe may have hypotonia and arreflexia. In between attacks patients are often normal or may have grip and eyelid myotonia. Older patients may have fixed proximal weakness.

Genetic Diagnosis

Patients with HyperPP have mutations in the sodium channel gene expressed in muscle, SCN4A. The mutations identified lead to increased sodium influx in the the presence of elevated potassium, triggering prolonged muscle membrane depolarisation and paralysis. 

HyperPP is dominantly inherited so there is 50% chance of passing it on to offspring. 

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Andersen Tawil Syndrome

Andersen Tawil Syndrome (ATS) is a a very rare form of periodic paralysis. It is characterised by the presence of a triad of symptoms:

  • Episodes of paralysis
  • Cardiac arrhythmias
  • Distinctive facial features

Clinical Presentation

Patients with ATS typically present in the 2nd decade with episodes of weakness. These episodes of weakness are most commonly associated with low potassium but can also occur with normal and high potassium levels. Weakness tends to occur in the axial and leg muscles but can affect the whole body from the neck down. Attacks may last hours to days and occasionally weeks. Patients with frequent attacks of weakness may develop axial weakness in later life. 

Cardiac arrhythmias are most commonly noted in the 2nd to 3rd decade and it is important that these patients all have yearly cardiac follow up to monitor for arrhythmias. In a small number of patients these arrhythmias may be fatal and can lead to sudden death. High risk patients may therefore be considered for insertion of an implantable cardioverter-defibrillator.

The majority of patients with ATS have distinctive facial features and skeletal changes. The most common changes are micrognathia and clinodactyly. Patients may also have low set ears, hypertelorism, short stature, small hands and feet and dental changes. 

Patients frequently have all 3 features of ATS described but it is increasingly being recognised that patients with milder disease may have only 1 or 2 of the characteristic triad of features. 

Genetic Diagnosis

ATS is associated with mutations in the potassium channel gene, KCNJ2. Around 30-40% of patients however may not have a genetic cause identified but to date no other causative gene has been identified. KCNJ2 is ubiquitously expressed which is why patients not only have muscle symptoms but also cardiac, skin and skeletal symptoms. 

ATS is dominantly inherited and therefore offspring have a 50% chance of inheriting the condition.

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