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At a glance

Periodic paralysis is characterized by episodes of flaccid muscle weakness occurring at irregular intervals. Periodic paralysis is part of group of channelopathies that involve cellular membrane ion channels affecting electrolyte conductance and lead to episodic muscle weakness.

Synonyms

Familial Periodic Paralysis; Hypokalemia, Hyperkalemia Myotonia; Paramyotonia Congenita; Potassium Aggravated Myotonia; Becker Myotonia Congenita; Thomsen Myotonia Congenita; Adynamia Episodica Hereditaria with or without Myotonia; Gamstorp Disease; Westphall Disease.

Classifications

Primary periodic paralysis can be classified according plasma potassium concentrations at the time of the attack and linked to the ion channel defect:

  • Hyperkalemic Periodic Paralysis (Sodium Channel): Gamstorp disease; paramyotonia congenita; potassium-aggravated myotonia.

  • Hypokalemic Periodic Paralysis (Calcium Channel): Westphall disease; thyrotoxic periodic paralysis (secondary form).

  • Normokalemic Periodic Paralysis (Chloride Channel): Becker myotonia congenita; Thomsen myotonia congenita.

Incidence

The frequency for all forms of periodic paralysis remains unknown. Hypokalemic periodic paralysis has a prevalence of 1:200,000 population, whereas hyperkalemic periodic paralysis is reported to 1:100,000. ☞Thyrotoxic Periodic Paralysis is more common in males (85%) of Asian descent, leading to a frequency of approximately 2%.

Genetic inheritance

All are autosomal dominant but penetrance seems to be variable in female carriers. Hypokalemic periodic paralysis is caused by a mutation in the alpha-1 unit of the dihydropyridine-sensitive calcium channel CACNL1A3 with the gene is located on chromosome 1q32.1 and mutations in the sodium channel SCN4A on 17q23.3. Hyperkalemic periodic paralysis is also caused by a mutation in the alpha subunit of the sodium channel SCN4A; the gene is located on chromosome 17q23.3. It is the same gene as paramyotonia congenita. The underlying mutation of normokalemic periodic paralysis is thought to be in the SCN4A p.M1592V gene. The chloride channelopathies are due to mutations of the CLCN1 gene on chromosome 7q34.

Pathophysiology

The physiopathologic basis of flaccid muscle weakness is inexcitability of the muscle membrane, ie, the sarcolemma. In the hypokalemic form, potassium outflow is diminished by altered calcium homeostasis in the muscle fibers; in the hyperkalemic form, the muscle fibers remain depolarized and their membranes are inexcitable.

Diagnosis

Based on history, clinical examination, and measurement of serum electrolytes during the attacks. It is confirmed by genetic testing.

Clinical aspects

  • Hypokalemic Form: Onset rarely occurs before the second decade of life. Attacks of muscle weakness typically occur at night or in the early morning. They are triggered by increased physical exercise, stress, cold, or a large carbohydrate intake. Paralysis is flaccid, affects mainly the girdle of the lower limbs, and spares the respiratory muscles as well as the muscles supplied by the cranial nerves. The attack usually lasts 6 to 24 hours. ECG signs of hypokalemia can be observed. Treatment: oral potassium chloride ...

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