Familial periodic paralysis

Familial periodic paralysis is a rare autosomal disorder characterized by episodes of flaccid paralysis with loss of deep tendon reflexes and unresponsiveness of muscles to electrical stimulation. There are 3 forms: hyperkalemic, hypokalemic, and normokalemic. The diagnosis is suggested by history and confirmed by provoking an episode (glucose with insulin to cause hypokalemia or potassium chloride to cause hyperkalemia). Treatment of familial periodic paralysis depends on the form.

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What causes familial periodic paralysis?

The hypokalemic form of familial periodic paralysis is caused by a mutation in the dihydropyridine receptor-associated calcium channel gene. The hyperkalemic form is caused by mutations in the gene encoding the alpha subunit of skeletal muscle sodium channels (SCN4A). The cause of the normokalemic form remains unclear; in some circumstances, it may be caused by a mutation in the gene encoding sodium channels.

Symptoms of Familial Periodic Paralysis

In the hypokalemic form, episodes usually appear before the age of 16. The day after active exercise, the patient often wakes up with weakness, which may be mild and limited to certain muscle groups or may involve all 4 limbs. Episodes are provoked by food rich in carbohydrates. The oculomotor muscles, muscles innervated by the bulbar group of cranial nerves, and respiratory muscles are spared. Consciousness is not affected. Potassium levels in the blood and urine are reduced. Weakness persists for up to 24 hours.

In the hyperkalemic form, episodes often begin at an earlier age and are usually shorter, more frequent, and less severe. Episodes are precipitated by postprandial exercise or fasting. Myotonia (delayed onset of relaxation after muscle contraction) is common. Eyelid myotonia may be the only symptom.

In the normokalaemic form, affected patients are sensitive to dietary potassium intake and experience episodes of mild muscle weakness with normal serum potassium levels.

Diagnosis of familial periodic paralysis

The best diagnostic indicator is the anamnesis - typical episodes. When measured during an episode, the serum potassium level may be altered. Familial periodic paralysis can sometimes be provoked by the introduction of glucose and insulin (hypokalaemic form) or potassium chloride (hyperkalemic form), but only experienced physicians should carry out these procedures, since respiratory muscle paralysis or intracardiac conduction disturbances may develop during a provoked episode.

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Treatment of familial periodic paralysis

Episodes of hypokalemic paralysis are treated with potassium chloride 2-10 g orally (without added sugar) or intravenous potassium. A low-carbohydrate, low-sodium diet is indicated; activities requiring muscular exertion and alcohol are avoided after periods of rest; acetazolamide 250-2000 mg orally once daily may help prevent hypokalemic episodes.

An incipient mild episode of hyperkalemic paralysis may be aborted by gentle exercise or carbohydrate ingestion at a rate of 2 g/kg. An established episode requires thiazides, acetazolamide, or inhaled beta-agonists. Severe attacks require intravenous calcium gluconate or glucose with insulin. Regular carbohydrate intake, low potassium diets, and avoidance of fasting and muscle-strenuous activity after meals and exposure to cold help prevent hypokalemic episodes.

In the normokalemic form, large doses of sodium improve the condition and reduce weakness. Glucose administration is ineffective. Familial periodic paralysis can be prevented by avoiding rest after exercise, excessive alcohol intake, and exposure to cold.