Familial Periodic Paralysis

Rare; hyperPP approximately 1:200,000 and hypoPP approximately 1:100,000

HyperPP with childhood onset; hypoPP with teenage onset

In hyperPP, succinylcholine may provoke severe myotonia, provide no relaxation, and cause hyperkalemia (resulting postop muscle weakness over days and rhythm disturbances).

HypoPP associated with supraventricular or conduction defect-type cardiac arrhythmias; weakness may be enhanced by β-adrenergic blocking drugs, and postop resp muscle weakness may occur.

Hypermetabolic crises (necessitating dantrolene use) reported in hypoPP pts.

Cold can trigger attack in both types of PP.

K ⁺ and glucose have opposite effects in the two disorders; in hyperPP, K ⁺ triggers attacks and glucose is cure, whereas in hypoPP, glucose-induced hypokalemia triggers attacks and K ⁺ is cure.

Cardiac complications (dysrhythmias) due to severe dyskalemia during attack.

Respiratory insufficiency during attack.

Channel defects in the sarcolemma lead to aberrant depolarization in the presence of dyskalemia, which inactivates sodium channels and renders muscle fibers inexcitable.

Autosomal dominant conditions; hypoPP with reduced penetrance in females.

HyperPP with frequent (daily) episodic attacks for minutes (to hours); episodes of weakness generalized, rarely bulbar and resp muscles involved in severe paralysis; hyperkalemia (in approximately 50%) during attacks; triggered by K ⁺ intake, rest after exercise, or cold; often additional EMG myotonia.

HypoPP with less frequent but more severe episodic attacks for hours (to days); weakness may be focal or generalized, usually sparing facial and resp muscles; invariably hypokalemia during episode; triggered by carbohydrates, cold, stress, specific medications (e.g., beta-agonists, corticosteroids, insulin); no myotonia.

Fixed proximal weakness often develops with increasing age in both types.

HyperPP caused by mutations in the voltage-gated sodium channel Na _v 1.4 gene (SCN4A). Mutant channels (inactivation defect) lead to persistent sodium influx and depolarization, muscle membrane becomes inexcitable.

HypoPP either caused by mutations in the CACNAS gene (encodes α _1s -subunit of dihydropyridine receptor) (type 1 hypoPP) or in approximately 10% by mutations in the SCN4A gene (type 2 hypoPP). Introduction of new accessory ion conduction pathways independent of normal conduction pathways, leads to paradoxical membrane depolarization in low potassium conditions causing inexcitability.