Primary periodic paralysis

Primary periodic paralyses are a group of rare disorders affecting skeletal muscle and characterized by episodic attacks of weakness caused by transient impairment of fiber excitability. Primary periodic paralyses include hypokalemic periodic paralysis, hyperkalemic periodic paralysis, and Andersen-Tawil syndrome. Attacks of weakness are generally associated with altered serum potassium concentrations and are often caused by specific triggers such as cold, rest after exercise, stress. The frequency, duration and severity of attacks vary greatly among patients and, although attacks tend to diminish over the lifetime, many patients develop a permanent weakness that can progress later in life up to the loss of ambulation. As regards muscle morphologic changes, fatty infiltration is a reliable marker, with specific pattern of muscle involvement and unrelated to the frequency of attacks of weakness. Primary periodic paralyses are caused by pathogenic variants in genes encoding ion channels expressed in the skeletal muscle and are inherited as autosomal dominant traits. Treatment includes the management of acute attacks of muscle weakness and the prophylactic prevention of episodes of weakness by combining avoidance of triggers and drugs to reduce their frequency and severity. New therapeutic strategies are now focused on drug repurposing and the search for new drugs able to stabilize the normal muscle fiber polarization. However, current treatments for periodic paralysis are far from satisfactory, and many patients continue to experience symptoms. Elucidating the pathogenesis of fixed muscle weakness in periodic paralysis patients will increase the chances of countering this debilitating condition.