The administration of diuretics such as hydrochlorothiazide (0.5 g daily), keeping the serum K below 5 mEq/L, also prevents attacks but risks inducing dangerous degrees of hypokalemia. When the myotonia is more troublesome than the weakness, mexiletine 200 mg tid is perhaps the best alternative, because it prevents both coldand exercise-induced myotonia but it does not influence frequency of acute attacks. Some additional benefit may be gained by adding inhaled beta-adrenergic agonists such as albuterol or salbutamol. Some studies suggest that 1 agent in this class, clenbuterol, may have a direct effect in blocking the sodium channel, independent of its activation of adrenergic receptors. Procainamide or the lidocaine derivative tocainide, in doses of 400 to 1,200 mg daily, is also useful for the myotonia (tocainide carries a small risk of agranulocytosis).
For the treatment of an acute and severe episode, intravenous calcium gluconate (1 to 2 g) often restores power. If after a few minutes this treatment is unsuccessful, intravenous glucose or glucose and insulin and hydrochlorothiazide should be tried so as to reduce the serum potassium concentration.
Several other clinical presentations of hereditary periodic paralysis have been linked to mutations of the gene encoding the alpha subunit of the skeletal muscle sodium channel and probably represent variants of the disease. One of these, described by Ricker and colleagues, has been designated myotonia fluctuans, because muscle stiffness fluctuated in severity from day to day. In other respects the clinical features resemble those of myotonia congenita, including provocation of attacks of myotonia by exercise. The muscle stiffness is only slightly sensitive to cold but is markedly aggravated by the ingestion of potassium and, interestingly, never progresses to muscular weakness or paralysis. Myotonia permanens is the name given to a severe, persistent myotonia and marked hypertrophy of muscles, particularly of the neck and shoulders. The EMG discloses continuous muscle activity. This disease was discovered in the course of genotyping a patient who earlier had been reported by Spaans and associates as an example of “myogenic” Schwartz-Jampel syndrome, but it affects the same channel as in hyperkalemic periodic paralysis.
Trudell and colleagues studied 14 patients from a large kindred with autosomal dominant myotonia, the main feature of which was periodic worsening of myotonia accompanied by muscle pain and stiffness, most severe in the face and hands. The symptoms were enhanced by cold (suggesting paramyotonia) and severe stiffness and palpable rigidity followed within 15 min of the ingestion of potassium but neither of these measures provoked muscle weakness. Muscle biopsy disclosed a normal ratio of types 1, 2A, and 2B fibers, further distinguishing this disorder from typical myotonia congenita, where 2B fibers may be reduced in number. All patients in this family who were treated with the carbonic anhydrase inhibitor acetazolamide had a dramatic resolution of symptoms within 24 h, hence the name acetazolamide-responsive myotonia. This disorder has been linked to the same molecular alteration of the sodium channel gene as occurs in hyperkalemic periodic paralysis (Ptácek et al, 1994b).
Rosenfeld and coworkers described yet another form of painful congenital myotonia attributable to a novel mutation in the sodium channel alpha-subunit gene (SCN4A). Affected members of this family experienced debilitating pain, particularly severe in the intercostal muscles. Also, the pain was resistant to treatment with acetazolamide and other antimyotonic drugs (mexiletine and tocainamide) and could not be provoked by ingestion of potassium-rich foods, differing from even rarer similar cases that are acetazolamide responsive.