Periodic Paralyses Treatment & Management

Updated: May 18, 2017
  • Author: Naganand Sripathi, MD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
  • Print
Treatment

Medical Care

Treatment is often necessary for acute attacks of hypokalemic periodic paralysis but seldom for hyperkalemic periodic paralysis. Prophylactic treatment is necessary when the attacks are frequent.

Dichlorphenamide, a carbonic anhydrase inhibitor, was approved by the FDA in August 2015 for the management of primary hyperkalemic periodic paralysis, primary hypokalemic periodic paralysis, and related variants. Approval was based on 2 randomized, double-blinded placebo-controlled studies that included 138 patients. Treatment with dichlorphenamide resulted in significantly fewer muscle weakness attacks/week compared with placebo (2.3 to 3.9 fewer attacks/week with hyperkalemic periodic paralysis; 2.2 fewer attacks/week with hypokalemic periodic paralysis). [14]

Hypokalemic periodic paralyses

During attacks, oral potassium supplementation is preferable to IV supplementation. The latter is reserved for patients who are nauseated or unable to swallow. Potassium chloride is the preferred agent for an acute attack (assuming a normal renal function). [15] A reasonable initial dose for a 60-120 kg man (ie, 0.5-1 mEq/kg) is 60 mEq. Typically, 40-60 mEq of K+ raises the potassium concentration by 1.0-1.5 mEq/L, and 135-160 mEq of K+ raises plasma potassium by 2.5-3.5 mEq/L. Aqueous potassium is favored for quicker results. If there is no response in 30 minutes, an additional 0.3 mEq/kg may be given. This should be repeated up to 100 mEq of potassium. Beyond this, monitoring of serum potassium is warranted prior to further supplementation. Typically, one should not exceed a total dose of 200 mEq in a day.

Intravenous potassium is reserved for cardiac arrhythmia or airway compromise due to ictal dysphagia or accessory respiratory muscle paralysis. IV potassium chloride 0.05-0.1 mEq/kg body weight in 5% mannitol as a bolus is preferable to continuous infusion. Mannitol should be used as solvent, as both sodium and dextrose worsen the attack. Only 10 mEq at a time should be infused with intervals of 20-60 minutes, unless in situations of cardiac arrhythmia or respiratory compromise. This is to avoid hyperkalemia at the end of an attack with shift of potassium from intracellular compartment into the blood. Continuous ECG monitoring and sequential serum potassium measurements are mandatory.

For prophylaxis, dichlorphenamide 50-100 mg BID may be considered for the management of primary hypokalemic periodic paralysis. Acetazolamide is an off-label alternative that is administered at a dose of 125-1500 mg/d in divided doses. Potassium-sparing diuretics like triamterene (25-100 mg/d) and spironolactone (25-100 mg/d) are second-line drugs to be used in patients in whom the weakness worsens, or in those who do not respond to carbonic anhydrase inhibitors. Spironolactone may cause gynecomastia, but this is less with eplerenone. Blood pressure monitoring is advised. Because these diuretics are potassium sparing, potassium supplements may not be necessary.

Approximately 50% of genotyped patients with HypoPP respond to acetazolamide. Poor response is predicted with substitution of arginine with smaller glycine in the residues of voltage sensors near the extracellular side of the sarcolemma. Almost 60% of patients with common CACNA1S mutations show favorable response to acetazolamide, whereas only 16% of patients with SCN4A mutations benefited from acetazolamide. In both cohorts, this poor response is predicted with substitution of arginine with smaller glycine in the residues of the voltage sensor near the extracellular side of the sarcolemma. [16]

Thyrotoxic periodic paralysis

Treatment consists of controlling thyrotoxicosis and beta-blocking agents. Potassium supplementation, dichlorphenamide, propranolol, and spironolactone may be helpful during the attacks as well as for prophylaxis. Dichlorphenamide 50-100 mg BID or propranolol in doses of 20-40 mg twice a day may be sufficient to control recurrent attacks of periodic paralysis.

Hyperkalemic periodic paralyses

Fortunately, attacks are usually mild and rarely require treatment. Weakness promptly responds to high-carbohydrate foods. Beta-adrenergic stimulants, such as inhaled salbutamol, also improve the weakness (but are contraindicated in patients with cardiac arrhythmias).

In severe attacks, therapeutic measures that reduce hyperkalemia are utilized. Continuous ECG monitoring is always needed during the treatment. Dichlorphenamide 50-100 mg BID is indicated for hyperkalemic periodic paralysis. Thiazide diuretics and carbonic anhydrase inhibitors are used as prophylaxis. Thiazide diuretics have few short-term side effects; they are tried as first-line treatment. Occasionally, thiazide diuretics may result in paradoxical hypokalemic weakness, which responds to potassium supplementation.

Paramyotonia congenita

Because weakness is uncommon, treatment is aimed at reducing myotonia. While the above-mentioned diuretics can be tried, they are often not effective. Mexiletine has been shown to be helpful but is contraindicated in patients with heart block.

Potassium-associated myotonia

Treatment with mexiletine or a thiazide diuretic may reduce the severity of the myotonia.

Andersen-Tawil syndrome

A combination of amiodarone and acetazolamide resulted in a long-lasting improvement in one study. [17]

Implantation of a cardiac defibrillator has rarely been performed.

Carbonic anhydrase inhibitors are used for preventing periodic paralysis.

Potassium supplementation prevents periodic paralysis and also reduces cardiac arrhythmia, shortening the QT interval.

For the control of cardiac symptoms, β-blockers or calcium channel blockers may be used.

Flecainide has been shown to be successful in treating bidirectional ventricular tachycardia, ventricular ectopy, and tachycardia-induced cardiomyopathy. [18]

Next:

Surgical Care

Malignant hyperthermia susceptibility has been noted in HypoPP with calcium channel mutations. It is prudent to monitor all patients with periodic paralysis for this complication.

Previous
Next:

Diet

See the list below:

  • Hypokalemic periodic paralyses: Low-carbohydrate and low-sodium diet may decrease the frequency of attacks.
  • Hyperkalemic periodic paralyses: Glucose-containing candy or carbohydrate diet with low potassium may improve the weakness.
Previous