To the Editor:
Hyperkalemic periodic paralysis (hyperPP) is a rare, autosomal dominant muscle channelopathy associated with mutations in the sodium voltage-gated channel alpha subunit (SCN4A).1 Clinically, hyperPP is characterized by intermittent episodes of muscle weakness in the context of elevated serum potassium levels.2 Options for preventative therapy include dietary/lifestyle modifications (eg, avoidance of potassium-rich foods, cold exposure, strenuous exercise, and fasting) and the carbonic anhydrase inhibitors dichlorphenamide and acetazolamide.2
We report the case of a 58-year-old White man who presented to our multidisciplinary team clinic for evaluation of progressively worsening, episodic muscle weakness. He recalled having symptoms since the age of 5 years and reported similar complaints by his mother, daughter, and other maternal family members. On average, he had 3–5 episodes per week, which lasted from a few hours to days, and were precipitated by exposure to cold and rest after strenuous exercise. The weakness was generalized and painless, with involvement of facial, trunk, and limb muscles. Electrodiagnostic studies showed normal sensory and motor conduction studies bilaterally, and needle electromyography showed short duration polyphasic motor unit potentials and early recruitment in proximal muscles consistent with a myopathic process. Genetic testing was positive for a pathogenic variant of SCN4A [c.2111C>T (p.Thr704Met)], and he was diagnosed with hyperPP based on the constellation of laboratory and clinical findings.
Despite lifestyle changes, the patient continued to have 3–5 attacks weekly. Acetazolamide was prescribed, and although the attack rate was reduced to approximately 3 per week, each attack lasted for several hours. Because of the suboptimal response to acetazolamide, he was switched to dichlorphenamide 50 mg twice daily, which was increased to 100 mg twice daily after 2 weeks. On a regimen of dichlorphenamide and ongoing lifestyle changes, he has experienced no attacks during the past 2 years. He continues to have symmetric proximal weakness, which commonly occurs with hyperPP in those >40 years, especially in those with a T704M mutation.3 After dichlorphenamide was initiated, he had taste changes and abdominal cramps with diarrhea, which were managed conservatively (eg, loperamide as needed) without changing the dichlorphenamide dose, and these side effects resolved after approximately 1 month.
This case demonstrated a successful response to dichlorphenamide in a patient with treatment refractory hyperPP. Dichlorphenamide is approved by the US Food and Drug Administration for the treatment of primary hyperPP, primary hypokalemic periodic paralysis (hypoPP), and related variants. The efficacy and safety of dichlorphenamide were supported by randomized, controlled trials in patients with hyperPP or hypoPP.4,5 There are no randomized, controlled studies of acetazolamide in patients with periodic paralysis and no head-to-head comparisons of dichlorphenamide and acetazolamide. This case illustrates that a patient with hyperPP who continues to experience attacks while on acetazolamide therapy may benefit from switching to dichlorphenamide. Further research is needed to assess whether dichlorphenamide use can lead to remission or prevent permanent muscle weakness in patients with hyperPP and to evaluate the efficacy of dichlorphenamide relative to other drugs.
1. Phillips L, Trivedi JR. Skeletal muscle channelopathies. Neurotherapeutics. 2018;15:954–965.
2. Statland JM, Fontaine B, Hanna MG, et al. Review of the diagnosis and treatment of periodic paralysis. Muscle Nerve. 2018;57:522–530.
3. Lehmann-Horn F, Rudel R, Jurkat-Rott K. Nondystrophic myotonias and periodic paralyses. In: Engel AG, Franzini-Armstrong C, ed. Myology. New York City, NY: McGraw-Hill; 2004:1257–1300.
4. Tawil R, McDermott MP, Brown R Jr, et al. Randomized trials of dichlorphenamide in the periodic paralyses. Working Group on Periodic Paralysis. Ann Neurol. 2000;47:46–53.
5. Sansone VA, Burge J, McDermott MP, et al. Randomized, placebo-controlled trials of dichlorphenamide in periodic paralysis. Neurology. 2016;86:1408–1416.