emDOCs Podcast – Episode 90: Hypokalemic Periodic Paralysis

Episode 90: Hypokalemic Periodic Paralysis

 Case:

• 20-year-old Caucasian male presents with severe pain and weakness in both of his thighs with inability to walk independently that started when he woke up that morning.
• Normal state of health prior to this. Two days before he had been welding for a number of hours in 105 F heat.
• Denied weakness of his upper extremities, paresthesias, vision changes, trouble swallowing or speaking, and drug or alcohol use.
• Exam: 2/5 strength when attempting to flex his bilateral thighs. Could not ambulate. Otherwise normal CN’s, sensation, upper extremity motor exam.

Differential:

• Guillain-Barre syndrome (GBS)
• Central disc herniation or spinal epidural abscess leading to cauda equina or conus medullaris syndrome
• Transverse myelitis
• Rhabdomyolysis

Case Conclusion:

• Review of outside studies:Normal CT of the cervical, thoracic, and lumbar spine, complete blood count (CBC), comprehensive metabolic panel (CMP), creatine kinase (CK), and lactate levels.
• Potassium level was 2.0 mEq/L. The patient received 40 mEq of oral potassium chloride prior to transfer.
• In ED, repeat potassium level was 2.6 mEq/L. TSH and other labs normal. Administered 40 mEq oral dose of potassium chloride.
• Neurology and the hospitalist consulted: diagnosis of hypokalemic periodic paralysis
• Oral repletion was continued until he reached a serum potassium level of 4.2 mEq/L two days after admission.
• Weakness completely resolved and discharged to follow up with neuromuscular neurology.

What is hypokalemic periodic paralysis?

• HypoPP is a form of primary periodic paralysis.
• There are three main types of primary periodic paralysis, including hypoPP, hyperkalemic periodic paralysis (hyperPP), and Anderson-Tawil syndrome.

Epidemiology:

• Prevalence of hypoPP is approximately 1 per 100,000. Two main subtypes, which include thyrotoxic hypoPP and familial hypoPP.
• Thyrotoxic hypoPP is more common than familial hypoPP and occurs only in the setting of active hyperthyroidism.
• Familial hypoPP is an autosomal dominant disorder with incomplete penetrance and more commonly presents in males.

Pathophysiology:

• Thyrotoxic hypoPP is caused by increased Na K ATPase pump activity that occurs in the setting of hyperthyroidism.
• Familial hypoPP is caused by mutations in one of two genes that impact skeletal muscle calcium or sodium channels.
• Both channelopathies lead to paradoxical depolarization and failure of excitation of muscle fibers in the setting of low extracellular potassium.
• HypoPP only impacts skeletal muscles, NOT smooth or cardiac muscle.
• There should be no cardiac or gastrointestinal (GI) involvement in hypoPP.

Presentation:

• First episode of hypoPP is usually before age 20, but can occur up to age 35.
• Usually presents with focal or generalized paralysis lasting anywhere from hours to days in the setting of a trigger.
• The physical location of weakness can vary with serial exams.
• Triggers for familial hypoPP episodes include rest after heavy exercise, emotional stress, physical stress such as fasting, pregnancy, cold weather, alcohol, beta adrenergic agonists, medications that cause hypokalemia, glucocorticoids, states of high insulin levels such as meals rich in carbohydrates, and high sodium intake.
• HypoPP episodes become less frequent after age 40.
• Permanent muscular weakness can occur; no way of predicting which patients will develop this. Permanent weakness usually affects the proximal lower extremities, happens in older patients, and develops late.

 Diagnosis:

• Can be made in the ED based on history, exam, lab testing.
• On exam, flaccid paralysis with little to no involvement of the bulbar or respiratory musculature.
• Labs: BMP, magnesium, TSH.

Management:

• Administration of PO or IV potassium. IV potassium is not necessary unless the patient cannot tolerate PO.
  • Recommended PO dose is 0.2-0.4 mEq/kg every 30 minutes with a maximum dose of 200–250 mEq/day.
  • If IV administration necessary, place on continuous cardiac monitoring and administer 20 mEq/ h with a maximum dose of 200 mEq/day.
• Avoid normal saline and dextrose-containing diluents.
• Consult neurology in the ED. If neurology is unavailable, the patient should only be discharged once potassium has been repleted and all weakness has resolved.
• Refer to neuromuscular neurology and genetics for further testing with EMG and for typical mutations.
• Prescribe oral potassium supplementation with consideration for concomitant magnesium supplementation to promote retention of potassium by the kidneys.
• Neurology may recommend discharging the patient with prescriptions for acetazolamide, dichlorphenamide, or potassium-sparing diuretics to prevent attack recurrence.
• Only dichlorphenamide is FDA-approved for this indication.
• Counsel patients on avoiding typical triggers and consider engaging in mild exercise (such as walking) at the onset of attacks (reduce episode severity).

Summary:

• HypoPP is a rare skeletal muscle channelopathy caused by hyperthyroidism or genetic mutation.
• Presentation involves flaccid paralysis, which can be focal or generalized, usually in the first two decades of life.
• Episodes are provoked by typical triggers, such as rest after heavy exercise, carbohydrate loading, heavy salt intake, physical or emotional stress, alcohol, and some medications.
• ED workup should exclude alternate causes of symptoms.
• Treatment involves restoring normal potassium levels.
• Patients need neuromuscular neurology follow up and lifestyle modifications.

References:

1. Statland JM, Fontaine B, Hanna MG, et al. Review of the Diagnosis and Treatment of Periodic Paralysis. Muscle Nerve. 2018;57(4):522-530.
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3. Kung AWC. Thyrotoxic Periodic Paralysis: A Diagnostic Challenge. The Journal of Clinical Endocrinology & Metabolism. 2006;91(7):2490-2495.
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8. Fournier E, Arzel M, Sternberg D, et al. Electromyography guides toward subgroups of mutations in muscle channelopathies. Ann Neurol 2004;56:650–661.
9. McManis PG, Lambert EH, Daube JR. The exercise test in periodic paralysis. Muscle Nerve 1986;9:704–710.
10. Tan SV, Matthews E, Barber M, et al. Refined exercise testing can aid DNA-based diagnosis in muscle channelopathies. Ann Neurol 2011;69:328–340.\ Griggs RC, Resnick J, Engel WK. Intravenous treatment of hypokalemic periodic paralysis. Arch Neurol 1983;40:539–540.