What sleep disorder is associated with hypokalemia (low potassium levels)?

Hypokalemic Periodic Paralysis is the Sleep Disorder Associated with Hypokalemia

Hypokalemic periodic paralysis (HypoPP) is a rare neuromuscular channelopathy that presents with episodes of muscle weakness triggered by low serum potassium levels, and notably, these paralytic attacks frequently occur during or immediately after sleep, with documented cases showing multiple sleep-onset REM periods (SOREMPs) on sleep studies that resolve when potassium levels are corrected. 1, 2, 3

Clinical Presentation and Sleep-Related Features

The hallmark presentation involves:

• Acute flaccid paralysis episodes that characteristically occur during sleep or upon awakening, affecting skeletal muscles below the neck while sparing respiratory muscles and consciousness 2, 3
• Transitory weakness episodes specifically triggered during and after sleep periods, distinguishing this from other causes of hypokalemia 1
• Serum potassium levels typically dropping to 1.7-2.1 mEq/L during attacks, with complete resolution of paralysis once potassium normalizes 2, 3
• ECG changes including U waves, ST depression, and T wave flattening characteristic of severe hypokalemia 4, 3

Unique Sleep Study Findings

A critical diagnostic feature documented in the literature:

• Multiple SOREMPs on MSLT (up to 5 sleep-onset REM periods) with shortened mean sleep latency (5 minutes) during active disease 1
• Complete normalization of sleep architecture after potassium correction, with SOREMPs disappearing and sleep latency extending to 13.5 minutes 1
• This suggests that increased extracellular potassium conductance related to HypoPP directly disrupts REM sleep regulation 1

Genetic and Acquired Forms

Hereditary Forms (Most Common)

• CACNA1S gene mutations (calcium channel defects) account for 60.5% of cases, presenting with lower serum potassium levels and higher rates of dyspnea during attacks 5
• SCN4A gene mutations (sodium channel defects) represent the second most common genetic cause 5
• Average age of symptom onset is 15.3 ± 9.7 years 5

Acquired Forms

• Associated with thyrotoxicosis, hyperaldosteronism, and hypercortisolism 2
• These secondary causes must be excluded before diagnosing primary HypoPP

Common Triggers to Identify

Patients should be specifically questioned about:

• Vigorous physical activity followed by rest periods 3, 5
• High carbohydrate meals causing insulin-mediated potassium shifts 5
• Sleep itself as a primary trigger for paralytic episodes 1, 3
• Cold exposure and emotional stress 5

Treatment Approach

Acute Management

• Immediate potassium supplementation (oral or IV depending on severity) with target correction to 4.0-5.0 mEq/L 6, 2, 3
• Cardiac monitoring is essential given the risk of life-threatening arrhythmias with potassium levels below 2.5 mEq/L 4
• Concurrent magnesium correction must be addressed, as hypomagnesemia makes hypokalemia refractory to treatment 4

Preventive Therapy

• Carbonic anhydrase inhibitors (acetazolamide) remain first-line, though only 50% of patients respond adequately 7, 5
• Topiramate has shown efficacy as an alternative carbonic anhydrase inhibitor, decreasing attack severity 7
• Potassium-sparing diuretics and antiepileptic drugs emerge as alternatives for acetazolamide non-responders 5
• Diuretics that decrease serum potassium have paradoxically resolved symptoms in hyperkalemic periodic paralysis variants 1

Critical Diagnostic Pitfalls

• Do not confuse with narcolepsy despite the presence of multiple SOREMPs—the key distinction is that SOREMPs in HypoPP completely resolve with potassium correction, whereas true narcolepsy persists 8, 1
• Ensure adequate sleep before MSLT if performed, as sleep deprivation can produce false-positive SOREMPs 8
• Check CSF hypocretin levels if diagnostic uncertainty exists—normal levels (>110 pg/mL) exclude narcolepsy type 1 8

Patient Education Priorities

The mainstay of preventing permanent muscle weakness is:

• Rigorous trigger avoidance through lifestyle modifications 3
• Recognition of early warning signs to initiate potassium supplementation before full paralysis develops 3
• Avoidance of high-carbohydrate meals and strenuous exercise followed by rest 5
• Proper education has been shown to end cycles of recurrent hospitalizations and reduce financial burden 3

Phenotypic Differences by Genetic Mutation

Patients with CACNA1S mutations specifically demonstrate:

• Lower serum potassium levels during attacks 5
• Distinct trigger profiles 5
• Higher proportion presenting with dyspnea during crises 5

This heterogeneous clinical expression necessitates genetic testing to optimize therapeutic strategies, as treatment response varies significantly based on the underlying genetic defect 5.