What are the clinical presentation and management of periodic paralysis?

Clinical Presentation of Periodic Paralysis

Periodic paralysis is characterized by episodes of flaccid muscle weakness or paralysis, with hypokalemic periodic paralysis being the most common form, typically presenting with low serum potassium levels during attacks, while hyperkalemic periodic paralysis presents with normal or elevated potassium levels.

Types and Etiology

Periodic paralysis disorders can be classified into two main categories:

1. Primary (Hereditary) Periodic Paralyses:

   • Caused by mutations in genes encoding muscle membrane ion channels 1
   • Main types include:
     • Hypokalemic periodic paralysis (HypoPP): Associated with mutations in calcium channel (CACNA1S) or sodium channel (SCN4A) genes 2
     • Hyperkalemic periodic paralysis (HyperPP): Associated with sodium channel (SCN4A) mutations 1
     • Andersen-Tawil syndrome (LQT7): Associated with potassium channel (KCNJ2) mutations, characterized by periodic paralysis, cardiac abnormalities, and distinctive facial features 3

2. Secondary (Acquired) Periodic Paralyses:

   • Most commonly associated with thyrotoxicosis (Thyrotoxic Periodic Paralysis) 4
   • Can be associated with renal tubular acidosis and other conditions 4

Clinical Presentation

Hypokalemic Periodic Paralysis

• Age of onset: Typically in adolescence or early adulthood (mean age 15.3 ± 9.7 years) 2
• Attack characteristics:
  • Episodes of flaccid weakness affecting one or more limbs
  • Duration: Several hours to several days 5
  • Typically spares respiratory muscles, but dyspnea may occur, especially in CACNA1S mutations 2
  • Serum potassium levels are low during attacks (<3.5 mEq/L)
• Triggers:
  • Carbohydrate-rich meals
  • Rest after exercise
  • Stress
  • Cold exposure
  • Specific triggers may vary based on genetic mutation 2

Hyperkalemic Periodic Paralysis

• Attack characteristics:
  • Episodes of weakness typically shorter than in hypokalemic form
  • May be associated with myotonia (delayed muscle relaxation)
  • Normal or elevated serum potassium during attacks
• Triggers:
  • Fasting
  • Rest after exercise
  • Potassium-rich foods
  • Cold exposure

Andersen-Tawil Syndrome (LQT7)

• Triad of symptoms:
  • Periodic paralysis (hypo- or hyperkalemic)
  • Cardiac abnormalities (prolonged QT interval, ventricular arrhythmias)
  • Distinctive facial features and skeletal abnormalities
• Presentation: Shows a prolonged QT interval with prominent U wave, polymorphic or bidirectional VT, facial dysmorphisms, and hyper/hypokalemic periodic paralysis 3

Thyrotoxic Periodic Paralysis (TPP)

• Demographics: More common in Asian males
• Clinical features:
  • Episodes of muscle weakness in the setting of thyrotoxicosis
  • Low serum potassium during attacks
  • May present with symptoms of hyperthyroidism (weight loss, palpitations, heat intolerance)
• Caution: Risk of rebound hyperkalemia during treatment 6

Diagnostic Approach

1. Clinical evaluation:

   • Detailed history of attack pattern, triggers, and family history
   • Physical examination during and between attacks

2. Laboratory testing:

   • Serum potassium levels during attacks (critical for classification)
   • Thyroid function tests to rule out thyrotoxic periodic paralysis
   • Renal function and acid-base status to identify secondary causes 4

3. Electrodiagnostic studies:

   • EMG may show reduced compound muscle action potential during attacks
   • May help differentiate from other neuromuscular disorders

4. Genetic testing:

   • For suspected primary forms (CACNA1S, SCN4A, KCNJ2 mutations)
   • Important for confirming diagnosis and guiding treatment 2

Differential Diagnosis

Periodic paralysis must be distinguished from other conditions that can cause episodic weakness:

• Guillain-Barré syndrome: Progressive ascending weakness, areflexia, sensory symptoms 3
• Metabolic or electrolyte disorders: Hypokalaemia from other causes, hypomagnesaemia, hypophosphataemia 3
• Inflammatory myositis: Progressive weakness, elevated muscle enzymes
• Myasthenia gravis: Fluctuating weakness, ocular symptoms, fatigability
• Conversion disorder: No electrolyte abnormalities, inconsistent examination

Management Considerations

1. Acute attack management:

   • For hypokalemic forms: Oral or IV potassium supplementation
   • For hyperkalemic forms: Carbohydrate intake, diuretics
   • Caution: Careful monitoring of potassium levels is essential to prevent rebound hyperkalemia, especially in TPP 6

2. Preventive therapy:

   • Dichlorphenamide has shown efficacy in both hypokalemic and hyperkalemic forms 5
   • Acetazolamide may improve muscle strength in hypokalemic periodic paralysis 5
   • Only about 50% of patients respond to oral acetazolamide treatment 2
   • Potassium-sparing diuretics and antiepileptic drugs are emerging alternatives 2

3. Lifestyle modifications:

   • Avoidance of known triggers
   • Regular, moderate exercise
   • Balanced diet with controlled carbohydrate intake

Prognosis

• Most episodes resolve spontaneously within hours to days
• Long-term prognosis varies:
  • Some patients develop fixed proximal weakness over time
  • Frequency of attacks may decrease with age
  • Quality of life can be significantly impacted by unpredictable attacks

Early recognition and appropriate management of periodic paralysis are essential to prevent complications and improve quality of life for affected individuals.