What are the indications to start salbutamol (albuterol) and ephedrine in a patient suspected to have Congenital Myasthenic Syndrome (CMS)?

Indications for Salbutamol and Ephedrine in Congenital Myasthenic Syndrome

Salbutamol (albuterol) and ephedrine are indicated as first-line treatments for patients with suspected Congenital Myasthenic Syndrome (CMS) specifically with DOK7 mutations or endplate acetylcholinesterase deficiency, where they can dramatically improve muscle strength and quality of life.

Specific CMS Subtypes Responding to Salbutamol/Ephedrine

The primary indications for starting these medications include:

• DOK7 mutations: Patients presenting with limb-girdle pattern weakness 1, 2, 3
• Endplate acetylcholinesterase deficiency: Patients with fatigable weakness 4
• Slow-channel syndrome: Some evidence of benefit with ephedrine 5

Clinical Presentation Warranting Treatment

Patients with suspected CMS who should be considered for salbutamol/ephedrine therapy typically present with:

• Progressive limb-girdle muscle weakness (proximal > distal)
• Fatigable weakness that worsens with activity
• Onset from birth to early childhood
• Possible respiratory involvement
• Facial weakness (less responsive to treatment)
• Worsening symptoms with acetylcholinesterase inhibitors like pyridostigmine

Diagnostic Criteria Before Starting Treatment

Before initiating therapy, the following should be established:

• Clinical suspicion of CMS based on presentation
• Genetic testing showing DOK7, COLQ (acetylcholinesterase deficiency), or other relevant mutations
• Neurophysiological testing showing decremental response on repetitive nerve stimulation
• Exclusion of other neuromuscular disorders through appropriate testing

Treatment Protocol

Salbutamol (Albuterol)

• Starting dose: 2 mg three times daily (6 mg/day) 2
• Can be titrated based on response
• Particularly effective in children with DOK7 mutations 1

Ephedrine

• Starting dose: 25 mg/day
• Can be gradually increased to 75-100 mg/day as needed 3
• Monitor for cardiovascular side effects

Expected Response

Patients should be monitored for:

• Improvement in proximal muscle strength (typically within weeks)
• Enhanced ability to perform activities of daily living
• Increased walking distance/endurance
• Reduced fatigability

Important Contraindications and Cautions

• Avoid acetylcholinesterase inhibitors (pyridostigmine) in patients with:

  • Endplate acetylcholinesterase deficiency
  • Slow-channel syndrome
  • DOK7 myasthenia
  • β2-laminin deficiency 4

• These medications can worsen symptoms in these specific CMS subtypes

Monitoring and Follow-up

• Clinical assessment using standardized measures (MRC scale, QMG score)
• 6-minute walk test to objectively measure improvement
• Regular monitoring for side effects including:
  • Tremor
  • Tachycardia
  • Anxiety
  • Hypertension

Clinical Pearls

• Response to salbutamol/ephedrine can be dramatic and often begins within weeks of starting treatment 1
• Improvement is typically more pronounced in proximal muscle groups than facial muscles 3
• Vital capacity measurements and repetitive stimulation tests may not improve to the same degree as clinical symptoms 3
• These medications are generally well-tolerated in CMS patients 2

The dramatic improvement in muscle strength and function with salbutamol or ephedrine therapy in specific CMS subtypes makes early diagnosis and appropriate treatment essential for improving morbidity and quality of life in these patients.