Are there conditions that present with both myopathic and myasthenia gravis (Myasthenia Gravis) features?

Overlap Syndromes with Features of Both Myopathy and Myasthenia Gravis

Yes, there are several conditions that can present with clinical features of both myopathy and myasthenia gravis, most notably immune checkpoint inhibitor-induced overlap syndrome and thymoma-associated overlap syndromes.

Immune Checkpoint Inhibitor-Induced Overlap Syndrome

Immune checkpoint inhibitor (ICPi) therapy can cause a rare but potentially fatal overlap syndrome with features of both myosthenia gravis and myositis 1.

• Clinical presentation:

  • Fatigable muscle weakness (myasthenic feature)
  • Ptosis and diplopia (myasthenic features)
  • Proximal muscle weakness (myopathic feature)
  • Elevated creatine kinase levels (myopathic feature)
  • Dysphagia and dysarthria (can occur in both)

• Diagnostic findings:

  • Positive anti-acetylcholine receptor antibodies (myasthenic feature)
  • Anti-striated muscle antibodies may be present
  • EMG showing both myopathic changes and decremental response
  • Muscle biopsy showing inflammatory infiltrates

• Prognosis: This overlap syndrome carries an ominous prognosis with high mortality rates, especially when myocarditis is also present 1.

Thymoma-Associated Overlap Syndromes

Thymomas can trigger multiple autoimmune conditions simultaneously, including both myasthenia gravis and inflammatory myopathies 2.

• Epidemiology:

  • Approximately 30-50% of patients with thymomas have myasthenia gravis
  • 10% of myasthenia gravis patients have thymomas
  • Presence of thymoma leads to more severe myasthenic symptoms

• Clinical features:

  • Ocular symptoms (ptosis, diplopia)
  • Generalized fatigable weakness
  • Proximal muscle weakness
  • Respiratory muscle involvement

Other Overlap Conditions

Congenital Myasthenic Syndromes with Myopathic Features

Some congenital myasthenic syndromes (CMS) can present with both myasthenic and myopathic features 3:

• Typically present in early childhood
• Fluctuating and fatigable weakness (myasthenic feature)
• Can sometimes present with limb-girdle distribution of weakness (myopathic feature)
• Caused by genetic mutations affecting neuromuscular junction proteins

Inflammatory Myopathies with Myasthenic Features

Dermatomyositis and polymyositis can occasionally present with myasthenic features 1:

• Primarily present with proximal muscle weakness
• Some patients may develop fatigable weakness
• May have positive anti-acetylcholine receptor antibodies in rare cases

Diagnostic Approach

1. Laboratory testing:

   • Creatine kinase levels (elevated in myopathies)
   • Anti-acetylcholine receptor antibodies (positive in MG)
   • Anti-MuSK antibodies (alternative MG marker)
   • Anti-striated muscle antibodies (may indicate thymoma)
   • Inflammatory markers (ESR, CRP)

2. Electrophysiologic testing:

   • EMG to detect myopathic changes (short duration, low amplitude motor units)
   • Repetitive nerve stimulation to detect decremental response (myasthenic feature)
   • Single fiber EMG for jitter (sensitive for MG)

3. Imaging:

   • Chest CT/MRI to evaluate for thymoma
   • MRI of muscles to assess for inflammation or atrophy

4. Tissue sampling:

   • Muscle biopsy to evaluate for inflammatory infiltrates
   • Thymus evaluation if thymectomy is performed

Treatment Considerations

Treatment of overlap syndromes requires addressing both the myasthenic and myopathic components:

1. For ICPi-induced overlap syndrome 1:

   • Discontinuation of the checkpoint inhibitor
   • High-dose corticosteroids (prednisone 1-2 mg/kg/day)
   • IVIG or plasma exchange for severe cases
   • Close monitoring for respiratory compromise and myocarditis

2. For thymoma-associated overlap syndromes:

   • Thymectomy (particularly indicated in the presence of thymoma) 2
   • Acetylcholinesterase inhibitors (pyridostigmine) for myasthenic symptoms
   • Immunosuppression with corticosteroids and steroid-sparing agents

3. Special precautions:

   • Caution with corticosteroids in myasthenia gravis as they may initially worsen symptoms 4
   • Careful use of acetylcholinesterase inhibitors as overdosage can lead to cholinergic crisis 5
   • Avoid medications that can exacerbate myasthenia (certain antibiotics, beta-blockers)

Clinical Pitfalls and Caveats

1. Diagnostic challenges:

   • Myasthenic crisis and cholinergic crisis can be difficult to distinguish but require opposite treatments 5
   • Weakness from myopathy may mask or mimic myasthenic symptoms

2. Treatment complications:

   • High-dose corticosteroids can cause acute myopathy, especially in patients with myasthenia gravis 4
   • Anticholinesterase agents and corticosteroids used together require close monitoring in patients with overlap syndromes

3. Monitoring requirements:

   • Regular assessment of respiratory function
   • Cardiac monitoring for patients with potential myocardial involvement
   • Regular creatine kinase measurements to monitor myopathy activity

The recognition and proper management of these overlap syndromes are crucial as they often present with more severe symptoms and carry a worse prognosis than either condition alone.