Management of Paraneoplastic Myasthenia
The management of paraneoplastic myasthenia requires prompt neurological consultation, identification of the underlying malignancy, and aggressive immunosuppressive therapy with corticosteroids as first-line treatment, followed by IVIG or plasmapheresis for moderate to severe cases. 1
Clinical Presentation and Diagnosis
Paraneoplastic myasthenia gravis (MG) is characterized by:
- Progressive symmetrical proximal muscle weakness
- Bulbar, ocular, neck, and respiratory symptoms at onset (distinctive non-limb symptom profile) 2
- Fatigability with repetitive use
- Possible concurrent myositis or myocarditis 1
Diagnostic workup should include:
- Anti-acetylcholine receptor (AChR) antibodies in blood
- If AChR antibodies are negative, test for MuSK and LRP4 antibodies
- Pulmonary function assessment (NIF and VC)
- CPK, aldolase, ESR, and CRP to evaluate for concurrent myositis
- Electrodiagnostic studies including repetitive stimulation and jitter studies
- Thoracic imaging to identify thymoma or other underlying malignancies 1, 2
Treatment Algorithm
Step 1: Assess Severity and Stabilize
- Grade 2 (mild generalized weakness): Hold immunotherapy if applicable, consult neurology, consider inpatient care
- Grade 3-4 (moderate to severe weakness, dysphagia, respiratory involvement): Admit to hospital with ICU capability, permanently discontinue immunotherapy if applicable 1
Step 2: Symptomatic Treatment
- Pyridostigmine (anticholinesterase): Start at 30 mg PO three times daily, gradually increase to maximum of 120 mg PO four times daily as tolerated 1, 3
- Monitor for cholinergic crisis (increased weakness, excessive secretions) which requires prompt discontinuation of anticholinesterase medications 4
- Discontinue medications that can worsen myasthenia: beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics 1
Step 3: Immunosuppressive Therapy
First-line: Corticosteroids (prednisone 0.5-1 mg/kg orally daily) 1, 3
- Caution: May initially worsen symptoms in MG
- Continue for 3-4 weeks before tapering based on symptom improvement
- Monitor for steroid-related complications, especially in patients with myasthenia 5
For moderate to severe cases (Grade 3-4):
Step 4: Treat Underlying Malignancy
- Thorough cancer screening, especially for thymoma in AChR-positive MG 3
- Surgical removal of thymoma when present 2
- Consider pre-thymectomy plasmapheresis or IVIG to minimize post-thymectomy MG exacerbation risk 2
- Treat other identified malignancies appropriately, as cancer treatment often improves paraneoplastic symptoms 3, 6
Step 5: Long-term Immunosuppression
If symptoms persist after initial treatment:
- Add non-steroid immunosuppressants (azathioprine, tacrolimus, cyclosporine A, mycophenolate mofetil) 3, 2
- Tacrolimus should be especially considered in difficult paraneoplastic MG cases 2
Monitoring and Follow-up
- Frequent pulmonary function assessment
- Daily neurological review for hospitalized patients
- Regular monitoring of muscle strength and fatigability
- Vigilance for respiratory compromise which may require ventilatory support 1
Important Considerations
- Paraneoplastic MG usually continues after thymectomy, requiring ongoing immunosuppression 2
- Distinguish between myasthenic crisis (disease worsening) and cholinergic crisis (medication overdose) as management differs radically 4
- Lambert-Eaton myasthenic syndrome (LEMS) is another paraneoplastic neuromuscular junction disorder, often associated with small cell lung cancer, requiring similar but distinct management approaches 7, 8
Prognosis
The prognosis of paraneoplastic MG is largely determined by: