Myasthenia Gravis: Diagnosis and Initial Management
Clinical Recognition
Myasthenia gravis presents with fatigable, fluctuating muscle weakness that worsens with activity and improves with rest, most commonly beginning with ocular symptoms (ptosis and diplopia) that progress to generalized weakness in 50-80% of patients within the first few years. 1
Key Clinical Features to Identify
Ocular manifestations: Ptosis (often asymmetric) that worsens with sustained upgaze, variable diplopia, and slow saccadic eye movements—critically, pupils are never affected (pupillary involvement excludes myasthenia and suggests third nerve palsy) 1, 2
Bulbar symptoms: Dysarthria, dysphagia, facial weakness with reduced expression, and difficulty chewing that worsens during meals 1, 2
Limb weakness: Proximal muscles affected more than distal, with neck weakness causing difficulty holding up the head 1, 3
Respiratory involvement: Shortness of breath with exertion, weak cough, inability to count to 15 on a single breath (signals imminent respiratory failure), or difficulty clearing secretions 1
Hallmark pattern: Symptoms fluctuate throughout the day, worsen with repetitive activity, and improve with rest 2, 4
Critical Red Flags Requiring Immediate Action
Any dysphagia or bulbar weakness precedes myasthenic crisis in >50% of cases—these patients need urgent pulmonary function testing (negative inspiratory force and vital capacity) and ICU-level monitoring capability. 1
Diagnostic Work-Up
Bedside Testing (Perform Immediately)
Ice pack test: Apply ice over closed eyelids for 2 minutes (for ptosis) or 5 minutes (for strabismus); improvement of ptosis by ≥2 mm or reduction in ocular deviation by ≥50% is highly specific for myasthenia gravis 1
Rest test: Have patient close eyes for several minutes; improvement in ptosis or diplopia supports the diagnosis 1
Serologic Testing (Order First-Line)
Anti-acetylcholine receptor (AChR) antibodies: Present in nearly all generalized MG but only 40-77% of ocular MG 1, 2
If AChR-negative: Order anti-muscle-specific kinase (MuSK) antibodies (positive in ~33% of seronegative cases) and anti-lipoprotein-related protein 4 (LRP4) antibodies 1, 4
Anti-striated muscle antibodies: Identifies patients at higher risk for thymoma 1
Electrodiagnostic Studies
Single-fiber EMG: >90% sensitivity for ocular MG; gold standard test 1, 3
Repetitive nerve stimulation: Less sensitive (positive in only one-third of ocular MG) but more widely available 3
Nerve conduction studies and needle EMG: Exclude peripheral neuropathy and detect concurrent myositis 1
Respiratory Assessment (Essential in All Cases)
Pulmonary function testing: Measure negative inspiratory force (NIF) and vital capacity in all patients with generalized symptoms or any dysphagia 1, 3
Clinical bedside test: Inability to count to 15 on single breath indicates imminent respiratory failure 1
Cardiac and Muscle Evaluation
Check troponin T, CPK, aldolase, ESR, and CRP to screen for concurrent myocarditis or myositis (especially in immune checkpoint inhibitor-associated MG) 5, 1
ECG and echocardiography if respiratory insufficiency, elevated CPK, or troponin present 5, 1
Imaging
Chest CT: Screen for thymoma (present in 10-15% of MG patients; 30-50% of thymoma patients have MG) 1, 2
Brain/spine MRI: Consider if atypical features present to exclude brainstem lesions or compressive pathology 1
Initial Management Algorithm
MGFA Class I (Ocular Symptoms Only)
Start pyridostigmine 30 mg orally three times daily, gradually increase to maximum 120 mg four times daily as tolerated. 5, 1, 3
Caveat: Only ~50% of ocular MG patients respond adequately to pyridostigmine alone 1, 3
If inadequate response after 2-4 weeks: Add prednisone 1-1.5 mg/kg orally daily (66-85% response rate) 1, 3
Neurology referral: Mandatory for all patients—do not manage definitively in primary care 1
MGFA Class II (Mild Generalized Weakness)
Hold immune checkpoint inhibitors if applicable; start pyridostigmine as above AND initiate prednisone 1-1.5 mg/kg orally daily. 5, 1
May resume checkpoint inhibitors only if symptoms completely resolve (neurology consultation required) 5
Monitor respiratory function with serial NIF and vital capacity 5, 3
MGFA Class III-V (Moderate-Severe Weakness, Any Dysphagia, Respiratory Involvement, or Myasthenic Crisis)
Permanently discontinue immune checkpoint inhibitors; admit to hospital with ICU capability; obtain urgent neurology consultation. 5, 1
Acute immunotherapy (choose one):
Plus corticosteroids: Methylprednisolone 1-2 mg/kg IV daily or prednisone 1-1.5 mg/kg orally daily 5, 1
Plus pyridostigmine: Continue or initiate as above 5
Monitoring:
- Frequent pulmonary function assessment (NIF/vital capacity every 4-6 hours) 5, 1
- Daily neurologic examination 5
- Continuous pulse oximetry and cardiac monitoring 5
Critical Medications to AVOID
Immediately discontinue and permanently avoid these drugs in all MG patients: 5, 1, 3
- β-blockers
- IV magnesium
- Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin)
- Aminoglycosides (gentamicin, tobramycin)
- Macrolide antibiotics (azithromycin, clarithromycin, erythromycin)
Common Pitfalls to Avoid
Assuming negative AChR antibodies exclude MG: 50% of ocular MG and 10-20% of generalized MG are seronegative—proceed with MuSK and LRP4 testing plus single-fiber EMG 1, 4
Missing early respiratory compromise: Dysphagia and bulbar weakness precede crisis in >50% of cases; always assess pulmonary function even if patient appears stable 1
Delaying treatment in "mild" cases: All grades warrant immediate work-up and intervention given potential for rapid progression to respiratory failure 5, 3
Overlooking concurrent myocarditis/myositis: Check troponin and CPK in all patients, especially those on immune checkpoint inhibitors (mortality significantly increased if present) 5, 1
Failing to screen for thymoma: Chest CT is mandatory in all newly diagnosed MG patients 1, 2
Prognosis and Long-Term Considerations
50-80% of patients with initial ocular symptoms progress to generalized MG within 2 years 1, 2, 4
Median duration of mechanical ventilation in myasthenic crisis: 12-14 days; 22% require intubation within first week 1
Remission or stabilization possible after 2-3 years of treatment in most patients 3
Immune checkpoint inhibitor-associated MG may be monophasic and not require long-term immunosuppression 5, 3