How is myasthenia gravis (MG) graded and treated?

Myasthenia Gravis Grading and Treatment

Grading System

Myasthenia gravis is graded using the Myasthenia Gravis Foundation of America (MGFA) severity classification system, which ranges from Class I (ocular symptoms only) to Class V (myasthenic crisis requiring intubation), with all grades warranting immediate workup and intervention given the potential for rapid progression to respiratory compromise. 1

MGFA Classification Structure

• Grade 2 (MGFA Class I-II): Ocular symptoms only (Class I) or mild generalized weakness (Class II) with some symptoms interfering with activities of daily living 1

• Grade 3-4 (MGFA Class III-V): Moderate to severe generalized weakness (Class III-IV) or myasthenic crisis (Class V), characterized by any of the following: 1

  • Limiting self-care with aids warranted 1
  • Weakness limiting walking 1
  • ANY dysphagia 1
  • Facial weakness 1
  • Respiratory muscle weakness 1
  • Rapidly progressive symptoms 1

Critical Grading Consideration

• No Grade 1 category exists in the clinical management algorithm, as even mild symptoms require intervention 1
• All grades warrant potential inpatient admission due to risk of rapid deterioration 1

Treatment Algorithm by Grade

Grade 2 Management (MGFA Class I-II)

Initial Symptomatic Treatment:

• Start pyridostigmine at 30 mg orally three times daily, gradually titrating to a maximum of 120 mg orally four times daily based on symptoms and tolerability 1, 2, 3
• Hold immune checkpoint inhibitors (if applicable) and may resume only after symptoms resolve and steroid taper is completed 1

Escalation to Immunosuppression:

• Add corticosteroids (prednisone 0.5-1.5 mg/kg orally daily) if pyridostigmine provides insufficient control 1, 2
• Wean steroids based on symptom improvement, beginning taper 3-4 weeks after initiation 1
• Neurology consultation is mandatory 1
• Strongly consider inpatient care as patients can deteriorate quickly 1

Grade 3-4 Management (MGFA Class III-V)

Immediate Actions:

• Permanently discontinue immune checkpoint inhibitors (if applicable) 1
• Admit patient with ICU-level monitoring 1, 4
• Immediate neurology consultation 1, 4

Pharmacologic Management:

• Continue pyridostigmine, adjusting dose based on improvement 1, 4
• Initiate or continue corticosteroids (methylprednisolone 1-2 mg/kg daily or prednisone equivalent), with taper beginning 3-4 weeks after initiation 1, 4
• Initiate IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) OR plasmapheresis for 5 days 1, 4
• Consider adding rituximab if refractory to IVIG or plasmapheresis 1

Monitoring Requirements:

• Frequent pulmonary function assessment with negative inspiratory force (NIF) and vital capacity (VC) 1, 4
• Daily neurologic review 1, 4
• Cardiac monitoring with troponin and ECG to evaluate for concomitant myocarditis 1

Essential Diagnostic Workup

Serologic Testing:

• AChR and antistriated muscle antibodies in blood 1, 2
• If AChR antibodies are negative, test for MuSK and LRP4 antibodies 1, 2
• Note: Absence of antibodies does not rule out the syndrome 1

Functional Assessment:

• Pulmonary function testing with NIF and VC 1, 4
• Electrodiagnostic studies including repetitive nerve stimulation and/or jitter studies, with single-fiber EMG having >90% sensitivity for ocular myasthenia 2, 4

Exclusion of Complications:

• CPK, aldolase, ESR, and CRP for possible concurrent myositis 1
• Troponin, ECG, and consider TTE and/or cardiac MRI for myocarditis 1
• MRI brain and/or spine to rule out CNS involvement or alternate diagnosis 1

Critical Medications to Avoid

Patients must strictly avoid the following medications that worsen myasthenic symptoms: 1, 2, 5

• β-blockers 1, 2
• IV magnesium 1, 2
• Fluoroquinolone antibiotics 1, 2, 5
• Aminoglycoside antibiotics 1, 2, 5
• Macrolide antibiotics 1, 2, 5
• Barbiturate-containing medications (e.g., butalbital) 5

Common Pitfalls and Caveats

Cholinergic Crisis vs. Myasthenic Crisis:

• Both present with extreme muscle weakness, making differentiation extremely difficult 3
• Cholinergic crisis results from pyridostigmine overdosage and requires prompt withdrawal of all anticholinesterase drugs 3
• Myasthenic crisis requires more intensive anticholinesterase therapy 3
• Edrophonium chloride testing and clinical judgment may be required for differentiation 3
• Atropine is recommended for cholinergic crisis but can mask signs of overdosage if used routinely 3

IVIG Misuse:

• IVIG should NOT be used for chronic maintenance therapy in myasthenia gravis 5
• IVIG is reserved for acute exacerbations (Grade 3-4) or crisis situations requiring hospitalization 5, 4
• The correct dose is 2 g/kg total over 5 days (0.4 g/kg/day), not ongoing maintenance dosing 5, 4

Progression Risk:

• Approximately 50-80% of patients presenting with isolated ocular symptoms (Grade 2, MGFA Class I) will develop generalized myasthenia within a few years 2
• Regular pulmonary function assessment is crucial given this progression risk 2, 5

Diagnostic Distinguishing Features:

• Pupils are characteristically NOT affected in myasthenia gravis, which distinguishes it from third nerve palsy 2
• Presence of pupillary involvement should prompt evaluation for alternative diagnoses 2