Myasthenia Gravis Diagnostic and Management Guidelines

Diagnostic Testing

The American Academy of Neurology recommends testing for anti-acetylcholine receptor (AChR) antibodies first, as they are present in approximately 80% of patients with generalized myasthenia gravis and confirm the diagnosis 1, 2
AChR antibodies should be the initial test, though sensitivity drops to only 50% in purely ocular myasthenia 1
Anti-muscle-specific kinase (MuSK) antibodies must be tested when AChR antibodies are negative, as approximately one-third of seronegative patients will be MuSK-positive 1, 2
Anti-striated muscle antibodies should be included in the initial workup 3, 2
Single-fiber electromyography (SFEMG) is the gold standard with >90% sensitivity for ocular myasthenia 1
Repetitive nerve stimulation is less sensitive (positive in only one-third of ocular cases) but more widely available 1
Ice pack test is highly specific for myasthenia gravis, particularly for ocular symptoms—apply ice pack over closed eyes for 2 minutes and observe for symptom reduction 1, 2
Edrophonium (Tensilon) test has 95% sensitivity for generalized MG and 86% for ocular MG, but requires experienced practitioners with atropine available due to muscarinic side effects 1

CT chest with contrast after diagnosis confirmation to evaluate for thymoma, which occurs in 10-20% of AChR-positive patients 1
Pulmonary function testing with negative inspiratory force (NIF) and vital capacity (VC) to assess respiratory muscle involvement 3, 1
CPK, aldolase, ESR, and CRP to evaluate for concurrent myositis 3, 1
Troponin and ECG (consider echocardiogram or cardiac MRI) to rule out concomitant myocarditis 3, 1

Start pyridostigmine at 30 mg orally three times daily and gradually increase to maximum 120 mg four times daily based on symptoms 3, 2
For Grade 2 disease (mild generalized weakness, MGFA class I-II): Pyridostigmine plus prednisone 0.5 mg/kg orally daily if symptoms interfere with activities of daily living 3
For Grade 3-4 disease (moderate to severe weakness, MGFA class III-V): Add IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) or plasmapheresis for 3-5 days 3, 2
Thymectomy should be evaluated in appropriate AChR-positive patients 2
Approximately 66-85% of patients respond positively to corticosteroids 2
Azathioprine can be used as third-line immunosuppressive therapy for moderate to severe disease 2

Immediately review and stop medications that worsen myasthenia, including β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics 3, 1, 2

Daily neurologic review and frequent pulmonary function assessment for Grade 3-4 patients 3
ICU-level monitoring may be necessary for rapidly progressive symptoms or respiratory muscle weakness 3
Regular assessment is crucial as 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years 2

Approximately 50% of patients with ocular myasthenia show minimal response to pyridostigmine alone, necessitating escalation to immunosuppressive therapy, such as corticosteroids, which demonstrate superior efficacy with 66-85% positive response rates compared to pyridostigmine's 50% response rate 4
Early corticosteroid treatment is warranted when ocular motility abnormalities persist despite pyridostigmine, as ocular symptoms are highly variable and not readily remedied with prisms 4
Strabismus surgery may be considered only after disease stabilization, typically requiring 2-3 years of medical treatment, and should be decided in collaboration with an experienced ophthalmologist and neurologist 4

Diagnosis and management requires collaboration between an experienced ophthalmologist and neurologist, with potential involvement of cardiothoracic surgery for thymectomy, and corticosteroids are the most consistently effective immunosuppressive agents but carry the highest incidence of potential side effects 4

Approximately 50% of patients, particularly those with ocular/strabismus manifestations, will show minimal response to pyridostigmine alone and require escalation 5

Corticosteroids demonstrate superior efficacy with 66-85% positive response rates compared to pyridostigmine's 50% response rate 5

Always perform thymectomy when thymoma is present 6, 5
Thymectomy may substantially reduce symptoms and should be evaluated in appropriate AChR-positive patients 5

Efgartigimod alfa-fcab is FDA-approved specifically for AChR-positive patients who are refractory to conventional therapy 5

Ocular symptoms are highly variable and not readily remedied with prisms 5
Ice pack test can temporarily reduce symptoms and aid diagnosis 5
Strabismus surgery should only be considered after disease stabilization, typically requiring 2-3 years of medical treatment 6, 5
Surgical management requires particular care with anesthetic agents given potential respiratory muscle weakness 6, 5