What lab work is involved in diagnosing Myasthenia gravis (MG) and Multiple Sclerosis (MS)?

Laboratory Workup for Myasthenia Gravis and Multiple Sclerosis

Myasthenia Gravis Diagnostic Laboratory Testing

The diagnostic workup for myasthenia gravis centers on autoantibody testing, with acetylcholine receptor (AChR) antibodies being the cornerstone test, positive in approximately 85% of generalized MG cases. 1, 2

Essential Antibody Panel

• Anti-acetylcholine receptor (AChR) antibodies are highly specific for MG and should be the first-line serological test, with 73% diagnostic sensitivity 1, 3, 2
• Anti-MuSK (muscle-specific tyrosine kinase) antibodies must be checked if AChR antibodies are negative, as this identifies a distinct MG subtype requiring different treatment approaches 1, 2
• Anti-LRP4 (lipoprotein-related protein 4) antibodies should be tested in patients seronegative for both AChR and MuSK antibodies 1, 2
• Anti-striated muscle antibodies are particularly important in thymoma-associated cases and guide treatment decisions 1, 4

Muscle Inflammation Markers

• Creatine kinase (CK) and aldolase levels should be measured to detect concurrent myositis, which dramatically changes prognosis and management 5, 1
• Transaminases (AST, ALT) and lactate dehydrogenase (LDH) can be elevated in inflammatory myositis and should be checked 5, 4
• Troponin levels are mandatory if CK is elevated or respiratory symptoms are present, as myocarditis carries high mortality risk 5, 1

Inflammatory Markers

• ESR and CRP should be measured as additional markers for inflammatory myositis 5, 1

Critical Pre-Treatment Testing

• Serum IgA levels must be checked before plasmapheresis or IVIG administration to prevent potentially fatal anaphylaxis 1
• Coagulation studies (PT/PTT) are required before plasmapheresis to assess bleeding risk 1

Respiratory Assessment Labs

• Baseline negative inspiratory force (NIF) and vital capacity (VC) measurements are essential for monitoring respiratory function 1

Multiple Sclerosis Diagnostic Laboratory Testing

Brain MRI with gadolinium is the most sensitive and specific test for MS diagnosis and must be performed in all suspected cases, but cerebrospinal fluid analysis provides critical complementary information about intrathecal inflammation. 6

Cerebrospinal Fluid Analysis

• Oligoclonal bands present in CSF but absent in serum provide moderate-level evidence of intrathecal inflammation characteristic of MS 6
• Elevated IgG index supports the diagnosis with moderate-level evidence 6
• IgM oligoclonal bands may indicate more aggressive disease and antibody-mediated mechanisms 7

Essential Exclusionary Testing

• Serum anti-aquaporin-4 (AQP4) antibodies are mandatory to exclude neuromyelitis optica spectrum disorder (NMOSD), which requires entirely different treatment and can coexist with MG 6, 8
• Antinuclear antibodies (ANA) and anti-phospholipid antibodies should be tested to exclude systemic lupus erythematosus and antiphospholipid syndrome 6

Imaging Requirements

• Brain MRI with gadolinium must demonstrate lesions in at least 2 of 4 characteristic locations: periventricular, cortical/juxtacortical, infratentorial, or spinal cord 6
• Complete spinal cord MRI is recommended even without spinal symptoms, as 30-40% of patients with clinically isolated syndrome have asymptomatic spinal cord lesions 6
• Gadolinium contrast identifies simultaneous enhancing and non-enhancing lesions, demonstrating dissemination in time on a single scan 6

Critical Diagnostic Pitfalls

For Myasthenia Gravis

• Immediately check IgA levels before administering IVIG or plasmapheresis—failure to do so can cause fatal anaphylaxis 1
• Screen for concurrent myocarditis with troponin and ECG if CK is elevated, as the combination of myocarditis and MG has ominous prognosis with high mortality 1
• Discontinue contraindicated medications including IV magnesium, beta-blockers, fluoroquinolones, aminoglycosides, and macrolides, which can precipitate respiratory failure 1

For Multiple Sclerosis

• MRI interpretation requires experienced readers aware of clinical context, as non-specific white matter lesions from vascular or metabolic causes can mimic MS 6
• A minimum 3-month interval is required between clinical events or between baseline and follow-up MRI to demonstrate dissemination in time 6
• Consider MS when optic neuritis occurs in MG patients, as this may be the first symptom of demyelinating CNS disease requiring shorter-interval monitoring 8

Overlap Considerations

• The co-occurrence of MG and MS is rare but documented, with both diseases potentially sharing humoral immune mechanisms 7, 9, 8
• When evaluating patients with either condition who develop new neurological symptoms, consider the possibility of the other disease developing 8