What are the differences in symptoms and treatment approaches between myasthenia gravis and Lambert-Eaton myasthenic syndrome?

Distinguishing Symptoms: Myasthenia Gravis vs Lambert-Eaton Myasthenic Syndrome

The most critical distinguishing feature is that myasthenia gravis characteristically presents with ocular and bulbar weakness in a craniocaudal (descending) pattern, while Lambert-Eaton myasthenic syndrome presents with proximal leg weakness in a caudocranial (ascending) pattern, with ocular involvement virtually excluding LEMS. 1

Initial Symptom Distribution

Myasthenia Gravis

• Ocular weakness occurs as the initial symptom in 59% of patients, manifesting as ptosis and extraocular movement abnormalities 1, 2
• Bulbar involvement (dysphagia, dysarthria, facial weakness) presents initially in 29% 1
• Limb weakness as the first symptom occurs in only 12% 1
• Pupils are characteristically spared, which serves as a key diagnostic feature 3
• Weakness is typically more proximal than distal and demonstrates fatigable or fluctuating characteristics 3

Lambert-Eaton Myasthenic Syndrome

• No patient presents with ocular weakness as the initial symptom 1
• Only 5% have bulbar weakness initially 1
• 95% present with limb weakness as the first symptom, specifically affecting the legs 1
• Weakness follows an ascending pattern from legs upward 1

Distribution at Maximum Severity

Myasthenia Gravis

• Purely ocular weakness in 25% 1
• Oculobulbar weakness in 5% 1
• Weakness restricted to limbs in only 2% 1
• Combined oculobulbar and limb involvement in 68% 1
• When limb weakness is confined to the arms alone, this pattern is only found in myasthenia gravis and never in LEMS 1
• 50-80% of patients with initial ocular symptoms will develop generalized myasthenia within a few years 2

Lambert-Eaton Myasthenic Syndrome

• No patients have weakness restricted to extraocular or bulbar muscles 1
• Legs are affected in 100% of LEMS patients 1
• Weakness never remains confined to the arms 1

Key Clinical Pearls for Differentiation

If a patient's first symptom is ocular weakness, LEMS is virtually excluded from the differential diagnosis 1. This single clinical feature has the highest discriminatory value between these conditions.

The direction of weakness progression is pathognomonic:

• Myasthenia gravis: craniocaudal (head to toe) 1
• LEMS: caudocranial (toe to head) 1

Diagnostic Confirmation

Myasthenia Gravis

• Anti-acetylcholine receptor (AChR) antibodies are present in approximately 80% of generalized cases but sensitivity drops to 50% in purely ocular disease 2
• Anti-MuSK antibodies should be tested when AChR antibodies are negative, as approximately one-third of seronegative patients will be MuSK-positive 2
• Ice pack test is highly specific for ocular symptoms—apply ice over closed eyes for 2 minutes and observe for symptom reduction 2, 3
• Single-fiber EMG has >90% sensitivity for ocular myasthenia 2
• Repetitive nerve stimulation shows decremental response 2

Lambert-Eaton Myasthenic Syndrome

• Repetitive nerve stimulation demonstrates incremental response (opposite of MG) 4
• Resting compound muscle action potential (CMAP) amplitudes are characteristically low 4
• Post-exercise facilitation is a hallmark finding 4

Treatment Approach Differences

Myasthenia Gravis

• Start pyridostigmine 30 mg orally three times daily, gradually increasing to maximum 120 mg four times daily 2, 5
• For Grade 2 disease: add prednisone 0.5 mg/kg orally daily if symptoms interfere with activities of daily living 2
• For Grade 3-4 disease: add IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) or plasmapheresis 2, 6
• Thymectomy should be evaluated in appropriate AChR-positive patients 2
• Approximately 66-85% of patients respond to corticosteroids 2

Lambert-Eaton Myasthenic Syndrome

• 3,4-diaminopyridine is the primary treatment, showing significant improvement in muscle strength scores and CMAP amplitudes 4, 7
• FIRDAPSE (amifampridine) dosing: can be titrated up to 80-100 mg daily in divided doses 7
• Intravenous immunoglobulin improves myometric limb strength with clinical improvement lasting up to 8 weeks 4
• The overall weighted mean difference in CMAP amplitude after 3,4-diaminopyridine treatment was 1.80 mV (95% CI 0.82 to 2.78), favoring treatment 4

Critical Medication Avoidance (Both Conditions)

Immediately discontinue medications that worsen neuromuscular transmission: β-blockers, IV magnesium (absolutely contraindicated in MG), fluoroquinolones, aminoglycosides, and macrolide antibiotics 2, 3, 6

Common Pitfalls

Do not assume LEMS if a patient has any ocular involvement—this virtually excludes the diagnosis 1. Conversely, do not diagnose myasthenia gravis if pupils are abnormal, as this should prompt evaluation for third nerve palsy or other neurologic causes 3.

Pyridostigmine alone is insufficient in approximately 50% of ocular myasthenia cases, requiring escalation to corticosteroids 2, 3. In LEMS, pyridostigmine is generally ineffective and 3,4-diaminopyridine is the cornerstone of treatment 7, 4.