What type of lung cancer is Lambert-Eaton myasthenic syndrome (LEMS) associated with?

Lambert-Eaton Myasthenic Syndrome is Strongly Associated with Small Cell Lung Cancer

Lambert-Eaton myasthenic syndrome (LEMS) is primarily associated with small cell lung cancer (SCLC), occurring in up to 60% of paraneoplastic LEMS cases. 1

Pathophysiology and Association

Lambert-Eaton myasthenic syndrome is a paraneoplastic neurologic disorder characterized by:

• Production of antibodies directed against voltage-gated calcium channels (VGCCs) on presynaptic nerve terminals 1
• Reduced acetylcholine release at the neuromuscular junction 2
• Proximal muscle weakness, particularly in the legs 3

The association with SCLC is particularly strong:

• Approximately 50-60% of LEMS cases are paraneoplastic in nature 3, 2
• Among paraneoplastic cases, SCLC accounts for the vast majority 1
• Other tumors are rarely associated with LEMS 2

Clinical Presentation and Diagnosis

Patients with LEMS typically present with:

• Proximal leg weakness that progresses proximally to distally 1, 2
• Reduced or absent deep tendon reflexes 2
• Autonomic dysfunction (dry mouth, constipation) 2

Diagnostic approach:

1. Clinical suspicion based on symptoms
2. Electrophysiological testing showing:
   • Small compound muscle action potentials (CMAPs) at rest
   • Significant increment (>100%) after brief exercise or high-frequency stimulation 2, 4
3. Serological testing for P/Q-type VGCC antibodies (positive in ~90% of cases) 4

Clinical Significance and Management

The presence of LEMS has important implications:

• LEMS can be an early indicator of underlying SCLC 3
• Diagnosis of LEMS should prompt immediate and thorough screening for SCLC 3
• Early detection of SCLC through LEMS diagnosis can lead to identification of limited-stage disease with better treatment outcomes 5

Management includes:

1. Treatment of underlying SCLC (priority) with chemotherapy and radiation therapy 6
2. Symptomatic treatment with 3,4-diaminopyridine (amifampridine) 7, 3
3. Immunosuppressive therapy for persistent symptoms 3

Prognosis

The prognosis for patients with LEMS varies:

• In non-tumor LEMS (NT-LEMS), life expectancy is normal 3
• In SCLC-associated LEMS, prognosis is determined by cancer progression 3
• Interestingly, patients with SCLC and LEMS may have better cancer outcomes than those with SCLC alone 6

Important Clinical Pearls

• NCCN guidelines recommend obtaining a comprehensive paraneoplastic antibody panel when neurologic paraneoplastic syndrome is suspected 1
• LEMS can precede the diagnosis of SCLC, making it a valuable early warning sign 1
• Successful treatment of SCLC often leads to improvement in LEMS symptoms 6
• Pre-treatment CMAP amplitude >3.0 mV is associated with better neurological outcomes 6