Neuroscience · Year 2 · from Neuroscience
Case 2: Lambert-Eaton Myasthenic Syndrome
Patient Presentation
Demographics: 58-year-old male
Chief Complaint: Progressive difficulty rising from a chair and climbing stairs over 2 months
History of Present Illness: A 58-year-old man with a 40-pack-year smoking history presents with gradually worsening proximal leg weakness. He has trouble getting out of low chairs and climbing stairs. Interestingly, he notes that his strength temporarily improves after a few seconds of sustained effort. He also reports dry mouth, constipation, and erectile dysfunction. He has lost 15 pounds unintentionally over 3 months.
Physical Examination:
- Vital signs: BP 142/88, HR 68, RR 16
- General: Thin, appearing older than stated age
- Neurological:
- Cranial nerves: Minimal ptosis; extraocular movements full
- Motor: 4/5 strength hip flexors and shoulder abduction initially, improving to 4+/5 with sustained effort (facilitation); distal strength preserved
- Sensory: Intact
- Reflexes: Absent initially; present after brief sustained muscle contraction (post-tetanic potentiation)
- Other: Dry oral mucosa
Workup:
- Voltage-gated calcium channel (VGCC) antibodies: Positive (P/Q-type)
- Electromyography/nerve conduction: Low compound muscle action potential (CMAP) amplitude at rest; >100% increment in CMAP amplitude after brief exercise
- CT chest: 3 cm spiculated mass in right upper lobe
- PET-CT: Hypermetabolic lung mass with mediastinal lymphadenopathy
- Lung biopsy: Small cell lung carcinoma
Diagnosis: Lambert-Eaton myasthenic syndrome (LEMS) as paraneoplastic syndrome secondary to small cell lung carcinoma
Treatment:
- Oncology referral for chemotherapy and radiation of small cell lung cancer
- 3,4-diaminopyridine (amifampridine) to enhance presynaptic acetylcholine release
- Pyridostigmine added for additional symptomatic benefit
- Surveillance for tumor response with expectation of LEMS improvement
Clinical Pearl: LEMS demonstrates the critical role of presynaptic calcium channels in neurotransmitter release. Antibodies against P/Q-type voltage-gated calcium channels impair calcium influx at the presynaptic terminal, reducing vesicle fusion and ACh release. The characteristic "facilitation" with sustained effort occurs because repeated depolarization allows calcium accumulation, temporarily overcoming the channel blockade. This distinguishes LEMS from myasthenia gravis, where weakness worsens with repeated effort.