Makindo Medical Notes

Related Subjects: |Lung Cancer |Hypercalcaemia |Oncological emergencies |Malignant Hyperparathyroidism due to PTHrP |Lambert-Eaton syndrome (LEMS) |Superior Vena Caval Obstruction syndrome

About

• 🧩 Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare autoimmune disorder, often a paraneoplastic syndrome, especially with small cell lung cancer (SCLC).
• 🔍 Symptoms may precede the cancer diagnosis → early screening is crucial.
• 👩‍🦱 Can also occur in younger autoimmune patients without malignancy.

Aetiology

• 🎯 Autoimmune attack on presynaptic voltage-gated calcium channels (VGCC), reducing acetylcholine release.
• 🧪 VGCC antibodies found in 75–100% with SCLC and 50–90% without cancer.
• 🫁 Malignancy (esp. SCLC) present in ~50% of LEMS cases.

Clinical Features

• 🦵 Proximal Weakness: Difficulty climbing stairs, rising from chair, lifting arms.
• 🔄 Facilitation: Strength improves briefly after exercise/repetition (unlike MG).
• ⚡ Autonomic Dysfunction: Dry mouth, constipation, erectile & bladder issues.
• 😮‍💨 Respiratory Weakness: Severe cases may need ventilatory support.

Differential Diagnosis

• 👁️ Myasthenia Gravis (MG): More ocular/bulbar involvement; worsens with repetition.
• 💪 Primary Myopathy: Mimics proximal weakness but without facilitation pattern.
• 🧠 Motor Neuron Disease (MND): Weakness plus UMN/LMN signs distinguish MND.

Investigations

• ❌ Tensilon Test: Usually negative (unlike MG).
• 🧪 Antibodies: P/Q-type VGCC ± M-type VGCC often positive.
• ⚡ Electrodiagnostics: Incremental response with high-frequency stimulation = hallmark.
• 🫁 Imaging (CXR/CT/PET): To look for SCLC or other malignancy.

Management

• 💊 Immunosuppression: Corticosteroids/azathioprine (less effective than in MG).
• 💉 Plasma Exchange / IVIG: Useful in refractory/severe cases.
• ⚡ 3,4-Diaminopyridine (3,4-DAP): Blocks K⁺ channels, prolongs AP, enhances acetylcholine release.
• 🤲 Symptomatic Support: Manage dry mouth, constipation, erectile issues.

Prognosis & Follow-up

• 📅 Annual cancer screening, esp. SCLC, as LEMS may precede diagnosis.
• 📊 Prognosis better if no malignancy or if cancer is detected and treated early.

Cases — Lambert–Eaton Myasthenic Syndrome (LEMS)

• Case 1 — Paraneoplastic LEMS (Small-Cell Lung Cancer) 🫁: A 62-year-old man with a 40 pack-year smoking history reports progressive difficulty climbing stairs and rising from chairs. Exam: proximal leg weakness, absent ankle reflexes that improve briefly after maximal voluntary contraction. CT chest reveals a hilar mass. Diagnosis: LEMS as a paraneoplastic syndrome due to small-cell lung cancer. Management: Treat underlying malignancy (chemotherapy/radiotherapy); symptomatic therapy with 3,4-diaminopyridine; physiotherapy.
• Case 2 — Autoimmune Non-Paraneoplastic LEMS 🧬: A 45-year-old woman presents with gradually worsening proximal weakness and dry mouth. Exam: fatigable weakness, reduced reflexes that improve after exercise, autonomic features (constipation, postural dizziness). Antibodies against voltage-gated calcium channels (VGCC) positive. No malignancy on screening. Diagnosis: Autoimmune LEMS without cancer. Management: 3,4-diaminopyridine; pyridostigmine may help; immunosuppression (azathioprine, prednisolone) if severe.
• Case 3 — Diagnostic Confusion with Myasthenia Gravis ⚖️: A 52-year-old woman is referred for “myasthenia gravis” after presenting with proximal weakness. However, she reports improvement of strength after brief exercise and autonomic symptoms (dry eyes, constipation). Reflexes are depressed but improve transiently with effort. EMG shows incremental response after repetitive stimulation. Diagnosis: LEMS misdiagnosed initially as MG. Management: Confirm with VGCC antibodies; malignancy screening; symptomatic treatment with 3,4-diaminopyridine; consider immunotherapy.

Teaching Commentary 🧠

Lambert–Eaton syndrome is a presynaptic neuromuscular junction disorder due to autoantibodies against P/Q-type voltage-gated calcium channels. Key features: - Weakness: proximal, especially legs; improves with exercise (“facilitation”). - Reflexes: reduced/absent but improve after effort. - Autonomic dysfunction: dry mouth, impotence, constipation, orthostatic hypotension. - Association: ~50% linked to small-cell lung cancer. Dx: EMG (incremental response), VGCC antibodies, malignancy screen. Rx: Treat malignancy, 3,4-diaminopyridine, immunosuppression, physio. ⚡ Contrast with Myasthenia Gravis: MG worsens with exertion, LEMS improves after exertion.