Which clinical feature best distinguishes myasthenia gravis (MG) from Lambert-Eaton myasthenic syndrome (LEMS)?

Explanation

## Distinguishing MG from LEMS ### Key Pathophysiological Difference **Key Point:** LEMS exhibits **incremental response** (strength improves with repeated muscle contraction), whereas MG shows **decremental response** (strength worsens with repeated use). ### Comparison Table | Feature | Myasthenia Gravis | Lambert-Eaton Myasthenic Syndrome | |---------|-------------------|-----------------------------------| | **Antibody target** | Nicotinic AChR or MuSK | Presynaptic P/Q-type calcium channels | | **Pathophysiology** | Reduced ACh receptors at NMJ | Reduced ACh release from motor terminal | | **Strength with repetition** | **Decreases** (fatigable) | **Increases** (facilitation) | | **Ocular involvement** | Common (60–90%) | Rare | | **Autonomic symptoms** | Absent | Present (dry mouth, impotence, constipation) | | **Associated malignancy** | Rare (thymoma) | Common (60–85%, SCLC) | | **Reflexes** | Normal | Diminished or absent | | **Response to edrophonium** | Positive | Negative | ### Clinical Pearl **High-Yield:** The **incremental response** (post-tetanic potentiation) in LEMS is the gold-standard discriminator. Patients report that symptoms improve after brief exercise, unlike MG where fatigue worsens performance. This is because: - In LEMS, repeated stimulation causes calcium accumulation in the presynaptic terminal, increasing ACh release. - In MG, each contraction depletes the limited pool of available receptors, worsening the deficit. ### Electrophysiological Confirmation - **Repetitive nerve stimulation (RNS):** MG shows decremental response (>10% amplitude drop); LEMS shows incremental response (>100% increase in amplitude after brief high-frequency stimulation). - **Single-fiber electromyography (SFEMG):** Increased jitter and blocking in both, but pattern differs. ## Why Each Distractor Is Wrong **Option 0 (Ocular symptoms are the presenting feature):** While ocular symptoms (ptosis, diplopia) are hallmark of MG (present in 60–90%), they are **rare in LEMS** (<10%). This is a feature of MG, not a discriminator between the two — both can present with systemic weakness. LEMS typically presents with proximal leg weakness and autonomic symptoms. **Option 2 (Anti-acetylcholine receptor antibodies are present):** Anti-AChR antibodies are specific to MG (80% of generalized MG, 50% of ocular MG) and are **absent in LEMS**. While this is a strong diagnostic marker for MG, it is not a **clinical feature** that a patient or examiner would observe at the bedside — it requires serology. The question asks for a **clinical feature** that distinguishes the two syndromes. **Option 3 (Autonomic symptoms are prominent):** Autonomic dysfunction (dry mouth, impotence, constipation, blurred vision, orthostatic hypotension) is characteristic of LEMS, not MG. This is a feature of LEMS, not a discriminator — it would point toward LEMS, not distinguish MG from LEMS in a comparative sense. The question structure implies we need the feature that **favors one over the other**; this option is too LEMS-specific and would not help a clinician differentiate if both conditions were in the differential.