U01.11.052 Neuromuscular junction diseases

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Learning Objectives

Differentiate between Myasthenia Gravis (MG) and Lambert-Eaton Myasthenic Syndrome (LEMS) based on their unique immunologic targets. Master the clinical “rules of thumb” regarding muscle use, reflexes, and associated malignancies (Thymic vs. Lung).

1. Comparison of NMJ Disorders

While both conditions present with proximal muscle weakness, their pathophysiology occurs on opposite sides of the synaptic cleft, leading to distinct clinical behaviors.

Feature Myasthenia Gravis (MG) Lambert-Eaton (LEMS)
Pathophysiology Autoantibodies to postsynaptic ACh receptors. Autoantibodies to presynaptic voltage-gated Ca2+ channels.
Mechanism ACh receptor destruction/blockade. Reduced ACh release (L comes before M).
Muscle Use Worsens with use (fatigable). Improves with use (potentiation).
Reflexes Normal / Spared. Hyporeflexia or absent.
Autonomic Sx None. Dry mouth, constipation, impotence.
Associated With Thymoma, thymic hyperplasia. Small cell lung cancer (SCLC).

2. Clinical Presentation Details

MG often begins with ocular symptoms, whereas LEMS is more likely to present as a paraneoplastic syndrome in a patient with a smoking history.

  • Myasthenia Gravis: Often presents with ptosis and diplopia. Bulbar involvement (dysphagia/difficulty chewing) is a major concern.
  • Lambert-Eaton: Weakness is typically in the legs first. Improvement occurs because repeated stimulation “forces” more calcium into the presynaptic terminal.

Activity: NMJ Pathophysiology Flowchart Mapping

High-Yield Mnemonics:

  • L vs M: Lambert-Eaton is Limbs (starts in legs) and Lungs (SCLC). Myasthenia is Mouth/Eyes (bulbar/ocular).
  • The Alphabet Rule: L (Lambert) comes before M (Myasthenia), just as Presynaptic comes before Postsynaptic.
  • Reflexes: Lambert = Low reflexes. Myasthenia = Maintained reflexes.

Activity: