Disorders of the Neuromuscular Junction
Neuromuscular junction disorders
Myasthenia gravis (MG) causes fatigable ptosis, diplopia, bulbar and proximal weakness, with normal reflexes and sensation. Antibodies against acetylcholine receptor (AChR) are found in most generalized cases; MuSK and LRP4 antibodies occur in seronegative cases, and MuSK MG often has prominent bulbar and respiratory involvement. Thymoma is associated with AChR-positive MG and warrants chest imaging.
Repetitive nerve stimulation shows a decrement greater than 10% at 2-3 Hz in MG, best seen in proximal or facial muscles. Single-fiber EMG shows increased jitter, the most sensitive test. Routine NCS are normal, including sensory responses and CMAP amplitudes, unless the disease is severe.
Lambert-Eaton myasthenic syndrome (LEMS) is presynaptic, with proximal leg weakness, areflexia, autonomic symptoms, and a low baseline CMAP that facilitates after 10 seconds of exercise or high-frequency (20-50 Hz) stimulation. It is paraneoplastic in many cases (small cell lung cancer) and associated with voltage-gated calcium channel antibodies. Botulism causes descending weakness, autonomic dysfunction, and incremental responses; congenital myasthenic syndromes present in infancy or childhood with variable patterns.
Traps: a normal decrement study does not exclude ocular MG; test facial muscles and use single-fiber EMG. In LEMS, the baseline CMAP is low, so a normal CMAP argues against it. Do not confuse post-exercise facilitation with the decrement of MG. Ice-pack testing and edrophonium are adjuncts, not substitutes for antibody testing.
Worked example: a patient with proximal weakness, dry mouth, absent reflexes, and a low ulnar CMAP that doubles after exercise has LEMS; check VGCC antibodies and screen for lung cancer.
Rule of thumb: decrement at low frequency indicates MG; increment after exercise or high frequency indicates LEMS.