Disorders of Neuromuscular Transmission

Myasthenia gravis is the most common disorder affecting the neuromuscular junction (incidence: 5 per 100,000). Ocular involvement accounts for initial complaints in 75% of patients. Of patients presenting with ocular myasthenia, 50–80% eventually develop generalized myasthenia, usually within two years of onset. Myasthenia gravis is an autoimmune disease caused by the presence of antibodies against acetylcholine receptors, which leads to decreased number of available receptors (usually less than one-third that of normal). It is associated with other autoimmune diseases, including thymoma, dysthyroidism, sarcoidosis, pernicious anemia, aplastic anemia, and collagen vascular diseases (e.g., rheumatoid arthritis, lupus, ankylosing spondylitis, ulcerative colitis, Sjögren’s syndrome). ■ Side effects: cholinergic (e.g., bradycardia, angina, bronchospasm) ■ Steps for performing Tensilon test: 1. Prepare 10 mg/mL Tensilon in a tuberculin syringe, 0.6 mg atropine in a tuberculin syringe, and 10 mL normal saline. 2. Establish intravenous access using butterfly needle; flush with 1 mL normal saline. 3. Inject 0.2 mL Tensilon, flush with 1 ml normal saline, and wait 1 min for possible side effects. 4. Inject 0.6 mL Tensilon, flush with 1 mL normal saline, then attach atropine syringe. 5. Wait 3 min; improvement of ptosis or diplopia constitutes a positive test. Improvement of ptosis after application of ice for 2 min on the ptotic eyelid constitutes a positive test. The ice test is especially useful for very young, elderly, or ill patients. Improvement of ptosis or ocular alignment after 30–45 min of sleep constitutes a positive test. ■ Repetitive nerve stimulation with supramaximal stimuli delivered at 2–3 Hz: Rapid decrement of the amplitude of compound muscle action potentials (CMAPs) ≥10–15% confirms the diagnosis in 95% of cases. ■ Single-fiber electromyography (EMG; e.g., frontalis muscle) is highly sensitive (88–99% sensitivity). A positive test consists of increased jitter (increased latency between nerve stimulation and action potential of muscle fibers) and increased blockage (response failure). Acetylcholine receptor antibody is not detectable in about 15% of patients. Muscle-specific kinase is detected in 20% patients who have no acetylcholine receptor antibody and is usually detected in patients with generalized myasthenia gravis.