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Disorders of neuromuscular transmission affect the neuromuscular junction. They may involve
Common features of these disorders include fluctuating fatigue and muscle weakness with no sensory deficits.
Eaton-Lambert syndrome:
This disorder is due to impaired acetylcholine release from presynaptic nerve terminals (see Overview of Cancer: Neurologic paraneoplastic syndromes).
Botulism:
Also due to impaired release of acetylcholine from presynaptic nerve terminals, botulism develops when toxin produced by Clostridium botulinum spores irreversibly binds to the terminal cholinergic nerve endings (see Anaerobic Bacteria: Botulism). The result is severe weakness, sometimes with respiratory compromise. Other systemic symptoms may include mydriasis, dry mouth, constipation, urinary retention, and tachycardia due to unopposed sympathetic nervous system activity (anticholinergic syndrome). These systemic findings are absent in myasthenia gravis.
In botulism, electromyography (EMG) detects a mild decremental response to low-frequency (2- to 3-Hz) repetitive nerve stimulation but a pronounced incremental response after 10 sec of exercise or with rapid (50-Hz) repetitive nerve stimulation.
Drugs or toxic chemicals:
Cholinergic drugs, organophosphate insecticides, and most nerve gases block neuromuscular transmission by excessive acetylcholine action that depolarizes postsynaptic receptors. Miosis, bronchorrhea, and myasthenic-like weakness (cholinergic syndrome) result.
Aminoglycoside and polypeptide antibiotics decrease presynaptic acetylcholine release and sensitivity of the postsynaptic membrane to acetylcholine. At high serum levels, these antibiotics may increase neuromuscular block in patients with latent myasthenia gravis. Long-term penicillamine treatment may cause a reversible syndrome that clinically and electromyographically resembles myasthenia gravis. Excessive Mg po or IV (with blood levels approaching 8 to 9 mg/dL) can also induce severe weakness resembling a myasthenic syndrome.
Treatment consists of eliminating the drug or toxic chemical and providing necessary respiratory support and intensive nursing care. Atropine 0.4 to 0.6 mg po tid decreases bronchial secretions in patients with cholinergic excess. Higher doses (eg, 2 to 4 mg IV q 5 min) may be necessary for organophosphate insecticide or nerve gas poisoning.
Disorders With Neuromuscular Manifestations
Stiff-person syndrome:
The syndrome affects the CNS but has neuromuscular manifestations. It often occurs in patients with type 1 diabetes. It may be autoimmune and can occur as a paraneoplastic syndrome (most often with breast, lung, or colon cancer or with Hodgkin lymphoma). Autoantibodies against several proteins involved in GABA (γ-aminobutyric acid)-glycine synapses are present, affecting primarily inhibitory neurons that originate in the anterior horn of the spinal cord.
Progressive stiffness develops insidiously in the trunk and abdomen and, to a lesser degree, in the legs and arms. Patients are otherwise normal, and examination detects only muscle hypertrophy and stiffness. EMG shows only the electrical activity of normal contraction.
Only symptomatic therapy is available. Diazepam is the only drug that consistently relieves muscle stiffness. Results of plasmapheresis are inconsistent.
Isaacs' syndrome:
This syndrome, generally thought to be a channelopathy, sometimes occurs as a paraneoplastic syndrome. It may also occur in other disorders (eg, myasthenia gravis, thymoma, cancer, amyloidosis) or can be inherited. Cause is unknown. Abnormalities are thought to originate in a peripheral nerve because they are abolished by curare but usually persist after general anesthesia.
The limbs are most affected. The sine qua non is myokymia—continuous muscle twitching described as bag-of-worms movements. Other symptoms include carpopedal spasms, intermittent cramps, increased sweating, and pseudomyotonia (impaired relaxation after a strong muscle contraction but without the typical waxing-and-waning EMG abnormality of true myotonia). Carbamazepine or phenytoin may relieve these symptoms.
Last full review/revision February 2008 by Michael Rubin, MDCM
Content last modified February 2008
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