Disorder of neuromuscular transmission

Disruption of neuromuscular transmission occurs due to defects in postsynaptic receptors (e.g., myasthenia) or presynaptic release of acetylcholine (e.g., botulism), as well as breakdown of acetylcholine in the synaptic cleft (effect of drugs or neurotoxic agents). Fluctuations in the degree of muscle weakness and fatigue are typical.

Diseases in which there is a violation of neuromuscular transmission

Eaton-Lambert syndrome develops when the release of acetylcholine from presynaptic nerve endings is impaired.

Botulism is a consequence of impaired release of acetylcholine by the presynaptic terminal due to irreversible binding of the toxin Clostridium botulinum to it. Symptoms include severe weakness up to respiratory failure and signs of increased sympathetic tone due to blocking of parasympathetic activity: mydriasis, dry mouth, constipation, urinary retention, tachycardia, which does not occur in myasthenia. EMG shows a moderate decrease in response to low-frequency (2-3 per 1 second) irritation of the nerve and an increase in response with an increase in the frequency of irritation (50 imp/s) or after short-term (10 s) muscle work.

Drugs or toxic substances may impair the function of the neuromuscular synapse. Cholinergic drugs, organophosphorus insecticides, and most nerve gases block neuromuscular transmission by depolarizing the postsynaptic membrane due to excessive action of acetylcholine on its receptors. The result is miosis, bronchorrhea, and myasthenic-like weakness. Aminoglycosides and polypeptide antibiotics reduce presynaptic release of acetylcholine and the sensitivity of the postsynaptic membrane to it. In the setting of latent myasthenia, high serum concentrations of these antibiotics aggravate the neuromuscular block.

Long-term treatment with penicillamine may be accompanied by a reversible syndrome that clinically and by EMG resembles myasthenia. Excess magnesium (blood level 8-9 mg/dl) is fraught with the development of severe weakness, which also resembles myasthenic syndrome. Treatment includes elimination of toxic effects, intensive observation and, if necessary, artificial ventilation. To reduce excessive bronchial secretion, atropine 0.4-0.6 mg orally 3 times a day is prescribed. In case of poisoning with organophosphorus insecticides or nerve gas, higher doses (2-4 mg intravenously over 5 min) may be required.

Stiff-person syndrome is the sudden onset of progressive rigidity of the trunk and abdominal muscles, and to a lesser extent, the limbs. There are no other abnormalities, including EMG. This autoimmune syndrome develops as a paraneoplastic syndrome (more often in breast, lung, and rectal cancer and in Hodgkin's disease). Autoantibodies against several proteins associated with GABA glycine synapses affect primarily the inhibitory neurons of the anterior horns of the spinal cord. Treatment is symptomatic. Diazepam significantly reduces muscle rigidity. The results of plasmapheresis are contradictory.

Isaacs syndrome (synonyms: neuromyotonia, armadillo syndrome) manifests itself mainly by complaints about the functioning of the limbs. Myokymia appears - muscle fasciculations that look like a conglomerate of worms moving under the skin. Other complaints: carpopedal spasms, intermittent cramps, increased sweating and pseudomyotonia (impaired relaxation after strong muscle contraction, but without the typical for true myotonia increase-decrease in EMG). Initially affects the peripheral nerve, since curare removes complaints, and under general anesthesia the symptoms persist. The cause is unknown. Carbamazepine or phenytoin reduce complaints.

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