There are different etiologies for neuromuscular junction disorders (NMJD) discussed in the literature whereby myasthenia gravis (MG), belonging to the autoimmune category, is the most common form. Other causes are congenital or toxic (eg, botulism).
MG is a disease that interferes with the transmission of acetylcholine at the neuromuscular junction, leading to proximal muscle weakness and fatigue. In the majority of cases, it is caused by the binding of circulating autoantibodies to postsynaptic nicotinic Ach receptors. This in turn prevents acetylcholine, the neurotransmitter that is responsible for muscle contraction at the motor end plate, from connecting to its receptor. There is a generalized, an ocular, and a paraneoplastic variant of MG. The abovementioned autoantibodies can be found in about 80% of those with the generalized form of MG. In about 10% of patients with MG, a thymoma can be detected, which goes along with anti-titin antibodies.
A more uncommon disorder of neuromuscular junction transmission is Lambert-Eaton myasthenic syndrome (LEMS), which is also an autoimmune disorder. Most often it presents with progressive proximal muscle weakness, especially in the lower extremities, autonomic dysfunction, and areflexia. Different than myasthenia gravis, strength may temporarily improve with exertion due to buildup of acetylcholine. The pathophysiology of LEMS is based on antibodies directed against presynaptic voltage-gated calcium channels (VGCC), and there is a strong association with malignancy, especially with small-cell lung cancer (SCLC). Treatment is focused on the underlying cause (removal of the tumor). Immune-directed therapy with steroids and plasma exchange is applied as well.
Acute onset of symmetric descending weakness associated with bilateral cranial neuropathies (diplopia, nystagmus, ptosis, dysphagia, facial weakness) should raise red flags to consider botulism. Urinary retention and constipation can occur as well. Botulism is a rare potentially life-threatening disease caused by the toxin of the ubiquitously appearing gram-positive, spore-forming, obligate anaerobic bacterium Clostridium botulinum. There are different forms, namely, foodborne, infant, wound, adult enteric, and inhalational botulism. Foodborne botulism, for instance, is caused by the consumption of these pathogens in home-canned foods like vegetables or fruits. When botulism is suspected, the clinician ought to contact the State Health Department instantly to obtain antitoxin as the treatment of choice. Equine serum heptavalent botulism antitoxin is used for adults. Wound botulism requires antibiotics (penicillin G or metronidazole) after the administration of antitoxin.