It is now well established on the basis of observations in both animals and humans that the primary site of action of toxin is at a neuromuscular junction, more specifically on the presynaptic membrane. The toxin interferes with the release of acetylcholine from peripheral motor nerves at the neuromuscular synapse. The physiologic defect is similar to the one that characterizes the myasthenic syndrome of Lambert-Eaton (see Chap. 46) but different from that of myasthenia gravis.
Symptoms usually appear within 12 to 36 h of ingestion of the tainted food. Anorexia, nausea, and vomiting occur in most patients. As a rule, blurred vision and diplopia are the initial neural symptoms; their association with ptosis, strabismus, and extraocular muscle palsies, particularly of the sixth nerve, may at first suggest a diagnosis of myasthenia gravis. In botulism, however, accommodation is lost and the pupils are often unreactive to light. Other symptoms of bulbar involvement—nasality of voice, hoarseness, dysarthria, dysphagia, and an inability to phonate—follow in quick succession. These, in turn, are followed by progressive weakness of the muscles of the face, neck, trunk, and limbs, and by respiratory insufficiency. Despite the oropharyngeal weakness, it is not unusual for the gag reflex to be retained. Tendon reflexes are lost in cases of severe generalized weakness. These symptoms and signs evolve rapidly, over 2 to 4 days as a rule, and may be mistaken for those of the Guillain-Barré syndrome. Sensation remains intact, however, and the spinal fluid shows no abnormalities. Severe constipation is characteristic of botulism, perhaps as a result of paresis of smooth muscle of the intestine. Consciousness is retained throughout the illness unless severe degrees of anoxia develop as a result of respiratory failure. In the past, the mortality was greater than 60 percent, but it has declined greatly in recent decades, with improvements in the intensive care of acute respiratory failure and the effectiveness of C. botulinum antitoxins.
The clinical diagnosis can be confirmed by electrophysiologic studies. Specifically, there is reduced amplitude of evoked muscle potentials and an increase in amplitude with rapid repetitive nerve stimulation (the opposite of what is found in myasthenia gravis). In patients who recover, improvement begins within a few weeks, first in ocular movement, then in other cranial nerve functions. Complete recovery of paralyzed limb and trunk musculature may take many months.
The three types of botulinum toxins—A, B, and E—cannot be distinguished by their clinical effects alone, so that the patient should receive the trivalent antiserum as soon as the clinical diagnosis is made. This antitoxin can be obtained from the Centers for Disease Control and Prevention in Atlanta, Georgia. An initial dose of 10,000 U is given intravenously after intradermal testing for sensitivity to horse serum, followed by daily doses of 50,000 U intramuscularly until improvement begins. Penicillin or metronidazole are given to eradicate the organism in a wound (but are not as useful if the exogenous preformed toxin has been ingested).
Guanidine hydrochloride (50 mg/kg) has been somewhat useful in reversing the weakness of limb and extraocular muscles. Antitoxin and guanidine probably change the course of the illness relatively little and recovery depends on the effectiveness of respiratory care, maintenance of fluid and electrolyte balance, prevention of infection, and so on.