BOTULINUM TOXIN: PATHOGENESIS AND CLINICAL MANIFESTATIONSBotulinum toxin is produced primarily by Clostridium botulinum, a spore-forming obligate anaerobe. The toxin targets neurons and mainly causes a flaccid muscle paralysis. The use of botulinum toxin as a biological weapon would most likely take the form of aerosolization or food contamination. This concern has heightened since Iraq’s acknowledgement in 1995 of the production of 19,000 L of botulinum toxin, three times the amount needed to annihilate the entire human population.
PathogenesisBotulinum toxin is a zinc-dependent metalloprotease that exists in seven distinct antigenic types (A through G). Only types А, В, E, and F cause human disease. These four types act by a similar mechanism and produce similar clinical manifestations when either inhaled or ingested. Botulinum toxin can be inactivated by heat (>85°C for at least 5 minutes).Clostridium botulinum has three modes of entry into the human body: wound contamination, foodborne, and inhalation. After toxin is absorbed, it enters the bloodstream and travels to peripheral cholinergic synapses, primarily the neuromuscular junction. Once at these sites, botulinum toxin is internalized and enzymatically prevents the release of acteylcholine. Recovery of neuromuscular function requires new synapses to form. Symptoms of botulism typically develop 12 to 72 hours after exposure. This incubation period depends on the amount of toxin absorbed and the rate of absorption. Person-to-person transmission of botulism does not occur.
Clinical ManifestationsBotulism is an acute symmetrical descending flaccid paralysis that often begins in the bulbar musculature. Prominent bulbar palsies typically include diplopia, dysarthria, dysphonia, and dysphagia (the so-called 4 Ds). Pupillary dilatation and subsequent blurry vision may also be present. The symmetric descending paralysis usually begins in the upper extremities and then progresses down the trunk and to the lower extremities, highlighted by the loss of deep tendon reflexes. Finally, respiratory muscle paralysis occurs.Features that discriminate botulism from other paralyses include the following:- Patients are afebrile- Mental status remains clear- Sensory deficits are not observed- Neurologic findings are symmetric*213/348/5*