Diagnosis Synopsis
Botulism is caused by a group of paralytic neurotoxins produced by the spore-forming, anaerobic, gram-positive bacillus Clostridium botulinum. Intoxication can occur naturally from contaminated foods or rarely as a result of wound or intestinal colonization in humans. There are seven types of botulinum toxins, A through G, although only A, B, E and F have been implicated in the poisoning of humans. Botulism is classified as a Category A bioterrorism agent because of its ease of dissemination and high mortality rate. When used as a biological weapon, botulinum toxin is most likely to be dispersed as an aerosol for inhalation, although it could be added to the food or water supply. Botulinum toxins are, by weight, the most toxic agents known, with an LD50* of only 0.001 mcg/kg.

Botulinum toxin irreversibly binds to the pre-synaptic cholinergic neuromuscular junction, blocking acetylcholine release and manifesting as a symmetric, progressive, descending flaccid paralysis with bulbar palsies after an 18 to 36 hour incubation period (occasionally up to several days). Multiple cranial nerve palsies are evident early in the course of the disease. Symptom severity ranges from mild to frank paralysis. Severe poisonings may require months of ventilatory support.

Patients are afebrile, with initial complaints of blurred vision, diplopia and mydriasis with photophobia, ptosis, ophthalmoplegia, hoarseness, dysarthric speech and dysphagia. Constipation, dry mouth and urinary retention may also occur. Symptoms progress in a descending pattern to produce a skeletal muscle paralysis that may cause sudden respiratory arrest and death if untreated. Following an aerosol release, the toxin may be swallowed as well as inhaled. Patients remain awake, alert, and oriented throughout the entire illness. In food acquired cases, nausea, vomiting and diarrhea may precede the paralysis and cases will cluster around consumption of the contaminated food at a restaurant or from improper home canning. Botulism has a mortality rate of 5 to 10% (up to 30% in victims over 60 years of age).

Botulism is not contagious and is not spread person-to-person.
Botulinum toxins are odorless and colorless in solution. Five minutes of heating the toxin above 85 degrees Centigrade will inactivate the toxin.
An antitoxin is available from the CDC.
People at higher risk for contracting foodborne botulism are nursing home residents, dormitory residents, wedding guests and festival and other large event attendees. Intestinal botulism occurs in infants and IV drug users are likely candidates for wound botulism.
Foodborne botulism is a public health emergency and must be reported to state or local health departments as well as the CDC.

Precautions:
To prevent aerosol inhalation use a HEPA or N-95 filter mask (lacking those, a surgical mask may provide some protection). Minute quantities of C. botulinum acquired by ingestion, inhalation or absorption can cause death.
All materials suspected of containing toxin must be handled with caution. Prior to the shipment of any botulism-associated specimen, the designated laboratory must be notified and approved by the state health department.

*LD50 (LD = lethal dose) is the amount of a material, given all at once, which causes death in 50% of its recipients.

Look For
Look for the classic triad of botulism: symmetric, descending flaccid paralysis with prominent bulbar palsies; an afebrile patient; and a clear sensorium.
Remember the "4Ds" of the bulbar palsies: diplopia, dysarthria, dysphonia, and dysphagia.

Diagnostic Pearls
Symptoms of botulism may be similar to that of some snakebite envenomations. Snake exposure should be questioned and patient examined for fang marks.
The toxin does not penetrate brain parenchyma so patients typically do not exhibit confusion.

Differential Diagnosis & Pitfalls
Constricted pupils and convulsions may indicate exposure to a nerve agent chemical weapon.
Marine toxins (tetrodotoxin, saxitoxin)
Guillain-Barre (ascending paralysis)
Tick paralysis
Myasthenia gravis
CVA
Drug overdose (depressants, atropine)
Snake bite
Lambert-Eaton syndrome
CNS infection
CNS tumor

Best Tests
Suggestive clinical exam findings in combination with a history of possible exposure are necessary for a presumptive diagnosis. Laboratory diagnostic testing is available only at the CDC and some state and county public health laboratories.

Management Pearls
If administered very early in the course of the intoxication, antitoxin (equine) is effective in reducing the severity of the symptoms.
Supportive care in the ICU is essential. Depending on the severity of symptoms, intubation and mechanical ventilation may be necessary. Monitor for aspiration pneumonia and respiratory failure. Most patients eventually recover, although supportive care may take weeks to months.
In the United States, botulism is reportable in every state and the District of Columbia.

Therapy
In the U.S. equine botulinum antitoxin is available from the CDC via state and local health departments; it is effective in treating exposure to the most common types of botulism (A, B, and E). The dose has changed over time and clinicians are encouraged to review the package insert with their local health authorities.
Currently, the dose is a 10-mL vial, diluted 1:10 in 0.9% saline solution delivered as a slow intravenous infusion. One vial provides between 5500 and 8500 IU of each type-specific antitoxin. In food borne botulism one dose is typically sufficient; the amount of antibody in the vial far exceeds the serum toxin levels found. In the event of a bioterror attack, with potentially high exposure, the patient should be retested for toxin after treatment. Serum sickness, urticaria and anaphylaxis are possible side effects.

Medical Disclaimer:
The information contained in this web page is intended to be an adjunct to traditional medical information sources. It is not intended to be a substitute for professional medical judgment.

Authors and Editors:
Tener Goodwin Veenema PhD, MPH, MS, CPNP