The occurrence of an epidemic of afebrile patients with progressive symmetrical descending flaccid paralysis strongly suggests botulinum intoxication. Foodborne outbreaks tend to occur in small clusters and have never occurred in soldiers on military rations such as MREs (Meals, Ready to Eat). Higher numbers of cases in a theater of operations should raise at least the consideration of a BW` attack with aerosolized botulinum toxin.

Individual cases might be confused clinically with other neuromuscular disorders such as Guillain-Barre syndrome, myasthenia gravis, or tick paralysis. The edrophonium or Tensilon® test may be transiently positive in botulism, so it may not distinguish botulinum intoxication from myasthenia. The cerebrospinal fluid in botulism is normal and the paralysis is generally symmetrical, which distinguishes it from enteroviral myelitis. Mental status changes generally seen in viral encephalitis should not occur with botulinum intoxication.

It may become necessary to distinguish nerve agent and/or atropine poisoning from botulinum intoxication. Nerve agent poisoning produces copious respiratory secretions, miotic pupils, convulsions, and muscle twitching, whereas normal secretions, mydriasis, difficulty swallowing, and progressive muscle paralysis is more likely in botulinum intoxication. Atropine overdose is distinguished from botulism by its central nervous system excitation (hallucinations and delirium) even though the mucous membranes are dry and mydriasis is present. The clinical differences between botulinum intoxication and nerve agent poisoning are depicted in Appendix H.

Laboratory testing is generally not critical to the diagnosis of botulism. Mouse neutralization (bioassay) remains the most sensitive test, and serum samples should be drawn and sent to a laboratory capable performing of this test. PCR might detect C. botulinum genes in an environmental sample. Detecting toxin in clinical or environmental samples is sometimes possible by ELISA or ECL. Clinical samples can include serum, gastric aspirates, stool, and respiratory secretions. Survivors do not usually develop an antibody response due to the very small amount of toxin necessary to produce clinical symptoms. Exposure does not confer immunity.

Differential Diagnosis of Botulism

Note: This differential diagnosis applies to botulism in adults and older children; infant botulism is not included, since that condition is distinct from what would be expected during a bioterrorism attack.


Features that distinguish each condition from botulisma

Guillain-Barre syndrome (GBS) (particularly Miller Fisher variant)

—Classic GBS results in ascending paralysis
—Miller Fisher variant may be descending and may have pronounced cranial nerve involvement; it usually includes a triad of ophthalmoplegia, ataxia, and areflexia (5% of GBS cases are of the Miller Fisher variant)b
—Abnormal CSF protein 1-6 wk after illness onset (although may be normal early in clinical course)
—Paresthesias commonly occur (often stocking/glove pattern)
—EMG shows abnormal nerve conduction velocity; facilitation with repetitive nerve stimulation does not occur (as with botulism)
—History of antecedent diarrheal illness (suggestive of Campylobacter infection, which accounts for about one third of GBS cases)
—Outbreaks of GBS do not occur (unlike botulism)

Myasthenia gravis

—Dramatic improvement with edrophonium chloride (ie, a positive Tensilon test), although some botulism patients may exhibit partial improvement following administration of edrophonium chloride (ie, a borderline Tensilon test)
—EMG shows decrease in muscle action potentials with repetitive nerve stimulation

Tick paralysisc

—Ascending paralysis
—Paresthesias are common
—Careful examination reveals presence of tick attached to skin
—Recovery occurs within 24 hr after tick removal
—EMG shows abnormal nerve conduction velocity and unresponsiveness to repetitive stimulation
—Usually does not involve cranial nerves

Lambert-Eaton syndrome

—Commonly associated with carcinoma (often oat cell carcinoma of lung)
—Although EMG findings are similar to those in botulism, repetitive nerve stimulation shows much greater augmentation of muscle action potentials, particularly at 20-50 Hz
—Increased strength with sustained contraction
—Deep tendon reflexes often absent; ataxia may be present
—Usually does not involve cranial nerves

Stroke or CNS mass lesion

—Paralysis usually asymmetric
—Brain imaging (CT or MRI) usually abnormal
—Sensory deficits common
—Altered mental status may be present


—Febrile illness
—CSF shows pleocytosis and increased protein
—Altered mental status may be present
—Paralysis often asymmetric

Paralytic shellfish poisoning or ingestion of puffer fish

—History of shellfish (ie, clams, mussels) or puffer fish ingestion within several hours before symptom onset
—Paresthesias of mouth, face, lips, extremities commonly occur

Belladonna toxicity

—History of recent exposure to belladonna-like alkaloids
—Altered mental status

Aminoglycoside toxicity

—History of recent exposure to aminoglycoside antibiotics
—More likely to occur in the setting of renal insufficiency
—Most commonly seen with neomycin
—Most commonly associated with other neuromuscular blocking agents such as succinylcholine and paralytics

Other toxicities (hypermagnesemia, organophosphates, nerve gas, carbon monoxide)

—History of exposure to toxic agents
Carbon monoxide toxicity: altered mental status may occur, cherry-colored skin
Hypermagnesemia: history of use of cathartics or antacids may be present, elevated serum magnesium level
Organophosphate toxicity: fever, excessive salivation, altered mental status, paresthesias, miosis

Other conditions

—CNS infections (particularly brainstem infections)
—Inflammatory myopathy
—Diabetic neuropathy
—Viral infections
—Streptococcal pharyngitis (pharyngeal erythema and sore throat can occur in botulism owing to dryness caused by parasympathetic cholinergic blockade)

Abbreviations: CSF, cerebrospinal fluid; EMG, electromyogram; CT, computed tomography; MRI, magnetic resonance imaging.

aSee References: Arnon 2001, Campbell 1981, Cherington 1998, Werner 2000.
bSee References: Sobel 2005, Dorr 2006.
cSee References: Felz 2000.

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