Botulism
From the EM Model
12.0 Nervous System Disorders
12.7 Neuromuscular Disorders

The evaluation and management of patients who present with peripheral neurologic complaints can cause anxiety and frustration for emergency physicians because of the wide variety of benign and life-threatening illnesses that are associated with those complaints and the fact that patients can present early in the disease process when it is more difficult to discern a specific diagnosis. Additionally, patients with peripheral neuropathies are generally only a small percentage of the patients that a typical emergency physician sees. In this review, an uncommon yet life-threatening peripheral neuropathy, botulism, will be described.

In order to diagnose a peripheral neuropathy, it is first important to differentiate it from a central neuropathy, which can be difficult because features of the history and physical examination for both overlap. Important elements to elicit in the history are the symptom onset, duration, provocative and alleviating factors, prodromal symptoms, and the degree of the neurologic deficit. The neurologic examination should focus on the following areas: sensory, motor, reflexes, and upper motor neuron signs. On the sensory examination, peripheral lesions are generally restricted to a single dermatome with a sharp border of demarcation.

With central lesions, especially spinal lesions, sensory symptoms are more commonly bilateral and involve multiple dermatomes. One area that is commonly overlooked on the sensory examination is the trunk. Specifically, patients with a thoracic spine lesion may have sensation that is symmetric and present over the legs, but in reality and in comparison to the trunk it is diminished but just not recognized by the patient or examiner.

The classic stocking-glove sensory deficit is a peripheral neuropathy that is most commonly seen with diabetes and chronic alcohol use. On motor examination, peripheral lesions usually cause unilateral weakness that is limited to the muscle group that is innervated by the involved nerve.

A central neuropathy will have weakness or paralysis distal to the site of the lesion. The findings with these central lesions are more commonly bilateral and can have associated upper motor neuron signs such as spasticity, hyperreflexia, and clonus. In some instances, the patient will complain of leg weakness but have no demonstrable weakness on the initial examination. One maneuver to help demonstrate weakness is to have the patient squat down and rise to the standing position without any assistance. Most patients without weakness are able to do this with only minor difficulty. If the patient is unable to rise or cannot rise without assistance then there is weakness.

A second maneuver to differentiate weakness in the calf muscles is to have the patient perform a unilateral heel raise while standing flatfooted on one foot only. The patient is permitted to balance with a hand, but most of the weight should be on that one foot. Then have the patient switch feet and perform the same test with the opposite foot. Most emergency physicians are not strong enough to use their arms to elicit a patient’s calf weakness. However, this maneuver uses the patient’s body weight and is very good at bringing out more subtle weakness.

In peripheral neuropathies the reflexes that are involved with the specific nerve are generally diminished or absent. Other reflexes will be normal. For central lesions, the patient may have hyporeflexia to areflexia, although there may also be hyperreflexia and clonus. Other important areas to evaluate are continence of urine and feces and impotence. Urinary and fecal incontinence nearly always indicate a central lesion.

Occasionally arm weakness or numbness from peripheral neuropathy or radiculopathy can be difficult to distinguish from stroke. As a rule, strokes do not cause limb pain, so associated pain typically excludes stroke as a cause. Paresthesias are common in radiculopathy and peripheral neuropathy but uncommon in stroke, which usually involves loss of sensation rather than hyperesthesias or paresthesias.

Case Presentation

A 4-month-old girl is brought in by her parents who are concerned because the child has been feeding poorly for the past several days. Her mother says that she switched from breast to bottle feeding 2 weeks ago and that her daughter “just doesn’t seem interested in eating.” Both parents state that the child has had one bowel movement in the past week, which is unusual for her, but they attributed that to the change in feedings. Other than being slightly less active than normal, there are no other complaints.

The child has an uncomplicated birth history and has been healthy since her delivery. There are no sick contacts in the household, and the child stays at home with her mother during the day. Her immunizations are current.

Vital signs are heart rate 132, respiratory rate 22, rectal temperature 37.3°C (99.2°F), and pulse oximetry 96% on room air. Physical examination reveals an ill-appearing child, lying quietly in her mother’s arms. The child is drooling and has some pooling of secretions in her mouth. She has coarse lung sounds, but she is not tachypneic or retracting. Her abdomen is soft and nontender. Most notably, the child has poor muscle tone and does not resist any part of the examination. She does not interact at all with you or her parents.

Botulism

Botulism is a paralytic disease caused by the bacteria Clostridium botulinum, which produces a heat-stable neurotoxin that engenders a diffuse peripheral neuropathy. There are three distinct varieties of the disease, food-borne, wound, and infantile, the last of which has more recently been termed intestinal botulism. All have similar clinical manifestations, but the manner of acquisition and the populations affected by each are unique.

This disease is relatively uncommon, with only 171 cases reported in 2006 to the Centers for Disease Control and Prevention (CDC).¹ Because of its rarity, the disease is frequently confused with other neurologic and infectious diseases. It has such significant morbidity that most patients present initially to an emergency department for evaluation and management of their symptoms.

Pathophysiology

Botulism’s effect on nerve terminals is the same in all three varieties. After the toxin has entered the bloodstream, it is taken up at the presynaptic nerve terminals by endocytosis. Through a chain reaction of biochemical events, the toxin inhibits the release of acetylcholine from the presynaptic terminal. This action essentially limits motor and autonomic neuron function.^2,3 Because the effects of the toxin are irreversible, clinical recovery does not occur until new neuromuscular junctions are created.

Infantile (intestinal) botulism is the most common form of the disease and accounts for approximately two- thirds of all cases.¹ It is caused by the ingestion of botulism spores, which then germinate, colonize, and produce toxin in an infant’s colon.⁴ The disease is classically associated with feeding honey to infants, but only 15% of recent cases have been linked to honey.¹ The source of the remaining cases has not been identified, but the ingestion of environmental agents such as contaminated soil and vacuum cleaner dust is thought to be a likely cause.^3,5 This disease primarily affects infants, because their gastrointestinal tracts have yet to be colonized by the competitive flora that protect adults and older children.⁵

Food-borne botulism is caused by the ingestion of preformed toxin and is responsible for approximately 20% of cases.¹ Reports are clustered in the western states, particularly Alaska, where improper canning techniques and failure to cook home-canned food properly are blamed. Occasionally, commercially produced food products are responsible. In the summer of 2007, four cases of food-borne botulism were reported. All were connected to the ingestion of Castleberry’s Hot Dog Chili Sauce, and each of those cases presented to a different emergency department.⁶

Wound botulism is the rarest of the three entities.¹ It classically occurs when a wound becomes contaminated with Clostridia-laden soil. The bacteria then flourish and produce the toxin, which is systemically absorbed.² Clostridia-contaminated wounds usually do not appear as grossly infected as one might expect.

In the United States, cases of wound botulism are found almost exclusively in injection drug users, typically with subcutaneous rather than intravenous injection. Recently, a cluster of cases was associated with “black tar” heroin use.⁷

CRITICAL DECISION

What clinical clues suggest the diagnosis of botulism?

The incubation period of infantile (intestinal) botulism is nearly impossible to pinpoint. Constipation is often the initial symptom and can be present for days before neurologic symptoms occur.² Cranial nerves are affected first, resulting in the loss of facial expression and decreased suck and cry. Initially, these findings are very subtle. As neurologic deterioration continues, the baby will develop poor head control and diffuse hypotonia (“floppy baby”).⁴ Symptoms progress over hours to days (mean of 4.2 days) before the child is hospitalized and the disease is recognized.⁵ As in adults, respiratory paralysis is responsible for botulism mortality. Infantile botulism is thought to be an occasional etiology for sudden infant death syndrome.⁵

Food-borne and wound botulism have indistinguishable symptoms. The incubation period for food-borne botulism is between 12 and 72 hours.¹ Determining a precise incubation period for wound botulism is difficult, if not impossible. Symptoms of both conditions usually start with cranial nerve deficits: Diplopia, facial weakness, dysphagia, ptosis, and speech changes are all common findings. Paralysis then descends, affecting the upper extremities before the lower. Respiratory muscle paralysis occurs as the process descends. The autonomic nervous system is also affected, resulting in dry mouth, postural hypotension, paralytic ileus, and pupillary abnormalities.

In one emergency department case series of food-borne botulism, all 29 patients had at least three of the following: weakness, dry mouth, double vision, and difficulty speaking.⁸ In a larger case series of 705 patients, 68% had at least three of the following symptoms on admission: nausea and vomiting, dysphagia, diplopia, dry mouth, and fixed and dilated pupils.²

CRITICAL DECISION

Are there any confirmatory tests for botulism that can be performed in the emergency department?

In all three varieties of botulism, the diagnosis is clinical. Stool, wound, and blood should be tested for toxin and cultured. However, these are of no help in the emergency department diagnosis and management of the condition. Routine diagnostic studies are helpful only to rule out other conditions. The best way to confirm the diagnosis of infantile botulism is through identification of the toxin in the stool, which may be difficult, as these patients are usually very constipated.⁵

CRITICAL DECISION

What immediate life threats must be addressed in a patient with botulism?

All patients with suspected botulism should be admitted to the ICU for observation and supportive care. The primary concern is the evaluation and management of the patient’s airway and respiratory status. If there is any concern for airway or respiratory compromise, the patient should be immediately intubated and maintained on mechanical ventilation until the toxin’s effects have worn off, which can take weeks. Even if the patient’s respiratory status is good on initial evaluation, it must be reassessed frequently, because this disease can progress rapidly.

CRITICAL DECISION

Other than supportive care, what can be done for a patient with botulism?

In addition to supportive care, all patients with food-borne and wound botulism should be treated with one vial of botulism antitoxin.1 Because this is derived from horse serum, all patients should have skin testing for hypersensitivity before administration. The antitoxin has been shown to decrease mortality and reduce hospital length of stay. Although it prevents progression of the disease, it does not reverse the paralysis, as the toxin binds irreversibly. The antitoxin can be obtained through state and local health departments and the CDC.¹

In patients with wound botulism, the wound should be débrided. Antibiotics should be given for coexisting infection, but no studies have shown that their administration hastens recovery from the paralysis.

For infantile botulism, supportive care is, again, the backbone of treatment. Antibiotics are ineffective.⁵ The antitoxin is not used in infants out of concern about reactions to the horse serum derivative.

Recently, human botulism immune globulin (HBIG) has been made available by the FDA for infantile botulism only. Like the antitoxin, it has been shown to decrease ICU length of stay, ventilation requirements, and mortality.⁹ It can be obtained by calling the Infant Botulism Treatment and Prevention Program at 510-231-7600.

Case Resolution

The infant who was not feeding normally was recognized to have an at-risk airway and ventilatory status and was immediately intubated. A sepsis workup was initiated, including a CBC, urinalysis, blood and urine cultures, a chest radiograph, and a lumbar puncture. Results of a thorough ophthalmoscopic examination and a noncontrast computed tomography scan of the head were normal. The child was empirically started on vancomycin, ceftriaxone, and acyclovir and admitted to the pediatric ICU for further management.

One day after admission, all cultures were negative, and infantile botulism was considered. Minimal stool was obtained and sent to the state laboratory, where it was found to be positive for botulinus toxin. Her providers called the Infant Botulism Treatment and Prevention Program and obtained HBIG, which was administered at a dose of 50 mg/kg. She had a prolonged period of mechanical ventilation but was eventually discharged home with no residual morbidity.

Summary

Emergency physicians have the difficult job of rapidly evaluating and managing disease that may be presenting quite early in its evolution. Through diligence and attention to detail, emergency physicians should be able to identify botulism. Once this disease is suspected, the initial management is directed toward ensuring that the airway is protected and that the patient does not require immediate or urgent ventilatory assistance. Once this lifesaving intervention has been considered or implemented, emergency physicians should further evaluate these patients and involve the appropriate consultants to admit the patient to the hospital. It is important to remember that laboratory testing from the emergency department is unlikely to confirm this disease process, although it could help rule out other etiologies for the patient’s symptoms.

Pearls

• Consider the diagnosis of botulism in toxic-appearing infants.
• All patients with suspected botulism should be admitted to the ICU.
• Findings that suggest the diagnosis of botulism are dry mouth, double vision, difficulty speaking, dysphagia, diplopia, and fixed and dilated pupils.
• Contact the CDC or local health department to obtain HBIG or botulism antitoxin as soon as the diagnosis is suspected.
• Pitfalls
• Not identifying subtle weakness by conducting a squat down or heel raise test.
• Failing to initiate rapid airway control and respiratory support in a patient who is deteriorating secondary to presumed botulism.

References

1. Centers for Disease Control and Prevention. Emergency Preparedness and Response. Botulism: Information and Guidance for Clinicians Online. Available at: http://www.bt.cdc.gov/agen/botulism/clinicians. Accessed August 31, 2009.
2. Greenberg D, Aminoff M, Simon R, eds. Clinical Neurology. 5th ed. Chicago, IL: McGraw-Hill; 2002.
3. Lawrence DT, Dobmeier SG, Bechtel LK, Holstege CP. Food poisoning. Emerg Med Clin North Am. 2007;25(2):357-373; abstract ix.
4. Schreiner MS, Field E, Ruddy R. Infant botulism: a review of 12 years’ experience at the Children’s Hospital of Philadelphia. Pediatrics. 1991;87(2):159-165.
5. Long SS. Infant botulism. Pediatr Infect Dis J. 2001;20(7):707-709.
6. Botulism associated with commercially canned chili sauce—Texas and Indiana, July 2007. MMWR Morb Mortal Wkly Rep. 2007;56(30):767-769.
7. Passaro DJ, Werner SB, McGee J, et al. Wound botulism associated with black tar heroin among injecting drug users. JAMA. 1998;279:859-863.
8. Ruthman JC, Hendricksen DK, Bonefeld R. Emergency department presentation of type A botulism. Am J Emerg Med. 1985;3:203-205.
9. Arnon SS, Schechter R, Maslanka SE, et al. . N Engl J Med. 2006;354:462-471.