Botulism

• Acute paralytic illness caused by a neurotoxin produced by Clostridium botulinum
• Skeletal muscle paralysis and dysautonomia are the hallmarks of botulism
• There are four major forms of human botulism:
  1. Food borne botulism (“classic form”)
  2. Infant botulism (most common form)
  3. Wound botulism
  4. Adult intestinal toxemia (or “hidden botulism”)
• Two minor, extremely rare forms of human botulism are:
  1. Inhalational botulism
  2. Iatrogenic botulism
• If clinically stabilized, slow but full recovery should be expected

Clostridium botulinum

• Obligate anaerobic, gram positive bacillus which, along with its spores, is found ubiquitously in soil, aquatic sediment and GI tract of grazing livestock and wild animals
• Botulinum spores require temperatures of ≥120oC to kill and may survive for decades in fluid or dry media
• Seven types of C. botulinum are differentiated by the antigenicity of their toxin (types A to G)
• Types A, B and E arte the most common cause of human botulism
• Botulinum toxin cleaves intracellular proteins and inhibits fusion of synaptic vesicles and release of ACh into the synaptic cleft
  • Toxins A, C and E cleave synaptosomal-associated protein (SNAP-25)
  • Toxins B, D and F cleave synaptobrevin/vesicle-associated membrane protein (VAMP)
  • Toxin C cleaves syntaxin

Food botulism

• Initial symptoms are abdominal cramps, distention, nausea and vomiting
• Blurred vision, photophobia, diplopia, ptosis, dysarthria, dysphonia and dysphagia gradually set in
• Descending symmetrical muscle weakness of varying degree follows
• Neck muscles are usually the first peripheral muscles to be affected, followed by respiratory and limb muscles
• Autonomic dysfunction is often present and affects both sympathetic and parasympathetic system
• Dysautonomia may be more severe and longer lasting than neuromuscular symptoms
• Typical autonomic symptoms include: orthostatic hypotension, xerostomia, ileus, urinary retention, mydriasis, bradycardia, impaired sudomotor skin responses
• Rapidity of progression and severity of symptoms depends on the inoculated dose of botulinum toxin
• Untreated food botulism has a mortality of 60%
• 30% of patients with food botulism require mechanical ventilation lasting days to weeks

Vehicles associated with food-borne botulism

• Home-canned or processed low-acid (pH >4.6) foods including vegetables, meats, fish or seafood, fermented or salted fish products, relish or salsa, chilies
• Baked potatoes in aluminum foil
• Garlic oil
• Cheese sauce
• Sautéed onions under butter sauce

Infant botulism

• Most common form of botulism
• Incidence estimated 2.1 cases per 100,000 live births in the United States
• Typically affected ages are between 2 weeks and 1 year (median 10 weeks)
• Presentation:
  • Constipation
  • Weak cry
  • Lethargy
  • Difficulty feeding
  • Poor sucking
  • Dysautonomia
  • Progressive weakness of limb and bulbar muscles develops in hours to days. Weakness manifests as poor head control and progresses to descending flaccid paresis
  • Respiratory distress is often a late manifestation
  • Severity may be highly variable from mild hypotonia to sudden unexpected death
• Mortality rate is ~5%

Wound botulism

• Occurs by introduction of C. botulinum spores in wounds followed by in vivo formation of botulinum toxin
• May occur in traumatic or surgical wounds
• Increasingly recognized in intravenous drug users
• Has been reported following inhalation of cocaine
• Similar neurologic features to food botulism but no abdominal symptoms
• Similar clinical outcomes with food botulism

Adult intestinal toxemia botulism (“hidden botulism”)

• Normally C. botulinum spores cannot germinate in the generally acidic environment of the adult human GI tract
• Adult intestinal toxemia occurs when C. botulinum spores successfully germinate in and colonize the GI tract.
• Achlorhydria, Crohn’s disease, antibiotic therapy and several other spontaneous and iatrogenic abnormalities of the small and large bowel predispose to the condition
• Clinical presentation and outcomes are similar to food botulism

Iatrogenic botulism

• The majority of cases of iatrogenic botulism have occurred as a complication when using botulinum toxin to treat dystonia, blepharospasm and spasticity
• Botulism resulting from application of botulinum toxin for cosmetic purposes is more unusual due to the significantly lower doses applied compared to the above conditions

Inhalational botulism

• A single report of three cases in Germany in 1962 occurred in a group of laboratory technicians experimenting with aerosolized botulinum toxin
• Botulinum toxin is a potential biologic weapon and several attempts to exploit it have taken place in the past

Diagnosis

Neurotoxin assay and C. botulinum cultures

• A bioassay for the detection of botulinum toxin in gastric, serum or stool samples or infected food is available
• The sensitivity of the assay is 60-70% for samples collected within 2 days from symptom onset
• Gastric or stool sample cultures for C. botulinum may be positive in ~60% of food botulism cases
• Wound cultures in suspected wound botulism cases may be positive in ~57% of cases

Electrophysiologic studies

• Findings in botulism are similar to those in Lambert-Eaton myasthenic syndrome but tend to be more variable among muscle groups and change over a period of days. Posttetanic facilitation may last longer in botulism (up to 20 min)
• Decreased compound muscle action potential amplitudes are seen in 85–92% of patients
• Compound sensory nerve action potential amplitudes, conduction velocities and distal latencies in both motor and sensory fibers are normal
• 57% of patients with infant botulism may have a decremental response to low-frequency (2–5 Hz) repetitive nerve stimulation
• Incremental response may be seen as a result of posttetanic facilitation, after either high-frequency (30–50 Hz) repetitive nerve stimulation or 10 sec of isometric exercise
• 54% of patients with infant botulism may have low-amplitude and polyphasic motor unit potentials and fibrillation potentials

Management

• Supportive measures
• Intubation and mechanical ventilation if needed
• Equine-derived botulinum antitoxin is considered standard of care in the treatment of food botulism but the efficacy of the antitoxin has not been demonstrated in any randomised controlled trial

References

• Botulism in an adult associated with food-borne intestinal infection with Clostridium botulinum. N Engl J Med. 1986;315(4):239–41. doi: 10.1056/NEJM198607243150407
• Clinical electrophysiology of infantile botulism. Muscle Nerve. 1983;6(6):448–52. doi: 10.1002/mus.880060609
• Botulism: cause, effects, diagnosis, clinical and laboratory identification, and treatment modalities. Disaster Med Public Health Prep. 2007;1(2):122–34. doi: 10.1097/DMP.0b013e318158c5fd
• Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin. Mov Disord. 2004;19 Suppl 8Suppl 8:S2–6. doi: 10.1002/mds.20003
• Clinical trial of plasma exchange and high-dose intravenous immunoglobulin in myasthenia gravis. Myasthenia Gravis Clinical Study Group. Ann Neurol. 1997;41:789-796. doi: 10.1002/ana.410410615
• One man’s poison: clinical applications of botulinum toxin. N Engl J Med. 1999;341:118–20. doi: 10.1056/NEJM199907083410209
• Pathogenesis of human botulism. Ann N Y Acad Sci. 1998;841:122–39. doi: 10.1111/j.1749-6632.1998.tb10920.x
• Management of botulism. Ann Pharmacother. 2003;37(1):127–31. doi: 10.1345/aph.1C034