Botulism

1. See Also
   1. Infant Botulism
   2. Biological Neurotoxin
2. Etiology
   1. Clostridium botulinum
3. Pathophysiology: Toxin mediated disease
   1. Botulinum toxins A, B and E are pathogenic in humans
   2. Botulinum toxin binds to presynaptic nerve terminal
      1. Neuromuscular terminal
      2. Cholinergic autonomic site
   3. Receptor binding is irreversible
      1. Receptors are replaced however over time
   4. Affects neuromuscular junction only
      1. Prevents presynaptic acetylcholine release
      2. Results in bulbar palsy and skeletal Muscle Weakness
      3. Does not cause sensory deficit or pain
   5. Botulinum toxin medical uses (Botox)
      1. Treatment for oculomotor disorders
         1. Strabismus
         2. Blepharospasm
      2. Treatment for Dystonias
         1. Torticollis
         2. Hemifacial spasm
4. Transmission
   1. Aerosol spread as warfare Biological Toxin
   2. Wound infection
      1. Associated with trauma and heroin use
      2. Course differs from Foodborne Illness
         1. Longer incubation period: 4 to 14 days
         2. Minimal gastrointestinal symptoms
   3. Foodborne Illness (ingestion of bacteria or toxin)
      1. Toxin types A and B in the United States
         1. West of the Mississippi: Type A toxins
         2. East of the Mississippi: Type B toxins
      2. See Infant Botulism (e.g. honey ingestion)
      3. Improperly preserved canned foods (e.g. tomatoes)
      4. In-ground vegetables (potatoes, onions, Garlic)
      5. Meat products in Europe (Toxin Type B)
      6. Vegetable products in China (Toxin Type A)
      7. Preserved fish (Toxin type E)
         1. Found in Alaska, Japan, Russia, Scandinavia
5. Symptoms
   1. Sudden onset symptoms
      1. Symptoms follow ingestion or exposure by 1-5 days
   2. Descending symmetric paralysis
      1. Early changes: Cranial Nerves affected first
         1. Diplopia with blurred vision (90%)
         2. Dysphagia (76%)
         3. Dysarthria
         4. Dysphonia (55%)
      2. Later changes
         1. Generalized Weakness (58%)
   3. Associated symptoms
      1. Nausea or Vomiting (56%)
      2. Dizziness
      3. Headache
      4. Abdominal Pain or cramping
      5. Diarrhea or Constipation
      6. Anticholingergic symptoms may also be present
6. Signs
   1. Early signs
      1. Bilateral Cranial Nerve 6 (Abducens Nerve) paralysis
      2. Mydriasis with sluggish pupil reaction
      3. Nystagmus
      4. Ptosis
      5. Diminished Gag Reflex
      6. Swollen Tongue
   2. Later signs
      1. Symmetrical descending flaccid paralysis
      2. Hyporeflexia
      3. Incoordination
      4. Irregular respirations to respiratory failure
   3. Distinguishing features from other causes
      1. Mentation clear
      2. Patient is usually afebrile
      3. Neurologic changes are bilateral and descending
7. Differential Diagnosis
   1. Myasthenia Gravis
   2. Guillain Barre Syndrome
   3. Eaton-Lambert Syndrome
   4. Trichinosis
   5. Cerebrovascular Accident
   6. Electrolyte disturbance
      1. Hypocalcemia
      2. Hypermagnesemia
   7. Tick Paralysis or Tick Toxicosis (ascending paralysis)
   8. Other toxin exposure
      1. Organophosphate Poisoning
      2. AtropinePoisoning
      3. Shellfish Poisoning or puffer fish Poisoning
8. Labs
   1. Patient sources
      1. Serum for Botulinum toxin (positive in 1/3 of cases)
      2. Gastric contents for Botulinum toxin
      3. Stool for Botulinum toxin (positive in 1/3 of cases)
      4. Stool for culture (positive in 60% of cases)
      5. Wound culture (if present) for organisms
   2. Test suspected food source for toxin
   3. Classic testing
      1. Lab mice die after ingesting suspected food source
      2. Illness reversed by type specific antitoxin
9. Diagnostic testing: Electromyogram (EMG)
   1. Protocol
      1. Initial supramaximal single nerve stimulation
      2. Repetitive stimulation at 40 to 50 hz
   2. Differentiates from other neuromuscular conditions
      1. Single maximal stimulus: Diminished action potentials
      2. Repetitive stimuli: Facilitation of action potentials
      3. Hypermagnesemia may give similar EMG
10. Management: General
    1. Contact Centers for Disease Control for suspected cases
    2. Supportive care
    3. Ventilator support often required
    4. Antibiotic use only recommended in wound Botulism
    5. Gastric Decontamination if very recent ingestion
11. Management: Antitoxin (from CDC)
    1. Skin Test for Horse Serum Sensitivity first
    2. May shorten disease course if used early
    3. Trivalent equine antitoxin
       1. Risk of Serum Sickness and Anaphylaxis
    4. Depreciated Heptavalent equine antitoxin
       1. Covers types A, B, C, D, E, F, G
       2. Reduced risk of Serum Sickness
       3. Effective if given prior to or early in symptoms
12. Prevention
    1. Avoid honey in infants under 1 year of age
       1. See Infant Botulism
    2. DOD Pentavalent toxoid vaccine
       1. Covers types A, B, C, D, E
       2. Dose: 0.5 SC at 0, 2, and 12 weeks, then annually
       3. Protective Antibody >90% after 1 year
13. Prognosis
    1. Untreated: Mortality 60% from respiratory failure
    2. Treated with intensive support: Mortality <7%
14. References
    1. Bartlett in Goldman (2000) Cecil Medicine, p. 1673-4
    2. Schechter in Behrman (2000) Nelson Pediatrics, p. 875-8
    3. Shearer in Marx (2002) Rosen's Emergency Med, p. 1525
    4. Arnon (2001) JAMA 285:1059-70
15. Resources
    1. CDC Disease Information
       1. http://www.cdc.gov/ncidod/dbmd/diseaseinfo