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Botulism

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Botulism, Clostridium botulinum, C. botulinum, Botulinum Toxin, Wound Botulism

  • Etiology
  1. Clostridium botulinum
  • Pathophysiology
  • Toxin mediated disease
  1. Botulinum Toxin is heat labile (inactivated at high Temperature)
  2. Botulinum Toxin has 7 different serotypes
    1. Botulinum Toxins A, B and E are pathogenic in humans
  3. Botulinum Toxin is typically cleaved into active heavy chains and light chains
    1. Heavy chains irreversibly bind acetylcholine containing Neurons
    2. Light chains interfere with acetylcholine exocytosis
  4. Botulinum Toxin binds to presynaptic nerve terminal
    1. Neuromuscular terminal
    2. Cholinergic autonomic site
  5. Receptor binding is irreversible
    1. Receptors are replaced however over time
  6. Affects neuromuscular junction only
    1. Prevents presynaptic acetylcholine release
    2. Results in bulbar palsy (CN 9-12), Autonomic Dysfunction and skeletal Muscle Weakness
    3. Does not cause sensory deficit or pain
  7. Botulinum Toxin medical uses (Botox)
    1. Treatment for oculomotor disorders
      1. Strabismus
      2. Blepharospasm
    2. Treatment for Dystonias
      1. Torticollis
      2. Hemifacial spasm
  • Transmission
  1. Not spread from person to person
  2. Aerosol spread as warfare Biological Toxin
    1. Incubation: 1 to 5 days
  3. Wound Infection
    1. Associated with Trauma and IV Drug Abuse (e.g. Heroin use)
    2. Course differs from Foodborne Illness
      1. Longer incubation period: 4 to 14 days
      2. Minimal gastrointestinal symptoms
  4. Foodborne Illness (ingestion of Bacteria or preformed toxin)
    1. Incubation: 12-72 hours (median 24 hours)
    2. 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
    3. Ingested spores (esp. from honey) may also cause Botulism in high risk patients
      1. Spores germinate in Stomach, grow and produce toxin (incubates over weeks)
      2. Infants (See Infant Botulism)
      3. Altered gastrointestinal tract (e.g. Gastric Bypass surgery, Proton Pump Inhibitors)
    4. Improperly preserved canned foods (e.g. tomatoes)
    5. In-ground vegetables (potatoes, onions, Garlic)
      1. Potatoes baked in aluminum foil
    6. Meat products in Europe (Toxin Type B)
    7. Vegetable products in China (Toxin Type A)
    8. Preserved fish (Toxin type E)
      1. Found in Alaska, Japan, Russia, Scandinavia
  • Symptoms
  1. Sudden onset symptoms
    1. Symptoms follow ingestion or exposure by 12-72 hours, or inhalation by 12-80 hours
  2. Descending symmetric paralysis
    1. Early changes: Cranial Nerve palsy occurs first
      1. Diplopia with blurred vision (90%)
      2. Dysphagia (76%)
      3. Dysarthria
      4. Dysphonia (55%)
    2. Later changes
      1. Generalized Weakness (58%)
  3. Anticholinergic Symptoms
    1. Dry Mouth
    2. Decreased tears
    3. Blurred Vision
    4. Dizziness
    5. Urinary Retention
    6. Abdominal Pain or cramping (ileus)
    7. Constipation
  4. Other symptoms
    1. Nausea or Vomiting (56%)
    2. Headache
    3. Fever (Wound Botulism)
  • Signs
  1. Early signs
    1. Bilateral Cranial Nerve 6 (Abducens Nerve) paralysis
    2. Ptosis
    3. Mydriasis with sluggish pupil reaction
    4. Nystagmus
    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, descending and motor (not sensory)
  • Differential Diagnosis
  1. See Floppy Infant
  2. Myasthenia Gravis
  3. Guillain Barre Syndrome
  4. Eaton-Lambert Syndrome
  5. Trichinosis
  6. Cerebrovascular Accident
  7. Electrolyte disturbance
    1. Hypocalcemia
    2. Hypermagnesemia
  8. Tick Paralysis or Tick Toxicosis (ascending paralysis)
  9. Other toxin exposure
    1. Organophosphate Poisoning
    2. Atropine Poisoning
    3. Shellfish Poisoning or puffer fish Poisoning
  • Labs
  1. Precautions
    1. Labs are sent, but typically delayed, and diagnosis and management is started empirically
  2. 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
  3. Test suspected food source for toxin
  4. Classic testing (historical)
    1. Lab mice die after ingesting suspected food source
    2. Illness reversed by type specific antitoxin
  5. Other testing to consider
    1. Lumbar Puncture (evaluate differential diagnosis)
  • Diagnostics
  1. Negative Inspiratory Force
  2. 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
  3. Other testing
    1. Edrophonium Testing
  • Management
  • General
  1. Contact Centers for Disease Control for suspected cases
  2. Supportive care
  3. Ventilator support often required
    1. Follow Vital Capacity on serial Pulmonary Function Testing
  4. Gastric Decontamination if recent ingestion in foodborne Botulism
    1. Consider even in delayed presentation
    2. If no ileus, may give Laxatives and enemas
  5. Surgical Wound Debridement in Wound Botulism
    1. Indicated even in benign appearing wounds
  6. Antibiotic precautions
    1. Antibiotics are only recommended in Wound Botulism
    2. First-Line
      1. Penicillin G 3 million units IV q4 hours
    3. Alternative (if Penicillin allergic)
      1. Metronidazole (Flagyl) 500 mg IV every 8 hours
    4. Avoid Aminoglycosides and Clindamycin
  7. Antitoxin
    1. Indicated in both food-borne and Wound Botulism in adults and children over age 1 year
    2. See below
  8. Other measures
    1. Tetanus Toxoid booster
  • Management
  • Antitoxin (from CDC)
  1. May shorten disease course if used early
  2. Indicated in both food-borne and Wound Botulism in adults and children over age 1 year
  3. Depreciated Heptavalent equine antitoxin (preferred)
    1. Available from CDC and from state department
    2. Covers types A, B, C, D, E, F, G
    3. Reduced risk of Serum Sickness
    4. Effective if given prior to or early in symptoms
  4. Trivalent equine antitoxin (replaced by heptavalent Vaccine)
    1. Risk of Serum Sickness and Anaphylaxis
    2. Skin Test for Horse Serum Sensitivity first
    3. Do not use in Infant Botulism
  • 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
  • Prognosis
  1. Untreated: Mortality 60% from Respiratory Failure
  2. Treated with intensive support: Mortality <7%
  • Resources
  • References
  1. (2019) Sanford Guide, acccessed 6/5/2019
  2. Bartlett in Goldman (2000) Cecil Medicine, p. 1673-4
  3. Schechter in Behrman (2000) Nelson Pediatrics, p. 875-8
  4. Seeyave (2015) Crit Dec Emerg Med 29(5): 13-21
  5. Shearer in Marx (2002) Rosen's Emergency Med, p. 1525
  6. Sun and Tomaszewski (2017) Crit Dec Emerg Med 31(6): 24
  7. Arnon (2001) JAMA 285:1059-70 [PubMed]