20.3 Toxin-Mediated Paralysis & Neuromuscular Crises: Botulism, Tetanus, Tick Paralysis & Myasthenic Crisis

Botulism

Botulinum toxin cleaves the SNARE proteins required for presynaptic acetylcholine release at both the neuromuscular junction and autonomic synapses.

• Forms: foodborne (home-canned foods), wound botulism (injection drug use, particularly black tar heroin), infant botulism (honey, spores), iatrogenic (cosmetic or therapeutic injection), inhalational (bioterrorism), and adult intestinal colonization.
• Classic features:
  • Symmetric, descending paralysis that starts with the cranial nerves: diplopia, ptosis, blurred vision from fixed dilated pupils, dysarthria, dysphagia, and facial weakness.
  • Clear sensorium and no sensory loss.
  • Afebrile, unless there is a wound infection.
  • Autonomic (anticholinergic) features: dry mouth, ileus, urinary retention, and orthostatic hypotension.
  • Progressive respiratory failure from bulbar and diaphragmatic weakness.
• Differential: Guillain-Barré syndrome and its Miller Fisher variant (ascending, with areflexia and albuminocytologic dissociation in the CSF), myasthenia gravis (fatigable, responds to acetylcholinesterase inhibitors), Lambert-Eaton syndrome (incremental response on repetitive stimulation), tick paralysis, organophosphate poisoning, and stroke.
• Confirmation: toxin assay (mouse bioassay) and culture of serum, stool, gastric contents, or wound; electrodiagnostic studies show a low compound muscle action potential amplitude with facilitation after high-frequency repetitive stimulation or exercise.
• Treatment:
  1. Antitoxin immediately on clinical suspicion, because it only neutralizes toxin that is still circulating and cannot reverse paralysis already established. Equine heptavalent antitoxin (types A to G) is used in adults and children, obtained through public health authorities; human-derived botulism immune globulin (BabyBIG) is used for infant botulism. Watch for hypersensitivity to equine product.
  2. Monitor and support ventilation: follow vital capacity and negative inspiratory force; intubate for bulbar failure or falling vital capacity.
  3. Wound botulism: debride the wound and give antibiotics (penicillin or metronidazole). Avoid aminoglycosides and clindamycin, which impair neuromuscular transmission.
  4. Supportive care for weeks to months, because recovery requires regeneration of nerve terminals. Report to public health immediately.
  5. Do not use acetylcholinesterase inhibitors as therapy; they are ineffective.

Tetanus

Tetanospasmin blocks the release of inhibitory glycine and GABA from spinal interneurons, removing inhibition of motor neurons and sympathetic outflow.

• Presentation: trismus (lockjaw) and risus sardonicus, neck and back rigidity progressing to opisthotonus, and generalized spasms triggered by light, noise, or touch in a fully conscious patient. Laryngeal spasm causes sudden asphyxia.
• Autonomic instability emerges in the second week: labile hypertension and tachycardia alternating with bradycardia and hypotension, sweating, and arrhythmias.
• Clinical diagnosis: there is no confirmatory test, and a wound is not always found. Neonatal tetanus follows unsterile cord care.
• Management:
  1. Wound debridement.
  2. Metronidazole (preferred; penicillin is a GABA antagonist and is a second choice).
  3. Human tetanus immune globulin (3,000 to 6,000 units IM, part infiltrated around the wound) to neutralize unbound toxin; intrathecal administration is used in some settings.
  4. Spasm control: high-dose benzodiazepines (diazepam or midazolam infusions) and magnesium sulfate, which reduces spasms and autonomic instability. Intrathecal baclofen is an option.
  5. Neuromuscular blockade and mechanical ventilation for spasms refractory to sedation; secure the airway early, often with tracheostomy, because laryngospasm is lethal and the course lasts weeks.
  6. Autonomic instability: magnesium, labetalol or esmolol (avoid short-acting beta-blockade without alpha coverage in severe cases), morphine, and clonidine or dexmedetomidine.
  7. A dark, quiet environment with clustered care; nutrition support for a very high metabolic rate; thromboprophylaxis.
  8. Immunize: natural infection does not confer immunity, so give the tetanus toxoid series during recovery.

Tick Paralysis

• Mechanism: a salivary neurotoxin from an attached female tick (Dermacentor species in North America; Ixodes holocyclus in Australia, which can worsen after removal).
• Presentation: ascending, symmetric flaccid paralysis with areflexia over days, often with ataxia, in a child or adult with an attached tick (frequently hidden in hair). Sensation and sensorium are preserved; fever is absent.
• Diagnosis: find the tick. Examine the scalp, behind the ears, the axillae, and the groin carefully.
• Treatment: remove the tick; recovery usually begins within hours to days in North American cases. Supportive ventilation is sometimes required. Antitoxin exists for the Australian species. No antibiotic is needed for paralysis itself.

Myasthenic Crisis Versus Cholinergic Crisis

Myasthenic crisis is respiratory failure from myasthenia gravis requiring ventilatory support.

• Triggers: infection, surgery, aspiration, pregnancy, tapering immunosuppression, and drugs: aminoglycosides, macrolides, fluoroquinolones, telithromycin, magnesium, beta-blockers, calcium-channel blockers, iodinated contrast, neuromuscular blockers, and immune checkpoint inhibitors.
• Monitoring: forced vital capacity below about 15 to 20 mL/kg, negative inspiratory force weaker than about −20 to −30 cmH2O, bulbar weakness with secretions, and a rising PaCO2 all indicate intubation. Do not wait for hypoxemia.
• Noninvasive ventilation (BiPAP) can avert intubation in selected patients with hypercapnia but not severe bulbar dysfunction and secretions.
• Treatment:
  • Plasma exchange or IVIG; plasma exchange may work faster in crisis, and the two are broadly comparable in trials.
  • Corticosteroids, recognizing a possible transient worsening in the first days.
  • Start or optimize longer-term immunosuppression (azathioprine, mycophenolate, rituximab, complement inhibitors, FcRn antagonists).
  • Hold or reduce acetylcholinesterase inhibitors while intubated, because they increase secretions and offer little benefit during ventilation.
  • Treat the trigger and stop offending drugs.
  • For intubation, use a reduced dose of a nondepolarizing agent (patients are very sensitive) or avoid paralytics; succinylcholine requires higher doses and is generally avoided.
• Cholinergic crisis results from excess acetylcholinesterase inhibitor and causes weakness with muscarinic excess: miosis, salivation, lacrimation, bronchorrhea, diarrhea, bradycardia, and fasciculations. Treat by withholding the inhibitor and giving atropine for secretions. The distinction matters because the treatments are opposite; in modern practice, myasthenic crisis is far more common.
• Thymectomy is beneficial in generalized acetylcholine receptor antibody-positive myasthenia and is arranged after recovery, not during crisis.