Makindo Medical Notes

Botulinum toxins, which are among the most toxic substances known, can be lethal in doses as low as 0.001 µg/kg. These toxins block the release of acetylcholine from presynaptic nerve terminals, resulting in generalized flaccid paralysis with autonomic dysfunction.

About

• Botulism is caused by exposure to one of eight related neurotoxins (A to H).
• An infectious disease that leads to weakness and paralysis due to impaired acetylcholine (Ach) release at the neuromuscular junction.
• Affects both smooth and skeletal muscles.

Aetiology

• Caused by exotoxins produced by the anaerobic, gram-positive, spore-forming bacterium Clostridium botulinum.
• The organism is commonly found in environmental sources such as soil.
• The toxin binds irreversibly to presynaptic nerve terminals.
• Once internalized, it prevents acetylcholine release by cleaving proteins involved in neuroexocytosis.

Methods of Contracting Botulism

• Ingestion of poorly preserved or improperly canned food contaminated with the toxin.
• Infant botulism: Ingestion of honey containing spores, which germinate and colonize the infant's gut due to the absence of normal flora.
• Wound botulism: Spores from the environment enter wounds, germinate under anaerobic conditions, and release toxins (common in IV drug users with infected abscesses).
• Adult botulism: Seen in individuals with gastrointestinal surgery or abnormalities that predispose them to infection.

Clinical Features

• Rapid onset of weakness, typically 2-36 hours after toxin ingestion.
• Weakness progresses from top to bottom, starting with cranial nerves and moving to respiratory muscles and limbs.
• Bulbar symptoms include diplopia (cranial nerves III, IV, VI), dysarthria, and dysphagia.
• Autonomic involvement: Symptoms such as hypotension, nausea, diarrhoea, constipation, and dilated pupils.
• In pediatric cases, presents as "floppy baby syndrome" with constipation and generalized weakness.

Differential Diagnosis

• Myasthenia Gravis (pupils unaffected in MG).
• Guillain-Barré syndrome (consider if sensory loss is present).
• Lambert-Eaton Myasthenic Syndrome (LEMS), Diphtheria, Miller-Fisher syndrome, Shellfish poisoning.
• Organophosphate poisoning.

Investigations

• Perform basic labs: FBC, U&E, arterial blood gases, and toxicology screening.
• Detect botulinum toxin in stool, blood, or food samples.
• Nerve conduction studies: Show reduced amplitude and increased response amplitude with repeated stimulation.

Management

• Administer Botulinum Antitoxin immediately—this can reduce mortality from 46% to 10% if given promptly.
• Intubation and mechanical ventilation may be required for respiratory muscle paralysis.
• Provide supportive intensive care, including gastric lavage if contaminated food was recently ingested.
• Enemas can be administered to clear the bowel of toxins but avoid magnesium-based ones as they can enhance toxin effects.
• Administer appropriate antibiotics for wound botulism or secondary infections.

Prognosis

• Worse prognosis is associated with Type A toxin, which causes more severe illness and higher mortality.
• Recovery can take months, as new presynaptic endplates and neuromuscular junctions must regenerate.
• Most patients eventually achieve complete recovery.