Tetrodotoxin (TTX) poisoning is a rare neurotoxic marine poisoning that causes a sensorimotor neuropathy that in severe cases causes respiratory muscle paralysis and potentially death. TTX occurs in many different organisms including the blue-ringed octopus saliva (bites), some xanthid crabs and most commonly in bony fish of the Order Tetraodontiformes, which include puffer fish (Tetraodontidae) in Japan and toad fish in Australia. The majority of cases are reported from the Pacific and coastal parts of Asia, best known in Japan as fugu poisoning.

TTX is a sodium channel blocker that is well described and now used commonly as a pharmacological tool. Blocking sodium channels results in interruption of nerve conduction which clinically manifests as paralysis.

TTX poisoning causes both sensory and motor neurological features, associated wit mild gastrointestinal symptoms such as nausea. The onset of toxicity occurs more rapidly with more severe poisoning, and severe poisoning develops over an hour.. Major clinical features are:
  1. perioral numbness and paresthesia
  2. ataxia due to weakness
  3. distal to proximal muscle weakness (peripheral, bulbar, ocular) and respiratory muscle paralysis
A clinical grading system is provided in the table.

Table 1: Clinical grading system for tetrodotoxin poisoning modified from Fukuda and Tani
Clinical Features
Grade 1
Perioral paresthesiae and numbness, plus or minus gastrointestinal symptoms (mainly nausea)
Grade 2
Numbness of the face, tongue and more distal parts. Early motor paralysis; incoordination, ataxia and slurred speech. Normal reflexes.
Grade 3
Flaccid paralysis, including bulbar, ocular, distal and respiratory muscles causing respiratory failure, aphonia and fixed/dilated pupils. Normal level of consciousness (no central effects).
Grade 4
Respiratory failure and hypoxia. Hypotension, bradycardia and cardiac dysrhythmias. Unconsciousness may occur.

Treatment is supportive care and patients with severe toxicity will require early intervention and mechanical ventilation. The duration may be for up to 5 days. There is no antidote.


1. Isbister GK, Kiernan MC. Neurotoxic marine poisoning. Lancet Neurol. 2005; 4(4): 219-28.

2. Isbister GK, Son J, Wang F, Maclean CJ, Lin CS, Ujma J, Balit CR, Smith B, Milder DG, Kiernan MC. Puffer fish poisoning: a potentially life-threatening condition. Medical Journal of Australia. 2002; 177(11-12): 650-3.

3. Kiernan MC, Isbister GK, Lin CY, Burke D, and Bostock H. Acute Tetrodotoxin induced Neurotoxicity Following Ingestion Of Puffer Fish. Annals of Neurology. 2005.