Acute tetrodotoxin‐induced neurotoxicity after ingestion of puffer fish

Abstract

This study documents the effects of puffer-fish poisoning on peripheral nerve. Excitability measurements investigated membrane properties of sensory and motor axons in four patients. The median nerve was stimulated at the wrist, with compound muscle potentials recorded from abductor pollicis brevis and compound sensory potentials from digit 2. Stimulus-responses, strength-duration time constant (tau(SD)), threshold electrotonus, and current-threshold relations were recorded. The urine of each patient tested positive for tetrodotoxin. Compared with controls, axons were of higher threshold, compound muscle action potentials and compound sensory nerve action potentials were reduced in amplitude, latency was prolonged, and tau(SD) was reduced. In recovery cycles, refractoriness, superexcitability, and late subexcitability were decreased. Threshold electrotonus of motor axons exhibited distinctive abnormalities with less threshold decline than normal on depolarization and greater threshold increase on hyperpolarization (p < 0.0005 for each patient). The changes in excitability were reproduced in a mathematical model by reducing sodium (Na(+)) permeabilities by a factor of two. This study confirms that the neurotoxic effects of puffer-fish poisoning can be explained by tetrodotoxin blockade of Na(+) channels. It demonstrates the ability of noninvasive nerve excitability studies to detect Na(+) channel blockade in vivo and also the utility of mathematical modeling to aid interpretation of altered excitability properties in disease.

Oxaliplatin and Axonal Na+ Channel Function In vivo

“…Axonal excitability in human subjects is assessed using ''threshold tracking,'' where threshold indicates the stimulus current required to produce a target potential, which can be adjusted online by computer (i.e., tracked) to assess excitability. Excitability studies have shown alterations in axonal Na + channel function in toxic and metabolic neuropathies (15,16) and in patients with genetic mutations in Na + channels (17). Such information cannot be gained using standard nerve conduction studies, which provide information about the number of conducting fibers (amplitude) and the speed of the fastest conducting fibers (latency and conduction velocity).…”

A Case of Severe Puffer Fish Poisoning: Serum Tetrodotoxin Concentration Measurements for 4 Days after Ingestion

“…TTX blocks Na+ conductance by binding extracellularly at receptor site 1 of Na+ channels. Therefore, Na+ influx is prevented, action potentials do not occur, and nerve excitability is suppressed [9]. However, the fish themselves do not exhibit TTX toxicity because there is no TTX-binding site in the Na+ channels of puffer fish.…”

Sensory and motor axons are different: implications for neurological disease

“…Similarly the Na + current can be decreased by blocking the channels with, e.g., tetrodotoxin, as occurs in puffer fish poisoning. 26 Conduction of impulse trains results in hyperpolarisation of the active axons, and this is greater in motor axons than sensory. In the presence of a severely impaired safety margin some axons may become incapable of conducting further impulses.…”