Statistics from Altmetric.com
Tetrodotoxin intoxication results from ingesting puffer fish or other animals containing the toxin. Clinical presentation is mainly acute motor weakness and respiratory paralysis. Death is common in the worst affected victims. Although the severity of the symptoms generally depends on the amount of toxin ingested, it may be influenced by the victim’s medical condition, as described in this report. The patient was a 52 year old uraemic woman. The uraemia was of undefined aetiology. Over the past 3 years she has received regular haemodialysis. One day both she and her husband, a healthy 55 year old man, ate a fish soup. About 4 hours after the meal she developed a headache and a lingual and circumoral tingling sensation and numbness at the distal parts of all four limbs. She was dizzy and unsteady, had difficulty in swallowing, and became very weak. She was taken to the emergency service and was placed on machine assisted ventilation as respiratory distress and cyanosis developed. Her husband remained asymptomatic throughout this time.
The patient’s condition kept on deteriorating, developing eventually into a comatous-like state with no spontaneous or reflexive eye opening or limb movement within 30 minutes of intubation. On neurological examination, the pupillary light reflex was absent and oculocephalic manoeuvre elicited no ocular movements. All four limbs were areflexic and Babinski’s signs were absent. Brain CT and laboratory studies of arterial blood gas (under assisted ventilation), electrolytes, liver function, blood glucose, and CSF study were unremarkable. An examination of renal function indicated chronic renal insufficiency with mild azotaemia (urea nitrogen 70 mg/dl, creatinine 9.1 mg/dl). An EEG, recorded 18 hours after the onset of symptoms when the neurological condition was unchanged, showed posterior dominant alpha waves intermixing with trains of short duration, diffuse theta waves. When brief noxious stimuli were applied to the sternum, they were replaced transiently by beta activities. The findings suggested that the profound neurological dysfunction might be peripheral in origin. The patient was given a course of haemodialysis according to the set schedule for uraemia at 21 hours after onset of the symptoms. Her condition improved dramatically within an hour. She could open her eyes and she communicated and answered questions correctly by blinking. Pupillary reflex recovered and voluntary eye movements were limited only at the extreme lateral gaze. Muscle power was grade 3 and 4 in the proximal and distal parts of the four limbs. Tendon reflexes were still absent. She was taken off mechanical ventilation the next day. Her clinical condition continued to improve and her symptoms subsided in a stepwise pattern, in response to each course of haemodialysis (figure). When recalling, she could remember certain events such as the recording of the EEG, but was “too weak to move” at that time. She regained her initial strength by the time she was discharged on day 16.
When analysing the remains of the cooked fish (identified asYongeichthys nebulosus), tetrodotoxin was demonstrated by thin layer chromatography, high performance liquid chromatography, and cellulose acetate membrane electrophoresis. Toxicity was assayed by using Institute of Cancer Research strain adult male mice and the toxicity score was 25 mouse units (MU)/g in fish muscle (1 MU=0.178 μg in the ICR strain mouse).1
Tetrodotoxin exerts its effect through binding with and blocking the voltage dependent sodium channel.2 The voltage clamp experiments showed that tetradotoxin diminished the early sodium inward current responsible for the depolarisation of excitatory membrane. The gating properties of the sodium channel, such as the activation and inactivation mechanism, are not altered—that is, the sodium channel is not permanently damaged and its function recovers when the bound toxin is released. In uraemia, ion conductance through the sodium channel is also impaired. Sodium permeability through excitatory membranes is reduced and small inward sodium current and reduced action potential amplitudes are noted in experimental uraemic neuropathy.3By contrast with the effects of tetrodotoxin, uraemia changes the basic property of the sodium channel by an increased inactivation and an impaired activation mechanism. The excitability of peripheral nerves will be more significantly depressed when these two conditions combine. The synergistic effect of uraemia and tetrodotoxin is obvious in this incident in which the patient and her husband ingested roughly an equal amount of tetrodotoxin (about 200 μg, calculated from toxic score times the weight of ingested fish). The amount is about 10% of the estimated lethal dose in humans—2200 μg/60 kg body weight4 (body weights of the patient and her husband were 54.5 and 62 kg respectively)— and caused no clinical evidence of poisoning in the healthy person. It was of interest that the CNS was relatively spared from the toxicity as the EEG showed a posterior dominant, promptly reactive alpha rhythm and the patient retained consciousness when the symptoms were at their most severe.
One of the most striking clinical features in our patient was the response to haemodialysis. Despite the small amount of toxin ingested, the dramatic improvement of her clinical condition was most likely attributed to the rapid elimination of absorbed toxin in the course of haemodialysis, rather than spontaneous recovery. The physical and chemical properties of tetrodotoxin are also supportive to this hypothesis.5 It has a low molecular weight (C11H17N3O8), is water soluble, and is not significantly bound to protein —all these features are often found in toxins amenable to haemodialysis. Traditionally, the management of tetrodotoxin intoxication is mainly supportive, such as gastric lavage to remove unabsorbed toxin and machine assisted ventilation when respiration is severely affected. We suggest that haemodialysis may be an effective method in the treatment of tetrodotoxin intoxication.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.