• View in gallery
    Figure 1.

    Location of Taiwan, Pratas Island, and the South China Sea. The patients caught the gastropods 5–10 nautical miles southeast of Pratas Island and similar mollusks 50–80 nautical miles south of the island two days before.

  • View in gallery
    Figure 2.

    The gastropod Nassisarus glans.

  • View in gallery
    Figure 3.

    Gas chromatography–mass spectroscopy of A, tetrodotoxin; B, urine of case 4; and C, blood of case 4.

  • View in gallery
    Figure 4.

    Time, location, and species of gastropods in five cases of tetrodotoxication in Taiwan since 1990.

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TETRODOTOXICATION WITH NASSAURIS GLANS: A POSSIBILITY OF TETRODOTOXIN SPREADING IN MARINE PRODUCTS NEAR PRATAS ISLAND

HSIN L. YINInstitute of Forensic Medicine, Ministry of Justice, Taipei, Taiwan, Republic of China; Department of Neurology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan, Republic of China

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HUNG S. LINInstitute of Forensic Medicine, Ministry of Justice, Taipei, Taiwan, Republic of China; Department of Neurology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan, Republic of China

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CHIH C. HUANGInstitute of Forensic Medicine, Ministry of Justice, Taipei, Taiwan, Republic of China; Department of Neurology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan, Republic of China

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DENG F. HWANGInstitute of Forensic Medicine, Ministry of Justice, Taipei, Taiwan, Republic of China; Department of Neurology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan, Republic of China

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JIA S. LIUInstitute of Forensic Medicine, Ministry of Justice, Taipei, Taiwan, Republic of China; Department of Neurology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan, Republic of China

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WEI H. CHENInstitute of Forensic Medicine, Ministry of Justice, Taipei, Taiwan, Republic of China; Department of Neurology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan, Republic of China

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Tetrodotoxication was observed in six patients who ate gastropods from the South China Sea near Pratas Island. The pathogenic gastropod was Nassauris glans, which had not been previously mentioned in human tetrodotoxication. An extremely high level of tetrodotoxin was found in the causative gastropods, and a variety of clinical signs were observed in the survivors. The postmortem autopsy of two patients showed severe distension and hypersecretion of the alimentary tract, suggestive of a cholinergic crisis as the cause of their early death. A recognition of education regarding the risk of tetrodotoxication by N. glans in the study area is important to prevent further tragedy. A retrospective review of the tetrodotoxication in this region may aid in understanding the changes and route of tetrodotoxication in marine products, and provide valuable information for preventive measures.

INTRODUCTION

Common marine toxins include ciguatoxin, domoic acid, histidine, and saxitoxin. Tetrodotoxin (TTX; C11H17N3O8, molecular weight = 319.3) is a marine neurotoxin abundant in the order Tetraodontidae and is found in ocean sunfishes, porcupine fishes, and fugu, which are among the most poisonous of all marine life. These species inhabit the shallow waters of the temperate and tropical zones. The incidence of tetrodotoxication has decreased in recent decades,1 but intoxication still occurs in 100 to 200 persons annually and is distributed mainly in Asia, especially Japan, Taiwan, and the southeast coast of China. Although tetrodotoxication is usually caused by eating of puffer fish, accidental intake from other marine products has become an important source of poisoning recent years because TTX is also found in a variety of seafood such as blue-ringed octopus, crabs, and gastropods. Clinically, tetrodotoxication disturbs the sensory, autonomic and neuromuscular functions, and results in respiratory failure and death.14 We report six patients with tetrodotoxication due to an unusual source, the gastropod Nassisarus glans. The recognition of tetrodotoxication from seafood other than puffer fish should be emphasized. Our observation of the patients’ clinical and neurologic complications in relation to the gastropod and blood levels of TTX level is also reported.

MATERIALS AND METHODS

On the evening of April 12, 2004, perioral numbness, acroparesthesia, dizziness, breathing difficulty, and chest tightness developed within 15 minutes to two hours in six sailors who had eaten cooked gastropods from the South China Sea 5–10 nautical miles southeast of Pratas Island (Dungsha Tao, Tung Sha Island) (Figure 1). Unfortunately, two of the sailors rapidly became unconscious and died within two hours. The other four sailors were taken to the emergency service of Chang Gung Memorial Hospital (Kaohsiung, Taiwan) by the coast guard 10 hours after eating the gastropods. The gastropod was identified as N. glans (Figure 2). The length of each specimen was 3–4 cm and the weight was 5–10 grams. The survivors claimed that they had also eaten N. glans caught approximately 50–80 nautical miles south of Pratas Island two days before, but no one showed any discomfort.

Clinical description.

Case 1.

A 44-year-old man experienced acute numbness of the mouth, lips, fingers, and toes after eating gastropods. Dimmed vision, muscle weakness, fatigue, headache, dizziness, and nausea/vomiting were also present. Progressive acronumbness began before his arrival at the hospital. Hypesthesia of the acral limbs and a fluctuation of the heart rate were found on admission. The symptoms subsided within three days.

Case 2.

A 35-year-old man experienced acute numbness of the mouth, lips, fingers, and toes after eating gastropods. Dimmed vision, muscle weakness, fatigue, headache, and nausea/vomiting were also present. Progressive acronumbness occurred before his arrival at the hospital. Hypesthesia of the acral limbs was found on admission. His symptoms subsided within 24 hours.

Case 3.

A 34-year-old man experienced acute numbness of the mouth, lips, fingers, and toes after eating gastropods. Dimmed vision, muscle weakness, throat tightness, fatigue, dizziness, and nausea/vomiting were also present. Progressive acronumbness, slurred speech, and breathing difficulty occurred before hospital arrival. Hypesthesia of the acral limbs, dysarthria and a fluctuation of the heart rate were found on admission. His symptoms subsided within five days.

Case 4.

A 22-year-old man experienced acute numbness of the mouth, lips, fingers, and toes after eating gastropods. Dimmed vision, muscle weakness, throat tightness, fatigue, headache, dizziness, and nausea/vomiting were also present. Progressive acronumbness, slurred speech, four-limb weakness, and breathing difficulty began before his arrival at the hospital. Hypesthesia of the acral limbs, dysarthria, tetraparaesis with hyporeflexia, and a fluctuation of the heart rate were found on admission. The symptoms subsided within five days.

Case 5.

A 40-year-old man experienced acute numbness of the mouth, lips, fingers, and toes after eating gastropods. Dimmed vision, muscle weakness, fatigue, headache, dizziness, and nausea/vomiting were also present. Progressive acronumbness, breathing difficulty, and chest tightness occurred within half an hour. He died on the way to the hospital two hours after onset.

Case 6.

A 24-year-old man experienced acute numbness of the mouth, lips, fingers, and toes after eating gastropods. Dimmed vision, muscle weakness, fatigue, headache, dizziness, and nausea/vomiting were also present. Progressive acronumbness, four-limbs weakness, slurred speech, and breathing difficulty occurred within half an hour. He died on the way to the hospital two hours after onset.

Analysis of TTX.

The toxicity of TTX in N. glans was measured in a mouse assay model and expressed as mouse unit (MU)/g. Tetrodotoxin was extracted according to previous reports.5,6 Briefly, edible parts of the gastropods were dissected. The dissected tissue was weighed, homogenized with 10 volumes of 1% acetic acid in methanol for 5 minutes, and centrifuged twice at 2,000 × g for 20 minutes. The supernatants were combined, concentrated under reduced pressure, and examined for toxicity using the mouse assay for TTX.6 The TTX level was examined in the blood and urine of cases 1–4. No blood or urine specimen was obtained from cases 5 and 6 who died on the way to the emergency service. The TTX in the urine and blood samples was qualitatively analyzed by a gas chromatography–mass spectroscopy method previously described.5

Laboratory and electrophysiologic studies.

Biochemical, hematologic, coagulation, cholinesterase, urinalysis, electrocardiographic, nerve conduction velocity, F wave, and H reflex tests were conducted and a chest radiograph was obtained for each patient upon admission. A follow-up study of the abnormal results was repeated within one month after onset.

RESULTS

Concentration of TTX in gastropod and human specimens.

The level of TTX in the causative gastropod ranged from 185 to 1,980 MU/g (mean ± SD = 521 ± 559 MU/g) in the digestive gland, from 483 to 2,764 MU/g (998 ± 498 MU/g) in muscle tissue, and from 1,849 to 10,361 MU/g (5,180 ± 1,832 MU/g) in each gastropod. These concentrations were extremely high compared with previous reports.

Gas chromatography–mass spectrometry showed a positive reaction (parent peak m/z = 4.07; base peak m/z = 392; fragment peak m/z = 376) in urine of all patients and in blood of only cases 3 and 4 (Figure 3). The amount of TTX in urine was higher than that in blood. The relative concentration of TTX in urine was at least two-fold higher in cases 3 and 4 than in cases 1 and 2.

Clinical and neurologic features.

Mild fever was observed in cases 2 and 3. Their blood pressures were normal. However, a fluctuation in the pulse rate (ranging from 45 to 81/minute) was observed in cases 1, 3, and 4. Tachypnea was also seen in all of the patients, but their arterial blood gas did not show carbon dioxide retention, hypoxia, or an acid-base imbalance. Outweighed, symmetric acral numbness was the initial symptom in all patients. This sensory symptom developed first at the lower lip, followed by the upper lip, and fingers (from thumb to the small finger) and toes (from the big toe to the small toe). The patients also complained of weakness, headache, dizziness, and fatigue. A sore throat/throat tightness and nausea/vomiting were also observed in cases 3 and 4 (Table 1).

Subjective sensorum with tingling or a numb sensation was present in all patients. An objective pinprick and cotton fine touch sensory impairment was identified in cases 2, 3, and 4. Dysarthria was observed in cases 3 and 4. Additional mild paraparesis and hyporeflexia in the lower legs in symmetry was observed in case 4. Intermittent sinus bradycardia indicating dysautonomia was detected in cases 1, 3, and 4.

Laboratory data.

Biochemical hematologic, cholinesterase and urinalysis test results were normal, except for mild neutrophilia in cases 1 and 2. Mild thrombocytopenia and a prolonged activated partial thromboplastin time were observed in cases 3 and 4. All chest radiographs were normal. Electrocardiograms showed no conduction disturbances.

Electrophysiologic study.

A nerve conduction velocity test was performed in cases 1–4 after admission. Prolongation of proximal latency, F wave latency (the duration of onset of the second compound muscle action potential in an antidromic stimulation of a motor nerve), and dispersion (the percentage increase in duration of the proximal compound muscle action potential compared with the distal one in a motor nerve; an increase more than 150% was considered abnormal) was identified in all cases. Conversely, the amplitude, conduction velocity, and H reflex were normal. The distal latency of motor nerves was preserved compared with their proximal latency. These results clearly indicated a demyelinating change of the motor nerves. The median nerve was the most frequent one involved, but the damage to the tibial nerve was more severe than that to the other motor nerves. The magnitude of neuronopathy was similar between the upper and lower limbs (Table 2).

Postmortem autopsy.

A postmortem autopsy was conducted in cases 5 and 6. There was no morphologic abnormality in their organs, except for a severe distention and hypersecretion of the stomach. Tissue taken from the brain, lungs, and heart showed only nonspecific postmortem changes. There was no significant cellular infiltration, thrombosis, or large infarct. Toxicologic tests of urine and blood showed no alcohol, benzodiazepine, or illicit drugs.

Clinical course.

Cases 5 and 6 died shortly after ingestion of the gastropods on their way to the emergency service. Cases 1–4 recovered completely within one week, and their abnormal laboratory data and electrophysiological results returned to normal within one month after intoxication.

DISCUSSION

The decrease in tetrodotoxication from puffer fish may be the result of improvements in clinical management and cooking gastropods, recognition of the tetrodotoxic species, and an awareness of the signs of toxicity. Conversely, an increased incidence of intoxication caused by other marine products, such as gastropods, has been observed. Tetrodotoxin has been isolated from a variety of gastropods, and some have caused human tetrodotoxication. In Taiwan, at least 18 species of gastropods contain TTX (Table 3),5,712 and 11 eaten on the west coast of Taiwan near the Bashi Channel (Taiwan Strait) have resulted in five domestic cases of tetrodotoxication in the past 10 years (Figure 4).5,7,8 The location of the six cases of tetrodotoxication in this report are the furthest from Taiwan. Since there is no rapid test for TTX, regular examination of marine products, expeditious reporting of contaminated seafood, and education of fishery personnel and the general population are crucial for preventing this disease.

Some species of the family Nassariidae, such as Niotha clathrata, Zeuxis scalaris, and Zeuxis siquijorensis, but not N. glans, have been reported to cause poisoning in humans. N. glans was firstly described at 1758 by Linnaeus. It is distributed mainly in the Indo-Pacific region and the South China Sea, and may also be found near the Mascarene Islands and Mauritius or in the Red Sea. There has been no report of poisoning in humans or marine animals caused by N. glans. We cannot exclude contamination by tetrodotoxin-secreting bacteria such as Vibrio or Pseudomonas in the South China Sea, where some puffer fish, such as the Amblyrhynchotes rufopunctatus, are found. However, the survivors experienced no toxic effects after eating N. glans in the area on a previous occasion. This suggests regional contamination. Therefore, it is necessary to alert and educate sailors, fishermen, and inhabitants of the area of the possibility of tetrodotoxication with N. glans near Pratas Island.

Tetrodotoxication is generally divided into four stages based on the clinical symptoms.13 These are mild acronumbness of the lips, fingers, and tongue; exacerbation of acronumbness and development of muscle weakness; motor paralysis involving the limbs and latter bulbar muscle; and a change of consciousness and respiratory muscle paralysis. However, a precise correlation between the biologic activity of TTX and clinical features is lacking because only a few cases of tetrodotoxication have had blood or urine TTX levels measured. Many patients are diagnosed as having tetrodotoxication based on a dubious contact history of marine products or only clinical signs. The relationship between the TTX level and dysautonomia in different parts of the body has not been established. Coagulopathy, as found in our patients, has also not been reported.

Although there were only four survivors, we observed three groups of clinical symptoms: common and early symptoms, irrespective of the TTX level, including acral numbness, somatic discomforts, and dizziness; cardiovascular dysautonomia that did not correlate with the TTX level; and symptoms correlated with a higher TTX level, including motor function (bulbar symptoms, breathing difficulty, dysarthria, limb weakness), gut dysautonomia (nausea/vomiting), and blood disorders (thrombocytopenia, coagulopathy). Some findings, such as early and common sensory symptoms, and a progressive motor dysfunction developing from the peripheral to the central compartment can be correlated with previous observations. An early sensorum of acral numbness and dizziness may reflect a relatively sensitive or low-threshold voltage-gated sodium channel in the sensory afferent, such as the peripheral sensory fiber and vestibular nerve, which are vulnerable to tetrodotoxic blocking.

Dysautonomia is frequently observed in tetrodotoxication. Although the precise mechanism is not fully understood, TTX can block the TTX-sensitive sodium channel, abolish the response in cardiac nerves, ventricular myocytes and brain arterioles, or terminate release of neurotransmitters in a dose-dependent manner. In a TTX-treated animal model, an involvement of both nicotinic and muscarinic transmission, but not the cholinesterase level simulating an anti-cholinesterase effect, was demonstrated.13,14 The blood cholinesterase levels were normal in our patients. Clinically, dysautonomia associated with tetrodotoxication depends on a counterbalance between parasympathetic and sympathetic changes in both the central and peripheral compartments, as well as any pre-existing disease that involves the sodium channel. Nevertheless, the cholinergic crisis is usually predominant in tetrodotoxication. In our patients, occurrence of cardiac dysautonomia did not correlate with the TTX level, but gut dysautonomia showed a correlation with this level. This difference may be due to a complex counteracting cardiac pacing and dominant parasympathetic control in the gut. A diversity of autonomic neurons may also mediate the variable response during poisoning. The normal pupil sizes and light reflexes on presentation of in our patients may suggest a marker for favorable recovery from tetrodotoxication.

A mild decrease in the platelet count and prolongation of the activated partial thromboplastin time were found in cases 3 and 4. Until now, there has been no report concerning co-agulopathy in tetrodotoxication. Tetrodotoxin does not activate platelets and shows no effect on membrane resting potential, except for inhibition of aggregation induced by thrombin through a suppression of intracellular calcium mobilization.15 Hemodilution or dissemination of intravascular coagulation is not likely because there is no corresponding change in hemostasis. Excessive eating of gastropods was unlikely in our patients. However, TTX enters the liver, dissolves in the cytosol, and disturbs mitochondrion and reticulum formation.16 Tetrodotoxin may therefore inhibit protein synthesis and reduce coagulation factor secretion, especially the short-lived proteins in the intrinsic coagulation pathway.

In conjunction with previous experiences based on a small sample of patients, the nerve conduction velocity study also exhibited a diffuse conduction block of peripheral nerves simulating diffuse demyelination in the survivors.1,1719 Although some investigators reported a correlation between the severity of the conduction block and the blood TTX level or clinical course,1719 we did not observe a similar result in our patients. Tetrodotoxin may block the sodium channel at the node of Ranvier and, therefore, slow the conduction block, simulating demyelinating change. Morphologic and biochemical changes in mitochondrial dysfunction have been observed in the peripheral nerves of animals with tetrodotoxication.20,21 Therefore, we believe that TTX exerts both a channel blockade and neuronal mitochondriopathy to block nerve conduction. A variable degree of conduction block in our patients may reflect a different severity of tetrodotoxication mitochrondriopathy in their peripheral nerves. Rapid recovery of conduction velocity in patients with tetrodotoxication may be due to less severe mitochrondriopathy. If so, treatment targeted at a recovery of the mitochondrial function may yield benefits for the dense neuromuscular complications in patients with tetrodotoxication.

The prognosis of tetrodotoxication depends on the total amount of TTX ingested. In humans, a dose as low as 1–2 mg (5,000–10,000 MU) is fatal. Death occurs in more than half of patients with tetrodotoxication and is usually due to respiratory failure or cardiac arrhythmia. Although there is still no antidote for tetrodotoxication, treatment targeted at reversing the cholinergic crisis, mitochondriopathy, and sodium channel blockade should be investigated. Nevertheless, close observation and monitoring of the vital functions are necessary for patients with tetrodotoxication, even if their TTX levels are low and clinical symptoms are mild.

Table 1

Demography, clinical and neurologic deficits, and laboratory data*

Case 1 Case 2 Case 3 Case 4
* PT = prothrobin time; aPTT = activated partial thromboplastin time.
† Normal laboratory values: leukocyte count = 4,000–10,000/mL; neutrophil ratio = 55–65%; platelet count = 150,000–400,00/mL; hematocrit = 38–45%; cholinesterase = <10,000 U/L.
Arterial blood pressure, mm of Hg 120/70 110/70 116/70 120/80
Radial pulse rate/minute 45–51 60–64 50–68 52–81
Body temperature, °C 36.2 37.6 37.6 36.8
Respiratory rate/minute 19 18 18 20
Clinical features
    Fever Mild Mild
    Numbness of mouth, distal limbs ++ ++ ++ ++
    Sore throat/throat tightness ++ ++
    Weakness + + + +
    Headache + + +
    Dizziness + + + +
    Fatigue + + + +
    Palpitation
    Nausea/vomiting + ++ ++
    Breathing difficulty + +
Neurologic deficits
    Visual acuity decrease
    Papillary change
    Cranial nerves palsy Dysarthria Dysarthria
    Motor weakness, upper limb
    Motor weakness, lower limb +
    Hyporeflexia +
    Fasciculation
    Acral sensorum + + + +
    Cerebellar ataxia
Electrocardiogram Sinus bradycardia Normal Sinus bradycardia Sinus bradycardia
Laboratory data†
    Leukocyte count, cells/mL 11,900 5,600 7,400 4,900
    Neutrophils, % 75 75.1 63.9 63.4
    Platelet count, cells/mL 314,000 185,000 142,000 118,000
    Hematocrit, % 40.8 40.9 40.2 41.8
    PT (patient/control), seconds 11.0/11.0 10.8/11.0 13.1/11.0 11.5/11.0
    aPTT (patient/control), seconds 28.7/28.6 27.3/28.6 35.2/28.6 35.7/28.6
    Cholinesterase, U/L 6,791 5,791 4,454 5,870
Table 2

Results of the nerve conduction velocity studies*

Parameters Case 1 Case 2 Case 3 Case 4
* NS = within reference range; ↑ = data over the maximal limit.
† Includes median, ulnar, and sural nerves.
‡ Tibial nerve.
Distal latency, motor (msec)
    Median nerve NS ↑ 12.5% NS NS
    Ulnar nerve NS NS NS NS
    Peroneal nerve NS ↑ 14–30% NS ↑ 8%
    Tibial nerve NS ↑ 30% NS ↑ 14%
Proximal latency, motor (msec)
    Median nerve ↑ 7–18% ↑ 17–27% ↑ 7% ↑ 14%
    Ulnar nerve NS ↑ 7–12% NS NS
    Peroneal nerve NS ↑ 6–13% NS ↑ 4–9%
    Tibial nerve NS ↑ 28–30% NS ↑ 17%
Distal and proximal latency, sensory (msec)† NS ↑ 15% NS ↑ 20%
Amplitude (uV) NS NS NS NS
Conduction velocity, motor (cm/sec) NS NS NS NS
Conduction velocity, sensory (cm/sec)† NS NS NS NS
Dispersion + + + +
F wave latency
    Upper limb ↑ 10–15% ↑ 2–13.6% ↑ 2–9% ↑ 8–16%
    Lower limb ↑ 11–17% ↑ 7–11% NS ↑ 8–19%
H reflex‡ NS NS NS NS
Table 3

Gastropods in Taiwan that contain tetrodotoxin

Human tetrodotoxication
    Oliva miniacea Oliva mustelina Oliva nirasei
    Nassarius conoidalis Nassarius castus Nassarius clathrata
    Nassarius gruneri Zeuxis sufflatus Zeuxis scalaris
    Poilinices didyma Alectron papillosus
Non-human tetrodotoxication
    Nassarius livescens Natica lineate Natica vitellus
    Zeuxis castus Babylonia formosae Rapana venosa
    Zeuxis siquijorensis
Figure 1.
Figure 1.

Location of Taiwan, Pratas Island, and the South China Sea. The patients caught the gastropods 5–10 nautical miles southeast of Pratas Island and similar mollusks 50–80 nautical miles south of the island two days before.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 73, 5; 10.4269/ajtmh.2005.73.985

Figure 2.
Figure 2.

The gastropod Nassisarus glans.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 73, 5; 10.4269/ajtmh.2005.73.985

Figure 3.
Figure 3.

Gas chromatography–mass spectroscopy of A, tetrodotoxin; B, urine of case 4; and C, blood of case 4.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 73, 5; 10.4269/ajtmh.2005.73.985

Figure 4.
Figure 4.

Time, location, and species of gastropods in five cases of tetrodotoxication in Taiwan since 1990.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 73, 5; 10.4269/ajtmh.2005.73.985

*

Address correspondence to Wei H. Chen, Department of Neurology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China. E-mail: e49130@ms14.hinet.net

Authors’ addresses: Hsin L. Yin, Institute of Forensic Medicine, Ministry of Justice, Taipei, Taiwan, Republic of China. Hung S. Lin, Chih C. Huang, Jia S. Liu, and Wei H. Chen, Department of Neurology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China. Deng F. Hwang, Department of Food Science, National Tai-wan Ocean University, Keelung, Taiwan, Republic of China.

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    Torda TA, Sinclair E, Ulyatt DB, 1973. Puffer fish (tetrodotoxin) poisoning: clinical record and suggested management. Med J Aust 1 :599–602.

    • Search Google Scholar
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