A 60-year-old man with end-stage renal disease caused by diabetic nephropathy treated with hemodialysis for 14 months was admitted to our hospital reporting neurologic symptoms. The prior evening, he ingested 8 gastropods (whelks) harvested from the sea of northern Japan (Fig 1) that were cooked in their own shells. He went to bed as usual, but awoke 6 hours later with nausea, drowsiness, dyspnea, limb weakness, facial palsy, and diplopia. He could not raise his head or get out of bed. His medications include antiplatelet and anticoagulant agents, isosorbide mononitrate for angina pectoris, and 1α-hydroxyvitamin D3 for secondary hyperparathyroidism. On presentation, he was afebrile with blood pressure of 149/92 mm Hg and pulse rate of 70 beats/min. Barre and Mingazzini signs were positive, and his mouth opened only 15 mm. There was no neck stiffness, muscle atrophy, or involuntary movements, and Babinski reflex was not observed. Deep tendon reflexes were diminished in the lower extremities. Blood work showed the following values: creatine kinase, 116 U/L; C-reactive protein, 0.10 mg/dL (1.0 mg/L); and white blood cell count, 6.2 × 103/μL (6.2 × 109/L). Computed tomography and magnetic resonance imaging of the head showed only chronic small ischemic changes. Although his friends who did not have end-stage renal disease had ingested the same gastropods, they did not experience similar symptoms.
Figure 1. Neptunea arthritica. The gastropod in this photograph was purchased at the same time as the gastropods that the patient ingested.
■ What is the most likely diagnosis?
■ How might the diagnosis be confirmed?
■ What treatment might be initiated?
Discussion
What is the most likely diagnosis?
After ingesting gastropods 16 hours before, tetramine poisoning was suspected. Tetramine (tetramethylammonium ion) is a natural neurotoxin that exists in the salivary gland of gastropods of the family Buccinidae, Neptunea arthritica and Neptunea intersculpta, living in cold temperate seas.1 It is a quaternary ammonium compound that has an acetylcholine-like structure that stimulates both nicotinic and muscarinic receptors.2 Tetramine poisoning occurs by consumption of these gastropods without removal of the salivary gland. A variety of symptoms, such as headache, dizziness, seasickness, visual impairment, and, in severe cases, motor paralysis and respiratory arrest, are observed. Symptoms of tetramine poisoning typically appear within 30 minutes of gastropod ingestion. However, in this case, symptoms of poisoning were not observed until 12 hours after gastropod ingestion (Fig 2). Tetramine absorption may have been delayed because of diabetic gastroparesis, resulting in the increased time between ingestion and the appearance of toxicity.
Figure 2. Plasma tetramine concentration and clinical course of the patient.
How might the diagnosis be confirmed?
Although measurement of plasma tetramine has not been reported previously, we applied the method of Kawashima et al3 for determining tetramine concentration in gastropod tissues. When the patient arrived at the hospital, plasma tetramine concentration was 2.16 μg/mL. Measurement of plasma tetramine is feasible and useful for the diagnosis of tetramine poisoning.
What treatment might be initiated?
Without definitively identifying the toxic agent on presentation, hemoperfusion using an activated charcoal column was performed, followed by hemodialysis (Fig 2). After hemoperfusion, dysarthria improved and the patient was able to maintain a sitting position. After hemodialysis, he was able to stand without assistance.
There is no specific therapy for tetramine poisoning. In a healthy individual, tetramine is excreted rapidly in urine and symptoms commonly disappear within a few hours.2 Excretion of tetramine may be delayed, and symptoms of tetramine poisoning sometimes may be serious and prolonged in patients with decreased kidney function because more than 95% of this poison is excreted through the kidney.4 Kidney failure in our patient resulted in severe limb weakness and diplopia for 8 hours until hemoperfusion was started. Intensive hemodialysis may promote rapid improvement of tetramine poisoning symptoms.
When the patient arrived at the hospital, plasma tetramine concentration was 2.16 μg/mL. After direct hemoperfusion and hemodialysis, plasma tetramine concentration had decreased to 1.11 µg/mL and 0.38 μg/mL, respectively. Tetramethylammonium ion has a molecular weight of 74 Da and thus low plasma protein binding,5 indicating that plasma tetramine could be removed sufficiently by means of hemodialysis. In anuric patients, emergent hemodialysis may be essential.
Final Diagnosis
Tetramine poisoning.
Acknowledgements
The authors thank Yusuke Mashima, MD, Masato Hoshikawa, MD, Hitoshi Sato, MD, Kazunobu Ichikawa, MD, and Ami Ikeda, MD, as colleagues of clinical practice.
References
1. 1Koyama K, Yamashita M, Katou I, Takaiwa K, Naito H, Hashimoto K. Case report of Neptunea poisoning. [Japanese]Jpn J Acute Med. 1986;10:371–375.
2. 2Anthoni U, Bohlin L, Larsen C, et al.Tetramine: Occurrence in marine organisms and pharmacology. Toxicon. 1989;27:707–716. MEDLINE |
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3. 3Kawashima Y, Nagashima Y, Shiomi K. Determination of tetramine in marine gastropods by liquid chromatography/electrospray ionization-mass spectrometry. Toxicon. 2004;44:185–191. MEDLINE |
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4. 4Neef C, Oosting R, Meijer DK. Structure-pharmacokinetics relationship of quaternary ammonium compounds (Elimination and distribution characteristics). Naunyn Schmiedebergs Arch Pharmacol. 1984;328:103–110. MEDLINE |
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5. 5Neef C, Meijer DK. Structure-pharmacokinetics relationship of quaternary ammonium compounds (Correlation of physicochemical and pharmacokinetic parameters). Naunyn Schmiedebergs Arch Pharmacol. 1984;328:111–118. MEDLINE |
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Case provided and authored bySatoshi Takasaki, MD,1 Tsuneo Konta, MD,1 Kazuo Shiomi, PhD,2 and Isao Kubota, MD,11Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata; and 2Department of Food Science and Technology, Tokyo University of Marine Science and Technology, Tokyo, Japan.
Address correspondence to Satoshi Takasaki, MD, Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.stakasak@med.id.yamagata-u.ac.jp
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