Tetrodotoxin (TTX) poisoning is an uncommon yet severe condition characterized by symptoms such as paresthesia, motor paralysis, and autonomic dysfunction. Although movement disorders are rare in TTX poisoning, a family cluster experienced opsoclonus‐myoclonus after consuming fish fillets with detectable low‐level of TTX in one blood sample. This possibly suggests the wider range of manifestations of TTX poisoning.
Three family members, a 39‐year‐old mother (Patient 1) and her 8‐year‐old (Patient 2) and 6‐year‐old daughters (Patient3), were admitted to the ICU with generalized jerking and altered consciousness after consuming fish fillets labeled as “red tilapia” in a hot‐pot meal. They consumed approximately 200–300 g, 100 g and 20–30 g of fish, respectively. Three hours post‐meal, both daughters, exhibited nausea, vomiting and limb jerking. Approximately an hour later, Patient 1 experienced vomiting, dizziness and limb paresthesia, followed by limb jerking. Hypersalivation and high blood pressure of 170/106 mmHg were noted in Patient 1 upon reaching the primary hospital but were absent in the others. Their conditions progressed to stuporous‐comatose states, with abnormal saccadic eye movements consistent with opsoclonus and cortico‐subcortical myoclonus (Video 1). All were intubated and given intravenous midazolam (0.1 mg/kg/h for Patient 2 and 3, and 0.3 mg/kg/h for Patient 1) to control myoclonus before referred to our hospital.
Video 1.
Segment 1. Patient 1 with chaotic, multidirectional saccadic oscillations of eyes consistent with opsoclonus and generalized myoclonic jerks primarily involved distal extremities. Segment 2. Patient 2 with generalized myoclonus affecting the face, trunk, and proximal and distal extremities. Segment 3. Patient 3 with opsoclonus and generalized myoclonus affecting the face, trunk, and proximal and distal extremities.
Initial investigations showed unremarkable metabolic parameters. While Patient 2 and 3 recovered within 24 h, Patient 1, still unconscious, underwent further tests revealing nonspecific white matter changes in brain MRI, normal cerebrospinal fluid, and continuous generalized delta activity in EEG. Opsoclonus‐myoclonus in Patient 1 was controlled within 72 h with additional intravenous levetiracetam (2000 mg/day) and sodium valproate (1200 mg/day), allowing uneventful extubation. Toxin screening on day 4, including TTX, acetylcholinesterase, and strychnine, detected low‐level TTX in Patient 1 (less than 0.5 ppb by LC–MS), but was negative in the daughters. Upon regaining consciousness, none exhibited motor or sensory deficit.
TTX is a potent sodium channel blocker (VGSC) found in certain pufferfish species primarily in the skin, liver, and reproductive organs. It is water‐soluble and heat‐stable, making it resistant to cooking. 1 , 2 Despite regulations banning pufferfish importation, trading, and consumption, accidental consumption still occurs due to its lower market price. Although red tilapia and pufferfish look different, they share a similar firm white flesh (Fig. S1).
Movement disorders associated with TTX poisoning are infrequent and often accompanied by other neurological manifestations. Literatures reported cases of ataxia and a single case of myoclonus in severe presentation (Table 1). The impaired consciousness and opsoclonus‐myoclonus in our cases likely result from TTX's effect on VGSCs, which are widely distributed in the PNS and CNS including the cerebral cortex, deep brain nuclei, cerebellum and brainstem. 2 , 5
TABLE 1.
| Authors | Country | Source of toxin | Number of patients | Onset (min) | Associated abnormal movements | Other neurological features | Treatment | Outcomes |
|---|---|---|---|---|---|---|---|---|
| Isbister et al | Australia | Pufferfish (Tetractenos hamilton) | 8 |
30–90 |
Gait ataxia | Perioral and extremity paresthesia, dizziness, limb weakness, dysarthria, ophthalmoplegia | NA | Mild weakness and ataxia of the lower limbs remained for a week |
| Al‐Sulaimani et al | Lebanon | Pufferfish (Lagocephalus sceleratus) | 1 | 60 (360 for ataxia) | Ataxia | Generalized body numbness, dizziness | Activated charcoal, systemic hydrocortisone and antihistamine | Residual dizziness improved over the next few days |
| Al Dhuhaibat et al | United Arab Emirates | Pufferfish (Lagocephalus sceleratus) | 1 | After meal for tongue numbness (120 for ataxia) | Ataxia | Perioral and hand numbness, central body and tongue weakness, absent DTR | Supportive care and physiotherapy | Mild Dizziness for two weeks |
| Puech et al | Reunion Island | Pufferfish (Lagocephalus sceleratus) | 3 | 120 | Ataxia (2 cases) |
Perioral and extremity paresthesia, vertigo Dysarthria, motor deficit, nonreactive mydriasis, absent DTR |
None | No neurologic sequelae |
| 120 | Myoclonus (1 case) | Intubation and mechanical ventilation, IV norepinephrine and IV atropine | No neurologic sequelae | |||||
| Wan et al | Hong Kong | Pufferfish | 1 | 150 | Truncal ataxia | Perioral and extremity paresthesia, motor deficit, dizziness | NA | Mild truncal ataxia |
Abbreviations: NA, not applicable; TTX, level was not available.
The presence of TTX in Patient 1's serum, albeit at low‐level, suggests TTX poisoning as the likely cause. However, delayed specimen collection due to unavailability of laboratory tests in our medical facility, limited the accuracy in reflecting the clinical severity, as earlier sampling might have revealed elevated TTX levels, given the pronounced symptoms indicative of cerebral and brainstem involvement in our cases. Despite TTX's serum half‐life of around 12 h, 6 it was detectable on day four in Patient 1, possibly due to the larger quantity of fish she consumed. Other toxic agents, including acetylcholinesterase inhibitors and strychnine, were excluded by serology tests and the unlikely exposure history (Table S1).
Author Roles
(1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique.
O.U.: 3A
S.B.: 3A
R.B.: 3B
J.S.: 3B
Disclosures
Ethical Compliance Statement: The authors confirm that the ethics board clearance was not required for this work. The subject has provided written video consent. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.
Funding Sources and Conflicts of Interest: No specific funding was received for this work, and the authors declare no conflicts of interest relevant to this work.
Financial Disclosures for the Previous 12 Months: Author RB has received a salary from Chulalongkorn University and a stipend from the Royal Society of Thailand; he has also received consultancy and/or honoraria/lecture fees from Abbott, Boehringer Ingelheim, Britannia, Ipsen, Novartis, Teva‐Lundbeck, Takeda, and Otsuka pharmaceuticals. He has received research funding from the Thailand Science and Research Innovation Bureau, Thailand Research Fund, Crown Property Bureau, Chulalongkorn University, and the National Science and Technology Development Agency. He holds patents for laser‐guided walking stick, portable tremor device, nocturnal monitoring, and electronic Parkinson's disease symptom diary, as well as copyright on Parkinson's mascot, dopamine lyrics, and teaching video clips for common nocturnal and gastrointestinal symptoms for Parkinson's disease. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Supporting information
Supplementary Figure S1. Comparison of the body and flesh of pufferfish and red tilapia.
(A) Pufferfish have a dark gray‐brownish coloration with irregular black spots on their back, and their belly is covered in tiny spines. They have a unique ability to inflate themselves into balloon‐like shapes when they feel threatened. (B) On the other hand, red tilapia has a flat body, relatively small head, with distinctive reddish‐pink scales. (C) Slices of pufferfish flesh, with large, white, firm muscles. (D) Slices of red tilapia flesh with smaller white muscles and a pinkish tint in areas near the skin.
Supplementary Table S1. Summary of distinguishing features of tetrodotoxin, acetylcholinesterase inhibitors and strychnine poisoning.
References
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Associated Data
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Supplementary Materials
Supplementary Figure S1. Comparison of the body and flesh of pufferfish and red tilapia.
(A) Pufferfish have a dark gray‐brownish coloration with irregular black spots on their back, and their belly is covered in tiny spines. They have a unique ability to inflate themselves into balloon‐like shapes when they feel threatened. (B) On the other hand, red tilapia has a flat body, relatively small head, with distinctive reddish‐pink scales. (C) Slices of pufferfish flesh, with large, white, firm muscles. (D) Slices of red tilapia flesh with smaller white muscles and a pinkish tint in areas near the skin.
Supplementary Table S1. Summary of distinguishing features of tetrodotoxin, acetylcholinesterase inhibitors and strychnine poisoning.