Neurophysiologie Clinique/Clinical Neurophysiology (2013) 43, 299—302

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Acute paralysis after seafood ingestion Paralysie aiguë après ingestion de fruits de mer M. Fernández-Fígares a,∗, V. Fernández a, M.J. Postigo a, P. Feron b a

Servicio de Neurofisiología Clínica, Hospital Regional Universitario Carlos Haya, Avda. Carlos Haya s/n, 29010 Málaga, Espa˜ na b Unidad de Cuidados Intensivos, Hospital Regional Universitario Carlos Haya, Málaga, Espa˜ na Received 18 December 2012; accepted 22 August 2013 Available online 3 September 2013

KEYWORDS General acute paralysis; Tetrodotoxin; Paralytic shellfish poisoning; Poisoning respiratory failure; Nerve inexcitability

MOTS CLÉS Paralysie générale aiguë ; Tétrodotoxine ; Défaillance respiratoire par empoisonnement ; Inexcitabilité nerveuse

Summary The first European case of tetrodotoxin intoxication is reported in a patient who ingested a trumpet shellfish from the Atlantic Ocean in Southern Europe. He suffered general acute paralysis with respiratory failure necessitating ventilation. Early neurophysiologic studies showed complete peripheral nerve inexcitability, with no recordable sensory or motor responses, and normal electroencephalography. Tetrodotoxin was detected in high quantities in the patient’s blood and urine through high performance liquid chromatography-mass spectrometry analysis. Seventy-two hours after admission the patient recovered normal strength, reflexes and sensation. © 2013 Elsevier Masson SAS. All rights reserved. Résumé Le premier cas européen d’intoxication par tétrodotoxine est rapporté chez un patient ayant ingéré un coquillage trompette de l’océan Atlantique, dans le sud de l’Europe. Il a développé une paralysie générale aiguë et une insuffisance des muscles respiratoire justifiant une intubation. Les études neurophysiologiques ont montré une inexcitabilité nerveuse initiale totale, motrice et sensitive, et un électroencéphalogramme normal. La tétrodotoxine du mollusque a été retrouvée en quantités élevées dans le sang et l’urine du patient par une analyse en chromatographie liquide à haute performance couplée à une spectrométrie de masse. L’évolution a été rapidement favorable en 72 heures. © 2013 Elsevier Masson SAS. Tous droits réservés.

Introduction

∗

Corresponding author. E-mail address: mfi[email protected] (M. Fernández-Fígares).

Toxins are substances that are synthesized by living organisms, which are harmful to humans. These can be produced by some bacteria, fungi, vertebrates, or marine microorganisms [11], which usually live in symbiosis with reefs in

0987-7053/$ – see front matter © 2013 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.neucli.2013.08.013

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tropical and subtropical waters. Some micro-algae synthesize a large group of toxins, known as ‘‘paralytic shellfish poisoning’’, which have a chemical structure consisting of a common quinazolinic derivative with different associated ions. The toxin is especially accumulated in the fish skin and gonads and in the mollusk intestine and liver, and its level increases by bioaccumulation throughout the food chain from micro-algae to humans. While toxins do not affect fishes [6], humans can be affected. Tetrodotoxin (TTX) is considered the most lethal toxin originating in the marine environment. Its name comes of the Tetraodontidae family, but it was later found in other fishes and mollusks [15]. We present the case of a man who ingested a contaminated trumpet shellfish captured in the southern coast of Europe with large concentrations of TTX.

After 48 hours, only motor responses could be recorded. These were abnormal with reduced amplitude but a normal morphology of the compound muscle action potentials, prolonged distal latencies, and reduced conduction velocities. No signs of temporal dispersion or conduction block were noted at any stimulation points (Table 2). F-wave latencies were either absent or prolonged (Table 3). Repetitive ulnarnerve stimulation at 3 and 10 Hz gave rise to normal results. There was no spontaneous activity at needle EMG, and motor unit potentials and recruitment were normal. After 4 weeks, sensory nerve action potentials were still absent or of low amplitudes with prolonged distal latencies (Table 2). Motor conduction velocities and other conduction parameters had returned to normal (Table 1). Normal F-wave responses were obtained (Table 3).

Case report

Biochemical studies

The patient was a 49-year-old male, without any previous story or treatments. A few minutes after eating the ventral serving of trumpet shellfish, he started to feel perioral numbness, which then extended towards both arms, followed by abdominal pain, nausea and throwing up. Some minutes later on, he developed palsy. Upon the arrival of the emergency services, he was conscious, with general muscle weakness, absence of brainstem and deep reflexes but normal vital signs. Oro-tracheal intubation and mechanical ventilation were required because of breathing difficulties. Computed tomography and magnetic resonance imaging were normal, both at supra tentorial and brainstem levels. Heart rhythm was normal at 95 beats per minute. Laboratory results, including liver and renal function, blood examination, coagulation and cerebrospinal fluid were normal. He was admitted in the intensive care unit (ICU) where the only administrated sedatives were Midazolam® 10 mg and Succinylcholine® 80 mg for intubation. The patient still presented general muscle weakness. After 24 hours, he started to show minimal motor activity, with a completely normal level of consciousness during the following hours. After 6 hours, he started moving his neck muscles, and the oro-tracheal tube was removed after 24 hours. The patient was discharged from the ICU 72 hours after admission, having recovered normal levels of strength, reflexes and sensation.

The non-ingested part of the shellfish was frozen and a mollusk bioassay was carried out to determine the biotoxins. The results showed 151 and 25,500 ␮g of toxin/100 grams in the mollusk’s meat and digestive glands, respectively; these values are much higher than the upper limit allowed by Spanish legislation (80 ␮g/100 grams). The remaining part of the mollusk and patient’s urine and blood samples were both sent to the department of pharmacology laboratory, Santiago University, Spain, in order to be analyzed in the same conditions. High-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis was carried out. The mass spectrometer was operated in enhanced mass spectrum (EMS) mode to confirm the TTX presence, and in enhanced product ion (EPI) mode to quantify the toxin. A sample of the trumpet shell digestive gland was homogenized and extracted according to the official procedure for PSP [14]. The level of TTX in the trumpet shellfish was 24.85 mg/100 grams of digestive gland and in the patient’s urine and blood samples 285.38 ng/mL and 24.54 ng/mL, respectively. Therefore, the presence of TTX in the mollusk and the patient’s blood and urine was confirmed.

Neurophysiological examinations Neurophysiological studies were performed 24 hours, 48 hours, and 4 weeks after ingestion. Results were compared with previously established normative data. An electroencephalogram was performed after 24 hours, while the patient was intubated, but without any sedatives or muscle relaxants. It was normal, with alpha and beta rhythms and good reactivity. Electroneurography (ENG) of median, ulnar, peroneal, tibial, and facial nerves with surface and needle intramuscular recording electrodes (Sierra II, Cadwell® ) showed profound loss of nerve excitability, without any recordable motor or sensory responses even with supramaximal intensities (100 mA, 1 ms) (Tables 1 and 2). Insertion activity was abolished and no spontaneous or voluntary activity could be detected by needle electromyography (EMG).

Discussion All cases of TTX intoxication described so far appeared in the tropical and subtropical regions of Asia and the Pacific [1,4,7,13] or in the USA, in which case these were caused by fish imported from Japan or Taiwan [2]. Our case is the first report of TTX intoxication from fish captured in the European coast. The trumpet shellfish ingested by the patient belonged to the species Charonia lampas lampa. It had been captured in the Portuguese coast. Both the intensity and speed of development of symptoms depend on concentrations of the toxin in the mollusk digestive glands. No antidote is available after toxin ingestion and the specific treatment must be supportive. The ingestion without treatment has a mortality rate that can reach 60%. In our case, the onset and severity of symptoms corresponded to the maximum degree of TTX intoxication. Just before consumption, the shellfish was boiled for 45 minutes, but this failed to reduce toxicity as TTX is heatstable, nor is it damaged by freezing [12].

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Table 1 Comparative data between motor nerve conductions studied 24 hours, 48 hours and 4 weeks after the onset of symptoms. Motor nerve conduction of median nerve to abductor pollicis brevis muscle, ulnar nerve to abductor digiti minimi muscle, peroneal nerve to extensor digitorum brevis muscle, tibial nerve to abductor hallucis muscle, and facial nerve to orbicular oculi. Pathological findings in bold letters. Note the absence of motor responses after 24 hours, the improvement after 48 hours and near normalization in 4 weeks. Motor nerves

Left median Right median Left ulnar Right ulnar Left peroneal Right peroneal Left tibial Right tibial Left facial Right facial

24 h

48 h

4 weeks

Normal values

DL

DA

DV

DL

DA

DV

DL

DA

DV

DL

DA

DV

ABS * ABS * ABS * ABS * ABS *

ABS * ABS * ABS * ABS * ABS *

ABS * ABS * ABS * ABS * * *

4.06 * 4.5 * 5.5 * 3.83 * 3.75 *

5.6 * 5.1 * 1.89 * 4.87 * 0.23 *

37.1 * 36.3 * 36.09 * 28. * * *

* 3.6 * 3.2 4.8 4.7 3.59 3.67 * 2.58

* 9.4 * 7.6 4.6 3.11 11.31 8.88 * 0.74

* 49.8 * 52.0 54.8 49.59 39.54 43.01 * *

< 4.2 < 4.2 < 4.2 < 4.2 < 5.2 < 5.2 < 5.2 < 5.2 < 3.5 < 3.5

> 5.0 > 5.0 > 5.0 > 5.0 > 3.0 > 3.0 > 4.0 > 4.0 > 1.0 > 1.0

> 50.0 > 50.0 > 50.0 > 50.0 > 40.0 > 40.0 > 40.0 > 40.0

ABS: absent; DA: distal amplitude (mV); DL: distal latency (ms); DV: distal velocity (m/s); asterisk: not done or not calculated.

Table 2 Comparative data between antidromic sensory nerve conductions studied 24 and 4 weeks after the onset of symptoms. Antidromic sensory nerve conduction of median nerve to II digit, ulnar nerve to V digit, radial nerve to dorsal I digit, superficial peroneal nerve to anterior lateral malleolus, and sural nerve to lateral malleolus. Pathological findings in bold letters. Note the absence of antidromic sensory responses after 24 and 48 hours and the improvement after 4 weeks. Sensory nerves

Left median Right median Left ulnar Right ulnar Left radial Right radial Left sural Right sural Left superficial peroneal Right superficial peroneal

24 h

48 h

4 weeks

Normal values

DL

DA

DV

DL

DA

DV

DL

DA

DV

DL

DA

DV

ABS ABS ABS ABS ABS ABS ABS * ABS *

ABS ABS ABS ABS ABS ABS ABS * ABS *

ABS ABS ABS ABS ABS ABS ABS * ABS *

ABS ABS ABS ABS * * * * ABS *

ABS ABS ABS ABS * * * * ABS *

ABS ABS ABS ABS * * * * ABS *

* 4.25 * 4.47 * 2.81 3.84 4.00 4.38 4.31

* 17.16 * 8.45 * 17.6 7.64 6.35 2.35 6.79

* 40 * 29.08 * 42.70 31.25 30.05 27.40 32.48

< 3.2 < 3.2 < 3.7 < 3.7 < 2.7 < 2.7 < 4.0 < 4.0 < 4.6 < 4.6

> 10.0 > 10.0 > 10.0 > 10.0 > 10.0 > 10.0 > 5.0 > 5.0 > 5.0 > 5.0

> 40.0 > 40.0 > 40.0 > 40.0 > 50.0 > 50.0 > 40.0 > 40.0 > 40.0 > 40.0

ABS: absent; DA: distal amplitude (mV); DL: distal latency (ms); DV: distal velocity (m/s); asterisk: not done or not calculated.

Table 3 Comparative data between F-waves responses studied 24 hours, 48 hours and 4 weeks after the onset of symptoms. F-waves responses of ulnar nerve to abductor digiti minimi muscle, tibial nerve to abductor hallucis muscle, and peroneal nerve to extensor digitorum brevis muscle. Pathological findings in bold letters. Note the absence of F-waves responses after 24 hours and the improvement after 48 hours and 4 weeks. F-waves responses

Left ulnar Right ulnar Left tibial Right tibial Left peroneal

24 h

48 h

4 weeks

Normal values

DL

DL

DL

DL

ABS * ABS * *

40.16 * 65.26 * 61.65

* 32.43 52.21 48.59

< 30.0 < 30.0 < 60.0 < 60.0 < 60.0

ABS: absent; DL: distal latency (ms); asterisk: not done or not calculated.

302 When intoxication is severe, intubation and mechanical ventilation are required although the cortical function could be normal. The toxin is eliminated from the blood, becoming undetectable after 24 hours [9]. Although we extracted blood and urine samples 30 hours after ingestion, there were still high toxin concentrations in the urine. The prognosis can be considered excellent if there are no complications deriving from ventilatory and cardiovascular support. TTX binds to the sodium channel of the nerve [3,8]. This results in transient and quickly reversible nerve dysfunction caused by ion channel blockade, which was manifested in our patient by a complete loss of muscle response. The clinical diagnosis was based on the sudden appearance of symptoms after ingesting the shellfish. EEG was normal, which suggests functional integrity of the cerebral cortex. Both ENG and EMG demonstrated generalized axonal blocks, compatible with a ‘‘sensory-motor demyelinating polyneuropathy’’. These abnormalities mimic fulminant Guillain-Barre syndrome, which, however, does not recover so quickly. ‘‘Acute motor conduction block neuropathy’’, a purely motor variant of Guillain-Barre syndrome, could be excluded because of sensory involvement. There is no other disease with acute loss of sensory and motor responses that starts to recover within 24 hours. Other etiologies of acute paralysis, like myasthenia gravis or other disorders of the neuromuscular junction caused by drug or intoxications have a different clinical presentation. The fact that the meal had been boiled, the short latency of symptom onset, and normal repetitive studies, allowed ruling out paralysis due to intoxication by Clostridium botulinum, which is a thermo-sensitive toxin and acts through different pathophysiological mechanisms. Other causes of toxic neuropathies [5] could be ruled out on the basis of patient’s story, neurophysiological findings, and blood and urine tests. Some other natural toxics can also cause acute paralysis: toxins of vegetal origin (buckthorn, Lathyrus sativus, ergotoxin-claviceps purpurera. . .), insect and reptile toxins (snakes, ticks, others), and marine toxins (ciguatoxine-Gambierdiscus toxicus, tetrodotoxin, saxitoxin-dinoflagelado catenella). Diagnostic confirmation requires analysis of both fish samples and patient’s blood and urine [5,10,14]. Our first determination was by bioassay, which is not specific for the type of toxin and has poor specificity. A second analysis was therefore carried out using HPLC-MS, which is a trusted technique to detect and quantify toxins. High amounts of TTX were detected both in samples of the trumpet shellfish and patient’s fluids. Similar results and technology have been reported in other cases of human TTX intoxication [10,14].

Conclusion This case warns about to the possibility of a very harmful toxin, which comes from fish introduced to the European

M. Fernández-Fígares et al. coast. Safety regulations should to be defined in other to detect and prevent it. Therefore, TTX intoxication should be considered in the differential diagnosis of acute paralysis. In this case, the neurophysiologic examination provided the earliest arguments for a peripheral-nerve involvement suggestive of this diagnosis. Biochemical studies should, of course, be performed in order to confirm the presence of TTX, but they require more time, all the more as biological samples need to be sent to other specialized laboratories.

Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.

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