Brain mechanisms of abnormal temperature perception in cold allodynia induced by ciguatoxin.

OBJECTIVE: Cold allodynia occurs as a major symptom of neuropathic pain states. It remains poorly treated with current analgesics. Ciguatoxins (CTXs), ichthyosarcotoxins that cause ciguatera, produce a large peripheral sensitization to dynamic cold stimuli in Aδ-fibers by activating sodium channels without producing heat or mechanical allodynia. We used CTXs as a surrogate model of cold allodynia to dissect the framework of cold allodynia-activated central pain pathways. METHODS: Reversible cold allodynia was induced in healthy male volunteers by shallow intracutaneous injection of low millimolar concentrations of CTX into the dorsal skin of the forefoot. Cold and warm stimuli were delivered to the treated and the control site using a Peltier-driven thermotest device. Functional magnetic resonance imaging (fMRI) scans were acquired with a 3T MRI scanner using a blood oxygen level-dependent (BOLD) protocol. RESULTS: The CTX-induced substantial peripheral sensitization to cooling stimuli in Aδ-fibers is particularly retrieved in BOLD changes due to dynamic temperature changes and less during constant cooling. Brain areas that responded during cold allodynia were almost always located bilaterally and appeared in the medial insula, medial cingulate cortex, secondary somatosensory cortex, frontal areas, and cerebellum. Whereas these areas also produced changes in BOLD signal during the dynamic warming stimulus on the control site, they remained silent during the warming stimuli on the injected site. INTERPRETATION: We describe the defining feature of the cold allodynia pain percept in the human brain and illustrate why ciguatera sufferers often report a perceptual temperature reversal. ANN NEUROL 2017;81:104-116.

Digital Technologies and Open Data Sources in Marine Biotoxins' Risk Analysis: The Case of Ciguatera Fish Poisoning.

Currently, digital technologies influence information dissemination in all business sectors, with great emphasis put on exploitation strategies. Public administrations often use information systems and establish open data repositories, primarily supporting their operation but also serving as data providers, facilitating decision-making. As such, risk analysis in the public health sector, including food safety authorities, often relies on digital technologies and open data sources. Global food safety challenges include marine biotoxins (MBs), being contaminants whose mitigation largely depends on risk analysis. Ciguatera Fish Poisoning (CFP), in particular, is a MB-related seafood intoxication attributed to the consumption of fish species that are prone to accumulate ciguatoxins. Historically, CFP occurred endemically in tropical/subtropical areas, but has gradually emerged in temperate regions, including European waters, necessitating official policy adoption to manage the potential risks. Researchers and policy-makers highlight scientific data inadequacy, under-reporting of outbreaks and information source fragmentation as major obstacles in developing CFP mitigation strategies. Although digital technologies and open data sources provide exploitable scientific information for MB risk analysis, their utilization in counteracting CFP-related hazards has not been addressed to date. This work thus attempts to answer the question, "What is the current extent of digital technologies' and open data sources' utilization within risk analysis tasks in the MBs field, particularly on CFP?", by conducting a systematic literature review of the available scientific and grey literature. Results indicate that the use of digital technologies and open data sources in CFP is not negligible. However, certain gaps are identified regarding discrepancies in terminology, source fragmentation and a redundancy and downplay of social media utilization, in turn constituting a future research agenda for this under-researched topic.

Exacerbation of asthma by Florida "red tide" during an ocean sailing trip.

A 36-year-old man with adult-onset nonallergic triad asthma developed acute bronchospasm and copious sputum production during an offshore sailing excursion on the Gulf Coast of Florida. Symptoms were linked to proximity to blooms of the marine dinoflagellate Karenia brevis (red tide) and heavy aerosolized brevetoxin exposure, and symptoms recurred during rechallenge. Patients with respiratory disease who are planning a visit to red tide-prone seaside areas should be cautioned to bring their pulmonary medications, and clinicians should be aware that reactive airway symptoms may be triggered by exposure to red tide.

Ciguatera: Australian perspectives on a global problem.

Ciguatera is a global disease caused by the consumption of certain warm-water fish that have accumulated orally effective levels of sodium channel activator toxins (ciguatoxins) through the marine food chain. Symptoms of ciguatera arising from the consumption of ciguateric fish include a range of gastrointestinal, neurological and cardiovascular disturbances. This review examines progress in our understanding of ciguatera from an Australian perspective, especially the laboratory-based research into the problem that was initiated by the late "Bob" Endean at the University of Queensland.

Ciguatera neurotoxin poisoning mimicking burning mouth syndrome.

Burning mouth syndrome is a condition in which the patient perceives a sensation of intraoral burning, typically of the anterior tongue. This article presents a case report of a patient presenting for orofacial pain evaluation in whom ciguatera neurotoxin poisoning is diagnosed. The clinician should be aware of neurotoxin poisoning as a possible cause of symptoms of burning mouth, especially among patients who have recently traveled to a tropical area. Recognition of this condition in this case highlights the need for a detailed and accurate patient history.

Ciguatera in Réunion Island (SW Indian Ocean): epidemiology and clinical patterns.

One hundred and fifty-nine ichtyosarcotoxic outbreaks, including 477 people, were recorded in the island of Réunion (SW Indian ocean) between 1986 and 1994. Ciguatera outbreaks represented 78.6% of the total cases and its annual incidence rate was estimated to be 0.78/10,000 residents. Symptoms caused by ciguatera poisoning are not different from those reported in Pacific and Caribbean islands, except for the additional symptoms of hallucinatory poisoning in 16% of the patients. Serranidae fish, including species of great commercial value, were the most commonly incriminated accounting for 50% of the outbreaks.

Organic neurotoxins in seafoods.

Toxins formed by organic micro-organisms may accumulate within certain tissues of predacious sea animals, which may serve as a source of seafood poisoning for the higher food chain. Such toxins are distinct from inorganic chemicals or infectious agents which may have contaminated the seafoods. Distinct clinical syndromes have emerged, and the individual toxins have been identified. Clinical manifestations of each begin with a gastrointestinal prodrome and headache, followed by sensorimotor deficits. Bulbar and cognitive changes are associated with the more lethal tetrodotoxin, saxitoxin, and domoic acid toxin. Tetrodotoxin and saxitoxin block sodium channels, while ciguatoxin opens them. Domoic acid stimulates excitatory amino acids at the NMDA receptors.

[Ciguatera poisoning in Spanish travellers]. / Intoxicación por ciguatoxina en viajeros.

BACKGROUND AND OBJECTIVE: Ciguatera poisoning appears after ingestion of contaminated fish from tropical coral reefs. Due to the diversity of clinical symptoms and the absence of a specific test in humans, the diagnosis is often difficult. PATIENTS AND METHOD: A retrospective study of 10 patients consulting for a clinical and epidemiological picture compatible with ciguatera poisoning after a trip to tropical countries between 1993 and 2000. RESULTS: Most infections but one were acquired in the Caribbean area and there were 8 females. Clinical manifestations started within the first 24 hours after fish ingestion. Chief symptoms were diarrhea and nausea, followed by neurological symptoms, mainly limbs paresthesias that persisted for several weeks. CONCLUSIONS: The severity of clinical symptoms was variable and not related to age or initial symptoms. Ciguatera poisoning has to be considered in the diagnosis of acute gastroenteritis affecting travellers to tropical areas.

Ciguatera: current concepts.

Ciguatera poisoning develops after ingestion of certain coral reef-associated fish. With travel to and from the tropics and importation of tropical food fish increasing, ciguatera has begun to appear in temperate countries with more frequency. The causative agents are certain varieties of the protozoan dinoflagellate Gambierdiscus toxicus, but bacteria associated with these protozoa may have a role in toxin elaboration. A specific "ciguatoxin" seems to cause the symptoms, but toxicosis may also be a result of a family of toxins. Toxicosis develops from 10 minutes to 30 hours after ingestion of poisoned fish, and the syndrome can include gastrointestinal and neurologic symptoms, as well as chills, sweating, pruritus, bradycardia, tachycardia, and long-lasting weakness and fatigue. More severe features are rare. In this review, the pathophysiologic features and symptoms of ciguatera are reviewed and compared with those of other seafood-related syndromes. Although no definitive therapy is known, the most promising treatment for ciguatera is intravenous administration of mannitol. Physicians should warn patients who are traveling to endemic areas about this toxicosis.

Neurotoxins: a neuroscience nursing challenge.

Societal awareness of toxins in general has been heightened in the past few decades with the increased focus on environmental concerns. The medical profession has been aware of the effects of some toxins such as lead and mercury for centuries, while other toxins have more recently been identified. Neuroscience nurses are challenged to be aware of the neurological effects of lesser known toxins, such as ciguatera and methyl bromide, and to meet the complex needs of patients who are suffering from the effects of toxic levels of these substances.

[Evaluation of Antilles fish ciguatoxicity by mouse and chick bioassays]. / Evaluation de la ciguatoxicité de poissons des antilles par les bioessais souris et poussin.

Ciguatera is a common seafood poisoning in Western Atlantic and French West Indies. Ciguatera fish poisoning in the Caribbean is a public health problem. A toxicological study was carried out on 178 Caribbean fish specimens (26 species) captured off Guadeloupe and Saint Barthelemy between 1993 and 1999. The mouse bioassay and the chick feeding test were used to control fish edibility. Ciguatoxins presence was assumed when symptomatology was typical of ciguatera in mouse and chick. Fishes were classified in three groups: non toxic fish (edible), low toxic fish (not edible) and toxic fish (not edible). 75% of fishes were non toxic. Toxic fish specimens belonged to four families of high trophic level carnivores: Carangidae, Lutjanidae, Serranidae et Sphyraenidae. Percentages of toxic fishes to humans reached 55% for Caranx latus and 33% for Caranx bartholomaei and Caranx lugubris. Only a significant correlation between weight and toxicity was only found for C. latus and snappers. Small carnivorous groupers (Serranidae) were also toxic. Atoxic fish species were (a) pelagic fish (Coryphaena hippurus, Auxis thazard and Euthynnus pelamis), (b) invertebrates feeders (Malacanthus plumieri, Balistes vetula), (c) small high-risk fish or (d) fish of edible benthic fish families. Liver of four fishes (Mycteroperca venenosa, Caranx bartholomaei, Seriola rivoliana, Gymnothorax funebris) contained ciguatoxins at a significant level although their flesh was safe. This study confirms the usefulness of mouse and chick bioassays for sanitary control of fish.

Acute cervico-facial oedema and loss of consciousness following ingestion of barracuda fish.

A young male presented with acute cervico-facial swelling and loss of consciousness, following ingestion of barracuda flesh. He recovered after administration of anti-histamines and steroids. Toxicity associated with barracuda is discussed.

Severe bradycardia and prolonged hypotension in ciguatera.

Ciguatera results when ciguatoxin-contaminated coral reef fish from tropical or subtropical waters are consumed. The clinical features that present in affected persons are mainly gastrointestinal, neurological, general, and much less commonly, cardiovascular. We report the case of a 50-year-old man who developed the characteristic combination of acute gastrointestinal and neurological symptoms after the consumption of an unidentified coral reef fish head. In addition to those symptoms, he developed dizziness, severe bradycardia (46 bpm) and prolonged hypotension, which required the administration of intravenous atropine and over three days of intravenous fluid replacement with dopamine infusion. Patients with ciguatera can develop severe bradycardia and prolonged hypotension. Physicians should recognise the possible cardiovascular complications of ciguatera and promptly initiate treatment with intravenous atropine, intravenous fluid replacement and inotropic therapy if such complications are observed.

Neurology of ciguatera.

Ciguatera is a widespread ichthyosarcotoxaemia with dramatic and clinically important neurological features. This severe form of fish poisoning may present with either acute or chronic intoxication syndromes and constitutes a global health problem. Ciguatera poisoning is little known in temperate countries as a potentially global problem associated with human ingestion of large carnivorous fish that harbour the bioaccumulated ciguatoxins of the photosynthetic dinoflagellate Gambierdiscus toxicus. This neurotoxin is stored in the viscera of fish that have eaten the dinoflagellate and concentrated it upwards throughout the food chain towards progressively larger species, including humans. Ciguatoxin accumulates in all fish tissues, especially the liver and viscera, of "at risk" species. Both Pacific (P-CTX-1) and Caribbean (C-CTX-1) ciguatoxins are heat stable polyether toxins and pose a health risk at concentrations above 0.1 ppb. The presenting signs of ciguatera are primarily neurotoxic in more than 80% of cases. Such include the pathognomonic features of postingestion paraesthesiae, dysaesthesiae, and heightened nociperception. Other sensory abnormalities include the subjective features of metallic taste, pruritus, arthralgia, myalgia, and dental pain. Cerebellar dysfunction, sometimes diphasic, and weakness due to both neuropathy and polymyositis may be encountered. Autonomic dysfunction leads to hypotension, bradycardia, and hypersalivation in severe cases. Ciguatoxins are potent, lipophilic sodium channel activator toxins which bind to the voltage sensitive (site 5) sodium channel on the cell membranes of all excitable tissues. Treatment depends on early diagnosis and the early administration of intravenous mannitol. The early identification of the neurological features in sentinel patients has the potential to reduce the number of secondary cases in cluster outbreaks.

Evaluation of the stick enzyme immunoassay in Caranx sp. and Seriola dumerili associated with ciguatera.

The stick enzyme immunoassay (S-EIA) using monoclonal antibody to ciguatoxin (MAb-CTX) was used to examine clinically implicated fish and to pre-screen two species of fish, Caranx sp. (ulua or jack) and Seriola dumerili (kahala or amberjack), supplied by sports fishermen. All of the clinically implicated fish from the Department of Health gave S-EIA values greater than or equal to 1.3. The Caranx sp. and Seriola dumerili considered safe (less than or equal to 1.2 value) and consumed after testing gave no false-negative results. The S-EIA procedure using MAb-CTX proved to be specific, sensitive, and simple to use in the laboratory. It also proved to be useful in screening two large carnivorous fish for ciguatoxin and related polyethers prior to consumption.

[Effect of ciguatoxins on the cardiocirculatory system]. / Effet des ciguatoxines sur le système cardio-circulatoire.

The aim of the present review was to collect the main observations reported until now concerning the cardio-circulatory effects of polyether toxins, called ciguatoxins, which are involved in an endemic intoxication named ciguatera found in tropical and subtropical countries. Ciguatera is caused by the ingestion of fishes contaminated with the dinoflagellate Gamberdiscus toxicus. Due to both tropical fish exportation destined for food and tourism, the disease has now spread out to temperate areas. Several toxins have been isolated and purified from different fish species living in different geographical areas. They are classified into three main groups by the nature of certain cycles of their carbon skeleton. Clinical reports show evidence that ciguatera intoxication affect both electrocardiograms and blood pressure. In most cases, ciguateric intoxication mainly evoked bradycardia, hypotension, and the alteration of S-T segment in the electrocardiogram. Isolated and purified ciguatoxins strongly altered the morphology of cardiac tissue inducing swelling of the cells and alterations of cellular organelles. These toxins impair the conduction of cardiac nerves and increase the opening probability of Na+ channels in intracardiac ganglions. Depending on the concentration applied, the substances exerted either a fast positive inotropic effect or a negative inotropic effect on the contraction of mammalian atrial and ventricular cardiac muscle. These effects were attributed to a release of noradrenaline and acetylcholine from neural terminals of the autonomic nervous system present in cardiac tissue. They also exert a slow delayed inotropic effect on the contraction which has been attributed to a direct effect of the toxins on tetrodotoxin-sensitive voltage-dependent Na+ channels of cardiac membranes. Ciguatoxins depolarized the membrane of mammalian atrial and ventricular preparations and shifted the threshold of sodium current activation to more negative membrane potentials. In conclusion, the inotropic effects of ciguatoxins on cardiac tissues mainly depend on the toxin concentration sensitivity of autonomic nerve terminals, which released noradrenaline and/or acetylcholine, while the ciguatoxin-induced increase of the sodium influx could be involved in the cardiac cell swelling which coincides with reports in which ciguatoxins induced a mannitol-inhibited swelling of the Node of Ranvier.