a. Clinical Syndrome.
(a) Saxitoxin is the parent compound of a family of chemically related neurotoxins. In nature they are predominantly produced by marine dinoflagellates, although they have also been identified in association with such diverse organisms as blue-green algae, crabs, and the blue-ringed octopus. Human intoxications are principally due to ingestion of bivalve molluscs which have accumulated dinoflagellates during filter feeding. The resulting intoxication, known as paralytic shellfish poisoning (PSP), is known throughout the world as a severe, life-threatening illness requiring immediate medical intervention.
(b) Saxitoxin and its derivatives are water-soluble compounds that bind to the voltage-sensitive sodium channel, blocking propagation of nerve-muscle action potentials. Consistent with this mechanism of action, victims typically present with neurological symptoms and in severe cases, death results from respiratory paralysis.
(c) The natural route of exposure to these toxins is oral. In a BW scenario, the most likely route of delivery is by inhalation or toxic projectile. In addition, saxitoxin could be used in a confined area to contaminate water supplies.
(2) Clinical Features. After oral exposure, absorption of toxins from the gastrointestinal tract is rapid. Onset of symptoms typically begins 10-60 minutes after exposure, but may be delayed several hours depending upon the dose and individual idiosyncrasy. Initial symptoms are numbness or tingling of the lips, tongue and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may be present, but typically occur in a minority of cases. Other symptoms may include a feeling of light headedness, or floating, dizziness, weakness, aphasia, incoherence, visual disturbances, memory loss and headache. Cranial nerves are often involved, especially those responsible for ocular movements, speech, and swallowing. Induced reflexes are normal and the patient remains conscious. Respiratory distress and flaccid muscular paralysis are the terminal stages and can occur 2-12 hours after intoxication. Death results from respiratory paralysis. Clearance of the toxin is rapid and survivors for 12-24 hours will usually recover. Complete recovery may require 7-14 days. There are no known cases of inhalation exposure to saxitoxin in the medical literature, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.
(1) Routine Laboratory Findings. Routine laboratory evaluation is not particularly helpful. Cardiac conduction defects may develop. Elevation of serum creatine kinase levels in some patients has been reported.
(2) Differential Diagnosis. Exposure to tetrodotoxin or the ciguatera toxins can manifest very similar signs and symptoms. Ciguatoxins (by oral exposure) typically demonstrate a much greater degree of gastrointestinal involvement, and can also be differentiated by a history of eating finfish rather than shellfish. Tetrodotoxin intoxication is nearly identical to that caused by the saxitoxins except that hypotension typically plays a greater role in severe intoxication. Differential diagnosis may require toxin detection. Gas chromatographic analysis of food or stomach contents can rule out pesticide exposure.
(3) Specific Laboratory Tests. Diagnosis is confirmed by detection of toxin in the food, water, stomach contents or environmental samples. Saxitoxin, neosaxitoxin, and several other derivatives can be detected by ELISA or by mouse bioassay. Specific toxins can be differentiated by high pressure liquid chromatography (HPLC). The Association of Official Analytical Chemists has adopted an official method for mouse bioassay for the analysis of seafood.
c. Therapy. Management is supportive and standard management of poison ingestion should be employed if intoxication is by the oral route. Toxins are rapidly cleared and excreted in the urine, so diuresis may increase elimination. Charcoal hemoperfusion has been advocated, but remains unproven in its utility. Incubation and mechanical respiratory support may be required in severe intoxication. Timely resuscitation would be imperative, albeit very difficult, after inhalation exposure on the battlefield. Specific antitoxin therapy has been successful in animal models, but is untested in humans.
d. Prophylaxis. No vaccine against saxitoxin exposure has been developed for human use.