Amnesic Shellfish Poisoning

This information is courtesy of Lora E. Fleming, NIEHS Marine and Freshwater Biomedical Sciences Center

ASP is a newly identified marine toxin disease, first reported from Canada and later identified as a continuing problem in Washington State and Oregon. After an initial gastroenteritis with neurologic symptoms, some persons with ASP develop apparent permanent neurologic deficits, especially dementia. It is caused by the consumption of contaminated shellfish.

At the end of November 1987, 153 cases of acute intoxication after ingestion of toxic mussels were reported in Canada associated with blooms of the marine diatom Pseudonitschia pungens. Dinoflagellate samples taken from the Cardigan River estuary were found to contain >1% domoic acid dry weight. Contaminated mussels had digestive glands engorged with P. pungens.

Clinical Presentation:

Acute symptoms of ASP included vomiting, diarrhea, and in some cases, there followed confusion, loss of memory, disorientation and even coma. The acute symptoms were mild compared with PSP. Permanent neurologic sequelae, especially cognitive disfunction, were most likely in persons who developed neurologic illness with 48 hours, males, in older patients (> 60 yrs), and in younger persons with pre-existing illnesses such as diabetes, chronic renal disease and hypertension with a history of transient ischemic attacks. Three elderly patients died directly and one died indirectly from the intoxication; 19 people required hospitalization with 12 admitted to intensive care units due to seizures, coma, profuse respiratory secretions or unstable blood pressure.

The acute symptom frequencies were the following: vomiting (76%), abdominal cramps (50%), diarrhea (4%), severe headache (43%), and loss of short-term memory (25%). Acutely, the patients had headache, hyporeflexia, hemiparesis, ophthalmoplegia and abnormalities of arousal ranging from agitation to coma; in addition; seizures and myoclonus were observed acutely, especially around the face.

Teitlebaum et al. (1990) studied 14 persons with severe neurologic disease. In neuropsychological testing performed several months after the acute episode, 12/14 persons had severe antegrade memory deficits with relative preservation of other cognitive functions. 11/14 persons had clinical and electromyographic evidence of pure motor or sensory motor neuronopathy or axonopathy. The PET results in 4/14 persons showed decreased glucose metabolism in the medial temporal lobes. The neuropathology for the 4 fatal cases, revealed neuronal necrosis and loss, predominantly in the hippocampus and amygdala. All 14 with severe neurologic disease reported confusion and disorientation within 1.5 to 48 hours after consumption. The maximal neurologic deficits were seen 4 hours post ingestion of least affected and 72 hours in those most affected, with maximal improvement 24 hours to 12 weeks post ingestion. Acute coma was associated with the slowest recovery. Seizures ceased by 4 months but were frequent upto 8 weeks.

Relative preservation of intellect and higher cortical function appears to distinguish this disease from Alzheimer's Disease, and the absence of confabulation with well preserved frontal lobe function is not typical of Korsakoff's syndrome.

Diagnosis:

The mouse assay used for ASP testing is the same as for PSP. The relative potency of ASP toxins appear to be less than PSP. In addition, involuntary scratching of shoulders with hind legs by the mice was noted and is not typical of PSP. HPLC analysis can quantify domoic acid from contaminated shellfish in ASP episodes.

Management and Treatment:

At this point, the treatment of ASP is symptomatic and supportive. Teitelbaum et al (1990) noted that the seizures respond to iv diazepam and phenobarbital. Three patients were resistent to dilantin for seizure control.

As with many of the marine toxin induced diseases, the initial or index case(s) are often the tip of the iceberg. Therefore any suspected cases of ASP should be reported to the appropriate public health authorities for follow up to ascertain other cases and to prevent further spread. And every effort should be made to obtain contaminated materials and their source.

Since an estimated concentration of 200 ug/g wet weight domoic acid appeared to affect some consumers, with a safety factor of 0.1 applied, Canada has set a concentration of domoic acid of 20 ug/g wet weight above which shellfish commercial operations should be closed. Finally, this epidemic has lead to new attention to the diatoms, especially the appearance of the mucilage from diatoms with species of Nitzschia.

ASP Chemical Structure

Molecular Mechanism of Action:

Domoic acid, and its co-existing natural chemical analogs act as a potent excitatory neurotransmitter. An estimated concentration of 200 ug/g wet weight domoic acid appeared to affect some human consumers.

Domoic acid is heat-stable and similar to its biochemical analogues, kainic acid and glutamic acid and binds at the same receptor site in CNS. Lesions in human brain, especially in the hippocampus, have been reported in the ASP human cases which are similar to those seen in rats after kainic acid iv administration. When rats are exposed experimentally to domoic acid and its analogues, they get limbic seizures, memory and gait abnormalities, and degeneration of the hippocampus. In animals, domoic acid is three times more potent than kainic acid and 30-100 more potent than glutamic acid.

Recent work by Novelli et al (1992) demonstrated that domoic acid from mussels is more neurotoxic for cultured human neurons than purified domoic acid. This increase is believed to be due to domoic acid potentiation, even in subtoxic amounts, of the excitotoxic effect of glutamic acid and aspartic acid. Glutamic and aspartic acids are present in high concentrations in mussel tissue. This neurotoxic synergism may occur through a reduction in the voltage dependent Mg2+ block at the NMDA receptor associated channel, following activation of non-NMDA receptors by domoic acid.

In humans, domoic acid appears to cause a non-progressive acute neuronopathy involving anterior horn cells or a diffuse axonopathy predominantly affecting motor axons. The acute neuronal hyperexcitation syndrome presumably results from the stimulus of central and possibly peripheral neurons, followed by chronic loss of function in neural systems susceptible to excitotoxic degeneration (ie. hippocampus and anterior horn cells of spinal cord).

References:

  • Baden D., L.E. Fleming, and J.A. Bean. 1995. Chapter: Marine Toxins. in: Handbook of Clinical Neurology: Intoxications of the Nervous System Part II. Natural Toxins and Drugs. FA deWolff (Ed). Amsterdam: Elsevier Press, pgs. 141-175.

  • Debonnel, G., L. Beaushesne and C. Demonigny. 1989. Domoic acid, the alleged mussel toxin, might produce ite neurotoxic effect through kainate receptor acitivation: an electrophysiologic study in the rat dorsal hippocampus. Canadian Journal of Physiology and Pharmacology 67: 29-33.

  • Lawrence, J.F., C.F. Charbonneau, C. Menard, M.A. Quilliam and P.G. Sim. 1989. Liquid chromatographic determination of domoic acid in shellfish products using the paralytic shellfish poison extraction procedure of the Association of Official Analytical Chemists. Journal of Chromatography 462: 349-356.

  • Novelli, A., J. Kispert, T. Fernandez-Sanchez, A. Torreblanca and V. Zitko. 1992. Domoic acid-containing toxic mussels produce neurotoxicity in neuronal cultures through a synergism between excitatory amino acids. Brain Research 577: 41-48.

  • Perl, T.M., L. Bedard, T. Kosatsky, J.C. Hockin, E.C.D. Todd and R. Remis. 1990. Encephalopathy Caused by Contaminated Mussels - Perl et al. New England Medical Journal 322: 1775-80.

  • Subba Rao, D.V., M.A. Quilliam and R. Pocklington. 1988. Domoic acid - a neurotoxic amino acid produced by the marine diatom Nitzschia pungens in culture. Canadian Journal of Fisheries and Aquatic Science 45: 2076-2079.

  • Teitelbaum, J.S., R.J. Zatorre, S. Carpenter, D. Gendron, A.C. Evans, A. Gjedde and N.R. Cashman. 1990. Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels. New England Journal of Medicine 322: 1781-87.

  • Wright, J.L.C., R.K. Boyd, A.S.W. De Freitas et al. 1989. Identification of ic acid, a neuroexcitatory amino acid, in toxic mussels from eastern Prince Edward Island. Canadian Journal of Chemistry 67: 481-490.


Last updated: July 31, 2012