domoic-acid and Neuromuscular-Diseases

Recent applications of modern neurobiological techniques have provided an impetus to understanding mechanisms of neurotoxicity. Environmental chemicals, including aluminium, and the organocompounds of mercury, lead and tin, may trigger neurodegenerative disorders. Regional differences in toxicity may be related to the complexity of the amino acid excitatory systems and the ability of individual cell systems to handle long-term abusive stimulation.

Topics: Animals; Brain; Brain Damage, Chronic; Environmental Exposure; Humans; Kainic Acid; Neuromuscular Diseases; Neurotoxins; Organometallic Compounds

In late 1987 there was an outbreak in Canada of gastrointestinal and neurologic symptoms after the consumption of mussels found to be contaminated with domoic acid, which is structurally related to the excitatory neurotransmitter glutamate. We studied the neurologic manifestations in 14 of the more severely affected patients and assessed the neuropathological findings in 4 others who died within four months of ingesting the mussels. In the acute phase of mussel-induced intoxication, the patients had headache, seizures, hemiparesis, ophthalmoplegia, and abnormalities of arousal ranging from agitation to coma. On neuropsychological testing several months later, 12 of the patients had severe anterograde-memory deficits, with relative preservation of other cognitive functions. Eleven patients had clinical and electromyographic evidence of pure motor or sensorimotor neuronopathy or axonopathy. Positron-emission tomography of four patients showed decreased glucose metabolism in the medial temporal lobes. Neuropathological studies in the four patients who died after mussel-induced intoxication demonstrated neuronal necrosis and loss, predominantly in the hippocampus and amygdala, in a pattern similar to that observed experimentally in animals after the administration of kainic acid, which is also structurally similar to glutamate and domoic acid. We conclude that intoxication with domoic acid causes a novel and distinct clinicopathologic syndrome characterized initially by widespread neurologic dysfunction and then by chronic residual memory deficits and motor neuronopathy or axonopathy.

Topics: Animals; Bivalvia; Brain; Disease Outbreaks; Electromyography; Food Contamination; Glucose; Humans; Kainic Acid; Marine Toxins; Memory Disorders; Motor Neurons; Myoclonus; Necrosis; Nervous System Diseases; Neuromuscular Diseases; Neurotransmitter Agents; Prince Edward Island; Seizures; Temporal Lobe; Tomography, Emission-Computed

Topics: Animals; Bivalvia; Canada; Disease Outbreaks; Gastroenteritis; Humans; Kainic Acid; Neuromuscular Depolarizing Agents; Neuromuscular Diseases