Neurotoxic Seafood Poisoning

By Jean Lo, MD

Introduction

Thousands of cases of seafood poisoning with neurologic symptoms present to health care providers annually. Neurotoxic seafood poisoning most often occurs following consumption of fish and shellfish. Almost 25% of food poisoning in the United Stated between 1978 and 1982 were from fish or shellfish chemical poisoning. Gastrointestinal (GI) symptoms and neurological manifestations are common. Knowing where the fish or shellfish was caught can often aid in establishing the diagnosis. However, refrigerated transport of seafood now complicates the assessment. While evaluating patients with seafood poisoning with neurological symptoms, health care providers must consider other etiologies as well.

Case 1 presentation

A 30 year old male was brought to the Emergency Department (ED) 6 hours after eating sea bass. His symptoms included perioral numbness and tingling, a strange metallic taste, and reversal of temperature discrimination. He was also mildly hypotensive and bradycardic.

Questions

1. What is the likely causative agent?
2. Where are the likely sources?
3. What is the physiologic mechanism by which the agent exerts its effects?

Case 2 presentation

A 25 year old female was brought to the ED 24 hours after eating a Japanese seafood delicacy at a sushi restaurant. Shortly after ingestion, she developed lip and tongue paresthesias. Four hours after ingestion, she became nauseated, vomited, and had abdominal pain. She presented with decreased strength in both of her legs.

Questions

1. What is the likely causative agent?
2. What are the likely sources?
3. What is the physiologic mechanism by which the agent exerts its effects?

Ciguatera poisoning

Ciguatera poisoning is the most common vertebrate fishborne poisoning in the US. Hawaii and Florida together report 90% of all cases in this country. Most poisonings occur between May and August. Ciguatera poisoning most frequently occurs after ingestion of warm-water, bottom-dwelling shore reef fish, including barracuda, sea bass, parrot fish, red snapper, grouper, amber jack, sturgeon, and kingfish.

Photosynthetic dinoflagellates such as Gambierdiscus toxicus, and bacteria within the dinoflagellates are thought to be the origin of ciguatera poisoning, due to production of ciguatoxin and possibly other toxins. Ciguatoxin binds to voltage-sensitive sodium channels in diverse tissues and increases the sodium permeability of the channel. Symptoms usually begin 2-6 hours after ingestion. GI symptoms usually subside within 24-48 hours, while cardiovascular and neurological symptoms may persist for days to weeks.

The following symptoms have been reported after ciguatera poisoning:

• Nausea, vomiting, profuse water diarrhea
• Abdominal pain with cramps
• Diaphoresis
• Myalgias, arthralgias, ataxia, weakness
• Headaches, blurry vision, vertigo
• Seizure
• Peripheral dysthesias and paresthesias
• Numbness and tingling of the tongue, lips, throat, and perioral area
• A strange metallic taste
• Sensation of loose, painful teeth
• Reversal of temperature discrimination
• Bradycardia and hypotension

Ciguatoxin can be transmitted in breast milk and crosses the placenta. Management of ciguatera poisoning is mainly supportive, with intravenous fluids and antiemetics. Bradycardia and hypotension may be treated with atropine and alpha-adrenergic agonists. Persistent neurological symptoms can be managed with amitriptyline, 25mg BID. Intravenous mannitol, 1gm/kg has been used with some success to treat neurological symptoms of ciguatoxin. Initiation within 48 hours after symptom onset has been advocated, although improvement has been shown in patients who have been symptomatic up to eight weeks.

Neurotoxic shellfish poisoning: brevitoxin

Neurotoxic shellfish poisoning is related to the ingestion of brevitoxin found in the shellfish, including oysters, clams, mussels, and scallops. Brevitoxin originates from the dinoflagellate Karenia brevis, which contains Protogonylaulax catanella. Toxic red tides along the Florida Gulf coast are due to high concentrations of Karenia brevis. The impact of red tides includes massive fish kills, and potentially fatal bioconcentration in marine mammals, sea turtle and sea birds. Although most commonly found along the southwest Florida coast, brevitoxin has been reported throughout the entire US and Mexico Gulf coasts and the Atlantic coast north to North Carolina. The most common season of poisoning is between November and March.

Brevitoxin binds to voltage-gated sodium channels and stimulates sodium flux through these channels of both nerves and muscles. Increased sodium influx causes airway smooth muscle contraction by releasing acetylcholine from postganglionic parasympathetic nerve endings resulting in bronchospasm. GI symptoms and neurological symptoms can also occur and can appear simultaneously. Symptom onset ranges between 15 minutes to 18 hours. The following symptoms have been associated with brevitoxin.

• GI symptoms
  • Nausea, vomiting, diarrhea
  • Rectal burning
• Neurological symptoms
  • Paresthesias that begin in the circumoral region, then progress to the pharynx, trunk, and extremities
  • Myalgias
  • Vertigo, ataxia
  • Convulsions
  • Decreased reflexes
  • Reversal of hot and cold temperature sensation
• Bradycardia
• Mydriasis
• Bronchospasm, cough

Management of neurotoxic shellfish poisoning is mainly supportive. Respiratory symptoms such as wheezing and bronchospasm can usually be managed with b₂ agonists and antimuscarinic bronchodilators.

Paralytic shellfish poisoning: saxitoxin

Paralytic shellfish poisoning may occur after consumption of shellfish, clams, oysters, mussels, and scallops. Poisoning has also occurred through consumption of fish and crustaceans. Sand crabs, reef crabs, and purple starfish also contain saxitoxins. Saxitoxin-containing seafood can be found along the Pacific Northwest and Northeast Atlantic coast. The common season of this poisoning is between May and November.

Moraxella bacterium found in the dinoflagellate Protogonylaulax amarensis and Protogonylaulax tamarensis produce saxitoxin. Saxitoxins are also found in the freshwater blue-green algae, Aphanizomenon flos-aquae, Anabena circinalis, Lyngbya majuscula, and Oscillatoria mougeotti. Saxitoxin acts through blockade of the voltage-sensitive sodium channels, thus blocking propagation of nerve and skeletal muscle action potentials. Symptoms usually occur within 30 minutes of ingestion. GI symptoms are less common, while neurological symptoms predominate.

• GI symptoms
  • Nausea
  • Vomiting
  • Diarrhea
  • Abdominal pain
• Neurological symptoms
  • Paresthesias and numbness of the mouth and extremities
  • Sensation of floating
  • Headache
  • Ataxia, vertigo
  • Muscle weakness
  • Paralysis
  • Cranial nerve dysfunction such as dysphagia, dysarthria, dysphonia, transient blindness

Mortality is reported to be 2.6 to 23.2% in series of paralytic shellfish poisoning, and is most often secondary to respiratory failure. Symptoms usually occur within 12 hours after symptom onset. The prognosis is good if the patient survives the first 12 hours. Muscle weakness may persist for weeks in surviving victims. Management includes supportive care and early intervention for respiratory failure.

Tetrodotoxin

Tetrodotoxin is found in puffer fish, puffer-like fish including globe fish, balloon fish, blowfish, toad fish, gastropod mollusks including Natica lineata (lined moon shell) and Tutufa lissostoma (frog shell), the blue-ring octopus, horseshoe crab eggs, starfish, flatworms, and newts such as Taricha granulose in California, Oregon, and southern Alaska.

The most well known puffer fish is called fugu, the Japanese puffer fish that is considered a seafood delicacy. The flavor of fugu is considered to be at its best from November to February. These are the months when the toxin content of the ovaries and liver in these fish increases. In 1989, the Food and Drug Administration (FDA) legalized the importation of puffer fish, but required that before exportation from Japan, the fish must be laboratory tested and certified by two Japanese organizations to be tetrodotoxin free. Tetrodotoxin-containing puffer fish is still served in some restaurants under the supervision of certified chefs, and coveted for its mild neurologic properties when eaten.

Tetrodotoxin acts via inhibition of sodium channels and blocking propagation of nerve and skeletal muscle action potentials. Symptoms usually occur within minutes of ingestion, and initially include:

• Headache
• Diaphoresis
• Dysethesias and paresthesias of the lips, tongue, mouth, face, fingers, and toes
• Dysphagia, dysarthria, nausea, vomiting, abdominal pain may ensue

Subsequent symptoms occur in 4-24 hours of ingestion:

• Generalized malaise, loss of coordination, weakness, fasciculation, and ascending paralysis
• Hypotension

Mortality has approached 50% after tetrodotoxin ingestion in some series, but is usually thought to be much lower with ventilatory support. Management is meticulous supportive care, and early airway protection.

Amnestic shellfish poisoning: domoic acid

Several historical outbreaks have increased the awareness about amnestic shellfish poisoning. In November 1987, 107 individuals became ill after consuming mussels harvested on Prince Edward Island in Canada. This outbreak resulted in three fatalities. In 1991, 20 individuals became ill after consuming razor clams in Washington State. No deaths were reported during this outbreak. In 1991, hundreds of brown pelicans in Monterey Bay, California consumed domoic acid-containing anchovies, resulting in death in many of the birds.

Amnestic shellfish poisoning is caused by domoic acid, a tricarboxylic amino acid that is a structural analog of glutamic and kainic acids. Domoic acid binds to kainic receptors in the central nervous system and results in neuronal loss within the thalamus, forebrain, and hippocampus, which is responsible for long term memory. Domoic acid is produced by the phytoplankton Nitzschia pungens and Pseudonitzschia australis. Domoic acid poisoning is found along the Pacific Coast of North America, eastern Canadian Atlantic coast, and Gulf of Mexico.

Symptoms usually begin 15 minutes to 38 hours after ingestion of contaminated shellfish. GI symptoms precede neurological symptoms, and most often occur within 24 hours, while neurological symptoms usually occur after 48 hours. Symptoms most commonly encountered include:

• GI symptoms:
  • Nausea
  • Vomiting
  • Diarrhea
  • Abdominal pain
• Neurological symptoms:
  • Memory loss
  • Hemiparesis
  • Ophthalmoplegia
  • Purposeless chewing
  • Grimacing
  • Seizures
  • Coma
• Hemodynamic instability
• Cardiac dysrhythmias

Mortality is 2%, usually in older patients. Up to 10% of individuals may suffer long-term anterograde memory deficits and motor and sensory neuropathy.

Case 1 answers

1. What is the likely causative agent?
   Ciguatoxin. The ingestion of sea bass, reversal of temperature discrimination, and hypotension and bradycardia are predominant clues.
2. Where are the likely sources?
   Ciguatoxin originates from photosynthetic dinoflagellates like Gambierdiscus toxicus, and bacteria within the dinoflagellates. Dinoflagellates are the main food source for small fish, leading eventually to bioconcentration into larger predator fish such as barracuda, sea bass, parrot fish, red snapper, grouper, amber jack, sturgeon, and kingfish. Ciguatoxin can be found in higher concentrations in the flesh, adipose tissue, and viscera of these larger fish.
3. What is the physiologic mechanism by which ciguatoxin exerts its effects?
   Ciguatoxin binds to voltage-sensitive sodium channels in diverse tissues and increases the sodium permeability of the channel.

Case 2 answers

1. What is the likely causatic agent?
   Tetrodotoxin. The lip and tongue paresthesias, subsequent GI symptoms, and finally ascending paralysis are characteristic.
2. Where are the likely sources?
   Tetrodotoxin is found in puffer fish such as Fugu vermicularis. Tetrodotoxin can also be found in puffer-like fish including globe fish, balloon fish, blowfish, and toad fish, and in gastropod mollusks, the blue-ring octopus, horseshoe crab eggs, starfish, flatworms, and some newts.
3. What is the physiologic mechanism by which tetrodotoxin exerts its effects?
   Tetrodotoxin acts via inhibition of sodium channels and blocking propagation of nerve and skeletal muscle action potentials.