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Nausea, blurry vision, hallucinations—Dx?

THE CASE

A 55-year-old Asian woman was brought to the emergency department by her husband, with symptoms of nausea, blurry vision, headache, and hallucinations. Her husband told us that he and his wife had flown to New Orleans to embark on a Caribbean cruise 5 days earlier. The next morning—their first full day on the ship—his wife became nauseous and her vision was blurred. She went to the ship’s doctor, who treated her for motion sickness.

On Day 3, she developed a right-sided headache at the back of her head and neck. The patient refused to go to the hospital at the first Mexican port and waited until the ship arrived in Belize. She was taken ashore for a computed tomography (CT) scan, which was negative. She stayed the night in the hospital.

The next day, the patient developed weakness and numbness in her left arm. She was seen by a neurologist and given amitriptyline, and underwent a second CT scan. When this scan, too, was read as negative, she and her husband flew home to Phoenix and sought care at our emergency department. There, the patient had a third CT scan, which showed temporal edema suggestive of encephalitis. Foodborne illness—or something else?
Samuel N. Grief, MD, FCFP

A neurologist performed a lumbar puncture and found nonspecific pleocytosis in the spinal fluid. The patient was started on aggressive antiviral therapy, including intravenous acyclovir, as well as steroids, but she showed no improvement. The symptoms continued, and the patient had vivid hallucinations: She reported seeing mermaids waving in the windows and children running around the hospital halls and ceilings.

An extensive serological workup followed, and was negative for: cytomegalovirus, dengue virus, West Nile virus, Lyme disease, coxsackievirus, syphilis, Cryptococcus, Coccidioides, mumps, measles, antinuclear antibodies, lupus, malaria, and herpes simplex virus.

THE DIAGNOSIS

After ruling out the other possible etiologies, and noting that the patient had eaten fish the day before the symptoms developed, the hospitalist, neurologist, and infectious disease specialist agreed that the most likely diagnosis was ciguatera poisoning. A literature search revealed the recommended treatment: a mannitol infusion of a 20% solution, 1 g/kg, with a piggyback of 250 mL over 30 minutes,1 every 6 hours as needed.

A dramatic improvement

The patient’s headache and arm weakness improved within 24 hours of receiving the mannitol. Her mental status improved as well as the blurry vision.

Two days later, the patient received a second mannitol infusion and was discharged the next day, although she still had mild weakness in her left arm and lingering hallucinations. A 2-week follow-up appointment with the neurologist was scheduled so that she could have a third mannitol treatment for her persistent visual changes.

DISCUSSION

Ciguatera poisoning—a little-known marine toxin

Ciguatera toxin is a lipid-soluble, heat-stable marine toxin2 made by dinoflagellates such as Gambierdiscus toxicus in tropical and subtropical waters. Larger fish eat the herbivore fish that have eaten the dinoflagellates and the toxin bioaccumulates until it reaches large predatory fish like barracuda, grouper, snapper, and sea bass.3 Although the toxin is harmless to fish, it can cause serious gastrointestinal (GI), neurological, and cardiovascular symptoms in humans. Cold allodynia—ie, cold stimuli experienced as painful or hot—is considered pathognomonic.

The patient was started on aggressive therapy, including intravenous acyclovir, as well as steroids, but she showed no improvement.Although the condition is rare, the incidence is on the rise. There were an estimated 20,000 cases of ciguatera poisoning worldwide in 1997,4 and >100,000 cases in 2010.5 In addition, the Centers for Disease Control and Prevention reported 14 “ciguatoxin” outbreaks in the United States between 2009 and 2010.6-8 The endemic area of ciguatera seems to be spreading, as well. Once confined to fish caught in tropical waters like the Caribbean, ciguatera-laden fish have been caught off the coast of South Carolina and North Carolina.9

A triad of symptoms

Patients with ciguatera poisoning may present with the following triad of symptoms:
• GI problems (nausea, vomiting, diarrhea), which usually occur one to 2 days postexposure,
• neurological symptoms (hallucinations, headache, ataxia), which typically occur 2 to 4 days postexposure, and
• cardiovascular symptoms (bradycardia, hypotension), which are the least common and typically occur only in severe cases.10

Our patient’s eating history and onset of symptoms suggested that she ingested the ciguatera toxin in New Orleans the night before leaving on the cruise, yet she did not experience cold allodynia. Her medical treatment was prolonged, with multiple exclusion tests resulting in a 19-day hospital stay.

No consensus regarding Tx

The medical management of this rare condition is still in its infancy, and there is no consensus regarding treatment.11 In addition, while there are specific assays for fish tissue,12 there appears to be no diagnostic test for humans.

 

 

Our patient’s immediate response to a mannitol infusion was consistent with other reported cases of ciguatera poisonings.1 However, mannitol therapy came into question in 2002, when a randomized trial comparing it with normal saline for ciguatera poisoning found that both provided immediate symptom relief.11

THE TAKEAWAY

As tropical fish exports reach new markets and world travel increases, the number of ciguatera cases is likely to continue to rise. The lack of both a specific diagnostic test and an evidence-based treatment highlights the importance of taking a thorough food history—and considering this unusual toxin, as well as more common foodborne pathogens—in patients who present with GI and neurological symptoms.

References

 

1. Palafox N, Jain L, Pinano A, et al. Successful treatment of ciguatera fish poisoning with intravenous mannitol. JAMA. 1988;259:2740-2742.

2. Swift AEB, Swift TR. Ciguatera. Clin Toxicol. 1993;31:1-29.

3. Eastaugh J, Shepherd, S. Infectious and toxic syndromes from fish and shellfish consumption. A review. Arch Intern Med. 1989;149:1735-1740.

4. Lipp EK, Rose JB. The role of seafood in foodborne diseases in the United States of America. Rev Sci Tech. 1997;16:620-640.

5. Schoemaker R, House D, Ryan J. Defining the neurotoxin derived illness chronic ciguatera using markers of chronic systemic inflammatory disturbances: a case/control study. Neurotoxicol Teratol. 2010;32:633-639.

6. Hall AJ, Wikswo ME, Manikonda K, et al. Acute gastroenteritis surveillance through the national outbreak reporting system, United States. Emerg Infect Dis. 2013;19:1305-1309.

7. Pennotti R, Scallan E, Backer L, et al. Ciguatera and scombroid fish poisoning in the United States. Foodborne Pathogens Dis. 2013;10:1059-1066.

8. Centers for Disease Control and Prevention (CDC). Surveillance for foodborne disease outbreaks—United States, 2009-2010. MMWR Morb Mortal Wkly Rep. 2013;62:41-47.

9. Centers for Disease Control and Prevention (CDC). Cluster of ciguatera fish poisoning—North Carolina, 2007. MMWR Morb Mortal Wkly Rep. 2009;58:283-285.

10. Morris JG Jr, Lewin P, Hargrett N, et al. Clinical features of ciguatera fish poisoning: a study of the disease in the US Virgin Islands. Arch Intern Med. 1982;142:1090-1092.

11. Schnorf H, Taurarii M, Cundy T. Ciguatera fish poisoning: A double-blind randomized trial of mannitol therapy. Neurology. 2002;58:873-880.

12. Hokama Y, Nishimura K, Takenaka W, et al. Simplified solidphase membrane immunobead assay (MIA) with monoclonal anti-ciguatoxin antibody (MAb-CTX) for detection of ciguatoxin and related polyether toxins. J Nat Toxins. 1998;7:1-21.

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John Stacey, DO
Laurie Farricielli, MD
Midwestern University, COM, Glendale, Ariz (Dr. Stacey); Scottsdale Shea Hospital, Ariz (Dr. Farricielli)
drfarricielli@cox.net

The authors reported no potential conflict of interest relevant to this article.

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John Stacey; DO; Laurie Farricielli; MD; ciguatera; ciguatera toxin; nausea; blurry vision; hallucinations; ciguatera poisoning; marine toxin
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John Stacey, DO
Laurie Farricielli, MD
Midwestern University, COM, Glendale, Ariz (Dr. Stacey); Scottsdale Shea Hospital, Ariz (Dr. Farricielli)
drfarricielli@cox.net

The authors reported no potential conflict of interest relevant to this article.

Author and Disclosure Information

 

John Stacey, DO
Laurie Farricielli, MD
Midwestern University, COM, Glendale, Ariz (Dr. Stacey); Scottsdale Shea Hospital, Ariz (Dr. Farricielli)
drfarricielli@cox.net

The authors reported no potential conflict of interest relevant to this article.

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THE CASE

A 55-year-old Asian woman was brought to the emergency department by her husband, with symptoms of nausea, blurry vision, headache, and hallucinations. Her husband told us that he and his wife had flown to New Orleans to embark on a Caribbean cruise 5 days earlier. The next morning—their first full day on the ship—his wife became nauseous and her vision was blurred. She went to the ship’s doctor, who treated her for motion sickness.

On Day 3, she developed a right-sided headache at the back of her head and neck. The patient refused to go to the hospital at the first Mexican port and waited until the ship arrived in Belize. She was taken ashore for a computed tomography (CT) scan, which was negative. She stayed the night in the hospital.

The next day, the patient developed weakness and numbness in her left arm. She was seen by a neurologist and given amitriptyline, and underwent a second CT scan. When this scan, too, was read as negative, she and her husband flew home to Phoenix and sought care at our emergency department. There, the patient had a third CT scan, which showed temporal edema suggestive of encephalitis. Foodborne illness—or something else?
Samuel N. Grief, MD, FCFP

A neurologist performed a lumbar puncture and found nonspecific pleocytosis in the spinal fluid. The patient was started on aggressive antiviral therapy, including intravenous acyclovir, as well as steroids, but she showed no improvement. The symptoms continued, and the patient had vivid hallucinations: She reported seeing mermaids waving in the windows and children running around the hospital halls and ceilings.

An extensive serological workup followed, and was negative for: cytomegalovirus, dengue virus, West Nile virus, Lyme disease, coxsackievirus, syphilis, Cryptococcus, Coccidioides, mumps, measles, antinuclear antibodies, lupus, malaria, and herpes simplex virus.

THE DIAGNOSIS

After ruling out the other possible etiologies, and noting that the patient had eaten fish the day before the symptoms developed, the hospitalist, neurologist, and infectious disease specialist agreed that the most likely diagnosis was ciguatera poisoning. A literature search revealed the recommended treatment: a mannitol infusion of a 20% solution, 1 g/kg, with a piggyback of 250 mL over 30 minutes,1 every 6 hours as needed.

A dramatic improvement

The patient’s headache and arm weakness improved within 24 hours of receiving the mannitol. Her mental status improved as well as the blurry vision.

Two days later, the patient received a second mannitol infusion and was discharged the next day, although she still had mild weakness in her left arm and lingering hallucinations. A 2-week follow-up appointment with the neurologist was scheduled so that she could have a third mannitol treatment for her persistent visual changes.

DISCUSSION

Ciguatera poisoning—a little-known marine toxin

Ciguatera toxin is a lipid-soluble, heat-stable marine toxin2 made by dinoflagellates such as Gambierdiscus toxicus in tropical and subtropical waters. Larger fish eat the herbivore fish that have eaten the dinoflagellates and the toxin bioaccumulates until it reaches large predatory fish like barracuda, grouper, snapper, and sea bass.3 Although the toxin is harmless to fish, it can cause serious gastrointestinal (GI), neurological, and cardiovascular symptoms in humans. Cold allodynia—ie, cold stimuli experienced as painful or hot—is considered pathognomonic.

The patient was started on aggressive therapy, including intravenous acyclovir, as well as steroids, but she showed no improvement.Although the condition is rare, the incidence is on the rise. There were an estimated 20,000 cases of ciguatera poisoning worldwide in 1997,4 and >100,000 cases in 2010.5 In addition, the Centers for Disease Control and Prevention reported 14 “ciguatoxin” outbreaks in the United States between 2009 and 2010.6-8 The endemic area of ciguatera seems to be spreading, as well. Once confined to fish caught in tropical waters like the Caribbean, ciguatera-laden fish have been caught off the coast of South Carolina and North Carolina.9

A triad of symptoms

Patients with ciguatera poisoning may present with the following triad of symptoms:
• GI problems (nausea, vomiting, diarrhea), which usually occur one to 2 days postexposure,
• neurological symptoms (hallucinations, headache, ataxia), which typically occur 2 to 4 days postexposure, and
• cardiovascular symptoms (bradycardia, hypotension), which are the least common and typically occur only in severe cases.10

Our patient’s eating history and onset of symptoms suggested that she ingested the ciguatera toxin in New Orleans the night before leaving on the cruise, yet she did not experience cold allodynia. Her medical treatment was prolonged, with multiple exclusion tests resulting in a 19-day hospital stay.

No consensus regarding Tx

The medical management of this rare condition is still in its infancy, and there is no consensus regarding treatment.11 In addition, while there are specific assays for fish tissue,12 there appears to be no diagnostic test for humans.

 

 

Our patient’s immediate response to a mannitol infusion was consistent with other reported cases of ciguatera poisonings.1 However, mannitol therapy came into question in 2002, when a randomized trial comparing it with normal saline for ciguatera poisoning found that both provided immediate symptom relief.11

THE TAKEAWAY

As tropical fish exports reach new markets and world travel increases, the number of ciguatera cases is likely to continue to rise. The lack of both a specific diagnostic test and an evidence-based treatment highlights the importance of taking a thorough food history—and considering this unusual toxin, as well as more common foodborne pathogens—in patients who present with GI and neurological symptoms.

THE CASE

A 55-year-old Asian woman was brought to the emergency department by her husband, with symptoms of nausea, blurry vision, headache, and hallucinations. Her husband told us that he and his wife had flown to New Orleans to embark on a Caribbean cruise 5 days earlier. The next morning—their first full day on the ship—his wife became nauseous and her vision was blurred. She went to the ship’s doctor, who treated her for motion sickness.

On Day 3, she developed a right-sided headache at the back of her head and neck. The patient refused to go to the hospital at the first Mexican port and waited until the ship arrived in Belize. She was taken ashore for a computed tomography (CT) scan, which was negative. She stayed the night in the hospital.

The next day, the patient developed weakness and numbness in her left arm. She was seen by a neurologist and given amitriptyline, and underwent a second CT scan. When this scan, too, was read as negative, she and her husband flew home to Phoenix and sought care at our emergency department. There, the patient had a third CT scan, which showed temporal edema suggestive of encephalitis. Foodborne illness—or something else?
Samuel N. Grief, MD, FCFP

A neurologist performed a lumbar puncture and found nonspecific pleocytosis in the spinal fluid. The patient was started on aggressive antiviral therapy, including intravenous acyclovir, as well as steroids, but she showed no improvement. The symptoms continued, and the patient had vivid hallucinations: She reported seeing mermaids waving in the windows and children running around the hospital halls and ceilings.

An extensive serological workup followed, and was negative for: cytomegalovirus, dengue virus, West Nile virus, Lyme disease, coxsackievirus, syphilis, Cryptococcus, Coccidioides, mumps, measles, antinuclear antibodies, lupus, malaria, and herpes simplex virus.

THE DIAGNOSIS

After ruling out the other possible etiologies, and noting that the patient had eaten fish the day before the symptoms developed, the hospitalist, neurologist, and infectious disease specialist agreed that the most likely diagnosis was ciguatera poisoning. A literature search revealed the recommended treatment: a mannitol infusion of a 20% solution, 1 g/kg, with a piggyback of 250 mL over 30 minutes,1 every 6 hours as needed.

A dramatic improvement

The patient’s headache and arm weakness improved within 24 hours of receiving the mannitol. Her mental status improved as well as the blurry vision.

Two days later, the patient received a second mannitol infusion and was discharged the next day, although she still had mild weakness in her left arm and lingering hallucinations. A 2-week follow-up appointment with the neurologist was scheduled so that she could have a third mannitol treatment for her persistent visual changes.

DISCUSSION

Ciguatera poisoning—a little-known marine toxin

Ciguatera toxin is a lipid-soluble, heat-stable marine toxin2 made by dinoflagellates such as Gambierdiscus toxicus in tropical and subtropical waters. Larger fish eat the herbivore fish that have eaten the dinoflagellates and the toxin bioaccumulates until it reaches large predatory fish like barracuda, grouper, snapper, and sea bass.3 Although the toxin is harmless to fish, it can cause serious gastrointestinal (GI), neurological, and cardiovascular symptoms in humans. Cold allodynia—ie, cold stimuli experienced as painful or hot—is considered pathognomonic.

The patient was started on aggressive therapy, including intravenous acyclovir, as well as steroids, but she showed no improvement.Although the condition is rare, the incidence is on the rise. There were an estimated 20,000 cases of ciguatera poisoning worldwide in 1997,4 and >100,000 cases in 2010.5 In addition, the Centers for Disease Control and Prevention reported 14 “ciguatoxin” outbreaks in the United States between 2009 and 2010.6-8 The endemic area of ciguatera seems to be spreading, as well. Once confined to fish caught in tropical waters like the Caribbean, ciguatera-laden fish have been caught off the coast of South Carolina and North Carolina.9

A triad of symptoms

Patients with ciguatera poisoning may present with the following triad of symptoms:
• GI problems (nausea, vomiting, diarrhea), which usually occur one to 2 days postexposure,
• neurological symptoms (hallucinations, headache, ataxia), which typically occur 2 to 4 days postexposure, and
• cardiovascular symptoms (bradycardia, hypotension), which are the least common and typically occur only in severe cases.10

Our patient’s eating history and onset of symptoms suggested that she ingested the ciguatera toxin in New Orleans the night before leaving on the cruise, yet she did not experience cold allodynia. Her medical treatment was prolonged, with multiple exclusion tests resulting in a 19-day hospital stay.

No consensus regarding Tx

The medical management of this rare condition is still in its infancy, and there is no consensus regarding treatment.11 In addition, while there are specific assays for fish tissue,12 there appears to be no diagnostic test for humans.

 

 

Our patient’s immediate response to a mannitol infusion was consistent with other reported cases of ciguatera poisonings.1 However, mannitol therapy came into question in 2002, when a randomized trial comparing it with normal saline for ciguatera poisoning found that both provided immediate symptom relief.11

THE TAKEAWAY

As tropical fish exports reach new markets and world travel increases, the number of ciguatera cases is likely to continue to rise. The lack of both a specific diagnostic test and an evidence-based treatment highlights the importance of taking a thorough food history—and considering this unusual toxin, as well as more common foodborne pathogens—in patients who present with GI and neurological symptoms.

References

 

1. Palafox N, Jain L, Pinano A, et al. Successful treatment of ciguatera fish poisoning with intravenous mannitol. JAMA. 1988;259:2740-2742.

2. Swift AEB, Swift TR. Ciguatera. Clin Toxicol. 1993;31:1-29.

3. Eastaugh J, Shepherd, S. Infectious and toxic syndromes from fish and shellfish consumption. A review. Arch Intern Med. 1989;149:1735-1740.

4. Lipp EK, Rose JB. The role of seafood in foodborne diseases in the United States of America. Rev Sci Tech. 1997;16:620-640.

5. Schoemaker R, House D, Ryan J. Defining the neurotoxin derived illness chronic ciguatera using markers of chronic systemic inflammatory disturbances: a case/control study. Neurotoxicol Teratol. 2010;32:633-639.

6. Hall AJ, Wikswo ME, Manikonda K, et al. Acute gastroenteritis surveillance through the national outbreak reporting system, United States. Emerg Infect Dis. 2013;19:1305-1309.

7. Pennotti R, Scallan E, Backer L, et al. Ciguatera and scombroid fish poisoning in the United States. Foodborne Pathogens Dis. 2013;10:1059-1066.

8. Centers for Disease Control and Prevention (CDC). Surveillance for foodborne disease outbreaks—United States, 2009-2010. MMWR Morb Mortal Wkly Rep. 2013;62:41-47.

9. Centers for Disease Control and Prevention (CDC). Cluster of ciguatera fish poisoning—North Carolina, 2007. MMWR Morb Mortal Wkly Rep. 2009;58:283-285.

10. Morris JG Jr, Lewin P, Hargrett N, et al. Clinical features of ciguatera fish poisoning: a study of the disease in the US Virgin Islands. Arch Intern Med. 1982;142:1090-1092.

11. Schnorf H, Taurarii M, Cundy T. Ciguatera fish poisoning: A double-blind randomized trial of mannitol therapy. Neurology. 2002;58:873-880.

12. Hokama Y, Nishimura K, Takenaka W, et al. Simplified solidphase membrane immunobead assay (MIA) with monoclonal anti-ciguatoxin antibody (MAb-CTX) for detection of ciguatoxin and related polyether toxins. J Nat Toxins. 1998;7:1-21.

References

 

1. Palafox N, Jain L, Pinano A, et al. Successful treatment of ciguatera fish poisoning with intravenous mannitol. JAMA. 1988;259:2740-2742.

2. Swift AEB, Swift TR. Ciguatera. Clin Toxicol. 1993;31:1-29.

3. Eastaugh J, Shepherd, S. Infectious and toxic syndromes from fish and shellfish consumption. A review. Arch Intern Med. 1989;149:1735-1740.

4. Lipp EK, Rose JB. The role of seafood in foodborne diseases in the United States of America. Rev Sci Tech. 1997;16:620-640.

5. Schoemaker R, House D, Ryan J. Defining the neurotoxin derived illness chronic ciguatera using markers of chronic systemic inflammatory disturbances: a case/control study. Neurotoxicol Teratol. 2010;32:633-639.

6. Hall AJ, Wikswo ME, Manikonda K, et al. Acute gastroenteritis surveillance through the national outbreak reporting system, United States. Emerg Infect Dis. 2013;19:1305-1309.

7. Pennotti R, Scallan E, Backer L, et al. Ciguatera and scombroid fish poisoning in the United States. Foodborne Pathogens Dis. 2013;10:1059-1066.

8. Centers for Disease Control and Prevention (CDC). Surveillance for foodborne disease outbreaks—United States, 2009-2010. MMWR Morb Mortal Wkly Rep. 2013;62:41-47.

9. Centers for Disease Control and Prevention (CDC). Cluster of ciguatera fish poisoning—North Carolina, 2007. MMWR Morb Mortal Wkly Rep. 2009;58:283-285.

10. Morris JG Jr, Lewin P, Hargrett N, et al. Clinical features of ciguatera fish poisoning: a study of the disease in the US Virgin Islands. Arch Intern Med. 1982;142:1090-1092.

11. Schnorf H, Taurarii M, Cundy T. Ciguatera fish poisoning: A double-blind randomized trial of mannitol therapy. Neurology. 2002;58:873-880.

12. Hokama Y, Nishimura K, Takenaka W, et al. Simplified solidphase membrane immunobead assay (MIA) with monoclonal anti-ciguatoxin antibody (MAb-CTX) for detection of ciguatoxin and related polyether toxins. J Nat Toxins. 1998;7:1-21.

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Nausea, blurry vision, hallucinations—Dx?
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