Amnesia
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This is the Pick Your Poison podcast. I’m your host Dr. JP and I’m here to share my passion for poisons in this interactive show. Will our patient survive this podcast? It’s up to you and the choices you make. Our episode today is called Amnesia. Want to know what disease affects both sea lions and humans? What toxin inspired a horror film and has also been used as a deworming agent? Listen to find out!
Today's episode is inspired by a few of my very smart middle school listeners and starts in California. A friend has invited you to stay with her on the coast in a large rental house where her extended family’s gathered for a reunion, planning a weekend of eating, drinking, and hiking along the beach.
You arrive in time for dinner, a seafood feast including oysters, mussels, fish, crab, lobster and sushi. Seated around a large table, the family is laughing and catching up. Knowing you don’t eat seafood, your friend passes you the vegetarian sushi rolls. Your sitting next to her grandfather, a retired surgeon. He regales you with stories about his time as a medic in the Vietnam war. A few hours after dinner, he retires early due to an upset stomach.
At 4am, you’re frantically shaken awake by your friend, saying something is wrong with grandpa. He's been vomiting all night long. The family members were aware, but not alarmed. Now however, he's confused.
You throw some clothes on over your pajamas and go to Grandpa's room. Concerned family members stand around his bedside. He’s actively vomiting. You grab some nausea medicine from your travel first aid kit and tell him to put it under his tongue. Once he stops throwing up, you ask a few questions. Despite having spoken to you for several hours last night, he doesn't remember who you are. You don't make too much of this given that he’s 85, but your friend looks shocked, saying his memory is normally extremely sharp. He then asks where he is and why he’s not at home, clearly not aware they’ve rented this house for the family reunion. This is definitely an altered mental status.
You recommend taking him to the local emergency department. As usual you wouldn’t be the ER doctor in real life. Fortunately, this is fiction so grandpa is your patient.
The emergency department nurse checks his vital signs, noting a normal temperature of 98.5 or 36.9 Celsius. His heart rate is 110 beats per minute, slightly fast. His blood pressure is 120/80, with a respiratory rate of 18 and oxygen saturation 100% on room air.
You start his physical exam with questions to determine his level of orientation. He knows his name and that he’s in a hospital, but he doesn't know the date or the year. The rest of the exam is unremarkable, including clear heart and lungs, no abdominal tenderness and a nonfocal neurological exam with good strength.
In summary, we have an 85-year-old with an altered mental status, a mildly elevated heart rate, and an otherwise unrevealing physical exam. This scenario is very common in the emergency department, so you start your standard work up including labs, a urinalysis to check for a urinary tract infection, and an EKG. I’d do a head CT for things like a brain mass, and an infectious work up including a chest x-ray for pneumonia. Given the vomiting, I'd also check a CT abdomen/pelvis looking for infections or a bowel obstruction. Generally, we’d expect abdominal pain in addition to vomiting, but occasionally in elderly patients’ cholecystitis, infection in the gallbladder, or bowel obstructions present atypically with an altered mental status.
You start IV fluids and order more nausea medicine. His heart rate improves into the 90s. All of his results come back. His EKG and labs are normal, including his creatinine and liver function tests. His urine shows no signs of infection. His head CT is negative, as is the CT of his abdomen.
Your phone beeps with a text from your friend. Several other family members have developed nausea, vomiting and diarrhea. All are mildly ill, no one else is confused. Maybe everyone got a stomach virus at the same time, but more likely this is a foodborne illness, like food poisoning. You’re glad you ate the vegetarian option, rather than the seafood.
Can we test for food poisoning? People love to come to the ED asking for this. We rarely do. Why? Yes, we can test for some infections in the stool, but the results take days to come back, so they aren’t useful. Either way most cases of food poisoning are mild and resolve, like stomach viruses, with time and antibiotics aren’t routinely recommended.
Your friend says grandpa ate only cooked seafood, specifically fish and mussels. He didn’t eat anything from the raw bar, having had a bad experience with oysters in the past. Question #1. Properly cooked food rules out the possibility of foodbourne illness.
A. True
B. False
Answer: B false. While cooking does kill most bacteria, it doesn’t kill everything. More on this in a minute.
Does our patient have food poisoning? Obviously, nausea and vomiting shortly after a meal, along with the history of other ill family members raises concern. But have you ever heard of some one with food poisoning being confused? Probably not. His altered mental status is a red flag. Sure, an older person with a severe case of food poisoning could become altered. But this isn’t a severe case of food poisoning. He’s only had symptoms for 12 hours. He hasn’t vomited since the nausea medicine and reports only 1-2 soft stools, no significant diarrhea. Dehydration can certainly cause an altered mental status, but again his creatinine was normal and his heart rate came down with fluids, so he’s not dehydrated.
The nurse calls you back to the bedside, concerned because he’s now more agitated. He points to the blood pressure cuff, asking what’s squeezing his arm, telling you to take it off. This from a retired physician? Admittedly he’s a surgeon and surgeons don’t like using things like blood pressure cuffs and stethoscopes, preferring scalpels, but still he doesn’t remember what a cuff is for? This is not good. The nurse says he’s been getting out of bed and trying to leave, he no longer knows he’s in a hospital. His mental status has deteriorated, on our watch, in the few hours he’s been in the hospital. Worse, our workup hasn’t even given us a hint as to the cause.
Question #2. What medical problems does our patient currently have?
A. Amnesia
B. Dementia
C. Delirium
D. Psychosis
Answer: A and C. Amnesia is the medical term for memory loss. We don’t use the term a lot, it’s been co-opted in a dramatic fashion by Hollywood, but any memory loss, and there are many different types, are amnesia. He’s also delirious, meaning confused and disoriented. Dementia, like Alzheimer’s, occurs slowly over a longer period of time. Psychosis includes seeing things that don’t exist like auditory or visual hallucinations.
We need to come up with something, a working diagnosis at least. We have a bit of a dilemma, here. Common things being common, if the whole family is sick with food poisoning, it’s most likely our patient has food poisoning too. I like, in my practice of medicine, when the diagnosis falls in line with Occam's razor. Occam’s razor is when all of the symptoms fit with a single diagnosis. Neat and elegant. It's what we do on this podcast, taking the patient's symptoms and narrowing them down to fit the single toxin.
But, I don’t like this altered mental status, and I’m reluctant to dismiss it because I don't think it fits with a mild case of food poisoning. You don’t need me to tell you many things causing an altered mental status are life-threatening. In real life, the patients haven't read the textbook as we like to say, and often things are much messier, following Hickam's dictum rather than Occam’s razor. Dr John Hickam said the patient can “have as many diseases as they damn well please.”
What now? The next step in the emergent evaluation of delirium and an altered mental status, is probably a lumbar puncture, or a spinal tap, putting us between a rock and a hard place. The lumbar puncture will diagnosis meningitis, or more likely in our patient, encephalitis. I hear you saying meningitis is a life-threatening disease, just do the LP. True. It’s also not that simple. An LP is invasive, and more importantly difficult to do on a patient who won’t cooperate and doesn’t understand why they’re undergoing a painful procedure.
The patient himself can’t consent, as he’s altered. You have a long discussion with your friend, and the patient’s wife and daughter about the risks and benefits. They decide they want the procedure. Fortunately, with the help of a little sedation, he’s cooperative. You send the spinal fluid to the lab for analysis.
While awaiting the results, you admit him to internal medicine. A few hours later, the LP results come back negative. Good news, no sign of meningitis or encephalitis. Your friend calls you from upstairs, crying. Her grandfather is having a seizure. Bad news. The internal medicine team gives him an antiepileptic, seizure medicine, and orders an MRI and an EEG.
As we've discussed in the past, epilepsy is common typically beginning in childhood or young adulthood. New onset seizures in older patients are much more worrisome because they are typically a marker of other problems, like cancer or infection. You speak to the internist and become even more concerned when he says it was a unilateral seizure, occurring only on the patient’s right side. He thanks you for doing the LP earlier, the negative result helps narrow down the causes. You check in with your friend about the other family members, everyone else is getting better, no one else is confused.
We could talk at great length about differential diagnosis for altered mental status, vomiting, and focal seizures but that would take all day. Let's focus in on the likely culprit, the seafood dinner. A foodborne illness remains likely, but this clearly isn’t a typical case of bacterial food poisoning, so let’s consider some other options.
Is this an allergic reaction? Anaphylaxis causes nausea and vomiting, yes, but he doesn’t have a rash, difficulty breathing, or anything else you’d expect.
Seafood can carry vibrio cholera. Yep, cholera causing profuse watery diarrhea. Remember the description of rice water stools due to cholera and arsenic? Our patient’s main issue at this point is not vomiting or diarrhea, but an altered mental status so no to vibrio.
Hepatitis A is found in oysters, for example. Definitely vomiting, but also jaundice and elevated liver function tests which he doesn’t have.
Scombroid caused by improperly stored fish, causes flushing, nausea, vomiting and abdominal pain. Bacteria present in the fish break down histidine to histamine causing the symptoms which are mild and short-lived. Cooking doesn’t stop scombroid or another disease called Ciguatera. Ciguatera, again from fish, causes generalized weakness, vomiting and diarrhea. Patients develop and unusual and characteristic symptoms, reversal of hot and cold sensations. Rather than improper storage, it’s cause by a dinoflagellate ie algea on the fish. Ciguatera doesn’t fit, but dinoflagellates bring us to another group of diseases caused by harmful algal blooms.
Question 3. Time to Pick Your Poison! Which of the following do you think our patient has?
A. Diarrhetic shellfish poisoning
B. Paralytic shellfish poisoning
C. Neurotoxic shellfish poisoning
D. Amnestic shellfish poisoning
Answer: A. Amnestic shellfish poisoning. Each of these diseases is caused by different algae, causing different syndromes. In the interest of time, today we are going to focus only on Amnestic Shellfish poisoning, also called ASP. It’s caused by microscopic algae, diatoms, also called microplankton, named Pseudo-nitzschia. The organism produces domoic acid, the actual toxin responsible for the symptoms, including nausea, vomiting, diarrhea, dizziness, short term memory loss, confusion, seizures, coma and death. Interestingly, the risk of developing more severe symptoms of ASP after exposure to domoic acid, increases with age and is more likely to occur in men.
What does domoic acid do? It binds to glutamate receptors in the brain. If you recall from previous episodes, glutamate is an excitatory neurotransmitter. Domoic acid prevents glutamate receptors from closing, resulting in overstimulation, clinically manifesting as seizures.
Amnestic shellfish poisoning was first described after an outbreak in Canada on Prince Edward Island in November 1987 due to contaminated mussels. There's a very nice description of the epidemiological investigation published in the New England Journal in 1990 if you’re interested. It also causes neurons to die. Autopsies on patients who died showed changes in the hippocampus and amygdala, regions of the brain associated with memory and learning.
Back to our patient. Can you test for domoic acid? Yes, but not in a hospital lab. The right course of action would be to call the local health department about the outbreak and for help with where and how to send specimens for testing. The results won’t come back in a timely fashion, as is typical with other toxicology testing.
You ask your friend about the seafood. She says most of it was catered by a local restaurant. The mussels, however, an uncle found and harvested in a cove near the house. Uh oh. Commercially raised seafood undergoes rigorous safety testing, so algal diseases aren’t a risk. Foraged shellfish, of course, is another story. You speak with the physician at the local health department. He tells you there’s an advisory not to eat seafood harvested from the local beaches due to risk of algal blooms at this time of the year. In fact, many coastal areas post maps and schedules reporting safety of foraging different types of species.
Question # 4. If the uncle harvesting the mussels had looked closely, he could’ve identified algal contamination of the water.
A. True
B. False
Answer: B False. These types of outbreaks are classically associated with red tides where algae overgrowths turn the water red. Other colors are possible including yellow, green and even purple. Clear water doesn’t mean it’s safe. Pseudo-nitzschia, in fact, doesn’t change the water color. Thus the term harmful algal blooms rather than red tides. These episodes are increasing as global warming increases ocean temperatures. How does excessive algae in the water result in human poisoning? Bioaccumulation. As bivalves, like oysters and mussels, filter water, the algae accumulate and can be passed on to larger animals who eat the seafood, like crabs, lobsters, birds, sea lions, whales and humans.
ASP and other algal poisonings are uncommon in humans, but algal blooms make water unsafe to drink, fish unsafe to eat, and kill marine life. Even the air may be contaminated, causing asthma exacerbations in susceptible beachgoers.
Back to our patient. He has several more seizures, but eventually recovers and returns home. He continues to have short-term memory loss and has had to be reintroduced to his great grandchildren several times. Your friend says he’s been practicing with their photos and showing signs of improvement. The rest of the family recovered after a day of vomiting with no other symptoms.
This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings. If I’ve learned one thing from this podcast, its wherever you find a toxin you'll also find a medicine. Seaweed containing low levels of domoic acid in Japan has been used since at least the 9th century as an antihelminth, or a deworming agent. Toxicity is not reported from its medical use, presumably due to the low concentration.
As I said, ASP disease is rare in humans. However, it’s not rare in marine life. In 2023 in California, amnestic shellfish poisoning and domoic acid affected sea lions, contaminating their dietary staples of sardines and anchovies. The unfortunate animals washed up on shore altered lethargic confused and having seizures. Many were treated with IV fluids and anti-seizure medicine. Domoic acid toxicity affects marine life from small oysters all the way up to very large animals like blue whales.
Earlier I mentioned the middle schoolers reading a short story which inspired this episode. It’s today's pop culture consult. What movie was based in part on a real life domoic acid toxicity? Question 5.
A. The Birds
B. Jaws
C. Deep Blue Sea
D. Arachnophobia
Answer: The birds. Alfred Hitchcock based his 1963 movie The Birds in part on the Daphne du Maurier short story of the same name about birds attacking a farmer. He also took inspiration from a real-life event in Capitola California in 1961. Locals described birds falling out of the sky, dive-bombing houses and cars, screaming like babies, and vomiting up fish. At the time the cause was unknown, later research in the ‘90s on preserved specimens revealed the birds had domoic acid toxicity from the fish they ate.
Researching the podcast, I was horror struck by the descriptions of filming during the movie. Despite spending the equivalent of 2 million of today’s money on mechanical birds, the onscreen appearance looked fake. Instead, 25,000 real birds, crows and ravens were captured. The poor birds bit and scratched the handlers and actors. Apparently, whiskey was mixed with the bird’s food to sedate them for some scenes. In others, birds were thrown at actress Tippi Hedren for days attacking and pecking her. Birds were even tied to her clothing. As if that wasn’t enough, the birds were infested with lice which was transferred to crew members on the set. Yikes.
Last question in today’s podcast. Chronic exposure to domoic acid in sea lions causes which of the following problems.
A. Epilepsy
B. Heart failure
C. Brain damage
D. Behavioral changes
Follow the Twitter and Instagram feeds both @pickpoison1 and you’ll see the answer when I post it. Remember, never try anything on this podcast at home or anywhere else.
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While I’m a real doctor this podcast is fictional, meant for entertainment and educational purposes, not medical advice. If you have a medical problem, please see your primary care practitioner. Thank you. Until next time, take care and stay safe.