A 30-year-old chemistry PhD candidate develops progressive difficulty walking and speaking months after a seemingly minor laboratory incident. His stroke evaluation, MRI, and lumbar puncture reveal nothing. What toxic exposure can hide for months, cross ordinary laboratory protection, and turn only a few drops into a fatal neurologic mystery?
Transcript
This is the Pick Your Poison Podcast. I’m Dr JP. ER doctor. Toxicologist, and unapologetic lover of all things poison. Want to know What toxin is so terrifying that it killed its own creators, penetrates standard laboratory precautions in seconds, and can shut down an entire research facility if a single drop spills?"
Stay right here to find out.
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Today’s episode starts with a toxicology consult. You’re on call for the tox service when you get a consult from the neurology team. They ask you to see a patient in room 451. They say he’s a 30-year-old PhD candidate who has had a progressive neurological decline they cannot explain.
You walk into the room to see a 30-year-old man lying in bed. He’s awake and alert. He says hi when you enter and, at first glance, is very well-appearing, especially for someone who’s been in the hospital for a week. As I’m sure you know, the time that patients stay in the hospital has declined dramatically over the years. For example, in the 1950s, if you had a heart attack, you’d stay in the hospital for six weeks. Now, it’s a day or two. So, if you’ve been in the hospital for a week, in medical terms, this is a very, very long time. And this guy is not in the ICU on a ventilator, for example, so what’s going on here?
He looks well—that is, until he sits up in bed. You notice he’s shaking, not like trembling in fear, but rather his whole upper body, as soon as he lifts it off the bed, appears to be rocking back and forth. You see he’s struggling to control it and try’s to grab the railings of the bed to steady himself. He misses several times before getting a grasp on it.
You introduce yourself and say you’d like to go through what you’ve learned from his chart, make sure you understand correctly, and see if he has any additional details to add.
The neurologists tell you he has a past medical history of asthma but was otherwise healthy prior. He occasionally took an albuterol inhaler for the asthma but doesn’t have any other medical problems. He was admitted to the hospital a week ago for difficulty walking and difficulty speaking. The emergency department did a stroke evaluation, including a CT scan, lab work, and an MRI. These tests all came back normal, ruling out a stroke.
The neurology team recommended a lumbar puncture to rule out things like encephalitis. It was also negative. The patient had fallen several times a home, so he was admitted. There was no evidence of multiple sclerosis or other neurological problems with long names and complicated pathology. Good news on one hand, because nobody wants to be diagnosed with these things, but bad news on the other, because the patient’s symptoms continued to worsen, and no one—not the neurologists or the internists—could find a cause.
You ask him how he’s feeling today. His speech is a little bit garbled but understandable, and you can see he’s working hard to try to communicate with you to answer this simple question. This is clearly not the fluent speech of a 30-year-old PhD candidate. He says he’s having some crampy abdominal pain and diarrhea, but he is mainly concerned that his difficulty speaking and walking has continued to worsen. You ask if he has taken any supplements or any medicines other than the albuterol inhaler. He says no. You ask about tobacco, alcohol, and drugs. He says no again. You move on to the physical exam.
His vital signs are as follows: temperature 98.6°F, or 37°C; heart rate 75 beats per minute; blood pressure 120/80; respiratory rate 18; and oxygen saturation 100% on room air.
He’s awake and alert and answering questions appropriately, though his speech is garbled, as noted. Otherwise, his cranial nerves are intact, including his extraocular movements, His neck is supple, no signs of a stiff neck or meningitis. Heart and lungs are normal, no abdominal tenderness. His muscle strength is good.
As we noted before, he is having shaking of his body. This is called truncal ataxia. It’s usually a sign of something wrong in the cerebellum.
Question #1. What cerebellar toxin do we see very commonly in the emergency department?
1. Fentanyl
2. Alcohol
3. Acetaminophen, ie Tylenol or paracetamol
Answer. B. alcohol affects the cerebellum that's why people who are drunk can't walk straight as it affects balance and posture. Acetaminophen and fentanyl with typically use, at least, don't affect it.
You do a few quick tests to check his coordination. You ask him to take one finger and touch his nose, and then reach out to touch your finger. He keeps pointing past it, which we call past-pointing. You ask him to run the heel of one foot up and down the shin of the other foot. That should be pretty simple. I’m sure you can do it easily right now, and he’s not able to do it. These are more cerebellar findings, which the neurologists tested for and documented in much greater detail than our quick bedside tests here.
If you want to know which doctors do the best physical exams, it’s hands-down neurologists. They can examine a patient at the bedside and pinpoint exactly where a lesion is in the brain. It’s amazing.
There’s one question we haven’t asked that we need some more details on. Question #2. Is it:
•Hobbies
•Occupation
•Relationships
•Automobile
Answer: When we have a difficult toxicology case, we always want to know about the patient’s occupation. That said, if you answered hobbies, full credit. As you know, some hobbies may turn toxic—home brewing for example. If anybody from law enforcement is listening, let me guess: Did you say relationships? Good point also. Very often, if malicious poisoning occurs, a romantic partner is involved. And if you said automobile, there is definitely toxic stuff related to cars, but none at the top of my list here.
The patient says he doesn’t drive. And doesn’t have a relationship or a hobby because he’s too busy with his occupation, i.e., working to get his PhD. You ask him his discipline, and he says chemistry.
Uh-oh. He could probably be poisoned with just about anything.
You ask the patient about his research. He talks for several minutes. You have difficulty understanding anything he’s saying—not in this case due to dysarthria, or garbled speech, but rather because you simply don’t know what he’s talking about.
You try a different approach and say, “What toxic compounds are in your lab?” He starts on a long list. These you can understand. They fall into several categories. Things like hydrochloric acid. We talked about caustics in prior episodes. He doesn’t have skin or esophageal burns, so this doesn’t fit. Benzene, a very toxic compound; however, it causes leukemia, not his problem. Nitrogen gas, which could be an asphyxiant, meaning he could stop breathing. Doesn’t fit. Cyanide salts.
Question number three. Could this be cyanide toxicity?
1. Yes
2. No
Answer B. No, cyanide is extremely toxic, as you know, but it causes cardiac arrest, not ongoing neurological problems. The lab has compounds causing hepatotoxicity, i.e., liver failure. His liver function tests are normal.
Basically, none of these fit.
Let’s look at this from the angle of cerebellar toxins. I mentioned alcohol is right up there on the list, but this is clearly not alcohol intoxication. Another one that would be great is phenytoin, or Dilantin, an antiepileptic. However, he’s not taking any medicines. It’s easy to send a level, but I don’t know how he would get into it accidentally. Lithium—also easy to send a level—immunosuppressants and chemotherapeutics, but he says no meds.
Drugs of abuse are on the list—cocaine, fentanyl, and definitely PCP—but he’d have other symptoms, not just cerebellar toxicity.
Heavy metals can cause it. We’ve talked about lead toxicity before. This doesn’t quite fit, while you could definitely get these symptoms, I would also expect some peripheral nerve problems, like leg weakness, etc. But the patient did mention he was having abdominal symptoms, and whenever you have GI symptoms with neurological symptoms, I always like to think about heavy metals.
You run through the list out loud, telling him you don’t think lead fits, and he agrees that there’s none in his lab as far as he knows. Thallium, called the poisoner’s poison, but toxicity causes extremely excruciating pain in the extremities, as well as loss of hair and eyebrows, so no. Manganese, in miners, causes significant neurological degeneration. He says no to manganese. Mercury, you say, doubting that there would be mercury in a lab.
Question #4. Time to pick your poison. He does report a potential exposure to a metal. Could this be:
•Mercury
•Lead
•Thallium
Answer: A. Mercury.
He reports he got a few drops of a mercury compound called dimethylmercury on his latex glove but says it was a few months ago, and it was only a few tiny drops.
We’ve talked about mercury in the past in the Mad as a Hatter episode. Briefly, there are 3 main types of exposure. First, elemental, like if you break open an old-fashioned thermometer. You can hold the mercury in your hand, older listeners have probably done this, without getting toxicity. Poisoning occurs when the vapors get into your lungs. If you vacuum up the mercury after a thermometer breaks, this is risky.
Then there’s inorganic mercury exposure, typically mercury salts, and often from occupational exposure. The Alice in Wonderland Mad Hatter character is a great description. He has erethism, or pathological shyness, a tremor, and an altered mental status. This picture really doesn’t fit with our patient.
The third type is organic mercury exposure. This is from fish high in mercury, for example. Though, as I said before, benefits of eating fish and its protective effects on your heart far outweigh the small amount of mercury exposure you get. But if you have massive organic mercury, you end up with the Minamata Bay disaster in Japan. This is where a corporation was dumping massive amounts of methylmercury into Minamata Bay, and those nearby developed horrible neurological problems. You can listen to that episode for more.
Dimethylmercury is a different form of organic mercury exposure. It’s extremely rare. If you’ve heard of it at all, it’s probably because you were reading the news in the past few weeks, which inspired me to do this episode. Essentially, in Boston, a chemistry student arrived at the emergency department saying he had synthesized dimethylmercury in a lab at MIT. It resulted in a citywide HAZMAT response because this compound is so extremely toxic.
But the patient says he was wearing gloves, and he was only exposed to a drop or two. Question 5:
This is dimethylmercury exposure.
•Yes
•No
Answer: A. Yes. This is all it takes to become poisoned by this extremely toxic compound. But what about the gloves, did I hear you say? Well, unfortunately, it’s a very lipid-soluble substance, meaning that it can and does penetrate through regular latex gloves.
You hope that the patient can’t see the look of horror passing across your face under your mask before you manage to freeze it back into your neutral doctor’s expression.
“I think we should do some mercury testing,” you say to the patient, then step out of the room to compose yourself. If it is dimethylmercury exposure, there is essentially no treatment, and it’ll almost certainly be fatal.
You catch the neurology team rounding in the hospital and express your concerns. The neurology attending’s eyes widen, and she says, “Dimethylmercury? Isn’t that the one that killed the Dartmouth scientist?”
You say yes, and a grim expression crosses her face.
Okay, so what is dimethylmercury? First, it’s extremely rare. Most of what we know about it comes from a Dartmouth scientist who was poisoned in the 1990s and a few occupational deaths in the 1800s. We never have all the information we’d like in toxicology, but a few human cases is especially unusual. Fortunately.
“How do you treat this?” the neurology intern asks.
You and the neurology attending look at each other, then back at the intern.
“Well,” you say, “we can try to chelate him, but the likelihood of it working is low, The truth is his prognosis is grim.”
“What chelator would you use?” he asks.
It’s a good question. We’ve talked about options for chelation in the past. And as I’ve said before, different chelators are available in different countries, so we’ll keep this fairly general. We have an oral option called succimer. And then there are intravenous and intramuscular options like dimercaprol, also called British anti-Lewisite, and DMPS. Oftentimes, we determine what chelator to use based on the severity of the patient’s symptoms, but in this case, we have a different consideration.
One of the risks of chelation is actually increasing the heavy-metal concentration in the brain. This is usually temporary, because as the metal is chelated from the body, it also shifts out of the brain. Chelators can’t cross the blood-brain barrier and don’t go into the brain itself. We do worry about this risk a little bit, but in most cases of heavy metal toxicity, the overall benefit in removing it from the body far outweighs the risk of a small, temporary increase in the brain.
Methylmercury is an exception.
Because it’s mostly in the brain. It’s lipid soluble, making it easy for it to cross the blood-brain barrier. Succimer is least likely to increase the brain concentration, and is therefore the preferred chelator for this toxin.
Is there a test for mercury? Yes, you can definitely test for mercury in the blood and urine. Also the hair, though in the hospital, we usually do body-fluid, not hair analysis.
The patient’s 24 hour urine mercury level comes back at 200 mcg. Massively high. Normal is less than 10 and more than 50 is considered toxic. Confirming your diagnosis.
You recommend a course of succimer. The next day, the intern approaches you excitedly, saying the mercury levels have increased in the urine to 15,000 mcg. Question 6.
This is:
A. Good
B. Bad
It does mean the chelation is working and pulling mercury out of the body to be excreted in the urine. Unfortunately, in the case of the Dartmouth professor, chelation did increase urinary mercury but ultimately did nothing to treat the disease.
To illustrate just how toxic dimethylmercury is in real life, let me tell you her story. She tragically died after an accidental exposure in the ’90s. Her research was on on the toxicity of heavy metals. She reported getting just a few drops of dimethylmercury on her hand. She was wearing latex gloves at the time. This happened in August. In January, she was admitted to the hospital complaining of difficulty walking and speaking. She also complained of nausea, abdominal pain, and diarrhea. Her whole-blood mercury level came back at 4,000 micrograms per liter. What’s normal? One to eight. Her urinary mercury came back at 200 micrograms per liter. Chelation with succimer was started. Before the chelation, the amount of mercury in her urine over a 24-hour period was 250 micrograms. During chelation, it went as high as 40,000 micrograms. Despite this, her clinical status continued to deteriorate. In February, 22 days after the neurological symptoms began, she was in a vegetative state. Per the patient’s advance directives, care was withdrawn in June, and she died.
On autopsy, it was found that she had extremely high concentrations of mercury in her brain, six times higher than what was measured in her blood.
As I said before, there are only a few other published cases of dimethylmercury toxicity, and all were fatal. In 1865, two people helping to synthesize dimethylmercury for the first time died several weeks later, and the third reported death that we know about was also in a laboratory worker after synthesizing it.
Inhalation of the vapors of dimethylmercury can be toxic. The Dartmouth professor was working in a hood, so she shouldn’t have inhaled it. Questions then arose about her gloves. Permeation studies on latex gloves show that they do not stop dimethylmercury, and workers need special PPE—for example, a flexible plastic glove underneath a heavier neoprene glove.
One good thing that did arise from this tragic death is that use of dimethylmercury has been even further restricted. It used to be used to calibrate NMR spectrometers, used to identify chemical structures. This has now changed. In addition, I understand it’s very difficult to synthesize dimethylmercy by accident, so hopefully the healthcare practitioners out there listening will never see a case of this. But if I’ve learned one thing from toxicology, it’s that somebody out there is always doing something they shouldn’t or isn’t doing what they think they’re doing.
Back to our patient. You and the hospital team have a difficult conversation with him about the diagnosis and more importantly, the prognosis. After another week, he's in a vegetative state. His parents say their son expressed his wishes while still lucid. He didn’t want to be kept alive by artificial means. He dies peacefully a few weeks later.
Fortunately, this is a fictional case as our all our cases, but it is based on real poisonings.
Why does dimethylmercury cause such a delayed onset of symptoms? It’s a combination of slow toxicokinetics (distribution, biotransformation, and gradual CNS accumulation. Damage accrues silently until a functional threshold of neuronal loss is crossed and symptoms appear.
The last question in today's podcast is also our pop culture consult. In the Alice in Wonderland movie with Johnny Depp as the Mad Hatter do you know why his hair was orange and what it has to do with mercury toxicity?
1. A step in the dying process turned the furs orange
2. Orange hair is a side effect of mercury poisoning
3. Hatters wore orange uniforms
Follow the X and Instagram feeds both @pickpoison1 for the answer. 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. Until next time, take care and stay safe.