#1

While you scroll through these intriguing posts, a team of doctors, and other experts, is hard at work trying to solve some of the most puzzling medical cases currently playing out. The Undiagnosed Diseases Network (UDN) is a research study funded by the United States' National Institutes of Health.
To date, they've received 8967 cases, have managed to diagnose 1054 and have discovered 50 new conditions. Among the cases UDN is currently working on is one of a 15-year-old teenager who suddenly experienced a decline in language and memory (cognitive regression), sudden muscle jerks (myoclonus), increased muscle tone in her lower limbs (limb hypertonia), and more.
#2

Now, that’s not an uncommon presentation for people in their early twenties but there was just something odd about him. He was very off and intermittently agitated but I couldn’t put my finger on it, it was weird, it wasn’t quite like the other new-onset schizophrenia patients we see. (I’m an ER doctor)
He was an otherwise normal guy. College graduated. Gainfully employed. No medical problems.
Workup totally benign. Really starts just looking like a first break psych presentation
A few hours in he spiked a fever and I decided to do an LP. These we rarely do without a good reason but none of it fit, and LP had low probability of showing anything meaningful, but I thought with the fever I at least had to try.
LP goes without issue and since I didn’t really know what I was looking for I clicked pretty much all the boxes for CSF labs I could send…
One of which came back positive. He had anti-NMDA Encephalitis. Which is incredibly rare and unfortunate.
Edit: For anyone interested there’s a fascinating book called Brain on Fire about this condition.
Edit 2: For those who wanted an update on him, I followed his chart for a little. There was clinical value in learning more about this outcome so that I or others I work with might be better clinicians by recognizing the patterns/symptoms. He never came back around. Had multiple seizures. Ends up on a ventilator and got transferred to our academic mothership. He couldn’t be extubated successfully so ended up with trach & PEG. I stopped following the chart after awhile, I can only argue that there’s clinical value in it without it becoming unprofessional for so long, then it would be more personal curiosity driven which is not appropriate. In that time that I did check, I never saw any substantial improvement.
#3

There's also the case of a 5-year-old little girl who presents with developmental delay, immunodeficiency, and skin changes.
"The participant was born at 32 weeks and was not breathing (respiratory failure)," reads the UDN site, adding that the pregnancy was complicated by twins and the mom's use of substances. "Her twin passed away at birth due to multiple birth defects (including club foot, omphalocele, heart displacement)."
#4

#5
I moved to my hometown and had just started working at the ER of a new hospital, when I listen to my collegues talk about a strange case.
A 19 yo woman has been having strange neurological symptoms. She started with some mild dizzyness that was suspected as a inner ear issue that was tested and discarded after she developed difficulty to do fine movements with her hands. She had been tested with a TP and a CT scan of the brain back then, with no abnormalities showing up.
After that she started to have trouble speaking and was seen at a private clinic (we have public and private health centers here), where she was admitted for a week with nothing showing up on her new CT scan, lab work, spinal tap, MRI. She was sent home where the mother found a progression on her speak difficulty and decided to seek help at the small town hospital where they live, to then end up being sent to our ER, with the suspicion of an encephalitis vs a ruptured aneurism.
While I was writing up some papers of my own patients, my collegues were talking about the case and it sparked my curiosity because I had known of 2 other similar cases back at the hospital I had done my residence. Heck, I even remember taking with the neurology and the neurosurgery residents about those 2 cases for hours, while also talking about other prion diseases (Kuru, Fatal Familial Insomnia and Scarpie).
I remember looking at the older clinician of this new hospital (who ended up as one of my best friends after a few months there) and asked if they were suspecting Creutzfeld Jakob, and she looked at me at disbelief.
We then talked to the neurologist who came to examine her and he also agreed on our observation
She got tested and ended up passing away a week before her test came back as positive.
Scary as heck disease.
#6

The surviving twin was slow to develop language and motor skills. At 2 years old, she began using fewer words before stopping speaking altogether. Currently, she can speak in short sentences.
"She has issues with balance and falls frequently. She is taller than expected for her age. However, her weight is proportional to her height (98th percentile for weight and height)," UDN notes. "The skin on the bottom of her right foot is thickened and cracking (palmoplantar keratoderma). She also has eczema. Starting at 3, she has had many treatment-resistant warts."
#7
Super weird. Sometimes it's actually a zebra.
#8

#9
Back in 2009, I started having right shin pain. Achy pain that wouldn't go away. It progressed rapidly in a few hours to what felt like being hit with a sledgehammer. I worked at a hospital and so I went to the ER every day for a week straight. The pain was almost unmanageable and nothing helped it. If I moved around, it got a little better but if I stood still the pain migrated to my ankle and felt explosive.
I had: x-rays, ultrasounds, blood cultures, and a blood test after being dismissed for the first few days. I had 3 days of IV antibiotics with the assumption it was an infection although the blood work didn't really show much. I saw a Rheumatologist who thought maybe it was a rheumatological disorder.
But the pain persisted. My leg looked fine. There was no swelling. No redness. No tenderness. You could push on all parts of my shin and ankle and it didn't increase the pain. The pain was just there.
A week and a bit after it first started, I bent down at work to plug in my space heater and immediately felt like I couldn't breathe. My heart felt like it was slamming through my chest. At first I thought it was my asthma and maybe some anxiety because of the pain and I almost left to go home. But my heart rate would not come down and I was really having trouble catching my breath.
My coworker wheeled me to the ER and they gave me a CT scan which showed a massive saddle pulmonary embolism. I think the report said something like 80-85% occlusion. My heart rate laying still was in the 160s and any movement spiked it into the 180s and above (which constantly set off the alarms haha). The doctor I had seen to remove the IV after the short course of antibiotics said "I bet you thought we thought you were crazy."
I spent a night in the ER and then went to the ward for 2 days and then I went home. When I saw the internal medicine doctor in followup, she had a med student with her and the doctor said to the student "in your career, you will never see patient with this type of clot burden who didn't end up in the ICU or the morgue."
Why did I have the clot? No one knows. I went through all genetic testing and nothing came back. The best guess is that I had taken Yazmin (a birth control pill) for just 30 days before developing the clot and that's what triggered it.
One of the cases the team has managed to crack is that of baby Ezra. When he was two weeks old, his mother noticed that his skin had an unusual, swirling pigmentation. Two weeks later, his head had grown unusually large, and he was having trouble lifting it. He had a seizure at 6 months old.
The family approached the UDN, and three months later, the medical mystery was solved. "Ezra had a rare genetic disorder called Smith-Kingsmore syndrome caused by changes to the MTOR gene, which plays an essential role in cell growth and function." reports the Association of American Medical Colleges (AAMC) site. "Only about 10 in 10,000 individuals are affected by MTOR disorders."
There is no cure or treatment for the syndrome but his mother says she's relieved that Ezra has finally been diagnosed.
#10
When my little brother was an infant in 2001, he had a real bad intussusception, almost passed away, but thankfully he made it. An intussusception, btw, is when your intestines get folded and tangled together. I recall the doctor comparing it to when you take your sock off and it comes off all inside out.
When my younger cousin was a kid, ~2013(?), he ALSO had an intussusception. His was solved with them blowing air through his intestines, he didn’t have to go through all the surgery and colostomy bags and drama that my brother did. Still odd and scary though.
In 2018, my mf’ing CAT got an intussusception... or something similar. I had to rush her to the closest vet for emergency surgery, and they removed a whole mess of her colon. The vet described her intestines as “tangled like a garden hose”. What the hell.
AND NOW, at this moment, as we speak, my future father-in-law is in the ICU of a hospital after getting a section of his intestines removed. Tomorrow he shall go back into surgery to have things reattached.
So the question remains: what is it about me that causes people nearby to get their insides all messed up? My intestines are fine as far as I know, all I’ve ever had removed is my gallbladder. How mysterious.
#11
#12
#13

People will have excruciating pain but all the blood tests and scans in the world are normal. No doctor believes these people are pretending. There are theories as to how this happens but no one knows why it happens. Why is it that some people are prone to getting functional disorders and others are not.
#14

#15
So we had a premature baby in my NICU that just kept having issues, not gaining weight. Not eating. Poor temp control. Mom had hypothyroidism, but the family was very crunchy and felt they knew better than doctors. So instead of taking levythyroxine she took over the counter iodine supplements that she dosed out herself after talking to her "naturopath". Well turns out the iodine crosses the breastmilk and he didn't tell her that.
And since iodine was a supplement and not a medication she never told the lactation consultants.
Anyways this kids thyroid levels were all over the place and she exhibited all of the symptoms of neonatal hypothyroidism. They started her on all the medications and none of them worked.
Eventually one of our doctors, that has been a neonatologist since before neonatology existed as its own specialty.
He sits down and is talking with the family that are VERY crunchy and VERY upset that their daughter isn't improving. He just straight asks the mom "Do you take iodine?" She says that she does. The entire unit just breathed a whole sigh of relief. And the biggest irony much like a case in House, the baby's condition was completely inflicted upon her by her mother, who swore that she knew better than the doctors.
#16
I was having weird “spells” where I could barely move or speak and was mostly unresponsive. Awake, aware, just sort of trapped in my own body. I’d feel fine but so tired afterwards. Once it happened at work they sent me to the doctor in the middle of my shift. But by the time I got to see her, I was fine again.
She asked me some questions and very seriously said that I was in the right risk group and showing the right signs of multiple sclerosis. I worked with MS patients so I knew exactly what I was in for, and I was terrified. She sent me off for a bunch of tests including an MRI.
Turns out, I had a sinus infection that was so severe it was weeks away from ending me. It was causing me to have seizures - that was literally the only symptom. She said it was causing a lot of pressure and was close to crossing over the membrane of my skull (or something - it’s been over 20 years now). If I’d waited any longer, I would have passed away. A couple weeks on some intense antibiotics and I’m fine. The only long term result is I now have epilepsy, which has been controlled for more than 11 years.
#17
They both became rather popular rather quickly.
#18
First day, I couldn’t get my breath. I thought maybe I hadn’t prepared well, so I stayed back with the less experienced group.
Good thing I did.
Somewhere between Denver and Colorado Springs’ base camp, I threw a clot. I thought it was just a cramp in my calf from flying from sea level to altitude.
Nope.
If I hadn’t gone to urgent care, I probably wouldn’t be here now. I had the worst headache I’ve ever had.
They called the helicopter transport to take me to Denver. I was barely conscious when they loaded me onto the helicopter. The pain was awful.
Many people don’t understand that going from sea level, flying to a mountainous area, and trying to hike the fourteeners might not be a good choice.
I was extremely lucky that clot didn’t travel to my brain.
#19
The lesson there is that we treat HTN every single day all day long. So it’s super easy to just treat it and move on. But sometimes it’s important to ask “why” and dig deeper. I also feel like having a good “spidey sense” has paid off for me in clinic many times.
#20

Something magical happened during this colonoscopy. Her blood sugars went from very elevated (200s to 300s) just before the colonoscopy to MUCH better controlled afterwards. Insulin was entirely stopped. Eventually we got her on a starting dose of GLP1 and that is all she has needed since then. Life changing colonoscopy.


