progressive multifocal leukoencephalopathy

No, but that's okay.

It's PJP and PML that we see at usually less than 200.

All right.

We got another one.

So what now should you be, like, if you want to check this and look into it more, what other things are you hoping to accomplish?

Well, once you're at less than 200, you think about the P's and the H.

So in this case, I would be thinking about, is there any risk of PJP? Is there any risk of PML? Is there any risk potentially of histo? And that kind of also depends upon their endemic area of where they're at and if there's exposure risk for that.

And then again, any kind of time they can have that Kaposi, they can have invasive.

that came during clinical trials of zidovidine monotherapy.

And since that time, tuberculosis, pneumocystis, CNS disease with cryptococcus, PML, and CMV retinitis, and Kaposi's sarcoma are key other conditions that are related to iris.

There are a few infections like toxoplasmosis, CNS toxoplasmosis, that rarely have been reported to cause iris.

I had this list in mind thinking about what could be causing a unmasking iris if the symptoms that he was having was not from the pneumocystis.

If you make no immunoglobulins, you run serious infectious risk.

If you look at like the bulimiamab data, and it's a different indication in lupus, but there's like a one in 10,000-ish risk of PML.

which is, as we all know from our days covering Biogen, is a very deadly reactivation of an infection called the GSC virus.

So, you know, there's some level of inevitability that, like, you will increase infections.

Herpes viruses are less likely to affect the brainstem, but it has also been described.

We can also think about JC virus and progressive multifocal leukoencephalopathy or PML when we're thinking about the posterior fossa.

This patient was known to have been exposed to JC virus because their JC virus serology was positive, but that usually has a much more indolent course and it's not usually associated with some of the other infectious symptoms that the patient has.

Other rare things that can sometimes affect the brainstem include Whipple's disease.

Okay, so just to summarize, Michelle, you and your team were, of course, considering a wide differential diagnosis for this rhombencephalitis.

You thought about bacteria like listeria.

Of course, viruses was high up on the list like enterovirus, flaviviruses like West Nile, HSV, and even JC virus-associated PML.

Autoimmune conditions were high on the list like an MS relapse, NMO, MOG, and even Bichette's you considered.

Only the 200-milligram dose was formally compared with placebo on nominal p-values, and Gilead's own statement skips the lower doses.

For an integrin blocker, there were no PML cases in this 12-week trial.

Phase 3 monotherapy is planned for 2027, which puts the weight on choosing its dose.

J&J and Odyssey added two more oral programs in UC.

And this one is significantly less reversible.

PML, progressive multifocal leukoencephalopathy.

PML sounds like an absolute nightmare scenario.

What is this?

It is a rare, severe demyelinating disease of the central nervous system, but it is not caused directly by the toxic chemical nature of the drug itself.

A kidney transplant patient who is heavily immunosuppressed on tacrolimus develops acute severe headaches, new onset seizures, and cortical blindness during their third week post-transplant.

An emergency MRI reveals T2 and flare hyperintensities, predominantly located in the subcortical white matter of the bilateral parietooccipital lobes.

What is the most likely clinical diagnosis? A progressive multifocal leukoencephalopathy, or PML.