Sara Dong: Hi, everyone.
Welcome to Febrile, a cultured podcast for all things infectious disease.
We use consult questions to dive into ID clinical reasoning, diagnostics,
and anti-microbial management.
I'm Sara Dong, your host.
Today's episode is actually a bit of a sequel or extension of a prior
episode, which I will mention at the end if you want to refer back, so
as not to give it away right away.
Although you may be able to guess when I introduce our guests.
So let's meet them.
Christine Pho: My name is Christine Pho.
I am a medical student in my fourth year at UT Southwestern in Dallas.
Sara Dong: Christine is planning to apply for an internal medicine residency.
Our second guest is Dr.
Daniel Stanton.
Daniel Stanton: I'm Daniel.
I'm one of the first year fellows in infectious disease at UTMB in Galveston.
Sara Dong: UTM B is the University of Texas Medical Branch in Galveston,
Texas, which is where Daniel also completed medical school and residency
And last but not least is our guest discussant
Clinton White: Hi, I'm Clinton White.
I'm a Professor in the Infectious Disease Division at the University
of Texas Medical Branch.
Sara Dong: Dr.
White's clinical interests and expertise include parasitology, tropical medicine,
HIV, and opportunistic infections.
He serves on the editorial board of a number of journals and
directs the IDSA-ASTMH guidelines committee for neurocysticercosis.
So before we get to the case, Febrile is everyone's favorite cultured
podcast, so we kick off the episode by having our guests share some culture.
So really it can be anything that's brought you happiness recently.
I'll start off with you Christine
Christine Pho: Sure.
I recently had the opportunity to try some Asian American fusion restaurants.
So, I had Blood Bros.
BBQ in Houston, which is a Texas barbecue place that also has Asian spices and
influences, and I also got to try Cris and John in Dallas, which is a
Mexican Vietnamese restaurant as well.
Sara Dong: Cool.
That sounds great.
what about you, Daniel?
Daniel Stanton: So, I just got back from a trip to Florida, uh, Disney World,
and I got the opportunity to visit the Star Wars theme park section of the
Disney World, and I, uh, was blessed to be able to make my own lightsaber.
I'm like a huge Star Wars nerd, I got to make my own personal lightsaber finally.
Sara Dong: And how about you Clinton?
Clinton White: Um, yeah, I was actually a music major in college, and recently I've
been listening to a lot of piano music, um, and particularly Chopin's Nocturne No.
1 and some pieces by Eric Satie that have sort of a, a melancholy, uh, tone to them.
Sara Dong: Oh, what?
This is such a great variety.
I love it.
Um, well, Christine, I'll hand it over to you to tell us about
the case and get us started.
. Christine Pho: A 41 year old male prison inmate with a past medical history of
hypertension presented with one year of worsening headache associated with
nausea, vomiting, and weight loss.
The headache is diffuse and worse while supine, radiates to
his neck and causes stiffness.
Over the last three months, his headache now causes him to feel pressure behind
his eyes and he has developed nausea and vomiting several times per week
associated with 40 pounds of weight loss.
Patient has also had recurrent sudden falls that are associated with
sudden movement over the past year.
He denies any specific triggers or prodrome of symptoms before his falls.
Denies fevers, chills, night sweats, seizures, or focal neurologic deficits.
He has been incarcerated for five years and he works as a cook.
He is a Mexican immigrant who came to the U.
S.
in his teens and last visited Mexico six years ago.
Daniel Stanton: So I just want to say a few things that stand out
about the case right off the bat.
All of his symptoms kind of are painting the picture of someone that has high
intracranial pressure, , including these, diffuse headaches that
are worse when he's laying down.
The pressure like features behind his eyes with nausea and
vomiting and weight loss now.
So it, it's just overall showing this picture of high intracranial pressure.
It's also based on the timing and the very slow progression of things
starting over a year ago with the worsening over the last three months.
This is a chronic process more so than like a quickly progressive process.
So we're thinking if infectious wise, very slow growing infections,
things like mycobacterial, maybe neurosyphilis, um, a fungal organism
or parasitic organism, maybe some of our opportunistic infections.
The next things we really would want to do in this case, get a very
detailed physical exam, particularly a neuro and a retinal exam.
Um, then we would obviously want to go to imaging to see if there's any features
that are changes on his anatomy from any of this increased intracranial pressure.
After the imaging if we don't find anything, any masses, we'd do a lumbar
puncture, really looking at the cells and the differential on the cells more
than anything, and then establish his HIV status and syphilis serologies.
Also, non infectious wise, things that might cause this are things like
malignancy if they've metastasized to the leptomeninges, or vasculitis,
things of that nature as well.
So, you want to tell us a little bit more about the physical exam, Christine?
Christine Pho: Sure, his physical exam was significant for an ataxic gait,
some discomfort with neck flexion without rigidity, slight diffuse
hyperreflexia, and bilateral papilledema.
He didn't have any problems with mentation and no cranial nerve deficit
or weakness, and he had negative Brudzinski's and negative Kernigs sign.
So, we went ahead and got labs and imaging on him.
So, his labs were significant for leukocytosis of 12, 000 white cells
per microliter with eosinophilia.
He also had a HIV and syphilis test that were negative.
And he had a lumbar puncture that was performed with a CSF analysis that showed
undetectable glucose, high protein, and an elevated white count of 47
with a high percentage of eosinophils.
He had a CT of the head that showed severe hydrocephalus with transcentorial flow
of CSF but no other significant findings.
He then had an MRI brain with and without contrast, that was
limited by motion artifact.
It was notable for communicating hydrocephalus
and leptomeningeal enhancement.
Daniel Stanton: So, with like we said before, this being a chronic
process, we now have more evidence that there's a meningitis going on.
The glucose consumption on the lumbar puncture, the really high
protein with the pleocytosis and this leptomeningeal enhancement
that's been showing up on the MRI.
Um, this leads to a really broad differential diagnosis just
thinking about chronic meningitis.
Um, things like Cryptococcus, maybe some endemic fungal infections in the U.
S.
like Coccidioides.
Um, Tuberculous meningitis comes into play since he's an incarcerated person.
Um, Brucellosis could have this appearance, neurocysticercosis, and
uh, other things like leptomeningeal cancers can also give you this kind of
changes and appearance of meningitis.
But because he's had this eosinophilic predominance of the pleocytosis, you think
of a much more narrow bit of of organisms.
The first few that come to mind are the ones you always get from a textbook.
Things like...
Angiostrongylus, or the rat lungworm, um, Baylisascaris, the neural larval
migrans, and, uh, Gnathostomiasis.
But no matter what we did on taking his history, I think we, uh, couldn't get
him to admit to eating any snails or traveling to Southeast Asia recently.
So we, uh, quickly dismissed those from our differential.
Things like drug allergies were high on things we were discussing, as
well as, uh, the neurocysticercosis.
Clinton White: So, if you think about neurocysticercosis, the main way we make
that diagnosis is with imaging studies.
The CT can be done as was done in this case.
It showed hydrocephalus and not a lot more.
The CTs often will show cysts in the brain parenchyma or can show
calcifications as well, neither of which was seen in this case.
MRIs are considerably better than CT at demonstrating cysts, particularly in
the ventricles and subarachnoid space.
Um, there are other methods that can be used to confirm the diagnosis.
For example, serologies can be used to suggest exposure.
There are newer methods like antigen detection, um, quantitative PCR, and
even in some cases are diagnosed by next generation sequencing of the spinal fluid.
So there are newer sequences on the MRI scans, um, that can
demonstrate things, particularly when they're missed on other sequences.
Uh, one of them is called Fiesta.
Daniel Stanton: Christine, you think you can tell us what we've done next?
Christine Pho: MRI brain was repeated with three dimensional Fiesta sequence
and showed two large cysts with visible scolixes in the fourth ventricle
and enlargement of the cisterna magna with extensive cystic debris.
In addition, there was multifocal subarachnoid cysts consistent
with racemose neurocysticosis.
An MRI spine was performed with and without contrast that
showed no significant findings.
We sent out labs to the CDC for neurocysticercosis enzyme linked
immunoelectrotransfer blot, EITB, and it returned positive for both serum and CSF.
Clinton White: So, this, uh, patient had neurocysticercosis.
Um, a previous episode, number 64, had Dr.
Christina Coyle discuss some aspects of neurocysticercosis.
We'll, I'll reiterate a few of them, but focus on some things that she
didn't have time to talk about.
Um, it's important when you think about neurocysticercosis that
you realize that it's a series of diseases and not just one infection.
So if you told someone you had a Staph infection, you'd want to know,
well, is this an abscess in the skin, or a bacteremia from a catheter, or
endocarditis, and they'd all have a little bit different management.
And the same is true for, uh, Taenia solium infections causing cysticercosis.
Um, they're very different presentations, depending on whether the cysts
are just in the brain parenchyma.
If they are, whether they're viable cysts, degenerating cysts,
or just residual calcifications.
You also can have extra parenchymal cysts, which are the most serious forms of
disease, including ones in the ventricle or ones in the subarachnoid space.
And often you'll have multiple different forms at the same time.
So in this case, he had both, uh, cysts in his ventricles and
cysts in the subarachnoid space.
So the diagnosis in this case was confirmed by the Fiesta imaging, which
showed scolices within, uh, cystic lesions, the so called, uh, "dot and
hole" sign, uh, which is pretty much diagnostic of neurocysticercosis.
With neurocysticercosis, it's different from other infectious diseases in
that the organisms are not in most cases proliferating a whole lot.
And so the acute management, the initial management should focus on
getting their symptoms under control.
If they have seizures, the first order of business is to get
them on anti seizure medicines.
If they have hydrocephalus, that usually requires neurosurgery.
If they have diffuse cerebral edema, it requires, uh, use of,
uh, anti inflammatory drugs.
So, those are all important aspects of the initial management.
So, Christina, you want to follow up?
Christine Pho: So just to go over his management, he was started on
high dose dexamethasone, and then subsequently in neurosurgery, performed
a suboccipital craniotomy, whereupon accessing the cisterna magna, enumeral
cysts were found and were removed.
The fourth ventricle was accessed inferiorly and the cysts removed
and confirmed by neuroendoscopy.
An extraventricular drain was placed and albendazole and
praziquantel therapy was started.
The extraventricular drain was converted to a ventricular peritoneal
shunt and methotrexate was started inpatient with plans to taper
the steroid slowly outpatient.
He is currently convalescing well.
Clinton White: So in this case, he did have, some evidence of
communicating hydrocephalus, which can be due to inflammation,
and he was started on steroids.
So when we treat this disease, particularly in those with mixed forms,
we think about the more serious forms of infection, and the treatment should focus
on what are the most serious forms, and what requires the most intensive therapy.
So, in this case, he can have, um, antiparasitics for the subarachnoid cysts.
Um, but, um, actually, it's very important to, uh, look at
the cysts in the ventricles.
The subarachnoid and ventricular cysts, it's interesting, tend to have a longer
subclinical period before they present.
Um, in a series we did from Houston, they were often 8 or
10 years after immigration.
So, this case, he had not been back in Mexico for a long period of time.
And that's kind of typical.
Um, so, seizures are associated with parenchymal neurocysticercosis.
But extraparenchymal disease is associated with hydrocephalus, such as in this case.
One of the interesting findings on this patient is he had these, uh, periodic
drop attacks, where, and actually, there's a term, Brun's syndrome, uh,
based on a neurosurgeon named Brun's who described this around 1900, just after
1900 in Germany where a cysticercosis typically in the third or fourth
ventricle moves around when you change positions and causes a sudden onset of
an acute, obstructive hydrocephalus.
So that was probably going on, in the past in this case and, would be a, real
big risk factor, um, for him not doing well if it was not addressed right away.
So in the fourth ventricular cysts, you really don't want to treat that medically.
And in fact, if you gave antiparasitics, it actually might interfere with his long
term treatment, uh, so that wasn't done.
Instead, we had a, a discussion with our neurosurgeons.
And, um, they said, well, why don't you just treat him medically?
And I said, well, he's got the cysts in the fourth ventricle.
And really, if that's not taken out, he's at risk for sudden death, which
is not something we like to happen in our patients under our care.
Um, So because of that we discussed this with the surgeons.
Well how do you get to the fourth ventricle?
Well there are two approaches.
Some cases of neurocysticercosis, they actually take a flexible neuroendoscope,
go up through the lateral ventricles, the third ventricle, and there are
descriptions of snaking it through the aqueduct and just pulling the cyst out.
However, there are critical structures on each side of the aqueduct, so
you don't really want to do that unless the aqueduct is quite dilated.
The other approach, is to approach it from behind and do a
craniotomy in the occipital lobe.
And then, either by micro dissection, by stereotactic approaches, or with
neuroendoscopy, you can get into the fourth ventricle and take the cyst out.
So, our patient had ventricular and subarachnoid cysts, and they
went in from a posterior approach.
As soon as they got in the subarachnoid space, they were...
enumerable, , cysts that sort of came out.
And so it, he clearly had a heavy burden of, subarachnoid disease.
The cysts in the ventricle could be removed easily.
And if that was all that had gone on, uh, he would be cured.
So ventricular cysticercosis, if you can take the cysts out
and cure them, that's great.
But he had so many cysts in the basilar cisterns and subarachnoid space, that he
was going to require long term therapy.
The debulking that was done in this case, uh, is helpful.
If you've got a lot of uh, parasites that you kill in the subarachnoid
space, it takes the body a long time to get rid of them, and so you'll have
chronic inflammation causing problems.
However, there are some cases that suggest maybe if you can get some of
them out, it might improve your outcome.
Typically, subarachnoid neurocysticcercosis has not responded
to the regimens of anti parasitic drugs that we use for other forms
of disease, for parenchymal disease.
And there are three approaches that have been, um, used in this
case.
In Mexico, they give high dose albendazole for a month and then repeat it again.
Some centers in the U.
S.
have used prolonged courses of albendazole, often lasting
months to even over a year.
More recently, there are studies using a combination of two anti parasitic
drugs, praziquantel and albendazole.
And the praziquantel is parasiticidal in itself, but even more importantly
elevates the levels of the active metabolite of, um, the albendazole, so
you get, uh, higher steady state levels.
Um, so, you know, that's often required and still may require
a long course of therapy.
So he's gotten debulking, his antiparasitics.
Um, it's really important that if you kill the parasites, you can
cause worsened inflammation.
And the inflammation really is the cause of a lot of the chronic processes.
So it's really important to get them on anti inflammatory medicines.
Typically, we'll start out with, uh, very, very high doses of, of steroids.
Um, I think he was started out on 24 milligrams a day of dexamethasone.
You don't want to keep people on that forever, and so drugs like methotrexate or
TNF inhibitors have been used as steroid sparing agents for chronic disease.
But he also has communicating hydrocephalus.
And, If you just give him antiparasitics, that's still going to be present.
And so in his case, he required, um, a placement of an external ventricular
drain and then a ventricular peritoneal shunt to manage the hydrocephalus.
But he also needs chronic anti inflammatory drugs
and chronic antiparasitics.
And, um, by the time he'd gotten his cysts out of the fourth ventricle and the ones
from the, uh, posterior fossa removed.
He was feeling great.
And I saw him in the hospital and he said, why can't I go home?
Sara Dong: Thank you so much.
You know, we crammed up a very complex case into a fairly short timeframe.
So I actually was hoping maybe you could give a quick overview
and summary of the case again.
And I'd love to hear any additional thoughts you have about how you
follow these patients in the clinic and, as they are recovering.
Clinton White: So, this patient had ventricular cysticercosis,
and that's a, that's typically requires, uh, it's a surgical
disease, it's not a medical disease.
So if you've got obstructive hydrocephalus or hydrocephalus rather than just
diffuse cerebral edema, that's a medical emergency and requires neurosurgery.
Uh, the ventricular cysts can be popped out, uh, most of the time
they're not very inflamed and, can come out easily by neurosurgery.
The ones in the lateral and third ventricle can be removed by these
neuroendoscopes and once you've taken them out, uh, the patient's cured.
Um, however, subarachnoid neurocysticercosis requires more
prolonged therapy and that includes chronic anti-inflammatory drugs, uh,
steroids and maybe steroid sparing agents and intensive, um, antiparasitic drugs.
We're not completely sure of the best antiparasitics, but praziquantel plus
albendazole may be better in some cases.
And since this disease takes a while, you need things to follow.
And we will typically follow the MRI scan.
But sometimes the MRI will not completely normalize.
And so there are other things that can be followed, and there are a
couple of tests that can be used to determine if you have viable cysts.
Those include a quantitative PCR assay and an antigen detection assay,
both of which can be performed in the serum or in the spinal fluid.
And if those have turned negative, um, you can actually stop the treatment, stop
the antiparasitic treatment, taper the steroids, and declare the patient cured.
So, you know, this patient had a good outcome.
It required aggressive treatment, a discussion with the neurosurgeons,
holding off on antiparasitic drugs until the cysts in the ventricles
were removed, and eventually starting a prolonged course of anti
inflammatory and antiparasitic therapy.
Thank you.
Sara Dong: Thank you to Christine, Daniel and Clinton for joining Febrile today.
As a quick reminder, you can also check out episode number 64, which is called
Revenge of the Cyst and featured Dr.
Cesar Berto and Dr.
Christina Coyle who also discussed a different case of neurocysticercosis.
Thanks again for listening to Febrile.
As always, you can check out the website, febrile podcast.com where
you'll find the Consult Notes, which are written complements of
the show with links to references, our library of ID infographics
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