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.
My name is Christine Pho. I am a medical student in my fourth year at UT Southwestern in Dallas.
Christine is planning to apply for an internal medicine residency. Our second guest is Dr. Daniel Stanton.
I'm Daniel. I'm one of the first year fellows in infectious disease at UTMB in Galveston.
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
Hi, I'm Clinton White. I'm a Professor in the Infectious Disease Division at the University of Texas Medical Branch.
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
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.
Cool. That sounds great. what about you, Daniel?
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.
And how about you Clinton?
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.
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.
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?
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.
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.
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.
Christine, you think you can tell us what we've done next?
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.
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?
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.
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?
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.
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.
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 and a link to our merch store. Please reach out if you have any suggestions for future shows or want to be more involved with Febrile. Thanks for listening, stay safe and I'll see you next time.