Transcript

PLEASE NOTE: While an effort has been made to correct errors in this AI-generated transcript, some mistakes may have been missed. This transcript should be taken merely as supporting material to the podcast discussion and neither is as an authoritative last word on the subject matter.

MIC CAVAZZINI: Welcome to Pomegranate Case Report, a podcast for trainees of the Royal Australasian College of Physicians. I’m Mic Cavazzini, but as usual, I’ll be handing over to Associate Professor Stephen Bacchi. He’s conducting a fellowship in Boston, where he has come across another fascinating case study, published two years ago in the journal Neurohospitalist. If you want to read along, the paper can be found in the show notes. But to test your diagnostic reasoning, just go with the flow as Stephen and his guests drip feed you the findings from the investigations on this patient.

She was a 52 year old female presenting with hand clumsiness and headache following recent neurosurgery. The diagnosis that was identified is one in which evidence for management is somewhat limited, and so the theme of uncertainty also comes out through this discussion. Here’s Dr Bacchi with the introductions.

STEPHEN BACCHI:   Hi, I'm Stephen. I'm a neurology Fellow at the Massachusetts General Hospital, and with me, I have HaeLynn Gim, who's a Harvard medical student in her third year of study. And with us we have Dr Galina Gheihman who is a general neurologist at Brigham and Women’s Hospital and Massachusetts General Hospital. She completed her residency in Mass General Brigham Neurology, where she served as Chief Resident in 2023-2024. Galina is also a member of the faculty at Harvard Medical School and co-leader of the Medical Education Certificate Program for the neurology residency. Thank you for joining us.

GALINA GHEIMAN:  Thanks so much for having me. Really excited to be here today.

HAELYNN GIM:           Excited to be here too.

STEPHEN BACCHI:   So as usual, we'll be discussing a previously published case report in a step-by-step manner, with a focus on content that's relevant to trainees in a generalist audience. So today, we have a 52-year-old female presenting with clumsiness and paresthesia of the right hand for several days. She also had a headache. She has a past medical history of migraines, and a family history of a Factor V Leiden mutation. Three weeks prior to presentation she had a suboccipital craniotomy for a Chiari I malformation.

Prior to going further, could you please outline to us what a Chiari malformation is? And, acknowledging you are a neurologist and not a neurosurgeon, in what types of situations may they require surgery?

GALINA GHEIMAN:  Yeah, great question. And even if we might not operate on it, it's certainly something we're going to encounter as a neurologist, which is my practice. So, great question. So, Chiari malformation refers to a condition where part of the brain tissue at the back of the brain will kind of droop down and extend into the spinal canal at the base of the skull. And there's different types of formation, some are more severe than others. And something that I learned actually recently, which is interesting to me, was actually that it's not very rare. In fact, it's quite common. About one in 100 MRIs will show a Chiari malformation. Now, less of those are symptomatic, about one in 1000 people, and of course, not everyone gets an MRI. But it's interesting to say that you know that structural abnormality is seen, and then not everyone is symptomatic.

Because of the location it is, it can sometimes lead to some obstruction of flow of the CSF, cerebrospinal fluid, and that can lead to symptoms like headaches or dizziness. And so, to your second question about when is a surgical intervention necessary, that's really when the carrier malformation is symptomatic, and when those symptoms become severe. Usually it starts with headaches, but can lead to progressive neurological symptoms as well; so, weakness or other types of findings, or you might sometimes see syringomyelia, which is a complication of the spinal cord itself. And when you see any of those conditions, that's when surgical operation may be necessary, and consultation with neurosurgery is needed.

And when they do decide to do the surgery, what it is is really a decompression, and so it's often a posterior approach, where you're decompressing the posterior fossa and kind of making room for CSF. And that's what this individual had—our patient had about three weeks before she presented to us.

HAELYNN GIM:           Okay, so on this presentation, physical examination revealed subtle right upper limb pronator drift and mild distal finger weak weakness. She was able to point to the location of the headache, which was in the left parietal region. CT scan demonstrated left parietal cerebral oedema. Brain MRI suggested an adjacent cortical vein thrombosis on susceptibility weighted imaging (SWI). Would you be able outline the nature of this diagnosis, and how is it different from a dural venous thrombosis?

GALINA GHEIMAN:  Yeah, so, this is a really interesting case, precisely because it's a pretty rare diagnosis. So, what you mentioned was a dural venous sinus thrombosis, and that's what most of us think about when we think about a cerebral venous thrombosis. Now, as you know, the veins in the brain will drain into the dural venous sinuses. And so, when there's a clot in one of those, that's what we call it a dural sinus thrombosis. However, the cortical veins on the surface of the brain, so those that are draining into the dural sinuses can also have a clot in them, and in that case, we would call it a cortical vein occlusion.

Now, cerebral venous thrombosis encompasses both of those things, but in this case, we're talking about an isolated cerebral vein thrombosis, which as you can imagine, is quite rare. In fact, in the literature, it's only been reported in 116 patients total. Of course, it may be more common than that. But part of the reason it's really hard to make the diagnosis is because it actually can just have such a variety of symptoms of presentation, and therefore it can be hard to actually pinpoint it as that being the cause.

So, the pathophysiology of what happens if that little area is infarcted and one of the superficial cerebral veins is that you can actually have a venous infarction as a result of that. And/or with blocking of the sinuses, you can just have increased intracranial pressure. As you remember, potentially, from medical school, the CSF drains into these dural sinuses. So, as you can imagine, both of those things can present over the course of about hours to days, sometimes weeks, depending on the size and the location.

But they're really, really tricky to diagnose. They're often misdiagnosed because they're so non-specific, and because even when there's been an infarction, it will not be in a typical vascular territory. So, people may not think about a vascular cause or aetiology for the presentation. Now, as you can imagine, I talked about increased intracranial pressure. So, we often see headaches, but because, unlike the venal sinus thrombosis, which is sort of external to the brain just increasing the overall pressure, because these are so localized, they can actually have focal neurological deficits. So, if you imagine there's a little cerebral infarction in a particular area of the brain, you may have some aphasia, or you may have a seizure because of the cortical irritability, and they're typically focal.

Now, our patient actually was able to point to a specific area. Lo and behold, this is actually where she had the clot on the left parietal lobe, leading to some of those sensory changes, paresthesia, a little bit of weakness on the right upper extremity. And interestingly enough, we often see this when we make a diagnosis of venous sinus thrombosis, because the vase themselves are near the meninges and they can be irritated, and that can be painful. And so, patients will point to the location of their clot, and it'll correlate with their CT. So that's a question I love to ask if someone comes in with a new headache, who doesn't have a headache history, is, can they, with one finger, point to the location of the headache? It doesn't always help you, but if you're thinking venous sinus thrombosis for other reasons it can. And what was rare in this case is, I’ve definitely seen it with venous sinus thrombosis, I've never seen it with the cortical vein thrombosis, having said that, I’ve only seen one. So, who knows? I'll have to ask others if I see this again.

STEPHEN BACCHI:   Brilliant. Thank you for that summary. So for non-neurologist listeners, it's dural venous thrombosis is the bigger draining vein, it's like a DVT of the brain. And the cortical veins are adjacent to these and smaller, and they can cause a variety of neurological symptoms that are not in classical vascular territories. I always find it a hard diagnosis, I think that the literature would probably bear that out. So, for the cerebral vein thrombosis, she was commenced on Apixaban, in this case, and her course was complicated by focal seizures, which manifested as recurrent right upper limb parasthesia and clumsiness followed by weakness. For these seizures she was commenced on levetiracetam. A workup for hypercoagulability was undertaken. And noting there was a family history of factor V Leiden, could you please describe your approach to a hypercoagulability workup? How is this similar/different from a young stroke screen?

GALINA GHEIMAN:  Yeah, great question. If I could just add one point to the prior note that you made about the challenge of diagnosis. Really, one of the questions we have to think about is how to make it, right? So, there's the clinical story, but actually the imaging is how it's made. And the one point I wanted to make is that when we think of a cortical venous sinus thrombosis, we usually think about CTVs, but they're not necessarily the best option here. Angiography, and rather, actually MRI can be better. And not just MR Angiography, but specifically a type of sequence that looks for that looks for metal, so either gradient echo sequences or SWI, which is susceptibility weighted. And the idea is there, when you have a blood clot, you have a lot of iron from the blood that's in one kind of focal location, and that can actually show some abnormalities on this type of sequence.

And so you're completely right, it's hard to diagnose and one of the teaching points we're trying to make with sharing this case, is it’s not just the clinical presentation, but how can you help yourself? And the way you can aid your diagnosis is with the use of MR and looking at these specific metal highlighting signals. In the case of SWI, there's like a blooming artifact, so it can actually help you spot a change, and then there might be some focal oedema.

But getting to getting to your point about management, so if we do make that diagnosis, and we've able to find the clot that is going to guide what we do. And we started, as you mentioned, anti-coagulation. Now the duration of that can depend on what we think the cause is. And in her case, we did have to consider hypercoagulability given the family history, but also just the risk of clots for a person of a young age. So, the hypercoagulability workup here was truly to try to understand was this just a one-time , rovoked, maybe in the setting of surgery or something else, kind of aetiology, or was there a hypercoagulability background?

And so for the hypercoagulability workup, we usually do testing of hereditary genes that can increase the risk of clotting in the venous system. So, in addition to Factor V Leiden the most common things would be prothrombin gene mutation, protein CNS deficiency, or anti-thrombin deficiency. Or thinking about some acquired causes like antiphospholipid syndrome, malignancy, hypercoagulability malignancy.

The question about stroke in the young is a really interesting one, because that's kind of the setting in which we do the most extensive workup. And so for an individual presenting with stroke, with typical stroke risk factors, we don't really add on these additional studies. However, in individuals who are younger, we have to think about hypercoagulability, and beyond that, we have to think about things like cardiac sources, PFO, atrial fibrillation, vasculopathies.

I think what we have to think about here, though, is which type of hypercoagulability are we referring to? At our center, we often talk about on rounds, you'll see the residents saying, “Well, is this arterial or is this venous hypercoagulability?” And so we send different testing. So for arterial hyper coagulability, which is actually what we are more worried about with strokes, we're thinking of things like antiphospholipid syndrome. And so those are different sets of testing than for venous hypercoagulability, where the person is coming in with signs of venous clots. And so, our patient really falls into more of that venous hypercoagulability category and so, for her, we felt we didn't need to do the more extensive testing, you know, looking for PFOs, or things that could cause an arterial stroke. In her case, we were really just worried about the hypercoagulability in the venous system, and so that was sort of sufficient for our workup in her case.

And I think it matters because it might change the course, the duration of anticoagulation. So, had we found a reason for hypercoagulability beyond this provoking factor, that might have been a reason to treat her a little bit differently. I also think for her, we do have to consider the post-surgical state. So, you know, she's not coming in fresh off the street. She's three weeks after a decompressive craniectomy. So that area has been manipulated in some way and I was actually interested when I had this case, about whether the surgery itself was a risk. So, looking through the literature, there's actually been a review that looked at the risk of venous sinus thrombosis as a complication of neurosurgical procedures. And they did find that procedures in the proximity of the dural sinuses, if they're manipulating them, especially in the posterior cranial fossa, can be a risk factor for this. So, the risk is almost 17%,  so it's not benign, it's a relatively frequent complication after posterior cranial fossa surgery. And the pre sigmoid approach, for those neurosurgeons out there, is a risk factor as well, But they think there might be some sinus injury, or there might be just changes in the flow dynamics of CSF after surgery that can predispose to both venous sinus clots. And, of course, most commonly the cerebral veins are actually propagated from the venous sinuses, which is why the isolated cortical vein is so rare, because usually they're actually propagated from the larger veins into the smaller veins. So having said all that, it's not a non-trivial risk factor, and I think has to be considered, in this patient's case.

HAELYNN GIM:           In this case, the hypercoagulability investigations were unrevealing. She was later followed up with a repeat MRI two months down the road. And on this follow up scan, the cerebral oedema had resolved, and the appearance of the cortical vein had normalized. In the setting of this improvement, how do you go about considering the duration of anticoagulation, I think, which you started to speak about. And for how long to continue the anti-seizure medication? I imagine there's some uncertainty in the evidence around aspects of these questions.

GALINA GHEIMAN:  There is definitely uncertainty. There isn't a specific guideline for this, but we do use general guidelines that can help our decision-making in this case. So typically for anticoagulation, our standard practice is, we think about, is this provoked or unprovoked? And I think in her case, it would kind of fall into the likely provoked category, given that there was surgical manipulation of the area. And so, when we think about the underlying trigger, like, is that going to be removed, or is there some underlying factor that was unprovoked that hasn't been removed? And so, for her, in the setting of that kind of provoked case, we usually do three to six months of anticoagulation, and often there's follow up imaging, and if we think that the risk factor has resolved, we can sort of wean that off. If we think the risk factor hasn't resolved, there's concerns, we may keep it on.

It's not really entirely a science, part of it is an art. Some times we ask, you know, what does the imaging look like? Is it resolving? Sometimes we ask, how severe were the presenting symptoms? And I often find if symptoms are more severe, people sometimes are a little bit more conservative, and may keep the anti-coagulation a little longer.

And on the flip side is the patient tolerating the anti-coagulation. So, this is a healthy individual who, you know, fortunately, didn't have a GI bleed or something like that, while on the anti-coagulation. But sometimes we get frail, elder adults, and we're, you know, trying to do the best we can, but there's complications, and that may be a reason to stop the treatment earlier. I also think you have to think about the underlying reason for it. So, in her case, you know, we said maybe surgical, there's certainly no genetic hypercoagulability, and for proof of point, there's no hypercoagulability malignancy, right? So, those are kind of situations where had we found a factor that needed anti coagulation, separately, that this was just, an iceberg effect, a presentation of some under other underlying factor, we'd have to continue it longer. But in this case, I think the provoking factor may have been the surgery.

Interestingly, in the same review I quoted before, and I can share that that paper, it's Trevisi and colleagues from 2024, they actually looked at this question as well. Do patients need to be on antithrombotics? And they found that of their systematic review they did, 50 or so of 250 patients were treated, some actually had bleeding complications, only six, so, you could say overall did well. But of those that didn't, they actually imaged everyone in follow up, and 50% of the non-treated patients actually had good recanalization as well, and really no symptoms. And so, you could say that overall, the clinical course they thought was relatively benign, and did show clear advantages to being on antithrombotics.

Now, what I say would not apply for our patient is she came in symptomatic with this, not just the clot, but the seizure as well. And so, I would sort of put her into at least the like three to six month category, and that's what we ended up doing for her. For the anti-seizure medicines, is a little bit different. Again, she doesn't have epilepsy. She doesn't have unprovoked seizures that are recurrent. She has a provoking factor with the imaging resolving, the underlying factors resolving, she could be weaned off. I think some people will probably would keep her on at least through the course of the anti coagulation, through the imaging, and once you feel like the anti coagulation is safe to come off. The anti seizure medicine can as well. But again, also more of an art than a practice, and certainly shared decision-making can play a role here too.

STEPHEN BACCHI:   Great. Thank you. So, now this patient's been managed by a team, I imagine. There were people who had both mentee and mentor roles in that team, and I know that one of your many areas of research interests is mentorship in medical education. I wonder if you could speak to us briefly about your views on mentorship in clinical and academic settings and some strategies that people can use to facilitate such mentorship.

GALINA GHEIMAN:  Yeah, thanks, Stephen, for the question. This is one of my many passion areas. I think mentorship is so key in the clinical setting and in academic settings. Mentors can provide guidance. They can guide you on your career development, also guide you in sort of professional development, to your identity as a physician and in the other things that you want to do in life. And in clinical practice it's especially important because so much of what we face in the clinic is not just like clear answers that we can find in a textbook, but really navigating complex decisions, navigating complex situations, trying to develop clinical reasoning, which, again, is kind of a practice and an art. You know, it's really those elements of the art of medicine and building confidence.

I think, when you have mentors who know you as a person and can see how you grow longitudinally, they can remind you of the things that you’ve done, the strengths that you have, even when you have those difficult days. In academia, it can be really key for career development, right? We think about like a PI guiding junior mentors. Sometimes it's hard to even advance if you don't have someone sponsoring you or advocating for you, and as I mentioned, also in that kind of role modeling and professional and personal identity formation.

I think that there's a couple of key strategies that can make mentorship effective. I think the key thing is that it takes intentionality, it doesn't just happen by chance. And that can be both on the part of the mentee and the mentor. So, for the mentor, setting expectations, having clear check ins. And also being open to bidirectional learning. Increasingly, we're thinking about the idea of reverse mentorship, where you may add something as the experienced mentor, but the mentee can offer fresh perspectives.

I've even had this experience on the wards, where medicine changes so fast that sometimes I return to the hospital and I'm on service, and the residents are talking about some new test, or some new, lab that we can send, or some new condition that like didn't exist six months ago. And so being open and being able to, as a mentor, say, “Hey, I don't know about that. Can you teach me that?” And this idea of bi directional learning and bi directional support, I think is very important.

I actually had an opportunity to write a commentary about this topic. And in for the journal Medical Education, and there I had a chance to kind of state a little bit, provoke a little do a call to action. And what I talked about was the idea of that we need to create formal programs. Now, not everyone will match with the formal mentor and jive with them, but the opportunity to be mentored, should be there for everyone. And in addition, there are things that departments and hospitals and centers can do to promote mentorship, and I think both creating formal programs but also creating just spaces for informal meeting between individuals, like, creating that space for coffee or that space for chats or networking nights, increasing the chance that you may find someone who you can connect with.

I think we also have to develop mentors and mentees. I mean, we're not taught this. You know, in medical school, we're not taught how to be a good mentee, how to be a good mentor, and we can teach it. There's actually a science to it. You can learn it. You can improve the way that you mentor and the way you are mentored. I think we should recognize and value mentors, because right now, they're essentially doing it in their free time, or in their non free time. And if we can value this as part of the job, part of the skill set. Imagine you could, not bill for your mentoring hours, but at least not be having to make up clinic late if you're taking time to meet with a mentee. And so, I think it's all up to each of us to kind of advocate for those system changes. And I kind of like to think about the research side of it too, you know, evaluate these programs that we're going to put in and see if they're making a difference for career development and wellbeing.

Also mentees out there who are listening, there's a lot you can do. It's not likely that you'll find a mentor if you sit and just hope so one of them will find you sitting on the side of the road. There's a lot you can do. So, a couple quick tips. I call it menteeship 101, or active menteeship. The first is really taking initiative, so building your own kind of mentorship portfolio, finding people with different perspectives. The second is really being prepared. So, come to meetings with a question, you know, ask for specific help, for specific tasks, provide your mentors with feedback and close the loop. They love to hear what you did with the advice that you gave them, and then really say thank you. Show your gratitude and pay it forward.

HAELYNN GIM:           Thank you. That's so valuable to hear as a medical student. To wrap up the case for listeners, could you please outline a couple of key learning points or take home messages that trainees could take from the case?

GALINA GHEIMAN:  I'd love to. So, I think the first again, is really the presentation of this cortical vein thrombosis is quite subtle. It can really be non-specific headaches and seizures, and so you have to have a good story or a good suspicion. That leads to point two, how do you make the diagnosis? Well, the reminder about that imaging can be your friend, in this case. You can be aided with MRI, and specifically susceptibility-weighted MRI, or GRE the sequences can be helpful, and, in fact, potentially more helpful than the traditional venous imaging. If isolated, it's better than the CTV, because you may not spot it on the CTV, because those veins are too small to be seen well with the with the CT scanner.

The third point is, treatment has to be individualized, and really dependent on what you think the cause is. If it's sort of unprovoked and there isn't some underlying nefarious other diagnosis, usually a three to six month course with repeat images is appropriate. But if you find something else, or there's concerns, a longer course may be indicated. And I actually like to plug another really great article on the topic. When I found this case, I turned to my mentors, Dr Klein, who is the senior authors in this case with myself, but he and actually Alan Ropper had written a New England Journal article review on this called cerebral venous thrombosis, where we learned that fact about the 116 others reported in the literature, and added our 117, so I'm happy to also share that article with you to for those who want to read a little bit more. We also spoke about the ubiquity of uncertainty, the need for team-based care, mentorship, and hopefully those topics are of interested, as well.

STEPHEN BACCHI:   Thank you again, Galina, it's been a fantastic discussion, and particularly some of those practical, actionable points about mentorship and mentorship, I think are really unique and hopefully good for listeners from a range of seniorities. So, for full details of the case, the article was titled, Isolated cortical vein thrombosis, and it was published in the neuro hospitalist in 2023 the first author, Dr Galina Gheiman, and last author, Dr Joshua Klein. And we'll include links to some of the other articles that were discussed in the show notes. Thanks again.

MIC CAVAZZINI: Many thanks also to Stephen Bacchi and HaeLynn Gim for giving up their time to produce this training resource. Please remember that this is a passion project they’ve developed in their spare time, and it should not be taken as the last word on this clinical topic. Rather, these case reports are way to demonstrate a systematic process by which basic physician trainees can work through long case presentations.

I’d love to hear what you think, so feel free to post a comment at the episode web page racp.edu.au/podcast or send an email to podcast@racp.edu.au. At the web site there are also links to all the papers you’ve heard mentioned, a full transcript, and coming soon, we’ll have some quizzes and other self-testing resources available for these pods too.

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This podcast was produced on the lands of the Gadigal clans of the Yura nation. I pay respect to their elders over tens of thousands of years. I’m Mic Cavazzini. Catch you next time.