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 for the Royal Australasian College of Physicians. I’m Mic Cavazzini, but if you haven’t listened before, these Case Report interviews have been developed by Associate Professor Stephen Bacchi. He is a neurologist in Adelaide, so apologies if brains have featured frequently in recent and forthcoming episodes. We’re always keen to hear suggestions from the whole range of listeners, so feel free to send an email to podcast@racp.edu.au.

So, today’s case report is actually the first one which was recorded. Call it the unreleased pilot if you want. Dr Bacchi’s intent with these is to model how case presentations should be queried. Today’s story takes place in August 2021. A 27-year-old male wakes up with weakness in the left arm and leg and gets himself admitted at Royal Adelaide Hospital. Shockingly, for an otherwise well young man with no significant medical history, a right middle cerebral artery acute ischaemic stroke is identified by CT angiogram. His condition deteriorates in hospital, and a mediastinal mass is discovered on review which gives a lead as to the distal cause.

STEPHEN BACCHI:            Hi, my name is Stephen. I'm a neurology registrar at the Lyell McEwan Hospital in the Northern Adelaide Local Health Network and today I've got with me Doctor Rudy Goh. Dr Goh is a neurology consultant with interests in clinical research and vascular neurology. He's currently conducting a PhD through the University of Adelaide and is the principal investigator on a number of prospective stroke clinical trials, and he's here with us today to discuss a case.

RUDY GOH:        Thanks for having me.

STEPHEN BACCHI:            So, today we'll be discussing a sad case of a young man who presented with a neurological syndrome and unfortunately did not have a good outcome. It's a case that I think it's very important that we all learn from has several important teaching points, both for neurologists and generalists. So, to start off with, we have a case with a 27-year-old male, who’s presented to hospital after he awoke with a left arm and left leg weakness. His initial examination showed that he was afebrile and in sinus rhythm with a moderate left facial droop, hemihypoesthesia and mild left-sided neglect. He was systemically well with no significant past medical history. So, Rudy, could you please discuss your approach to a code stroke, as is this is, in the setting of waking up with symptoms.

RUDY GOH:        So, in a setting of waking up with symptoms, we know that potentially through the WAKE-UP trial that, nine hours from the mid-time between their last known well time to the time that they wake up—so, for example, if they went to bed at 3am, and then they woke up at 10am, so, the middle of that will be about 6:30am—so, it will be nine hours after 6:30am, so your time that you can actually thrombolyze the patient does increase to that time provided that there is a DWI to T2 mismatch on the MRI. So, these are sequences in the MRI that can be done acutely in tertiary centres only.

Outside of these settings, there are specific situations which allow you to thrombolyze the patients, for example, if someone is in a really rural area that that would preclude them from accessing from thrombectomy services urgently—excluding those rare cases, usually patients would be precluded from thrombolysis outside of the four and a half hour window. That’s still the state of how things are at the moment and we're [doing] more trials, looking at extended-window thrombolysis as well as extended-window thrombectomy, which is currently at 24 hours.

STEPHEN BACCHI:            Thanks Rudy. So, just to recap, so when someone wakes up and has a code stroke, they're still a potentially interventional candidate to time is still brain and key pieces of information is when they went to bed and when they woke up with symptoms. And urgent access to neuroimaging is critical, in particular, MRI were feasible looking for a DWI-mismatch.

RUDY GOH:        Absolutely yes. And basically in the same way, and it's important to ensure that more patients have access to MRIs as soon as possible.

STEPHEN BACCHI:            So, in this case, we've got a multimodal CT scan of the brain, which has demonstrated a proximal, right MCA, or middle cerebral artery, M2 occlusion with a moderately sized perfusion lesion. In this instance, he was treated with aspirin and clopidogrel rather than endovascular thrombectomy or thrombolysis. Could you talk to us about the evidence at the moment around when endovascular thrombectomy and thrombolysis are indicated for patients with a large vessel occlusion? And when it's not?

RUDY GOH:        Yeah, so I'll start off with thrombolysis. I think thrombolysis, in the in the current state of evidence, we know from the trial data so far, that anyone with a NIHSS less than five is still an area that is still being studied at the moment. There are multiple trials, including the TEMPO-2 trial that we're running at the Royal Adelaide Hospital, that is essentially looking at whether we should be thromolyzing patients with minor stroke with me as defined by NIHSS five. With a NIHSS score of mroe more than five, these patients with significant deficits should all be thrombolysed as long as they meet the time criteria of within four and a half hours or with extended-window thrombolysis up to nine hours with the CT perfusion imaging in selected cases.

Now in regards to thrombectomy, patients with last vessel occlusions are now faced facing individualized decision-making processes at the moment even though the trial data again, is not conclusive in providing thrombectomy patients with large vessel occlusions and a NIHSS of less than five. However, if someone has for example, a poorly predictive hyperperfusion intensity ratio, which can predict the penumbra in a patient—you know what can be salvageable in a patient at that point in time, as reflected in the MRI and 24 hours—if that shows that the person is going to lose a lot of brain tissue at that point, then there might be a good case to go in and perform a thrombectomy on that patient even though they have only minimal deficits.

STEPHEN BACCHI:            Thanks Rudy, that's very interesting. So, there's some ongoing uncertainty and ongoing research in this area, it's important to support. So, in this case, we've got a young man and he's now been admitted. So, it's on day two after his symptom onset. And whilst an inpatient, he has developed a junctional bradycardia, with absent atrial contraction. Now, on review of his admission CT, it's considered the inferior aspect of the CT angiogram has actually demonstrated mediastinal mass. Now, in this context—he’s got a new bradycardia. he's got a mediastinal mass—there's significant consideration for a malignancy-associated cardioembolic stroke as the aetiology of his presentation. Now, we're acknowledging that this is an evolving case, and he hasn't had a complete workup at this stage. But normally, what are some of the features that make you think about malignancy as a cause for stroke? And how would you work up someone where you're considering malignancy as a cause of ischaemic stroke?

RUDY GOH:        That’s good question. So, starting off with the history itself, it's important to ask questions around constitutional symptoms. So, whether someone's lost weight, they lost their appetite, the have fever, or perhaps they're having night sweats that drench the bed, things like that, to give you a rough clue whether they couldn't have an underlying paraneoplastic phenomenon, that's occurring at the same time as their stroke. And otherwise, in terms of other malignancies, you know, asking a history of cancer or whether that could have recurred is really important, just going back to the history. And the thorough physical examination.

Because it's very easy to take a shortcut in thinking that anyone with a multi territory stroke is likely to have a cardioembolic stroke, but we have to acknowledge that there are also other potential causes of stroke such as infective endocarditis, or marantic endocarditis or malignancy and use endocarditis that can lead to strokes as well. So, it's important to perform a full systematic review and also with a thorough examination of the patient, not just looking at the neurological system, but also examining the cardiac system, looking for murmurs looking for systemic symptoms such as fever, and from an imaging point of view, as we as we discussed, looking for any multi-territory involvement, so, to see whether an embolus has travelled through multiple vessels, and that would suggest a very proximate cause of stroke, or one of which could be due to malignancy and use hypercoagulability and marantic endocarditis.

STEPHEN BACCHI:            Alright, thanks. So, when we're considering alternative or unusual causes of ischaemic stroke, malignancy is a possibility and it always comes back to our fundamentals for the trainees. So, a history physical examination, then investigations and imaging does have a role. So, there's features on the brain scan itself like the three territory sign, which might point someone towards malignancy as a cause, but ultimately, we need to consider other aetiologies as well. And malignancy workup often will start with something like a CT chest, abdomen, pelvis, which is what occurred here.

Prior to that though, the patient was changed from aspirin and clopidogrel to apixaban, five milligrams twice a day, due to the high pre-test probability of a cardioembolic malignancy-associated source. So, after that medication change, they proceeded to the CT chest, abdomen and pelvis, which demonstrated a number of significant abnormalities. So, there was a large, superior mediastinal mass that was causing superior vena cava obstruction. Then, there was also a left anterior thigh superficial fascia lesion, fairly large 70 millimeters by 15 millimeters, without inguinal or sub diaphragmatic lymphadenopathy. There was also multiple subtle sclerotic metastatic appearing lesions throughout the axial skeleton and sternum on this initial scan.

Subsequently, the patient proceeded to have a transthoracic echocardiogram to further elucidate the nature of the presumed cardioembolic source. And this again demonstrate multiple abnormalities, such as a distorted aortic root with a mass in the interatrial septum towards the aortic root with likely extension along the roof of the left atrium. They had a normal left ventricular ejection fraction and no other real significant abnormalities aside from the one glaring, significant abnormality. So, this is a challenging case already. There’s multiple abnormalities again require careful interpretation. This does raise the differential diagnosis of intracardiac mass, which is a fairly specialized area. And I think it's probably one where you're going to seek help from your colleagues, more often than not, and looking for the opinion of a cardiologist or cardiothoracic surgeon. And I think that'd be really interesting topic for future podcasts as well.

In this instance, the patient unfortunately proceeded to deteriorate. So, on day three of their admission, they developed a progressive left hemiparesis and became obtunded and had pupillary abnormalities with pupillary enlargement and a loss of reactivity. This is clearly a deeply concerning scenarios. For the trainees. Really, could you talk through your approach in this setting where someone's been admitted with a stroke and subsequently deteriorated with these signs? I

RUDY GOH:        So, when you're working on the ward, and you have an acutely deteriorating patient, it is important to organize to quickly perform a thorough neurological examination, but initially performing the examination succinctly with the NIHSS score, and also determining whether that's actually changed from the initial NIHSS score itself to give us give us an objective measure. And also be important to know if there are any changes within the NIHSS score, what has changed and what are the new deficits and what is old. It's very important to determine what is old and what is new in a neurological case, especially as it could herald in a patient with thrombolysis, for example, a repeat stroke, which could be amenable, even if a patient has been thrombolyzed, to clot retrieval.

We know that patients who have received from the lysis who deteriorate are more likely to have a recurrent stroke in fact, much more likely, rather than symptomatic intracranial haemorrhage. Therefore, it's really important that multimodal CT perfusion imaging, ideally is why a code stroke protocol is initiated immediately upon neurological deterioration. Otherwise, especially in this case, where there's a young man with a middle cerebral artery infarction, potentially with a large middle cerebral artery infarction, especially in patients below 60 years of age, it is important to think about decompressive hemicraniectomy, as these patients might have a significant mortality benefit, even though there might be not much morbidity benefit at this stage. It is very important to perform the procedure before any deterioration happens, because once any deterioration has happened, it's likely that you have missed the boat. So, to summarize, it is important to get a very thorough examination knowing what is old and what is new in terms of deficits and also to proceed to urgent imaging as soon as possible. Call up your friendly radiologists and say I need a scan right now. Let's get it done as time is brain.

STEPHEN BACCHI:            Thanks Rudy. So, to recap for the trainee, so the neurologically deteriorating patient after a stroke is a specific presentation with a specific set of differentials, which includes symptomatic intracranial haemorrhage following thrombolysis, but is not limited to that. And also includes the possibility of repeat ischaemic infarction, which are clearly managed differently. They need to perform a timely evaluation, looking for new changes and facilitate urgent head imaging, which we impart guided by this intern local protocols. Would that be fair to say?

RUDY GOH:        Yeah, absolutely.

STEPHEN BACCHI:            So, in this instance, a repeat non-contrast CT was sought urgently and did unfortunately demonstrate a large right parietal intraparenchymal haemorrhage with intraventricular shift. There was obstructive hydrocephalus and uncal herniation, along with parafalcine herniation. He did proceed to an emergency, right hemicraniecotomy. In this time, over the following day, the thigh lesion was biopsied. The patient was treated empirically for an infection with meropenem in voriconazole. And ultimately, the biopsy cultures grew an unexpected result with Aspergillus flavus identified. So, really, could you please talk to us about what are the normal indicators that you would see clinically to suggest infection as a cause of ischaemic stroke? And then what does that mean for the risk of haemorrhagic transformation like the patient has unfortunately suffered in this instance.

RUDY GOH:        So, when you have fever, when you have severe headache, things like; if a patient who is immunocompromised for example; and if someone's using intravenous drugs; or whether they have any indwelling long term venous catheters; or sort of imaging findings of having a mediastinal mass in this case, for example; or leptomeningeal enhancement seen within the brain; so, those are things that would make you suspect that there might be invasive infection of some sort; which in this case, unfortunately, only a few of these technical features were present. So, these are the things I generally look for.

STEPHEN BACCHI:            That's really helpful. And it is important to note that sometimes it can be occult, and that's why examination, re-examination is important. And it does have implications for the risk of haemorrhagic transformation. Could you talk to those risks briefly?

RUDY GOH:        So, we know that in patients with an ischaemic stroke, the risk for haemorrhagic transformation would include being on blood thinners. And some would argue that some anticoagulants make you at higher risk of haemorrhagic transformation as opposed to dual platelet therapy at the time of initial stroke, especially with anticoagulation, especially if they've been whether they've had—thrombolysis would increase the risk of haemorrhagic transformation as well.

In this case, where there is a patient with an infective course of endocarditis and leading to a stroke, essentially, if they have a nycotic aneurysm that would significantly increase the risk of having haemorrhagic transformation from that stroke itself. If they have on the CT scan or a digital subtraction angiography showing an early venous drainage sign, there will be an indicator of potential early haemorrhagic transformation, as well.

And it is important to keep this in mind, especially when thinking about surgery in infective endocarditis. Many tertiary centres and metropolitan centres have started infective endocarditis multidisciplinary meetings with collaborative efforts being put in by the infectious diseases, neurologists, as well as the cardiothoracic teams to try and optimize outcomes for patients with endocarditis, potentially requiring surgery in the acute setting after acute ischaemic stroke.

STEPHEN BACCHI:            Thanks. So, just to summarize, so, when there's an ischaemic stroke in the same infection, in particular, infective endocarditis, there can be an increased risk of haemorrhagic transformation, in particular, if there's my cardiac aneurysms. And these patients often require subspecialty management and multidisciplinary involvement. That'd be fair to say?

RUDY GOH:        Yep.

STEPHEN BACCHI:            Now in terms of our case, unfortunately, the patient on day six of their admission, had no neurological recovery. And he met clinical criteria for brain death, and this is very sad outcome and a young patient. His autopsy showed to simulated A flavus complex infection involving multiple territories or multiple regions, including the thigh, the mediastinum, and the brain itself. So, this infection was angioinvasive, and had infiltrated the brain parenchyma. And this is presumably the aetiology of the haemorrhagic transformation.

This case has demonstrated the potential severity of ischaemic stroke with the death of a young, otherwise well, patient. And it has also highlighted the importance of considering unusual or atypical aetiologies of ischaemic stroke beyond the conventional arteriosclerosis or atrial fibrillation that we deal with every day. What were your take home points from this case, Rudy?

RUDY GOH:        So, in any case of ischaemic stroke, especially in the young patient, it is important to think broadly, and not just to default to calling it a cardioembolic stroke, just because it affects multiple territories. And to look at the patient and perform a good systematic review, looking at the entire body, including the skin not forgetting the dermatological system as one of the largest organs in the body. Especially, looking at the thigh itself, was a good clue for what was going on in his patient.

And it's also important to involve our colleagues as well, to collaborate with other specialties such as the cardiologists, to try and provide the best care and outcome for our patients, especially when they have complicated clinical history and presentation. So, that we can put all our brain minds together to come up with a holistic plan for the patient that takes into account all of the abnormal findings that we have.

STEPHEN BACCHI:            Thank you for that. So, I really appreciate your time. Joining us on the podcast, Rudy. I think I've learned a lot from this case. We are grateful to the patient's family for having shared their story, so that we can all learn and we can all provide better care in future. It's always very sad when the young person dies from any cause, but ischaemic stroke particularly does strike quickly. And we're passionate about I think that we've learned several things from this case, and also highlighted a few areas of ongoing research where we can continue to develop medical knowledge in this field and work towards treating ischaemic strokes in future. So, thanks again Rudy, and we look forward to having you back on the podcast.

RUDY GOH:        Thanks, Stephen.

STEPHEN BACCHI:            And otherwise we look forward to the next discussion. Bye for now.

MIC CAVAZZINI: That was Associate Professor Stephen Bacchi with another fascinating Pomegranate Case Report. The actual paper was published in Case reports in Neurology, February 2024. The full-text is freely available under the title Disseminated Aspergillosis with Mediastinal Invasion Causing Fatal Stroke in an Immunocompetent Young Man. The first author was Dr Robert Yarham and the senior author, Prof Timothy Kleinig who conduct their research through University of Adelaide along with Dr Rudy Goh. 

To find more Case Reports go to racp.edu.au/podcast and then scroll through the episode archive. It’s easier to search for episodes from a pod browser like Spotify, Apple Podcasts or Castbox, but first you need to subscribe to Pomegranate Health. You can now even find us at the RACP Youtube Channel. As well as the [Case Report] format there are the [IMJ On-Air] episodes recorded with authors of articles published in the Internal Medicine Journal. The episodes prefaced with [Journal Club] adopt a similar format, but showcase impactful research published in other journals by members of the RACP.

In all of the above formats, the interview will be led by an RACP physician, whereas the episodes prefaced with the Ep number are those I’ve developed myself. They will cover a range of cultural and professional topics, not just clinical ones. And you’ll occasionally see episodes tagged [Guest Lecture], where I share with you particularly engaging seminars that I’ve come across. There truly is something for everyone. And don’t forget the College Learning Series located at elearning.racp.edu.au. These lectures are written around the Basic Training Curriculum and there are 19 lectures each on neurology and infectious diseases.

This podcast was recorded on the coastal lands of the Kaurna people in Adelaide and the Gadigal clans around Sydney Harbour. I pay respect to their elders past, present and in training. I’m Mic Cavazzini, thanks for listening.