Neurosurgery: Pituitary Tumours and Aneurysms
Good evening everybody and welcome to this evening’s webinar, Neurosurgery: Pituitary Tumours and Aneurysms. We are joined by our presenters this evening, Professor Antonio Di Ieva and Dr Shinuo Liu, and our facilitator, Dr Tim Senior.
Before we jump in, I would like to make an Acknowledgement of Country. We recognise the traditional custodians of the land and sea on which we live and work and we pay our respects to Elders past and present.
I would like to formally introduce our presenters now. Professor Antonio Di Ieva is a consultant neurosurgeon with 18 years of experience in brain, skull-based, peripheral nerve and spine surgery, as well as pain neuromodulation. He is a Professor at Macquarie University, Professor of Neurosurgery in Italy and Associate Professor of Neuroanatomy in Austria, with main interests in neuro-oncology, traumatic brain injury and concussion, skull-based surgery and pain neuromodulation. Professor Di Ieva is an Australian Research Council Future Fellow and Head of Computational Neurosurgery Lab at Macquarie University.
Dr Liu is a Fellow of the Royal Australasian College of Surgeons. He graduated from University of New South Wales Medicine with Honours and was trained at major Australasian Neurosurgical Centres including Royal North Shore, Auckland City, St George and Macquarie University Hospitals. During training, he completed an award-winning PhD and Masters of Surgery at Macquarie University. His academic and clinical subspecialty interests include fluids of the CNS, neurovascular conditions, spine and neuro-oncology. He has academic appointments at UNSW, UWS, Macquarie University and University of Auckland.
And finally our facilitator this evening, Dr Tim Senior. Tim is a GP at Tharawal Aboriginal Corporation in South Western Sydney. He is also an RACGP Medical Advisor for the National Faculty of Aboriginal and Torres Straight Islander Health, and Senior Lecturer in General Practice and Indigenous Health at UWS. So welcome, Antonio, Shinuo and Tim. And I am going to hand over to Tim now who is going to take us through our learning outcomes before we hand over to Antonio this evening. So, welcome, Tim.
Thank you very much, Sammi. Good evening to you all. I hope you are all keeping well and those of you in lock down are doing alright. These are our learning outcomes for this evening. So this is educational-speak for what we are going to get out of the next hour or so. So by the end of this online activity, you should be able to recognise radioanatomical features related to the diagnosis and treatment of tumours of the sellar and parasellar regions. Be aware of the different surgical options for the treatment of pituitary tumours, and optimise patients’ surgical post-surgical management. Discuss the treatment options, risks of management and follow up of both ruptured and unruptured aneurysms and discuss some of the landmark evidence that informs contemporary management of aneurysms.
So I would like to introduce Professor Antonio to start us off. Thank you very much.
Thank you very much, Tim and Sam. So, you should be able to see my screen now.
Yes, we can.
Sorry, it failed the first time. I do not know why.
That is alright.
So, good evening everyone. I am very glad to introduce the topic of pituitary surgery 3.34… skull-based surgery. So, we talk about the master gland. It has this definition because it is really astonishing to think how such a small gland in the centre of the skull and the head can control so much the metabolism of the human body. If you remember that anterior portion of the pituitary gland is called adenohypophysis and it produces six hormones whilst the posterior part is the neurohypophysis, producing two hormones regulated by the hypothalamus here in the brain, and all these combinations of hormones can control all the most important metabolic functions of the human body. The master gland is also in a position of paramount importance in the brain.
If can see there it is in the centre of the skull base in a structure called the sella and it is surrounded by structures called the cavernous sinuses in which there is the carotid artery and some nerves which go to the eyeball, including the third, fourth and the sixth nerve for the movement of the eye, as well as the trigeminal nerve branches. And upwards, over the pituitary gland there is the optic chiasm so it is very importantly related to vision, as well. And more above, we have the brain of course. Below the pituitary gland we have the sphenoid sinus which is a very important gate to reach the gland, as you will see later on.
So, when we talk about the pathologies of the pituitary gland, the most common one is the pituitary adenoma. It is pretty common. The prevalence is 20% of the general population and 77 cases in every hundred thousand people may have a pituitary adenoma. Generally it is defined as a so-called benign tumour, although I will explain that this is not always the case, and not all will require treatment, 50% do, but many other times we just do radiological follow up over time because they do not grow or they do not cause any trouble. They may be classified as a secreting if they secrete hormone, or they are just giving a mass effect on the structures around because they do not secrete anything. And just for the size, they can be defined as a microadenoma when it is smaller than 1 cm, or macroadenoma when they are bigger than 10 mm. Or they can be even giant, like 3 cm or 4 cm in diameter.
Pituitary adenoma is the commonest one, but there are many other tumours. Because if you consider that this is the skull base and the pituitary gland is here, this is what we call the parasellar region and whatever can come around can affect the pituitary gland as well. So it can be a meningioma for example, coming from the meninges or another tumour like a schwannoma, craniopharyngioma, paraganglioma and the other tumours that we will see some examples of later on.
So you may understand it is so complex it requires a complex team, and the pituitary team is formed by general practitioners as well as many specialists, including endocrinologists, neurosurgeons, neuroradiologists, ENT surgeon and so on. So you can imagine the GP is the central hub of a very complex network, and the multidisciplinary team meetings are very important meetings that we do to have a better characterisation of the lesion and to have a better agreement overall and optimal decision-making for our patients.
So, the neurosurgeon of course has different functions in his team. He is not just the surgeon himself, but he is also examining the patient from a neurological point of view and checking the images, checking the blood tests and assessing the indications for potential surgery. The endocrinologist is always involved, especially when the tumour is secreting. So there are some static tests to check the pituitary function, but also dynamic tests to see how the pituitary functions, all of its functions can be checked and ruled out. The endocrinologist is also very important when the tumour is not secreting, because of course the mass effect caused by the pituitary tumour can cause a compression on the normal pituitary gland. So instead of having a rise of the hormones, you can have a kind of hypopituitarism.
Neuro-ophthalmologist is involved when we have a microadenoma for example, where the tumour can compress the optic chiasma. And this is a typical bitemporal hemianopia in which the patient has a loss of the visual field, especially on the temporal part of the visual field, and it has a restriction to just the nasal parts. Sometimes, patients do not realise this kind of deficit because it comes very, very slowly over time and they just start to tilt and turn their head more and more, and many times they compensate for the deficit. And many times they come to do a visual field which is already as severe as this one. The neuro-ophthalmologist checks also for the function of the cranial nerves and moving of the eyeballs. So a patient having diplopia can be affected in terms of compression of the third or sixth nerve for example.
And it is very important to also have the involvement of the radiologist with some expertise in neuroradiology. And the radiologist does not give us just some indication of the features of the tumour itself, but also on the anatomical localisation. So we have, this is an MRI of a macroadenoma and you can see that it is very important to know if the tumour or which compartment is more involved with the tumour. So in this case, the tumour is compressing the optic chiasm and invading the cavernous sinus on the right side, wrapping the carotid artery.
And we have different classification systems to see how the tumour invades the compartment. The most important one is not just the Hardy classification system which is purely diagnostic but also the Knosp classification system that is even prognostic. Why? Because the tumour can be characterised by if it invades or not the cavernous sinus. In general we know that a grade 3 or grade 4 is a tumour wrapping the carotid artery and invading the cavernous sinus. And the why is it prognostic? Because we know that this kind of tumour most likely will not be cured just by surgery, because surgery can remove very easily this part, but the part in the cavernous sinus is very risky because of the risk of the carotid artery and the patient’s risk of ophthalmoparesis with the diplopia. So many times these classification systems give us an indication before the treatment, that most likely this patient will need for example surgery or something else. And this something else could be for example, gamma knife radiosurgery which is a very high dose of radiation all culminated in one single spot which is the tumour itself. And that is why it is classified as a surgery, but is a radiation treatment, basically.
So when I define the so-called benign tumours, this is an example that I have been using for many years just because it is an example that the pituitary tumour is not always benign. Imagine this patient has had three operations for a Cushing syndrome because there is an ACTH tumour. But after that she was not cured and she underwent a resection of the adrenal glands. After that, she had a regrowing of the tumour because this is called the Nelson syndrome. She underwent radiotherapy after that. She had ophthalmoparesis. She was blind in one eye. And you know, that day she underwent treatment with the temozolamide, that you may know is used for glioblastoma. So this is a benign tumour treated like a cancer, and eventually the patient even died after nine years of complications related to secretion of the ACTH and cortisol. So, it is not always a benign tumour. This is something that we defined and classified in a paper published seven years ago in Nature Reviews Endocrinology, in which for the first time we were talking about aggressive pituitary adenomas which behave almost like cancers. So these are something to be estimated in a better way.
In terms of treatment, we can treat with surgery, we can go to the pituitary gland by means of transcranial approach or endoscopic transcranial approaches or a combination of these approaches in what we call cranioendoscopic approaches. Nowadays, big part of the operations are performed endonasally with an endoscope, so with the help of an ENT surgeon. And you can well understand that this looks minimally invasive because we enter in the nostril which is an anatomic pathway, reaching the sphenoidal sinus which is our gateway not just for the pituitary gland, but for the entire skull base from the crista galli all the way to the clivus and so basically we can treat all the midline lesions on the skull base by means of extended approach in the sphenoidal sinus.
So here we go with some illustrative cases that I have collected over the last year, just to show some examples. This 34-year-old gentleman had a headache and visual deficit. It is interesting that when presented to me, he had already undergone a resection of 3 cm of tumour which was a gonadotrope type. Now after one year, he had a headache again and he spoke about the growth of the tumour. So imagine that the tumour with a maximal size of 3 cm grew to 2.8 cm. So the take home message for this specific case, is that pituitary adenoma are very, very slow to grow. It is very rare that the tumour can have such a big growth. So many times, there is a bad definition of cure of adenoma when the tumour was just biopsied rather than resected. Indeed, when I saw this patient, this was the big adenoma, but if you go to see the CT scan in the bone setting, you can see that this is the window that the first surgeon. So it basically means that from here it was impossible to remove all this tumour. So eventually it was just a very partial resection and what was called a recurrence was not recurrence, it was a remnant. And the remnant underwent a full resection which is shown here, so this is the operation I did in which shows the scar of the previous operation. This is the tumour, all the tumour exposed and the tumour at the end of the resection which is possible to show the abnormal anatomical landmarks of the sella. So in this case, this was a total resection. And so the take home message for this is there is a big difference between recurrence which is a something recurring over time, or a remnant which is something left over from the previous treatment.
Acromegaly is pretty rare but is important that GPs recognise this, because many times these patients come to the attention of the endocrinologist and neurosurgeon, really very, very late. Imagine this patient with diabetes, hypertension, sleep apnoea, which are all features of acromegaly, but the most important thing that was not considered by the patients and carers, was that his hands were growing over time and even this tongue was growing over time. When they did the test, the growth hormone was very, very high. But look for example at his hand. His hand was considered growing over time very slowly but this is a student of mine putting her hand in comparison to the patient’s hand, which is huge. And even the patient was changing their glove size every two or three years. And this is the tumour which was an acromegaly tumour or GHoma which can be completely cured by surgical resection without using any other treatment. And indeed, after total resection, you can see that very, very quickly the growth hormone falls down and over time the hormone which is triggered by the growth hormone, which is the IGF, Insulin Growth Factor produced by the liver, over time also normalises. So this patient starts to have better control of all of the problems related to acromegaly.
Cushing’s disease is sometimes pretty bad already when the tumour is very small like a microadenoma. This patient had hypertension, borderline glucose intolerance with acne, hirsutism, headaches, proximal muscle weakness and central obesity which are all features related to high level of cortisol in the blood, including the dorsal fat pad. So she had the cushingoid face with the moon facies and the striae on the belly. This is the typical resection we do and you can see that this is a normal gland, and the tumour here is very, very small. It is just five millimetres in diameter. But when the tumour is removed from this location, the patient can have a normalisation of the cortisol very, very, very quickly and so can be considered cured. So this the whole 5 mm resection of the microadenoma.
Apoplexy is one of the few emergencies we have with pituitary tumours. It means that an adenoma is very, very dormant many times, but when it bleeds can have a mass effect, very important, on the gland, so causing hypopituitarism and compression of optic chiasm. This patient for example already multiple episodes of apoplexy. But one of those brought the patient to Emergency because she felt very, very sick and that is what we saw. Huge bleeding in the cavity of the previous resection. And this is a typical surgery, in which basically you can see that we do not remove that much tumour. This is the only tumour, but basically this is more blood. So it is really fresh blood, or subacute bleeding in the cavity which is giving the rise to compression of the surrounding structures. So this is one of the few emergencies we have in pituitary surgery. And the postoperative imaging showed a complete resolution of the bleeding and the mass effect on the gland or on the pituitary and the optic chiasm.
Completely different lesion, but very similar features is the Rathke’s cyst. This is just a cyst. So basically it is a lining of epithelium which is filled with a kind of a liquid which looks like cerebral spinal fluid on MRI. And patient can become even blind. This patient came with a very bad bitemporal hemianopia and if you see the lesion, it looks like a huge tumour, but it is just a lesion which is cystic and with T2 looks like cerebral spinal fluid and on T1 looks again like CSF. So this not an adenoma. And what we do is try to remove the capsule, but this is not the most important thing. The most important thing is removing the mass effect. So many times we just create a hole in the lesion itself, in an operation that we call a marsupialization. So basically we create multiple holes in order to drain the liquid out and to reduce the mass effect. So this is the capsule which has been sent to the pathology centre and came back like a normal lining of a cyst, and we just created multiple holes. And as you can see from the postoperative MRI, there is no mass effect anymore because the cyst is completely gone and she recovered her vision very, very quickly, a few days after surgery.
A completely different lesion is a meningioma. As I told you, there are sellar and parasellar region tumours, completely different regions to the adenoma, and historically these tumours are treated by means of a transcranial approach. But nowadays we can have very selective choices in our approach, in which this is a meningioma coming from a structure called a tuberculum sellae in the skull base. And you can well see that easiest way is going from the nose and sphenoidal sinus to remove this tumour. So, this is the neuronavigation system bringing us to where we have to be. This is the tumour. This is the histopathology showing clearly the features of the meningioma and this is the surgery which has shown we can go in extended fashion upwards to remove the tumour, exposing the brain, exposing the arteries over the circle of Willis, exposing the optic nerves with a very, very small cut on the side of the dura which is less than 2 cm. But everything is done from the nose.
Craniopharyngioma is a completely different lesion and is very rare. It is a remnant of embryological structures. It is rare, but can be a lot of trouble, because many times they can give completely panhypopituitarism or diabetes insipidus or compression of the optic structures. So patients can show up with a hemianopia or even blindness sometimes. There are essentially two different kinds. One is mainly cystic. So this is a cystic craniopharyngioma and you can see from the surgery that we are talking about a cyst. So this is a lining. The difference with a Rathke’s cyst is that with a Rathke’s cyst, we do not have to remove the lining. In this case we try to remove as much as possible because otherwise we can have recurrence. And by removing this cyst you can see the normal structure. This is the pituitary stalk there. So the infundibulum. This is the frontal lobe of the brain and the pituitary gland is here. It is a very complex surgery just because we try to preserve all the structures around because for example looking here, there are very, very tiny arteries like this and we cannot close these arteries because these are terminal arteries going to the optic chiasm. So they are called the superior hypophyseal artery but if we close this, the patient can get blindness basically. So every structure has to be preserved, including here the anterior cerebral artery, the brain. So it is still a benign tumour but it can give rise to a lot of problems and looking at the optical nerve, how smooth and thin it is because it is compressed by the tumour for many, many years.
Now, craniopharyngioma can be also very solid, not cystic, and there is a subtype called papillary. This is an interesting case I did over the last few months. This was a very solid tumour compressing the optic tracts, not the optic nerves. And the patient was almost blind in one eye. And in this case, for some reason that is too long to explain, but basically I decided to do a transcranial approach to try to remove as much tumour as possible to decompress the optic tract. And the goal was achieved because although I did just a subtotal resection, the patient recovered their vision. The problem is that six months later, got a tumour which was double the size of what I already removed before. This was a real recurrence which is pretty rare for a craniopharyngioma, but to make the story short, this is the tumour growing evenly inside the third ventricle. So in this case I decided to do an endoscopic transcranial approach and in this case we were able to achieve a total resection, also because the patient had already complete dysfunction of the pituitary gland. So in this case we could be a little more aggressive because there was not so much to lose any more in terms of preservation of the pituitary stalk and we could attempt a total resection in order to decompress the optic nerves. And indeed, after the total resection, this is the last element of the tumour, and here it is shown that I am cutting it from the optic tract, this is the optic tract, and this is the last piece of the tumour left over. And as you may remember from the MRI the tumour was even going in the third ventricle, and indeed this is the endoscope from the nose in the third ventricle. So you can even do intraventricular surgery from the nose. And the fact that you can see the ventricle here shows that the ventricle is unblocked, so the tumour is completely out. And this is such a nice picture, that I will show you again, because it is not very common to see the third ventricle from an endoscopic approach. These are the foramina of Monro which link to the lateral ventricles. This is the fornix. This is the hypothalamus here. These are all the structures which were plugged by the tumour before surgery. And this is the MRI after surgery which showed complete resection and optic chiasm completely free.
The last tumour is chordoma. It is the last tumour that I want to show, that is also very rare. It is one in every one million people. And we are talking about benign tumours giving a lot of trouble. Chordoma is locally aggressive, so this is less benign than the other ones that we have seen before. It is very difficult to remove and many times, surgery is not definitive. Many times people have to undergo radiation therapy or even something much more aggressive like proton beam radiosurgery for the countries which have that kind of modality. So this is a young girl that I did years ago who came in with headache and double vision, and this is a tumour coming from the clivus, destroying, eroding the clivus. A very aggressive tumour. And we did an almost total resection, leaving something small. This very, very small thing grew after a few years and this is a patient I did when I was in Toronto for example and the patient to Boston to do proton beam radiosurgery later on. So it is a very complex pathology to treat.
The last matter is, whatever the treatment is, very important also is the postoperative management. If you remember the involvement of the team, how important having different disciplines in the preoperative assessment and interoperatively also, we need more disciplines like neurosurgeon and ENT surgeon for example. The postoperative assessment is the same. So the radiologist is very important. We need to understand if there is a remnant or recurrence, or the complications related to surgery. The neuro-ophthalmologist is very important to check the visual field, if that is getting better, worse or not, the ENT surgeon is involved to check the nose because there are potential nasal complications following the surgery, and according to the histopathology we might have involvement of other specialists, like the neuro-oncologists. You might have seen the involvement of the neuro-oncologist in aggressive pituitary adenoma before in which we had to use temozolomide for example. And sometimes there are additional oncologists because the patient might need gamma knife radiosurgery or refractory radiotherapy like the tumours I showed you before.
Are there medications which shrink pituitary tumours? And a specific question about whether we can start cabergoline as a GP before referring?
Yes. Thank you for following that. I was focussed on surgery that most likely I missed one thing, that all the tumours but the prolactinoma are surgical but for example the prolactinoma is the one that in general can be managed very, very well with just cabergoline, and this tumour shrinks very, very quickly. Remember two things. A tumour can shrink but it can still bleed, so can still need surgery, and 30% of prolactinoma can be resistant to the dopamine agonist. So 50% of prolactinoma are still surgical. However, there are other kinds of tumours, like even GHoma in which the medical treatment is still there but is not the first line. So, prolactinoma medical treatment is the first line, all the other tumours, surgery is the first line. I tell patients that they shrink tumour, but they have to keep going forever and as soon as they stop, the tumour comes back. In some patients they want surgery in that case, because they start to have side effect or intolerance to the cabergoline for example.
Lovely. Thank you very much.
Thanks to you, Tim.
Alright. Good evening everyone. My name is Shinuo and thank you for participating and staying awake. I know everyone would much rather be watching Netflix with their children and dogs. But aneurysms are pretty common, and I get a lot of questions about aneurysms so hopefully tonight, we can take away a couple of key messages that will allay fears of patients, you know, address really common questions, and I hope at the end of this talk you can really be able to chat to patients about unruptured aneurysms, maybe even a little bit about ruptured aneurysms and subarachnoid haemorrhage, because they are becoming really, really common questions in the community. So the title of the talk is “Bringing the Thunder”. For those of you who are fans of the hit Broadway musical Hamilton, you will get the reference, but of course you know the other thing it refers to is the thunderclap headache associated with aneurysmal subarachnoid haemorrhage. So let us get into it.
What is an aneurysm? Oh, it looks like the screen is not progressing.
Do you want to try putting it back in presentation mode and perhaps give the space bar or your right arrow on your keyboard a go? That is a bit strange that it is not progressing.
Very strange. Sorry, everyone.
Give it a go. Zoom likes to keep us on our toes.
Oh well, maybe I will just have to do that. How is that?
Try putting it up again. We should be able to progress it. In your bottom left corner there was little arrows that popped up, grey ones, but you can always right click on the slide. Oh, that looks like it is moving between those two.
Alright, a little hiccup. So, yes, so what is an aneurysm? An aneurysm is an abnormal dilatation of a cerebral vessel, okay? So, of an artery. So, the talk is not about you know, aneurysms outside of the skull. Okay? So cerebral aneurysms are a very different beast and we will come to that in a bit. But to get to the definition, an aneurysm usually forms on a branch point and it is important to understand that they involve abnormalities that encompass all three layers of the artery. So that is the intima, the media and the adventissure. And the classic, you know, text book you know description of the abnormality at the microscopic level is that there is a breakdown of the internal elastic lamina and we think that the reasons why aneurysms happen at branch points is because of the haemodynamic stress that occurs when blood has to you know, flow around the branch point and that leads to sheer stress and energy loss. So, it is probably a mixture of haemodynamics and some kind of inflammatory reaction that involves a whole variety of you know, inflammatory agents like TNF and interleukins and MMPs, metallo matrix proteinases.
So the reason why aneurysms in the brain are different compared with aneurysms in the abdominal aorta, is because aneurysms in the brain lie in the subarachnoid space. Okay? That is a very different environment compared to the retroperitoneum. So the other important thing is that the adventissure of the artery is quite different. It is very deficient compared to say a thoracic aorta aneurysm or a renal artery aneurysm and so this probably explains why there is a fairly high frequency of these aneurysms in the general population which we will again get to in a moment. So this is a dissected specimen from a patient who passed away of something else, but you can see an abnormal dilatation of this you know, of this bifurcation of the internal carotid artery into the middle cerebral and the anterior cerebral arteries. So that is a fairly common location. So the cerebral aneurysms found in the subarachnoid space, and that is what makes them dangerous, because if the aneurysm ruptures, then blood is spilled all into the subarachnoid space, and this is one of the most devastating causes of strokes in our community.
Aneurysms are found in the anterior circulation at least 85% of the time. So that means the internal carotid artery and its branches. So very common locations include the anterior communicating artery, the middle cerebral artery bifurcation, the posterior communicating artery about 15% of aneurysms are found in the basilar apex or the bifurcation of the basilar artery and the posterior inferior cerebellar arteries. Okay? There are other locations, but they are not that common.
So, so far we have been talking about saccular aneurysms or berry aneurysms, you know as they are commonly referred to, and they comprise of at least 90% to 95% of all you know, cerebral aneurysms. There are other types of aneurysms, so if you look at this diagram here, this is a bullet. So this poor person has a bullet lodged in you know, near the interhemispheric fissure between the two halves of the brain. And a delayed cerebral angiogram shows that there is a little aneurysm at a very unusual spot. And so this is what we call a traumatic aneurysm. And they are different from saccular aneurysms because they often do not involve abnormalities of all three layers of the artery. So, they can you know, be a complete blow out of an artery and the only thing covering the little blow out is a clot or a really thin layer of adventissure. So they are highly, highly dangerous. But of course they are very uncommon because we do not really have very many gunshot wounds in this country.
This is an example of what we call a giant aneurysm. So giant aneurysms are really quite uncommon. They comprise less than 5% of all saccular aneurysms and they are defined as anything bigger than an inch. Okay, so 2.5 centimetres. This series of diagrams demonstrates what we call a blister aneurysm, so they are often found on the internal carotid artery. So a blister aneurysm is often due to a dissection, so there a haematoma gets in between the intima and the media, or the tunica medial and the adventissure. And again, you get this really unstable blowout in the entire wall of the artery and the only thing that might be covering the wall of the artery might be some thin adventissure or maybe a blood clot. So they are very treacherous lesions.
Then finally, we have this very unusual aneurysm that is found on a very distal branch of the anterior cerebral artery and so this is in a patient with infective endocarditis. So very similar to say a traumatic aneurysm. You get little septic emboli that travel all the way to the distal branches and that causes an inflammation in the wall of the artery, and again you can have a highly unstable wall morphology. You might only have one or two layers covering you know, a defect, instead of all three layers in the saccular aneurysm.
Right, so how do aneurysms present? More and more, we are seeing aneurysms found incidentally. So a patient will have headaches or they have tinnitus or some kind of dizziness and they get a scan and then because MRI scans and CT scans are becoming A) more prevalent and B) more sophisticated, we can see even you know, three or four millimetre aneurysms. And so that is by far the most common way aneurysms are presenting these days, at least in Sydney. You know, people have a scan for another reason. Aneurysms generally do not cause symptoms, okay? They are found in the subarachnoid space, they keep enlarging, and the first time that many cause aneurysms present, is when they rupture. So that is with a subarachnoid haemorrhage. You will recall that the aneurysm arises in the subarachnoid space, so blood is spilt in the spaces that contain CSF. And so this is an example of a patient with a very classic aneurysm arising from the anterior communicating artery. I know this because this is what we call a flame haemorrhage in the frontal lobe. The patient has this characteristic high density. Okay, this white stuff that looks like a spider pattern. And so that blood is spilt all over the basil cisterns, okay? And hydrocephalus as a result of subarachnoid haemorrhage is very common and this patient certainly has it. So, subarachnoid haemorrhage, probably the second most common presentation.
There are other way aneurysms can present. So, a posterior communicating artery aneurysm is very close to the oculomotor nerve. And you can see that this is the internal carotid artery with an abnormal dilatation. So that is the aneurysm. And this here is the oculomotor nerve. So the oculomotor nerve has the autonomic fibres, the parasympathetic fibres that cause you know, dilatation of the pupil on the outside. And so when an aneurysm enlarges, it compresses all the fibres, you know, both the parasympathetic stuff on the outside as well as the motor fibres, and so you get a complete third nerve palsy. So the patient presents with complete ptosis, do the eyelid shut, the eye is down and out, and the pupils do not work. In diabetes however, you get this microvascular you know, ischemia alright? So that affects the motor fibres okay, in the middle. But the peripheral fibres where the parasympathetic fibres run are spared and so in diabetes you can actually get a third nerve palsy, but the pupil still works. So this is what we call a pupil-sparing you know, deficit. And so when a patient has both diabetes and a posterior communicating artery aneurysm, often you have to just rely on the examination of the pupil to figure out what is going on. Aneurysms can cause strokes, ischemic strokes if they are large okay, and they have thrombus within them. So this is an aneurysm in the internal carotid artery near the skull base. And this is an example of an embolic stroke where clot within the aneurysm has been thrown off. You get this distal MCA infarct. And so this is an MR angiogram showing this medially projecting aneurysm which is incompletely imaged because part of this is all thrombus. You cannot see it. And this catheter angiogram also does not show it. So, aneurysms can really cause embolic strokes, okay?
Right, so this is a really important slide. There are some pretty important statistics that I think will allay a lot of patient’s fears. Brain aneurysms are really common. We think they affect 2% to 3% of the general population, and yet subarachnoid haemorrhage, so aneurysmal subarachnoid haemorrhage, only occurs 10 out of one hundred thousand people every year. So in New South Wales, that is only 800 people compared to 3% of eight million people. I mentioned that if you get a subarachnoid haemorrhage, that is 5% of all strokes in our community. And if you do some fancy mathematics, we think that something like may half a percent or a quarter of a percent of all aneurysms rupture during a patient’s lifetime. So perhaps something like 99% of brain aneurysms will never, ever rupture. Okay? Aneurysms generally get diagnosed or present with a subarachnoid haemorrhage between patients in their forties and their sixties, and they peak during you know, the fifties. Women get aneurysms more than men, generally after menopause which is in the peak incident period. But before menopause, men and women are affected equally. We think something like 10% of people die you know, in the pre-hospital period, which is very significant and of those people who make it to hospital, something like two thirds of patients will end up with some kind of neurological deficit. So it is a really, really big problem for those 800 people in New South Wales who get an aneurysmal subarachnoid haemorrhage every single year.
So, if 99% of aneurysms probably do not rupture during a patient’s lifetime and most aneurysms are diagnosed incidentally, when a patient has an MRI because they got, you know, hit on the head with a cricket ball and here they are with an MRI brain with an MCA aneurysm, how do you decide whether a patient needs prophylactic treatment of the aneurysm? How do you counsel a patient as to whether this aneurysm is so-called safe, or so-called dangerous? So we look at two sets of factors. There are aneurysm-specific factors that the patient has no control over and then there are patient factors. And some of these are modifiable. So we think that smoking and high blood pressure and of course other you know, cardiovascular risk factors are strong contributors to aneurysm growth and even rupture. So it is probably those pro-inflammatory cytokines and cascade to do with smoking that causes this. And then with high blood pressure, you know, the more haemodynamically volatile the flow, the more stress is placed on the artery, the more likely you are going to form an aneurysm. There is nothing you can do about short stature or bicuspid aortic valves, but these are some of the patient factors that are thought to be associated with formation of aneurysms, and then the aneurysm size is important to determine whether it is going to stay the same or if it can be monitored or if it should be treated. We think that larger aneurysms are more likely to rupture. Some aneurysms you know in the midline or in the specific bifurcation points, so for example the anterior communicating artery or the basilar aneurysm because they are in the posterior circulation are more than likely to rupture. It is controversial whether multiple aneurysms are more likely to rupture, and then there are some other factors to do with you know, the morphology of the aneurysm, is it smooth or is it bumpy or you know, suggestive of heamodynamic instability within the fundus of the aneurysm.
So we take all of these into account and we are able to kind of counsel the patient on the natural history of aneurysms. But that is a pretty large talk, so we might save that for another day. Are there aneurysms that are inherently safe? And the answer is yes and no. But generally if an aneurysm is outside of the dura, they cannot cause a subarachnoid haemorrhage. So this is diagram of the internal carotid artery as it courses through the base of the skull, and it has to puncture through two layers of dura, okay? And the two layers of dura form these dural rings, okay, a distal and a proximal one. And so any aneurysm that is formed proximal to the distal dural ring, is not really, it is not really possible for these aneurysms to rupture and cause a subarachnoid haemorrhage. That is not to say they cannot cause problems, so if you have an aneurysm in the cavernous sinus, okay, so the cavernous segment of the internal carotid artery, they can enlarge and cause cranial nerve deficits or they can rupture and cause a carotid cavernous fistula. And these fistula can mean that you have really high flow of blood from the artery into the cavernous sinus which is venous. And patients present with chemosis and proptosis and have an angry red eye and it is pulsatile.
So, this is a demonstration of the pulsatile, you know, proptosed eye. And this is a cavernous sinus aneurysm. We might skip over this, but this sometimes aneurysms which you think might be outside of the dura will actually surprise us and they are actually found just on the diaphragma sellae. It is actually intradural so you have to sometimes get fancy MRI scans to determine whether they are intradural or extradural.
So how do we diagnose aneurysms? Well, the gold standard is with a catheter angiogram. So it is basically a coronary angiogram but you keep going higher and higher and you do internal carotid and vertebral artery injections. So that is the best test for it, but these days CT circle of Willis angiograms are getting better and better, and their sensitivity and specificity are in the orders of the high nineties, so very, very good for screening and diagnosis. MR angiograms are getting better every year, but not as good as CT angiograms but in some institutions such like the SAN for example, they do excellent MR angiograms. And that is an example of an MR angiogram showing an MCA artery bifurcation aneurysm okay, which is kind of fuzzy and you know, you think maybe there is an aneurysm there. And this is a CT angiogram of exactly the same patient and the aneurysm, you can see that you know, you have got a little branch coming off the neck of the aneurysm and so CTAs are very, very good. And of course, catheter angiogram gives you the best pictures and you can get reconstructions of the catheter angiograms.
Right. So, really briefly, if a patient has a thunderclap headache, alright, they really should be sent to the Emergency Department, and in the Emergency Department, a CT scan is performed. But if the CT scan is equivocal, so you cannot really see subarachnoid haemorrhage but the history is very suggestive of an aneurysmal subarachnoid haemorrhage, so worst headache, came on like a thunderclap, the lumbar puncture still remains the gold standard, okay? And the emergency physicians will do a lumbar puncture and send the CSF for bilirubin and oxyhaemoglobin analysis. So this is what we refer to as xanthochromia.
Family screening is a really common question. So to summarise, there really are not international guidelines on who should get screened, but we generally recommend that if two first degree relatives have aneurysms, then all the first degree relatives should be screened with an MR angiogram or a CT angiogram after the age of 18. Children do harbour aneurysms, but it is exceedingly rare. As rare as hens teeth. And if families have you know, if there are multiple family members with aneurysms, maybe the predilection for forming aneurysms and so it is a good idea to do screening every five years with CT or MR angiogram.
So briefly, how do we treat aneurysms? So aneurysms can be treated from the outside. So that is with open clipping of the aneurysm, with an aneurysm clip to reconstruct the artery, or they can be treated from within the artery with coils, with stents, that you know, ensure that the coil can be packed in tightly. Or with special flow diverter stents, okay, which allow blood to flow through the blood vessel but not into the aneurysm, so over time this will form a thrombus. So neurosurgeons do this. Interventional neuroradiologists and some dual trained neurosurgeons do these ones.
So what do we do as neurosurgeons? Most aneurysms are in the anterior circulation. So they often are in say the middle cerebral artery. And so, this is an example of a craniotomy, an open craniotomy called a pterional craniotomy because the bone flap is centred on the pterion. And so, given a general anaesthetic, the head is placed in rigid fixation, and I did not do this, but some neurosurgeons like giving funny haircuts. We do much more minimally invasive haircuts.
This is an example of an aneurysm clipping. So this patient has an elective repair of an aneurysm. This is the pterional craniotomy, that is the frontal lobe, that is the temporal lobe. So we are just opening the Sylvian fissure. So we do not transgress brain. We do not operate in the brain. It is all outside of the brain. So, these are middle cerebral artery branches, okay, which we skeletonise and we divide the arachnoid, okay, and we follow the blood vessels from the really distal branches proximally to where the aneurysm is found. So here we are, getting the aneurysm dissected, okay? Finding the proximal middle cerebral artery, and here is the aneurysm. Abnormal dilation. And we careful dissect all the branches off the aneurysm dome and then we place an aneurysm clip just across the neck of the aneurysm, nice and easy. We reconstruct the bifurcation of the middle cerebral artery and then we go, just reinforce the aneurysm, and then we puncture the aneurysm and no more blood has come out. So that is how we fix the aneurysm.
So, sorry about that. Alright. So, a brief, we probably will not talk about endovascular, but basically you know, there are ways to determine how tightly packed the coils are. So, there are a few large studies on aneurysms, so they include the ISUIA which is in the reference. So basically, big, multicentred randomised trials were conducted on cerebral aneurysms about 15 to 20 years ago, and the take-away message is that many small aneurysms do not rupture. And so these give you the risk of rupture of aneurysms of certain sizes over five years. And so, you really have to kind of get to the seven to 12 millimetres to get to the two to three, you know, two to 15% risk over five years of rupture, which is considerable.
ISAT is a trial comparing open surgery to endovascular treatment in ruptured aneurysms. And so the take-home message is that both are pretty good, but endovascular surgery probably gives slightly more people you know, good neurological outcomes over 10 years. Not by much. And so that has really changed the landscape of treatment of aneurysms. Far more coiling, far fewer open repairs.
And then there are tools available for us to you know, calculate the risk of an aneurysm rupturing you know in the next five years. They have problems, but they exist. And so in the community, you know when patients are discharged after a subarachnoid haemorrhage, or even sometimes elective aneurysm treatment, what do we have to look out for? So, hydrocephalus insidious. It is an insidious thing, it happens in 20% of people with ruptured aneurysms and you really have to look out for it. When patients have aneurysms, they have hydrocephalus and they really have to have treatment for that. So that is in the form of VP shunts. Patients can get Terson syndrome. So these are haemorrhages in the posterior compartment of the eye. So this shows a subhyaloid haemorrhage, and so you really have to look out for this. Ask patients can they see properly? Refer them to ophthalmologists. And then when aneurysms get treated, sometimes they can recur, so this becomes a chronic disease. So you can see how an aneurysm, this basilar aneurysm has been coiled, and then you get recurrences over time.
And this is a plug for Macquarie Neurosurgery, but we also in the field of you know, neurovascular neurosurgery, we also work in a multidisciplinary team. Patients often want to resume driving, so we have occupational therapists who we can refer to for driving assessments. You know, 60% of patients have neurological sequelae so we sometimes send them to neuropsychology. Patients might have seizures, you know for a long time, so we liaise with the neurologists. And of course, our interventional neuroradiology colleagues, we meet with them every single week and we discuss cases and what is the best management for our patients.
So that is it. Thank you very much.
Thank you very much, that was fantastic and we are finishing just on time. Thank you everyone for all your questions coming through as well and thanks to Professor Antonio and Dr Liu for answering those as we go. So these are our learning outcomes that we covered at the beginning. So hopefully if you look through that, we have covered all of those this evening. I would like to thank both our presenters tonight for covering so comprehensively such an interesting topic for us GPs, and thank you Sammi for organising it all behind the scenes.