IM Board Review #10 - Neuro-Oncology

And just like that, we have made it to the last episode of the IM Board Review Series! 

In this episode, we talk about all things neuro-oncology including:

• Presentation 
• Primary CNS tumors 
• Metastatic Brain Tumors
• Medical Management of Complications of CNS Tumors
• Paraneoplastic Syndromes

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The views expressed do not necessarily represent those of any associated organizations. The information in this podcast is for educational and informational purposes only and does not represent specific medical/health advice. Please consult with an appropriate health care professional for any medical/health advice.

Chapters

• 0:00 Neuro-Oncology
• 0:29 Presentation
• 2:21 Metastatic tumors
• 4:47 Primary CNS tumors
• 10:21 Medical Management of Complications of CNS tumors
• 14:50 Paraneoplastic syndromes

Transcript

Dr. Michael Kentris: 0:00

Hello and welcome back to the Neurotransmitters. I'm your host, dr Michael Kentris, and today we are concluding for now at least, our IM board review series on neurology topics, and our topic today is neuro-oncology. Same caveat as the rest of the recordings in this series is this is not an exhaustive discussion of the topic. This is intended for mostly those high-yield topics that are likely to show up on your boards. So let's start off with presentation. Typically, symptoms will often have a subacute to chronic onset, as opposed to something like stroke, which is more that hyperacute onset of symptoms. However, you may get these hyperacute or or acute symptoms, such as focal neurologic symptoms or seizures, when there are acute changes within the tumor, such as hemorrhages, or if a critical amount of edema or swelling accumulates and hits a tipping point right, a lack of cerebral compliance, and we'll talk about edema and herniation later on. One of our most common symptoms is, of course, headache, classically positional, worse with lying down, worse in the mornings, maybe also worsened by activities that can transiently raise intracranial pressure or ICP, such as coughing, sneezing, straining or Valsalva maneuvers. And then you can also get symptoms of increased ICP as well, such as nausea, vomiting, blurred vision. You may get some papilledema on fundoscopic exam. They may get also some isolated cranial nerve palsies. Sixth nerve palsy is a common one due to its long intracranial course. If the mass is in the posterior fossa you can also get symptoms that suggest hydrocephalus, as well as sometimes syncopal episodes due to some transient again pressure, due to different maneuvers that can cause episodes of stiffening, like flexor, extensor, posturing, things of that nature. Obviously, if there is a concern for an intracranial mass, imaging is the order of the day. So a lot of these people will start out getting CTs of the head, typically without contrast, just because those are what are obtained most emergently in the emergency department and those types of settings. But in most situations the preferred imaging is going to be an MRI brain, with and without contrast. Whenever we're worried about an intracranial mass, we do want to get contrasted images if possible.

Dr. Michael Kentris: 2:16

In broad strokes, we can think of intracranial masses as belonging to one of two categories. There are those that arise directly from the central nervous system or CNS, so primary CNS tumors. And then there are those that arise somewhere else in the body and metastasize to the brain, so metastatic brain tumors that arise from some primary cancer elsewhere in the body. Now let's start with the second category. So metastatic brain tumors are the most common type, broadly speaking, of intracranial tumor. Some of the common sources kind of mirror the common cancers in the general population, so lung, breast, kidney, melanoma. Often on MRI these will appear as ring-enhancing lesions at the gray-white cortical junction, and this is a common place for things that have hematogenous spread to kind of get captured is in that gray-white junction.

Dr. Michael Kentris: 3:04

Typically, if you're suspicious for metastatic disease, you're going to want to get imaging of the rest of the body, so typically a CT of the chest, abdomen and pelvis and or a full-body PET scan to try and find a primary source of the cancer. If there is no primary found on imaging, very often you may need to biopsy that brain tumor and or resect the brain tumor if the symptoms are severe enough. Treatment is typically dictated by what the underlying primary cancer is, with some special considerations for the intracranial mass, which may include things like radiation therapy either whole brain or stereotactic or focused beam radiotherapy, depending on where the lesions are located, how numerous they are, and so forth. A special case that can present is something called carcinomatous meningitis. So this is a fairly rare presentation that often appears with symptoms very similar to a meningitis encephalitis type of picture. The MRI of the brain in an ideal situation will show nodular meningeal enhancement, and this can be seen with any kind of cancer, but lymphoma or leukemia are considered somewhat classic in terms of this presentation. This may be seen with a phenomenon known as CNS escape of certain kinds of cancer after the initial treatment, where the cancer cells escape into the central nervous system and the chemotherapy that they were receiving wasn't particularly effective at penetrating the blood-brain barrier.

Dr. Michael Kentris: 4:23

In these situations, in addition to imaging, you're obviously going to want to get CSF studies, including cytology and or cytometry. This is sometimes called a quote liquid biopsy and has relatively low sensitivity, unfortunately. So if there is a high clinical suspicion, you may need to do multiple high-volume lumbar punctures. Up to three is sometimes the recommendation. If your clinical suspicion remains high, let's talk about a few primary CNS tumors.

Dr. Michael Kentris: 4:51

We're going to start off with the most common primary CNS tumor, which is a meningioma. Typically, these are benign. They can rarely be malignant, but they can still cause significant symptoms due to their mass effect and or some peritumoral edema. On MRI of the brain you'll usually see some homogeneous enhancement with a quote dural tail, which essentially is this little piece of the tumor that extends into the dura and also lights up with that contrast enhancement. So this is one of the few tumors that you can make a pretty confident diagnosis based on imaging alone. If there are no symptoms and the imaging characteristics are typical, without any of these high-risk features, they may not need surgery and can just be monitored over time.

Dr. Michael Kentris: 5:35

Next up is glioblastoma multiforme. This is the most aggressive type of glioma, a WHO World Health Organization grade 4 tumor. So gliomas are ranked from grade 1 to grade 4, grade 1 being low grade, grade 4 being a GBM or glioplastoma multiforme. Unfortunately, in addition to being the most aggressive type of glioma, it is also the most common. The only risk factor that we're very confident of is a history of radiation exposure. It does seem to correlate with developing. These. Mri of the brain will usually show a large lesion, although it can vary in size, typically with central necrosis, some heterogeneous enhancement and mass effect and peritumoral edema. One of the radiographic features that is very suspicious for a GBM is a butterfly lesion and this is where you have tumor crossing the midline, usually via the corpus callosum, and it can make a sort of butterfly type appearance.

Dr. Michael Kentris: 6:31

Treatment is usually a combination of surgery, radiation and chemotherapy, so, if possible, resection of as much of the tumor bulk as possible. One of the reasons that GBMs can have a high recurrence is that beyond the visible margins you can get this microscopic invasion of cancer cells, and so it does unfortunately have a high rate of recurrence. You'll also use radiation therapy as well as chemotherapy. The mainstays of chemotherapy include temozolomide. You'll also sometimes see a medication called bevacizumab added to the regimen, which is a VEGF or vascular endothelial growth factor inhibitor, and so this can help reduce the amount of blood supply to the tumor tissue, but it may increase the risk of other complications such as stroke or heart attack.

Dr. Michael Kentris: 7:18

The prognosis for GBM is generally not very good. Five-year survival is under 10% in most cases, and, depending on how aggressive the cancer is when it is first discovered, survival may be measured in months rather than years. Some of the features that may portend a better prognosis is actually in younger people, age under 45, if there is minimal residual tumor following resection, and if the person undergoes chemotherapy and radiation therapy as well. So all of these factors tend to be associated with better prognosis overall.

Dr. Michael Kentris: 7:48

Next up, we have primary CNS lymphoma, so this one is a bit of a hard entity to nail down. It can present with lots of different symptoms meningitis, encephalitis type symptoms, multiple cranial neuropathies, multiple neurologic deficits that can involve the spinal cord. So it can look like a lot of different things and a lot of times you're going to need to keep it on your differential diagnosis. If there's meningeal involvement, if there are these multifocal cranial nerves or multifocal central nervous system type symptoms, if any type of neoplastic process is on the list, this one is probably going to be on there for kind of these unusual presentations.

Dr. Michael Kentris: 8:28

One of the big risk factors for developing this is chronic immunodeficiency and this can be from either a history of HIV or from someone who is on chronic immunotherapy for some other condition. Pathologically it is typically a diffuse large B-cell lymphoma and on MRI in the test it'll say a quote single ring-enhancing lesion, but in reality it is not always a single lesion. This may also appear sometimes like an inflammatory disorder Think of things like vasculitis or even demyelinating disease like MS also. So again, it's one of these things that can mimic a lot of other conditions. So you have to keep it on your list when there's something that's just not quite right. In terms of recommended lab testing, you'll be obviously checking CBCs, cmps, things like that, checking for different autoimmune conditions, in particular things like sarcoidosis. You'll also be checking for HIV and then you'll be doing your routine CSF testing as well as cytology and flow cytometry. Further imaging will often include a whole body PET or CT and again you're looking to see is this in fact true primary CNS lymphoma or is this a more generalized lymphoma that has spread to the CNS?

Dr. Michael Kentris: 9:37

As far as treatment goes, these tend to be very responsive to steroid therapy. However, there has been some debate in recent years. Steroids such as dexamethasone, if given prior to diagnosis, may reduce the yield of biopsy or CSF testing, and so it's generally recommended to avoid giving empiric steroids prior to a definitive tissue diagnosis, if possible. There have been some papers in recent years that have questioned this traditional view, but that's the general recommendation at this point in time. Treatment usually involves methotrexate and rituximab plus or minus radiation therapy, and generally there is a good initial response to treatment. However, recurrence is unfortunately fairly common.

Dr. Michael Kentris: 10:21

Let's talk about some medical management of complications of CNS tumors, so obviously we've got a brain tumor. A very common thing that we run into are seizures. These are commonly seen more in low-grade rather than high-grade gliomas, and also more typically seen with tumors near the cortex, as opposed to those that are in deeper locations or in the posterior fossa, which makes sense because seizures are generated from the cortex. You can also get seizures very common with a couple specific kind of tumors, like gangliogliomas and disembryoplastic neuroepithelial tumors or DNETs, and very often these can cause medically refractory epilepsy in about 90% of patients. So typically, resection of these tumors should be done if possible.

Dr. Michael Kentris: 11:06

Now one question you may be asking yourself is what anti-seizure medication should I be choosing for these patients? Because there are dozens on the market. So we have to think what are the other things that are going on with this patient's medical story? If they're going to be getting chemotherapy, if they're going to be on medications that might cause certain kinds of organ dysfunction, we want to try and pick an anti-seizure medication that is not going to exacerbate those problems. So very often, our first choices are going to be either levotiracetam or lacosamide. The benefits of these two are that they are both available in IV form, so you can get them up to a therapeutic dose fairly quickly and they have a fairly low potential for interaction with chemotherapy. So on the flip side of that, we want to avoid some of these older anti-seizure medications due to interaction concerns, especially these hepatically metabolized ones. So things like phenobarbital, phenytoin, valproic acid, carbamazepine, for instance. There are others, right, there are dozens of anti-seizure medications out there, but these are some good rules of thumb to keep in mind.

Dr. Michael Kentris: 12:09

Typically, we do not start people with a brain tumor on prophylactic anti-seizure medications. However, if they do have tumor resection, very often we'll do a week of anti-seizure medication following that surgery. Now, if someone has a seizure after that one week period post-tumor resection, very likely they are going to need to be on anti-seizure medications for a longer period of time, perhaps lifelong. It depends on several factors, including like is there still some post-surgery edema? Are there things that could be irritative to the brain going on beyond just the scar tissue itself? So you can get this post resection epilepsy still develop, even after the tumor is gone, depending on the situation.

Dr. Michael Kentris: 12:49

So let's talk about edema. So sometimes it may not be the tumor itself but the edema that it causes in the surrounding brain tissue that can lead to the focal neurologic symptoms, increased intracranial pressure or, in the worst case scenario, even herniation. And in these situations you may see someone with an abrupt decline in mental status. You may see some changes in exam, the classic one being changes in pupil reactivity. Some changes in exam, the classic one being changes in pupil reactivity.

Dr. Michael Kentris: 13:17

Emergent options for treatment. We want to elevate the head to 30 degrees. We can hyperventilate to an arterial PCO2 of over 25 millimeters of mercury. You can also bolus with hypertonic saline or mannitol and you can give glucocorticoids such as dexamethasone, which helps to kind of calm down the blood-brain barrier, leading to improvement in some vasogenic edema. So all of these obviously have a little bit of differences in terms of from the time they're administered to the time of effect, but they are often considered bridge therapies to a neurosurgical intervention.

Dr. Michael Kentris: 13:47

Next up we have venous thromboembolism. So in cancer it's not surprising that sometimes people can have clotting disorders. So if the patient has a need for anticoagulation it is generally recommended to go ahead and anticoagulate them if they have no intracranial hemorrhages or their platelets are over 50,000. Some forms of metastatic cancer do have a slightly higher risk of hemorrhagic disease. The mnemonic is MRCTBB, that's, melanoma, renal cell carcinoma, choriocarcinoma, thyroid carcinoma or teratoma, bronchogenic carcinoma and breast carcinoma. These types of cancers can show up as hemorrhagic metastases and obviously if there is evidence of hemorrhage, you want to avoid anticoagulation if possible. But if there is no hemorrhage then you don't necessarily need to avoid anticoagulation, purely on the type of cancer. In fact, post resection it is recommended to start prophylactic anticoagulation as well as mechanical compression devices as soon as safely possible in hospitalized patients.

Dr. Michael Kentris: 14:50

Last up, we're going to talk about perineoplastic syndromes. So this is a broad family of very unusual neurologic presentations. So this is a family of antibody mediated neurologic syndromes. Now these can be either primary or perineoplastic and many of them are described. We're only going to talk about a handful today. These typically will be kind of subacute in onset, but they can be quite varied in their symptom presentation.

Dr. Michael Kentris: 15:18

Some of the things that may raise your suspicion is that you get this new onset of seizures or status epilepticus, new onset of psychosis, plus or minus seizures, new onset movement disorders such as ataxia chorea, myoclonus, tremors, opsoclonus myoclonus and various types of peripheral neuropathy as well. Again, the key to some of these is going to be the subacute timeline, so typically in the weeks to months onset. If this is occurring in the setting of a known cancer, then certain types of cancer will have certain associations with different perineoplastic syndromes. However, if you are seeing symptoms suggestive of a perineoplastic syndrome, then you do need to do an investigation for cancer and that's going to include our typical testing such as MRI, brain with and without contrast, csf testing and again those CAT scans or PET scans of the rest of the body as well, and then certain antibody testing also. So let's talk about a few of the rest of the body as well and then certain antibody testing also.

Dr. Michael Kentris: 16:14

So let's talk about a few of the more classic perineoplastic syndromes. So one of the ones that I think most people are familiar with is the NMDA receptor encephalitis. So this will typically present with kind of a subacute onset of psychosis that can progress to seizures and typically has an association with an ovarian teratoma. Small cell lung cancer is one of the cancers that has an association with an ovarian teratoma. Small cell lung cancer is one of the cancers that has an association with multiple different perineoplastic syndromes. One of the ones that we will think about are these voltage-gated potassium channels, in particular the LGI-1 type, and you can get brachiofacial dystonic seizures or the little twitches in the face and the arm, and these patients will often present with kind of a subacute cognitive decline. Paraneoplastic cerebellar degeneration is another classic one.

Dr. Michael Kentris: 17:02

The antibody is anti-YO or PCA1. Some of these antibodies unfortunately have more than one name, just to add to the complexity, but anti-YO is a good one to remember. And this has an association with breast cancer. And to flip this around, if you have a patient with a history of breast cancer who suddenly starts becoming ataxic, you need to differentiate is this related to chemotherapy, like is this a sensory ataxia or is this more of a central ataxia? An MRI brain showing cerebellar atrophy or even enhancement can be a very strong indicator that you're dealing with this. And then antibody testing for that anti-yo antibody can help really clinch the diagnosis.

Dr. Michael Kentris: 17:43

Stiff person syndrome is a challenging diagnosis to make. Oftentimes people have muscle rigidity, typically in the axial muscles more than the limbs, although it can be both. It does have a strong association with type 1 diabetes also. These are the anti-GAD antibodies, although there are some other antibodies that can also be associated with stiff person syndrome. There is an association with thymoma. However, you can also see these without any cancer at all. So one thing to keep in mind with the anti-GAD antibody you will see this elevated with type 1 diabetes without stiff person symptoms. So you do have to use your clinical judgment in these situations also.

Dr. Michael Kentris: 18:22

There are many kinds of neuropathy that can be associated with perineoplastic syndromes. The classic one is anti-Hugh, and this is also associated with small cell lung cancer. There are many antibodies that are associated with perineoplastic syndromes that we haven't talked about, and it feels like there are more being identified every year. We're not going to really go into those because it does start to get a little into the weeds. The best treatment for most of these is to treat the cancer. If there is a cancer identified, some of these patients, even if the cancer is treated, may need immunotherapy after that. Typical first-line treatments include things such as IVIG, methylprednisolone, plasma exchange, and chronic therapies can also include some of these, such as IVIG or plasma exchange, but you can also see other immunotherapy agents like azathioprine, mycophenolate, rituximab and sometimes other agents as well, depending on the situation.

Dr. Michael Kentris: 19:12

So we have reached the end and, to reiterate, this is not an exhaustive list. This is a very broad overview on some of the more common things that you may see either in practice or, at the very least, on your board exams. So, with that caveat in mind, I hope you found this helpful in your preparation and, if you haven't, do listen back to our other topics in the Internal Medicine Board Review series. I think this will help a lot of people who are prepping for that particular test and I'm probably biased, but I think it has some decent information there for folks who are working in primary care settings as well. As always, you can find more information about what we do at theneurotransmitterscom. You can find me on Twitter, slash X at D-R E N T R I S, dr Kentris, and you can reply in the show notes here as well If you want to drop us a line with any questions or show suggestions. Thank you again for listening and we'll see you next time.