November 13, 2024 • 20 mins
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
- Check out our website at www.theneurotransmitters.com to sign up for emails, classes, and quizzes!
- Would you like to be a guest or suggest a topic? Email us at contact@theneurotransmitters.com
- Follow our podcast channel on 𝕏 @neuro_podcast for future news!
- Find me on 𝕏 @DrKentris
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.
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Dr. Michael Kentris (00:00):
Hello and welcome back to the
Neurotransmitters.
I'm your host, dr MichaelKentris, and today we are
concluding for now at least, ourIM board review series on
neurology topics, and our topictoday is neuro-oncology.
Same caveat as the rest of therecordings in this series is
this is not an exhaustivediscussion of the topic.
(00:23):
This is intended for mostlythose high-yield topics that are
likely to show up on yourboards.
So let's start off withpresentation.
Typically, symptoms will oftenhave a subacute to chronic onset
, as opposed to something likestroke, which is more that
hyperacute onset of symptoms.
However, you may get thesehyperacute or or acute symptoms,
(00:44):
such as focal neurologicsymptoms or seizures, when there
are acute changes within thetumor, such as hemorrhages, or
if a critical amount of edema orswelling accumulates and hits a
tipping point right, a lack ofcerebral compliance, and we'll
talk about edema and herniationlater on.
One of our most common symptomsis, of course, headache,
classically positional, worsewith lying down, worse in the
(01:06):
mornings, maybe also worsened byactivities that can transiently
raise intracranial pressure orICP, such as coughing, sneezing,
straining or Valsalva maneuvers.
And then you can also getsymptoms of increased ICP as
well, such as nausea, vomiting,blurred vision.
You may get some papilledema onfundoscopic exam.
They may get also some isolatedcranial nerve palsies.
(01:29):
Sixth nerve palsy is a commonone due to its long intracranial
course.
If the mass is in the posteriorfossa you can also get symptoms
that suggest hydrocephalus, aswell as sometimes syncopal
episodes due to some transientagain pressure, due to different
maneuvers that can causeepisodes of stiffening, like
flexor, extensor, posturing,things of that nature.
(01:49):
Obviously, if there is aconcern for an intracranial mass
, imaging is the order of theday.
So a lot of these people willstart out getting CTs of the
head, typically without contrast, just because those are what
are obtained most emergently inthe emergency department and
those types of settings.
But in most situations thepreferred imaging is going to be
an MRI brain, with and withoutcontrast.
(02:11):
Whenever we're worried about anintracranial mass, we do want
to get contrasted images ifpossible.
In broad strokes, we can thinkof intracranial masses as
belonging to one of twocategories.
There are those that arisedirectly from the central
nervous system or CNS, soprimary CNS tumors.
And then there are those thatarise somewhere else in the body
and metastasize to the brain,so metastatic brain tumors that
(02:33):
arise from some primary cancerelsewhere in the body.
Now let's start with the secondcategory.
So metastatic brain tumors arethe most common type, broadly
speaking, of intracranial tumor.
Some of the common sources kindof mirror the common cancers in
the general population, so lung, breast, kidney, melanoma.
Often on MRI these will appearas ring-enhancing lesions at the
(02:56):
gray-white cortical junction,and this is a common place for
things that have hematogenousspread to kind of get captured
is in that gray-white junction.
Typically, if you're suspiciousfor metastatic disease, you're
going to want to get imaging ofthe rest of the body, so
typically a CT of the chest,abdomen and pelvis and or a
full-body PET scan to try andfind a primary source of the
(03:16):
cancer.
If there is no primary found onimaging, very often you may
need to biopsy that brain tumorand or resect the brain tumor if
the symptoms are severe enough.
Treatment is typically dictatedby what the underlying primary
cancer is, with some specialconsiderations for the
intracranial mass, which mayinclude things like radiation
therapy either whole brain orstereotactic or focused beam
(03:39):
radiotherapy, depending on wherethe lesions are located, how
numerous they are, and so forth.
A special case that can presentis something called
carcinomatous meningitis.
So this is a fairly rarepresentation that often appears
with symptoms very similar to ameningitis encephalitis type of
picture.
The MRI of the brain in anideal situation will show
(04:00):
nodular meningeal enhancement,and this can be seen with any
kind of cancer, but lymphoma orleukemia are considered somewhat
classic in terms of thispresentation.
This may be seen with aphenomenon known as CNS escape
of certain kinds of cancer afterthe initial treatment, where
the cancer cells escape into thecentral nervous system and the
chemotherapy that they werereceiving wasn't particularly
(04:20):
effective at penetrating theblood-brain barrier.
In these situations, in additionto imaging, you're obviously
going to want to get CSF studies, including cytology and or
cytometry.
This is sometimes called aquote liquid biopsy and has
relatively low sensitivity,unfortunately.
So if there is a high clinicalsuspicion, you may need to do
multiple high-volume lumbarpunctures.
(04:42):
Up to three is sometimes therecommendation.
If your clinical suspicionremains high, let's talk about a
few primary CNS tumors.
We're going to start off withthe 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 totheir mass effect and or some
(05:04):
peritumoral edema.
On MRI of the brain you'llusually see some homogeneous
enhancement with a quote duraltail, which essentially is this
little piece of the tumor thatextends into the dura and also
lights up with that contrastenhancement.
So this is one of the fewtumors that you can make a
pretty confident diagnosis basedon imaging alone.
(05:24):
If there are no symptoms andthe imaging characteristics are
typical, without any of thesehigh-risk features, they may not
need surgery and can just bemonitored over time.
Next up is glioblastomamultiforme.
This is the most aggressivetype of glioma, a WHO World
Health Organization grade 4tumor.
(05:44):
So gliomas are ranked fromgrade 1 to grade 4, grade 1
being low grade, grade 4 being aGBM or glioplastoma multiforme.
Unfortunately, in addition tobeing the most aggressive type
of glioma, it is also the mostcommon.
The only risk factor that we'revery confident of is a history
of radiation exposure.
It does seem to correlate withdeveloping.
(06:04):
These.
Mri of the brain will usuallyshow a large lesion, although it
can vary in size, typicallywith central necrosis, some
heterogeneous enhancement andmass effect and peritumoral
edema.
One of the radiographicfeatures that is very suspicious
for a GBM is a butterfly lesionand this is where you have
tumor crossing the midline,usually via the corpus callosum,
(06:27):
and it can make a sort ofbutterfly type appearance.
Treatment is usually acombination of surgery,
radiation and chemotherapy, so,if possible, resection of as
much of the tumor bulk aspossible.
One of the reasons that GBMscan have a high recurrence is
that beyond the visible marginsyou can get this microscopic
(06:48):
invasion of cancer cells, and soit does unfortunately have a
high rate of recurrence.
You'll also use radiationtherapy as well as chemotherapy.
The mainstays of chemotherapyinclude temozolomide.
You'll also sometimes see amedication called bevacizumab
added to the regimen, which is aVEGF or vascular endothelial
growth factor inhibitor, and sothis can help reduce the amount
(07:11):
of blood supply to the tumortissue, but it may increase the
risk of other complications suchas stroke or heart attack.
The prognosis for GBM isgenerally not very good.
Five-year survival is under 10%in most cases, and, depending
on how aggressive the cancer iswhen it is first discovered,
survival may be measured inmonths rather than years.
Some of the features that mayportend a better prognosis is
(07:34):
actually in younger people, ageunder 45, if there is minimal
residual tumor followingresection, and if the person
undergoes chemotherapy andradiation therapy as well.
So all of these factors tend tobe associated with better
prognosis overall.
Next up, we have primary CNSlymphoma, so this one is a bit
of a hard entity to nail down.
(07:55):
It can present with lots ofdifferent symptoms meningitis,
encephalitis type symptoms,multiple cranial neuropathies,
multiple neurologic deficitsthat can involve the spinal cord
.
So it can look like a lot ofdifferent things and a lot of
times you're going to need tokeep it on your differential
diagnosis.
If there's meningealinvolvement, if there are these
multifocal cranial nerves ormultifocal central nervous
(08:18):
system type symptoms, if anytype of neoplastic process is on
the list, this one is probablygoing to be on there for kind of
these unusual presentations.
One of the big risk factors fordeveloping this is chronic
immunodeficiency and this can befrom either a history of HIV or
from someone who is on chronicimmunotherapy for some other
condition.
(08:38):
Pathologically it is typicallya diffuse large B-cell lymphoma
and on MRI in the test it'll saya quote single ring-enhancing
lesion, but in reality it is notalways a single lesion.
This may also appear sometimeslike an inflammatory disorder
Think of things like vasculitisor even demyelinating disease
(08:58):
like MS also.
So again, it's one of thesethings that can mimic a lot of
other conditions.
So you have to keep it on yourlist when there's something
that's just not quite right.
In terms of recommended labtesting, you'll be obviously
checking CBCs, cmps, things likethat, checking for different
autoimmune conditions, inparticular things like
sarcoidosis.
You'll also be checking for HIVand then you'll be doing your
(09:19):
routine CSF testing as well ascytology and flow cytometry.
Further imaging will ofteninclude a whole body PET or CT
and again you're looking to seeis this in fact true primary CNS
lymphoma or is this a moregeneralized lymphoma that has
spread to the CNS?
As far as treatment goes, thesetend to be very responsive to
(09:41):
steroid therapy.
However, there has been somedebate in recent years.
Steroids such as dexamethasone,if given prior to diagnosis,
may reduce the yield of biopsyor CSF testing, and so it's
generally recommended to avoidgiving empiric steroids prior to
a definitive tissue diagnosis,if possible.
There have been some papers inrecent years that have
(10:03):
questioned this traditional view, but that's the general
recommendation at this point intime.
Treatment usually involvesmethotrexate and rituximab plus
or minus radiation therapy, andgenerally there is a good
initial response to treatment.
However, recurrence isunfortunately fairly common.
Let's talk about some medicalmanagement of complications of
(10:24):
CNS tumors, so obviously we'vegot a brain tumor.
A very common thing that we runinto are seizures.
These are commonly seen more inlow-grade rather than
high-grade gliomas, and alsomore typically seen with tumors
near the cortex, as opposed tothose that are in deeper
locations or in the posteriorfossa, which makes sense because
seizures are generated from thecortex.
(10:45):
You can also get seizures verycommon with a couple specific
kind of tumors, likegangliogliomas and
disembryoplastic neuroepithelialtumors or DNETs, and very often
these can cause medicallyrefractory epilepsy in about 90%
of patients.
So typically, resection ofthese tumors should be done if
(11:05):
possible.
Now one question you may beasking yourself is what
anti-seizure medication should Ibe choosing for these patients?
Because there are dozens on themarket.
So we have to think what arethe other things that are going
on with this patient's medicalstory?
If they're going to be gettingchemotherapy, if they're going
to be on medications that mightcause certain kinds of organ
(11:25):
dysfunction, we want to try andpick an anti-seizure medication
that is not going to exacerbatethose problems.
So very often, our firstchoices are going to be either
levotiracetam or lacosamide.
The benefits of these two arethat they are both available in
IV form, so you can get them upto a therapeutic dose fairly
quickly and they have a fairlylow potential for interaction
(11:46):
with chemotherapy.
So on the flip side of that, wewant to avoid some of these
older anti-seizure medicationsdue to interaction concerns,
especially these hepaticallymetabolized ones.
So things like phenobarbital,phenytoin, valproic acid,
carbamazepine, for instance.
There are others, right, thereare dozens of anti-seizure
medications out there, but theseare some good rules of thumb to
(12:07):
keep in mind.
Typically, we do not startpeople with a brain tumor on
prophylactic anti-seizuremedications.
However, if they do have tumorresection, very often we'll do a
week of anti-seizure medicationfollowing that surgery.
Now, if someone has a seizureafter that one week period
post-tumor resection, verylikely they are going to need to
(12:29):
be on anti-seizure medicationsfor 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 beirritative to the brain going on
beyond just the scar tissueitself?
So you can get this postresection epilepsy still develop
, even after the tumor is gone,depending on the situation.
(12:49):
So let's talk about edema.
So sometimes it may not be thetumor itself but the edema that
it causes in the surroundingbrain 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 maysee someone with an abrupt
decline in mental status.
You may see some changes inexam, the classic one being
(13:12):
changes in pupil reactivity.
Some changes in exam, theclassic one being changes in
pupil reactivity.
Emergent options for treatment.
We want to elevate the head to30 degrees.
We can hyperventilate to anarterial PCO2 of over 25
millimeters of mercury.
You can also bolus withhypertonic saline or mannitol
and you can give glucocorticoidssuch as dexamethasone, which
helps to kind of calm down theblood-brain barrier, leading to
(13:35):
improvement in some vasogenicedema.
So all of these obviously havea little bit of differences in
terms of from the time they'readministered to the time of
effect, but they are oftenconsidered bridge therapies to a
neurosurgical intervention.
Next up we have venousthromboembolism.
So in cancer it's notsurprising that sometimes people
can have clotting disorders.
So if the patient has a needfor anticoagulation it is
(13:58):
generally recommended to goahead and anticoagulate them if
they have no intracranialhemorrhages or their platelets
are over 50,000.
Some forms of metastatic cancerdo have a slightly higher risk
of hemorrhagic disease.
The mnemonic is MRCTBB, that's,melanoma, renal cell carcinoma,
choriocarcinoma, thyroidcarcinoma or teratoma,
(14:21):
bronchogenic carcinoma andbreast carcinoma.
These types of cancers can showup as hemorrhagic metastases
and obviously if there isevidence of hemorrhage, you want
to avoid anticoagulation ifpossible.
But if there is no hemorrhagethen you don't necessarily need
to avoid anticoagulation, purelyon the type of cancer.
In fact, post resection it isrecommended to start
(14:43):
prophylactic anticoagulation aswell as mechanical compression
devices as soon as safelypossible in hospitalized
patients.
Last up, we're going to talkabout perineoplastic syndromes.
So this is a broad family ofvery unusual neurologic
presentations.
So this is a family of antibodymediated neurologic syndromes.
(15:04):
Now these can be either primaryor perineoplastic and many of
them are described.
We're only going to talk abouta handful today.
These typically will be kind ofsubacute in onset, but they can
be quite varied in theirsymptom presentation.
Some of the things that mayraise your suspicion is that you
get this new onset of seizuresor status epilepticus, new onset
(15:26):
of psychosis, plus or minusseizures, new onset movement
disorders such as ataxia chorea,myoclonus, tremors, opsoclonus
myoclonus and various types ofperipheral neuropathy as well.
Again, the key to some of theseis going to be the subacute
timeline, so typically in theweeks to months onset.
If this is occurring in thesetting of a known cancer, then
(15:49):
certain types of cancer willhave certain associations with
different perineoplasticsyndromes.
However, if you are seeingsymptoms suggestive of a
perineoplastic syndrome, thenyou do need to do an
investigation for cancer andthat's going to include our
typical testing such as MRI,brain with and without contrast,
csf testing and again those CATscans or PET scans of the rest
(16:10):
of the body as well, and thencertain antibody testing also.
So let's talk about a few ofthe rest of the body as well and
then certain antibody testingalso.
So let's talk about a few of themore classic perineoplastic
syndromes.
So one of the ones that I thinkmost people are familiar with
is the NMDA receptorencephalitis.
So this will typically presentwith kind of a subacute onset of
psychosis that can progress toseizures and typically has an
(16:32):
association with an ovarianteratoma.
Small cell lung cancer is oneof the cancers that has an
association with an ovarianteratoma.
Small cell lung cancer is oneof the cancers that has an
association with multipledifferent perineoplastic
syndromes.
One of the ones that we willthink about are these
voltage-gated potassium channels, in particular the LGI-1 type,
and you can get brachiofacialdystonic seizures or the little
(16:52):
twitches in the face and the arm, and these patients will often
present with kind of a subacutecognitive decline.
Paraneoplastic cerebellardegeneration is another classic
one.
The antibody is anti-YO or PCA1.
Some of these antibodiesunfortunately have more than one
name, just to add to thecomplexity, but anti-YO is a
(17:13):
good one to remember.
And this has an associationwith breast cancer.
And to flip this around, if youhave a patient with a history
of breast cancer who suddenlystarts becoming ataxic, you need
to differentiate is thisrelated to chemotherapy, like is
this a sensory ataxia or isthis more of a central ataxia?
An MRI brain showing cerebellaratrophy or even enhancement can
(17:34):
be a very strong indicator thatyou're dealing with this.
And then antibody testing forthat anti-yo antibody can help
really clinch the diagnosis.
Stiff person syndrome is achallenging diagnosis to make.
Oftentimes people have musclerigidity, typically in the axial
muscles more than the limbs,although it can be both.
It does have a strongassociation with type 1 diabetes
(17:56):
also.
These are the anti-GADantibodies, although there are
some other antibodies that canalso be associated with stiff
person syndrome.
There is an association withthymoma.
However, you can also see thesewithout any cancer at all.
So one thing to keep in mindwith the anti-GAD antibody you
will see this elevated with type1 diabetes without stiff person
(18:17):
symptoms.
So you do have to use yourclinical judgment in these
situations also.
There are many kinds ofneuropathy that can be
associated with perineoplasticsyndromes.
The classic one is anti-Hugh,and this is also associated with
small cell lung cancer.
There are many antibodies thatare associated with
perineoplastic syndromes that wehaven't talked about, and it
feels like there are more beingidentified every year.
(18:39):
We're not going to really gointo those because it does start
to get a little into the weeds.
The best treatment for most ofthese is to treat the cancer.
If there is a cancer identified, some of these patients, even
if the cancer is treated, mayneed immunotherapy after that.
Typical first-line treatmentsinclude things such as IVIG,
methylprednisolone, plasmaexchange, and chronic therapies
(19:01):
can also include some of these,such as IVIG or plasma exchange,
but you can also see otherimmunotherapy agents like
azathioprine, mycophenolate,rituximab and sometimes other
agents as well, depending on thesituation.
So we have reached the end and,to reiterate, this is not an
exhaustive list.
This is a very broad overviewon some of the more common
things that you may see eitherin practice or, at the very
(19:23):
least, on your board exams.
So, with that caveat in mind, Ihope you found this helpful in
your preparation and, if youhaven't, do listen back to our
other topics in the InternalMedicine Board Review series.
I think this will help a lot ofpeople who are prepping for
that particular test and I'mprobably biased, but I think it
has some decent informationthere for folks who are working
(19:44):
in primary care settings as well.
As always, you can find moreinformation 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 inthe show notes here as well If
you want to drop us a line withany questions or show
suggestions.
Thank you again for listeningand we'll see you next time.
Hello and welcome back to the
Neurotransmitters.
I'm your host, dr MichaelKentris, and today we are
concluding for now at least, ourIM board review series on
neurology topics, and our topictoday is neuro-oncology.
Same caveat as the rest of therecordings in this series is
this is not an exhaustivediscussion of the topic.
(00:23):
This is intended for mostlythose high-yield topics that are
likely to show up on yourboards.
So let's start off withpresentation.
Typically, symptoms will oftenhave a subacute to chronic onset
, as opposed to something likestroke, which is more that
hyperacute onset of symptoms.
However, you may get thesehyperacute or or acute symptoms,
(00:44):
such as focal neurologicsymptoms or seizures, when there
are acute changes within thetumor, such as hemorrhages, or
if a critical amount of edema orswelling accumulates and hits a
tipping point right, a lack ofcerebral compliance, and we'll
talk about edema and herniationlater on.
One of our most common symptomsis, of course, headache,
classically positional, worsewith lying down, worse in the
(01:06):
mornings, maybe also worsened byactivities that can transiently
raise intracranial pressure orICP, such as coughing, sneezing,
straining or Valsalva maneuvers.
And then you can also getsymptoms of increased ICP as
well, such as nausea, vomiting,blurred vision.
You may get some papilledema onfundoscopic exam.
They may get also some isolatedcranial nerve palsies.
(01:29):
Sixth nerve palsy is a commonone due to its long intracranial
course.
If the mass is in the posteriorfossa you can also get symptoms
that suggest hydrocephalus, aswell as sometimes syncopal
episodes due to some transientagain pressure, due to different
maneuvers that can causeepisodes of stiffening, like
flexor, extensor, posturing,things of that nature.
(01:49):
Obviously, if there is aconcern for an intracranial mass
, imaging is the order of theday.
So a lot of these people willstart out getting CTs of the
head, typically without contrast, just because those are what
are obtained most emergently inthe emergency department and
those types of settings.
But in most situations thepreferred imaging is going to be
an MRI brain, with and withoutcontrast.
(02:11):
Whenever we're worried about anintracranial mass, we do want
to get contrasted images ifpossible.
In broad strokes, we can thinkof intracranial masses as
belonging to one of twocategories.
There are those that arisedirectly from the central
nervous system or CNS, soprimary CNS tumors.
And then there are those thatarise somewhere else in the body
and metastasize to the brain,so metastatic brain tumors that
(02:33):
arise from some primary cancerelsewhere in the body.
Now let's start with the secondcategory.
So metastatic brain tumors arethe most common type, broadly
speaking, of intracranial tumor.
Some of the common sources kindof mirror the common cancers in
the general population, so lung, breast, kidney, melanoma.
Often on MRI these will appearas ring-enhancing lesions at the
(02:56):
gray-white cortical junction,and this is a common place for
things that have hematogenousspread to kind of get captured
is in that gray-white junction.
Typically, if you're suspiciousfor metastatic disease, you're
going to want to get imaging ofthe rest of the body, so
typically a CT of the chest,abdomen and pelvis and or a
full-body PET scan to try andfind a primary source of the
(03:16):
cancer.
If there is no primary found onimaging, very often you may
need to biopsy that brain tumorand or resect the brain tumor if
the symptoms are severe enough.
Treatment is typically dictatedby what the underlying primary
cancer is, with some specialconsiderations for the
intracranial mass, which mayinclude things like radiation
therapy either whole brain orstereotactic or focused beam
(03:39):
radiotherapy, depending on wherethe lesions are located, how
numerous they are, and so forth.
A special case that can presentis something called
carcinomatous meningitis.
So this is a fairly rarepresentation that often appears
with symptoms very similar to ameningitis encephalitis type of
picture.
The MRI of the brain in anideal situation will show
(04:00):
nodular meningeal enhancement,and this can be seen with any
kind of cancer, but lymphoma orleukemia are considered somewhat
classic in terms of thispresentation.
This may be seen with aphenomenon known as CNS escape
of certain kinds of cancer afterthe initial treatment, where
the cancer cells escape into thecentral nervous system and the
chemotherapy that they werereceiving wasn't particularly
(04:20):
effective at penetrating theblood-brain barrier.
In these situations, in additionto imaging, you're obviously
going to want to get CSF studies, including cytology and or
cytometry.
This is sometimes called aquote liquid biopsy and has
relatively low sensitivity,unfortunately.
So if there is a high clinicalsuspicion, you may need to do
multiple high-volume lumbarpunctures.
(04:42):
Up to three is sometimes therecommendation.
If your clinical suspicionremains high, let's talk about a
few primary CNS tumors.
We're going to start off withthe 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 totheir mass effect and or some
(05:04):
peritumoral edema.
On MRI of the brain you'llusually see some homogeneous
enhancement with a quote duraltail, which essentially is this
little piece of the tumor thatextends into the dura and also
lights up with that contrastenhancement.
So this is one of the fewtumors that you can make a
pretty confident diagnosis basedon imaging alone.
(05:24):
If there are no symptoms andthe imaging characteristics are
typical, without any of thesehigh-risk features, they may not
need surgery and can just bemonitored over time.
Next up is glioblastomamultiforme.
This is the most aggressivetype of glioma, a WHO World
Health Organization grade 4tumor.
(05:44):
So gliomas are ranked fromgrade 1 to grade 4, grade 1
being low grade, grade 4 being aGBM or glioplastoma multiforme.
Unfortunately, in addition tobeing the most aggressive type
of glioma, it is also the mostcommon.
The only risk factor that we'revery confident of is a history
of radiation exposure.
It does seem to correlate withdeveloping.
(06:04):
These.
Mri of the brain will usuallyshow a large lesion, although it
can vary in size, typicallywith central necrosis, some
heterogeneous enhancement andmass effect and peritumoral
edema.
One of the radiographicfeatures that is very suspicious
for a GBM is a butterfly lesionand this is where you have
tumor crossing the midline,usually via the corpus callosum,
(06:27):
and it can make a sort ofbutterfly type appearance.
Treatment is usually acombination of surgery,
radiation and chemotherapy, so,if possible, resection of as
much of the tumor bulk aspossible.
One of the reasons that GBMscan have a high recurrence is
that beyond the visible marginsyou can get this microscopic
(06:48):
invasion of cancer cells, and soit does unfortunately have a
high rate of recurrence.
You'll also use radiationtherapy as well as chemotherapy.
The mainstays of chemotherapyinclude temozolomide.
You'll also sometimes see amedication called bevacizumab
added to the regimen, which is aVEGF or vascular endothelial
growth factor inhibitor, and sothis can help reduce the amount
(07:11):
of blood supply to the tumortissue, but it may increase the
risk of other complications suchas stroke or heart attack.
The prognosis for GBM isgenerally not very good.
Five-year survival is under 10%in most cases, and, depending
on how aggressive the cancer iswhen it is first discovered,
survival may be measured inmonths rather than years.
Some of the features that mayportend a better prognosis is
(07:34):
actually in younger people, ageunder 45, if there is minimal
residual tumor followingresection, and if the person
undergoes chemotherapy andradiation therapy as well.
So all of these factors tend tobe associated with better
prognosis overall.
Next up, we have primary CNSlymphoma, so this one is a bit
of a hard entity to nail down.
(07:55):
It can present with lots ofdifferent symptoms meningitis,
encephalitis type symptoms,multiple cranial neuropathies,
multiple neurologic deficitsthat can involve the spinal cord
.
So it can look like a lot ofdifferent things and a lot of
times you're going to need tokeep it on your differential
diagnosis.
If there's meningealinvolvement, if there are these
multifocal cranial nerves ormultifocal central nervous
(08:18):
system type symptoms, if anytype of neoplastic process is on
the list, this one is probablygoing to be on there for kind of
these unusual presentations.
One of the big risk factors fordeveloping this is chronic
immunodeficiency and this can befrom either a history of HIV or
from someone who is on chronicimmunotherapy for some other
condition.
(08:38):
Pathologically it is typicallya diffuse large B-cell lymphoma
and on MRI in the test it'll saya quote single ring-enhancing
lesion, but in reality it is notalways a single lesion.
This may also appear sometimeslike an inflammatory disorder
Think of things like vasculitisor even demyelinating disease
(08:58):
like MS also.
So again, it's one of thesethings that can mimic a lot of
other conditions.
So you have to keep it on yourlist when there's something
that's just not quite right.
In terms of recommended labtesting, you'll be obviously
checking CBCs, cmps, things likethat, checking for different
autoimmune conditions, inparticular things like
sarcoidosis.
You'll also be checking for HIVand then you'll be doing your
(09:19):
routine CSF testing as well ascytology and flow cytometry.
Further imaging will ofteninclude a whole body PET or CT
and again you're looking to seeis this in fact true primary CNS
lymphoma or is this a moregeneralized lymphoma that has
spread to the CNS?
As far as treatment goes, thesetend to be very responsive to
(09:41):
steroid therapy.
However, there has been somedebate in recent years.
Steroids such as dexamethasone,if given prior to diagnosis,
may reduce the yield of biopsyor CSF testing, and so it's
generally recommended to avoidgiving empiric steroids prior to
a definitive tissue diagnosis,if possible.
There have been some papers inrecent years that have
(10:03):
questioned this traditional view, but that's the general
recommendation at this point intime.
Treatment usually involvesmethotrexate and rituximab plus
or minus radiation therapy, andgenerally there is a good
initial response to treatment.
However, recurrence isunfortunately fairly common.
Let's talk about some medicalmanagement of complications of
(10:24):
CNS tumors, so obviously we'vegot a brain tumor.
A very common thing that we runinto are seizures.
These are commonly seen more inlow-grade rather than
high-grade gliomas, and alsomore typically seen with tumors
near the cortex, as opposed tothose that are in deeper
locations or in the posteriorfossa, which makes sense because
seizures are generated from thecortex.
(10:45):
You can also get seizures verycommon with a couple specific
kind of tumors, likegangliogliomas and
disembryoplastic neuroepithelialtumors or DNETs, and very often
these can cause medicallyrefractory epilepsy in about 90%
of patients.
So typically, resection ofthese tumors should be done if
(11:05):
possible.
Now one question you may beasking yourself is what
anti-seizure medication should Ibe choosing for these patients?
Because there are dozens on themarket.
So we have to think what arethe other things that are going
on with this patient's medicalstory?
If they're going to be gettingchemotherapy, if they're going
to be on medications that mightcause certain kinds of organ
(11:25):
dysfunction, we want to try andpick an anti-seizure medication
that is not going to exacerbatethose problems.
So very often, our firstchoices are going to be either
levotiracetam or lacosamide.
The benefits of these two arethat they are both available in
IV form, so you can get them upto a therapeutic dose fairly
quickly and they have a fairlylow potential for interaction
(11:46):
with chemotherapy.
So on the flip side of that, wewant to avoid some of these
older anti-seizure medicationsdue to interaction concerns,
especially these hepaticallymetabolized ones.
So things like phenobarbital,phenytoin, valproic acid,
carbamazepine, for instance.
There are others, right, thereare dozens of anti-seizure
medications out there, but theseare some good rules of thumb to
(12:07):
keep in mind.
Typically, we do not startpeople with a brain tumor on
prophylactic anti-seizuremedications.
However, if they do have tumorresection, very often we'll do a
week of anti-seizure medicationfollowing that surgery.
Now, if someone has a seizureafter that one week period
post-tumor resection, verylikely they are going to need to
(12:29):
be on anti-seizure medicationsfor 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 beirritative to the brain going on
beyond just the scar tissueitself?
So you can get this postresection epilepsy still develop
, even after the tumor is gone,depending on the situation.
(12:49):
So let's talk about edema.
So sometimes it may not be thetumor itself but the edema that
it causes in the surroundingbrain 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 maysee someone with an abrupt
decline in mental status.
You may see some changes inexam, the classic one being
(13:12):
changes in pupil reactivity.
Some changes in exam, theclassic one being changes in
pupil reactivity.
Emergent options for treatment.
We want to elevate the head to30 degrees.
We can hyperventilate to anarterial PCO2 of over 25
millimeters of mercury.
You can also bolus withhypertonic saline or mannitol
and you can give glucocorticoidssuch as dexamethasone, which
helps to kind of calm down theblood-brain barrier, leading to
(13:35):
improvement in some vasogenicedema.
So all of these obviously havea little bit of differences in
terms of from the time they'readministered to the time of
effect, but they are oftenconsidered bridge therapies to a
neurosurgical intervention.
Next up we have venousthromboembolism.
So in cancer it's notsurprising that sometimes people
can have clotting disorders.
So if the patient has a needfor anticoagulation it is
(13:58):
generally recommended to goahead and anticoagulate them if
they have no intracranialhemorrhages or their platelets
are over 50,000.
Some forms of metastatic cancerdo have a slightly higher risk
of hemorrhagic disease.
The mnemonic is MRCTBB, that's,melanoma, renal cell carcinoma,
choriocarcinoma, thyroidcarcinoma or teratoma,
(14:21):
bronchogenic carcinoma andbreast carcinoma.
These types of cancers can showup as hemorrhagic metastases
and obviously if there isevidence of hemorrhage, you want
to avoid anticoagulation ifpossible.
But if there is no hemorrhagethen you don't necessarily need
to avoid anticoagulation, purelyon the type of cancer.
In fact, post resection it isrecommended to start
(14:43):
prophylactic anticoagulation aswell as mechanical compression
devices as soon as safelypossible in hospitalized
patients.
Last up, we're going to talkabout perineoplastic syndromes.
So this is a broad family ofvery unusual neurologic
presentations.
So this is a family of antibodymediated neurologic syndromes.
(15:04):
Now these can be either primaryor perineoplastic and many of
them are described.
We're only going to talk abouta handful today.
These typically will be kind ofsubacute in onset, but they can
be quite varied in theirsymptom presentation.
Some of the things that mayraise your suspicion is that you
get this new onset of seizuresor status epilepticus, new onset
(15:26):
of psychosis, plus or minusseizures, new onset movement
disorders such as ataxia chorea,myoclonus, tremors, opsoclonus
myoclonus and various types ofperipheral neuropathy as well.
Again, the key to some of theseis going to be the subacute
timeline, so typically in theweeks to months onset.
If this is occurring in thesetting of a known cancer, then
(15:49):
certain types of cancer willhave certain associations with
different perineoplasticsyndromes.
However, if you are seeingsymptoms suggestive of a
perineoplastic syndrome, thenyou do need to do an
investigation for cancer andthat's going to include our
typical testing such as MRI,brain with and without contrast,
csf testing and again those CATscans or PET scans of the rest
(16:10):
of the body as well, and thencertain antibody testing also.
So let's talk about a few ofthe rest of the body as well and
then certain antibody testingalso.
So let's talk about a few of themore classic perineoplastic
syndromes.
So one of the ones that I thinkmost people are familiar with
is the NMDA receptorencephalitis.
So this will typically presentwith kind of a subacute onset of
psychosis that can progress toseizures and typically has an
(16:32):
association with an ovarianteratoma.
Small cell lung cancer is oneof the cancers that has an
association with an ovarianteratoma.
Small cell lung cancer is oneof the cancers that has an
association with multipledifferent perineoplastic
syndromes.
One of the ones that we willthink about are these
voltage-gated potassium channels, in particular the LGI-1 type,
and you can get brachiofacialdystonic seizures or the little
(16:52):
twitches in the face and the arm, and these patients will often
present with kind of a subacutecognitive decline.
Paraneoplastic cerebellardegeneration is another classic
one.
The antibody is anti-YO or PCA1.
Some of these antibodiesunfortunately have more than one
name, just to add to thecomplexity, but anti-YO is a
(17:13):
good one to remember.
And this has an associationwith breast cancer.
And to flip this around, if youhave a patient with a history
of breast cancer who suddenlystarts becoming ataxic, you need
to differentiate is thisrelated to chemotherapy, like is
this a sensory ataxia or isthis more of a central ataxia?
An MRI brain showing cerebellaratrophy or even enhancement can
(17:34):
be a very strong indicator thatyou're dealing with this.
And then antibody testing forthat anti-yo antibody can help
really clinch the diagnosis.
Stiff person syndrome is achallenging diagnosis to make.
Oftentimes people have musclerigidity, typically in the axial
muscles more than the limbs,although it can be both.
It does have a strongassociation with type 1 diabetes
(17:56):
also.
These are the anti-GADantibodies, although there are
some other antibodies that canalso be associated with stiff
person syndrome.
There is an association withthymoma.
However, you can also see thesewithout any cancer at all.
So one thing to keep in mindwith the anti-GAD antibody you
will see this elevated with type1 diabetes without stiff person
(18:17):
symptoms.
So you do have to use yourclinical judgment in these
situations also.
There are many kinds ofneuropathy that can be
associated with perineoplasticsyndromes.
The classic one is anti-Hugh,and this is also associated with
small cell lung cancer.
There are many antibodies thatare associated with
perineoplastic syndromes that wehaven't talked about, and it
feels like there are more beingidentified every year.
(18:39):
We're not going to really gointo those because it does start
to get a little into the weeds.
The best treatment for most ofthese is to treat the cancer.
If there is a cancer identified, some of these patients, even
if the cancer is treated, mayneed immunotherapy after that.
Typical first-line treatmentsinclude things such as IVIG,
methylprednisolone, plasmaexchange, and chronic therapies
(19:01):
can also include some of these,such as IVIG or plasma exchange,
but you can also see otherimmunotherapy agents like
azathioprine, mycophenolate,rituximab and sometimes other
agents as well, depending on thesituation.
So we have reached the end and,to reiterate, this is not an
exhaustive list.
This is a very broad overviewon some of the more common
things that you may see eitherin practice or, at the very
(19:23):
least, on your board exams.
So, with that caveat in mind, Ihope you found this helpful in
your preparation and, if youhaven't, do listen back to our
other topics in the InternalMedicine Board Review series.
I think this will help a lot ofpeople who are prepping for
that particular test and I'mprobably biased, but I think it
has some decent informationthere for folks who are working
(19:44):
in primary care settings as well.
As always, you can find moreinformation 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 inthe show notes here as well If
you want to drop us a line withany questions or show
suggestions.
Thank you again for listeningand we'll see you next time.
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