Brain Tumor Cancer Symptoms

hello and thank you all for joining usfor today's webinar the pituitary network association is a nonprofit organizationthat relies on the support of our members and donors we offer thiswebinar series to help educate patients their families and their healthcareproviders. during the webinar feel free to type in your questions at any timeplease note that all questions will be saved until the end of the webinar wehave a lot of time to answer as many questions as possible any questions thatare not answered will be reserved and answered by email today's webinar headaches and pituitarytumors as being presented by dr. garni barhoudarian.

dr. barkhoudarianis an assistant professorof neurosurgery and neuroscience at the john wayne cancer institute at st.john's health center in santa monica california. dr barhoudarian completedhis undergraduate education at ucla majoring in microbiology and humangenetics he attended the university of michigan medical school where he was theedgar akon neurosurgery research fellow he completed his neurosurgeryresidency at the ucla medical center then completed a fellowship in pituitarysurgery and neuroendoscopy at brigham and women's hospital and harvardmedical school dr. barhoudarian's clinical interests are minimally invasive skullbase surgery, pituitary disorders, benign

and malignant brain tumor surgery, neuroendoscopy, trigeminal neuralgia, and hemifacial spasm and mild to severe headinjury concussion. he is the director of the brain tumor center skull base andendoscopic microdissection laboratory dr. barkhoudarian is involved in anumber of clinical and translational research studies evaluating the geneticdiagnosis treatment and results of patients with malignant metastatic tumors meningiomas, chordomas and pituitary tumors. he is alsoevaluating children as well as active and former nfl athletes with chronicrepetitive concussions and brain injury. he has a special interest in theadvancement of technologies for

minimally invasive neurosurgicalprocedures. we are now going to turn thepresentation over to dr. barhoudarian there may be a brief delay as we changepresenters. okay can you see my screen? i can yes allright it is all yours. excellent i apologize for the delay i'm making mypicture smaller i can see what i will talk about ok can you hear me ok yes we can hear you just fine excellent, well first of all i'd like to thank you allfor inviting me to speak today at the pituitary network association it's truly an honor to be amember of this organization and it

really is our goal to try our best tohelp our patients with all sorts of different types of pituitary tumors andas many of you know some of them can be straightforward but others can be quitechallenging and i think one of the more challenging things that people have been tackling with pituitary tumors is the symptom of headaches. headaches can bepretty obvious in some cases and it's very clear that that's related to the tothe tumor or to the lesion that we see but often times it's kind of a grey zoneand i hope to spend the next 45 minutes or so to try to elucidate some light onthe issue of headaches and the symptom of these types of tumors. so withoutfurther ado will move forward here. as many

of you know the pituitary gland is themaster gland it's it's really the it's at the nexus of the brain and it involves so manydifferent systemic structures and organs involving everything ranging from growthand stress and sexual reproduction thirst regulations etc. but there's alsoother things that the pituitary gland controls along with its relationshipwith the hypothalamus that's a little bit more subtle and it's in these subtletieswhere the difficulties arise in managing some of our patients. the most interesting part from myperspective from a surgeon's perspective is it's location really is a deep in thecenter of the brain and it lies in the

nexus of a number of really criticalstructures so obviously the pituitary gland itself is a critical structure butalso the optic chiasm depicted this whitish grey band here is justabove the pituitary gland and any pressure on the chiasm can cause vision loss tunnel vision usually. it's right on either side of the carotid arteries which supply blood tothe brain and just past the carotid arteries are these important nerves that supplysensation to the base and also control eye movement. and of course there's the brainjust above it and just the size of it so any sort of tumor in this region canaffect any of these structures and you can get all sorts of different types ofpresentations which actually is one of

the reasons why it's so difficult tomake a good diagnosis of pituitary tumors in some cases. here is anexample where we move from the normal anatomy in this cartoon where the opticchiasm and the carotid arteries are well separated from the pituitary gland then youyou have a tumor that grows in this area and all of a sudden you havepressure on these and most of the time these are not invaded by the tumor butat least they're being pushed on and when that occurs you get dysfunctionin various symptoms. probably one of the more common symptomspeople get are headaches and we're going to spend a lot more time on that butalso it's important to know that people

can sustain vision loss or blurredvision, color loss etc tunnel vision. many sorts of endocrine abnormalities eitherdue to overproduction of hormones as we see in cushing's disease or acromegaly or in patients with prolactinomas. or hormone dysfunction which isthe opposite obviously which can occur independently of these different types ofsyndromes. and most commonly we see a combination of this above scenario andusually headaches play a role in at some level and in some of our patient's. i won't discuss the incidental findingthe incidentalomas as we call them. many times though people think these are incidental tumors they actually may not be we

just haven't really diagnosed the syndrome as well as we thought. there's a cartoon that i have borrowed from a colleague of mine atucla bill yong a pathologist who actually did a nice job characterizing the different types ofstructures that surround the pituitary gland so if this blue is the pituitary glandwe have the covering of the pituitary gland the meningioma of the meninges thebone surrounding it the cerebral spinal fluid that bathes it, thebrain, the optic nerves the chiasm and the hypothalamus and each points in this area there could bedifferent types of pathology that exists whether it's a pituitary adenoma of themost common type of pathology there

a rathke's cleft cyst or more uncommonthings like craniopharyngiomas, chordomas, granulomatosis, optic gliomas, etc. so we have todeal with all sorts of different types of diagnoses to to figure out exactlywhat we're dealing with this is an example in a patient who unfortunately did not survive but hadcushing's disease and had a micro adenoma very small adenoma causing forcushing's disease resulting in her demise this is taken about fifty yearsago by jules hardy and that's a good example of how significant even a smalltumor like this can affect a patient with that disorder. this on the other handis a patient who again many many years ago who had a very large pituitary adenoma and this even though itwasn't secreting any hormones cause.

problems because it grew so large thatultimately obstructed the normal flow of cerebral spinal fluid and developed hydrocephalus and then slippedinto a coma and so thankfully we don't see this common but these are kind ofthe extreme situations of pituitary tumors and how can present. there's all sorts of other types of tumors a rathke's cleft cyst, duramoids craniopharyngioma, meningioma epidermoids schwannomas and chordomas, and they all occur at different areas or regions surrounding the pituitary gland around the sella which is the home of the pituitary and each of these tend to present in somewhat of a unique way and will touch upon some of these next few slides sojust to kind of start things off i want

to discuss how we define headachesbelieve it or not there's an entire society dedicated to headaches and theinternational headache society and they have categorized every single time youcan think of including headaches that are associated with brain tumors so thisis their criteria and basically they say a headache with at least one of thefollowing characteristics and fulfilling c & d so c & d down here. so at least itbeing progressive localized worse in the morning or aggravated by coughing or bending forward. you'd want to see an intercranial neoplasm on the imaging although it's not always there at least it's not always visible and then the headaches usually temporalor spatial fashion related to the

neoplasm basically meaning that thetumor grows the headache gets worse and then here's the catch though the lastcomment states that the headache must resolve within seven days after surgeryfor removal of this lesion. this kind of circular logic that yes you have aheadache related to tumor but the only way to really prove it is by taking itout and see if it goes away well that probably would result in manyunnecessary operations in patients. so it's our job to try to figureout which patients headaches are actually related to the cyst or tumor in which patientsmay we may be able to treat medically and not need surgery. this is a studyfrom a while ago looking at the

different locations headaches associated with differenttypes of tumors this is believed in the nineteen fifties when this was publishedtalking about the location over to this region of the temples associate middlemeningeal artery the top of the head associated with the sagital sinus, the forehead and the orbit associated withall these different structures and in this does include the cavernous sinus of the pituitary region. so this is a they've already known that fifty,sixty yearsago when this was published and we'll talk a little more about the location of theheadaches this is a study that came out

of a fifteen years ago and basicallythey looked at about two hundred and eighty patients over a period of timewith any sort of brain tumor and they just wanted to see what are somecriteria that would be associated with headaches just to kind of get a sense ofwhat what really correlated with headaches so these are all sorts oftumors not just pituitary tumors in all comers 60% of patients had headaches andthe patients who did have headaches 50% actually had persistent headaches aftersurgery so we would categorize this a headaches that were not related to the tumor itself and that suggests that about 85% of patients who had headaches related tothe brain tumor got better after surgery.

suggesting that their headaches wererelated to the brain tumor directly so that was the start now they decided toexamine this a bit more carefully so they looked at patients who haveprogressive headaches versus not progressive critics in his piece of theprogressive headaches those who have more aggressive type of tumor like ametastatic brain tumor or glioblastoma were statistically significantly higherrisk of getting progressive headaches where as people who had kind of staticheadaches that they've always been there for many many years is non progressive headaches the mostcommon tumor was benign type of diagnosis of meningioma these are slow-growingtumors so it was interesting difference

between the progressive and the non progressive headaches. also the location if the tumor was above all thetutorials above the cerebrum of the brain these patients are typically atlower chance of presenting with headaches as opposed to a lower down inthe skull base or the cerebellum those patients had a much higher rate ofpresenting with headaches than their counterparts andinterestingly if there was a tumor in the ventricle which is the fluid filled areas of the brain these patients actually had a notable higherrate of presenting with headaches though there is other criteria that we willtalk about down the line that could

contribute to a progressive headache and the key on is the development of mass effects in addition to the tumor so say thetumor is obstructing the normal cerebral spinal fluid flow and the patient getshydrocephalus well these patient definitely have a higher risk of progressiveheadaches and also if there's any midline shift so enough pressure on oneside of the brain that it shifted over to the other side which we see from timeto time even in pituitary tumors then these patients could develop progressiveheadaches these are more serious types of tumors that we want to do it. sowhat are the typical symptoms associated with headaches from pituitary tumorsspecifically. this information was

gathered by my work with dr. ed lawsand his team at the brigham and women's hospital basically asking patients whohave pituitary tumors what type of headaches they had, their severityetcetera and we found that most patients had daily headaches that are typically bi-frontal meaning in the front forehead region or behind the eyes or they were at the vertexat the top of the head the general lasted 1-4 hours induration especially at their most severe most severe stages they could beunilaterally could be only on one side it didn't necessarily mean that it had to beon both sides to generate a headache and in general patients complain of these aremoderate or severe headaches they were

kind of mild forget about it headaches theywere definitely interfering with their lifestyle. in a minority of patientsabout 15% of patient's they would wake up because of or with the headache and thatwas actually key finding because that usually suggests that something with moreaggressive is going on in the brain and in rare cases but notoriously one could develop really sudden and severe onset headaches and when we hear that in thesetting of a pituitary tumor we have to be concerned that there is bleedinginto the tumor and a condition called the pituitary apoplexy can occur we'll talk more about that but the keypoint is in that setting you don't want

to sleep on it you don't want to take abunch of aspirin and you want to go straight to the emergency departmentbecause this is a surgical emergency until proven otherwise. so what are some of the mechanisms thatwe think can contribute to the headaches and we'll talk more about this in depthwith this slide i wanted to point out that you have a large cystic lesion herethis is an arachnoid cyst or rathke's cleft cyst and its pushing and stretching the normalcontents of surrounding the pituitary gland we think this is the number onemechanism of headaches meaning that the dura mater is being stretched and thenerve fibers that are on the dura mater

because the brain actually doesn't havenerve fibers is actually in the covering of the brain and pituitary gland thosewhen they stretch generate headaches interestingly though larger tumors areless likely to cause headaches because they generally tend to be slower growingand the brain can accommodate and the nerve fibers can accommodate and they don'tgenerate the pain signal that you expect cystic lesions like rathke's cleft cyst, arachnoid cyst, cystic craniopharyngiomas or cystic adenomas tend to be morelikely to present with with headaches because we think that the cyst isexpanding at a different rate than the rest of the tumor is and of course as i mentioned if there is bleeding into the

tumor, if theres hemorrhage or apoplexy thenthere's a higher rate headaches this was a breakdown of our patients who did haveheadaches and you can see in these patients we look at their typical headache andtheir most severe headache and in patients with macroadenomas their typical headache range about three to four most severe was about a five same with the microadenomas but patients with cystic lesions hadconsistently higher average rate higher severity of headaches so again pointing that cystic tumors tend to cause more significant headaches. this is a studythat came out about ten years ago looking at pituitary volume of headaches and characterizing the volume of the size of the

tumor and it's interesting that they'veconcluded that the size was not the only factor contributing to the headaches so they looked sixty-three patients 70% of these patients had headaches and this is theirscatterplot basically plotting the tumor volume measured in milliliterswith the headache score they had compiled and you can see there is no linear orlogarithmic correlation associated with this it's completely random you can havevery very large tumors with very little or no headaches and you can have verysmall tumors with significant headaches so there is a wide range that we'relooking at here they did note that if a tumor was invading some of the nearby structures tothe cavernous sinus which is where

the carotid artery lives and those veins and those nerves live as i was talking about earlier these tend to have a higher rate ofheadaches and is the patient already prone to headaches so if there's a family historyof headaches or if there's a history of migraines there's a higher rate that that patient will generate headacherelated to the tumor this is the data that they published after surgery so whether itwas through the nose through the brain or just radiation they found that 23patient's did improve eight actually got worse and nineteen really didn'tchange much so about a bit less than 50% of patients were either were better thanonly a fraction were worse. now here's the interesting part in a number of thesepatients who had hormone secreting

tumors so say acromegaly or cushing's disease when they were treated for their hormone secretion alone so sandostatin, octreotide or lanreotide their headaches all got better and also in patients with prolactin secretingtumors who were treated with cabergoline or bromocriptine their headaches mostly got better in this subpopulation so there is definitely a correlation with hormonesecretion and headaches particularly the acromegaly and cushin'gs subgroups and we think that there is a direct relationship with the the syndrome andthe headaches. so basically their conclusion was that 50 to 95 percent ofpatients could respond to surgery at least with some improvement of theheadachesand in their series that the

best improvement occurred in arachnoidcyst patients, rathke's cleft cyst patients and patients with pituitary apoplexy and resolution of the hormone secretion. so i'd like to switch gears just a little bit and talk about some of themechanisms we think about the little bit more depth with regards to the development ofthese headaches we talked a little bit about this already but the direct dural stretch is one mechanism that we feel is the most likely cause of theseheadaches but also their structures nearby so the trigeminal nerve with is the nerve that supplie sensations in the face of lives in the cavernous sinus they can get irritatedand you can get a syndrome called trigeminal neuralgia a different type of headache more like a facial painthan a headache if there's inflammation

surrounding the lesion so if it's aninfection or inflammatory process that itself can irritate the dura and cause headachesand if there's increased intracranial pressure either due to direct masseffect from a very large tumor or due to hydrocephalus with you mentioned earlierthat is itself can cause headaches in addition to the tumor being president andthen if there's any bleeding directly into the tumor theres just a sudden increase in this volume of the tumor that can cause headaches as well so we'll talkabout all these so as i mentioned direct dural stretch essentially couldoccur anytime you have deformation of the normal structures so the dura which isthis layer here that i'm tracing

covering the pituitary gland the cavernous sinuses which is the blue blood filled areas as well as the nerves that go to the eye and to the face well when we as in you saw this and thefigure before when this gets stretched the nerves get irritated this is a diagram of the different parts of the trigeminal nerve as it innervates the head which many people are already aware of this that most of the facial sensation isinnervated by the trigeminal nerve cranial nerve but this is the inside this ison the inside of the brain and pituitary gland lives right there right where myarrow is, it's called the sella turcica and the pituitary gland sits right there and thisentire area is innervated by the first

branch of the trigeminal nerve so come back here you see that the first branch the v one branch of the trigeminal nerveis innervating the eye and the forehead this is the most common location of theheadaches as we had mentioned for pituitary tumors. also it goes up to the top of thehead to the tip of it of the nerve extension and that's also another common location so these are all related to the location of the pituitary tumorsometimes however the pituitary tumor won't just stay here and we'llgo into the posterior fossa which is this purple area back there or out sideways and you'll get a pain that refers out to the cheek or towards the back ofthe head as a result you can see the

back of the head here or the cheek areathere. so here's an example this is not obviously not the same patient buthere's an example of a patient with a microadenoma as we have shown before that grows into a large macroadenoma as it progresses and you can see how thedura will get stretched to the point where you would expect it to cause some headaches not all the time but sometimes. this type of lesion is actually a cyst so this isa rathke's cleft cyst and i know that because it's splitting the anterior pituitary gland and the posterior pituitary glands and we see here that the rathke's cleft cyst quickly get largequickly meaning over a few months or

years but still it can enlarge andstretch into this area you can already assume that there's going to be somestretch of the pituitary gland these cysts can occur within thepituitary gland or above its up along the the course of the infundibulim with theconnection of the pituitary gland in the brain this is an example of a patient who hadheadaches related to a cyst above the gland and here we are in surgery andyou can see that there's a little bit of bowing through the dura its a little bit stretched we cut into the pituitary gland which is a common way of getting intothis area and we drained this rathke's

cleft cyst and headaches subside becausethe dura which is above it stops being stretched here you see after surgery this is a patient with an arachnoid cystthe fluid matches the cerebral spinal fluid within a system surrounding the brain andessentially this is a csf leak within the pituitary gland the csf is pushing into and stretching the pituitary gland so it's a decent amount of pressure and just by draining this wewere able to decrease the pressure so this is a similar patient this is bone that you're seeing so the bone isactually been thinned out by this process to the point that its eggshell thinand we can easily enter with the soft

instrument or a blunt instrument andwere able to open and expose this area as we move forward we enter them this we enter we see as soon as we enter the cavity with fluid gushes out andwe're going to introduce the endoscope into the cavity and you're going to see atthe top the area where there is a communicationwith the brain and the pituitary fossa and you can see there's going to be some fluid coming from just this area right up here the top left of the screen you'll see a small amountof fluid coming out and that's why this patient is developing the cyst and as a resultthese headaches because there is a direct communication in that area all we need to do is a obliterate that and the cyst will

not reform and the headaches should should resolve over time well trigeminal neuraligia is another condition that i treat and trigeminal neuralgia is a syndrome where the trigeminal nerveis irritated due to various reasons and the first thing we think about when wesee a patient with trigeminal neuralgia is to make sure that there aren't any structurallesions causing pressure invading the trigeminal nerve that would result inpain and so we get an mri in many times or a number of times we identify a tumor inthe area that could be pushing on the trigeminal nerve. however numerous times we we don't see that and we have to look at other causes thesymptoms of trigeminal neuralgia are a bit different

therefore it's basically severe stabbingor lancinating pain so this shooting pain down the face that could be triggered bysomething as simple as touching the face, chewing, brushing your teeth, or even air or wind touching the face can trigger this this intense pain pain out of proportion tothe stimulus and it's typically responsive to drugs like a cabergoline, sorry carbamazepine which is tegretol or other anti-seizure drugs or anti-epileptic drugs however in some cases it doesn't really respond well. if we've ruled out othercauses then we wonder if there's a blood vessel that's a sagging and pushing onthe nerve there which is one of the more common types of treatments for thisessentially what that does is it irritates the nerve and it causes a

short circuit what's called ephaptictransmission of the trigeminal nerve and allows for any sort of sensation to beinterpreted as pain by the break this is an example of a surgery where we'relooking down in the area you can see this white band right there in front of thebrainstem that's the trigeminal nerve and there's an artery right there indenting and and pushing into thetrigeminal nerve irritating it every time it pulsates and resulting in the pain ofpatient is experiencing so in this type of operation we would separate the arteryfrom the nerve by putting in different types of substances generallyteflon to separate the trigeminal

nerve from the from the surroundingstructures so here you see an endoscopic view of the trigeminal nerve and thearteries running right along it and all we all we do is put a little bit of teflonthere we go and secure that into place the teflon will prevent theartery from touching a nerve in the face the patient's pain is most of the timeimproved by this about 90% of the time this works when we see an arterytouching the nerve. as i mentioned before sometimes it's not an artery touching anerve sometimes it's a tumor or lesion along the nerve that could be theculprit so this is an example of a patient witha right-sided the images are flipped

right-sided facial pain in right-sided lesionthat's in this area where the trigeminal nerve lives called meckel's cave and it's extending towards the brain stem so this is the patient who really only has pain in the face andwe operate on this mainly to make a diagnosis and if it is something benign that should be removed then remove it completely and here we have our exposureand you can see this is where the pituitary gland lives up in the top leftof the screen this is the carotid artery that suppliesblood to the brain and it's actually going sideways and upwards here and this isthe covering of the nerve as it's coming

over the hump is it goes into the faceyou can see that little fibers of the nerve coming through and just behind it we see this solid structure here that solid structure is the lesion we cut into it and we biopsy that and in thispatient that the biopsy proved to be i believe in this patient proves to be agranulomatous process so it basically is an inflammation of the nerve itself andthat became a big mess and that was pushing on the nerve and just by diagnosing that were able toget her on the appropriate treatment and her pain her lesions got smaller and her pain went away

well other things can also irritate thenerve such as other inflammatory conditions like sarcoidosis or wegener's vasculitis, temporal arteritis, or even surgical products that we put in there at the time of surgery can irritate the nerve. well meningitis is definitely one of these conditions and wehad a patient come in with a pretty severe headaches nausea vomiting and thect scan showed a large lesion but nobody really investigated that she had been having low grade fevers and they just started her on steroids and she got a little bit better but actually then turn to took a turn for the worse and came to our hospital with meningitis, the meningitis was actually the cause of her headaches she had this very large tumor and it had actually had been associated with

cerebral spinal fluid fistula or leak and that was a conduit for bacteria to enter into the brain and these are her findingsand she actually had an elevated white blood cell counts of her blood quitesignificant low sodium level and multiple pituitary hormones that wereaffected we were able to treat her meningitiswhich was somewhat profound and once we got that under control immediate diagnosis of chordoma and we went forward with surgery and this is an interesting finding well we see the tumor in thisarea here we also see evidence of meningitis on the diffusion-weightedimage of the brain along surfaces

which is not a common finding but it isconcerning and requires urgent management and this is her operation here and yousee that she had a large tumor in this area we go to remove much of it and they'rejust a part that's not going into the brain stem and this is the part that wecarefully debulk and i will just speed this up in the interest of time and you can see there'sa tumor than remains as we're approaching in this area going towards the spine and the brainstem and we carefully remove as much of this tumor as we can safely in her casewas somewhat stuck to the brain and we don't want to damage the brain so weremove as much as we could and we left a

little coating behind just so that she would have normal function as she would wake up but after surgery she actually did well herheadaches got better her meningitis improved now that we have a seal preventing cerebral spinal fluid from from leaking and we're able to get her back to her daily life.but this is another example of inflammation of the of the dura so thisnormally should be a thin white line and you see it's much thicker you see alarge lesion here that's quite bright in the pituitary gland region and this is apatient with sarcoidosis so another inflammatory condition in this area. this is a patient that i took care of who had wegener's granulomatosis anotherinflammation and this interesting

situation was that not only did the pituitary gland get inflamed but the nerves to the eye the optic chiasm got inflamed that actually caused the patient to lose vision until we are able to treat her with a prettysignificant high-dose steroids and rituximab were able to get her lesion toshrink and her vision to improve. last, second to last is the topic of hydrocephalus hydrocephalus essentially translates towater on the brain basically it's a result of dysfunctionalcerebral spinal fluid circulation we have called it many things here thisis a hudrokephalon not to be confused with hydrocephalus essentially what happens is you have the normal fluid-filled cavities of the

brain and they're constantly makingfluid and allowing it to flow from this area here to this third ventricle heredown through this little aquaduct through the fourth ventricle it comes outthrough these holes here three holes here and it bathes the entire brain andspinal cord and then gets absorbed by the blood vessels at the top of the brain and this gives the brain some buoyancy keeps it from being moved around too much nourishes the brain and allows the nerves to work well that's a very important part of part of the brain physiology however ifyou have a blockage either within the system or in the absorption of the fluidthen this will all back up and get

larger because as i mentioned there's no off switch. this is called the choroid plexus because it looks like coral and water andit is actually producing the fluid in that area nonstop this is what it looks like underwater and so anytime you have a blockage anywhere along this flow we would worryabout hydrocephalus the fluid that it made bathes about theentire brain twenty five milliliters of which are just in the ventricles most ofit are actually bathing the brain is made continuously you make about 20to 30 millimeters per hour as and adults and you make about six hundred millilitersper day so the brain will make three or

four times the fluid it needs per day inthis area it relies on a sodium potassium pump relying on atp to pump it across and it utilizes the carbonic anhydrase enzyme to convert the water in the csf side so that's a target that we can utilize because acetazolamide which is a diuretic drug can be used to inhibit carbonic anhydrase and decreasescsf production although it's just a temporary effect for most patients there's some other drugs that can work but this is really the only drug that's been shown to helpdecrease in a little bit but not significantly so so in general to thingto remember that there really is no off switch with the system in the brain isnot smart enough ironically to know that

it needs to stop doing that and it hurtsitself in the process just an aside years ago i went to francewith bob bartlett from university of michigan and our victor vaughn medical history group and we got to visit the catacombs beneath the streets of south paris wherewe saw famous peoples skulls and bones buried there we also went to the museum and thepasteur institute we saw these skeletons and these skeletons are unfortunately children that passed away because they had hydrocephalus can see their heads are quite large andquite blown up there and it's because the skull actually accommodated to theexcess fluid there which cannot happen in an adult but it's eerily similar tosome of our favorite hollywood

characters here that we've seen. thisis probably true patient with hydrocephalus that they call as an alien inroswell. but going back to more serious topics the way we would treat a patientwith hydrocephalus is is one of two options either we shunt the fluid soit put a catheter into the fluid-filled areas that ventricles of the brainconnected to a valve underneath the skin and tunnel this tubing all the waydown to the belly or other structures into the body to absorb the fluid inthat generally will take care of the excess pressure that this is exerting this hasbeen used for fifty sixty years now. the other option is to perform what's calledan endoscopic third ventrical

ostomy which basically is kind oflike an internal shunt or a bypass connecting the inside and the outside ofthe brain and this is only useful when you have a blockage in that originalsystem as i've mentioned if you have a blockage say here or here you cancreate a perforation of the floor just behind the pituitary gland and the fluidwill flow through this area and will decrease the hydrocephalus in this areawell the hydrocephalus can contribute to these headaches as we talked aboutparticularly with patients with craniopharyngiomas because they tend to growinto the third ventricle and depending on the acuity we may need to treat thaturgently first before we do the surgery

for the craniopharyngioma or other offending lesion. this is a patient that we took care of who actually have been treatedanother facility with a large lesion that was proven to be a craniopharyngioma they approached this with a craniotomy and they actually put in a shunt at the same time to treat herhydrocephalus which she had at the time. so she came in and fortunately in her wound had brokendown and we had exposed hardware so we were obligated to remove the shunt and weput in a catheter to manage her pressures then we went through the noseand we debulked some of this tumor and we connected the fluid-filled areas of the ventricles tothe to the rest of the brain region to the subarachnoid space that actuallyrelieved her hydrocephalus and she didn't

even need ventricle the ventriculostomy tubing or a shunt anymore so she was able to become shunt free. so that's a thirdway of managing is to just remove the offending lesion as best as possible sheactually did well we we treated with radiation and their tumor actuallystrong and well controlled and this is a good example of a patient that we sawand i asked this to some of our students what is the most common missed lesion in the brain? and the answer is the second one the patient has a pituitary adenomacausing pressure on the optic chiasm but also has a colloid cyst causing significanthydrocephalus and in this patient the treatment that we opted for was to firstremove this colloid cyst because it was

causing hydrocephalus before weeffectively treated the pituitary gland which is causing hypopituitarism and wewere doing that because we didn't want to have a scenario where thehydrocephalus resulted in excess pressure and if we had a cerebral spinalfluid leak it wouldn't heal well so here we are into the ventricles and you can seethis choroid or coral looking structure that's making the fluid andjust going too fast forward through much of this and were able to remove the cystwhich is hiding behind this vein in this region here and by by opening this up wecreate an opening into this cavity here which is it was called the foramen ofmonro

and allowing us to decompress the areawell once we complete we can see into the third ventricle we have a gooddecompression and the patient actually did well without any worsening of his hydrocephalus and then we went on to take out the pituitary tumor and he's been recovering well since then. and finally i want to leave you with the concept of pituitary apoplexy and of all the types of headaches that we are discussing today this is probably the most concerning because not only is it about headaches, but it could be lifethreatening or site threatening both of which you want to address right away. so this is an example of a 43year old man who woke with acute sudden onset left eye blurred vision

and a sudden onset headache and his vision had actually gotten a little bit better since that episode but we saw him and werecommended him to undergo urgent surgery because he had notable vision loss andhypopituitarism and you can see here the visual fields were were affected by thislesion but he had hypothyroidism slightly elevated prolactin level andyou can see here pituitary adenoma with hemorrhage insidethis dark area is blood that had bled into the into the tumor area and sowe were able to decompress this patient and he did well. this is a study recentlylooking at the different presentations of patients with pituitary apoplexy andi don't know if you can see this well

a number of different conditions wethink can precipitate it including high lipids or hypercholesterolemia some people think dopamine agonists can actually cause this that's a controversial statement. some of the presenting symptoms headaches are common, oculomotor palsy so meaning double vision because the eyes aren't moving well it's actually very specific to this typeof condition and then hypopituitarism. so low thyroid, low growth hormone low cortisol and in general overall could be associated with pituitary apoplexy. and long-term we find that some peoplerespond well to early surgery and unfortunately some people have delayedsurgery and in in those cases we end up

with more some of the adverse effects ofthis. so if surgery is delayed there's a higher rate of visual loss visual fieldloss which is statistically significant and we think there may be a little bitof a higher rate of hypopituitarism although this wasn't statisticallysignificant so this is that patient with pituitary apoplexy here and i'm going to speed this up as well as we enter into the covering of the pituitary gland you see that that's thegland and you see that is quite vascular and when we entered into this areayou'll see that they're some blood products that will spill out with a necrotictumor, much of this tumor is necrotic this area there's some blood that spillsout for the cavity where the patient had

bled and so we will forward and removeas much of the tumor as we can safely here we are. now we're looking at thepituitary gland separating from the rest of the structures here we sealthat up with fat and collagen sponge. the patient did well afterwards after surgery this is his vision, visual fields at two months follow-up that showed that his vision actually had improved despite his onset headache sudden onset symptoms. so in pituitaryapoplexy the most common symptoms are a sudden onset headache they usually say it's the worst headache of my life it's like a gunshot to the head.

typically associated with vision lossusually tunnel vision or bitemporal hemianopsia hormone dysfunctions this extremefatigue just can't get out of bed and your very abulic your that's a warningsign on it's own and other neurological deficits of double vision facial pain numbness etcetera if any of these occur even in somebodywho we are monitoring their benign tumor we offer offered not to operate this is asurgical emergency and needs to be dealt with right away so we don't have permanent vision loss and permanent hormone dysfunction so to summarize i think the take home points of this talk are just be aware of

headaches that occur when your waking upthose tend to be associated with more aggressive disease in general. be aware of progressive headaches because not only could they be associated with moreaggressive symptoms more aggressive tumors but they could be associated withhydrocephalus or cerebral adema or cerebral brain swelling in the areasize is not everything and hormone resolution actually can help withheadache treatment. tumors with cysts or tumors with hydrocephalus are typicallyrespond well to surgery as far as headaches are concerns and as imentioned resolution from hypersecretion can be associated with improvement ofthe headaches and with that i'll leave

you and i'd be happy to answer any questions. thank you that was excellent, thank you. okay we do have some questions. the first one is it all headaches that resolve completely oneweek after surgery? my spouse had surgery for pituitaryadenoma and the headache lasted up to three weeks after surgery she had aspinal drain put in three weeks after surgery due to a leak? so then the definition by theinternational headache society with seven days and it's an arbitrary numberthat is not how these headaches actually resolve i would say a typical headachethat has dumped directly associate with a pituitary lesion takes a few weeks twoor three weeks to resolve it in your

case it sounds like you had aconfounding issue with having a spinal drain and spinal drains alone can causeheadaches so that may be muddying the water a little bit but i would see a few weeksis is generally a reasonable amount of time not ionly really get concerned whenthe headaches are still present at about two to three months in that case we wantto look at other causes make sure that the sinuses are clean there's no sinusitis issue that thepituitary region is stable we usually get a new mri at that point and then obviouslyrule out other causes of headaches ok what is the prognosis of relapse of anatypical pituitary tumor with a mitotic index greater than 2? differenttopic so we're talking about an atypical

pituitary adenoma generally the recurrance rate is a bit higher than the typical pituitary adenoma a typical adenoma normal recurrence rate is about 8 percent in 10years and atypical adenoma recurrs or progresses about depending on what study or read fifteento thirty percent in 10 years so it's two or three times as likely to recurand the other point is this was a study that came out about two years ago thatit's not just the grade of the adenoma it's also its invasiveness if you have ahigh atypical adenoma it is it has a certain rate ofrecurrence you have an invasive adenoma

it has a certain rate of the kurds butif you have an atypical invasive adenoma a lot more aggressive in these timesreporter progress and it's very hard to achieve remission in patients who wewould recommend very close follow-up and probably adequate therapy at the radiosurgery or or even she was all about has been used in some of these cases butthose are it's not just the pituitary grade that's that's cheap but also itsinvasiveness and sometimes it's hard to differentiate that on a pathology slidebecause the pathologist only just the meat of the tumor so you have to look atthe imaging and see if there's any invasion on the imaging and if you'relucky the pathologist will get some

dinner on the covering of the region andthat will actually help diagnose invasion as well ok can hire igf-1 cause headaches yes based on that study that i showedhigher education definitely can cause headaches we mechanism for his multipleit could be due to a tmj it could be due to sinus obliteration because he sayswith a camaro attention of your sinuses and sinusitis sometimes or at leastallergic rhinitis and also some of the bony aspects if you have significantneck pain that can also translate to headaches as well so there's numeroushouses for headaches with patients and

patient back regularly and they showedyou and that's like many of these patients who were treated with with evenjust somatostatin analogs improving their headache severity ok cansmall micro nano must cause headaches too so in our series that we looked at ahospital we did not find it knows they typically patients that we've operatedwith my grandmas had another process going on i don't they had a blockednumber two was your prior to therapy or their tuitions as these really arecorrectly and in those cases as we would say reaching remission wouldactually help with the headaches like to know there's a little bit fifty-fiftywith regard to responsive headaches and

then the other thing to remember is manypatients get mri's just because of the headaches and we see these small atanonymous so it's very likely that it could have been an incidental adenomanow we we identify and this is where it's really key to conservatives toreally characterize the headaches you get multiple images and see if thatgrows and if they had a pink it all with relation to the size of the tumor orwith relation to the severity of the headaches as a tumor change and thoseare those are some factors to think about because there's definitely a venndiagram overlap with headaches impatient with 22 cherry tumors ok thank youbecause of the gutter brain connection

via vasil vagal nerve is there anyliterature suggesting a connection between post gastric bypass or lap andand later development opportunity to terry tumor or dysfunction causing havocthat is a very good question i have not heard of that i have not seen that inour literature the vagus nerve actually is a bit separated from the petit jurysystem it's more control the brainstem level so hard to create a link there buti have not seen that in our letter ok thank terry glenn has been removedtotally remove a starter and regular blood work is done how can anyonedetermine what normal levels are in such a patient how can their levels becompared with charge is for patients

with no known allergies so we're talkingabout the hormone levels i believe so oftentimes we still go by normal levelsin patients who don't have to turn reasons that we want to see a cortisollevels and the igf-1 levels to be to patients who have not charity work ofcourse age and gender matched some of the challenges i think we see ourpatients who have hypothyroidism because the general public treat hypothyroidismby looking up the tsh thyroid-stimulating hormone level but inpatients with hypothyroidism due to the tutor really should have had both youcannot swallow that anymore so you actually have to follow your patient'ssymptoms as well as the t3 and t4 those

are the active and reactive normallevels and those would be the reverse rape monitoring that sixty differentlocation does not appear to torture and as hypothyroidism where you would justsay the other hormone beckett's a bit altered his prolactin particularly inpatients with a very very large 222 @ november we looked into this field hasbeen published but we we think there is a correlation with very very low levels concurrently with the ocean so a locallike novel after surgery is a bit deceiving compared to look like beforebut then the question that doesn't even really matter so really doesn't affectour patients along ok can enlarged

periventricular space mean anything whena person suffers autonomic dysfunction and has family history of meningioma aspituitary tumors and interventricular sis it's hard to say because now we'retalking about kind of a chicken and the egg situation one would say you havelarge ventricles because it's causing pressure and is it causing pressure onthe surrounding brain structures or the other large banks closed because of rainhas atrophied because of the process like you know side rieger syndrome orsomething that would cause dysfunction and that would require anevaluation by a neurologist who specializes in these to make surethey're there isn't something else going

on however there are some quite surethat we use to see if the ventricles are out of proportion to the size of thebrain and if you read some of those specialty sale maybe the ventricles arecausing some of those problems and there's a syndrome called normalpressure hydrocephalus that can result in some symptoms of decline incontinence and a typical tease butusually want to see some of those in a trial before treating those cats inwater shot the same person also commented i meant a small six millionmanner while robbing space in the basal ganglia to clarify that somethingdifferent

those that would be hard to say that ihave to look at the film's to be certain enterprise the water is function butgenerally bert roberts spaces are are thought to be something we wouldn'ttreat for sure and maybe sometimes not even related to the pathology being seenso it really is evaluated by a minor all is ok and the presence of persistentprogressive localized headache in the absence of hormone abnormalities oninitial down and just enough of a reason for evaluation by an endocrinologistversus just stand with the pcp internists so the question is a questionto be evaluated by an endocrinologist primary-care probably should discuss itwith your primary care physician

sometimes there are some subtledifferences in the hormone levels and not all of their being assessed so thatmay be a reason to talk to an endocrinologist who particularlysomebody who specializes in the particular a plan but i would want toknow more about the condition and also if there's any abnormality and what are the general symptoms i wasdiagnosed with a form element manner to carry my grandma the frontal headachesyou mentioned and often they are severe in nature and cause vomiting and mimicthe description of a migraine sensitive to light my endocrinologist simplyadvised me to wait and be rescan a year

although i have hypopituitarism andheadaches pressure on my head would you suggest a second opinion if so is therea different type of doctor i should be seeing other than an endocrinologistsounds like they had occurred offices is correct you know headaches with nausea with avery small to carry my credit is probably not caused by bad mic right nowit's too small to even cause pressure in the area if your hormones if you don'thave hypersecretion senior on like kissing disease or automatically then idon't think that's related to your headaches i would stick with your othercolleges to treat your future

dysfunction and reimage in the year asmentioned and helping my clients treated i i dont your primary care doctor or aneurologist ok could nice to mess and one i mean a compromise of the opticnerve from a nine-millimeter non secreting so nice time someone i earned my statusin one direction i think im assuming thats the case generally nice thatmissus an issue of either the brainstem or the nerves coming out of the brainstem that would control the issue of side of the brain stem and that itreally is that the iso to my status is actually generated down to that levelthe nerves that are coming

the jury heard discussing this belatedadmission they don't generate a nice night with so i don't think that's generally the case we have to look downat the brainstem in the throat physician evaluate you for your nice statements aswell ok i had a question that i received actually prior to 11 arcing and may havediscussed this a little bit but wanted to know if you encounter any cases wherepituitary tumors had caused headaches that manifested as trigeminal neuralgiapain was diagnosed with atypical trigeminal neuralgia house at four hoursonce they also began rather than in urban first of a few minutes

years before my two morrow is dying thatfinally diagnosed my research indicates that the nerve root for the giantsseminal event is directly behind the pituitary so it seems to me there mustbe some sort of connection also if they do know or have experience with this isthere any particular clinical significance associated with it so wedid discuss it has as you mentioned so i'm glad we talked about that but i'lli'll summarize in shorts and a generally the tutor to her in the set are aligneditself did not cause you're trying to look around it's usually two roads thatare over to the side that are either of the top of the sinus which is right nextto the teacher glad we're down into

records cave which is where theabsolutely exhausting and in those cases you could get right around so if youhave it invasive pituitary adenoma into the cavernous sinus are pushing on thecover of sizes could be related i don't know if you had surgery in with yourdiagnosis is it exactly but very hard to predict clinical significance based onthat i think that if there is compression and potentially surgeryremoval can help with the pain but i would really have to carefully look atyour meeting to make sure we can coordinate that well okay if a patienthas many of these systemic symptoms meaning daily debilitating

headaches fatigue in addition to suddenonset hypopituitarism vision loss in vision disturbances along with othercentral nervous system sometimes but a normal mri you say that not all thesetumor show up on an mri at that point i would definitely discussed this with aneurologist because if you have that kind of significant symptoms michael andnobody can be seen probably not because of your headaches but definitely talk toher oldest and also want to rule out there in your arms like cushing'sdisease but you probably typed your primary care doctor about that firstfive-millimeter not secreting pituitary tumor and a typical bilateral time andin general and all three branches i have

intense pressure in both ears and am ihad twenty-four seven of my doctors can explain why i have this pressure ontwenty seven hundred milligrams gabapentin economy from the operatingroom can you repeat that question here yes sorry about that i have afive-millimeter non secreting pituitary tumor and a typical bilateral trigeminalneuralgia in all three branches of intense pressure in both ears and in myhead 24 7 not have my doctors can gabapentin yeah i don't think theteacher at norma not small would be able to cause bilateral try to unroll i thinkthere's something else going on i would definitely recommend a neurologist whospecializes in trigeminal drought or

facial pain if these medications arecutting it there some other options but remove them to take it would probablynot up with your headaches ok i had surgery for acromegaly in 1997 and thenon to understand now we are 20 milligrams sense recently i was unableto get the shop for two months and got a severe headache was a minute to thehospital for two days and many tasks including bonds concluded that there was no reasonfor the headache two days later i got this and this and that i r 29 shot myheadache went away but the lack of injection have been the cause of theheadache if so any suggestions

percent to medicare so this won't happenagain i mean it certainly makes sense based on what you said certainly fitswith your i don't know if you like to buy it and acknowledges what type oftest they had you may want to look into that a little bit further the only otherway to prove it is to stop it again as if you had a comeback and resolve thegas then you have a pretty convincing argument there but it did i think thatfalls into line that you may have a direct link there there may be also acorrelation being on it for so long just the dopamine levels affected by thesenate staten then all of a sudden you lose that a fact that actually makecontributors while but now that's just

not facing down and he farted hardevidence may have pituitary tumors or meningioma and hydrocephalus been linkedto parkinson's no parkinson's is a different type of condition is it thegenerative condition and we have seen parkinson's with parkinson whitesyndrome with trauma or other structural the isn't but not really a tumor in thearea ok i have economically surgery to removemicro macro years ago surgery did not remove tumor i stillhave a headache have tried a number of medications and kinda just accepted thatnow i guess more than anything i just want to know if this is abnormal soundslike it fits with the central i'm not

sure if you're on medication to helptreat sir but but certainly that could help get your disease control and we'dlike to see if your headaches with that can hide yourself lesspressure ever be relieved by a csf leak through a fistula between maxillarysinus where infected tooth has eroded job interesting questions that's notwhat you'd want to really fight or selfless but we certainly have seen csfofficials as a result of elevated intracranial pressure that comes throughthe sphenoid bone and i haven't seen in the maxillary sinus but i have seen itin the sphenoid sinus and not require surgery to fix it but it doesn't solvethe issue of the hydrocephalus so you'd

want to get that created by aneurosurgeon and also you may want to make sure that is yes efforts ofresponsibility and sleeping in that area and and before it becomes an infectionok i ud releasing a synthetic hormone over the course of five years contributeto the development of a pituitary mike right now so i usually they are coatedwith progesterone type of hormone and i don't think that in itself can induce itwould be highly unusual i think that covers all of the questions we have andwe're getting past time frame here and you're getting calls from the are so ithink we will wrap it up this concludes our webinar presentation we did not geta chance to answer your question will be

answered them via email the pain and wishes to thank you forparticipating in a webinar a brief survey at the end please help us provideyou with the information you need i did have a question about whether ornot this will be available after it has been recorded and after a little bitadded and some converting it should be available on our website tomorrow so ifyou missed it or you have someone else that you want to have watched it it willbe available probably by tomorrow afternoon you have any questions you can contactus at webinar a pituitary door

or give us a call at 8:05 4999 973you're getting a bunch of little messages thank you thank you and so wedefinitely appreciate your time market area and that's great informationthat you provided for us thank you so much this concludes our webinar and untilnext month will do this again thank you thank you